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Fu X, Zhang H, Liu J, Li Y, Wang Z, Yang S, Liu D, Zhou Y, Chen P, DiSanto ME, Li H, Zhang X. Midline-1 inhibited high glucose-induced epithelial-mesenchymal transition, fibrosis and inflammation through WNT/β-catenin signaling in benign prostatic hyperplasia. Front Endocrinol (Lausanne) 2025; 16:1543295. [PMID: 40206598 PMCID: PMC11978649 DOI: 10.3389/fendo.2025.1543295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/07/2025] [Indexed: 04/11/2025] Open
Abstract
Background and objects Benign prostatic hyperplasia (BPH) is a common disease that impairs the life quality of elderly men. The close relationship of BPH and diabetes has been generally established, however, the exact molecular mechanism remains unclear. Midline-1 (MID1) is an E3 ubiquitin ligase belonging to Tripartite Motif family and its involvement in the initiation and progression of many diseases, such as diabetic kidney disease has been well accepted. This study aims to illuminate the potential impact of high glucose (HG) on prostatic cells and elucidate the molecular role of MID1 in the development of BPH. Methods In this work, human prostate specimens and cultured human prostate cell lines (BPH-1 and WPMY-1) were employed. The impact of HG treatment on these two lines was assessed and the expression and localization of MID1, along with its potential downstream target protein phosphatase 2A (PP2A), were determined using multiple experimental methods. MID1-overexpressing cell models were further used to investigate the function of MID1 in regulating inflammation, fibrosis and epithelial-mesenchymal transition (EMT). Results Herein we demonstrate diabetic individuals with BPH had lower expression of MID1 and higher expression of the catalytic subunit of PP2A (PP2Ac), larger prostate volume, higher international prostate symptom score (IPSS) and lower Qmax than non-diabetic groups. On a cellular level, HG treatment inhibited the expression of MID1, thus stimulating cellular proliferation and triggering EMT, fibrosis and inflammation of two prostatic cells via enhanced WNT/β-catenin signaling. Conclusions In general, our novel data demonstrate targeting MID1 might be a promising area of medical treatment for patients with both BPH and diabetes.
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Affiliation(s)
- Xun Fu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Urology, Peking Union Medical Collage Hospital, Beijing, China
| | - Hao Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jiang Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yan Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhen Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shu Yang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Daoquan Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yongying Zhou
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ping Chen
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Michael E. DiSanto
- Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, United States
| | - Hongjun Li
- Department of Urology, Peking Union Medical Collage Hospital, Beijing, China
| | - Xinhua Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Liu M, Chen R, Zheng Z, Xu S, Hou C, Ding Y, Zhang M, Bao M, He B, Li S. Mechanisms of inflammatory microenvironment formation in cardiometabolic diseases: molecular and cellular perspectives. Front Cardiovasc Med 2025; 11:1529903. [PMID: 39877020 PMCID: PMC11772298 DOI: 10.3389/fcvm.2024.1529903] [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: 11/18/2024] [Accepted: 12/26/2024] [Indexed: 01/31/2025] Open
Abstract
Cardiometabolic diseases (CMD) are leading causes of death and disability worldwide, with complex pathophysiological mechanisms in which inflammation plays a crucial role. This review aims to elucidate the molecular and cellular mechanisms within the inflammatory microenvironment of atherosclerosis, hypertension and diabetic cardiomyopathy. In atherosclerosis, oxidized low-density lipoprotein (ox-LDL) and pro-inflammatory cytokines such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) activate immune cells contributing to foam cell formation and arterial wall thickening. Hypertension involves the activation of the renin-angiotensin system (RAS) alongside oxidative stress-induced endothelial dysfunction and local inflammation mediated by T cells. In diabetic cardiomyopathy, a high-glucose environment leads to the accumulation of advanced glycation end products (AGEs), activating the Receptor for Advanced Glycation Endproducts (RAGE) and triggering inflammatory responses that further damage cardiac and microvascular function. In summary, the inflammatory mechanisms in different types of metabolic cardiovascular diseases are complex and diverse; understanding these mechanisms deeply will aid in developing more effective individualized treatment strategies.
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Affiliation(s)
- Menghua Liu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Rumeng Chen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiwei Zheng
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Shuling Xu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Chunyan Hou
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yining Ding
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Mengling Zhang
- School of Stomatology, Changsha Medical University, Changsha, China
| | - Meihua Bao
- Hunan key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China
| | - Binsheng He
- Hunan key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China
| | - Sen Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
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Amer J, Amleh A, Salhab A, Kolodny Y, Yochelis S, Saffouri B, Paltiel Y, Safadi R. High-fat diet mouse model receiving L-glucose supplementations propagates liver injury. Front Nutr 2024; 11:1469952. [PMID: 39742098 PMCID: PMC11687001 DOI: 10.3389/fnut.2024.1469952] [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: 07/24/2024] [Accepted: 11/11/2024] [Indexed: 01/03/2025] Open
Abstract
Background and aims Limited data link manufactured sweeteners impact on metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the effects of manufactured sugars (L-glucose) compared to natural sugars (D-glucose) on phenotype, molecular and metabolic changes in mice models fed with either regular diet (RD) or high fat diet (HFD). Methods C57BL/6 mice fed 16-weeks with either RD; 70% carbohydrate or HFD; 60% fat, with or without additional glucose (Glu, at 18% w/v) to drinking tap water at weeks 8-16; of either natural (D-Glu) or manufactured (L-Glu) sugars. Liver inflammation (ALT and AST serum levels, liver H&E histologic stains and cell viability profile by p-AKT), liver fibrosis [quantitated α smooth-muscle-actin (αSMA) by western blot and RT-PCR, Masson Trichrome staining (MTC) of liver tissue], liver lipid [steatosis stain by H&E, Adipose Differentiation-Related Protein (ADRP) lipid accumulation, serum and lipid peroxidation Malondialdehyde (MDA) markers by ELISA], glucose hemostasis (serum Glucose and C-peptide with HOMA-IR score calculation) and liver aspects [hepatic glucose transporter 2 (GLUT2), insulin receptor (IR) expressions and GYS2/PYGL ratio] evaluated. Results D- and L-Glu supplementations propagate hepatocytes ballooning and steatosis in HFD-fed mice and were associated with αSMA down-expressions by 1.5-fold compared to the untreated group while showed an acceleration in liver fibrosis in the RD-fed mice. Lipid profile (Steatosis, ADRP and MDA) significantly increased in HFD-fed mice, both Glu supplementations (mainly the L-Glu) increased serum MDA while decreased ADRP. HOMA-IR score and IR significantly increased in HFD-fed mice, with further elevation in HOMA-IR score following Glu supplementations (mainly L-Glu). The increase in HOMA-IR negatively correlated with IR and Glut2 expressions. D- and L-Glu supplementations showed significant decrease of Glycogenesis (low GYS2/PYGL ratio) and unchanged p-AKT pattern compared to their RD counterparts. Conclusion Our data indicate an increase in rate of de-novo lipogenesis (DNL) in RD-fed mice (High carbohydrate diet) and liver fibrosis following additional sugar supplementations. In contrast, HFD-fed mice (with pre-existing high lipid profile) supplemented with sugar showed less liver fibrosis, because of reduced de-novo fatty acids synthesis and subsequently, the lipid oxidation pathways become dominated and induce the net results of lipid clearance.
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Affiliation(s)
- Johnny Amer
- Liver Institute, Hadassah-Hebrew University Hospital, Jerusalem, Israel
| | - Athar Amleh
- Liver Institute, Hadassah-Hebrew University Hospital, Jerusalem, Israel
| | - Ahmad Salhab
- Liver Institute, Hadassah-Hebrew University Hospital, Jerusalem, Israel
| | - Yuval Kolodny
- Applied Physics Department, Center for Nanoscience and Nanotechnology, Hebrew University Givaat Ram, Jerusalem, Israel
| | - Shira Yochelis
- Applied Physics Department, Center for Nanoscience and Nanotechnology, Hebrew University Givaat Ram, Jerusalem, Israel
| | - Baker Saffouri
- Liver Institute, Hadassah-Hebrew University Hospital, Jerusalem, Israel
| | - Yossi Paltiel
- Applied Physics Department, Center for Nanoscience and Nanotechnology, Hebrew University Givaat Ram, Jerusalem, Israel
| | - Rifaat Safadi
- Liver Institute, Hadassah-Hebrew University Hospital, Jerusalem, Israel
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Lu JC, Lee P, Ierino F, MacIsaac RJ, Ekinci E, O’Neal D. Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery. J Diabetes Sci Technol 2024; 18:1500-1508. [PMID: 37162092 PMCID: PMC11531035 DOI: 10.1177/19322968231174040] [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] [Indexed: 05/11/2023]
Abstract
Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease in the world. It is known that maintaining optimal glycemic control can slow the progression of CKD. However, the failing kidney impacts glucose and insulin metabolism and contributes to increased glucose variability. Conventional methods of insulin delivery are not well equipped to adapt to this increased glycemic lability. Automated insulin delivery (AID) has been established as an effective treatment in patients with type 1 diabetes mellitus, and there is emerging evidence for their use in type 2 diabetes mellitus. However, few studies have examined their role in diabetes with concurrent advanced CKD. We discuss the potential benefits and challenges of AID use in patients with diabetes and advanced CKD, including those on dialysis.
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Affiliation(s)
- Jean C. Lu
- Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, Fitzroy, VIC, Australia
- Department of Endocrinology and Diabetes, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, VIC, Australia
| | - Petrova Lee
- Department of Nephrology, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
| | - Francesco Ierino
- Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, Fitzroy, VIC, Australia
- Department of Nephrology, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
- St Vincent’s Institute of Medical Research, Fitzroy, VIC, Australia
| | - Richard J. MacIsaac
- Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, Fitzroy, VIC, Australia
- Department of Endocrinology and Diabetes, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, VIC, Australia
| | - Elif Ekinci
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, VIC, Australia
- Department of Endocrinology and Diabetes, Austin Health, Heidelberg, VIC, Australia
- Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, VIC, Australia
| | - David O’Neal
- Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, Fitzroy, VIC, Australia
- Department of Endocrinology and Diabetes, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, VIC, Australia
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Wan Z, Zhang S, Zhuang G, Liu W, Qiu C, Lai H, Liu W. Effect of fine particulate matter exposure on gestational diabetes mellitus risk: a retrospective cohort study. Eur J Public Health 2024; 34:787-793. [PMID: 38783609 PMCID: PMC11293809 DOI: 10.1093/eurpub/ckae094] [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: 05/25/2024] Open
Abstract
BACKGROUND The literature on the association between fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM) risk has focused mainly on exposure during the first and second trimesters, and the research results are inconsistent. Therefore, this study aimed to investigate the associations between PM2.5 exposure during preconception, the first trimester and second trimester and GDM risk in pregnant women in Guangzhou. METHODS A retrospective cohort study of 26 354 pregnant women was conducted, estimating PM2.5, particulate matter with a diameter >10 µm (PM10), sulphur dioxide (SO2), carbon monoxide (CO) and ozone (O3) exposure during preconception and the first and second trimesters. Analyses were performed using Cox proportional hazards models and nonlinear distributed lag models. RESULTS The study found that exposure to PM2.5 or a combination of two pollutants (PM2.5+PM10, PM2.5+SO2, PM2.5+CO and PM2.5+O3) was found to be significantly associated with GDM risk (P < 0.05). In the second trimester, with significant interactions found for occupation and anaemia between PM2.5 and GDM. When the PM2.5 concentrations were ≥19.56, ≥25.69 and ≥23.87 μg/m3 during preconception and the first and second trimesters, respectively, the hazard ratio for GDM started to increase. The critical window for PM2.5 exposure was identified to be from 9 to 11 weeks before conception. CONCLUSIONS Our study results suggest that PM2.5 exposure during preconception and the first and second trimesters increases the risk of GDM, with the preconception period appearing to be the critical window for PM2.5 exposure.
