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Karimi M, Pirzad S, Pourfaraji SMA, Sedgi FM, Darouei B, Amani-Beni R, Kazemi K, Rabiee R. Effects of black seed (Nigella sativa L.) on cardiometabolic indices in type 2 diabetic patients: A systematic review and meta-analysis of RCTs. Complement Ther Med 2025; 90:103174. [PMID: 40210172 DOI: 10.1016/j.ctim.2025.103174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025] Open
Abstract
BACKGROUND Black seed is known for its health benefits in traditional medicine. While recent studies suggest it may improve cardiometabolic health, its impact on type 2 diabetes mellitus (T2DM) remains unclear. This study aims to meta-analysis randomized controlled trials (RCTs) to assess the effects of black seed supplementation on cardiometabolic indices in T2DM patients. METHODS Following PRISMA guidelines, a comprehensive database search was conducted up to January 2025, and data were extracted from relevant RCTs. Mean differences (MD) and standard deviations (SD) were analyzed using a random-effects model, heterogeneity was assessed, and publication bias was evaluated. RESULTS The pooled meta-analysis of 16 RCTs showed that black seed supplementation significantly reduced fasting blood glucose (FBG) (MD: -21.43 mg/dL; p = 0.005), hemoglobin A1c (HbA1c) (MD: -0.44; p = 0.01), total cholesterol (TC) (MD: -18.80 mg/dL; p = 0.04) and low-density lipoprotein (LDL) (MD: -19.53 mg/dL; p = 0.003). No significant effects were observed for 2-hour postprandial glucose (2-hpp), fasting insulin, homeostatic model assessment (HOMA), triglycerides (TG), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and body weight, or body mass index (BMI). Subgroup analyses revealed that black seed supplementation effectively reduced FBG for longer than 8 weeks; additionally, HbA1c, HOMA, and LDL in higher doses (>1 g/day), shorter durations (≤8 weeks), and use of the oil form. CONCLUSION Black seed supplementation appears to significantly improve FBG, HbA1c, TC, and LDL levels in patients with T2DM. However, no significant effects were observed on other metabolic parameters, including insulin, TG, liver enzymes, kidney function, or body weight. These findings suggest that black seed may be a beneficial adjunct therapy for glycemic and lipid control in T2DM patients but require further research to confirm its broader metabolic effects.
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Affiliation(s)
- Mehdi Karimi
- Faculty of Medicine, Bogomolets National Medical University (NMU), Kyiv, Ukraine.
| | - Samira Pirzad
- Faculty of Medicine, Islamic Azad University, Tehran Medical Sciences Branch (IAUTMU), Tehran, Iran
| | | | | | - Bahar Darouei
- Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Amani-Beni
- Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kimia Kazemi
- Department of Food Science and Technology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
| | - Reyhaneh Rabiee
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Lu G, Tang Y, Chen O, Guo Y, Xiao M, Wang J, Liu Q, Li J, Gao T, Zhang X, Zhang J, Cheng Q, Kuang R, Gu J. Aberrant activation of p53-TRIB3 axis contributes to diabetic myocardial insulin resistance and sulforaphane protection. J Adv Res 2025; 72:467-484. [PMID: 39069209 DOI: 10.1016/j.jare.2024.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/02/2024] [Accepted: 07/25/2024] [Indexed: 07/30/2024] Open
Abstract
INTRODUCTION Insulin resistance (IR) is associated with multiple pathological features. Although p53- or TRIB3-orchestrated IR is extensively studied in adipose tissue and liver, the role of p53-TRIB3 axis in myocardial IR remains unknown, and more importantly target-directed therapies of myocardial IR are missing. OBJECTIVES Considering the beneficial effects of sulforaphane (SFN) on cardiovascular health, it is of particular interest to explore whether SFN protects against myocardial IR with a focus on the regulatory role of p53-TRIB3 axis. METHODS Mouse models including cardiac specific p53-overexpressing transgenic (p53-cTg) mice and Trib3 knockout (Trib3-KO) mice, combined with primary cardiomyocytes treated with p53 activator (nutlin-3a) and inhibitor (pifithrin-α, PFT-α), or transfected with p53-shRNA and Trib3-shRNA, followed by multiple molecular biological methodologies, were used to investigate the role of p53-TRIB3 axis in SFN actions on myocardial IR. RESULTS Here, we report that knockdown of p53 rescued cardiac insulin-stimulated AKT phosphorylation, while up-regulation of p53 by nutlin-3a or p53-cTg mice blunted insulin sensitivity in cardiomyocytes under diabetic conditions. Diabetic attenuation of AKT-mediated cardiac insulin signaling was markedly reversed by SFN in p53-Tgfl/fl mice, but not in p53-cTg mice. Importantly, we identified TRIB3 was elevated in p53-cTg diabetic mice, and confirmed the physical interaction between p53 and TRIB3. Trib3-KO diabetic mice displayed improved insulin sensitivity in the heart. More specifically, the AMPKα-triggered CHOP phosphorylation and degradation were essential for p53 on the transcriptional regulation of Trib3. CONCLUSION Overall, these results indicate that inhibiting the p53-TRIB3 pathway by SFN plays an unsuspected key role in the improvement of myocardial IR, which may be a promising strategy for attenuating diabetic cardiomyopathy (DCM) in diabetic patients.
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Affiliation(s)
- Guangping Lu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Yufeng Tang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, China
| | - Ou Chen
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Yuanfang Guo
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Mengjie Xiao
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Jie Wang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Qingbo Liu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Jiahao Li
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Ting Gao
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Xiaohui Zhang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Jingjing Zhang
- Department of Cardiology at the First Hospital of China Medical University, and Department of Cardiology at the People's Hospital of Liaoning Province, Shenyang, Liaoning 110016, China
| | - Quanli Cheng
- Department of Cardiovascular Disease, First Hospital of Jilin University, Changchun, Jilin 130021, China.
| | - Rong Kuang
- NMPA Key Laboratory for Animal Alternative Testing Technology of Cosmetics, Zhejiang Institute for Food and Drug Control, Hangzhou, Zhejiang 310004, China.
| | - Junlian Gu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
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Abdelaziz HM, Abdelmageed ME, Suddek GM. Trimetazidine improves dexamethasone-induced insulin resistance and associated hepatic abnormalities in rats. Life Sci 2025; 375:123747. [PMID: 40404121 DOI: 10.1016/j.lfs.2025.123747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/25/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
INTRODUCTION Glucocorticoids (GC) are a widely prescribed anti-inflammatory and immunosuppressive medicine in clinics. The side effects GC of mostly insulin resistance (IR), dysregulated lipid metabolism and fatty liver, remain the major concern in patients. Understanding the mechanism of GC-induced hepatic steatosis is expected to provide an intervention target to avoid this side effect. AIM The present study aims to explore the beneficial effects of trimetazidine (TMZ) to combat DEXA-induced steatohepatitis and metabolic abnormalities. METHODS An in vivo IR model was established using male Wistar rats, which were administered TMZ at doses of 10 and 20 mg/kg for a duration of 14 days. Subsequently, from day 7 to day 14 of the study, the rats received DEXA (1 mg/kg, intraperitoneal (i.p.) injection). There were 5 groups, with each group consisting of 6 animals, as outlined: control group, TMZ control group, DEXA group, TMZ 10 + DEXA group, TMZ 20 + DEXA group. On the 14th day of the experiment, serum and hepatic samples were collected. RESULTS The findings indicate a marked reduction in OGTT results, fasting serum glucose and insulin levels, ALT and AST levels following treatment with TMZ. TMZ treatment also attenuated oxidative stress markers and improved the lipid profile. Additionally, the hepatic concentrations of high-mobility group box1 (HMGB1), phosphorylated Janus kinase 1 (p-JAK1), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and levels of NF-κB-p65 and interleukin-6 (IL-6) were significantly diminished by TMZ when compared with the DEXA-treated group. Furthermore, TMZ lowered B cell/lymphoma 2 (BCL-2) and caspase-3 levels and attenuated liver histopathological changes. CONCLUSION This study demonstrated that TMZ significantly improved DEXA-induced hepatic alterations by modulating the HMGB1/p-JAK1/p-STAT3/NF-κB pathway in liver. Our findings provide new evidence supporting the application of TMZ for treating DEXA-induced IR and hepatic steatosis.
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Affiliation(s)
- Howida M Abdelaziz
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
| | - Marwa E Abdelmageed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
| | - Ghada M Suddek
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
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Quarta S, Calabriso N, Carluccio MA, Albano C, Khalifa I, Wabitsch M, Blando F, Massaro M. Shielding Human Adipocytes From Inflammation: The Protective Potential of Polyphenol-Rich Opuntia ficus-indica Cladode Extract. Mol Nutr Food Res 2025:e70114. [PMID: 40377300 DOI: 10.1002/mnfr.70114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/28/2025] [Accepted: 04/29/2025] [Indexed: 05/18/2025]
Abstract
Opuntia ficus-indica (OFI) has attracted much attention as a source of antioxidant and antiinflammatory compounds. We hypothesize that the antioxidant content of OFI cladode extract may improve adipocyte dysfunction resulting from inflammatory stimulation of hypertrophic adipocytes. To this end, the properties of OFI cladode hydroalcoholic extract were evaluated in terms of antioxidant activity, regulation of adipocyte inflammation, and adipocyte/monocyte interaction in human adipocytes rendered dysfunctional by the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The major phenolic compounds identified were isorhamnetin derivatives and phenolic acids, including piscidic and eucomic acids. Our results show that OFI cladode extract exhibits antiradical activities and reduces the adhesion and transmigration activity of monocytes to inflamed adipocytes by inhibiting various cytokines, chemokines, and adhesion molecules such as interleukin (IL)-6 and IL-8 by ∼80%, monocyte chemotactic protein (MCP)-1, C-X-C motif chemokine ligand (CXC-L)10, macrophage colony-stimulating factor (M-CSF) from 40% to 50%, and intercellular adhesion molecule-1 (ICAM-1) by 70% at the higher concentration. In structurally and mechanistically by protein-ligand docking profiling study, piscidic acid proved to be the best potential candidate for a regulatory interaction with the activities of nuclear factor erythroid 2-related factor 2 (NRF-2) and nuclear factor-κB (NF-κB). In summary, these data highlight the potential of OFI as a dietary supplement in nutritional treatments aimed at combating the inflammatory stigmata of obesity.
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Affiliation(s)
- Stefano Quarta
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | - Nadia Calabriso
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
| | | | - Clara Albano
- National Research Council (CNR) Institute of Sciences of Food Production (ISPA), CNR, Lecce, Italy
| | - Ibrahim Khalifa
- Food Technology Department, Faculty of Agriculture, Benha University, Moshtohor, Egypt
| | - Martin Wabitsch
- Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany
| | - Federica Blando
- National Research Council (CNR) Institute of Sciences of Food Production (ISPA), CNR, Lecce, Italy
| | - Marika Massaro
- National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy
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Apostolopoulou M, Lambadiari V, Roden M, Dimitriadis GD. Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance. Endocr Rev 2025; 46:317-348. [PMID: 39998445 PMCID: PMC12063105 DOI: 10.1210/endrev/bnae032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Indexed: 02/26/2025]
Abstract
People with type 1 diabetes (T1D) are usually considered to exclusively exhibit β-cell failure, but they frequently also feature insulin resistance. This review discusses the mechanisms, clinical features, and therapeutic relevance of insulin resistance by focusing mainly on human studies using gold-standard techniques (euglycemic-hyperinsulinemic clamp). In T1D, tissue-specific insulin resistance can develop early and sustain throughout disease progression. The underlying pathophysiology is complex, involving both metabolic- and autoimmune-related factors operating synergistically. Insulin treatment may play an important pathogenic role in predisposing individuals with T1D to insulin resistance. However, the established lifestyle-related risk factors and peripheral insulin administration inducing glucolipotoxicity, hyperinsulinemia, hyperglucagonemia, inflammation, mitochondrial abnormalities, and oxidative stress cannot always fully explain insulin resistance in T1D, suggesting a phenotype distinct from type 2 diabetes. The mutual interaction between insulin resistance and impaired endothelial function further contributes to diabetes-related complications. Insulin resistance should therefore be considered a treatment target in T1D. Aside from lifestyle modifications, continuous subcutaneous insulin infusion can ameliorate insulin resistance and hyperinsulinemia, thereby improving glucose toxicity compared with multiple injection insulin treatment. Among other concepts, metformin, pioglitazone, incretin-based drugs such as GLP-1 receptor agonists, sodium-glucose cotransporter inhibitors, and pramlintide can improve insulin resistance, either directly or indirectly. However, considering the current issues of high cost, side effects, limited efficacy, and their off-label status, these agents in people with T1D are not widely used in routine clinical care at present.
