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Gopalsamy RG, Antony PJ, Athesh K, Hillary VE, Montalvão MM, Hariharan G, Santana LADM, Borges LP, Gurgel RQ. Dietary essential oil components: A systematic review of preclinical studies on the management of gastrointestinal diseases. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 140:156630. [PMID: 40085990 DOI: 10.1016/j.phymed.2025.156630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/24/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND The gut is responsible for the digestion and absorption of nutrients, immune regulation, and barrier function. However, factors like poor diet, stress, and infection, can disrupt the balance of the gut microbiota and lead to intestinal inflammation and dysfunction. PURPOSE This systematic review aims to evaluate the effects of dietary plants-derived essential oil components on gut health and intestinal functions in animal models. METHODS The literature was gathered from the Scopus, Web of Science, PubMed, and Embase databases by using related search terms, such as "dietary plants", "dietary sources", "essential oils", "gut health", "intestine", "anti-inflammatory", "antioxidant", and "gut microbiota". RESULTS The results indicate that plant-derived dietary essential oil components, such as butyrolactone-I, carvacrol, cinnamaldehyde, citral, D-limonene, eugenol, farnesol, geraniol, indole, nerolidol, oleic acid, thymol, trans-anethole, vanillin, α-bisabolol, α-linolenic acid, α-pinene, α-terpineol, β-carotene, β-caryophyllene, and β-myrcene have been found to regulate gut health by influencing vital signalling pathways associated with inflammation. Dietary essential oil components modulate the expression of tumor necrosis factor alpha, interleukin 1 beta (IL-1β), interleukin (IL)-6, IL-10, inducible nitric oxide synthase, cyclooxygenase-2, toll-like receptor-4, matrix metalloproteinase, and interferon gamma in mitigating gut inflammation. The primary signalling molecules controlled by these molecules were AMP-activated protein kinase (AMPK), protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase, mitogen-activated protein kinase, myeloid differentiation primary response 88, nuclear factor erythroid-2-related factor-2, and phosphoinositide 3-kinase (PI3K). Moreover, these phytochemicals have been shown to improve glucose homeostasis by regulating glucose transporter 4, glucagon-like peptide-1, peroxisome proliferator-activated receptor gamma, nuclear factor kappa B, AMPK, PI3K, and uncoupling protein-1. They can also reduce thiobarbituric acid reactive substance, malondialdehyde, and oxidative stress and enhance superoxide dismutase, catalase, and glutathione peroxidase levels. CONCLUSION In conclusion, dietary plants-derived essential oil components have the potential to mitigate inflammation and oxidative stress in the gut. However, additional clinical investigations are necessary to confirm their complete potential in improving human gut health functions.
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Affiliation(s)
- Rajiv Gandhi Gopalsamy
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, Kerala, India; Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Campus Prof. João Cardoso Nascimento, Aracaju, Sergipe, Brazil
| | - Poovathumkal James Antony
- Department of Microbiology, North Bengal University, St. Joseph's College, Darjeeling, West Bengal, India
| | - Kumaraswamy Athesh
- School of Sciences, Bharata Mata College (Autonomous), Kochi, Kerala, India
| | - Varghese Edwin Hillary
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, Kerala, India
| | | | | | | | - Lysandro Pinto Borges
- Department of Pharmacy, Federal University of Sergipe, São Cristovão, Sergipe, Brazil
| | - Ricardo Queiroz Gurgel
- Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Campus Prof. João Cardoso Nascimento, Aracaju, Sergipe, Brazil.
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Anghel L, Ciubară A, Patraș D, Ciubară AB. Chronic Obstructive Pulmonary Disease and Type 2 Diabetes Mellitus: Complex Interactions and Clinical Implications. J Clin Med 2025; 14:1809. [PMID: 40142617 PMCID: PMC11942939 DOI: 10.3390/jcm14061809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/01/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic conditions, frequently coexisting due to their shared pathophysiological mechanisms and risk factors. Epidemiological studies estimate that up to 30% of COPD patients have comorbid T2DM, contributing to worsened disease progression, more hospitalizations, and higher mortality rates. Systemic inflammation in COPD contributes to insulin resistance by increasing pro-inflammatory cytokines (TNF-α, IL-6, and CRP), which impair glucose metabolism and beta-cell function. Conversely, hyperglycemia in T2DM exacerbates oxidative stress, leading to endothelial dysfunction, reduced lung function, and impaired pulmonary repair mechanisms. A comprehensive narrative review was conducted to evaluate the interplay between COPD and T2DM, examining shared pathophysiological mechanisms, clinical consequences, and management strategies. The co-occurrence of COPD and T2DM accelerates disease development, elevates hospitalization rates, and deteriorates overall prognosis. Pharmacological interactions complicate illness treatment, requiring a multidisciplinary therapy strategy. Recent data underscore the need to integrate palliative care, facilitate shared decision-making, and provide psychological support to enhance patient outcomes. Efficient therapy of COPD-T2DM comorbidity necessitates a customized, interdisciplinary strategy that targets both respiratory and metabolic health. Preliminary prognostic dialogues, palliative care, and holistic lifestyle modifications can improve patient quality of life and clinical results.
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Affiliation(s)
- Lucreția Anghel
- Saint Apostle Andrew Emergency County Clinical Hospital, 177 Brailei St., 800578 Galati, Romania; (L.A.); (D.P.)
- Faculty of Medicine and Pharmacy, Dunarea de Jos University of Galati, 35 AI Cuza St., 800010 Galati, Romania;
| | - Anamaria Ciubară
- Faculty of Medicine and Pharmacy, Dunarea de Jos University of Galati, 35 AI Cuza St., 800010 Galati, Romania;
| | - Diana Patraș
- Saint Apostle Andrew Emergency County Clinical Hospital, 177 Brailei St., 800578 Galati, Romania; (L.A.); (D.P.)
- Doctoral School Biomedicine Science, University Galati, 800008 Galati, Romania
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Panuccio G, Correale P, d'Apolito M, Mutti L, Giannicola R, Pirtoli L, Giordano A, Labate D, Macheda S, Carabetta N, Abdelwahed YS, Landmesser U, Tassone P, Tagliaferri P, De Rosa S, Torella D. Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients. Basic Res Cardiol 2025; 120:153-169. [PMID: 39225869 PMCID: PMC11790807 DOI: 10.1007/s00395-024-01077-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 08/16/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.
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Affiliation(s)
- Giuseppe Panuccio
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany.
- Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
| | - Pierpaolo Correale
- Medical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA
| | - Maria d'Apolito
- Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
- Medical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy
| | - Luciano Mutti
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA
- Department of Applied Sciences and Biotechnology, Università dell'Aquila, L'Aquila, Italy
| | - Rocco Giannicola
- Medical Oncology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy
| | - Luigi Pirtoli
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA
| | - Antonio Giordano
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA
- Department of Medical Biotechnology, University of Siena, 53100, Siena, Italy
| | - Demetrio Labate
- Unit of Intensive Care Medicine and Anesthesia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy
| | - Sebastiano Macheda
- Unit of Intensive Care Medicine and Anesthesia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124, Reggio Calabria, Italy
| | - Nicole Carabetta
- Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Youssef S Abdelwahed
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), 10785, Berlin, Germany
| | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité Berlin, 12200, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), 10785, Berlin, Germany
- Berlin Institute of Health (BIH), 10178, Berlin, Germany
| | - Pierfrancesco Tassone
- Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA
| | - Pierosandro Tagliaferri
- Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Salvatore De Rosa
- Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Daniele Torella
- Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
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Manaer T, Sailike J, Sun X, Yeerjiang B, Nabi X. Therapeutic effects of composite probiotics derived from fermented camel milk on metabolic dysregulation and intestinal barrier integrity in type 2 diabetes rats. Front Pharmacol 2025; 15:1520158. [PMID: 39840100 PMCID: PMC11747018 DOI: 10.3389/fphar.2024.1520158] [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: 10/30/2024] [Accepted: 12/18/2024] [Indexed: 01/23/2025] Open
Abstract
Background In the Kazakh community of Xinjiang, China, fermented camel milk has been traditionally used to manage diabetes. This study evaluates the effects of composite probiotics derived from fermented camel milk (CPCM) on metabolic disturbances in a rat model of Type 2 diabetes (T2DM). Methods T2DM was induced in Wistar rats using streptozotocin. Experimental groups included a diabetic control, Metformin, and low- and high-dose CPCM. Measurements over 6 weeks included body weight (BW), fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), C-peptide (CP), lipid profiles, inflammatory markers, fecal short-chain fatty acids (SCFAs), and tight junction protein expression in colonic tissues. Results High-dose CPCM significantly increased BW by 22.2% (p < 0.05) and reduced FBG by 6.5 mmol/L (p < 0.001). The OGTT AUC decreased by 40.1% (p < 0.001), and HbA1c levels fell by 22.9% (p < 0.01). CP levels rose by 21.8% (p < 0.05). Lipid profiles improved: TC decreased by 40.0%, TG by 17.1%, and LDL-C by 30.4% (all p < 0.001). Fecal SCFAs, including acetate (75.4%, p < 0.001), methyl acetate (18.9%, p < 0.05), and butyrate (289.9%, p < 0.001), increased, with total SCFAs rising by 89.7% (p < 0.001). Inflammatory markers IL-1β (12.7%, p < 0.01), TNF-α (16.7%, p < 0.05), and IL-6 (17.3%, p < 0.01) were significantly reduced. Tight junction protein expression (ZO-1, occludin, claudin-1) and mucin (MUC2) in colonic tissues increased (p < 0.05). CPCM treatment also reduced serum total bile acids by 24.9%, while hepatic and fecal bile acids increased by 114.0% and 37.8% (all p < 0.001). CPCM lowered serum DAO, D-lactate, and LPS levels (all p < 0.001). mRNA levels of TGR5 and CYP7A1 in the liver, and TGR5 and FXR in the colon, were markedly elevated (all p < 0.001). Histological examinations revealed reduced pancreatic inflammation and hepatic steatosis, with restored colonic structure. Conclusion CPCM treatment significantly improved metabolic dysregulation in the T2DM rat model, reducing blood glucose and lipid levels, enhancing intestinal barrier function, and increasing insulin secretion. These findings highlight the therapeutic potential of CPCM in T2DM management and probiotics' role in metabolic health.
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Affiliation(s)
- Tabusi Manaer
- School of Pharmacy, Xinjiang Medical University, Urumchi, China
- Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi, China
- Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumchi, China
| | | | - Xin Sun
- Srational for Drug Control and Medical Device Varification of Xinjiang Military Command, Urumchi, China
| | - Baheban Yeerjiang
- School of Pharmacy, Xinjiang Medical University, Urumchi, China
- Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi, China
- Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumchi, China
| | - Xinhua Nabi
- School of Pharmacy, Xinjiang Medical University, Urumchi, China
- Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi, China
- Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumchi, China
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Dawi J, Misakyan Y, Affa S, Kades S, Narasimhan A, Hajjar F, Besser M, Tumanyan K, Venketaraman V. Oxidative Stress, Glutathione Insufficiency, and Inflammatory Pathways in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions. Biomedicines 2024; 13:18. [PMID: 39857603 PMCID: PMC11762874 DOI: 10.3390/biomedicines13010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/18/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
Type 2 diabetes mellitus (T2DM) is significantly associated with oxidative stress, resulting from the imbalance between reactive oxygen species (ROS) production and antioxidant defenses. This imbalance contributes to insulin resistance, β-cell dysfunction, and complications in organs like the vasculature and nervous system. Glutathione (GSH), a major antioxidant, is crucial for neutralizing ROS, but GSH levels are notably low in T2DM, exacerbating oxidative stress and inflammation. Elevated interleukin-6 (IL-6) levels further intensify inflammation and oxidative stress, disrupting insulin signaling and worsening complications such as nephropathy, retinopathy, and neuropathy. While lifestyle modifications and antioxidant supplementation are current approaches for managing oxidative stress, their effectiveness in preventing complications remains under study. Recent investigations suggest that GSH and Vitamin D3 supplementation may offer dual-action benefits, as Vitamin D3 not only has anti-inflammatory properties but also promotes GSH synthesis. This dual action helps mitigate both oxidative stress and inflammation, addressing key pathological features of T2DM. This review highlights the complex interactions between oxidative stress, GSH insufficiency, and IL-6, and emphasizes the potential of targeted therapies to improve the management and outcomes of T2DM.