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Affiliation(s)
- Zhenyan Wan
- Division of Neonatology, The Maternal and Children Health Care Hospital (Huzhong Hospital) of Huadu, Guangzhou, Guangdong, People’s Republic of China
| | - Shandan Zhang
- Division of Neonatology, The Maternal and Children Health Care Hospital (Huzhong Hospital) of Huadu, Guangzhou, Guangdong, People’s Republic of China
| | - Guiying Zhuang
- Division of Neonatology, The Maternal and Children Health Care Hospital (Huzhong Hospital) of Huadu, Guangzhou, Guangdong, People’s Republic of China
| | - Weiqi Liu
- Department of Clinical Laboratory, The Maternal and Children Health Care Hospital (Huzhong Hospital) of Huadu, Guangzhou, Guangdong, People’s Republic of China
| | - Cuiqing Qiu
- Medical Information Office, The Maternal and Children Health Care Hospital (Huzhong Hospital) of Huadu, Guangzhou, Guangdong, People’s Republic of China
| | - Huiqin Lai
- Department of Clinical Laboratory, Guanzhou Yuexiu Liurong Community Health Service Center, Guangzhou, Guangdong, People’s Republic of China
| | - Weiling Liu
- Department of Clinical Laboratory, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, People’s Republic of China
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Radfar F, Shahbazi M, Tahmasebi Boroujeni S, Arab Ameri E, Farahmandfar M. Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease. Sci Rep 2024; 14:15996. [PMID: 38987609 PMCID: PMC11237031 DOI: 10.1038/s41598-024-66637-2] [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: 01/27/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024] Open
Abstract
Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aβ25-35 had impaired spatial learning and memory, which was accompanied by higher levels of Aβ plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aβ25-35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.
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Affiliation(s)
- Forough Radfar
- Department of Behavioral and Cognitive Sciences in Sports, Sports and Health Sciences Faculty, University of Tehran, Tehran, 1417935837, Iran
| | - Mehdi Shahbazi
- Department of Behavioral and Cognitive Sciences in Sports, Sports and Health Sciences Faculty, University of Tehran, Tehran, 1417935837, Iran.
| | - Shahzad Tahmasebi Boroujeni
- Department of Behavioral and Cognitive Sciences in Sports, Sports and Health Sciences Faculty, University of Tehran, Tehran, 1417935837, Iran
| | - Elahe Arab Ameri
- Department of Behavioral and Cognitive Sciences in Sports, Sports and Health Sciences Faculty, University of Tehran, Tehran, 1417935837, Iran
| | - Maryam Farahmandfar
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, 14177-55469, Iran.
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Cheng Z, Kong Y, Yang W, Xu H, Tang D, Zuo Y. Association between serum copper and blood glucose: a mediation analysis of inflammation indicators in the NHANES (2011-2016). Front Public Health 2024; 12:1401347. [PMID: 38855446 PMCID: PMC11157037 DOI: 10.3389/fpubh.2024.1401347] [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: 03/18/2024] [Accepted: 05/07/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. METHODS The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. RESULTS Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 μg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. CONCLUSION Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.
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Affiliation(s)
- Zijing Cheng
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yuzhe Kong
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Wenqi Yang
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Haitao Xu
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Decheng Tang
- Department of Management Science, School of Management, Fudan University, Shanghai, China
| | - Yu Zuo
- Third Xiangya Hospital, Central South University, Changsha, China
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Mohanan A, Biju P, V B, V G. Unraveling Proto-Oncogene (ErbB2) Expression in Patients With Carcinoma Head of Pancreas and Chronic Pancreatitis Patients: A Case-Control Study. Cureus 2024; 16:e54859. [PMID: 38533139 PMCID: PMC10964396 DOI: 10.7759/cureus.54859] [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] [Accepted: 02/25/2024] [Indexed: 03/28/2024] Open
Abstract
Background The pre-malignant tendency of the normal, non-affected portion of the pancreas is not as well explored as the multicentricity documented in pancreatic cancer cases. In order to ascertain the expression of inflammatory markers and Erythroblastic Oncogene B (ErbB2) in the non-affected pancreas in patients with pancreatic cancer, a case-control study was carried out. Materials and methods In patients who underwent pancreatoduodenectomy for pancreatic cancer (PC), pro-inflammatory genes and a tumor marker, erythroblastic oncogene 2 (ErbB2) in the epidermal growth factor receptor family were analyzed in the pancreatic tissue at the cut surface of the normal pancreas using qRT-PCR. Twenty patients diagnosed with Chronic pancreatitis (CP) after Frey's surgical procedure were selected, and their pancreatic tissues were analyzed as controls. The HPLC-purified primers were designed using National Center for Biotechnology Information (NCBI) software. The primer's specificity was verified for gene expression analysis using the Basic Local Alignment Search Tool (BLAST). The genes under study were normalized using β-actin as the housekeeping gene, and the 2-ddct method was used to compute the fold change compared to the control sample. Results Patients with margin-positive were not included. Pro-inflammatory genes (TNF-α, NF-kβ, and COX-2) had significantly lower foldchange in PC patients compared to the CP group. The CP control group had higher levels of IL-6 gene expression than the PC group. Patients with pancreatic cancer had a considerably higher expression of the ErbB2 gene than patients with CP. Conclusion The upregulated ErbB2 gene in the unaffected pancreatic tissue of pancreatic cancer patients, when compared to controls, indicates that the remaining pancreas may have the capacity to cause cancer. Proto-oncogene may play a role in the pathophysiologic process in patients with pancreatic cancer.
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Affiliation(s)
- Abhina Mohanan
- Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, IND
| | - Pottakkat Biju
- Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, IND
| | - Balasubramaniyan V
- Biochemistry, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, IND
| | - Gladwin V
- Anatomy, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, IND
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Kistenev YV, Borisov AV, Zasedatel VS, Spirina LV. Diabetes noninvasive diagnostics and monitoring through volatile biomarkers analysis in the exhaled breath using optical absorption spectroscopy. JOURNAL OF BIOPHOTONICS 2023; 16:e202300198. [PMID: 37643222 DOI: 10.1002/jbio.202300198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 08/22/2023] [Accepted: 08/22/2023] [Indexed: 08/31/2023]
Abstract
The review is aimed on the analysis the abilities of noninvasive diagnostics and monitoring of diabetes mellitus (DM) and DM-associated complications through volatile molecular biomarkers detection in the exhaled breath. The specific biochemical reactions in the body of DM patients and their associations with volatile molecular biomarkers in the breath are considered. The applications of optical spectroscopy methods, including UV, IR, and terahertz spectroscopy for DM-associated volatile molecular biomarkers measurements, are described. The applications of similar technique combined with machine learning methods in DM diagnostics using the profile of DM-associated volatile molecular biomarkers in exhaled air or "pattern-recognition" approach are discussed.
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Affiliation(s)
- Yury V Kistenev
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
- Laboratory for Remote Sensing of the Environment, V.E. Zuev Institute of Atmospheric Optics SB RAS, Tomsk, Russia
| | - Alexey V Borisov
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Vyacheslav S Zasedatel
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russia
| | - Liudmila V Spirina
- Division of Biochemistry and Molecular Biology, Siberian State Medical University, Tomsk, Russia
- Laboratory of Tumor Biochemistry, Cancer Research Institute, National Research Medical Center, Tomsk, Russia
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Lee SR, Directo D. Fish Oil Supplementation with Resistance Exercise Training Enhances Physical Function and Cardiometabolic Health in Postmenopausal Women. Nutrients 2023; 15:4516. [PMID: 37960168 PMCID: PMC10650161 DOI: 10.3390/nu15214516] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/15/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Menopause is a condition associated with an increased risk of dysregulation in cardiovascular and metabolic health among older women. While fish oil (FO) has garnered great attention for its health-enhancing properties, its potential for enhancing cardiometabolic health in this demographic remains to be established. The purpose of this study was to determine the clinical efficacy of an 8 wk administration of FO combined with programmed resistance exercise training (RET) on physical function and risk factors associated with cardiometabolic health in healthy older women. Twenty, healthy, older women were randomly assigned to one of the two experimental groups: resistance training with placebo (RET-PL) or RET with fish oil (RET-FO). Physical function, blood pressure (BP), triglyceride (TG), and systemic inflammation and oxidative stress biomarkers were assessed before and after the intervention. Statistical significance was set at p ≤ 0.05. Physical function was greatly enhanced in both RET and RET-FO. Handgrip strength substantially increased only in RET-FO. RET-FO exhibited significant decreases in BP, TG, inflammatory cytokines (TNF-α and IL-6), and oxidative stress (MDA and 8-OHdG) levels, while no detectable changes were found in RET-PL. Our findings indicate that FO administration during 8 wks of RET appears to enhance muscle function and lower risk factors linked to cardiometabolic disorders in postmenopausal women.
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Affiliation(s)
- Sang-Rok Lee
- Department of Kinesiology, New Mexico State University, Las Cruces, NM 88003, USA;
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Mohammadi A, Rabizadeh S, Mirmoosavi S, Alemi H, Mirmiranpoor H, Bagheri S, Moradi K, Esteghamati A, Nakhjavani M. Eight Weeks of Vitamin C Supplementation Restores the Lost Correlation between Serum Leptin and C-reactive Protein (CRP) in Patients with Type 2 Diabetes; A Randomized, Double-blind, Parallel-group, Placebo-controlled Clinical Trial. Curr Pharm Des 2023; 29:3497-3503. [PMID: 37612864 DOI: 10.2174/1381612829666230823091226] [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: 01/26/2023] [Revised: 06/17/2023] [Accepted: 07/20/2023] [Indexed: 08/25/2023]
Abstract
OBJECTIVE Inflammation is a well-described factor in the pathophysiology of type 2 diabetes mellitus (DM), which has been a suspect in the alteration of correlations between CRP and leptin in patients with type 2 DM. AIM This study aimed to show the effect of vitamin C as an antioxidant on the correlation of the serum levels of C-reactive protein (CRP) and leptin in patients with type 2 DM. METHODS We recruited 70 patients with longstanding T2DM and randomly assigned them into two groups; one received 500 mg/day of vitamin C, and the other received a placebo for eight weeks. Both groups were matched regarding baseline characteristics such as age, gender, weight, and diabetic medications. RESULTS Out of 70 individuals, 57 participants were left in the study. After eight weeks of follow-up, leptin level was significantly increased in the Vitamin C group (MD = 3.48 change = 24%, p-value = 0.001) but did not change in the placebo group. Other markers such as Fasting plasma glucose, HbA1c, Creatinine, uric acid, Urea, cholesterol, HDL, LDL, TG, AST, ALT, insulin, and CRP did not significantly change in both groups (p value > 0.05). The significant changes in the leptin level among the vitamin C group also remained after controlling for age, BMI, Blood pressure (BP), Triglyceride (TG), and cholesterol. Also, the correlation between serum CRP and leptin became significant in the vitamin C group after eight weeks of follow-up but not in the placebo group. (rs = 0.730, p < 0.001 vs. rs = 0.286, p-value = 0.266 in placebo group). CONCLUSION This study shows vitamin C can restore CRP-leptin correlation in patients with type 2 diabetes and increase serum leptin levels. More studies are needed to clarify the mechanism of this restoration. CLINICAL TRIAL REGISTRATION NUMBER IRCT20160811029306N1.