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Affiliation(s)
- Maria Apostolopoulou
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibnitz Center for Diabetes Research at Heinrich-Heine University, 40225 Düsseldorf, Germany
- German Center of Diabetes Research (DZD), Partner Düsseldorf, 85764 München-Neuherberg, Germany
| | - Vaia Lambadiari
- 2nd Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens Medical School, 12462 Athens, Greece
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibnitz Center for Diabetes Research at Heinrich-Heine University, 40225 Düsseldorf, Germany
- German Center of Diabetes Research (DZD), Partner Düsseldorf, 85764 München-Neuherberg, Germany
| | - George D Dimitriadis
- 2nd Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens Medical School, 12462 Athens, Greece
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Wang J, Chen ZY, Shen J, Ni HJ, Sun J. Maternal Iron Levels and Association With Gestational Diabetes: A Systematic Review and Meta-Analysis. J Nutr Metab 2025; 2025:1772306. [PMID: 40313887 PMCID: PMC12045692 DOI: 10.1155/jnme/1772306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 04/02/2025] [Indexed: 05/03/2025] Open
Abstract
Background: This systematic review aimed to assess the association of iron level with gestational diabetes mellitus (GDM) risk. Methods: The relevant articles published between January 1, 1995 and January 17, 2023 were identified through a systematic literature search. This study used random effects to summarize the relative risks (RRs) 95% confidence intervals (CIs) of GDM risk and standardized mean differences. This study investigated the association of ferritin exposure with GDM combined with dose-response analysis and explored both linear and nonlinear trends. Results: This meta-analysis selected 30 studies with serum ferritin (SF), 18 studies with serum iron (SI), 4 studies with serum transferrin receptor (sTfR), 5 studies with total iron binding capacity (TIBC), and 4 studies with transferrin (TRF). The summarized RRs comparing persons with the highest concentration categories of SF with the lowest concentration categories of SF with an unadjusted odds ratio were 2.05 (1.67-2.53; I 2 = 62.8%, p < 0.001, z = 6.76, p < 0.001) and with an adjusted odds ratio were 1.82 (1.54-2.14; I 2 = 12.9%, p=0.312, z = 7.21, p < 0.001). Linear dose-response showed that an increase in SF of 5 μg/L increased the risk of GDM by 2.66% (1.026 [95% CI: 1.017, 1.036], n = 5). The nonlinear dose-response relationship also indicates that the increased SF is consistently associated with an increasing risk of GDM. Conclusion: High ferritin, high iron levels, and low TIBC are associated with an increased risk of GDM.
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Affiliation(s)
- Jinguang Wang
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Zhen-Yu Chen
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Jian Shen
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Huan-Juan Ni
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Jingli Sun
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
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Zhang K, Wang L, Gao W, Guo R. Retinol-binding protein 4 in skeletal and cardiac muscle: molecular mechanisms, clinical implications, and future perspectives. Front Cell Dev Biol 2025; 13:1587165. [PMID: 40276651 PMCID: PMC12018443 DOI: 10.3389/fcell.2025.1587165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Retinol-binding protein 4 (RBP4) has emerged as a critical adipokine involved in the pathophysiology of metabolic and cardiovascular diseases. Beyond its classical role in retinol transport, RBP4 influences insulin resistance, inflammation, lipid metabolism, mitochondrial function, and cellular apoptosis in both skeletal and cardiac muscles. Elevated levels of RBP4 are associated with obesity, type 2 mellitus diabetes, and cardiovascular diseases, making it a potential biomarker and therapeutic target. This comprehensive review elucidates the molecular mechanisms by which RBP4 affects skeletal and cardiac muscle physiology. We discuss its clinical implications as a biomarker for disease risk and progression, explore therapeutic strategies targeting RBP4, and highlight future research directions. Understanding the multifaceted roles of RBP4 could pave the way for novel interventions against metabolic and cardiovascular disorders.
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Affiliation(s)
- Kangzhen Zhang
- Department of Geriatrics, Nanjing Central Hospital, Nanjing, China
| | - Lijuan Wang
- Department of General Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Wei Gao
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Rong Guo
- Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
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Liu S, Chen X, Qi X, Bai J, Tong B, Zhang D, Yin X, Yu P. The role of metal ion metabolism in the pathogenesis of diabetes and associated complications. Front Endocrinol (Lausanne) 2025; 16:1541809. [PMID: 40248148 PMCID: PMC12003104 DOI: 10.3389/fendo.2025.1541809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 03/14/2025] [Indexed: 04/19/2025] Open
Abstract
Diabetes is a growing health concern, accompanied by significant complications like cardiovascular disease, kidney disease, and retinopathy. Metal ions, including iron, zinc, and copper, play a crucial role in maintaining human health through their balance within the body. Disruptions in metal ion balance can intensify diabetic conditions. For instance, iron overload induces oxidative stress, which harms islet β cells and impacts vascular complications of diabetes. Abnormal copper levels heighten insulin resistance, and zinc deficiency has a strong connection with type 1 diabetes. Future in - depth exploration of the association between metal metabolism and diabetes holds the potential to uncover novel treatment avenues, enhancing both the quality of life and health prognosis for patients.
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Affiliation(s)
- Siyuan Liu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College. Nanchang University, Nanchang, Jiangxi, China; The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Xuzhuo Chen
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College. Nanchang University, Nanchang, Jiangxi, China; The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Xinrui Qi
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jiahao Bai
- Laboratory of Pharmacy and Chemistry, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, China
| | - Bin Tong
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Deju Zhang
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong
Kong, Hong Kong, Hong Kong SAR, China
| | - Xiaoping Yin
- Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, China; Center for Clinical Precision Medicine, Jiujiang University, Jiujiang, China
| | - Peng Yu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China; Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Duan RC, Zhang YN, Wang YH, Xie BX, Du ZZ, Chen FJ. NPF and sNPF can regulate the feeding behaviour and affect the growth and antioxidant levels of the rice brown planthopper, Nilaparvata lugens. INSECT MOLECULAR BIOLOGY 2025; 34:302-310. [PMID: 39497249 DOI: 10.1111/imb.12971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/21/2024] [Indexed: 03/05/2025]
Abstract
Neuropeptide F (NPF) and short neuropeptide F (sNPF) are important neuropeptides and mainly affect feeding behaviour of insects. However, the regulation of insect feeding behaviour by NPF and sNPF appears to differ between species, and it is not clear how NPF and sNPF regulate the food intake of the brown planthopper (Nilaparvata lugens). Therefore, the functions of NPF and sNPF in regulating food intake and affecting the growth and antioxidant levels of N. lugens fed on host rice plants were investigated by knocking down NPF and sNPF respectively and simultaneously knocking down both of them by RNA interference. The results showed that NPF and sNPF were mainly expressed in the head of N. lugens, and N. lugens increased food intake after NPF and sNPF were knocked down, which was reflected in the prolonged duration of N4a and N4b waves in the electrical penetration graph (EPG) experiment after knocking down NPF and sNPF. In addition, knocking down NPF and sNPF led to the increase of body weight and mortality of N. lugens, and also led to the increase of antioxidant level of N. lugens. So it was concluded that NPF and sNPF could regulate food intake, maintain body weight stability and oxidative balance in N. lugens. Our study clarified the molecular mechanism of NPF and sNPF regulating feeding behaviour and affect the growth and antioxidant level of N. lugens.
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Affiliation(s)
- Rui-Chuan Duan
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Yu-Ning Zhang
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Yan-Hui Wang
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Bo-Xuan Xie
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
| | - Zheng-Ze Du
- College of Life Science, Nanjing Agricultural University, Nanjing, China
| | - Fa-Jun Chen
- Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing, China
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Cuadrado A, Cazalla E, Bach A, Bathish B, Naidu SD, DeNicola GM, Dinkova-Kostova AT, Fernández-Ginés R, Grochot-Przeczek A, Hayes JD, Kensler TW, León R, Liby KT, López MG, Manda G, Shivakumar AK, Hakomäki H, Moerland JA, Motohashi H, Rojo AI, Sykiotis GP, Taguchi K, Valverde ÁM, Yamamoto M, Levonen AL. Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases. Redox Biol 2025; 81:103569. [PMID: 40059038 PMCID: PMC11970334 DOI: 10.1016/j.redox.2025.103569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 02/13/2025] [Accepted: 02/24/2025] [Indexed: 03/22/2025] Open
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.
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Affiliation(s)
- Antonio Cuadrado
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
| | - Eduardo Cazalla
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Anders Bach
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark
| | - Boushra Bathish
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Sharadha Dayalan Naidu
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Gina M DeNicola
- Department of Metabolism and Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL, 33612, USA
| | - Albena T Dinkova-Kostova
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Raquel Fernández-Ginés
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | - Anna Grochot-Przeczek
- Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
| | - John D Hayes
- Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
| | - Thomas W Kensler
- Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
| | - Rafael León
- Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), 28007, Madrid, Spain
| | - Karen T Liby
- Indiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USA
| | - Manuela G López
- Department of Pharmacology, School of Medicine, Universidad Autónoma Madrid, Madrid, Spain; Instituto de Investigación Sanitario (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain; Instituto Teófilo Hernando, Madrid, Spain
| | - Gina Manda
- Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
| | | | - Henriikka Hakomäki
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jessica A Moerland
- Indiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USA
| | - Hozumi Motohashi
- Department of Medical Biochemistry, Graduate School of Medicine Tohoku University, Sendai, Japan; Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Ana I Rojo
- Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
| | | | - Keiko Taguchi
- Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan; Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Ángela M Valverde
- Instituto de Investigaciones Biomédicas "Sols-Morreale" UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain
| | - Masayuki Yamamoto
- Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Anna-Liisa Levonen
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
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Venkataraghavan S, Pankow JS, Boerwinkle E, Fornage M, Selvin E, Ray D. Epigenome-wide association study of incident type 2 diabetes in Black and White participants from the Atherosclerosis Risk in Communities Study. Diabetologia 2025; 68:815-834. [PMID: 39971753 PMCID: PMC12054846 DOI: 10.1007/s00125-024-06352-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 05/29/2024] [Indexed: 02/21/2025]
Abstract
AIMS/HYPOTHESIS DNA methylation studies of incident type 2 diabetes in US populations are limited and to our knowledge none include individuals of African descent. We aimed to fill this gap by identifying methylation sites (CpG sites) and regions likely influencing the development of type 2 diabetes using data from Black and White individuals from the USA. METHODS We prospectively followed 2091 Black and 1029 White individuals without type 2 diabetes from the Atherosclerosis Risk in Communities study over a median follow-up period of 17 years, and performed an epigenome-wide association analysis of blood-based methylation levels with incident type 2 diabetes using Cox regression. We assessed whether significant CpG sites were associated with incident type 2 diabetes independently of BMI or fasting glucose at baseline. We estimated variation in incident type 2 diabetes accounted for by the major non-genetic risk factors and the significant CpG sites. We also examined groups of methylation sites that were differentially methylated. We performed replication of previously discovered CpG sites associated with prevalent and/or incident type 2 diabetes. All analyses were adjusted for batch effects, cell-type proportions and relevant confounders. RESULTS At an epigenome-wide threshold (10-7), we detected seven novel diabetes-associated CpG sites, of which the sites at MICOS10 (cg05380846: HR 0.89, p=8.4 × 10-12), ZNF2 (cg01585592: HR 0.88, p=1.6 × 10-9), JPH3 (cg16696007: HR 0.87, p=7.8 × 10-9) and GPX6 (cg02793507: HR 0.85, p=2.7 × 10-8; cg00647063: HR 1.20, p=2.5 × 10-8) were identified in Black adults; chr17q25 (cg16865890: HR 0.8, p=6.9 × 10-8) in White adults; and chr11p15 (cg13738793: HR 1.11, p=7.7 × 10-8) in the meta-analysed group. The JPH3 and GPX6 sites remained epigenome-wide significant on adjustment for BMI, while only the JPH3 site retained significance after adjusting for fasting glucose. We replicated known type 2 diabetes-associated CpG sites, including cg19693031 at TXNIP, cg00574958 at CPT1A, cg16567056 at PLCB2, cg11024682 at SREBF1, cg08857797 at VPS25 and cg06500161 at ABCG1, three of which were replicated in Black adults at the epigenome-wide threshold and all of which had directionally consistent effects. We observed a modest increase in type 2 diabetes variance explained by the significantly associated CpG sites over and above traditional type 2 diabetes risk factors and fasting glucose (26.2% vs 30.5% in Black adults; 36.9% vs 39.4% in White adults). At the Šidák-corrected significance threshold of 5%, our differentially methylated region (DMR) analyses revealed several clusters of significant CpG sites, including a DMR consisting of a previously discovered CpG site at ADCY7 (pBlack=1.8 × 10-4, pWhite=3.6 × 10-3, pAll=1.6 × 10-9) and a DMR consisting of the promoter region of TP63 (pBlack=7.4 × 10-4, pWhite=3.9 × 10-3, pAll=1.4 × 10-5), which were differentially methylated across all racial and ethnic groups. CONCLUSIONS/INTERPRETATION This study illustrates improved discovery of CpG sites and regions by leveraging both individual CpG site analysis and DMR analyses in an unexplored population. Our findings include genes linked to diabetes in experimental studies (e.g. GPX6, JPH3 and TP63). The JPH3 and GPX6 sites were likely associated with incident type 2 diabetes independently of BMI. All the CpG sites except that at JPH3 were likely consequences of elevated glucose. Replication in African-descent individuals of CpG sites previously discovered mostly in individuals of European descent indicates that some of these methylation-type 2 diabetes associations are robust across racial and ethnic groups. This study is a first step towards understanding the influence of methylation on the incidence of type 2 diabetes and its disparity in two major racial and ethnic groups in the USA. It paves the way for future studies to investigate causal relationships between type 2 diabetes and the CpG sites and potentially elucidate molecular targets for intervention.
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Affiliation(s)
- Sowmya Venkataraghavan
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - James S Pankow
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Eric Boerwinkle
- The University of Texas Health School of Public Health, Houston, TX, USA
| | - Myriam Fornage
- Brown Foundation Institute for Molecular Medicine, The University of Texas Health Science Center, Houston, TX, USA
| | - Elizabeth Selvin
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, & Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Debashree Ray
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
- Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
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12
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Lundqvist T, Stenlid R, Halldin M. Hormonal Crossroads in Inborn Errors of the Metabolism Impact of Puberty and Dietary Interventions on Metabolic Health. Metabolites 2025; 15:235. [PMID: 40278364 PMCID: PMC12029320 DOI: 10.3390/metabo15040235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/21/2025] [Accepted: 03/26/2025] [Indexed: 04/26/2025] Open
Abstract
Background/Objectives: Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders characterized by enzymatic defects that disrupt metabolic pathways, leading to toxic metabolite accumulation, deficits, or impaired macromolecule synthesis. While strict dietary interventions are critical for managing many of these conditions, hormonal and metabolic changes during puberty introduce new challenges. Advancements in early diagnosis and treatment have significantly extended the lifespan of individuals with IEMs. However, this increased longevity is associated with heightened risks of new medical problems, including obesity, insulin resistance, and type 2 diabetes mellitus (T2DM), as these complications share mechanistic features with those seen in obesity and T2DM. Methods: This mini-review examines current knowledge of the intricate interplay between pubertal hormones and metabolic pathways in IEM patients. Results: We address critical questions, such as if puberty intensifies the risk of metabolic derangements in these individuals and if there is a metabolic intersection where these disorders converge, leading to shared complications. We highlight the impact of puberty-induced hormonal fluctuations, such as growth hormone (GH) surges and sex steroid activity, on disorders like phenylketonuria, urea cycle defects, and fatty acid oxidation disorders. Moreover, we explore the role of dietary interventions in mitigating or exacerbating these effects, emphasizing the importance of balancing nutritional needs during growth spurts. Conclusions: A multidisciplinary approach integrating endocrinology, nutrition, and emerging therapies is advocated to optimize metabolic health during puberty. Addressing these challenges is critical for improving long-term outcomes for individuals with IEMs, particularly during this pivotal developmental phase.