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Affiliation(s)
- John Dawi
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Yura Misakyan
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Stephen Affa
- Department of Chemistry, Physics, and Engineering, Los Angeles Valley College, Valley Glen, CA 91401, USA;
| | - Samuel Kades
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Ananya Narasimhan
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Fouad Hajjar
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Max Besser
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
| | - Kevin Tumanyan
- College of Podiatric Medicine, Western University of Health Sciences, Pomona, CA 91766, USA;
| | - Vishwanath Venketaraman
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; (J.D.); (Y.M.); (S.K.); (A.N.); (F.H.); (M.B.)
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Ferreira J, Roque S, Longatto-Filho A, Afonso J, Carneiro A, Vila I, Silva C, Cunha C, Mesquita A, Cotter J, Correia-Neves M, Mansilha A, Cunha P. Higher Levels of Cytokines in Patients with Chronic Limb-Threatening Ischemia. Ann Vasc Surg 2024; 106:255-263. [PMID: 38821475 DOI: 10.1016/j.avsg.2024.02.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/06/2024] [Accepted: 02/28/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Inflammation is a key element in the initiation and progression of peripheral arterial disease (PAD). Understanding the impact of inflammatory molecules, as cytokines in PAD could help us to improve the prognosis of these patients. The main goal of this study was to compare the serum level of cytokines between patients with claudication to those with chronic limb-threatening ischemia (CLTI). The second objective was to evaluate the relationship between the levels of cytokines and death or amputation rate. METHODS An observational, single-center, and prospective study was conducted from January 2018 to July 2022. The study was approved by the ethical commission of the Local Hospital (75/2017). Patients with PAD, suggested by the clinical history and objective examination and confirmed with ankle-brachial index, attending vascular surgery consultations of the first author were included. The following exclusion criteria were applied: i) bedridden individuals or subjects who refused to participate in the protocol; ii) diseases responsible for body composition changes or proinflammatory state; iii) recent diet change, iv) active malignancy, v) autoimmune disease, vi) active infection, vii) chronic renal failure (glomerular filtration rate <30 mL/min/1.73 m2), or viii) heart failure in the past 3 months. This cohort was observed at admission, 3, 6, and 12 months. A panel of 27 cytokines was determined with ELISA, at baseline. RESULTS We included 119 subjects (mean age: 67.58 ± 9.60 years old; 79.80% males), 65 patients with claudication and 54 with CLTI. From the 27 cytokines analyzed, patients with CLTI, when compared to those with claudication, had a higher serum level of 11 cytokines: IL1ra, IL-6, IL-8, IL12 p70, G-CSF, IP-10, MCP-1, MIP-1α, PDGF-β, RANTES, and TNF-α. From the group of patients with CLTI those who underwent a major amputation had a higher serum level of FGF-basic [median = 49.04; interquartile range = 37.03-52.49; versus median = 33.04; interquartile range = 28.60-38.98; P = 0.001]. CONCLUSIONS Patients with CLTI have higher serum level of inflammatory cytokines, which may have role in the prognosis of these patients.
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Affiliation(s)
- Joana Ferreira
- Vascular Surgery Department - Fisiologia e Cirurgia, Centro Hospitalar Universitário de São João, Porto, Portugal; Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal.
| | - Susana Roque
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal
| | - Adhemar Longatto-Filho
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal; Department of Pathology (LIM-14), University of São Paulo School of Medicine, São Paulo, Brazil; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | - Julieta Afonso
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal
| | | | - Isabel Vila
- Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Cristina Silva
- Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Cristina Cunha
- Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Amílcar Mesquita
- Vascular Surgery Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Jorge Cotter
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal; Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Margarida Correia-Neves
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal
| | - Armando Mansilha
- Vascular Surgery Department - Fisiologia e Cirurgia, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Pedro Cunha
- Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; Centro Académico Hospital da Senhora da Oliveira, Guimarães, Portugal; ICVS/3B's - PT Government Associated Laboratory, Braga/Guimarães, Portugal; Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, Guimarães, Portugal
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Xu F, Dou L, Yu D, Wu X, Liu L, Man Y, Huang X. A Novel "Endocrine Hormone": The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance. Int J Med Sci 2024; 21:2081-2093. [PMID: 39239539 PMCID: PMC11373541 DOI: 10.7150/ijms.97217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 07/24/2024] [Indexed: 09/07/2024] Open
Abstract
Insulin resistance is the primary contributor to the disruption in glucose homeostasis in the body, playing a significant causative role in many metabolic diseases. Insulin resistance is characterized by compensatory insulin secretion and reduced insulin responsiveness in target organs. Dysregulation of the interaction between insulin-secreting cells and insulin-responsive target organs is an important factor driving the progression of insulin resistance. Circulating endocrine hormones are important mediators mediating the interaction between insulin-secreting cells and insulin-responsive target organs. In addition to the classical hormones secreted by endocrine glands and organ-specific hormones secreted by metabolism-related organs (adipose tissue, muscle, liver, etc.), extracellular vesicles have been recognized as a novel class of endocrine hormones with a complex composition. Extracellular vesicles can transport signaling molecules, such as miRNAs and LncRNAs, to vital organs related to insulin resistance, in a manner akin to conventional hormones. The significant role in regulating the development of insulin resistance underscores the increasing interest in extracellular vesicles as essential contributors to this process. In this review, we summarize the three types of hormones (classical hormones, organokines and extracellular vesicles) that play a regulatory role in insulin resistance, and focus on the novel endocrine hormones, extracellular vesicles, to elaborate the mechanism of extracellular vesicles' regulation of insulin resistance progress from two aspects: the impact on insulin-secreting cells and the influence on insulin-responsive target organs. In addition, this paper outlines the clinical applications of extracellular vesicles in insulin resistance. A comprehensive understanding of the regulatory mechanisms and diagnostic status of the inter-organ network in insulin resistance has great potential to advance targeted therapeutic interventions and diagnostic markers, thereby benefiting both the prevention and treatment of insulin resistance.
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Affiliation(s)
- Fangzhi Xu
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
| | - Lin Dou
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
| | - Dongni Yu
- Department of Dermatology, Beijing hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100730, Beijing, P.R. China
| | - Xi Wu
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
| | - Longteng Liu
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
| | - Yong Man
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
| | - Xiuqing Huang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology of National Health Commission, 100730, Beijing, P.R. China
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Villarroel-Vicente C, García A, Zibar K, Schiel MA, Ferri J, Hennuyer N, Enriz RD, Staels B, Cortes D, Cabedo N. Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects. Bioorg Med Chem Lett 2024; 106:129770. [PMID: 38677560 DOI: 10.1016/j.bmcl.2024.129770] [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: 12/12/2023] [Revised: 04/17/2024] [Accepted: 04/23/2024] [Indexed: 04/29/2024]
Abstract
We have previously reported the total synthesis and structure-activity relationships (SAR) of 2-prenylated benzopyrans with PPAR agonist activity. Herein, we have described the synthesis and PPAR activity of 2-prenylated benzopyrans and 2-prenylated quinolines. The benzopyran nucleus was generated via enamine-catalyzed Kabbe condensation, and the quinoline nucleus via Friedländer condensation. Results demonstrated that both benzopyran (5a) and quinoline (4b) derivatives bearing a γ,δ-unsaturated ester displayed a pan-PPAR agonism. They were full PPARα agonists, but showed different preferences for PPARγ and PPARβ/δ activation. It was noteworthy that quinoline 4b displayed full hPPARα activation (2-fold than WY-14,643), weak PPARβ/δ and partial PPARγ activation. In addition, quinoline 4b showed anti-inflammatory effects on macrophages by reducing LPS-induced expression of both MCP-1 and IL-6. Therefore, 4b emerges as a first-in-class promising hit compound for the development of potential therapeutics aimed at treating metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and its associated cardiovascular comorbidities.
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Affiliation(s)
- Carlos Villarroel-Vicente
- Department of Pharmacology, University of Valencia, 46100 Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010 Valencia, Spain
| | - Ainhoa García
- Department of Pharmacology, University of Valencia, 46100 Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010 Valencia, Spain
| | - Khamis Zibar
- Univ Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000 Lille, France
| | - María Ayelén Schiel
- Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis-IMIBIO-SL-CONICET, Chacabuco 915, San Luis, Argentina
| | - Jordi Ferri
- Service of Endocrinology and Nutrition, University Clinic Hospital of Valencia, 46010 Valencia, Spain
| | - Nathalie Hennuyer
- Univ Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000 Lille, France
| | - Ricardo D Enriz
- Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis-IMIBIO-SL-CONICET, Chacabuco 915, San Luis, Argentina
| | - Bart Staels
- Univ Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000 Lille, France
| | - Diego Cortes
- Department of Pharmacology, University of Valencia, 46100 Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010 Valencia, Spain.
| | - Nuria Cabedo
- Department of Pharmacology, University of Valencia, 46100 Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010 Valencia, Spain.
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9
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Audu CO, Wolf SJ, Joshi AD, Moon JY, Melvin WJ, Sharma SB, Davis FM, Obi AT, Wasikowski R, Tsoi LC, Barrett EC, Mangum KD, Bauer TM, Kunkel SL, Moore BB, Gallagher KA. Histone demethylase JARID1C/KDM5C regulates Th17 cells by increasing IL-6 expression in diabetic plasmacytoid dendritic cells. JCI Insight 2024; 9:e172959. [PMID: 38912581 PMCID: PMC11383169 DOI: 10.1172/jci.insight.172959] [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: 06/13/2023] [Accepted: 05/10/2024] [Indexed: 06/25/2024] Open
Abstract
Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about pDCs in diabetic wound tissue and their interactions with naive CD4+ T cells. Diabetic wounds are characterized by increased levels of inflammatory IL-17A cytokine, partly due to increased Th17 CD4+ cells. This increased IL-17A cytokine, in excess, impairs tissue repair. Here, using human tissue and murine wound healing models, we found that diabetic wound pDCs produced excess IL-6 and TGF-β and that these cytokines skewed naive CD4+ T cells toward a Th17 inflammatory phenotype following cutaneous injury. Further, we identified that increased IL-6 cytokine production by diabetic wound pDCs is regulated by a histone demethylase, Jumonji AT-rich interactive domain 1C histone demethylase (JARID1C). Decreased JARID1C increased IL-6 transcription in diabetic pDCs, and this process was regulated upstream by an IFN-I/TYK2/JAK1,3 signaling pathway. When inhibited in nondiabetic wound pDCs, JARID1C skewed naive CD4+ T cells toward a Th17 phenotype and increased IL-17A production. Together, this suggests that diabetic wound pDCs are epigenetically altered to increase IL-6 expression that then affects T cell phenotype. These findings identify a therapeutically manipulable pathway in diabetic wounds.