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Affiliation(s)
- Ali Mohammadi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Mirmoosavi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Alemi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Mirmiranpoor
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sayna Bagheri
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamyar Moradi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
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12
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Battini V, Van Manen RP, Gringeri M, Mosini G, Guarnieri G, Bombelli A, Pozzi M, Nobile M, Radice S, Clementi E, Carnovale C. The potential antidepressant effect of antidiabetic agents: New insights from a pharmacovigilance study based on data from the reporting system databases FAERS and VigiBase. Front Pharmacol 2023; 14:1128387. [PMID: 36873988 PMCID: PMC9981969 DOI: 10.3389/fphar.2023.1128387] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 02/01/2023] [Indexed: 02/19/2023] Open
Abstract
Background: Growing evidence supports a bidirectional association between diabetes and depression; promising but limited and conflicting data from human studies support the intriguing possibility that antidiabetic agents may be used to relieve effectively depressive symptoms in diabetic patients. We investigated the potential antidepressant effects of antidiabetic drugs in a high-scale population data from the two most important pharmacovigilance databases, i.e., the FDA Adverse Event Reporting System (FAERS) and the VigiBase. Material and methods: From the two primary cohorts of patients treated with antidepressants retrieved from FDA Adverse Event Reporting System and VigiBase we identified cases (depressed patients experiencing therapy failure) and non-cases (depressed patients experiencing any other adverse event). We then calculated the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Empirical Bayes Regression-Adjusted Mean (ERAM) for cases versus non-cases in relation with the concurrent exposure to at least one of the following antidiabetic agent: A10BA Biguanides; A10BB Sulfonylureas; A10BG Thiazolidinediones; A10BH DPP4-inhibitors; A10BJ GLP-1 analogues; A10BK SGLT2 inhibitors (i.e., those agents for which preliminary evidence from literature supports our pharmacological hypothesis). Results: For GLP-1 analogues, all the disproportionality scores showed values <1, i.e., statistically significant, in both analyses [from the FAERS: ROR confidence interval of 0.546 (0.450-0.662); PRR (p-value) of 0.596 (0.000); EBGM (CI) of 0.488 (0.407-0.582); ERAM (CI) of 0.480 (0.398-0.569) and VigiBase: ROR (CI) of 0.717 (0.559-0.921); PRR (p-value) of 0.745 (0.033); EBGM (CI) of 0.586 (0.464-0.733); ERAM of (CI): 0.515 (0.403-0.639)]. Alongside GLP-1 analogues, DPP-4 Inhibitors and Sulfonylureas showed the greatest potential protective effect. With regard to specific antidiabetic agents, liraglutide and gliclazide were associated with a statistically significant decrease in all disproportionality scores, in both analyses. Conclusion: The findings of this study provide encouraging results, albeit preliminary, supporting the need for further clinical research for investigating repurposing of antidiabetic drugs for neuropsychiatric disorders.
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Affiliation(s)
- Vera Battini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | | | - Michele Gringeri
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | - Giulia Mosini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | - Greta Guarnieri
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | - Anna Bombelli
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | - Marco Pozzi
- Scientific Institute, IRCCS E Medea, Bosisio Parini, Italy
| | - Maria Nobile
- Scientific Institute, IRCCS E Medea, Bosisio Parini, Italy
| | - Sonia Radice
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
| | - Emilio Clementi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy.,Scientific Institute, IRCCS E Medea, Bosisio Parini, Italy
| | - Carla Carnovale
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital, Università degli Studi di Milano, Milan, Italy
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13
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Zhang Q, Guo M, Chen T, Cheng H, Yang Q, Zhao Z, She R, Yang X, Xiao W, Yang X, Li L. Walking and taking vitamin C alleviates oxidative stress and inflammation in overweight students, even in the short-term. Front Public Health 2022; 10:1024864. [PMID: 36276369 PMCID: PMC9581260 DOI: 10.3389/fpubh.2022.1024864] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 09/05/2022] [Indexed: 01/28/2023] Open
Abstract
Objective Obese or overweight is a risk factor for some chronic diseases, and oxidative stress and inflammation may be one of the molecular mechanisms leading to the persistence of these chronic diseases. Discovering interventions to alleviate oxidative stress and inflammation in the overweight/obese population, is very important for public health and health education. Methods A two-week panel intervention study (Run 0-Run 1-Run 2) was conducted. The subjects were 77 overweight/obese undergraduates attending Dali University, with a BMI>24 kg/m2. The physical indices measured at the end of each run included BMI, waist circumference, serum ROS, TNF-α, IL-1β and urinary 8-OHdG. Students were allocated to one of four intervention groups: No intervention (control); walking; taking vitamin C; and walking + taking vitamin C. Results The results demonstrated (1) Walking significantly alleviated ROS levels, and this was consistent in Run 1 and Run 2; (2) During Run1, all three intervention modes reduced levels of 8-OHdG, but there was a statistically insignificant increase during Run 2; (3) No alleviating effects of the three intervention modes on TNF-α levels during Run 1 and Run 2 were observed; (4) The alleviating effects of the three intervention modes on IL-1β levels during Run 1 and Run 2 were clear. Conclusion Walking and taking vitamin C can reduce levels of ROS, 8-OHdG and IL-1β, but not TNF-α, in overweight/obese participants. These interventions may become potential preventive measures for the overweight against obese-induced oxidative stress and inflammation.
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Affiliation(s)
- Qian Zhang
- Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali, China,School of Public Health, Dali University, Dali, China
| | - Miao Guo
- Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing, China
| | - Tianyi Chen
- Department of Environmental Health, School of Public Health, Fudan University, Shanghai, China
| | - Huizhi Cheng
- School of Public Health, Dali University, Dali, China
| | - Qianwen Yang
- School of Public Health, Dali University, Dali, China
| | - Zhuohui Zhao
- Department of Environmental Health, School of Public Health, Fudan University, Shanghai, China
| | - Rong She
- Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali, China
| | - Xiaoyan Yang
- Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali, China
| | - Wen Xiao
- Institute of Eastern-Himalaya Biodiversity Research, Dali University, Dali, China
| | - Xu Yang
- Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali, China,Xianning Medical College, Hubei University of Science and Technology, Hubei, China,*Correspondence: Lijuan Li
| | - Lijuan Li
- Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali, China,School of Public Health, Dali University, Dali, China,Xu Yang
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14
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Aggarwal H, Pathak P, Gupta SK, Kumar Y, Jagavelu K, Dikshit M. Serum and cecal metabolic profile of the insulin resistant and dyslipidemic p47 phox knockout mice. Free Radic Res 2022; 56:483-497. [PMID: 36251883 DOI: 10.1080/10715762.2022.2133705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Involvement of NOX-dependent oxidative stress in the pathophysiology of metabolic disorders as well as in the maintenance of metabolic homeostasis has been demonstrated previously. In the present study, the metabolic profile in p47phox-/- and WT mice fed on a chow diet was evaluated to assess the role of metabolites in glucose intolerance and dyslipidemia under altered oxidative stress conditions. p47phox-/- mice displayed glucose intolerance, dyslipidemia, hyperglycemia, insulin resistance (IR), hyperinsulinemia, and altered energy homeostasis without any significant change in gluconeogenesis. The expression of genes involved in lipid synthesis and uptake was enhanced in the liver, adipose tissue, and intestine tissues. Similarly, the expression of genes associated with lipid efflux in the liver and intestine was also enhanced. Enhanced gut permeability, inflammation, and shortening of the gut was evident in p47phox-/- mice. Circulating levels of pyrimidines, phosphatidylglycerol lipids, and 3-methyl-2-oxindole were augmented, while level of purine was reduced in the serum. Moreover, the cecal metabolome was also altered, as was evident with the increase in indole-3-acetamide, N-acetyl galactosamine, glycocholate, and a decrease in hippurate, indoxyl sulfate, and indigestible sugars (raffinose and melezitose). Treatment of p47phox-/- mice with pioglitazone, marginally improved glucose intolerance, and dyslipidemia, with an increase in PUFAs (linoleate, docosahexaenoic acid, and arachidonic acid). Overall, the results obtained in p47phox-/- mice indicate an association of IR and dyslipidemia with altered serum and cecal metabolites (both host and bacterial-derived), implying a critical role of NOX-derived ROS in metabolic homeostasis.
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Affiliation(s)
- Hobby Aggarwal
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India.,Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Priya Pathak
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Sonu Kumar Gupta
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Yashwant Kumar
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad, India
| | | | - Madhu Dikshit
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India.,Translational Health Science and Technology Institute, Faridabad, India
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15
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Fang XX, Wang H, Song HL, Wang J, Zhang ZJ. Neuroinflammation Involved in Diabetes-Related Pain and Itch. Front Pharmacol 2022; 13:921612. [PMID: 35795572 PMCID: PMC9251344 DOI: 10.3389/fphar.2022.921612] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 05/12/2022] [Indexed: 12/25/2022] Open
Abstract
Diabetes mellitus (DM) is a global epidemic with increasing incidence, which results in diverse complications, seriously affects the patient quality of life, and brings huge economic burdens to society. Diabetic neuropathy is the most common chronic complication of DM, resulting in neuropathic pain and chronic itch. The precise mechanisms of diabetic neuropathy have not been fully clarified, hindering the exploration of novel therapies for diabetic neuropathy and its terrible symptoms such as diabetic pain and itch. Accumulating evidence suggests that neuroinflammation plays a critical role in the pathophysiologic process of neuropathic pain and chronic itch. Indeed, researchers have currently made significant progress in knowing the role of glial cells and the pro-inflammatory mediators produced from glial cells in the modulation of chronic pain and itch signal processing. Here, we provide an overview of the current understanding of neuroinflammation in contributing to the sensitization of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, we also summarize the inflammation mechanisms that contribute to the pathogenesis of diabetic itch, including activation of glial cells, oxidative stress, and pro-inflammatory factors. Targeting excessive neuroinflammation may provide potential and effective therapies for the treatment of chronic neuropathic pain and itch in DM.
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Affiliation(s)
- Xiao-Xia Fang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
- Department of Medical Functional Laboratory, School of Medicine, Nantong University, Nantong, China
| | - Heng Wang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Hao-Lin Song
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Juan Wang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Zhi-Jun Zhang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
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16
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Efrat M, Stein A, Pinkas H, Unger R, Birk R. Sugar Consumption Is Negatively Associated with Semen Quality. Reprod Sci 2022; 29:3000-3006. [PMID: 35606632 DOI: 10.1007/s43032-022-00973-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/15/2022] [Indexed: 11/24/2022]
Abstract
Recently, in parallel to decrease in semen quality, the consumption of sugar has risen sharply. This provided the rationale to study the association between whole dietary sugar consumption and semen quality. Our aim was to investigate the association between sugar consumption and semen quality. The final cross-sectional study population (n = 280 of initial n = 593, after applying inclusion and exclusion criteria) attending routine semen analysis at sperm bank laboratory was subject to semen quality analysis according to WHO criteria (volume, sperm concentration, total sperm count, percentage total motility, and percentage normal morphology) and filled food frequency questionnaire (FFQ) and lifestyle questionnaire. Associations between consumed sugars and semen quality were analyzed using multivariate regression adjusted to relevant cofounders for 2 food components containing sugar including soft drinks (SoftD) and total added sugar to food products (SugProd). We found negative association between higher consumption of dietary sugar in all 2 dietary sub-categories and sperm concentration. Significant sperm concentration decrements of 18% and 23% were associated with SoftD median consumption of 0.2 drinks/day (IQR; 0.1-0.5 drinks/day). Significant sperm concentration decrements of 15% and 17% were associated with median SugProd consumption of 25 teaspoons of added sugar/day (IQR; 19-31 teaspoons of added sugar/day). In conclusion, our study findings demonstrate that sugar consumption is negatively associated with sperm concentration.
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Affiliation(s)
- Michal Efrat
- Department of Nutrition, Faculty of Health Sciences, Ariel University, 40700, Ariel, Israel.,The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel
| | - Anat Stein
- Sperm Bank and Male Infertility Clinic, Belinson Hospital, Petah-Tiqva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Haim Pinkas
- Sperm Bank and Male Infertility Clinic, Belinson Hospital, Petah-Tiqva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ron Unger
- The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel
| | - Ruth Birk
- Department of Nutrition, Faculty of Health Sciences, Ariel University, 40700, Ariel, Israel.