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Affiliation(s)
- Thomas Lundqvist
- Department of Women’s and Children’s Health, Karolinska Institutet, 171 76 Stockholm, Sweden
- Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Rasmus Stenlid
- Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden
| | - Maria Halldin
- Department of Women’s and Children’s Health, Karolinska Institutet, 171 76 Stockholm, Sweden
- Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, 171 76 Stockholm, Sweden
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13
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Kılınç GE, Vergi Y. Nutritional Approach to Diabetic Sarcopenia: A Comprehensive Review. Curr Nutr Rep 2025; 14:48. [PMID: 40106009 PMCID: PMC11922993 DOI: 10.1007/s13668-025-00637-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE OF THE REVIEW The aim of this review is to discuss and evaluate diabetic sarcopenia (DS) and its relationship with nutrition by discussing the mechanisms of diabetic sarcopenia in detail and comprehensively reviewing the literature. RECENT FINDINGS Type 2 diabetes (T2DM) affects approximately 25% of people aged 50 years and over and indicates a significant the cost of health for the elderly. Nutrition is an important part of these treatment approaches, and in this review, the literature was comprehensively reviewed, focusing on understanding the mechanisms of DS and discussing its relationship with nutrition. A comprehensive search was conducted on Web of Science, Google Scholar, Scopus, Science Direct, and PubMed from inception up to July 2024. The aim of nutritional treatment for DS is to improve muscle mass, muscle strength and physical performance while improving diabetes-related metabolic risk and glucose levels. In this context, it is important to determine energy intake in individuals with DS according to calorie intake exceeding 30 kcal/kg. For these individuals, a protein intake of at least 1-1.2 g/kg/day is recommended, with an emphasis on the number and timing of meals and a nutritional pattern rich in branched chain amino acids (BCAA). In addition, it is important to adopt a diet rich in antioxidants and to choose diet patterns that contain sufficient levels of macro and micronutrients. The Mediterranean diet model can be a good diet option for individuals with DS. Comprehensive studies in this field are needed so that clinicians can make specific dietary recommendations for DS.
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Affiliation(s)
- Gül Eda Kılınç
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Ondokuz Mayıs University, Samsun, Turkey.
| | - Yeliz Vergi
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Mersin University, Mersin, Turkey
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14
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Gómez Del Val A, Sánchez A, Freire-Agulleiro Ó, Martínez MP, Muñoz M, Olmos L, Medina JS, Comerma-Steffensen SG, Simonsen U, Rivera L, López M, Contreras C, Prieto D. Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H 2O 2. Free Radic Biol Med 2025; 230:222-233. [PMID: 39929293 DOI: 10.1016/j.freeradbiomed.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 01/25/2025] [Accepted: 02/04/2025] [Indexed: 02/24/2025]
Abstract
OBJECTIVE Erectile dysfunction (ED) is considered an early manifestation of cardiovascular disease (CVD), endothelial dysfunction being the link between CVD and vasculogenic ED. Mitochondrial reactive oxygen species (mtROS) have been involved in the vascular complications of metabolic disorders. The aim of this study was to assess the impact of obesity on endothelial function, redox metabolism and mitochondrial bioenergetics of penile erectile tissue. METHODS Wistar rats were fed a high-fat diet (HFD) or standard diet (STD), and penile vascular function was assessed in microvascular myographs. mtROS levels were measured by mitoSOX (O2.-) and Amplex Red (H2O2) fluorimetry, and the effect of the mitochondrial antioxidant mitoTempo on endothelium-dependent relaxations was tested. Mitochondrial respiration of intact microarteries was assessed with an Agilent Seahorse XF Pro analyzer, and the expression of mitochondria redox regulators was analysed by Western blot. RESULTS Endothelium-dependent relaxations to acetylcholine (ACh) and to the mitoKATP channel activator BMS191095 were reduced in penile arteries from HFD. mtROS levels were significantly increased and associated with upregulation of the endothelial NADPH oxidase 4 (Nox4) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in HFD erectile tissue. MitoTempo inhibited endothelial relaxations in control and HFD penile arteries. The bioenergetic profile was significantly reduced in HFD penile arteries compared to STD rats. CONCLUSIONS Mitochondrial dysfunction with impaired bioenergetics and reduced mitoKATP channel-mediated relaxation underlie endothelial and vascular dysfunction of erectile tissue in obesity, despite a compensatory mechanism that enhances Nox4-derived endothelial vasodilator mtROS. Therapeutic strategies aimed to stabilize mitochondria could restore redox balance and improve mitochondrial bioenergetics thus preventing oxidative stress and vascular dysfunction underlying metabolic disease associated ED.
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Affiliation(s)
| | - Ana Sánchez
- Department of Physiology, Madrid Complutense University, Madrid, Spain
| | - Óscar Freire-Agulleiro
- NeurObesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain
| | - María Pilar Martínez
- Department of Anatomy and Embriology, Madrid Complutense University, Madrid, Spain
| | - Mercedes Muñoz
- Department of Physiology, Madrid Complutense University, Madrid, Spain
| | - Lucia Olmos
- Department of Physiology, Madrid Complutense University, Madrid, Spain
| | | | | | - Ulf Simonsen
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark
| | - Luis Rivera
- Department of Physiology, Madrid Complutense University, Madrid, Spain
| | - Miguel López
- NeurObesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain
| | | | - Dolores Prieto
- Department of Physiology, Madrid Complutense University, Madrid, Spain.
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15
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Cendek BD, Bayraktar B, Sapmaz MA, Akay A, Ustun YE, Keskin HL, Erel O. Effect of maternal body mass index on inflammatory biomarkers and dynamic thiol-disulfide homeostasis during pregnancy. BMC Pregnancy Childbirth 2025; 25:280. [PMID: 40082814 PMCID: PMC11907970 DOI: 10.1186/s12884-025-07387-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Accepted: 02/27/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND The aim of this study was to investigate the relationship between maternal body mass index (BMI), a modifiable factor during the reproductive period, and inflammation and oxidative stress by assessing dynamic thiol-disulfide homeostasis (TDH) in both the mother and fetus. METHOD This prospective cohort study was conducted between May and June 2024 at a tertiary obstetric care center. The inclusion criteria consisted of healthy pregnant women aged over 18 years, between 37 and 41 weeks of gestation, who had not used medications other than iron and folic acid supplements, with newborns birth weight between 2,500 grams (g) and 4,500 g, and Apgar scores ≥ 7 at the 5th minute after birth. Maternal peripheral blood (5 mL) was collected at delivery admission, and 3 mL of fetal blood was obtained from the umbilical cord after delivery. Participants (n = 125) were categorized into three BMI-based groups: (1) non-obese at both pre-pregnancy and delivery (BMI < 30 kg/m², n = 72); (2) non-obese at pre-pregnancy but gained weight to a BMI classified as obese at delivery (BMI < 30 kg/m² pre-pregnancy, ≥ 30 kg/m² at delivery, n = 29); and (3) obese at both pre-pregnancy and delivery (BMI ≥ 30 kg/m², n = 24). RESULTS Maternal serum native thiol (SH) (306.21 ± 49.19 µmol/L vs. 270.9 ± 60.12 µmol/L vs. 276.9 ± 59.18 µmol/L, p = 0.004) and total thiol (SH + SS) (337.88 ± 52.43 µmol/L vs. 303.8 ± 62.13 µmol/L vs. 306 ± 58.01 µmol/L, p = 0.006) levels were significantly higher in the non-obese at both pre-pregnancy and delivery group compared to the other groups. Disulfide (SS) levels and thiol-disulfide ratios (SS/SH, SS/total thiol, and SH/total thiol) showed no significant differences among groups (p > 0.05, for all). In fetal cord blood, SH, SS, SH + SS levels, and thiol-disulfide ratios were not significantly different among the groups (p > 0.05, for all). CONCLUSION Maternal obesity, whether longstanding or newly developed during pregnancy, disrupts TDH and reduces antioxidant capacity, increasing susceptibility to oxidative damage and may affect maternal and fetal health. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Busra Demir Cendek
- Department of Obstetrics and Gynecology, Health Sciences University Etlik Zubeyde Hanim Maternity, Teaching and Research Hospital, Ankara, Turkey.
- Department of Obstetrics and Gynecology, Republic of Turkey Ministry of Health Ankara Etlik City Hospital, Ankara, Turkey.
| | - Burak Bayraktar
- Department of Obstetrics and Gynecology, Division of Perinatology, Health Sciences University Etlik Zubeyde Hanim Maternity, Teaching and Research Hospital, Ankara, Turkey.
- Department of Obstetrics and Gynecology, Division of Perinatology, Republic of Turkey Ministry of Health Ankara Etlik City Hospital, Ankara, Turkey.
| | - Mehmet Alican Sapmaz
- Department of Obstetrics and Gynecology, Republic of Turkey Ministry of Health Ankara Etlik City Hospital, Ankara, Turkey
| | - Arife Akay
- Department of Obstetrics and Gynecology, Health Sciences University Etlik Zubeyde Hanim Maternity, Teaching and Research Hospital, Ankara, Turkey
| | - Yaprak Engin Ustun
- Department of Obstetrics and Gynecology, Health Sciences University Etlik Zubeyde Hanim Maternity, Teaching and Research Hospital, Ankara, Turkey
| | - Huseyin Levent Keskin
- Department of Obstetrics and Gynecology, Republic of Turkey Ministry of Health Ankara Etlik City Hospital, Ankara, Turkey
| | - Ozcan Erel
- Department of Biochemistry, Ankara Yildirim Beyazit University, Ankara, Turkey
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16
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Wang T, Zhang M, Shi W, Li Y, Zhang T, Shi W. Atherogenic index of plasma, high sensitivity C-reactive protein and incident diabetes among middle-aged and elderly adults in China: a national cohort study. Cardiovasc Diabetol 2025; 24:103. [PMID: 40045300 PMCID: PMC11883954 DOI: 10.1186/s12933-025-02653-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 02/17/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND The atherogenic index of plasma (AIP) and systematic inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), are predictors of diabetes, but their combined impacts on incident diabetes are poorly understood. Using a nationally representative cohort in China, we aimed to investigate the association of AIP and hsCRP with incident diabetes among middle-aged and elderly adults. METHODS This cohort comprised 9,112 participants aged at least 45 years from 125 cities in the China Health and Retirement Longitudinal Study who were free of diabetes at baseline in 2011. Of these, 5,048 participants were followed up until 2015. The AIP was calculated as Log10[TG (mg/dL)/HDL-C(mg/dL)]. Multivariate logistic regression and linear mixed-effect (LME) models were performed to evaluate the associations of AIP, hsCRP, and incident diabetes as well as glycemic biomarkers. Receiver operating characteristic (ROC) curves were used to evaluate their diagnostic values. We conducted a mediation analysis to assess the direct and indirect associations between AIP and hsCRP with diabetes. RESULTS 489 (9.7%) cases developed diabetes during four years. Higher levels of AIP and hsCRP were independently associated with diabetes. Compared to the lowest quartile of AIP or hsCRP, the highest quartile of AIP (adjusted odds ratio, aOR 2.53, 95% CI: 1.90-3.38) and hsCRP (aOR 2.38, 1.79-3.16) was significantly associated with incident diabetes. The joint effects showed that participants with higher levels of AIP and hsCRP had significantly higher aOR of 2.76 (2.13-3.57). The LME models showed AIP and hsCRP were related to an increased level of fasting blood glucose and glycated hemoglobin. The combination of AIP and hsCRP has better predictive efficacy (area under the curve, AUC: 0.628, 0.601-0.654) for incident diabetes than alone. Mediation analyses showed that high AIP significantly mediated 25.4% of the association between hsCRP and diabetes, and hsCRP simultaneously mediated 5.7% of the association between AIP and diabetes. CONCLUSIONS This cohort suggests combined effects and mutual mediation between the AIP and hsCRP on incident diabetes in China. Our findings provide clinical implications for monitoring and managing AIP and hsCRP levels to mitigate the development of diabetes.
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Affiliation(s)
- Tongshuai Wang
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China
- Clinical Research Unit Office, Tongren Hospital Shanghai Jiao Tong University School of Medicine, 200336, Shanghai, China
| | - Mengru Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China
| | - Wenxing Shi
- Department of Pharmaceutical and Biomedical Engineering, Clinical College of Anhui Medical University, Anhui, 230031, China
| | - Yongzhen Li
- Clinical Nutrition Department, Starkids Children's Hospital, Shanghai, New Hong Qiao Campus for Children's Hospital of Fudan University, Shanghai, 201106, China
- School of Public Health, Peking University, Beijing, 100191, China
| | - Tiantian Zhang
- School of Public Health, Fudan University, Shanghai, 200032, China
| | - Wenming Shi
- Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Pudong New District, Shanghai, 201204, China.