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Affiliation(s)
- Christopher O Audu
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
- Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
| | - Sonya J Wolf
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Amrita D Joshi
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Jadie Y Moon
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - William J Melvin
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Sriganesh B Sharma
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Frank M Davis
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Andrea T Obi
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Rachel Wasikowski
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Lam C Tsoi
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Emily C Barrett
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Kevin D Mangum
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Tyler M Bauer
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Steven L Kunkel
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
- Department of Pathology, School of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Beth B Moore
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Katherine A Gallagher
- Section of Vascular Surgery, Department of Surgery, and
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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10
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Nikooyeh B, Zargaraan A, Ebrahimof S, Kalayi A, Zahedirad M, Yazdani H, Rismanchi M, Karami T, Khazraei M, Jafarpour A, Neyestani TR. Added γ-oryzanol boosted anti-inflammatory effects of canola oil in adult subjects with type 2 diabetes: a randomized controlled clinical trial. Eur J Nutr 2024; 63:425-433. [PMID: 37971692 DOI: 10.1007/s00394-023-03275-w] [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: 07/08/2023] [Accepted: 10/25/2023] [Indexed: 11/19/2023]
Abstract
PURPOSE This study was conducted to examine the effects of daily intake of γ-oryzanol (ORZ)-fortified canola oil, as compared with plain canola and sunflower oils, on certain inflammatory and oxidative stress biomarkers in adult subjects with Type 2 Diabetes (T2D). METHODS We randomly allocated 92 adult subjects with T2D from both sexes to one of the following groups to receive: (a) ORZ-fortified canola oil (ORZO; n1 = 30); (b) unfortified canola oil (CANO; n2 = 32); or (c) sunflower oil (SUFO; n3 = 30) for 12 weeks. Dietary and laboratory evaluations were performed initially and finally. RESULTS Serum hs-CRP concentrations significantly decreased in ORZO group (from 3.1 ± 0.2 to 1.2 ± 0.2 mg/L), as compared with CANO (p = 0.003) and SUFO (p < 0.001) groups. Serum IL-6 significantly decreased just in ORZO (- 22.8%, p = 0.042) and CANO groups (- 19.8%, p = 0.038). However, the between-group differences were not significant. Serum IL-1β slightly decreased in ORZO (- 28.1%, p = 0.11) and increased in SUFO (+ 20.6%, p = 0.079) but between-group difference was statistically significant (p = 0.017). Serum IFN-γ concentrations decreased significantly only in ORZO (from 3.3 ± 0.08 to 2.9 ± 0.21 IU/mL, p = 0.044). Salivary IgA concentrations increased significantly in all three intervention groups. Notwithstanding, only the difference between ORZO and CANO groups was statistically significant (p = 0.042). Similarly, circulating malondialdehyde concentrations significantly decreased in all three groups but with no between-group significant difference. CONCLUSIONS Daily consumption of ORZ-fortified canola oil, compared with unfortified canola and sunflower oils, for 12 weeks resulted in boosting of certain anti-inflammatory effects of canola oil. These findings may have preventive implications for both clinicians and policy makers. This clinical trial was registered at clinicaltrials.gov (03.08.2022; NCT05271045).
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Affiliation(s)
- Bahareh Nikooyeh
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azizollaah Zargaraan
- Department of Food and Nutrition Policy and Planning Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition and Food Science, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran
| | - Samira Ebrahimof
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Kalayi
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maliheh Zahedirad
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hootan Yazdani
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Rismanchi
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Taher Karami
- Department of Research and Development, Kourosh Food Industry, Tehran, Iran
| | | | - Ali Jafarpour
- Quality Assurance Unit, Kourosh Food Industry, Tehran, Iran
| | - Tirang R Neyestani
- Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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11
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García A, Vila L, Duplan I, Schiel MA, Enriz RD, Hennuyer N, Staels B, Cabedo N, Cortes D. Benzopyran hydrazones with dual PPARα/γ or PPARα/δ agonism and an anti-inflammatory effect on human THP-1 macrophages. Eur J Med Chem 2024; 265:116125. [PMID: 38185055 DOI: 10.1016/j.ejmech.2024.116125] [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: 07/13/2023] [Revised: 01/02/2024] [Accepted: 01/03/2024] [Indexed: 01/09/2024]
Abstract
Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry. In an attempt to discover novel and safety PPAR activators, we efficiently prepared benzopyran hydrazone/hydrazine derivatives containing benzothiazole (series 1) or 5-chloro-3-(trifluoromethyl)-2-pyridine moiety (series 2) with a 3- or 7-carbon side chain at the 2-position of the benzopyran nucleus. Benzopyran hydrazones 4 and 5 showed dual hPPARα/γ agonism, while hydrazone 14 exerted dual hPPARα/δ agonism. These three hydrazones greatly attenuated inflammatory markers such as IL-6 and MCP-1 on the THP-1 macrophages via NF-κB activation. Therefore, we have discovered novel hits (4, 5 and 14), containing a hydrazone framework with dual PPARα/γ or PPARα/δ partial agonism, depending on the length of the side chain. Benzopyran hydrazones emerge as potential lead compounds which could be useful for treating metabolic diseases.
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Affiliation(s)
- Ainhoa García
- Department of Pharmacology, University of Valencia, 46100, Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010, Valencia, Spain
| | - Laura Vila
- Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010, Valencia, Spain
| | - Isabelle Duplan
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000, Lille, France
| | - María Ayelén Schiel
- Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis-IMIBIO-SL-CONICET, Chacabuco, 917-5700, San Luis, Argentina
| | - Ricardo D Enriz
- Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis-IMIBIO-SL-CONICET, Chacabuco, 917-5700, San Luis, Argentina
| | - Nathalie Hennuyer
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000, Lille, France.
| | - Bart Staels
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U-1011-EGID, F-59000, Lille, France
| | - Nuria Cabedo
- Department of Pharmacology, University of Valencia, 46100, Burjassot, Valencia, Spain; Institute of Health Research-INCLIVA, University Clinic Hospital of Valencia, 46010, Valencia, Spain.
| | - Diego Cortes
- Department of Pharmacology, University of Valencia, 46100, Burjassot, Valencia, Spain.
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12
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Ibrahim L, Yasin K, Abbas L, Ismael Y, Mousa A, Alkarajeh M, Hamdan Z, Nazzal Z. Exploring the relation between Interleukin-6 and high-sensitive cardiac troponin T in asymptomatic hemodialysis patient: A cross-sectional study. PLoS One 2024; 19:e0296965. [PMID: 38271442 PMCID: PMC10810457 DOI: 10.1371/journal.pone.0296965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 12/25/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND High-sensitive cardiac troponin T (h-cTnT), which serves as a marker for myocardial damage, has also been linked to adverse outcomes in asymptomatic hemodialysis patients. This study aims to explore the correlation between interleukin-6 (IL-6) and h-cTnT in asymptomatic hemodialysis patients to unravel the relationship between inflammation and cardiovascular risk. METHODS A cross-sectional study involving 81 patients was conducted from November 2022 to March 2023 at An-Najah National University Hospital in Palestine. We gathered clinical data, including comorbidities, and obtained blood samples for measuring IL-6 and h-cTnT levels. We performed statistical analyses, including correlation tests and linear regression, to assess the associations between these variables. RESULTS The study revealed a notable increase in both h-cTnT and IL-6 levels, and a significant correlation between the two (rho = 0.463, P<0.001) in asymptomatic hemodialysis patients. Likewise, h-cTnT levels displayed positive correlations with age (rho = 0.519, P<0.001) and negative correlations with albumin (rho = -0.297, p = 0.007) and transferrin saturation (rho = -0.227, P = 0.042). IL-6 levels exhibited correlations with age (rho = 0.422, P<0.001), albumin (rho = -0.389, P<0.001), iron (rho = -0.382, P<0.001), and transferrin saturation (rho = -0.362, P = 0.001). Notably, higher h-cTnT levels were associated with diabetes, hypertension, a history of coronary artery disease, cerebrovascular accidents, older age, and male gender. CONCLUSION This study underscores the significant association between the inflammatory marker IL-6 and h-cTnT in asymptomatic hemodialysis patients, suggesting that inflammation may play an essential role in the elevation of h-cTnT levels. This association may have implications for predicting cardiovascular events and guiding interventions to reduce cardiovascular disease morbidity and mortality in hemodialysis patients.
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Affiliation(s)
- Leen Ibrahim
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Katreen Yasin
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Leen Abbas
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Yahya Ismael
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Ahmed Mousa
- Faculty of Medicine and Health Sciences, Biomedical and Sciences Labs, An-Najah National University, Nablus, Palestine
| | - Mohammad Alkarajeh
- Faculty of Medicine and Health Sciences, Department of Nephrology, An-Najah National University Hospital, Nablus, Palestine
| | - Zakaria Hamdan
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
- Faculty of Medicine and Health Sciences, Department of Nephrology, An-Najah National University Hospital, Nablus, Palestine
| | - Zaher Nazzal
- Faculty of Medicine and Health Science, Department of Medicine, An-Najah National University, Nablus, Palestine
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13
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Liang H, Li F, Zhang L, Li L, Guo B. Ceramides and pro-inflammatory cytokines for the prediction of acute coronary syndrome: a multi-marker approach. BMC Cardiovasc Disord 2024; 24:47. [PMID: 38218768 PMCID: PMC10788003 DOI: 10.1186/s12872-023-03690-1] [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: 11/23/2023] [Accepted: 12/24/2023] [Indexed: 01/15/2024] Open
Abstract
BACKGROUND There is a growing body of evidence supporting the significant involvement of both ceramides and pro-inflammatory cytokines in the occurrence and progression of acute coronary syndrome (ACS). METHODS This study encompassed 216 participants whose laboratory variables were analysed using standardised procedures. Parameters included baseline serum lipid markers, comprising total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides (TGs), lipoprotein(a) (LPa), fasting blood glucose, B-natriuretic peptide and hypersensitive C-reactive protein. Liquid chromatography-tandem mass spectrometry measured the concentrations of plasma ceramides. Enzyme-linked immunosorbent assay quantified tumour necrosis factor-α (TNF-α), interleukin 6 (IL6) and IL8. The correlation between ceramides and inflammatory factors was determined through Pearson's correlation coefficient. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression evaluated the diagnostic potential of models incorporating traditional risk factors, ceramides and pro-inflammatory cytokines in ACS detection. RESULTS Among the 216 participants, 138 (63.89%) were diagnosed with ACS. Univariate logistic regression analysis identified significant independent predictors of ACS, including age, gender, history of diabetes, smoking history, TGs, TNF-α, IL-6, ceramide (d18:1/16:0), ceramide (d18:1/18:0), ceramide (d18:1/24:0), ceramide (d18:1/20:0) and ceramide (d18:1/22:0). Multivariate logistic regression analysis revealed significant associations between gender, diabetes mellitus history, smoking history, LPa, IL-6, ceramide (d18:1/16:0) and ACS. Receiver operating characteristic analysis indicated that model 4, which integrated traditional risk factors, IL-6 and ceramide (d18:1/16:0), achieved the highest area under the curve (AUC) of 0.827 (95% CI 0.770-0.884), compared with model 3 (traditional risk factors and ceramide [d18:1/16:0]) with an AUC of 0.782 (95% CI 0.720-0.845) and model 2 (traditional risk factors and IL-6), with an AUC of 0.785 (95% CI 0.723-0.846) in ACS detection. CONCLUSIONS In summary, incorporating the simultaneous measurement of traditional risk factors, pro-inflammatory cytokine IL-6 and ceramide (d18:1/16:0) can improve the diagnostic accuracy of ACS.