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17
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Arreola-Diaz R, Majluf-Cruz A, Sanchez-Torres LE, Hernandez-Juarez J. The Pathophysiology of The Antiphospholipid Syndrome: A Perspective From The Blood Coagulation System. Clin Appl Thromb Hemost 2022; 28:10760296221088576. [PMID: 35317658 PMCID: PMC8950029 DOI: 10.1177/10760296221088576] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by a hypercoagulability associated to vascular thrombosis and/or obstetric morbidity, is caused by the presence of antiphospholipid antibodies such as lupus anticoagulant, anti-β-2-glycoprotein 1, and/or anticardiolipin antibodies. In the obstetrical APS, antiphospholipid antibodies induce the production of proinflammatory cytokines and tissue factor by placental tissues and recruited neutrophils. Moreover, antiphospholipid antibodies activate the complement system which, in turn, induces a positive feedback leading to recruitment of neutrophils as well as activation of the placenta. Activation of these cells triggers myometrial contractions and cervical ripening provoking the induction of labor. In thrombotic and obstetrical APS, antiphospholipid antibodies activate endothelial cells, platelets, and neutrophils and they may alter the multimeric pattern and concentration of von Willebrand factor, increase the concentration of thrombospondin 1, reduce the inactivation of factor XI by antithrombin, increase the activation of factor XII, and reduce the activity of tissue plasminogen activator with the subsequent production of plasmin. All these effects result in less permeable clots, denser, thinner, and with more branched fibrin fibers which are more difficult to lysate. As a consequence, thrombosis, the defining clinical criterion of APS, complicates the clinical course of the patient.
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Affiliation(s)
- R Arreola-Diaz
- Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - A Majluf-Cruz
- Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico
| | - L E Sanchez-Torres
- Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - J Hernandez-Juarez
- CONACyT-Facultad de Odontologia, Universidad Autonoma Benito Juarez de Oaxaca, Oaxaca de Juarez, Mexico
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18
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Nikbaf-Shandiz M, Tutunchi H, Khoshbaten M, Nazari Bonab H, Ebrahimi-Mameghani M. Propolis supplementation in obese patients with non-alcoholic fatty liver disease: effects on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation. Food Funct 2022; 13:11568-11578. [DOI: 10.1039/d2fo01280d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Possible mechanisms of action of propolis in the management of NAFLD.
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Affiliation(s)
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manuchehr Khoshbaten
- Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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19
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He L, Hu X, Day DB, Yan M, Teng Y, Liu XL, Yan E, Xiang J, Qiu X, Mo J, Zhang Y, Zhang JJ, Gong J. The associations of nitrated polycyclic aromatic hydrocarbon exposures with plasma glucose and amino acids. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 289:117945. [PMID: 34426189 DOI: 10.1016/j.envpol.2021.117945] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/22/2021] [Accepted: 08/08/2021] [Indexed: 06/13/2023]
Abstract
Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults. Five urinary amino-PAHs (1-aminonaphthalene, 2-aminonaphthalene, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene) were measured as biomarkers of nitro-PAH exposures. We measured plasma concentrations of glucose and six amino acids that can regulate insulin secretion, including aspartate (Asp), glutamate (Glu), glutamine (Gln), alanine (Ala), Arginine (Arg), and ornithine (Orn). We found that increasing concentrations of 9-aminophenanthrene were significantly associated with increasing glucose levels and with decreasing Asp, Glu, Ala, and Orn levels. We estimated that 26.4 %-43.8 % of the 9-aminophenanthrene-associated increase in glucose level was mediated by Asp, Glu, and Orn. These results suggest that exposure to certain nitro-PAHs affects glucose homeostasis, partly resulting from the depletion of insulin-stimulating amino acids (Asp, Glu, and Orn).
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Affiliation(s)
- Linchen He
- Nicholas School of the Environment, Duke University, Durham, NC, 27708, USA; Global Health Institute, Duke University, Durham, NC, 27708, USA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA
| | - Xinyan Hu
- BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; Center for Environment and Health, Peking University, Beijing, 100871, China
| | - Drew B Day
- Seattle Children's Research Institute, Seattle, WA, 98145, United States
| | - Meilin Yan
- BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; Center for Environment and Health, Peking University, Beijing, 100871, China
| | - Yanbo Teng
- Duke Kunshan University, Kunshan City, Jiangsu Province, 215316, China
| | - Xing Lucy Liu
- Global Health Institute, Duke University, Durham, NC, 27708, USA
| | - Erik Yan
- Global Health Institute, Duke University, Durham, NC, 27708, USA; Duke Kunshan University, Kunshan City, Jiangsu Province, 215316, China
| | - Jianbang Xiang
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, United States
| | - Xinghua Qiu
- BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; Center for Environment and Health, Peking University, Beijing, 100871, China
| | - Jinhan Mo
- Department of Building Science, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Beijing, 100084, China
| | - Yinping Zhang
- Department of Building Science, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Beijing, 100084, China
| | - Junfeng Jim Zhang
- Nicholas School of the Environment, Duke University, Durham, NC, 27708, USA; Global Health Institute, Duke University, Durham, NC, 27708, USA; Duke Kunshan University, Kunshan City, Jiangsu Province, 215316, China
| | - Jicheng Gong
- BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; Center for Environment and Health, Peking University, Beijing, 100871, China.
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20
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Singh R, Mohapatra L, Tripathi AS. Targeting mitochondrial biogenesis: a potential approach for preventing and controlling diabetes. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021. [DOI: 10.1186/s43094-021-00360-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Diabetes mellitus is a lingering hyperglycemic ailment resulting in several life-threatening difficulties. Enduring hyperglycemia often persuades the buildup of reactive oxygen species that are the significant pathological makers of diabetic complications. The mitochondrial dysfunction, with mitochondrial damage and too much production of reactive oxygen species, have been proposed to be convoluted in the progress of insulin resistance. Numerous studies advocate that agents that enhance the mitochondrial number and/or decrease their dysfunction, could be greatly helpful in management of diabetes and its complications.
Main body
Mitochondrial biogenesis is an extremely delimited procedure arbitrated by numerous transcription influences, in which mitochondrial fusion and fission happen in synchronization in a standard vigorous cell. But this synchronization is greatly disturbed in diabetic condition designated by modification in the working of several important transcription factors regulating the expressions of different genes. Numerous preclinical and clinical investigations have suggested that, the compromised functions of mitochondria play a significant protagonist in development of pancreatic β-cell dysfunction, skeletal muscle insulin resistance and several diabetic complications. However, there are several phytoconstituents performing through numerous alleyways, either unswervingly by motivating biogenesis or indirectly by constraining or averting dysfunction and producing a beneficial effect on overall function of the mitochondria.
Conclusion
This review describes standard mitochondrial physiology and anomalous modifications that transpire in answer to persistent hyperglycemia in diabetes condition. It also discusses about the different phytoconstituents that can affect the biogenesis pathways of mitochondria and thus can be used in the treatment and prevention of diabetes.
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21
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Bansal A, Hadimani CP. Low Plasma Ascorbate Levels in Type 2 Diabetic Patients With Adequate Dietary Vitamin C. J Lab Physicians 2021; 13:139-143. [PMID: 34483559 PMCID: PMC8409123 DOI: 10.1055/s-0041-1730751] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2022] Open
Abstract
Background Dietary intake of antioxidative vitamin C plays a protective role in the prevention of oxidative damage in diabetics, demanding increased requirement of vitamin C. Hyperglycemia results in impaired uptake of vitamin C in the cell. The present study was conducted to compare the plasma ascorbate levels in type 2 diabetic patients and controls consuming adequate dietary vitamin C. Methodology Fifty consented type 2 diabetes mellitus (T2DM) patients who were on treatment with oral hypoglycemic drugs and consuming adequate vitamin C in diet were taken in the study and 50 healthy controls equitably matched for age, gender between 40 and 70 years, and dietary intake of vitamin C were compared. Dietary intake of vitamin C was estimated by a food frequency questionnaire. Subjects consuming more than 35 mg/d of vitamin C were included in the study. Fasting blood sugar was estimated by glucose oxidase and peroxidase method and estimation of ascorbic acid was done by using 2, 4 dinitro phenyl hydrazine method. Result The mean ± standard deviation levels of plasma ascorbate levels in diabetic subjects were 0.22 ± 0.12 mg/dL, which were significantly lower as compared with controls with plasma ascorbate level of 0.47 ± 0.15 mg/dL. In diabetic subjects, insignificant positive correlation was observed between these parameters with r -value 0.168 and p -value 0.245. Conclusion This study concludes that even with the recommended dietary intake of vitamin C low plasma ascorbate levels were found among T2DM patients, which necessitates increased demand and dietary advice to diabetic patients on consuming foods rich in vitamin C more than the recommended daily allowance.
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Affiliation(s)
- Abhishek Bansal
- Department of Biochemistry, KLE Academy of Higher Education and Research (KAHER), J.N. Medical College, Belagavi, Karnataka, India
| | - Chetana P Hadimani
- Department of Biochemistry, KLE Academy of Higher Education and Research (KAHER), J.N. Medical College, Belagavi, Karnataka, India
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Beeraka NM, Tomilova IK, Batrak GA, Zhaburina MV, Nikolenko VN, Sinelnikov MY, Mikhaleva LM. Recent Insights into the Nutritional Antioxidant Therapy in Prevention and Treatment of Diabetic Vascular Complications - A comprehensive Review. Curr Med Chem 2021; 29:1920-1935. [PMID: 34375177 DOI: 10.2174/0929867328666210810142527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 05/25/2021] [Accepted: 06/04/2021] [Indexed: 11/22/2022]
Abstract
Diabetes mellitus (DM) and DM-induced vascular complications are a significant global healthcare problem causing a decrease in patient quality of life. The main reason for the disability and mortality of patients is rapidly progressing micro- and macroangiopathies. Currently, free radical oxidation is recognized as one of the main mechanisms in the development of DM and associated complications. Under normal physiological conditions, the level of free radicals and antioxidant defense capabilities is balanced. However, imbalance occurs between the antioxidant defense system and pro-oxidants during chronic hyperglycemia and may invoke formation of excess free radicals, leading to activation of lipid peroxidation and accumulation of highly toxic products of free radical oxidation. This is accompanied by varying degrees of insulin deficiency and insulin resistance in DM patients. Simultaneously with the activation of free radical generation, a decrease in the activity of antioxidant defense factors (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamins C and E) and an acceleration of diabetic complications is seen. Therefore, we hypothesize that antioxidants may play a positive role in the treatment of DM patients to prevent DM-induced vascular complications. However this has not been sufficiently studied. In this review, we discuss recent insights into the potential underlying mechanisms of oxidative stress induced diabetic complications, and implications of antioxidants in mitigation of DM-induced vascular complications.