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17
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Lei J, Liao Z, Duan W, Li Q, Duan L, Tang H, Luo H, Huang H, Li H. Association between oxidative balance score and all-cause mortality in stroke survivors. Sci Rep 2025; 15:7628. [PMID: 40038405 PMCID: PMC11880293 DOI: 10.1038/s41598-025-91721-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/24/2025] [Indexed: 03/06/2025] Open
Abstract
Stroke is the second leading cause of death globally. Oxidative stress plays a critical role in the development of stroke. The Oxidative Balance Score (OBS) is a tool used to assess the combined impact of diet and lifestyle on the body's antioxidant capacity. The study included stroke survivors from the National Health and Nutrition Examination Survey (1999-2018), with a total of 1,781 participants and a median follow-up duration of 6.5 years, during which 786 participants (39.59%) died. The relationship between OBS and all-cause mortality was assessed using the Cox proportional hazards model. The results indicated that individuals in higher OBS quartiles had lower mortality rates. Specifically, patients in the fourth quartile had a 41% reduced risk of all-cause mortality compared to those in the first quartile (HR = 0.59, 95% CI = 0.42-0.84, p = 0.003). Restricted cubic spline analysis revealed a linear inverse relationship between OBS and all-cause mortality. Subgroup analysis further demonstrated that the inverse association persisted across various population subgroups. Overall, our study suggests that higher levels of OBS can reduce the risk of all-cause mortality in stroke survivors and provides new evidence for their diet and lifestyle.
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Affiliation(s)
- Jinglin Lei
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Zhiyi Liao
- Department of Burns and Plastic Surgery, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Wentao Duan
- Department of Critical Care Medicine, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Qiuli Li
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Lili Duan
- Translational Medicine Institute, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, China
| | - Hailiang Tang
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Hanyao Luo
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Hao Huang
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China
| | - Haipeng Li
- Department of Neurology, The Chenzhou Affiliated Hospital, Hengyang Medical School, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000, Hunan, China.
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Klootwyk BM, Fleury GM, Albright S, Deiters A, Floreancig PE. Difunctional oxidatively cleavable alkenyl boronates: application to cellular peroxide sensing from a fluorophore-quencher pair. Chem Commun (Camb) 2025; 61:3375-3378. [PMID: 39887215 PMCID: PMC11784462 DOI: 10.1039/d5cc00090d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 01/27/2025] [Indexed: 02/01/2025]
Abstract
This manuscript describes the development of difunctional alkenyl boronates that contain an oxidatively releasable cargo and an amine for attaching to groups that can improve physical properties or enhance cellular targeting. The design is applied to a FRET-based system that delivers a selective fluorescence response in oxidatively stressed cells.
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Affiliation(s)
- Brittany M Klootwyk
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
| | - Grace M Fleury
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
| | - Savannah Albright
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
| | - Alexander Deiters
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
| | - Paul E Floreancig
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
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19
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Rodriguez-Hernandez Z, Bel-Aguilar J, Moreno-Franco B, Grau-Perez M, Redon J, Gomez-Ariza JL, Garcia-Barrera T, Olmedo P, Gil F, Cenarro A, Civeira F, Puzo J, Casasnovas JA, Banegas JR, Sotos-Prieto M, Ortola R, Laclaustra M, Rodriguez-Artalejo F, Garcia-Esquinas E, Tellez-Plaza M, Pastor-Barriuso R. Differential association of selenium exposure with insulin resistance and β-cell function in middle age and older adults. Nutr Diabetes 2025; 15:5. [PMID: 39948355 PMCID: PMC11825691 DOI: 10.1038/s41387-025-00361-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
OBJECTIVE To assess whether the role of selenium on pre-diabetes is differential by age, given comorbidities and decreased β-cell function in older adults. RESEARCH DESIGN AND METHODS We evaluated the cross-sectional association of blood selenium with the homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) in middle-aged (Aragon Workers Health Study [AWHS], N = 1186), and older (Seniors ENRICA [Study on Nutrition and Cardiovascular Risk in Spain]-2 [SEN-2], N = 915) diabetes-free adults. A subsample of participants from AWHS (N = 571) and SEN-2 (N = 603) had glucose and insulin repeated measurements for longitudinal analysis. We validated the cross-sectional dose-response associations in the 2011-2018 National Health and Nutrition Examination Survey (NHANES, N = 1317 middle age and N = 960 older) participants. Selenium was measured in whole blood with ICP-MS in AWHS, SEN-2 and NHANES. RESULTS The cross-sectional geometric mean ratios (95% confidence intervals) per two-fold selenium increase were 1.09 (1.01, 1.19) for HOMA-IR and 1.15 (1.06, 1.24) for HOMA-β in AWHS; and 1.13 (0.98, 1.31) and 1.03 (0.90, 1.18), in SEN-2. The cross-sectional dose-response associations were consistent in NHANES, with mostly increasingly positive trends for both HOMA endpoints in younger adults and a plateau at levels >~150 μg/L in older adults. The longitudinal dose-response consistently showed positive associations at high selenium dose for both HOMA endpoints in the younger, but not the older, study population. CONCLUSIONS Increased blood selenium was associated with increased insulin resistance and β-cell function in middle-aged, but not in older individuals, especially for β-cell function. The results suggest that selenium-associated insulin resistance might induce compensatory increased β-cell function at younger ages, being this compensatory capacity decreased with aging.
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Affiliation(s)
- Zulema Rodriguez-Hernandez
- Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Biotechnology, Universitat Politècnica de València, Valencia, Spain
- Institute of Genetic Epidemiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Javier Bel-Aguilar
- Department of Statistics and Operational Research, University of Valencia, Valencia, Spain
| | - Belen Moreno-Franco
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario Miguel Servet, Zaragoza, Spain
- Department of Preventive Medicine and Public Health, Universidad de Zaragoza, Zaragoza, Spain
- CIBERCV (CIBER de Enfermedades Cardiovasculares), Madrid, Spain
| | - Maria Grau-Perez
- Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- Department of Statistics and Operational Research, University of Valencia, Valencia, Spain.
- Big data Unit, Instituto de Investigación Sanitaria Hospital Clinic de Valencia INCLIVA, Valencia, Spain.
| | - Josep Redon
- Big data Unit, Instituto de Investigación Sanitaria Hospital Clinic de Valencia INCLIVA, Valencia, Spain
| | - Jose L Gomez-Ariza
- Research Center on Health and The Environment (RENSMA), Department of Chemistry "Prof.J.C.Vílchez Martín", University of Huelva, Fuerzas Armadas Ave., Huelva, Spain
| | - Tamara Garcia-Barrera
- Research Center on Health and The Environment (RENSMA), Department of Chemistry "Prof.J.C.Vílchez Martín", University of Huelva, Fuerzas Armadas Ave., Huelva, Spain
| | - Pablo Olmedo
- Department of Legal Medicine, Toxicology, and Physical Anthropology, School of Medicine, University of Granada, Granada, Spain
| | - Fernando Gil
- Department of Legal Medicine, Toxicology, and Physical Anthropology, School of Medicine, University of Granada, Granada, Spain
| | - Ana Cenarro
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario Miguel Servet, Zaragoza, Spain
- CIBERCV (CIBER de Enfermedades Cardiovasculares), Madrid, Spain
| | - Fernando Civeira
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario Miguel Servet, Zaragoza, Spain
- CIBERCV (CIBER de Enfermedades Cardiovasculares), Madrid, Spain
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain
| | - Jose Puzo
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario San Jorge, Huesca, Spain
| | - Jose A Casasnovas
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario Miguel Servet, Zaragoza, Spain
- CIBERCV (CIBER de Enfermedades Cardiovasculares), Madrid, Spain
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain
| | - Jose R Banegas
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Mercedes Sotos-Prieto
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA
- IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Rosario Ortola
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Martin Laclaustra
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Hospital Universitario Miguel Servet, Zaragoza, Spain
- CIBERCV (CIBER de Enfermedades Cardiovasculares), Madrid, Spain
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain
| | - Fernando Rodriguez-Artalejo
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Esther Garcia-Esquinas
- Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Maria Tellez-Plaza
- Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid, Madrid, Spain.
| | - Roberto Pastor-Barriuso
- Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
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20
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Gao Y, Peng Y, Shi L, Zhang S, Bai R, Lang Y, He Y, Zhang B, Zhang Z, Zhang X. A colorimetric fluorescent probe for reversible detection of HSO 3-/H 2O 2 and effective discrimination of HSO 3-/ClO - and its application in food and bioimaging. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 326:125275. [PMID: 39481270 DOI: 10.1016/j.saa.2024.125275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 09/27/2024] [Accepted: 10/08/2024] [Indexed: 11/02/2024]
Abstract
In view of the significant role of reactive sulfur species (RSS) and reactive oxygen species (ROS) in maintaining the redox homeostasis of organisms, we proposed a colorimetric fluorescent probe (HTN) for reversible detection of HSO3-/H2O2 and effective discrimination of HSO3-/ClO-. C = C is the active site for the Michael addition of HSO3- and the oxidation of ClO-. When HTN interacts with HSO3- and ClO-, it exhibits fluorescence quenching. The addition of oxidizing H2O2 to the system can restore the conjugate structure of the addition product of HSO3- (HTN-HSO3-) and the fluorescence recovery, but it cannot restore the structure of the oxidation product of ClO- (HTN-ClO-). By studying the change of the reversibility/non-reversibility of the probe structure with the addition of H2O2, the purpose of reversible detection of HSO3-/H2O2 and distinguishing HSO3-/ClO- is achieved. In addition, HTN can not only be used as a fluorescent ink to detect HSO3- on the test paper, but also has excellent detection effect on HSO3- and ClO- in real food samples and water samples. Meantime, HTN has good biocompatibility and can target mitochondria to achieve reversible detection of HSO3-/H2O2 and effective discrimination of HSO3-/ClO- in living cells. Therefore, HTN has great potential as a molecular tool for studying redox homeostasis in the interaction network of complex living systems.
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Affiliation(s)
- Yuexing Gao
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China
| | - Yan Peng
- Affiliated Hospital, North China University of Science and Technology, Tangshan 063008, China
| | - Lei Shi
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China.
| | - Siyun Zhang
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China
| | - Ruiyang Bai
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China
| | - Yunhe Lang
- College of Pharmacy, North China University of Science and Technology, Tangshan 063210, China
| | - Yonggui He
- Affiliated Hospital, North China University of Science and Technology, Tangshan 063008, China
| | - Buyue Zhang
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China
| | - Ziyi Zhang
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China
| | - Xiufeng Zhang
- College of Chemical Engineering, North China University of Science and Technology, Tangshan 063210, China.
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21
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Liu F, Wang K, Nie J, Deng MG. Unraveling the Link: Mendelian Randomization Reveals Causal Relationship Between Selenium and Metabolic Syndrome. Biol Trace Elem Res 2025; 203:790-798. [PMID: 38776021 DOI: 10.1007/s12011-024-04237-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 05/15/2024] [Indexed: 11/28/2024]
Abstract
Observational studies have linked selenium and metabolic syndrome (MetS), but the causality remains unclear. Therefore, this study intends to determine the causal relationship between selenium and the risk of MetS and its component features [body mass index (BMI), waist circumference adjusted for BMI (WCadjBMI), triglycerides (TC), HDL-cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (FBI), systolic blood pressure (SBP), and diastolic blood pressure (DBP)]. This study was designed as the two-sample Mendelian randomization (MR), and genetic variants were obtained from the genome-wide association studies. The inverse variance weighted (IVW) was applied as the primary method, and the MR-Egger, weighted median, and MR-PRESSO were supplemented to assess its robustness. The Bonferroni method was used to correct p-values for multiple tests. Genetically incremented selenium level was related to higher odds ratios of developing the MetS (OR = 1.054, 95% CI = 1.016-1.094, p = 0.0049). As for components, significant causal links were identified between selenium and BMI (β = 0.015, p = 1.321 × 10-5), WCadjBMI (β = 0.033, p = 2.352 × 10-4), HDL-C (β = -0.036, p = 1.352 × 10-8), FBG (β = 0.028, p = 0.001), and FBI (β = 0.028, p = 0.002). No significant association was discovered for SBP (β = -0.076, p = 0.218) and DBP (β = 0.054, p = 0.227). These results were generally supported by the weighted median and MR-PRESSO methods. Our study provided evidence of the causal effect of selenium on MetS risk from the genetic perspective in the European population, and further investigation across diverse populations was warranted.
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Affiliation(s)
- Fang Liu
- School of Public Health, Wuhan University, Wuhan, 430071, China
| | - Kai Wang
- Department of Public Health, Wuhan Fourth Hospital, Wuhan, 430000, China
| | - Jiaqi Nie
- Xiaogan Municipal Center for Disease Control and Prevention, Xiaogan, 432000, Hubei, China
| | - Ming-Gang Deng
- Department of Psychiatry, Wuhan Mental Health Center, Wuhan, 430012, Hubei, China.
- Department of Psychiatry, Wuhan Hospital for Psychotherapy, Wuhan, 430012, Hubei, China.
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22
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Kusama K, Oka K, Yashiro Y, Yoshida K, Miyaoka H, Tamura K. Effect of Cordyceps militaris extract containing cordycepin on the adipogenesis and lipolysis of adipocytes. FEBS Open Bio 2025; 15:335-345. [PMID: 39572891 PMCID: PMC11788751 DOI: 10.1002/2211-5463.13930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/10/2024] [Accepted: 11/06/2024] [Indexed: 02/04/2025] Open
Abstract
Obesity, a global health concern, results from an energy imbalance leading to lipid accumulation. In the present study, Cordyceps militaris extract (CM) and its primary component, cordycepin, were investigated to characterize their potential effects on adipogenesis and lipolysis. Treatment with CM or cordycepin reduced lipid droplets and increased hormone-sensitive lipase activation in 3T3-L1 cells. In a diabetic obese mouse model, CM and cordycepin lowered serum low-density lipoprotein/very low-density lipoprotein levels and reduced oxidative stress and cell senescence markers. Thus, cordycepin inhibits preadipocyte differentiation and promotes lipolysis, which may serve as a novel obesity treatment. Further studies, including clinical trials, are required to validate the clinical potential of cordycepin.