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Affiliation(s)
- Huiqing Liang
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050000, China
- Department of Cardiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China
| | - Fangjiang Li
- Department of Cardiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China
| | - Liang Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100020, China
| | - Lin Li
- Beijing Health Biotech Co. Ltd, Beijing, 102200, China
| | - Bingyan Guo
- Department of Internal Medicine, Hebei Medical University, No 361 Zhongshan East Road, Changan District, Shijiazhuang, 050000, China.
- Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China.
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14
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Marsili F, Potgieter P, Birkill CF. Adaptive Autonomic and Neuroplastic Control in Diabetic Neuropathy: A Narrative Review. Curr Diabetes Rev 2024; 20:38-54. [PMID: 38018186 DOI: 10.2174/0115733998253213231031050044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 08/31/2023] [Accepted: 09/28/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as diabetic neuropathy (DN). Despite a tremendous body of research, the pathogenesis of DN remains largely elusive. Currently, two schools of thought exist regarding the pathogenesis of diabetic neuropathy: a) mitochondrial-induced toxicity, and b) microvascular damage. Both mechanisms signify DN as an intractable disease and, as a consequence, therapeutic approaches treat symptoms with limited efficacy and risk of side effects. OBJECTIVE Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications. RESULTS A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications.
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Affiliation(s)
| | - Paul Potgieter
- Research Department, Algiamed Technologies, Burnaby, Canada
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15
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Agarwal S, Ghosh R, Verma G, Khadgawat R, Guchhait P. Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation. Clin Exp Immunol 2023; 214:197-208. [PMID: 37498307 PMCID: PMC10714189 DOI: 10.1093/cei/uxad086] [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: 04/27/2023] [Revised: 06/23/2023] [Accepted: 07/26/2023] [Indexed: 07/28/2023] Open
Abstract
The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1β, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet-leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D.
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Affiliation(s)
- Sakshi Agarwal
- Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India
| | - Riya Ghosh
- Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India
| | - Garima Verma
- Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India
| | - Rajesh Khadgawat
- Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Guchhait
- Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India
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16
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Shao J, Liu C, Wang J. Advances in research on molecular markers in immune checkpoint inhibitor-associated myocarditis. CANCER INNOVATION 2023; 2:439-447. [PMID: 38125765 PMCID: PMC10730003 DOI: 10.1002/cai2.100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/26/2023] [Accepted: 09/04/2023] [Indexed: 12/23/2023]
Abstract
Immune checkpoint inhibitors (ICIs) play a crucial role in the immunotherapy of malignant tumors, preventing immune evasion by tumor cells and activating autoimmune cells to eliminate the tumor. Despite their proven effectiveness in antitumor therapy, potential immune-related adverse effects must be recognized, particularly ICI-associated myocarditis (ICIAM). ICIAM is the most lethal form of organ immunotoxicity, with a significant impact on short-term mortality. However, ICIAM is predominantly asymptomatic or mildly nonspecific. It is difficult to diagnose, especially due to the lack of unique molecular markers. This article aims to provide a comprehensive overview of the progress made in identifying molecular markers for ICIAM.
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Affiliation(s)
- Jun Shao
- Department of General MedicineFirst Medical Center of PLA General HospitalBeijingChina
| | - Chuanbin Liu
- Western Medical Branch of PLA General HospitalBeijingChina
| | - Jing Wang
- Department of General MedicineFirst Medical Center of PLA General HospitalBeijingChina
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17
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Nie Y, Zhou H, Wang J, Kan H. Association between systemic immune-inflammation index and diabetes: a population-based study from the NHANES. Front Endocrinol (Lausanne) 2023; 14:1245199. [PMID: 38027115 PMCID: PMC10644783 DOI: 10.3389/fendo.2023.1245199] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
Background Systemic Immune-Inflammation Index (SII) has been reported to be associated with diabetes. We aimed to assess possible links between SII and diabetes. Methods Data were obtained from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. After removing missing data for SII and diabetes, we examined patients older than 20 years. Simultaneously, the relationship between SII and diabetes was examined using weighted multivariate regression analysis, subgroup analysis, and smooth curve fitting. Results There were 7877 subjects in this study, the average SII was 524.91 ± 358.90, and the prevalence of diabetes was 16.07%. Weighted multivariate regression analysis found that SII was positively associated with diabetes, and in model 3, this positive association remained stable (OR = 1.04; 95% CI: 1.02-1.06; p = 0.0006), indicating that each additional unit of SII, the possibility of having diabetes increased by 4%. Gender, age, BMI, regular exercise, high blood pressure, and smoking did not significantly affect this positive link, according to the interaction test (p for trend>0.05). Discussion Additional prospective studies are required to examine the precise connection between higher SII levels and diabetes, which may be associated with higher SII levels.
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Affiliation(s)
- Yiqi Nie
- School of Medical Information Engineering, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
- Anhui Computer Application Research Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Hefei, Anhui, China
| | - Haiting Zhou
- School of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Jing Wang
- School of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Hongxing Kan
- School of Medical Information Engineering, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
- Anhui Computer Application Research Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Hefei, Anhui, China
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18
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Barouei J, Martinic A, Bendiks Z, Mishchuk D, Heeney D, Slupsky CM, Marco ML. Type 2-resistant starch and Lactiplantibacillus plantarum NCIMB 8826 result in additive and interactive effects in diet-induced obese mice. Nutr Res 2023; 118:12-28. [PMID: 37536013 DOI: 10.1016/j.nutres.2023.07.003] [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: 12/16/2022] [Revised: 07/14/2023] [Accepted: 07/14/2023] [Indexed: 08/05/2023]
Abstract
Little is known about how combining a probiotic with prebiotic dietary fiber affects the ability of either biotic to improve health. We hypothesized that prebiotic, high-amylose maize type 2-resistant starch (RS) together with probiotic Lactiplantibacillus plantarum NCIMB8826 (LP) as a complementary synbiotic results in additive effects on the gut microbiota in diet-induced obese mice and other body sites. Diet-induced obese C57BL/6J male mice were fed a high-fat diet adjusted to contain RS (20% by weight), LP (109 cells every 48 hours), or both (RS+LP) for 6 weeks. As found for mice fed RS, cecal bacterial alpha diversity was significantly reduced in mice given RS+LP compared with those fed LP and high-fat controls. Similarly, both RS+LP and RS also conferred lower quantities of cecal butyrate and serum histidine and higher ileal TLR2 transcript levels and adipose tissue interleukin-6 protein. As found for mice fed LP, RS+LP-fed mice had higher colonic tissue TH17 cytokines, reduced epididymal fat immune and oxidative stress responses, reduced serum carnitine levels, and increased transcript quantities of hepatic carnitine palmitoyl transferase 1α. Notably, compared with RS and LP consumed separately, there were also synergistic increases in colonic glucose and hepatic amino acids as well antagonistic effects of LP on RS-mediated increases in serum adiponectin and urinary toxin levels. Our findings show that it is not possible to fully predict outcomes of synbiotic applications based on findings of the probiotic or the prebiotic tested separately; therefore, studies should be conducted to test new synbiotic formulations.
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Affiliation(s)
- Javad Barouei
- Integrated Food Security Research Center, College of Agriculture and Human Sciences, Prairie View A&M University, Prairie View, TX; Department of Food Science & Technology, University of California, Davis, CA
| | - Alice Martinic
- Department of Nutrition, University of California, Davis, CA
| | - Zach Bendiks
- Department of Food Science & Technology, University of California, Davis, CA
| | - Darya Mishchuk
- Department of Food Science & Technology, University of California, Davis, CA
| | - Dustin Heeney
- Department of Food Science & Technology, University of California, Davis, CA
| | - Carolyn M Slupsky
- Department of Food Science & Technology, University of California, Davis, CA; Department of Nutrition, University of California, Davis, CA
| | - Maria L Marco
- Department of Food Science & Technology, University of California, Davis, CA.
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Ménégaut L, Laubriet A, Crespy V, Leleu D, Pilot T, Van Dongen K, de Barros JPP, Gautier T, Petit JM, Thomas C, Nguyen M, Steinmetz E, Masson D. Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis. Cardiovasc Diabetol 2023; 22:248. [PMID: 37710315 PMCID: PMC10503074 DOI: 10.1186/s12933-023-01979-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 09/03/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. METHODS The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. RESULTS In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. CONCLUSION Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. TRIAL REGISTRATION The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).
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Affiliation(s)
- Louise Ménégaut
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
- CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France
| | - Aline Laubriet
- Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France
| | - Valentin Crespy
- Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France
| | - Damien Leleu
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
- CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France
| | - Thomas Pilot
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
| | - Kevin Van Dongen
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
| | - Jean-Paul Pais de Barros
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
- Lipidomic Analytic Platform, Université Bourgogne Franche-Comté, Dijon, France
| | - Thomas Gautier
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
| | - Jean-Michel Petit
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
- Department of Endocrinology and metabolic diseases, CHU Dijon, Dijon, France
| | - Charles Thomas
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
| | - Maxime Nguyen
- Université Bourgogne, LNC UMR1231, Dijon, France
- INSERM, UMR1231, Dijon, France
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France
- CHU Dijon Department of Anesthesiology and Intensive Care, Dijon, France
| | - Eric Steinmetz
- Department of Cardiovascular and Thoracic Surgery, CHU Dijon, Dijon, France
| | - David Masson
- Université Bourgogne, LNC UMR1231, Dijon, France.
- INSERM, UMR1231, Dijon, France.
- Université Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France.
- CHU Dijon, Laboratory of Clinical Chemistry, Dijon, France.
- UFR des sciences de santé, Bvd Jeanne d'Arc, Dijon, 21000, France.
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20
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Nirenjen S, Narayanan J, Tamilanban T, Subramaniyan V, Chitra V, Fuloria NK, Wong LS, Ramachawolran G, Sekar M, Gupta G, Fuloria S, Chinni S, Selvaraj S. Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes. Front Immunol 2023; 14:1216321. [PMID: 37575261 PMCID: PMC10414543 DOI: 10.3389/fimmu.2023.1216321] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 06/26/2023] [Indexed: 08/15/2023] Open
Abstract
Background Impaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes. Purpose of review Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review. Recent findings Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value. Summary The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals' patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.
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Affiliation(s)
- S. Nirenjen
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - J. Narayanan
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - T. Tamilanban
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Vetriselvan Subramaniyan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Jalan Lagoon Selatan, Bandar Sunway, Petaling Jaya, Selangor, Malaysia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
| | - V. Chitra
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | | | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
| | - Gobinath Ramachawolran
- Department of Foundation, RCSI & UCD Malaysia Campus, Jalan Sepoy Lines, Georgetown, Pulau Pinang, Malaysia
| | - Mahendran Sekar
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | | | - Suresh V. Chinni
- Department of Biochemistry, Faculty of Medicine, Bioscience, and Nursing, MAHSA University, Jenjarom, Selangor, Malaysia
- Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
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21
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Salles C, Freitas MC, Souza A, Ribeiro P, Dias C, Rosa M, Meira e Cruz M. Metabolomic approach for obstructive sleep apnea in adults: a systematic review. Sleep Biol Rhythms 2023; 21:265-277. [PMID: 38469078 PMCID: PMC10899929 DOI: 10.1007/s41105-023-00445-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 01/08/2023] [Indexed: 02/11/2023]
Abstract
Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression.