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Affiliation(s)
- Narasimha M Beeraka
- Center of Excellence in Regenerative Medicine and Molecular Biology (CEMR), Department of Biochemistry, JSS Academy of Higher Education & Research (JSS AHER),Mysuru, Karnataka, India
| | - Irina K Tomilova
- Federal State Budgetary Educational Institution of Higher Education Ivanovo State Medical Academy, Ministry of Health of the Russian Federation, Ivanovo. Russian Federation
| | - Galina A Batrak
- Center of Excellence in Regenerative Medicine and Molecular Biology (CEMR), Department of Biochemistry, JSS Academy of Higher Education & Research (JSS AHER),Mysuru, Karnataka, India
| | - Maria V Zhaburina
- Center of Excellence in Regenerative Medicine and Molecular Biology (CEMR), Department of Biochemistry, JSS Academy of Higher Education & Research (JSS AHER),Mysuru, Karnataka, India
| | - Vladimir N Nikolenko
- Sechenov First Moscow State Medical University (Sechenov University), Moscow 119146. Russian Federation
| | - Mikhail Y Sinelnikov
- Sechenov First Moscow State Medical University (Sechenov University), Moscow 119146. Russian Federation
| | - Liudmila M Mikhaleva
- Research Institute of Human Morphology, Russian Academy of Medical Science, Moscow 117418. Russian Federation
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Sayegh M, Henderson J, Farquharson AJ, Horgan G, Ranawana V, Drew JE. Inter-Individual Variation in Postprandial Glycemic Responses in Women Co-Ingesting Green Leafy Vegetables with a Carbohydrate Meal: Interactions with the Sirtuin System. Mol Nutr Food Res 2021; 65:e2000923. [PMID: 33852192 DOI: 10.1002/mnfr.202000923] [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: 09/21/2020] [Revised: 02/17/2021] [Indexed: 11/12/2022]
Abstract
SCOPE Green leafy vegetables (GLV) may improve postprandial glycemic responses (PGR) and metabolic health. However, inter-individual variations (IIV) preclude conclusive evidence. Sirtuin system is emerging as a key player in blood glucose control. This study investigates IIV in PGR in women co-ingesting GLV with a carbohydrate meal and interactions with the sirtuin system. METHODS AND RESULTS Volunteers (n = 31 women) consume rice, rice with bok choy, or spinach (75g available carbohydrate) on separate occasions. Postprandial glucose, insulin, adropin, and lipid levels are measured. Anthropometric measurements and sex hormones are measured. GeXP assay measures whole blood postprandial gene expression profiles of 25 markers involved in sirtuin signaling. GLV consumption has no significant effect on PGR, which shows high variation. PGR correlated with age, but no other consistent associations are observed. Sirtuin gene expression profiles reveal distinct stratified subgroups associated with PGR, lipid, insulin, fat mass, waist/hip circumferences, and adropin levels. CONCLUSION PGR to co-ingesting GLV with a carbohydrate meal are highly variable in this cohort and fail to reveal a significant reduction in PGR. Variable responses are largely independent of menopausal status and meal consumed. However, lower expression of sirtuin gene targets is associated with higher PGR and with markers linked to health status.
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Affiliation(s)
- Marietta Sayegh
- The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Jaye Henderson
- The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Andrew J Farquharson
- The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Graham Horgan
- Biomathematics and Statistics Scotland, University of Aberdeen, Aberdeen, AB25 2ZD, UK
| | - Viren Ranawana
- The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Janice E Drew
- The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
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Baliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, Christodoulou I, Spandidos DA, Kyriakopoulos AM, Zoumpourlis V. Ameliorative effect of taurine against diabetes and renal-associated disorders (Review). MEDICINE INTERNATIONAL 2021; 1:3. [PMID: 36699147 PMCID: PMC9855276 DOI: 10.3892/mi.2021.3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/25/2021] [Indexed: 01/28/2023]
Abstract
To develop novel therapeutic methods for both diabetic and renal disorders, scientists had initially focused on elucidating the molecular mechanisms of taurine in established cell lines and mouse models. Although a large amount of data have been revealed, taurine has been confirmed to be the next step of novel promising therapeutic interventions against diabetic disorders. Taurine appears to ameliorate diabetes 1-related complications in various organs through its antioxidant, anti-inflammatory and anti-hormonal actions. In type 2 diabetes, taurine has been positively implicated in glucose homeostasis, exerting potent hypoglycemic, anti-obesity, hypotensive and hypolipidemic effects. Of particular interest is that taurine provides protection against renal dysfunction, including hypertension and proteinuria, specific glomerular and tubular disorders, acute and chronic renal conditions, and diabetic nephropathy. The ameliorative effects of taurine against renal disorders are based on its osmoregulatory properties, its association with signaling pathways and its association with the renin-angiotensin-aldosterone system (RAAS). Further clinical studies are required to ensure the importance of research findings.
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Affiliation(s)
- Stella Baliou
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
| | - Maria Adamaki
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
| | - Petros Ioannou
- Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Aglaia Pappa
- Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Mihalis I. Panayiotidis
- Department of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus
- Cyprus School of Molecular Medicine, 2371 Nicosia, Cyprus
| | - Ioannis Christodoulou
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece
| | | | - Vassilis Zoumpourlis
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
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Investigation of the synergistic effect of glimepiride and rosuvastatin on alloxan-induced diabetic rat. J Diabetes Metab Disord 2021; 19:1415-1422. [PMID: 33553033 DOI: 10.1007/s40200-020-00662-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 10/12/2020] [Indexed: 10/23/2022]
Abstract
Purpose Diabetes mellitus is characterized by having a multitude of life-threatening secondary complications, particularly dyslipidemia, which ultimately leads to the development of comorbid diseases, such as cardiovascular diseases. This research work was designed to investigate the synergistic effect of glimepiride (1 mg/kg b.w.) and rosuvastatin (10 mg /kg b.w.) on alloxan-induced diabetic rats having dyslipidemia. Methods Diabetes was induced by injecting alloxan (120 mg/kg b.w.) intraperitoneally. The experiment was conducted to determine the level of blood glucose, HbA1c, lipid profile, and body weight variation of rats. Results This study's outcomes suggested that the combination therapy showed more statistically significant effect on blood glucose level, HbA1c level, lipid profile, and body weight variation than any single therapy. While the glimepiride monotherapy showed a statistically considerable effect on blood glucose level, HbA1c level, and body weight variation, the rosuvastatin treated group gave statistically non-significant effect on these parameters except body weight variation, which was found as downward trend. In addition, the rosuvastatin treated group showed a healthy lipid profile compared to glimepiride treated group. Conclusions Concluding the results of this study, it can be said that the treatment of glimepiride in combination with rosuvastatin may be more efficacious than monotherapy for preventing diabetes in rats with dyslipidemia.
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Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets. SCIENCE CHINA-LIFE SCIENCES 2021; 64:1702-1719. [PMID: 33481164 DOI: 10.1007/s11427-020-1840-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 10/15/2020] [Indexed: 01/24/2023]
Abstract
Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.
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Myeloid FBW7 deficiency disrupts redox homeostasis and aggravates dietary-induced insulin resistance. Redox Biol 2020; 37:101688. [PMID: 32853822 PMCID: PMC7451763 DOI: 10.1016/j.redox.2020.101688] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 08/10/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023] Open
Abstract
The E3 ubiquitin ligase FBW7 plays critical roles in multiple pathological and physiological processes. Here, we report that after high-fat diet (HFD) feeding for 16 weeks, myeloid-specific FBW7-deficient mice demonstrate increased redox stress, inflammatory responses and insulin resistance. Macrophages activation under FBW7 deficiency decreases substrate flux through the pentose phosphate pathway (PPP) to produce less equivalents (NADPH and GSH) and aggravate the generation of intracellular reactive oxygen species (ROS) in macrophages, thereby over-activating proinflammatory reaction. Mechanistically, we identify that pyruvate kinase muscle isozyme M2 (PKM2) is a new bona fide ubiquitin substrate of SCFFBW7. While challenged with HFD stress, pharmacological inhibition of PKM2 protects FBW7-deficient macrophages against production of ROS, proinflammatory reaction and insulin resistance. Intriguingly, we further find an inverse correlation between FBW7 level and relative higher H2O2 level and the severity of obesity-related diabetes. Overall, the results suggest that FBW7 can play a crucial role in modulating inflammatory response through maintaining the intracellular redox homeostasis during HFD insults.
Myeloid FBW7 deficiency aggravates HFD-induced oxidative stress, inflammation and insulin resistance. PKM2 is a new bona fide ubiquitin substrate of SCFFBW7. FBW7 divert glycolysis to combat oxidative stress via PKM2 in macrophages. FBW7 expression inversely correlates with ROS level to govern obesity-related metabolic disorder.
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Yan LH, Mu B, Pan D, Shi YN, Yuan JH, Guan Y, Li W, Zhu XY, Guo L. Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes. J Int Med Res 2020; 48:300060520937866. [PMID: 32691685 PMCID: PMC7375730 DOI: 10.1177/0300060520937866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Aims Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. Materials and methods One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-β, early-phase insulin secretion index InsAUC30/GluAUC30, and total-phase insulin secretion index InsAUC120/GluAUC120. Results Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-β level, early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. Conclusion SIBO may be involved in lower levels of insulin release and worse glycemic control.
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Affiliation(s)
- Li-Hui Yan
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Biao Mu
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China.,Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Da Pan
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China.,Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ya-Nan Shi
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Ji-Hong Yuan
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Yue Guan
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Wang Li
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Xiao-Yi Zhu
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
| | - Lei Guo
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China
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Kang J, Liao J, Xu S, Xia W, Li Y, Chen S, Lu B. Associations of exposure to fine particulate matter during pregnancy with maternal blood glucose levels and gestational diabetes mellitus: Potential effect modification by ABO blood group. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 198:110673. [PMID: 32361495 DOI: 10.1016/j.ecoenv.2020.110673] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 04/16/2020] [Accepted: 04/21/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Previous studies have examined the relationships between prenatal fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM), but the results were inconsistent. Furthermore, the possible effect modification by ABO blood group has not been explored. OBJECTIVES To assess the associations of PM2.5 exposures during pregnancy with maternal glucose levels as well as GDM, and further to evaluate the potential effect modification by ABO blood group. METHODS Between January 2013 and January 2015, 4783 pregnant women were enrolled in our study based on a birth cohort in Wuhan. Daily PM2.5 exposure levels for each woman during pregnancy were estimated using a spatial-temporal land-use regression model. Linear regressions with general estimating equations (GEE) were performed to assess the associations between trimester-specific PM2.5 exposures and maternal glucose levels. Modified Poisson regressions with GEE analyses were used to evaluate the impacts of PM2.5 exposures during each trimester on the risk of GDM. The associations of PM2.5 exposure during the whole study period with glucose levels and GDM were estimated using multiple linear regression model and modified Poisson regression model, respectively. We conducted a stratified analysis to explore the potential effect modification by ABO blood group. RESULTS Among all the 4783 participants, 394 (8.24%) had GDM. Exposure to PM2.5 was found to be positively associated with elevated fasting glucose level during the whole study period [0.382 mg/dL, 95% confidence interval (CI): 0.179-0.586, per 10 μg/m3 increase in PM2.5], the first trimester (0.154 mg/dL ,95% CI: 0.017-0.291) and the second trimester (0.541 mg/dL, 95% CI: 0.390-0.692). No statistically significant results were observed between PM2.5 and 1-h and 2-h glucose levels during any study period. Increased risks of GDM for each 10 μg/m3 increase in PM2.5 levels were observed during the whole study period [relative risk (RR): 1.120, 95% CI: 1.021-1.228] and the first trimester (RR: 1.074, 95% CI: 1.012-1.141), but not the second trimester (RR: 1.035, 95% CI: 0.969-1.106). Stratified analysis indicated that the associations of PM2.5 exposures with GDM were more pronounced among pregnant women with blood group A, but no significant effect modifications were observed. CONCLUSION Our study enriched epidemiological evidence linking PM2.5 exposures during pregnancy to elevated maternal glucose levels and increased risk of GDM. More importantly, we first highlighted that the impact of PM2.5 on GDM might be greater among pregnant women with blood group A.
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Affiliation(s)
- Jiawei Kang
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Jiaqiang Liao
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Wei Xia
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Siyi Chen
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Bin Lu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China.