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Affiliation(s)
- Kazuya Kusama
- Department of Endocrine PharmacologyTokyo University of Pharmacy and Life SciencesJapan
| | - Kodai Oka
- Department of Endocrine PharmacologyTokyo University of Pharmacy and Life SciencesJapan
| | - Yumi Yashiro
- Department of Endocrine PharmacologyTokyo University of Pharmacy and Life SciencesJapan
| | - Kanoko Yoshida
- Department of Endocrine PharmacologyTokyo University of Pharmacy and Life SciencesJapan
| | - Hiroaki Miyaoka
- Department of Biomolecular Organic ChemistryTokyo University of Pharmacy and Life SciencesJapan
| | - Kazuhiro Tamura
- Department of Endocrine PharmacologyTokyo University of Pharmacy and Life SciencesJapan
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23
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Chatzikalil E, Arvanitakis K, Kalopitas G, Florentin M, Germanidis G, Koufakis T, Solomou EE. Hepatic Iron Overload and Hepatocellular Carcinoma: New Insights into Pathophysiological Mechanisms and Therapeutic Approaches. Cancers (Basel) 2025; 17:392. [PMID: 39941760 PMCID: PMC11815926 DOI: 10.3390/cancers17030392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is rising in global incidence and mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disease, is strongly linked to metabolic conditions that can progress to liver cirrhosis and HCC. Iron overload (IO), whether inherited or acquired, results in abnormal iron hepatic deposition, significantly impacting MASLD development and progression to HCC. While the pathophysiological connections between hepatic IO, MASLD, and HCC are not fully understood, dysregulation of glucose and lipid metabolism and IO-induced oxidative stress are being investigated as the primary drivers. Genomic analyses of inherited IO conditions reveal inconsistencies in the association of certain mutations with liver malignancies. Moreover, hepatic IO is also associated with hepcidin dysregulation and activation of ferroptosis, representing promising targets for HCC risk assessment and therapeutic intervention. Understanding the relationship between hepatic IO, MASLD, and HCC is essential for advancing clinical strategies against liver disease progression, particularly with recent IO-targeted therapies showing potential at improving liver biochemistry and insulin sensitivity. In this review, we summarize the current evidence on the pathophysiological association between hepatic IO and the progression of MASLD to HCC, underscoring the importance of early diagnosis, risk stratification, and targeted treatment for these interconnected conditions.
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Affiliation(s)
- Elena Chatzikalil
- Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece;
- “Aghia Sofia” Children’s Hospital ERN-PeadCan Center, 11527 Athens, Greece
| | - Konstantinos Arvanitakis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece; (K.A.); (G.K.); (G.G.)
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Georgios Kalopitas
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece; (K.A.); (G.K.); (G.G.)
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Matilda Florentin
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece; (K.A.); (G.K.); (G.G.)
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Theocharis Koufakis
- Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
| | - Elena E. Solomou
- Department of Internal Medicine, University of Patras Medical School, 26500 Rion, Greece
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24
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Wang Z, Ji W, Wang Y, Li L, Wang K, Liu H, Yang Y, Zhou Y. Association between exposure to ambient air pollutants and metabolic syndrome in the vicinity of the Taklamakan Desert. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 290:117525. [PMID: 39674022 DOI: 10.1016/j.ecoenv.2024.117525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/23/2024] [Accepted: 12/08/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND Air pollution is a recognized contributor to metabolic syndrome (MetS); but studies in developing regions, including China, remain limited, especially in severely polluted areas near the Taklamakan Desert. METHODS Health data from 2,689,455 individuals aged ≥ 18 years in five regions near the Taklamakan Desert were analyzed. MetS diagnosed followed the 2016 Chinese Adult Dyslipidaemias Management Guidelines. Spatio-temporal data from satellite observations were employed to estimate ambient pollution levels, encompassing particulate matter with diameters of up to 1.0 µm (PM1), 2.5 µm (PM2.5), and 10 µm (PM10), along with Ozone (O3) and Carbon monoxide (CO). To investigate the association between air pollutants and the prevalence of MetS and its components, Spatial Generalized Linear Mixed Models were applied, with adjustments made for relevant covariates. Additional stratified and sensitivity analyses were conducted to further investigate these relationships. RESULTS The study observed a 20.43 % prevalence of MetS. Non-linear analysis indicated a significant association between all pollutants and MetS prevalence. A 10 μg/m³ increase in concentration was associated with the following respective odds ratios: PM1 (1.341, 95 % CI: 1.331, 1.351), PM2.5 (1.036, 95 % CI: 1.034, 1.037), PM10 (1.006, 95 % CI: 1.005, 1.007), O3 (1.385, 95 % CI: 1.374, 1.396), and CO (1.015,95 %, CI: 1.0147, 1.016). The reliability of these associations was supported by further sensitivity analyses, accounting for variations in age, sex, physical activity, and smoking status. Additional analysis indicated links between pollutants and MetS components, including abdominal obesity, glucose metabolism, and lipid profiles. CONCLUSIONS There is an observed association between long-term exposure to air pollution and a heightened risk of MetS, particularly in men, younger individuals, those who are physically inactive, and smokers.
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Affiliation(s)
- Zhe Wang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
| | - Weidong Ji
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
| | - Yushan Wang
- Center of Health Management, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830000, China; Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830000, China
| | - Lin Li
- School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang 830054, China
| | - Kai Wang
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, Xinjiang 830054, China
| | - Hongze Liu
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
| | - Yining Yang
- Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830000, China; Department of Cardiology, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830000, China.
| | - Yi Zhou
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
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25
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Zhang S, Wang N, Gao Z, Gao J, Wang X, Xie H, Wang CY, Zhang S. Reductive stress: The key pathway in metabolic disorders induced by overnutrition. J Adv Res 2025:S2090-1232(25)00031-1. [PMID: 39805424 DOI: 10.1016/j.jare.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/04/2024] [Accepted: 01/05/2025] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health. AIM OF REVIEW In this review, we present an extensive array of evidence for the occurrence of reductive stress and its significant implications mainly in metabolic and cardiovascular diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW Reductive stress is defined as a shift in the cellular redox balance towards a more reduced state, characterized by an excess of endogenous reductants (such as NADH, NADPH, and GSH) over their oxidized counterparts (NAD+, NADP+, and GSSG). While oxidative stress has been the predominant mechanism studied in obesity, metabolic disorders, and cardiovascular diseases, growing evidence underscores the critical role of reductive stress. This review discusses how reductive stress contributes to metabolic and cardiovascular pathologies, emphasizing its effects on key cellular processes. For example, excessive NADH accumulation can disrupt mitochondrial function by impairing the electron transport chain, leading to decreased ATP production and increased production of reactive oxygen species. In the endoplasmic reticulum (ER), an excess of reductive equivalents hampers protein folding, triggering ER stress and activating the unfolded protein response, which can lead to insulin resistance and compromised cellular homeostasis. Furthermore, we explore how excessive antioxidant supplementation can exacerbate reductive stress by further shifting the redox balance, potentially undermining the beneficial effects of exercise, impairing cardiovascular health, and aggravating metabolic disorders, particularly in obese individuals. This growing body of evidence calls for a reevaluation of the role of reductive stress in disease pathogenesis and therapeutic interventions.
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Affiliation(s)
- Shiyi Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhichao Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohui Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Xie
- Institute of Translational Medicine, Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Cong-Yi Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Shu Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Sun H, Pan C, Yan M, Wang Z, He J, Zhang H, Yang Z, Wang Z, Wang Y, Liu H, Yang X, Hou F, Wei J, Yu P, Chen X, Tang NJ. Effects of PM 2.5 components on hypertension and diabetes: Assessing the mitigating influence of green spaces. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 959:178219. [PMID: 39719762 DOI: 10.1016/j.scitotenv.2024.178219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 12/26/2024]
Abstract
BACKGROUND Particulate matter with diameters ≤2.5 μm (PM2.5) is a significant air pollutant associated with hypertension and diabetes. However, the specific contributions of its components and their joint exposure with green spaces remain poorly understood, especially in developing regions. OBJECTIVES This study aims to investigate the individual and joint impacts of PM2.5 and its components on the middle-aged and older adults, identify primary risk factors, and assess disease risks associated with simultaneous exposure to green spaces. METHOD We conducted a prospective cohort study in Tianjin from 2014 to 2021, involving individuals aged ≥45 years. Satellite-based machine learning models quantified PM2.5 components, including black carbon (BC), organic matter (OM), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-). Residential greenness was assessed using the Normalized Difference Vegetation Index (NDVI). A time-varying Cox proportional hazards model analyzed associations between PM2.5 components and the incidence of hypertension and diabetes. The quantile g-computation model evaluated joint exposure effects and relative contributions of the components. Pollutants and NDVI were dichotomized using median values and combined to create a joint exposure model, aimed at exploring the potential effects of NDVI. Stratified analyses were performed to identify vulnerable subpopulations. RESULTS Over 241,528.73 person-years of follow-up, there were 15,747 (38.34 %) new cases of hypertension and 8945 (13.59 %) new cases of diabetes. Each standard deviation (SD) increase in OM was associated with increased incidence of hypertension (hazard ratio: 1.609; 95 % confidence interval: 1.583, 1.636) and diabetes (1.484; 1.453, 1.515). Joint exposure to components is linked to higher incidence of hypertension and diabetes, with OM identified as the primary contributor. The joint exposure model indicated elevated population risk in areas with low NDVI and high PM2.5 concentrations, particularly affecting males and individuals younger than 60 years. CONCLUSIONS Long-term exposure to higher levels of PM2.5 components is significantly associated with increased hypertension and diabetes, with OM potentially being the primary contributor. Joint exposure to green space may mitigate these risks. These findings highlight how PM2.5 sources impact health, informing more effective governance measures.
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Affiliation(s)
- Hongyue Sun
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China
| | - Chengjie Pan
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China
| | - Mengfan Yan
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China
| | - Zhongli Wang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
| | - Jiayu He
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Honglu Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Ze Yang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Zinuo Wang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Yiqing Wang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Hongyan Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China; Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin 300134, China
| | - Xueli Yang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
| | - Fang Hou
- Community Health Service Center, Jiefang Road, Tanggu Street, Binhai New Area, Tianjin 300451, China
| | - Jing Wei
- Department of Atmospheric and Oceanic Science, Earth System Science Interdisciplinary Center, University of Maryland, College Park, MD 20740, USA
| | - Pei Yu
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China; Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin 300134, China; Department of Nephrology & Blood Purification Center, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Xi Chen
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China.
| | - Nai-Jun Tang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin 300070, China
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Chen X, Xie N, Feng L, Huang Y, Wu Y, Zhu H, Tang J, Zhang Y. Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies. Chin Med J (Engl) 2025; 138:15-27. [PMID: 39503316 PMCID: PMC11717531 DOI: 10.1097/cm9.0000000000003230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Indexed: 01/11/2025] Open
Abstract
ABSTRACT Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
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Affiliation(s)
- Xingyu Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Na Xie
- Sichuan International Science and Technology Center for Stress Medicine, West China School of Basic Medical Sciences and Forensic Medicine and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, China
| | - Lixiang Feng
- Sichuan International Science and Technology Center for Stress Medicine, West China School of Basic Medical Sciences and Forensic Medicine and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yujing Huang
- Sichuan International Science and Technology Center for Stress Medicine, West China School of Basic Medical Sciences and Forensic Medicine and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yuyao Wu
- Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Macao 999078, China
| | - Huili Zhu
- Department of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Jing Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yuanyuan Zhang
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China
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Wang L, Li J, Tang P, Zhu D, Tai L, Wang Y, Miyata T, Woodgett JR, Di LJ. GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders. Circ Res 2025; 136:91-111. [PMID: 39629559 DOI: 10.1161/circresaha.124.325187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 11/18/2024] [Accepted: 11/20/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported. METHODS GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3βADKO and GSK3αADKO). A comprehensive whole-body metabolism analysis was performed on obese GSK3βADKO mice induced by a high-fat diet. RNA sequencing was conducted on AT of both obese GSK3βADKO and GSK3αADKO mice. Various analyses, including vessel perfusion studies, lipolysis analysis, multiplex protein assays, in vitro protein phosphorylation assays, and whole-mount histology staining, were performed on AT of obese GSK3βADKO mice. Tube-formation experiments were performed using 3B-11 endothelial cells cultured in the conditional medium of matured adipocytes under hypoxic conditions. Chromatin precipitation and immunofluorescence studies were conducted using cultured adipocytes with GSK3 inhibition. RESULTS Our findings provide the first evidence that adipocyte-specific knockout of GSK3β expands AT vascularization and mitigates obesity-related metabolic disorders. GSK3β deficiency, but not GSK3α, in adipocytes activates AMPK (AMP-activated protein kinase), leading to increased phosphorylation and nuclear accumulation of HIF-2α, resulting in enhanced transcriptional regulation. Consequently, adipocytes increased VEGF (vascular endothelial growth factor) expression, which engages VEGFR2 on endothelial cells, promoting angiogenesis, expanding the vasculature, and improving vessel perfusion within obese AT. GSK3β deficiency promotes AT remodeling, shifting unhealthy adipocyte function toward a healthier state by increasing insulin-sensitizing hormone adiponectin and preserving healthy adipocyte function. These effects lead to reduced fibrosis, reactive oxygen species, and ER (endoplasmic reticulum) stress in obese AT and improve metabolic disorders associated with obesity. CONCLUSIONS Deletion of GSK3β in adipocytes activates the AMPK/HIF-2α/VEGF/VEGFR2 axis, promoting vasculature expansion within obese AT. This results in a significantly improved local microenvironment, reducing inflammation and effectively ameliorating metabolic disorders associated with obesity.