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Affiliation(s)
- Cristina Salles
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
| | - Maria Clara Freitas
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
| | - Amancio Souza
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
- Public Health Sciences, University of California, San Diego, USA
| | - Paulo Ribeiro
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
- Chemistry Institute, Federal University of Bahia, Salvador, Brazil
| | - Cristiane Dias
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
| | - Michele Rosa
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
- Cardiovascular Centre of University of Lisboa, CCUL, Falculty of Medicine, University of Lisboa, Lisboa, Portugal
| | - Miguel Meira e Cruz
- International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil
- Centro Europeu do Sono, European Center of Sleep, Lisboa, Portugal
- Faculty São Leopoldo Mandic, Faculty São Leopoldo Mandic, Campinas, Brazil
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22
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Lewis ST, Greenway F, Tucker TR, Alexander M, Jackson LK, Hepford SA, Loveridge B, Lakey JRT. A Receptor Story: Insulin Resistance Pathophysiology and Physiologic Insulin Resensitization's Role as a Treatment Modality. Int J Mol Sci 2023; 24:10927. [PMID: 37446104 DOI: 10.3390/ijms241310927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, β cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, β-cell mass is reduced due to apoptosis and β cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.
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Affiliation(s)
| | - Frank Greenway
- Clinical Trials Unit, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 77808, USA
| | - Tori R Tucker
- Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92617, USA
| | - Michael Alexander
- Department of Surgery, University of California Irvine, Orange, CA 92686, USA
| | - Levonika K Jackson
- Well Cell Global, Medical and Scientific Advisory Board, Houston, TX 77079, USA
| | - Scott A Hepford
- Well Cell Global, Medical and Scientific Advisory Board, Houston, TX 77079, USA
| | - Brian Loveridge
- Well Cell Global, Medical and Scientific Advisory Board, Houston, TX 77079, USA
| | - Jonathan R T Lakey
- Department of Surgery, University of California Irvine, Orange, CA 92686, USA
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92868, USA
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23
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Lempesis IG, Georgakopoulou VE. Physiopathological mechanisms related to inflammation in obesity and type 2 diabetes mellitus. World J Exp Med 2023; 13:7-16. [PMID: 37396883 PMCID: PMC10308320 DOI: 10.5493/wjem.v13.i3.7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 02/15/2023] [Accepted: 04/10/2023] [Indexed: 06/16/2023] Open
Abstract
Overweight, obesity, and type 2 diabetes mellitus pose global health problems that are ever-increasing. A chronic low-grade inflammatory status and the presence of various pro-inflammatory markers either in circulation or within dysfunctional metabolic tissues are well established. The presence of these factors can, to some extent, predict disease development and progression. A central role is played by the presence of dysfunctional adipose tissue, liver dysfunction, and skeletal muscle dysfunction, which collectively contribute to the increased circulatory levels of proinflammatory factors. Weight loss and classical metabolic interventions achieve a decrease in many of these factors' circulating levels, implying that a better understanding of the processes or even the modulation of inflammation may alleviate these diseases. This review suggests that inflammation plays a significant role in the development and progression of these conditions and that measuring inflammatory markers may be useful for assessing disease risk and development of future treatment methods.
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Affiliation(s)
- Ioannis G Lempesis
- Department of Infectious Diseases-COVID-19 Unit, Laiko General Hospital, Athens 11527, Greece
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24
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Narayanan S, Röhl S, Lengquist M, Kronqvist M, Matic L, Razuvaev A. Transcriptomic and physiological analyses reveal temporal changes contributing to the delayed healing response to arterial injury in diabetic rats. JVS Vasc Sci 2023; 4:100111. [PMID: 37519334 PMCID: PMC10372325 DOI: 10.1016/j.jvssci.2023.100111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 04/12/2023] [Indexed: 08/01/2023] Open
Abstract
Objective Atherosclerosis is a leading cause of mortality in the rapidly growing population with diabetes mellitus. Vascular interventions in patients with diabetes can lead to complications attributed to defective vascular remodeling and impaired healing response in the vessel wall. In this study, we aim to elucidate the molecular differences in the vascular healing response over time using a rat model of arterial injury applied to healthy and diabetic conditions. Methods Wistar (healthy) and Goto-Kakizaki (GK, diabetic) rats (n = 40 per strain) were subjected to left common carotid artery (CCA) balloon injury and euthanized at different timepoints: 0 and 20 hours, 5 days, and 2, 4, and 6 weeks. Noninvasive morphological and physiological assessment of the CCA was performed with ultrasound biomicroscopy (Vevo 2100) and corroborated with histology. Total RNA was isolated from the injured CCA at each timepoint, and microarray profiling was performed (n = 3 rats per timepoint; RaGene-1_0-st-v1 platform). Bioinformatic analyses were conducted using R software, DAVID bioinformatic tool, online STRING database, and Cytoscape software. Results Significant increase in the neointimal thickness (P < .01; two-way analysis of variance) as well as exaggerated negative remodeling was observed after 2 weeks of injury in GK rats compared with heathy rats, which was confirmed by histological analyses. Bioinformatic analyses showed defective expression patterns for smooth muscle cells and immune cell markers, along with reduced expression of key extracellular matrix-related genes and increased expression of pro-thrombotic genes, indicating potential faults on cell regulation level. Transcription factor-protein-protein interaction analysis provided mechanistic evidence with an array of transcription factors dysregulated in diabetic rats. Conclusions In this study, we have demonstrated that diabetic rats exhibit impaired arterial remodeling characterized by a delayed healing response. We show that increased contractile smooth muscle cell marker expression coincided with decreased matrix metalloproteinase expression, indicating a potential mechanism for a lack of extracellular matrix reorganization in the impaired vascular healing in GK rats. These results further corroborate the higher prevalence of restenosis in patients with diabetes and provide vital molecular insights into the mechanisms contributing to the impaired arterial healing response in diabetes. Moreover, the presented study provides the research community with the valuable longitudinal gene expression data bank for further exploration of diabetic vasculopathy.
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Affiliation(s)
| | | | | | | | | | - Anton Razuvaev
- Correspondence: Anton Razuvaev, MD, PhD, Department of Molecular Medicine and Surgery, BioClinicum J8:20, Visionsgatan 4, Karolinska Institutet, SE-171 76, Stockholm, Sweden
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25
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Liu J, Chen L, Zheng X, Guo C. Identification of immune-related genes in acute myocardial infarction based on integrated bioinformatical methods and experimental verification. PeerJ 2023; 11:e15058. [PMID: 37214088 PMCID: PMC10198157 DOI: 10.7717/peerj.15058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 02/22/2023] [Indexed: 05/24/2023] Open
Abstract
Background Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. The etiology of AMI is complex and has not been fully defined. In recent years, the role of immune response in the development, progression and prognosis of AMI has received increasing attention. The aim of this study was to identify key genes associated with the immune response in AMI and to analyze their immune infiltration. Methods The study included a total of two GEO databases, containing 83 patients with AMI and 54 healthy individuals. We used the linear model of microarray data (limma) package to find the differentially expressed genes associated with AMI, performing weighted gene co-expression analysis (WGCNA) to further identify the genes associated with inflammatory response to AMI. We found the final hub genes through the protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) regression model. To verify the above conclusions, we constructed mice AMI model, extracting myocardial tissue to perform qRT-PCR. Furthermore, the CIBERSORT tool for immune cells infiltration analysis was also carried out. Results A total of 5,425 significant up-regulated and 2,126 down-regulated genes were found in GSE66360 and GSE24519. A total of 116 immune-related genes in close association with AMI were screened by WGCNA analysis. These genes were mostly clustered in the immune response on the basis of GO and KEGG enrichment. With construction of PPI network and LASSO regression analysis, this research found three hub genes (SOCS2, FFAR2, MYO10) among these differentially expressed genes. The immune cell infiltration results revealed that significant differences could be found on T cells CD4 memory activated, Tregs (regulatory T cells), macrophages M2, neutrophils, T cells CD8, T cells CD4 naive, eosinophils between controls and AMI patients.
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Affiliation(s)
- Jian Liu
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Lu Chen
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xiang Zheng
- Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Caixia Guo
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Chhor M, Law W, Pavlovic M, Aksentijevic D, McGrath K, McClements L. Diagnostic and prognostic biomarkers reflective of cardiac remodelling in diabetes mellitus: A scoping review. Diabet Med 2023; 40:e15064. [PMID: 36782075 DOI: 10.1111/dme.15064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 01/19/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023]
Abstract
AIMS The aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease. We aim to discuss the biomarkers' pathophysiological roles as a reflection of the cardiac remodelling mechanisms in the presence of DM. METHODS We performed the literature search to include studies from 2003 to 2021 using the following databases: MEDLINE, Scopus, Web of Science, PubMed, and Cochrane library. Articles that met our inclusion criteria were screened and appraised before being included in this review. The PRISMA guidelines for Scoping Reviews were followed. RESULTS Our literature search identified a total of 43 eligible articles, which were included in this scoping review. We identified 15 different biomarkers, each described by at least two studies, that were used to determine signs of cardiac remodelling in cardiovascular disease (CVD) and people with DM. NT-proBNP was identified as the most frequently employed biomarker in this context; however, we also identified emerging biomarkers including hs-CRP, hs-cTnT, and Galectin-3. CONCLUSION There is a complex relationship between DM and cardiovascular health, where more research is needed. Current biomarkers reflective of adverse cardiac remodelling in DM are often used to diagnose other CVDs, such as NT-proBNP for heart failure. Hence there is a need for identification of specific biomarkers that can detect early signs of cardiac remodelling in the presence of DM. Further research into these biomarkers and mechanisms can deepen our understanding of their role in DM-associated CVD and lead to better preventative therapies.
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Affiliation(s)
- Michael Chhor
- School of Life Sciences, Faculty of Science, University of Technology Sydney, New South Wales, Sydney, Australia
| | - William Law
- School of Life Sciences, Faculty of Science, University of Technology Sydney, New South Wales, Sydney, Australia
| | - Milan Pavlovic
- Department of Internal Medicine - Cardiology, Faculty of Medicine, University of Nis, Nis, Serbia
| | - Dunja Aksentijevic
- Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Kristine McGrath
- School of Life Sciences, Faculty of Science, University of Technology Sydney, New South Wales, Sydney, Australia
| | - Lana McClements
- School of Life Sciences, Faculty of Science, University of Technology Sydney, New South Wales, Sydney, Australia
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Marar RI, Abbasi MA, Prathivadhi-Bhayankaram S, Acevedo AD, Villarraga H, Anavekar N, Bhatt VR, Paludo J. Cardiotoxicities of Novel Therapies in Hematologic Malignancies: Chimeric Antigen Receptor T-Cell Therapy and Bispecific T-Cell Engager Therapy. JCO Oncol Pract 2023:OP2200713. [PMID: 36930845 DOI: 10.1200/op.22.00713] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
Abstract
The field of malignant hematology is transforming with novel immunotherapeutic approaches. Unfortunately, quality of life, treatment efficacy, and life expectancy are negatively affected by cardiotoxic side effects of treatment. To date, the exact mechanism and incidence of cardiotoxicity associated with these therapies is unclear. These events are believed to be triggered or occur concurrently with cytokine release syndrome. Furthermore, there are no formal guidelines to provide evaluation, treatment, and surveillance. We aim to synthesize available literature with updates on the cardiotoxic effects of novel therapies used in malignant hematologic disorders, with a focus on chimeric antigen receptor T-cell therapy and bispecific T-cell engager therapy, along with a proposed algorithm that may guide pretreatment evaluation, monitoring during treatment, and post-treatment surveillance.