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D P, Puvvada RC, M VA. Association of vitamin C status in diabetes mellitus: prevalence and predictors of vitamin C deficiency. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2020. [DOI: 10.1186/s43094-020-00040-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Postprandial Glycemia, Insulinemia, and Antioxidant Status in Healthy Subjects after Ingestion of Bread made from Anthocyanin-Rich Riceberry Rice. Nutrients 2020; 12:nu12030782. [PMID: 32188005 PMCID: PMC7146297 DOI: 10.3390/nu12030782] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/13/2020] [Accepted: 03/13/2020] [Indexed: 02/07/2023] Open
Abstract
Riceberry rice, a gluten-free grain, contains many nutrient components, including carbohydrates, proteins, certain fatty acids, and micronutrients, as well as bioactive non-nutrient compounds, such as polyphenolic compounds. This study aimed to evaluate the effect of bread made from anthocyanin-rich Riceberry rice on the postprandial glycemic response, glucagon-like peptide-1 (GLP-1), antioxidant status, and subjective ratings of appetite. In the crossover design, 16 healthy participants (six men and 10 women) completed four sessions involving blood collection in the fasting state and at 30, 60, 90, 120, 150, and 180 min after food consumption (50 g of available carbohydrate) in a randomized order: 1) glucose solution, 2) wheat bread (WB), 3) Riceberry rice bread (RRB), and 4) Hom Mali bread (HMB). Consumption of RRB resulted in significantly lower postprandial plasma glucose concentration at 30 and 60 min when compared to HMB. No difference in postprandial glucose concentration between RRB and WB was observed. In addition, postprandial plasma insulin showed a significant decrease in the group which received RRB at 15 and 60 min, as compared to HMB. In comparison with 50 g of glucose, as a reference, the glycemic index (GI) of RRB, WB, and HMB was 69.3 ± 4.4, 77.8 ± 4.6, and 130.6 ± 7.9, respectively. Interestingly, the ferric-reducing ability of plasma (FRAP) level was shown to significantly increase after consumption of RRB. In the meantime, a significant decrease in the postprandial FRAP level was also observed following an intake of WB and HMB. All breads caused increases in the postprandial plasma protein thiol group and had similar effects on hunger, fullness, desire to eat, and satiety ratings. However, consumption of RBB, WB, and HMB did not change plasma GLP-1 and malondialdehyde (MDA) levels when compared to the baseline. The findings suggest that anthocyanin-rich Riceberry rice can be a natural ingredient for gluten-free bread which reduced glycemic response together with improvement of antioxidant status in healthy subjects.
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Gray ID, Kross AR, Renfrew ME, Wood P. Precision Medicine in Lifestyle Medicine: The Way of the Future? Am J Lifestyle Med 2020; 14:169-186. [PMID: 32231483 PMCID: PMC7092395 DOI: 10.1177/1559827619834527] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 12/21/2018] [Accepted: 02/08/2019] [Indexed: 02/06/2023] Open
Abstract
Precision medicine has captured the imagination of the medical community with visions of therapies precisely targeted to the specific individual's genetic, biological, social, and environmental profile. However, in practice it has become synonymous with genomic medicine. As such its successes have been limited, with poor predictive or clinical value for the majority of people. It adds little to lifestyle medicine, other than in establishing why a healthy lifestyle is effective in combatting chronic disease. The challenge of lifestyle medicine remains getting people to actually adopt, sustain, and naturalize a healthy lifestyle, and this will require an approach that treats the patient as a person with individual needs and providing them with suitable types of support. The future of lifestyle medicine is holistic and person-centered rather than technological.
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Affiliation(s)
- Ian D. Gray
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Andrea R. Kross
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Melanie E. Renfrew
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Paul Wood
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
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Dhas Y, Banerjee J, Damle G, Mishra N. Serum 25(OH)D concentration and its association with inflammation and oxidative stress in the middle-aged Indian healthy and diabetic subjects. Steroids 2020; 154:108532. [PMID: 31672627 DOI: 10.1016/j.steroids.2019.108532] [Citation(s) in RCA: 5] [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: 07/26/2019] [Revised: 10/18/2019] [Accepted: 10/24/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Vitamin D deficiency is associated with inflammation and oxidative stress. We have studied the association of 25-hydroxyvitamin D [25(OH)D] with markers of inflammation and oxidative stress. METHODS We have recruited total 180 male and female subjects aged between 30 and 50 years and divided them into two groups as control (n = 90) and T2DM (n = 90). We have measured 25(OH)D concentration, markers of inflammation including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) and markers of oxidative stress including malondialdehyde (MDA) and oxidized low-density lipoprotein (Ox-LDL) by using standard methods. RESULTS We stratified control and T2DM groups by 25(OH)D concentration and it indicates that in severe deficiency and sufficiency category IL-6, IL-1β, TNF-α, and Ox-LDL were significantly different while in moderate deficiency category only MDA was significantly different, among control and T2DM groups. In an insufficiency category, IL-6, IL-1β, TNF-α, MDA, and Ox-LDL were significantly different among control and T2DM groups. Correlation analysis indicates a negative correlation of 25(OH)D with IL-6, IL-1β, TNF-α, and Ox-LDL among total subjects. Further, logistic regression analysis demonstrated a significant association of different categories of 25(OH)D with IL-6, IL-1β, TNF-α, and Ox-LDL before and after adjustment to body mass index and waist to hip ratio. CONCLUSION This study suggest that vitamin D may have significant implications in the prevention of inflammation and oxidative stress.
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Affiliation(s)
- Yogita Dhas
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, Maharashtra 412115, India
| | - Joyita Banerjee
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, Maharashtra 412115, India
| | - Gauri Damle
- Madhunayani Diabetes Care & Eye Laser Centre, Pune, India
| | - Neetu Mishra
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Pune, Maharashtra 412115, India.
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Li MC, Mínguez-Alarcón L, Bellavia A, Williams PL, James-Todd T, Hauser R, Chavarro JE, Chiu YH. Serum beta-carotene modifies the association between phthalate mixtures and insulin resistance: The National Health and Nutrition Examination Survey 2003-2006. ENVIRONMENTAL RESEARCH 2019; 178:108729. [PMID: 31521963 PMCID: PMC6759414 DOI: 10.1016/j.envres.2019.108729] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 08/16/2019] [Accepted: 09/04/2019] [Indexed: 05/28/2023]
Abstract
Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12-85 from the National Health and Nutrition Examination Surveys (2003-2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of -0.07 (95% CI = -0.14, -0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum β-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum β-carotene. As this is the first human report on the protective role of serum β-carotene on DEHP induced insulin resistance, future studies are needed.
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Affiliation(s)
- Ming-Chieh Li
- Department of Public Health, China Medical University College of Public Health, Taichung, 40402, Taiwan
| | - Lidia Mínguez-Alarcón
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
| | - Andrea Bellavia
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
| | - Paige L Williams
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
| | - Tamarra James-Todd
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
| | - Russ Hauser
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Jorge E Chavarro
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard, Medical School, Boston, MA, 02115, USA
| | - Yu-Han Chiu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
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Yuan W, Ma C, Zhou Y, Wang M, Zeng G, Huang Q. Negative regulation of eNOS-NO signaling by over-SUMOylation of PPARγ contributes to insulin resistance and dysfunction of vascular endothelium in rats. Vascul Pharmacol 2019; 122-123:106597. [PMID: 31479752 DOI: 10.1016/j.vph.2019.106597] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 08/22/2019] [Accepted: 08/30/2019] [Indexed: 12/11/2022]
Abstract
SUMOylation of peroxisome proliferator-activated receptor gamma (PPAR γ) plays important regulatory role in its transcriptional activity. Our recent studies in vitro found that over-SUMOylation of PPARγ, like high glucose and high fat (HG/HF), induced endothelial insulin resistance (IR). However, whether such an event occurs in rats remains unclear. Therefore, our study aimed at investigating whether PPARγ over-SUMOylation could mimic high sucrose/fat diet (HFD) to induce endothelial IR and dysfunction and explored its underlying mechanisms. Normal chow-fed rats were intravenously infected with adenoviruses carrying the wild type cDNAs encoding PPARγ, SUMO1 and PIAS1 (protein inhibitor of activated STAT1). HFD-fed rats were regarded as a positive control. Body physical and biochemical parameters, glucose tolerance and vessel function were detected. The expression and SUMOylation levels of PPARγ were measured by western blotting and co-immunoprecipitation. Our results showed that like HFD, PPARγ over-SUMOylation induced endothelial IR and dysfunction via a negative regulation of eNOS-NO pathway. More importantly, we found that PPARγ over-SUMOylation induced endogenous SUMOylation cascade and exacerbated endothelial IR and dysfunction.The findings will deepen the understanding on PPARγ SUMOylation-regulating insulin signaling network and offer a potential target for prevention and cure of diabetic vascular complications.
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Affiliation(s)
- Wanwan Yuan
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi 330006, PR China; Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, PR China
| | - Cong Ma
- Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China
| | - Yumeng Zhou
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi 330006, PR China; Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, PR China
| | - Mengxi Wang
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi 330006, PR China; Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, PR China
| | - Guohua Zeng
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi 330006, PR China; Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, PR China
| | - Qiren Huang
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi 330006, PR China; Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, PR China.
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Parohan M, Sadeghi A, Khatibi SR, Nasiri M, Milajerdi A, Khodadost M, Sadeghi O. Dietary total antioxidant capacity and risk of cancer: a systematic review and meta-analysis on observational studies. Crit Rev Oncol Hematol 2019; 138:70-86. [DOI: 10.1016/j.critrevonc.2019.04.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 11/30/2018] [Accepted: 04/01/2019] [Indexed: 01/04/2023] Open
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1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:1292891. [PMID: 30984332 PMCID: PMC6431519 DOI: 10.1155/2019/1292891] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 01/21/2019] [Indexed: 12/31/2022]
Abstract
Several in vitro studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly in vivo. This study was designed to study the neurotoxicity of TaClo in vivo by stereotactically injecting TaClo into the striatum of Wistar rats. After the TaClo injections, rats were subjected to an open field test, and their distance travelled and tracks showed decreasing trends over time. The results of liquid chromatography-mass spectrometry analysis showed that the motor dysfunction of the TaClo-treated rats was accompanied by reduced dopamine levels in the striatum. Based on the diffusion tensor imaging data, the apparent diffusion coefficient of the nigrostriatal pathway was significantly increased, and subsequent histological staining revealed the demyelination of nigrostriatal fibres after the TaClo treatment. TaClo induced a loss of tyrosine hydroxylase-positive cells in the substantia nigra compacta. Regarding the underlying mechanism, TaClo caused oxidative stress in the nigrostriatal system by increasing the production of reactive oxygen species and reducing the mitochondria membrane potential. Meanwhile, the elevated expression of Iba-1, TNF-α, IL-6, Cox-2, and iNOS indicated microglial activation and a strong innate immune response in the nigrostriatal system. In addition, activated caspase-3 levels were increased. Thus, both mitochondrial impairments and the innate immune response are involved in TaClo-induced neurotoxicity.
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Teodoro JS, Nunes S, Rolo AP, Reis F, Palmeira CM. Therapeutic Options Targeting Oxidative Stress, Mitochondrial Dysfunction and Inflammation to Hinder the Progression of Vascular Complications of Diabetes. Front Physiol 2019; 9:1857. [PMID: 30705633 PMCID: PMC6344610 DOI: 10.3389/fphys.2018.01857] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 12/11/2018] [Indexed: 12/29/2022] Open
Abstract
Type 2 diabetes mellitus is a leading cause of morbidity and mortality worldwide, given its serious associated complications. Despite constant efforts and intensive research, an effective, ubiquitous treatment still eludes the scientific community. As such, the identification of novel avenues of research is key to the potential discovery of this evasive "silver bullet." We focus on this review on the matter of diabetic injury to endothelial tissue and some of the pivotal underlying mechanisms, including hyperglycemia and hyperlipidemia evoked oxidative stress and inflammation. In this sense, we revisited the most promising therapeutic interventions (both non-pharmacological and antidiabetic drugs) targeting oxidative stress and inflammation to hinder progression of vascular complications of diabetes. This review article gives particular attention to the relevance of mitochondrial function, an often ignored and understudied organelle in the vascular endothelium. We highlight the importance of mitochondrial function and number homeostasis in diabetic conditions and discuss the work conducted to address the aforementioned issue by the use of various therapeutic strategies. We explore here the functional, biochemical and bioenergetic alterations provoked by hyperglycemia in the endothelium, from elevated oxidative stress to inflammation and cell death, as well as loss of tissue function. Furthermore, we synthetize the literature regarding the current and promising approaches into dealing with these alterations. We discuss how known agents and therapeutic behaviors (as, for example, metformin, dietary restriction or antioxidants) can restore normality to mitochondrial and endothelial function, preserving the tissue's function and averting the aforementioned complications.