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Affiliation(s)
- Li Wang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
- The Ministry of Education Frontiers Science Center for Precision Oncology (L.W., L.D.), University of Macau, China
- Proteomics, Metabolomics and Drug development core facility, Faculty of Health Sciences (L.W.), University of Macau, China
| | - Jiajia Li
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Ping Tang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Dongliang Zhu
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Lixin Tai
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Yuan Wang
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
| | - Tsukiko Miyata
- Lunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.)
| | - James R Woodgett
- Lunenfeld-Tanenbaum Research Institute, Sinai Health and Department of Medical Biophysics, University of Toronto, Ontario, Canada (T.M., J.R.W.)
| | - Li-Jun Di
- Department of Biomedical Sciences, Faculty of Health Sciences (L.W., J.L., P.T., D.Z., L.T., Y.W., L.D.), University of Macau, China
- The Ministry of Education Frontiers Science Center for Precision Oncology (L.W., L.D.), University of Macau, China
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Ying Z, Jiang K, Liu J, Zhao Y, Yao J, Ying X, Ren Y. Two new chromones from Portulaca oleracea L. and their bioactivities. Nat Prod Res 2025:1-8. [PMID: 39749406 DOI: 10.1080/14786419.2024.2447053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/27/2024] [Accepted: 12/22/2024] [Indexed: 01/04/2025]
Abstract
Two new chromones, oleracone H (1) and oleracone I (2), were isolated from Portulaca oleracea L. and identified by UV, IR, UHPLC-ESI-QTOF/MS, 1D NMR, 2D NMR, and CD spectra. In 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical quenching assay, oleracone H (1) and oleracone I (2) presented scavenging activities with IC50 values (half maximal inhibitory concentration) of 16.33 ± 0.20 μM and 22.36 ± 0.41 μM and the abilities of inhibiting the inflammatory factors IL-1β and TNF-α of the two compounds were superior to that of the positive control at 10 μM.
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Affiliation(s)
- Zheming Ying
- School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, P.R. China
| | - Kaiyun Jiang
- School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, P.R. China
| | - Jing Liu
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, P.R. China
| | - Yingdai Zhao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, P.R. China
| | - Junjie Yao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, P.R. China
| | - Xixiang Ying
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, P.R. China
| | - Yanling Ren
- School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, P.R. China
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Zhu S, Ruan F, Ye L, Jiang S, Yang C, Zuo Z, He C. Black phosphorus quantum dots induce lipid accumulation through PPARγ activation and mitochondrial dysfunction in adipocytes. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 958:177972. [PMID: 39662394 DOI: 10.1016/j.scitotenv.2024.177972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 12/02/2024] [Accepted: 12/04/2024] [Indexed: 12/13/2024]
Abstract
Black phosphorus quantum dots (BPQDs) are believed to have broad prospects for application. Obesity has garnered significant attention, but the association between BPQDs and lipid metabolism has not been thoroughly investigated. Mice were orally exposed to BPQDs at doses of 0.1 and 1 mg/kg for 28 d. The exposed mice exhibited reduced insulin sensitivity, hypertrophy of white adipose tissues, and reduced thermogenic function of brown adipose tissues. In white adipocyte line (3T3-L1), exposure to 5-20 μg/mL BPQDs induced lipid accumulation, oxidative stress, and upregulated the expression of PPARγ and genes involved in de novo lipogenesis. Moreover, both a reactive oxygen species (ROS) scavenger and a PPARγ inhibitor were able to attenuate lipid accumulation and downregulate the expression of lipid-associated genes in white adipocytes. In mouse brown adipocytes, BPQDs exposure caused oxidative stress, mitochondrial dysfunction, and downregulation of thermogenic genes such as UCP1. The ROS scavenger attenuated the oxidative stress and improved the mitochondrial thermogenic function in brown adipocytes. In summary, this work demonstrates that oxidative stress induced by BPQDs mediates the lipid accumulation possibly through PPARγ activation and mitochondrial dysfunction of adipose tissues, highlighting the potential obesogenic effect of BPQDs. Our findings provide novel insights into the biosafety of BPQDs and their potential health risks to humans, offering important considerations for the sustainable application of BP materials. ENVIRONMENTAL IMPLICATION: BPQDs are a novel type of nanomaterials with unique physicochemical properties, and have broad applications in various fields, particularly in biomedicine. However, during the production and use of BPQDs as medical materials, they inevitably contact with the human body for long periods of time. Therefore, it is necessary to investigate the effects of BPQDs on organisms under long-term exposure, especially lipid metabolism. This study would be helpful decreasing the environmental health risk of BP materials and promoting their sustainable development of nanotechnology in biomedicine.
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Affiliation(s)
- Sihao Zhu
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Fengkai Ruan
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Lingxiao Ye
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Suhua Jiang
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Chunyan Yang
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Zhenghong Zuo
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Chengyong He
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Department of Endocrinology, Xiang'an Hospital of Xiamen University, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China..
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Nath D, Barbhuiya PA, Sen S, Pathak MP. A Review on In-vivo and In-vitro Models of Obesity and Obesity-Associated Co-Morbidities. Endocr Metab Immune Disord Drug Targets 2025; 25:458-478. [PMID: 39136512 DOI: 10.2174/0118715303312932240801073903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 06/20/2024] [Accepted: 06/26/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Obesity is becoming a global pandemic with pandemic proportions. According to the WHO estimates, there were over 1.9 billion overweight individuals and over 650 million obese adults in the globe in 2016. In recent years, scientists have encountered difficulties in choosing acceptable animal models, leading to a multitude of contradicting aspects and incorrect outcomes. This review comprehensively evaluates different screening models of obesity and obesity-associated comorbidities to reveal the advantages and disadvantages/limitations of each model while also mentioning the time duration each model requires to induce obesity. METHODS For this review, the authors have gone through a vast number of article sources from different scientific databases, such as Google Scholar, Web of Science, Medline, and PubMed. RESULTS In-vivo models used to represent a variety of obesity-inducing processes, such as diet-induced, drug-induced, surgical, chemical, stress-induced, and genetic models, are discussed. Animal cell models are examined with an emphasis on their use in understanding the molecular causes of obesity, for which we discussed in depth the important cell lines, including 3T3-L1, OP9, 3T3-F442A, and C3H10T1/2. Screening models of obesity-associated co-morbidities like diabetes, asthma, cardiovascular disorders, cancer, and polycystic ovarian syndrome (PCOS) were discussed, which provided light on the complex interactions between obesity and numerous health problems. CONCLUSION Mimicking obesity in an animal model reflects multifactorial aspects is a matter of challenge. Future studies could address the ethical issues surrounding the use of animals in obesity research as well as investigate newly developed models, such as non-mammalian models. In conclusion, improving our knowledge and management of obesity and related health problems will require ongoing assessment and improvement of study models.
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Affiliation(s)
- Digbijoy Nath
- Faculty of Pharmaceutical Science, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
- Centre for Research on Ethnomedicine, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
| | - Pervej Alom Barbhuiya
- Faculty of Pharmaceutical Science, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
- Centre for Research on Ethnomedicine, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
| | - Saikat Sen
- Faculty of Pharmaceutical Science, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
- Centre for Research on Ethnomedicine, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
| | - Manash Pratim Pathak
- Faculty of Pharmaceutical Science, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
- Centre for Research on Ethnomedicine, Assam Down Town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, 781026, India
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Rahbari S, Sharifi SD, Salehi A, Pahlavan S, Honarbakhsh S. Omega-3 fatty acids mitigate histological changes and modulate the expression of ACACA, PFK1 and ET-1 genes in broiler chickens under environmental stress: a pulmonary artery, cardiomyocyte and liver study. Poult Sci 2024; 103:104387. [PMID: 39476610 PMCID: PMC11550354 DOI: 10.1016/j.psj.2024.104387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 10/01/2024] [Accepted: 10/01/2024] [Indexed: 11/13/2024] Open
Abstract
The aim of this study was to investigate the effects of omega-3 fatty acids on blood biochemical parameters, histological changes in pulmonary artery, cardiomyocytes, and liver, as well as the expression of ACACA, PFK1, and ET-1 genes in broiler chickens under environmental stress (high stoking density). A total of 420 one-day-old male Ross broilers were used in a 2 × 2 factorial arrangements, with 2 levels of environmental stress (without and with stress; 9 and 17 birds/m2, respectively) and 2 levels of omega-3 fatty acids (low and high; 0.057 and 0.5% of the diet, respectively) in a completely randomized design comprising 4 treatments and 5 replicates per each. The body weight decreased at d 40 because of environmental stress (P ≤ 0.05). The ascites heart index (AHI) in broilers fed high omega-3 fatty acids diets was lower (P = 0.062) than broiler fed low omega-3 fatty acids diet (0.279 vs. 0.316). Stressed birds showed a higher neutrophil: lymphocyte ratio compared to non-stressed birds (P ≤ 0.05). Broiler chickens receiving high omega-3 fatty acids diets exhibited elevated levels of hematocrit (HCT), hemoglobin (HGB), and lymphocytes (P ≤ 0.05). The neutrophil: lymphocyte ratio, and serum concentration of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) decreased in broilers fed high omega-3 fatty acids diets (P ≤ 0.05). In stressed broilers on a high omega-3 diet, pulmonary artery wall thickness decreased (P ≤ 0.05). Additionally, under stress, myocardial cell diameter, hepatocyte and cell nucleus diameter significantly increased (P ≤ 0.05). Stressed broilers showed an increased relative fold change in PFK1 enzyme activity but reduced ET-1 mRNA expression in the liver compared to stressed birds on a high omega-3 diet (P ≤0.05). In conclusion, the results indicate that dietary omega-3 fatty acids have the potential to alleviate the adverse histological changes in the pulmonary artery, cardiomyocytes, and liver, while also modulating the expression of genes ACACA, PFK1, and ET-1 that are influenced by environmental stress in broiler chickens.
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Affiliation(s)
- Shahgol Rahbari
- Department of Animal and Poultry Science, Faculty of Agricultural Technology, University of Tehran, Pakdasht, Tehran, Iran
| | - Seyed Davood Sharifi
- Department of Animal and Poultry Science, Faculty of Agricultural Technology, University of Tehran, Pakdasht, Tehran, Iran
| | - Abdolreza Salehi
- Department of Animal and Poultry Science, Faculty of Agricultural Technology, University of Tehran, Pakdasht, Tehran, Iran.
| | - Sara Pahlavan
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Shirin Honarbakhsh
- Department of Animal and Poultry Science, Faculty of Agricultural Technology, University of Tehran, Pakdasht, Tehran, Iran
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Gong Z, Zhang L, Shi Y. The potential role of uric acid in women with polycystic ovary syndrome. Gynecol Endocrinol 2024; 40:2323725. [PMID: 39718393 DOI: 10.1080/09513590.2024.2323725] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/23/2024] [Accepted: 02/21/2024] [Indexed: 12/25/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age and is associated with a variety of multi-system complications. The prevailing treatment strategy for PCOS is to individualize the interventions based on individual symptoms and patient complaints. However, optimal efficacy in treatment necessitates a focus on addressing the underlying pathogenic mechanisms. Uric acid (UA), the end product of purine metabolism, has been suggested to be involved in the development of several diseases, including PCOS. However, the precise mechanisms by which UA may affect PCOS remain incompletely understood. This literature review aims to investigate the correlation between UA and the various clinical presentations of PCOS, such as hyperandrogenism, insulin resistance (IR), ovulation disorders, obesity, and other related manifestations, through the analysis of epidemiological and clinical studies. The purpose of this study is to improve our comprehension of how UA contributes to each aspect of PCOS and their interrelationship, thus identifying the potential role of UA as a facilitator of PCOS. Furthermore, we explore potential pathways linking UA and PCOS, and propose therapeutic interventions based on these findings to optimize the management of this condition.
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Affiliation(s)
- Zhentao Gong
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
| | - Lingshan Zhang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Yingli Shi
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
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Ahmed I, Chakraborty R, Faizy AF, Moin S. Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review. J Diabetes Metab Disord 2024; 23:1699-1718. [PMID: 39610516 PMCID: PMC11599646 DOI: 10.1007/s40200-024-01496-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 08/21/2024] [Indexed: 11/30/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterised by impaired insulin secretion and action, often exacerbated by oxidative stress. Recent research has highlighted the intricate involvement of epigenetic mechanisms, particularly DNA methylation, in the pathogenesis of T2DM. This review aims to elucidate the role of DNA methylation as an epigenetic modifier in oxidative stress-mediated beta cell dysfunction, a key component of T2DM pathophysiology. Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defence mechanisms, is a hallmark feature of T2DM. Beta cells, responsible for insulin secretion, are particularly vulnerable to oxidative damage due to their low antioxidant capacity. Emerging evidence suggests that oxidative stress can induce aberrant DNA methylation patterns in beta cells, leading to altered gene expression profiles associated with insulin secretion and cell survival. Furthermore, studies have identified specific genes involved in beta cell function and survival that undergo DNA methylation changes in response to oxidative stress in T2DM. These epigenetic modifications can perpetuate beta cell dysfunction by dysregulating key pathways essential for insulin secretion, such as the insulin signalling cascade and mitochondrial function. Understanding the interplay between DNA methylation, oxidative stress, and beta cell dysfunction holds promise for developing novel therapeutic strategies for T2DM. Targeting aberrant DNA methylation patterns may offer new avenues for restoring beta cell function and improving glycemic control in patients with T2DM. However, further research is needed to elucidate the complex mechanisms underlying epigenetic regulation in T2DM and to translate these findings into clinical interventions.