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Affiliation(s)
- Rosalyn I Marar
- Division of Hematology-Oncology, University of Nebraska Medical Center, Omaha, NE
| | | | | | | | | | - Nandan Anavekar
- Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Vijaya Raj Bhatt
- Division of Hematology-Oncology, University of Nebraska Medical Center, Omaha, NE
| | - Jonas Paludo
- Division of Hematology-Oncology, Mayo Clinic, Rochester, MN
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Löb S, Knabl J, Vattai A, Schmoeckel E, Kuhn C, Mittelberger J, Wöckel A, Mahner S, Jeschke U. Obesity in pregnancy is associated with macrophage influx and an upregulated GRO-alpha and IL-6 expression in the decidua. J Reprod Immunol 2023; 156:103800. [PMID: 36640674 DOI: 10.1016/j.jri.2023.103800] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/10/2023] [Indexed: 01/13/2023]
Abstract
About one third of all reproductive-aged women are affected by obesity. Maternal obesity is linked to an adverse outcome for both mother and child. The expression of the pro-inflammatory IL-6 and GRO-alpha as well as the infiltration of macrophages in the placenta of obese, non-diabetic pregnancies was examined by immunohistochemistry in comparison to the placenta of normal weight women. In obese pregnancies the influx of macrophages was significantly increased (p = 0.012). The protein expression of IL-6 and GRO-alpha was significantly elevated (p = 0.036 and p < 0.001, respectively) in the decidua of adipose females.
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Affiliation(s)
- Sanja Löb
- Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany
| | - Julia Knabl
- Department of Obstetrics, Klinik Hallerwiese, Sankt-Johannis-Mühlgasse 19, 90419 Nürnberg, Germany; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Maistrasse 11, 80337 Munich, Germany
| | - Aurelia Vattai
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Maistrasse 11, 80337 Munich, Germany
| | - Elisa Schmoeckel
- Department of Pathology, LMU Munich, Marchioninistr. 27, 81377 Munich, Germany
| | - Christina Kuhn
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany
| | - Johanna Mittelberger
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany
| | - Achim Wöckel
- Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany
| | - Sven Mahner
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Maistrasse 11, 80337 Munich, Germany
| | - Udo Jeschke
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Maistrasse 11, 80337 Munich, Germany; Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany.
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29
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Dincă AL, Meliț LE, Gurzu S, Mocan S, Ghiga DV, Mărginean CO. Helicobacter pylori—The Bridge between Local and Systemic Inflammation in Children. APPLIED SCIENCES 2023; 13:2162. [DOI: 10.3390/app13042162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Helicobacter pylori (H. pylori)-associated inflammatory status is no longer a debatable topic in children. The aim of our study was to to compare the inflammatory status in pediatric patients with H. pylori gastritis and non-H. pylori gastritis versus control group. We performed a prospective study on 68 children with dyspeptic symptoms which were divided into 3 groups: 14 children with H. pylori gastritis (group 1), 26 children with non-H. pylori gastritis (group 2) and 28 children with no pathological findings—control group (group 3). Several laboratory parameters, histopathological and immunohistochemistry tests were performed in all children for detecting inflammatory status. We noticed a significant difference in terms of rural area between the three groups (p = 0.0404). Comparing the laboratory parameters between the three groups, we noticed significant differences in terms of serological tests (p = 0094), and NLR (p = 0.0253), the latter being significantly higher in children with H. pylori-induced gastritis as compared to those with non-H. pylori gastritis (0.0107). According to the Dunn’s Multiple Comparison Test, we noticed a significantly elevated neutrophil level in children with H. pylori-induced gastritis when compared to non-H. pylori gastritis group (p = 0.0146), as well as a significantly increased eosinophil count in patients with non-H. pylori gastritis as compared to control group (p = 0.0417). The immunohistochemistry method pointed out no significant variation concerning interleukin (IL 6) between children with gastritis and control group [RR = 1.283, IC (95%): 0.9404–1.751, p = 0.0988]. Additionally, children with gastritis regardless of the etiology have a significant risk of associating increased gastric expression of tumor necrosis factor alpha (TNF α) [RR = 3.967; CI (95%): 1.283–12.263; p = 0.0063]. Moreover, TNF α was significantly associated with presence of H. pylori gastritis (p = 0.0002). The early detection of local inflammation triggered by this infection might preempt gastric carcinogenesis, while identifying H. pylori-induced systemic inflammation lowers the risk of severe extraintestinal manifestations.
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Affiliation(s)
- Andreea Ligia Dincă
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| | - Lorena Elena Meliț
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| | - Simona Gurzu
- Department of Pathology, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
- Department of Pathology, County Emergency Clinical Hospital of Târgu Mureș, Gheorghe Marinescu Street No. 50, 540139 Târgu Mureș, Romania
- Research Center of Oncopathology and Translational Medicine (CCOMT), “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 50, 540139 Târgu Mureș, Romania
| | - Simona Mocan
- Department of Pathology, County Emergency Clinical Hospital of Târgu Mureș, Gheorghe Marinescu Street No. 50, 540139 Târgu Mureș, Romania
| | - Dana Valentina Ghiga
- Department of Scientific Medical Research Methodology, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology from Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
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Gandhi GR, Hillary VE, Antony PJ, Zhong LLD, Yogesh D, Krishnakumar NM, Ceasar SA, Gan RY. A systematic review on anti-diabetic plant essential oil compounds: Dietary sources, effects, molecular mechanisms, and safety. Crit Rev Food Sci Nutr 2023; 64:6526-6545. [PMID: 36708221 DOI: 10.1080/10408398.2023.2170320] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic syndrome defined through the dysfunction of pancreatic β-cells driven by a confluence of genetic and environmental elements. Insulin resistance, mediated by interleukins and other inflammatory elements, is one of the key factors contributing to the progression of T2DM. Many essential oils derived from dietary plants are beneficial against various chronic diseases. We reviewed the anti-diabetic properties of dietary plant-derived essential oil compounds, with a focus on their molecular mechanisms by modulating specific signaling pathways and other critical inflammatory mediators involved in insulin resistance. High-quality literature published in the last 12 years, from 2010 to 2022, was collected from the Scopus, Web of Science, PubMed, and Embase databases using the search terms "dietary plants," "essential oils," "anti-diabetic," "insulin resistance," "antihyperglycemic," "T2DM," "anti-diabetic essential oils," and anti-diabetic mechanism." According to the results, the essential oil compounds, including cinnamaldehyde, carvacrol, zingerone, sclareol, zerumbone, myrtenol, thujone, geraniol, citral, eugenol, thymoquinone, thymol, citronellol, α-terpineol, and linalool have been demonstrated to contain strong anti-diabetic effects via modulating various signal transduction pathways linked to glucose metabolism. Additionally, in diabetes-related animal models, they can also considerably reduce the expression of TNF-α, IL-1β, IL-4, IL-6, iNOS, and COX-2. The main signaling molecules regulated by these compounds include AMPK, GLUT4, Caspase-3, PPARγ, PPARα, NF-κB, p-IκBα, MyD88, MCP-1, SREBP-1c, AGEs, RAGE, VEGF, Nrf2/HO-1, and SIRT-1. They can also significantly inhibit the generation of TBARS and MDA, reduce oxidative stress, increase insulin levels, adiponectin, and glycoprotein enzymes, boost antioxidant enzymes like SOD, CAT, and GPx, as well as reduce glutathione and vital glycolytic enzymes. Besides, they can significantly lower the levels of liver enzymes and lipid profile markers. Moreover, most essential oil compounds are generally safe based on animal studies. In conclusion, dietary plant-derived essential oil compounds have potential anti-diabetic effects by influencing different signaling pathways and molecular targets linked to glucose metabolism, and should be safe and beneficial against diabetes and related complications.
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Affiliation(s)
- Gopalsamy Rajiv Gandhi
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, India
| | - Varghese Edwin Hillary
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, India
| | | | - Linda L D Zhong
- Biomedical Sciences and Chinese Medicine, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Devarajan Yogesh
- Department of Biochemistry, University of Madras, Chennai, India
| | | | - Stanislaus Antony Ceasar
- Division of Plant Molecular Biology and Biotechnology, Department of Biosciences, Rajagiri College of Social Sciences, Kochi, India
| | - Ren-You Gan
- Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
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Khomari F, Kiani B, Alizadeh-Fanalou S, Babaei M, Kalantari-Hesari A, Alipourfard I, Mirzaei F, Yarahmadi S, Bahreini E. Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:7285036. [PMID: 36647426 PMCID: PMC9840543 DOI: 10.1155/2023/7285036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/17/2022] [Accepted: 12/22/2022] [Indexed: 01/09/2023]
Abstract
Background Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Methods Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. Results HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Conclusions Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.
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Affiliation(s)
- Fatemeh Khomari
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Bahar Kiani
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shahin Alizadeh-Fanalou
- Nephrology and Kidney Transplant center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Babaei
- Department of Clinical Sciences, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Ali Kalantari-Hesari
- Department of Clinical Sciences, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Iraj Alipourfard
- Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia, Bankowa 9, 40-007 Katow, Poland
| | - Fatemeh Mirzaei
- Department of Anatomical Sciences, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Sahar Yarahmadi
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Elham Bahreini
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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He B, Wang K, Xiang J, Bing P, Tang M, Tian G, Guo C, Xu M, Yang J. DGHNE: network enhancement-based method in identifying disease-causing genes through a heterogeneous biomedical network. Brief Bioinform 2022; 23:6712302. [PMID: 36151744 DOI: 10.1093/bib/bbac405] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 08/01/2022] [Accepted: 08/21/2022] [Indexed: 12/14/2022] Open
Abstract
The identification of disease-causing genes is critical for mechanistic understanding of disease etiology and clinical manipulation in disease prevention and treatment. Yet the existing approaches in tackling this question are inadequate in accuracy and efficiency, demanding computational methods with higher identification power. Here, we proposed a new method called DGHNE to identify disease-causing genes through a heterogeneous biomedical network empowered by network enhancement. First, a disease-disease association network was constructed by the cosine similarity scores between phenotype annotation vectors of diseases, and a new heterogeneous biomedical network was constructed by using disease-gene associations to connect the disease-disease network and gene-gene network. Then, the heterogeneous biomedical network was further enhanced by using network embedding based on the Gaussian random projection. Finally, network propagation was used to identify candidate genes in the enhanced network. We applied DGHNE together with five other methods into the most updated disease-gene association database termed DisGeNet. Compared with all other methods, DGHNE displayed the highest area under the receiver operating characteristic curve and the precision-recall curve, as well as the highest precision and recall, in both the global 5-fold cross-validation and predicting new disease-gene associations. We further performed DGHNE in identifying the candidate causal genes of Parkinson's disease and diabetes mellitus, and the genes connecting hyperglycemia and diabetes mellitus. In all cases, the predicted causing genes were enriched in disease-associated gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, and the gene-disease associations were highly evidenced by independent experimental studies.
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Affiliation(s)
- Binsheng He
- Academician Workstation, Changsha Medical University, Changsha 410219, China.,Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, P. R. China.,School of pharmacy, Changsha Medical University, Changsha 410219, P. R. China
| | - Kun Wang
- School of Mathematical Sciences, Ocean University of China, Qingdao 266100, China
| | - Ju Xiang
- Academician Workstation, Changsha Medical University, Changsha 410219, China
| | - Pingping Bing
- Academician Workstation, Changsha Medical University, Changsha 410219, China.,Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, P. R. China.,School of pharmacy, Changsha Medical University, Changsha 410219, P. R. China
| | - Min Tang
- School of Life Sciences, Jiangsu University, Zhenjiang 212001, Jiangsu, China
| | - Geng Tian
- Geneis (Beijing) Co., Ltd., Beijing 100102, China
| | - Cheng Guo
- Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
| | - Miao Xu
- Broad institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
| | - Jialiang Yang
- Academician Workstation, Changsha Medical University, Changsha 410219, China.,Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, P. R. China.,School of pharmacy, Changsha Medical University, Changsha 410219, P. R. China.,Geneis (Beijing) Co., Ltd., Beijing 100102, China
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Wang D, Liu J, Zhong L, Li S, Zhou L, Zhang Q, Li M, Xiao X. The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 2022; 13:1045235. [PMID: 36467062 PMCID: PMC9717685 DOI: 10.3389/fphar.2022.1045235] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/26/2022] [Indexed: 10/27/2023] Open
Abstract
Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs). Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4. Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: -1.21; 95% CI: -1.91, -0.52, p < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, p = 0.02) and leptin (SMD: -0.22; 95% CI: -0.43, -0.01, p = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: -0.38; 95% CI: -0.61, -0.15, p = 0.001). Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.