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Affiliation(s)
- João S Teodoro
- Center for Neurosciences and Cell Biology, Department of Life Sciences, University of Coimbra, Coimbra, Portugal
| | - Sara Nunes
- Laboratory of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research, University of Coimbra, Coimbra, Portugal
| | - Anabela P Rolo
- Center for Neurosciences and Cell Biology, Department of Life Sciences, University of Coimbra, Coimbra, Portugal
| | - Flávio Reis
- Laboratory of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research, University of Coimbra, Coimbra, Portugal
| | - Carlos M Palmeira
- Center for Neurosciences and Cell Biology, Department of Life Sciences, University of Coimbra, Coimbra, Portugal
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Abstract
Traffic-related particulate matter (PM) is a major source of outdoor air pollution worldwide. It has been recently hypothesized to cause cardiometabolic syndrome, including cardiovascular dysfunction, obesity, and diabetes. The environmental and toxicological factors involved in the processes, and the detailed mechanisms remain to be explored. The objective of this study is to assess the current scientific evidence of traffic-related PM-induced cardiometabolic syndrome. We conducted a literature review by searching the keywords of “traffic related air pollution”, “particulate matter”, “human health”, and “metabolic syndrome” from 1980 to 2018. This resulted in 25 independent research studies for the final review. Both epidemiological and toxicological findings reveal consistent correlations between traffic-related PM exposure and the measured cardiometabolic health endpoints. Smaller sizes of PM, particularly ultrafine particles, are shown to be more harmful due to their greater concentrations, reactive compositions, longer lung retention, and bioavailability. The active components in traffic-related PM could be attributed to metals, black carbon, elemental carbon, polyaromatic hydrocarbons, and diesel exhaust particles. Existing evidence points out that the development of cardiometabolic symptoms can occur through chronic systemic inflammation and increased oxidative stress. The elderly (especially for women), children, genetically susceptible individuals, and people with pre-existing conditions are identified as vulnerable groups. To advance the characterization of the potential health risks of traffic-related PM, additional research is needed to investigate the detailed chemical compositions of PM constituents, atmospheric transformations, and the mode of action to induce adverse health effects. Furthermore, we recommend that future studies could explore the roles of genetic and epigenetic factors in influencing cardiometabolic health outcomes by integrating multi-omics approaches (e.g., genomics, epigenomics, and transcriptomics) to provide a comprehensive assessment of biological perturbations caused by traffic-related PM.
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Lytrivi M, Igoillo-Esteve M, Cnop M. Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes? Curr Opin Pharmacol 2018; 43:40-45. [PMID: 30142486 DOI: 10.1016/j.coph.2018.08.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 07/25/2018] [Accepted: 08/02/2018] [Indexed: 01/05/2023]
Abstract
Type 2 diabetes is a common complex disease. Relatively little is known about the underlying pathophysiology. Mild islet inflammation has been suggested to play a pathogenic role; here we review the available evidence. Mild islet inflammation is histologically detected in pancreas sections of type 2 diabetic patients. In experimental models, it can be triggered by excess nutrients, amyloid, lipopolysaccharide, and endoplasmic reticulum and oxidative stress. Transcriptome studies do not consistently identify pro-inflammatory gene expression signatures in type 2 diabetic islets, and genetic evidence calls into question the causality of inflammation. Several anti-inflammatory medications confer a modest glucose-lowering effect, supporting the role for inflammation in type 2 diabetes. Whether these anti-inflammatory therapies target inflammation in islets or in other metabolically relevant tissues remains unknown.
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Affiliation(s)
- Maria Lytrivi
- ULB Center for Diabetes Research, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.
| | - Mariana Igoillo-Esteve
- ULB Center for Diabetes Research, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Miriam Cnop
- ULB Center for Diabetes Research, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium.
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41
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Güemes A, Georgiou P. Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes. Bioelectron Med 2018; 4:9. [PMID: 32232085 PMCID: PMC7098234 DOI: 10.1186/s42234-018-0009-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 06/10/2018] [Indexed: 12/16/2022] Open
Abstract
Diabetes is a disease caused by a breakdown in the glucose metabolic process resulting in abnormal blood glucose fluctuations. Traditionally, control has involved external insulin injection in response to elevated blood glucose to substitute the role of the beta cells in the pancreas which would otherwise perform this function in a healthy individual. The central nervous system (CNS), however, also plays a vital role in glucose homoeostasis through the control of pancreatic secretion and insulin sensitivity which could potentially be used as a pathway for enhancing glucose control. In this review, we present an overview of the brain regions, peripheral nerves and molecular mechanisms by which the CNS regulates glucose metabolism and the potential benefits of modulating them for diabetes management. Development of technologies to interface to the nervous system will soon become a reality through bioelectronic medicine and we present the emerging opportunities for the treatment of type 1 and type 2 diabetes.
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Affiliation(s)
- Amparo Güemes
- Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, South Kensington Campus, London, UK
| | - Pantelis Georgiou
- Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, South Kensington Campus, London, UK
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42
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Veloso CC, Oliveira MC, Rodrigues VG, Oliveira CC, Duarte LP, Teixeira MM, Ferreira AVM, Perez AC. Evaluation of the effects of extracts of Maytenus imbricata (Celastraceae) on the treatment of inflammatory and metabolic dysfunction induced by high-refined carbohydrate diet. Inflammopharmacology 2018; 27:539-548. [PMID: 29855750 DOI: 10.1007/s10787-018-0496-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 05/17/2018] [Indexed: 01/14/2023]
Abstract
The Maytenus genus is a member of the Celastraceae family. Numerous medicinal uses were assigned to species of this genus, with the use of roots, bark, and leaves for the treatment of gastric ulcers, as anti-inflammatory, analgesic, antiallergic, antitumor, among others. Several studies have demonstrated that natural products derived from plants have an important role in the prevention and treatment of obesity. Accordingly, we evaluated the effect of Maytenus imbricata extracts in the treatment of obesity induced by diet rich in refined carbohydrate (HC). BALB/c mice were fed chow or HC diet for 8 weeks. At the beginning of the 9th week, the HC group was subdivided into three groups: (i) group of animals that continued to consume only HC diet; (ii) the group of animals fed HC diet supplemented with ethyl acetate extract of M. imbricata roots (HC + EAE); (iii) the group of animals fed HC diet supplemented with extract in hexane/ethyl ether (HC + HEE). The period of extracts supplementation was 4 weeks. It was observed that EAE and EHE when added to the HC diet modulated the metabolic and inflammatory changes, such as: reduced the adipocytes area, improved glucose intolerance, reduced the levels of triglycerides and resistin in serum, and the number of total leukocytes in blood. In the epididymal adipose tissue, the extracts reduced proinflammatory mediators' concentration. According to the results, it was concluded that the species Maytenus imbricata has the potential to be used for the treatment of obesity.
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Affiliation(s)
- C C Veloso
- Pharmaceutical Sciences Faculty, Federal University of Amazonas (UFAM), Manaus, Amazonas, Brazil. .,Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas (UFAM), Av. General Rodrigo Octávio Jordão Ramos, 3000, Coroado I, Manaus, Amazonas, 69.077-000, Brazil.
| | - M C Oliveira
- Department of Nutrition, Nursing School, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.,Imunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - V G Rodrigues
- Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - C C Oliveira
- Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - L P Duarte
- Department of Chemistry, Institute of Exact Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - M M Teixeira
- Imunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - A V M Ferreira
- Department of Nutrition, Nursing School, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.,Imunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - A C Perez
- Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil
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Balbi ME, Tonin FS, Mendes AM, Borba HH, Wiens A, Fernandez-Llimos F, Pontarolo R. Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetol Metab Syndr 2018; 10:18. [PMID: 29568330 PMCID: PMC5853104 DOI: 10.1186/s13098-018-0318-5] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 03/03/2018] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Vitamins are essential micronutrients with antioxidant potential that may provide a complementary treatment for patients with chronic diseases. Our aim was to assess the effect of vitamin supplementation on the antioxidant status and glycemic index of type 2 diabetes mellitus patients. METHODS We performed a systematic review with meta-analyses. Electronic searches were conducted in PubMed, Scopus, and Web of Science (December 2017). Randomized controlled trials evaluating the effect of any vitamin or vitamin complex supplementation on antioxidant status as primary outcome were included. The outcomes considered were: reduction of malondialdehyde (MDA); augmentation of glutathione peroxidase (GPx); changes in total antioxidant capacity (TAC), enhance in superoxide dismutase enzyme-SOD, and thiobarbituric acid reactive substances (TBARS). Outcomes of glycemic control were also evaluated. Pairwise meta-analyses were performed using software Review Manager 5.3. RESULTS Thirty trials fulfilled the inclusion criteria, but only 12 could be included in the meta-analyses of antioxidant outcomes. The most commonly studied vitamins were B, C, D and E. Vitamin E was related to significant reduction of blood glucose as well as glycated hemoglobin compared to placebo, while both vitamins C and E were mainly associated with reducing MDA and TBARS and elevating GPx, SOD and TAC, compared to placebo. However, outcome reports in this field are still inconsistent (e.g. because of a lack of standard measures). CONCLUSIONS Supplementation of vitamin E may be a valuable strategy for controlling diabetes complications and enhancing antioxidant capacity. The effects of other micronutrients should be further investigated in larger and well-designed trials to properly place these complementary therapies in clinical practice.
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Affiliation(s)
- Maria E. Balbi
- Pharmaceutical Sciences Postgraduate Programme, Universidade Federal do Paraná, Curitiba, Brazil
| | - Fernanda S. Tonin
- Pharmaceutical Sciences Postgraduate Programme, Universidade Federal do Paraná, Curitiba, Brazil
| | - Antonio M. Mendes
- Pharmaceutical Sciences Postgraduate Programme, Universidade Federal do Paraná, Curitiba, Brazil
| | - Helena H. Borba
- Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Av. Prof. Lothario Meissner 632, Curitiba, 80210-170 Brazil
| | - Astrid Wiens
- Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Av. Prof. Lothario Meissner 632, Curitiba, 80210-170 Brazil
| | - Fernando Fernandez-Llimos
- Research Institute for Medicines (iMed.ULisboa), Department of Social Pharmacy, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Roberto Pontarolo
- Department of Pharmacy, Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Av. Prof. Lothario Meissner 632, Curitiba, 80210-170 Brazil
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Wu M, Song J, Zhu C, Wang Y, Yin X, Huang G, Zhao K, Zhu J, Duan Z, Su L. Association between cadmium exposure and diabetes mellitus risk: a prisma-compliant systematic review and meta-analysis. Oncotarget 2017; 8:113129-113141. [PMID: 29348892 PMCID: PMC5762577 DOI: 10.18632/oncotarget.21991] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/21/2017] [Indexed: 12/16/2022] Open
Abstract
Cadmium (Cd) is a pollutant with multiple adverse health effects: cancer, renal dysfunction, osteoporosis and fracture, and cardiovascular disease. Several population-based studies found an association between Cd and diabetes mellitus (DM), but this association is inconsistent with other research. We conducted meta-analysis to examine relationship between urinary/blood Cd exposure and DM risk. Pertinent studies were identified by searching PubMed and Embase databases, and combined odds ratio (OR) and corresponding 95% confidence interval (CI) were applied to evaluate said association. Meta-analysis showed that high U-Cd exposure is not correlated with DM risk (OR = 1.19; 95% CI = 0.83–1.71), and high B-Cd exposure is also not associated with increased risk of DM (OR = 1.16; 95% CI = 0.84-1.62) in the general population. Subgroup and sensitivity analysis proved similar results, with little evidence of publication bias. This meta-analysis suggests that high U-Cd/B-Cd exposure may not be risk factor for DM in general populations. However, large prospective studies are needed to confirm this finding.