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Affiliation(s)
- Istiaque Ahmed
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital Aligarh Muslim University, Aligarh, Uttar Pradesh 202002 India
| | - Ritoja Chakraborty
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital Aligarh Muslim University, Aligarh, Uttar Pradesh 202002 India
| | - Abul Faiz Faizy
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital Aligarh Muslim University, Aligarh, Uttar Pradesh 202002 India
| | - Shagufta Moin
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital Aligarh Muslim University, Aligarh, Uttar Pradesh 202002 India
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Shen R, Chen YX, Chen Y, Sayed ZN, Yi M, Sun C, Zhang B, Fang J. An activatable red emitting fluorescent probe for monitoring vicinal dithiol protein fluctuations in a stroke model. Chem Commun (Camb) 2024; 60:13774-13777. [PMID: 39499213 DOI: 10.1039/d4cc04971c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
Vicinal dithiol proteins (VDPs) facilitate cellular redox homeostasis, modulate protein synthesis and participate in post-translational modifications through the dynamic equilibrium of dithiol and disulfide bonds. Herein, an activatable red emitting fluorescent probe, VDP-red, is developed for detecting VDPs. With the aid of this probe, we have discovered for the first time a reduction in the levels of reduced VDPs in a stroke mouse model. This work provides a fresh viewpoint for understanding stroke mechanisms.
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Affiliation(s)
- Ruipeng Shen
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Ya-Xiong Chen
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Yating Chen
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Zahid Nasim Sayed
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Meirong Yi
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Chunlin Sun
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Baoxin Zhang
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Jianguo Fang
- State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
- School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, China.
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Huang J, Zhang J, Li L, Chen M, Li Y, Yu X, Dong S, Wang Q, Chen J, Yang Q, Xu S. Triglyceride-glucose index and hsCRP-to-albumin ratio as predictors of major adverse cardiovascular events in STEMI patients with hypertension. Sci Rep 2024; 14:28112. [PMID: 39548181 PMCID: PMC11567964 DOI: 10.1038/s41598-024-79673-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 11/11/2024] [Indexed: 11/17/2024] Open
Abstract
This study aimed to evaluate the association between the triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein-to-albumin ratio (hsCAR) and the prognosis of patients with STEMI and hypertension. A total of 699 patients diagnosed with STEMI and hypertension were included in this study database. Compared to the low TyG index group (< 7.8), the high TyG index group (≥ 7.8) was associated with an increased risk of MACE (HR 2.09, 95% CI = 1.58-2.77; P < 0.001). Similarly, a higher hsCAR (≥ 0.15) was linked to an increased risk of MACE (HR 1.46, 95% CI = 1.12-1.90; P = 0.005). Subsequently, we categorized the population into four groups based on the defined cutoff points. Compared to the low TyG-low hsCAR subgroup, the other three subgroups demonstrated an elevated risk of MACE. Among patients treated with PCSK9 and SGLT2 inhibitors, the combined effect of the TyG index and hsCAR on MACE was attenuated. Finally, The combined TyG index and hsCAR model exhibited optimal performance (AUC = 0.71, 95% CI = 0.67-0.75; P < 0.001). This study demonstrates that the TyG index and hsCAR provide strong combined predictive power. The synergistic utilization offers a comprehensive approach to cardiovascular risk assessment.
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Affiliation(s)
- Jinyong Huang
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Junyi Zhang
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Linjie Li
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Meiyan Chen
- Department of Emergency, Qilu Hospital of Shandong University, Shandong, China
| | - Yongle Li
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Xiangdong Yu
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Shaozhuang Dong
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Qing Wang
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Jun Chen
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Qing Yang
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Shaopeng Xu
- Department of Cardiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
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Bucarey JL, Trujillo-González I, Paules EM, Espinosa A. Myokines and Their Potential Protective Role Against Oxidative Stress in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Antioxidants (Basel) 2024; 13:1363. [PMID: 39594505 PMCID: PMC11591161 DOI: 10.3390/antiox13111363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/04/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024] Open
Abstract
Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver's antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health.
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Affiliation(s)
- José Luis Bucarey
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile;
| | - Isis Trujillo-González
- Nutrition Research Institute, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; (I.T.-G.); (E.M.P.)
| | - Evan M. Paules
- Nutrition Research Institute, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; (I.T.-G.); (E.M.P.)
| | - Alejandra Espinosa
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile;
- Center of Interdisciplinary Biomedical and Engineering Research for Health, Universidad de Valparaíso, San Felipe 2172972, Chile
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Li N, Hao L, Li S, Deng J, Yu F, Zhang J, Nie A, Hu X. The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease. J Inflamm Res 2024; 17:8061-8083. [PMID: 39512865 PMCID: PMC11542495 DOI: 10.2147/jir.s490418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 10/18/2024] [Indexed: 11/15/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder with a rising prevalence. It begins with lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD is complex and involves multiple factors, with oxidative stress playing a crucial role. Oxidative stress drives the progression of MASLD by causing cellular damage, inflammatory responses, and fibrosis, making it a key pathogenic mechanism. The Nuclear Factor Erythroid 2-Related Factor 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against a spectrum of endogenous and exogenous insults, particularly oxidative stress. It plays a pivotal role in mediating antioxidant, anti-inflammatory, and anti-apoptotic responses. Many studies indicate that activating the Nrf2/HO-1 signaling pathway can significantly mitigate the progression of MASLD. This article examines the role of the Nrf2/HO-1 signaling pathway in MASLD and highlights natural compounds that protect against MASLD by targeting Nrf2/HO-1 activation. The findings indicate that the Nrf2/HO-1 signaling pathway holds great promise as a therapeutic target for MASLD.
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Affiliation(s)
- Na Li
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Liyuan Hao
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Shenghao Li
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Jiali Deng
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Fei Yu
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Junli Zhang
- Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, People's Republic of China
| | - Aiyu Nie
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Xiaoyu Hu
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
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Fiorenza M, Onslev J, Henríquez-Olguín C, Persson KW, Hesselager SA, Jensen TE, Wojtaszewski JFP, Hostrup M, Bangsbo J. Reducing the mitochondrial oxidative burden alleviates lipid-induced muscle insulin resistance in humans. SCIENCE ADVANCES 2024; 10:eadq4461. [PMID: 39475607 PMCID: PMC11524190 DOI: 10.1126/sciadv.adq4461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 09/23/2024] [Indexed: 11/02/2024]
Abstract
Preclinical models suggest mitochondria-derived oxidative stress as an underlying cause of insulin resistance. However, it remains unknown whether this pathophysiological mechanism is conserved in humans. Here, we used an invasive in vivo mechanistic approach to interrogate muscle insulin action while selectively manipulating the mitochondrial redox state in humans. To this end, we conducted insulin clamp studies combining intravenous infusion of a lipid overload with intake of a mitochondria-targeted antioxidant (mitoquinone). Under lipid overload, selective modulation of mitochondrial redox state by mitoquinone enhanced insulin-stimulated glucose uptake in skeletal muscle. Mechanistically, mitoquinone did not affect canonical insulin signaling but augmented insulin-stimulated glucose transporter type 4 (GLUT4) translocation while reducing the mitochondrial oxidative burden under lipid oversupply. Complementary ex vivo studies in human muscle fibers exposed to high intracellular lipid levels revealed that mitoquinone improves features of mitochondrial bioenergetics, including diminished mitochondrial H2O2 emission. These findings provide translational and mechanistic evidence implicating mitochondrial oxidants in the development of lipid-induced muscle insulin resistance in humans.
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Affiliation(s)
- Matteo Fiorenza
- August Krogh Section for Human Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
| | - Johan Onslev
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Carlos Henríquez-Olguín
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
- Exercise Science Laboratory, Faculty of Medicine, Universidad Finis Terrae, Santiago 1509, Chile
| | - Kaspar W. Persson
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Sofie A. Hesselager
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Thomas E. Jensen
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Jørgen F. P. Wojtaszewski
- August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Morten Hostrup
- August Krogh Section for Human Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
| | - Jens Bangsbo
- August Krogh Section for Human Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, Denmark
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40
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Rehan I, Khan S, Ullah R. Integrating Laser-Induced Breakdown Spectroscopy and Ensemble Learning as Minimally Invasive Optical Screening for Diabetes. APPLIED SPECTROSCOPY 2024; 78:1154-1163. [PMID: 39233644 DOI: 10.1177/00037028241278902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/06/2024]
Abstract
Diabetes mellitus is a prevalent chronic disease necessitating timely identification for effective management. This paper introduces a reliable, straightforward, and efficient method for the minimally invasive identification of diabetes mellitus through nanosecond pulsed laser-induced breakdown spectroscopy (LIBS) by integrating a state-of-the-art machine learning approach. LIBS spectra were collected from urine samples of diabetic and healthy individuals. Principal component analysis and an ensemble learning classification model were used to identify significant changes in LIBS peak intensity between the diseased and normal urine samples. The model, integrating six distinct classifiers and cross-validation techniques, exhibited high accuracy (96.5%) in predicting diabetes mellitus. Our findings emphasize the potential of LIBS for diabetes mellitus identification in urine samples. This technique may hold potential for future applications in diagnosing other health conditions.
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Affiliation(s)
- Imran Rehan
- Department of Physics, Islamia College University Peshawar, Khyber Pakhtunkhwa, Pakistan
- National Institute of Lasers and Optronics College, Pakistan Institute of Engineering and Applied Sciences, Nilore, Islamabad, Pakistan
| | - Saranjam Khan
- Department of Physics, Islamia College University Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Rahat Ullah
- National Institute of Lasers and Optronics College, Pakistan Institute of Engineering and Applied Sciences, Nilore, Islamabad, Pakistan
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Clemen R, Dethloff W, Berner J, Schulan P, Martinet A, Weltmann KD, von Woedtke T, Grune T, Wende K, Bekeschus S. Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles. Redox Biol 2024; 77:103372. [PMID: 39378614 PMCID: PMC11492613 DOI: 10.1016/j.redox.2024.103372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/10/2024] Open
Abstract
Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.
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Affiliation(s)
- Ramona Clemen
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany
| | - Wiebke Dethloff
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany
| | - Julia Berner
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany; Department of Dermatology and Venerology, Rostock University Medical Center, 18057, Rostock, Germany
| | - Paul Schulan
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany
| | - Alice Martinet
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany; Department of Dermatology and Venerology, Rostock University Medical Center, 18057, Rostock, Germany
| | - Klaus Dieter Weltmann
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany
| | - Thomas von Woedtke
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany; Institute for Hygiene and Environmental Medicine, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475, Greifswald, Germany
| | - Tilman Grune
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, 10785, Berlin, Germany; German Center for Diabetes Research (DZD), 85764, Muenchen-Neuherberg, Germany; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany; Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, 1090, Austria
| | - Kristian Wende
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany
| | - Sander Bekeschus
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489, Greifswald, Germany; Department of Dermatology and Venerology, Rostock University Medical Center, 18057, Rostock, Germany.
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Jia F, Sun J, Liu X, Liu Y. Life Essentials 8 score and risk of metabolic syndrome: A dose-response analysis in the US population. PLoS One 2024; 19:e0312674. [PMID: 39480760 PMCID: PMC11527257 DOI: 10.1371/journal.pone.0312674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 10/11/2024] [Indexed: 11/02/2024] Open
Abstract
BACKGROUND There is limited research on the relationship between Life Essentials 8 (LE8) score and metabolic syndrome (MetS). Our aim is to examine the association between LE8 cardiovascular health metrics and risk of MetS in a nationally representative sample. METHODS We conducted a cross-sectional study using data from 23,253 adults aged ≥20 years from the National Health and Nutrition Examination Survey (2005-2018). LE8 score (range 0-100) was calculated based on the American Heart Association's definitions of ideal cardiovascular health behaviors (physical activity, diet, smoking, and body mass index) and factors (total cholesterol, blood pressure, fasting plasma glucose, and fasting triglycerides). Metabolic syndrome comprises a cluster of metabolic disorders, including obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariable logistic regression and restricted cubic spline models, mediation analysis, subgroup analysis and weighted quantile sum (WQS) regression were used to assess the relationship between LE8 score and MetS risk. RESULTS A total of 23,253 participants were included, of whom 7,932 had MetS and 15,321 did not. The average age of the participants was 50.7 years (standard deviation (SD) 12.3), with 49.24% being male. Participants with high LE8 category (80-100 points) had 98% lower odds of having MetS compared to those with low LE8 category (0-49 points) after adjusting for potential confounders (adjusted odds ratio [OR]: 0.02; 95% confidence interval [CI]: 0.02-0.03; P < 0.001). There was a monotonic decreasing dose-response relationship between LE8 score and predicted probability of MetS (P-overall <0.001; P-nonlinear <0.001). Several biomarkers including serum albumin, uric acid and neutrophil count emerged as potential mediators. CONCLUSIONS While our studies suggest a potential association between cardiovascular health factors and reduced MetS risk, the cross-sectional nature of our study limits causal inferences. The LE8 score could still serve as a useful screening tool to identify individuals at high risk for MetS, facilitating targeted prevention and treatment strategies.
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Affiliation(s)
- Feng Jia
- The First Hospital of Jilin University, Changchun, China
| | - Jiaxuan Sun
- The First Hospital of Jilin University, Changchun, China
| | - Xiangliang Liu
- The First Hospital of Jilin University, Changchun, China
| | - Yahui Liu
- The First Hospital of Jilin University, Changchun, China
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43
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Spinedi E, Docena GH. Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation. Int J Mol Sci 2024; 25:11741. [PMID: 39519291 PMCID: PMC11546880 DOI: 10.3390/ijms252111741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/23/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
White adipose tissue (WAT) and the gut are involved in the development of neuroinflammation when an organism detects any kind of injury, thereby triggering metainflammation. In fact, the autonomous nervous system innervates both tissues, although the complex role played by the integrated sympathetic, parasympathetic, and enteric nervous system functions have not been fully elucidated. Our aims were to investigate the participation of inflamed WAT and the gut in neuroinflammation. Firstly, we conducted an analysis into how inflamed peripheral WAT plays a key role in the triggering of metainflammation. Indeed, this included the impact of the development of local insulin resistance and its metabolic consequences, a serious hypothalamic dysfunction that promotes neurodegeneration. Then, we analyzed the gut-brain axis dysfunction involved in neuroinflammation by examining cell interactions, soluble factors, the sensing of microbes, and the role of dysbiosis-related mechanisms (intestinal microbiota and mucosal barriers) affecting brain functions. Finally, we targeted the physiological crosstalk between cells of the brain-WAT-gut axis that restores normal tissue homeostasis after injury. We concluded the following: because any injury can result not only in overall insulin resistance and dysbiosis, which in turn can impact upon the brain, but that a high-risk of the development of neuroinflammation-induced neurodegenerative disorder can also be triggered. Thus, it is imperative to avoid early metainflammation by applying appropriate preventive (e.g., lifestyle and diet) or pharmacological treatments to cope with allostasis and thus promote health homeostasis.