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Affiliation(s)
- Dongmei Wang
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jieying Liu
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ling Zhong
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Shunhua Li
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Liyuan Zhou
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Zhang
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Ming Li
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xinhua Xiao
- Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Gál K, Asbóth G, Vass M, Bíró A, Markovich A, Homoki J, Fidler G, Paholcsek M, Cziáky Z, Németh N, Remenyik J, Soltész P. Monitoring and recovery of hyperglycaemia-induced endothelial dysfunction with rheopheresis in diabetic lower extremity ulceration with hyperviscosity. Diab Vasc Dis Res 2022; 19:14791641221131788. [PMID: 36357361 PMCID: PMC9661626 DOI: 10.1177/14791641221131788] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
AIMS Rheopheresis is an extracorporeal haematotherapy that improves haemorheological status by filtering proteins that enhance blood viscosity. It also has anti-inflammatory effects by removing inflammatory cytokines. Our study aims to examine the effects of rheopheresis on the endothelial status in diabetic lower extremity ulceration. METHODS In vitro experiments were performed in a HUVEC model to mimic hyperglycaemic stress. We determined the changes in gene expression levels of IL-6, IL-8, TNF-alpha, endothelin convertase enzyme, ET-1, and NO synthase, as well as the ROS and intracellular GSH levels upon hyperglycaemia. In in vivo studies, two rheopheresis procedures were performed on seven patients with diabetic lower extremity ulceration with hyperviscosity, and we measured the changes in plasma concentrations of ET-1, TXB2, SOD enzyme activity, and extracellular components of the glutathione pool depending on treatments. RESULTS Our results showed that hyperglycaemia increases endothelial expression of inflammatory cytokines, ET-1, and endothelin convertase enzyme, while NO synthase was decreased. As a result of rheopheresis, we observed decreased ET-1 and TXB2 concentrations in the plasma and beneficial changes in the parameters of the glutathione pool. CONCLUSION To summarize our results, hyperglycaemia-induced oxidative stress and endothelial inflammation can be moderated by rheopheresis in diabetic lower extremity ulceration with hyperviscosity.
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Affiliation(s)
- Kristóf Gál
- Division of Angiology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Georgina Asbóth
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Melinda Vass
- Division of Angiology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Bíró
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Arnold Markovich
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Judit Homoki
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Gábor Fidler
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Melinda Paholcsek
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Zoltán Cziáky
- Agricultural and Molecular Research and Service Group, University of Nyíregyháza, Nyíregyháza, Hungary
| | - Norbert Németh
- Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Judit Remenyik
- Department of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management University of Debrecen, Debrecen, Hungary
| | - Pál Soltész
- Division of Angiology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Pál Soltész, Division of Angiology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Móricz Zsigmond krt. 22, Debrecen 4032, Hungary.
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Becerikli M, Reinkemeier F, Dadras M, Wallner C, Wagner JM, Drysch M, Sogorski A, von Glinski M, Lehnhardt M, Hahn SA, Behr B. TGF-beta pathway inhibition as the therapeutic acceleration of diabetic bone regeneration. J Orthop Res 2022; 40:1810-1826. [PMID: 34775640 DOI: 10.1002/jor.25212] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/10/2021] [Accepted: 10/30/2021] [Indexed: 02/04/2023]
Abstract
Bone regeneration and fracture healing are impaired in diabetic patients due to defective functions of associated cells. Thus, the search for molecular causes and new treatment strategies are of particular clinical relevance. We investigated the gene expression profile of bones from type 2 diabetic (db- /db- ) mice and wild-type (wt) mice by comparative microarray analyses before and after placing tibial defects and examined the expression of several osteogenesis- and osteoclastogenesis-related markers by quantitative real-time polymerase chain reaction. In regenerating wt bones, pathways related to, for example, inhibition of matrix metalloproteases were activated, whereas in db- /db- bones activation of pathways related to, for example, osteoarthritis, transforming growth factor-beta (Tgfb), or hypoxia-inducible factor 1a were detected during regeneration. We defined the Tgfb pathway as a potential therapeutic target and locally applied a single dose (0.5 µg) of the Tgfb 1, 2, and 3 neutralizing antibody 1D11 on tibial defects in db- /db- mice (n = 7). Seven days postoperation, histological and immunohistochemical stainings were performed. Decreased bone regeneration, osteogenic differentiation, osteoclast invasion, and angiogenesis in db- /db- mice were significantly restored by local 1D11 application in comparison to the phosphate-buffered saline controls. Thus, local treatment of db- /db- bony defects with Tgfb neutralizing antibody 1D11 might be considered a good candidate for the successful acceleration of bone regeneration.
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Affiliation(s)
- Mustafa Becerikli
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Felix Reinkemeier
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Mehran Dadras
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Christoph Wallner
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Johannes M Wagner
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Marius Drysch
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Alexander Sogorski
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Maxi von Glinski
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Marcus Lehnhardt
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
| | - Stephan A Hahn
- Department of Molecular GI-Oncology (MGO), Clinical Research Center (ZKF), Ruhr-University Bochum, Bochum, Germany
| | - Björn Behr
- Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
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Old and New Aspects of H. pylori-Associated Inflammation and Gastric Cancer. CHILDREN 2022; 9:children9071083. [PMID: 35884067 PMCID: PMC9322908 DOI: 10.3390/children9071083] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/17/2022] [Accepted: 07/18/2022] [Indexed: 12/16/2022]
Abstract
H. pylori is involved in the development of 80% of gastric cancers and 5.5% of all malignant conditions worldwide. Its persistence within the host’s stomach causes chronic inflammation, which is a well-known hallmark of carcinogenesis. A wide range of cytokines was reported to be involved in the initiation and long-term persistence of this local and systemic inflammation. IL-8 was among the first cytokines described to be increased in patients with H. pylori infection. Although, this cytokine was initially identified to exert a chemoattracting effect that represents a trigger for the activation of inflammatory cells within H.-pylori-infected mucosa, more recent studies failed in encountering any association between IL-8 and H. pylori infection. IL-6 is a multifunctional, pleiotropic and multipotent cytokine involved in mediating the interaction between innate and adaptive immunity with a dichotomous role acting as both a proinflammatory and an anti-inflammatory cytokine depending on the signaling pathway. IL-1α functions as a promoter of angiogenesis and vascular endothelial cell proliferation in gastric carcinoma since it is closely related to H.-pylori-induced inflammation in children. IL-1β is an essential trigger and enhancer of inflammation. The association between a low IL-1β level and an increased TNF-α level might be considered a risk factor for peptic ulcer disease in the setting of H. pylori infection. IL-10 downregulates both cytotoxic inflammatory responses and cell-mediated immune responses. H. pylori uses the immunosuppressive role of IL-10 to favor its escape from the host’s immune system. TGFβ is a continuous inflammatory mediator that promotes the adherence of H. pylori to the host’s cells and their subsequent colonization. The role of H.-pylori-induced inflammatory responses in the onset of gastric carcinogenesis seems to represent the missing puzzle piece for designing effective preventive and therapeutic strategies in patients with H.-pylori-associated gastric cancer.
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Park S, Lee JJ, Lee J, Lee JK, Byun J, Kim I, Ha JH. Lowering n-6/ n-3 Ratio as an Important Dietary Intervention to Prevent LPS-Inducible Dyslipidemia and Hepatic Abnormalities in ob/ob Mice. Int J Mol Sci 2022; 23:ijms23126384. [PMID: 35742829 PMCID: PMC9224551 DOI: 10.3390/ijms23126384] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may modulate obesity-related disorders, such as inflammation and dyslipidemia. An emerging research question is to understand the dietary intervention strategy that is more important regarding n-3 PUFA consumption: (1) a lower ratio of n-6/n-3 PUFAs or (2) a higher amount of n-3 PUFAs consumption. To understand the desirable dietary intervention method of n-3 PUFAs consumption, we replaced lard from the experimental diets with either perilla oil (PO) or corn oil (CO) to have identical n-3 amounts in the experimental diets. PO had a lower n-6/n-3 ratio, whereas CO contained higher amounts of PUFAs; it inherently contained relatively lower n-3 but higher n-6 PUFAs than PO. After the 12-week dietary intervention in ob/ob mice, dyslipidemia was observed in the normal chow and CO-fed ob/ob mice; however, PO feeding increased the high density lipoprotein-cholesterol (HDL-C) level; further, not only did the HDL-C level increase, the low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels also decreased significantly after lipopolysaccharide (LPS) injection. Consequently, extra TG accumulated in the liver and white adipose tissue (WAT) of normal chow- or CO-fed ob/ob mice after LPS injection; however, PO consumption decreased serum TG accumulation in the liver and WAT. PUFAs replacement attenuated systemic inflammation induced by LPS injection by increasing anti-inflammatory cytokines but inhibiting pro-inflammatory cytokine production in the serum and WAT. PO further decreased hepatic inflammation and fibrosis in comparison with the ND and CO. Hepatic functional biomarkers (aspartate aminotransferase (AST) and alanine transaminase (ALT) levels) were also remarkably decreased in the PO group. In LPS-challenged ob/ob mice, PO and CO decreased adipocyte size and adipokine secretion, with a reduction in phosphorylation of MAPKs compared to the ND group. In addition, LPS-inducible endoplasmic reticulum (ER) and oxidative stress decreased with consumption of PUFAs. Taken together, PUFAs from PO and CO play a role in regulating obesity-related disorders. Moreover, PO, which possesses a lower ratio of n-6/n-3 PUFAs, remarkably alleviated metabolic dysfunction in LPS-induced ob/ob mice. Therefore, an interventional trial considering the ratio of n-6/n-3 PUFAs may be desirable for modulating metabolic complications, such as inflammatory responses and ER stress in the circulation, liver, and/or WAT.
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Affiliation(s)
- Seohyun Park
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea; (S.P.); (J.L.)
| | - Jae-Joon Lee
- Department of Food and Nutrition, Chosun University, Gwangju 61452, Korea;
| | - Jisu Lee
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea; (S.P.); (J.L.)
| | - Jennifer K. Lee
- Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA;
| | - Jaemin Byun
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA;
| | - Inyong Kim
- Food and Nutrition Department, Sunchon University, Suncheon 57922, Korea
- Correspondence: (I.K.); (J.-H.H.)
| | - Jung-Heun Ha
- Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea; (S.P.); (J.L.)
- Research Center for Industrialization of Natural Neutralization, Dankook University, Yongin 16890, Korea
- Correspondence: (I.K.); (J.-H.H.)