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Affiliation(s)
- Ming Wu
- Department of Emergency Medicine, Guizhou Provincial People's Hospital, Guizhou, China
| | - Jukun Song
- Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China
| | - Chen Zhu
- Guiyang Hospital of Stomatology, Medical College, Zunyi Medical College, Guiyang, China
| | - Yadong Wang
- Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China
| | - Xinhai Yin
- Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China
| | - Guanglei Huang
- Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China
| | - Ke Zhao
- Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guizhou, China
| | - Jianguo Zhu
- Department of Urology, Guizhou Provincial People's Hospital, Guizhou, China
| | - Zhuhui Duan
- Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Hangzhou, China
| | - Lingkai Su
- Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Hangzhou, China
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Resistin as a Prooxidant Factor and Predictor of Endothelium Damage in Patients with Mild Acute Pancreatitis Exposed to Tobacco Smoke Xenobiotics. Mediators Inflamm 2017; 2017:3039765. [PMID: 29081601 PMCID: PMC5634610 DOI: 10.1155/2017/3039765] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 07/27/2017] [Indexed: 12/17/2022] Open
Abstract
Objectives The study was aimed to assess the influence of tobacco smoke exposure on the intensity of inflammation measured by IL-6, α1-antitripsin (AAT) and α1-acid glycoprotein (AGP) concentrations, and Cd level and oxidative stress intensity measured by advanced oxidation protein product (AOPP) concentration in the blood of healthy subjects and AP patients during hospitalization. Endothelin-1 (ET-1) and resistin concentrations, markers of endothelium injury, were determined. Results An increased IL-6 concentration in healthy smokers compared to nonsmokers and AP patients compared to controls was shown. An increased AAT and AGP concentrations during hospitalization of AP patients were noted, in both smokers (AAT, AGP) and nonsmokers (AAT). In comparison to control groups, in AP patients, a 2-fold increased resistin concentration correlating with ET-1 concentration and decreased albumin concentration accompanied by increased AOPP concentration were demonstrated. AOPP concentration was higher in smokers with AP compared to nonsmokers and gradually enhanced during their hospitalization. Conclusions Tobacco smoke exposure can have a proinflammatory effect in both healthy subjects and AP patients. Increased resistin concentration in AP patients negatively correlating with albumin concentration has prooxidative effect on this protein resulting in enhanced AOPP level. Increased resistin concentration can intensify AAT and AGP production during AP.
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Wilson R, Willis J, Gearry R, Skidmore P, Fleming E, Frampton C, Carr A. Inadequate Vitamin C Status in Prediabetes and Type 2 Diabetes Mellitus: Associations with Glycaemic Control, Obesity, and Smoking. Nutrients 2017; 9:E997. [PMID: 28891932 PMCID: PMC5622757 DOI: 10.3390/nu9090997] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/04/2017] [Accepted: 09/06/2017] [Indexed: 02/07/2023] Open
Abstract
Vitamin C (ascorbate) is an essential micronutrient in humans, being required for a number of important biological functions via acting as an enzymatic cofactor and reducing agent. There is some evidence to suggest that people with type 2 diabetes mellitus (T2DM) have lower plasma vitamin C concentrations compared to those with normal glucose tolerance (NGT). The aim of this study was to investigate plasma vitamin C concentrations across the glycaemic spectrum and to explore correlations with indices of metabolic health. This is a cross-sectional observational pilot study in adults across the glycaemic spectrum from NGT to T2DM. Demographic and anthropometric data along with information on physical activity were collected and participants were asked to complete a four-day weighed food diary. Venous blood samples were collected and glycaemic indices, plasma vitamin C concentrations, hormone tests, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were analysed. A total of 89 participants completed the study, including individuals with NGT (n = 35), prediabetes (n = 25), and T2DM managed by diet alone or on a regimen of Metformin only (n = 29). Plasma vitamin C concentrations were significantly lower in individuals with T2DM compared to those with NGT (41.2 µmol/L versus 57.4 µmol/L, p < 0.05) and a higher proportion of vitamin C deficiency (i.e. <11.0 µmol/L) was observed in both the prediabetes and T2DM groups. The results showed fasting glucose (p = 0.001), BMI (p = 0.001), smoking history (p = 0.003), and dietary vitamin C intake (p = 0.032) to be significant independent predictors of plasma vitamin C concentrations. In conclusion, these results suggest that adults with a history of smoking, prediabetes or T2DM, and/or obesity, have greater vitamin C requirements. Future research is required to investigate whether eating more vitamin C rich foods and/or taking vitamin C supplements may reduce the risk of progression to, and/or complications associated with, T2DM.
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Affiliation(s)
- Renée Wilson
- Department of Medicine, University of Otago, Christchurch 8011, New Zealand.
| | - Jinny Willis
- Lipid and Diabetes Research Group, Canterbury District Health Board, Christchurch 8011, New Zealand.
| | - Richard Gearry
- Department of Medicine, University of Otago, Christchurch 8011, New Zealand.
| | - Paula Skidmore
- Department of Human Nutrition, University of Otago, Dunedin 9016, New Zealand.
| | - Elizabeth Fleming
- Department of Human Nutrition, University of Otago, Dunedin 9016, New Zealand.
| | - Chris Frampton
- Department of Medicine, University of Otago, Christchurch 8011, New Zealand.
| | - Anitra Carr
- Department of Pathology, University of Otago, Christchurch 8011, New Zealand.
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Zhang Y, Yi W, Yao J, Yu X, Qian C, Hu Z. Hypoxia serves a key function in the upregulated expression of vascular adhesion protein‑1 in vitro and in a rat model of hemorrhagic shock. Mol Med Rep 2017. [PMID: 28627649 PMCID: PMC5562078 DOI: 10.3892/mmr.2017.6727] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hemorrhagic shock following major trauma results in mortality, but the function of vascular adhesion protein-1 (VAP-1), implicated in intracranial hemorrhage, remains unknown. This study aimed to determine whether expression of the AOC3 gene and its encoded protein, VAP-1, is altered by hypoxia. Rat hepatic sinusoidal endothelial cells (RHSECs) and rat intestinal microvascular endothelial cells (RIMECs) were transduced with a viral vector carrying AOC3, and AOC3 mRNA expression levels were measured by reverse transcription-quantitative polymerase chain reaction. VAP-1 protein expression levels were measured by western blot analysis and compared between normoxic and hypoxic conditions. Following this, AOC3 mRNA and VAP-1 protein expression levels in hepatic and intestinal tissues were assessed in a rat model of hemorrhagic shock with or without fluid resuscitation; and serum semicarbazide-sensitive amine oxidase (SSAO) activity was measured by fluorometric assays. The effects of 2-bromoethylamine (2-BEA) on AOC3/VAP-1 levels and 24 h survival were investigated. AOC3 mRNA and VAP-1 protein levels were increased in RHSECs and RIMECs by hypoxia, and in hepatic and intestinal tissues from rats following hemorrhagic shock. Hypoxia increased serum SSAO activity in these animals. 2-BEA reduced AOC3 mRNA and VAP-1 protein levels in hepatic and intestinal tissues from rats following hemorrhagic shock, and appeared to improve survival in animals not receiving resuscitation following hemorrhagic shock. In conclusion, hemorrhagic shock upregulates AOC3/VAP-1 expressions, and this potentially occurs via hypoxia. Therefore, inhibition of VAP-1 may be beneficial in the setting of hemorrhagic shock. Further studies are required to confirm these findings and to establish whether VAP-1 may be a valid target for the development of novel therapies for hemorrhagic shock.
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Affiliation(s)
- Yuxing Zhang
- Department of General Surgery, Navy General Hospital, Beijing 100048, P.R. China
| | - Wei Yi
- Department of General Surgery, China People's Liberation Army No. 94 Hospital, Nanchang, Jiangxi 330002, P.R. China
| | - Jun Yao
- Department of General Surgery, Shanghai Changzheng Hospital, Shanghai 200003, P.R. China
| | - Xiaojun Yu
- Department of Gastroenterological Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
| | - Cheng Qian
- Department of General Surgery, Huzhou Maternity & Child Care Hospital, Huzhou, Zhejiang 313000, P.R. China
| | - Zhiqian Hu
- Department of General Surgery, Shanghai Changzheng Hospital, Shanghai 200003, P.R. China
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Hartati FK, Widjanarko SB, Widyaningsih TD, Rifa’i M. Anti-Inflammatory evaluation of black rice extract inhibits TNF-α, IFN-γ and IL-6 cytokines produced by immunocompetent cells. FOOD AGR IMMUNOL 2017. [DOI: 10.1080/09540105.2017.1332006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Fadjar Kurnia Hartati
- Post Graduate Program, Faculty of Agricultural, Brawijaya University, Malang, Indonesia
- Department of Food Technology, Faculty of Agricultural, Dr. Soetomo University, Surabaya, Indonesia
| | - Simon Bambang Widjanarko
- Department of Food Science and Technology, Faculty of Agricultural Technology, Brawijaya University, Malang, Indonesia
| | - Tri Dewanti Widyaningsih
- Department of Food Science and Technology, Faculty of Agricultural Technology, Brawijaya University, Malang, Indonesia
| | - Muhaimin Rifa’i
- Biology Department, Faculty of Mathematic and Natural Sciences, Brawijaya University, Malang, Indonesia
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Extracts of Mauritian Carica papaya (var. solo) protect SW872 and HepG2 cells against hydrogen peroxide induced oxidative stress. Journal of Food Science and Technology 2017; 54:1917-1927. [PMID: 28720948 DOI: 10.1007/s13197-017-2626-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 04/04/2017] [Accepted: 04/05/2017] [Indexed: 10/19/2022]
Abstract
In line with literature documenting the pluripotent activities of tropical fruits, this study evaluated the antioxidant effects of Carica papaya fruit extracts at cellular level. Investigations using cellular models of oxidative stress provided complementary evidence of the antioxidant activities of papaya fruit. At 2 mg dry weight ml-1, extracts of seed from ripe and unripe fruit significantly reduced oxidative stress levels within human pre-adipocytes (SW872) and hepatocellular carcinoma cells (HepG2) exposed to hydrogen peroxide (H2O2). Maintenance of mitochondrial viability, reduction of intracellular reactive oxygen species levels and mediation of pro-inflammatory cytokine secretory levels (tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1) were all indicative of its cytoprotective effects against oxidative-inflammation. This work demonstrates that the Mauritian Solo papaya is an important source of natural antioxidants that could be used for the dietary modulation of oxidative stress and inflammation.
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She Y, Jiang L, Zheng L, Zuo H, Chen M, Sun X, Li Q, Geng C, Yang G, Jiang L, Liu X. The role of oxidative stress in DNA damage in pancreatic β cells induced by di-(2-ethylhexyl) phthalate. Chem Biol Interact 2017; 265:8-15. [DOI: 10.1016/j.cbi.2017.01.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Revised: 01/10/2017] [Accepted: 01/19/2017] [Indexed: 02/02/2023]
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