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Affiliation(s)
- Eduardo Spinedi
- Centro de Endocrinología Experimental y Aplicada (CENEXA-UNLP-CONICET-CICPBA), University of La Plata Medical School, La Plata 1900, Argentina
| | - Guillermo Horacio Docena
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP-UNLP-CONICET-CICPBA), School of Sciences, University of La Plata, La Plata 1900, Argentina
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44
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Superti F, Russo R. Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. Antioxidants (Basel) 2024; 13:1228. [PMID: 39456481 PMCID: PMC11505271 DOI: 10.3390/antiox13101228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/26/2024] [Accepted: 10/09/2024] [Indexed: 10/28/2024] Open
Abstract
Alpha-lipoic acid (ALA) is a bioactive molecule with significant health effects. The biological action of ALA has been ascribed to the characteristic antioxidant properties of the oxidized form (ALA) and its reduced counterpart the dihydrolipoic acid (DHLA) system. The ALA/DHLA combination represents an ideal antioxidant since it can quench radicals, is able to chelate metals, is amphiphilic, and has no major adverse effects. This unique system is able to scavenge reactive oxygen species, exerting a major effect on tissue levels of reduced forms of other antioxidants, including glutathione. For this reason, ALA is also known as the "antioxidant of antioxidants". This review analyzes the antioxidant, anti-inflammatory, and neuroprotective effects of ALA and discusses its applications as an ameliorative tool for chronic diseases and those associated with oxidative stress. Results from in vitro and in vivo studies demonstrated that ALA modulates various oxidative stress pathways suggesting its application, alone or in combination with other functional substances, as a useful support in numerous conditions, in which the balance oxidant-antioxidant is disrupted, such as neurodegenerative disorders. Based on several successful clinical studies, it has been also established that oral ALA supplements are clinically useful in relieving the complications of diabetes and other disorders including cardiovascular diseases and nerve discomforts suggesting that ALA can be considered a useful approach to improving our health.
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Affiliation(s)
- Fabiana Superti
- Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, RM, Italy;
- Association for Research on Integrative Oncology Therapies, (ARTOI) Foundation, Via Ludovico Micara, 73, 00165 Rome, RM, Italy
| | - Rosario Russo
- Giellepi S.p.A., Via G. Verdi, 41/Q, 20831 Seregno, MB, Italy
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45
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Sobieska K, Buczyńska A, Krętowski AJ, Popławska-Kita A. Iron homeostasis and insulin sensitivity: unraveling the complex interactions. Rev Endocr Metab Disord 2024; 25:925-939. [PMID: 39287729 PMCID: PMC11470850 DOI: 10.1007/s11154-024-09908-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2024] [Indexed: 09/19/2024]
Abstract
Diabetes has arisen as a noteworthy global health issue, marked by escalating incidence and mortality rates. Insulin, crucial for preserving euglycemia, acts as a vital energy provider for various tissues. Iron metabolism notably plays a significant role in the development of insulin resistance, a key factor in the onset of various metabolic disorders. The intricate interaction between iron and insulin signaling encompasses complex regulatory mechanisms at the molecular level, thereby impacting cellular reactions to insulin. The intricate interplay between insulin and glucagon, essential for precise regulation of hepatic glucose production and systemic glucose levels, may be influenced by certain microelements for instance zinc, copper, iron, boron, calcium, cobalt, chromium, iodine, magnesium and selenium. While significant progress has been achieved in elucidating the pathophysiological connections between iron overload and glucose metabolism, our understanding of the involvement of the Fenton reaction and oxidative stress in insulin resistance influencing many chronical conditions remains limited. Furthermore, the exploration of the multifaceted roles of insulin in the human body continues to be a subject of active investigation by numerous scientific researchers. This review comprehensively outlines the potential adverse impact of iron overload on insulin function and glucose metabolism. Additionally, we provide a synthesis of findings derived from various research domains, encompassing population studies, animal models, and clinical investigations, to scrutinize the multifaceted relationship between iron and insulin sensitivity. Moreover, we delineate instances of correlations between serum iron levels and various medical conditions, including the diabetes also gestational diabetes and obesity.
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Affiliation(s)
- Katarzyna Sobieska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Angelika Buczyńska
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Adam Jacek Krętowski
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Anna Popławska-Kita
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
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46
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Geaneotes PJ, Janosko CP, Afeke C, Deiters A, Floreancig PE. Potent and Selective Oxidatively Labile Ether-Based Prodrugs through Late-Stage Boronate Incorporation. Angew Chem Int Ed Engl 2024; 63:e202409229. [PMID: 38986017 DOI: 10.1002/anie.202409229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/09/2024] [Accepted: 07/09/2024] [Indexed: 07/12/2024]
Abstract
This manuscript describes a new strategy for prodrug synthesis in which a relatively inert ether group is introduced at an early stage in a synthetic sequence and functionalized in the final step to introduce a prodrug-activating group through a chemoselective process. Boryl allyloxy (BAO) ether groups are synthesized through several metal-mediated processes to form entities that are readily cleaved under oxidative conditions commonly found in cancer cells. The high cleavage propensity of the BAO group allows for ether cleavage, making these compounds substantially more hydrolytically stable in comparison to acyl-linked prodrugs while retaining the ability to release alcohols. We report the preparation of prodrug analogues of the natural products camptothecin and pederin from acetal precursors that serve as protecting groups in their synthetic sequences. The BAO acetal groups cleave in the presence of hydrogen peroxide to release the cytotoxic agents. The pederin-based prodrug shows dramatically greater cytotoxicity than negative controls and outstanding selectivity and potency toward cancer cell lines in comparison to non-cancerous cell lines. This late-stage functionalization approach to prodrug synthesis should be applicable to numerous systems that can be accessed through chemoselective processes.
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Affiliation(s)
- Paul J Geaneotes
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
| | - Chasity P Janosko
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
| | - Cephas Afeke
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
| | - Alexander Deiters
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
| | - Paul E Floreancig
- Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA
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Lin Y, Wang Y, Zhang Q, Gao R, Chang F, Li B, Huang K, Cheng N, He X. Single-Atom Ce-N-C Nanozyme Ameliorates Type 2 Diabetes Mellitus by Improving Glucose Metabolism Disorders and Reducing Oxidative Stress. Biomolecules 2024; 14:1193. [PMID: 39334959 PMCID: PMC11430424 DOI: 10.3390/biom14091193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/16/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) as a chronic metabolic disease has become a global public health problem. Insulin resistance (IR) is the main pathogenesis of T2DM. Oxidative stress refers to an imbalance between free radical production and the antioxidant system, causing insulin resistance and contributing to the development of T2DM via several molecular mechanisms. Besides, the reduction in hepatic glycogen synthesis also leads to a decrease in peripheral insulin sensitivity. Thus, reducing oxidative stress and promoting glycogen synthesis are both targets for improving insulin resistance and treating T2DM. The current study aims to investigate the pharmacological effects of single-atom Ce-N-C nanozyme (SACe-N-C) on the improvement of insulin resistance and to elucidate its underlying mechanisms using HFD/STZ-induced C57BL/6J mice and insulin-resistant HepG2 cells. The results indicate that SACe-N-C significantly improves hepatic glycogen synthesis and reduces oxidative stress, as well as pancreatic and liver injury. Specifically, compared to the T2DM model group, fasting blood glucose decreased by 29%, hepatic glycogen synthesis increased by 17.13%, and insulin secretion increased by 18.87%. The sod and GPx in the liver increased by 17.80% and 25.28%, respectively. In terms of mechanism, SACe-N-C modulated glycogen synthesis through the PI3K/AKT/GSK3β signaling pathway and activated the Keap1/Nrf2 pathway to alleviate oxidative stress. Collectively, this study suggests that SACe-N-C has the potential to treat T2DM.
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Affiliation(s)
- Yitong Lin
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yanan Wang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Qi Zhang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Ruxin Gao
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Fei Chang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Boran Li
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Kunlun Huang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of China, Beijing 100083, China
| | - Nan Cheng
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xiaoyun He
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of China, Beijing 100083, China
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Kuretu A, Mothibe M, Ngubane P, Sibiya N. Elucidating the effect of drug-induced mitochondrial dysfunction on insulin signaling and glucose handling in skeletal muscle cell line (C2C12) in vitro. PLoS One 2024; 19:e0310406. [PMID: 39288128 PMCID: PMC11407670 DOI: 10.1371/journal.pone.0310406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 08/31/2024] [Indexed: 09/19/2024] Open
Abstract
Efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine and clarithromycin are known potential mitochondrial toxicants. Mitochondrial toxicity has been reported to disrupt the chain of events in the insulin signalling pathway. Considering the upward trajectory of diabetes mellitus prevalence, studies which seek to uncover probable risk factors for developing diabetes should be encouraged. This study aimed to evaluate the intracellular mechanisms leading to the development of insulin resistance in the presence of various conventional pharmacological agents reported as potential mitochondrial toxicants in skeletal muscle cell line. Differentiated C2C12 preparations were exposed to multiple concentrations of efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine, and clarithromycin, separately. Glucose handling was evaluated by observing the changes in insulin-stimulated glucose uptake and assessing the changes in GLUT4 translocation, GLUT4 expression and Akt expression. The changes in mitochondrial function were evaluated by assessing mitochondrial membrane integrity, cellular ATP production, generation of intracellular reactive oxygen species, expression of tafazzin and quantification of medium malonaldehyde. Insulin stimulated glucose uptake was perturbed in C2C12 pre-treated with potential mitotoxicants. Additionally, ATP synthesis, alterations in mitochondrial membrane potential, excessive accumulation of ROS and malonaldehyde were observed in the presence of potential mitotoxicants. Particularly, we observed suppression of proteins involved in the insulin signalling pathway and maintenance of mitochondrial function namely GLUT4, Akt and tafazzin. Mitochondrial toxicants can potentially induce insulin resistance emanating from mitochondrial dysfunction. These new findings will contribute to the understanding of underlying mechanisms involved in the development of insulin resistance linked to mitochondrial dysfunction.
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Affiliation(s)
- Auxiliare Kuretu
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
| | - Mamosheledi Mothibe
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
| | - Phikelelani Ngubane
- School of Medical Sciences and Laboratory Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Ntethelelo Sibiya
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
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Mirnic J, Djuric M, Brkic S, Gusic I, Stojilkovic M, Tadic A, Veljovic T. Pathogenic Mechanisms That May Link Periodontal Disease and Type 2 Diabetes Mellitus-The Role of Oxidative Stress. Int J Mol Sci 2024; 25:9806. [PMID: 39337292 PMCID: PMC11432179 DOI: 10.3390/ijms25189806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/04/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Given the posited role of oxidative stress in the pathogenesis of both periodontitis and type 2 diabetes mellitus (T2DM), it may also serve as a link between these highly prevalent chronic inflammatory diseases. This view is supported by an ample body of evidence indicating that the severity and progression of periodontitis is in part driven by diabetes, while periodontal infection may hinder the attainment of adequate glycemic control in diabetic patients. Thus, this review focuses on the potential synergistic interactions along the oxidative stress-inflammation pathway characterizing both conditions. Because periodontitis and T2DM share the same risk factors and compromise patients' quality of life, to develop effective strategies for combatting both conditions, their mutual influence needs to be explored.
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Affiliation(s)
- Jelena Mirnic
- Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.S.); (T.V.)
| | - Milanko Djuric
- Dentistry Clinic of Vojvodina, Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.D.); (I.G.); (A.T.)
| | - Snezana Brkic
- Clinic for Infectious Diseases, Clinical Centre of Vojvodina, Department of Infectious Diseases, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Ivana Gusic
- Dentistry Clinic of Vojvodina, Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.D.); (I.G.); (A.T.)
| | - Marija Stojilkovic
- Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.S.); (T.V.)
| | - Ana Tadic
- Dentistry Clinic of Vojvodina, Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.D.); (I.G.); (A.T.)
| | - Tanja Veljovic
- Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (M.S.); (T.V.)
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50
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Xie Y, Gu Y, Li Z, He B, Zhang L. Effects of Different Exercises Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis. Nutrients 2024; 16:3007. [PMID: 39275322 PMCID: PMC11397086 DOI: 10.3390/nu16173007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 09/16/2024] Open
Abstract
BACKGROUND Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy. METHODS We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: "Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis" (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves. RESULTS The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (-3.64, 9.52); 2.37 (-0.40, 5.15); 1.80 (-1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (-0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (-0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (-1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are -1.60 (-6.98, 3.78); -2.76 (-7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are -0.52 (-2.58, 1.55); -1.83 (-4.71, 1.04); -2.46 (-5.69,0.76).). CONCLUSION Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal.
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Affiliation(s)
- Yongchao Xie
- Centre for Sport Nutrition and Health, Centre for Nutritional Ecology, School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou 450001, China; (Y.X.); (Z.L.)
| | - Yu Gu
- Henan Sports Medicine and Rehabilitation Center, Henan Sport University, Zhengzhou 450044, China;
| | - Zhen Li
- Centre for Sport Nutrition and Health, Centre for Nutritional Ecology, School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou 450001, China; (Y.X.); (Z.L.)
| | - Bingchen He
- Department of Physical Education, South China University of Technology, Guangzhou 510641, China;
| | - Lei Zhang
- Centre for Sport Nutrition and Health, Centre for Nutritional Ecology, School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou 450001, China; (Y.X.); (Z.L.)
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