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Costa TJ, De Oliveira JC, Giachini FR, Lima VV, Tostes RC, Bomfim GF. Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications. Front Physiol 2022; 13:787617. [PMID: 35360231 PMCID: PMC8961444 DOI: 10.3389/fphys.2022.787617] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/13/2022] [Indexed: 11/13/2022] Open
Abstract
A growing body of evidence highlights that several insults during pregnancy impact the vascular function and immune response of the male and female offspring. Overactivation of the immune system negatively influences cardiovascular function and contributes to cardiovascular disease. In this review, we propose that modulation of the immune system is a potential link between prenatal stress and offspring vascular dysfunction. Glucocorticoids are key mediators of stress and modulate the inflammatory response. The potential mechanisms whereby prenatal stress negatively impacts vascular function in the offspring, including poor hypothalamic–pituitary–adrenal axis regulation of inflammatory response, activation of Th17 cells, renin–angiotensin–aldosterone system hyperactivation, reactive oxygen species imbalance, generation of neoantigens and TLR4 activation, are discussed. Alterations in the immune system by maternal stress during pregnancy have broad relevance for vascular dysfunction and immune-mediated diseases, such as cardiovascular disease.
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Affiliation(s)
- Tiago J. Costa
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Júlio Cezar De Oliveira
- Health Education Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, Sinop, Brazil
| | - Fernanda Regina Giachini
- Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, Brazil
| | - Victor Vitorino Lima
- Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, Brazil
| | - Rita C. Tostes
- Health Education Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, Sinop, Brazil
| | - Gisele Facholi Bomfim
- Health Education Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, Sinop, Brazil
- *Correspondence: Gisele Facholi Bomfim,
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Polymorphisms and Gene-Gene Interaction in AGER/IL6 Pathway Might Be Associated with Diabetic Ischemic Heart Disease. J Pers Med 2022; 12:jpm12030392. [PMID: 35330392 PMCID: PMC8950247 DOI: 10.3390/jpm12030392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/10/2022] [Accepted: 02/22/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Although the genetic susceptibility to diabetes and ischemic heart disease (IHD) has been well demonstrated, studies aimed at exploring gene variations associated with diabetic IHD are still limited; Methods: Our study included 204 IHD cases who had been diagnosed with diabetes before the diagnosis of IHD and 882 healthy controls. Logistic regression was used to find the association of candidate SNPs and polygenic risk score (PRS) with diabetic IHD. The diagnostic accuracy was represented with AUC. Generalized multifactor dimensionality reduction (GMDR) was used to illustrate gene-gene interactions; Results: For IL6R rs4845625, the CT and TT genotypes were associated with a lower risk of diabetic IHD than the CC genotype (OR = 0.619, p = 0.033; OR = 0.542, p = 0.025, respectively). Haplotypes in the AGER gene (rs184003-rs1035798-rs2070600-rs1800624) and IL6R gene (rs7529229-rs4845625-rs4129267-rs7514452-rs4072391) were both significantly associated with diabetic IHD. PRS was associated with the disease (OR = 1.100, p = 0.005) after adjusting for covariates, and the AUC were 0.763 (p < 0.001). The GMDR analysis suggested that rs184003 and rs4845625 were the best interaction model after permutation testing (p = 0.001) with a cross-validation consistency of 10/10; Conclusions: SNPs and haplotypes in the AGER and IL6R genes and the interaction of rs184003 and rs4845625 were significantly associated with diabetic IHD.
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Santos FSD, Oliveira IOD, Mintem GC, Horta BL, Gigante DP. Epidemiology of interleukin-6: the 30-year follow-up of the 1982 Pelotas (Brazil) birth cohort study. Ann Hum Biol 2022; 48:525-533. [PMID: 35105198 DOI: 10.1080/03014460.2021.1998619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Cardiovascular diseases are the main cause of death globally. Interleukin-6 (IL-6) is a biomarker of cardiovascular risk. AIM To investigate factors associated with IL-6 concentration in serum, from early life up to 30 years of age. SUBJECTS AND METHODS In the 2012-2013 follow-up, IL-6 was measured in 2809 participants of the 1982 Pelotas Birth Cohort (1369 males). Multivariable linear regressions, stratified by sex, were performed to evaluate the associations of African ancestry, family income and maternal education at birth, monthly income and education at 30 years, smoking status, harmful alcohol intake, physical activity, and body composition with IL-6, considering a conceptual hierarchical framework. RESULTS Males with low educational levels and current smokers had the highest mean IL-6. Among females, African ancestry and low monthly income were associated with the highest mean values for the outcome. Physical activity had an inverse association with IL-6 concentration among females. A direct relationship was observed between the measures of adiposity on IL-6, in both sexes. CONCLUSION Body composition was the main predictor for the outcome evaluated in males and females. Thus, the avoidance of overweight remains an important strategy for the prevention and control of cardiovascular risk and biomarkers associated with these diseases.
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Affiliation(s)
| | | | - Gicele Costa Mintem
- Post-graduate Program in Nutrition and Food, Federal University of Pelotas, Pelotas, Brazil
| | - Bernardo Lessa Horta
- Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
| | - Denise Petrucci Gigante
- Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.,Post-graduate Program in Nutrition and Food, Federal University of Pelotas, Pelotas, Brazil
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Luk C, Haywood NJ, Bridge KI, Kearney MT. Paracrine Role of the Endothelium in Metabolic Homeostasis in Health and Nutrient Excess. Front Cardiovasc Med 2022; 9:882923. [PMID: 35557517 PMCID: PMC9086712 DOI: 10.3389/fcvm.2022.882923] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/04/2022] [Indexed: 02/02/2023] Open
Abstract
The vascular endothelium traditionally viewed as a simple physical barrier between the circulation and tissue is now well-established as a key organ mediating whole organism homeostasis by release of a portfolio of anti-inflammatory and pro-inflammatory vasoactive molecules. Healthy endothelium releases anti-inflammatory signaling molecules such as nitric oxide and prostacyclin; in contrast, diseased endothelium secretes pro-inflammatory signals such as reactive oxygen species, endothelin-1 and tumor necrosis factor-alpha (TNFα). Endothelial dysfunction, which has now been identified as a hallmark of different components of the cardiometabolic syndrome including obesity, type 2 diabetes and hypertension, initiates and drives the progression of tissue damage in these disorders. Recently it has become apparent that, in addition to vasoactive molecules, the vascular endothelium has the potential to secrete a diverse range of small molecules and proteins mediating metabolic processes in adipose tissue (AT), liver, skeletal muscle and the pancreas. AT plays a pivotal role in orchestrating whole-body energy homeostasis and AT dysfunction, characterized by local and systemic inflammation, is central to the metabolic complications of obesity. Thus, understanding and targeting the crosstalk between the endothelium and AT may generate novel therapeutic opportunities for the cardiometabolic syndrome. Here, we provide an overview of the role of the endothelial secretome in controlling the function of AT. The endothelial-derived metabolic regulatory factors are grouped and discussed based on their physical properties and their downstream signaling effects. In addition, we focus on the therapeutic potential of these regulatory factors in treating cardiometabolic syndrome, and discuss areas of future study of potential translatable and clinical significance. The vascular endothelium is emerging as an important paracrine/endocrine organ that secretes regulatory factors in response to nutritional and environmental cues. Endothelial dysfunction may result in imbalanced secretion of these regulatory factors and contribute to the progression of AT and whole body metabolic dysfunction. As the vascular endothelium is the first responder to local nutritional changes and adipocyte-derived signals, future work elucidating the changes in the endothelial secretome is crucial to improve our understanding of the pathophysiology of cardiometabolic disease, and in aiding our development of new therapeutic strategies to treat and prevent cardiometabolic syndrome.
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Affiliation(s)
- Cheukyau Luk
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
| | - Natalie J Haywood
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
| | - Katherine I Bridge
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
| | - Mark T Kearney
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
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Masood KI, Irfan M, Masood Q, Yameen M, Jamil B, Ram N, Rao S, Rottenberg M, Hasan Z. Latent
M. tuberculosis
infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)‐3 in the diabetic host. Scand J Immunol 2021; 95:e13134. [DOI: 10.1111/sji.13134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 01/06/2023]
Affiliation(s)
- Kiran Iqbal Masood
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Muhammad Irfan
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Qamar Masood
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Maliha Yameen
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Bushra Jamil
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Nanik Ram
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Shoaib Rao
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Martin Rottenberg
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
| | - Zahra Hasan
- Department of Pathology and Laboratory Medicine The Aga Khan University Karachi Pakistan
- Department of Medicine The Aga Khan University Karachi Pakistan
- Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
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Rafaqat S, Sharif S, Majeed M, Naz S, Manzoor F, Rafaqat S. Biomarkers of Metabolic Syndrome: Role in Pathogenesis and Pathophysiology Of Atrial Fibrillation. J Atr Fibrillation 2021; 14:20200495. [PMID: 34950373 DOI: 10.4022/jafib.20200495] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/11/2021] [Accepted: 05/12/2021] [Indexed: 12/14/2022]
Abstract
The relationship between Metabolic syndrome and Atrial Fibrillation is confirmed by many studies. The components of Metabolic syndrome cause remodeling of the atrial. Metabolic syndrome and metabolic derangements of the syndrome could be the cause of the pathogenesis of AF. This review article discusses the major biomarkers of Metabolic syndrome and their role in the pathogenesis of AF. The biomarkers are adiponectin, leptin, Leptin/ Adiponectin ratio, TNF-α, Interleukin-6, Interleukin-10, PTX3, ghrelin, uric acid, and OxLDL.The elevated plasma levels of adiponectin were linked to the presence of persistent AF. Leptin signaling contributes to angiotensin-II evoked AF and atrial fibrosis. Tumor necrosis factor-alpha involvement has been shown in the pathogenesis of chronic AF. Similarly, Valvular AF patients showed high levels of TNF-α. Increased left atrial size was associated with the interleukin-6 because it is a well-known risk factor for AF. Interleukin-10 as well as TNF-α were linked to AF recurrence after catheter ablation. PTX3 could be superior to other inflammatory markers that were reported to be elevated in AF. The serum ghrelin concentration in AF patients was reduced and significantly increased after treatment. Elevated levels of uric acid could be related to the burden of AF. Increased OxLDL was found in AF as compared to sinus rhythm control.
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Affiliation(s)
- Saira Rafaqat
- Department of Zoology,Lahore College for Women University, Near Wapda Flats Jail Rd, Jubilee Town, Lahore, Punjab 54000
| | - Saima Sharif
- Department of Zoology,Lahore College for Women University, Near Wapda Flats Jail Rd, Jubilee Town, Lahore, Punjab 54000
| | - Mona Majeed
- Senior Registrar, Emergency Department, Punjab Institute of Cardiology, Lahore, Pakistan
| | - Shagufta Naz
- Department of Zoology,Lahore College for Women University, Near Wapda Flats Jail Rd, Jubilee Town, Lahore, Punjab 54000
| | - Farkhanda Manzoor
- Department of Zoology,Lahore College for Women University, Near Wapda Flats Jail Rd, Jubilee Town, Lahore, Punjab 54000
| | - Sana Rafaqat
- Department of Biotechnology, Lahore College for Women University, Near Wapda Flats, Jail Rd, Jubilee Town, Lahore, Punjab 54000
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Dual-enhancement and dual-tag design for SERS-based sandwich immunoassays: evaluation of a metal-metal effect in 3D architecture. Mikrochim Acta 2021; 189:32. [PMID: 34932168 PMCID: PMC8692285 DOI: 10.1007/s00604-021-05125-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 12/02/2021] [Indexed: 01/07/2023]
Abstract
The design of a sandwich-type SERS immunoassay (surface-enhanced Raman spectroscopy) is demonstrated operating in dual surface enhancement and dual-tag paradigm. The capture and detection antibodies are linked to two SERS-active substrates and form together the three-dimensional (3D) structure after specific binding to interleukin 6. A variety of metal combinations is tested (Au–Ag, Au–Au, and Ag–Ag), but an enhanced electromagnetic field is generated only due to coupling of Ag and Au nanoparticles with an Au hexagonal nanoarray. The amplified in that way Raman signals improve the limit of detection over 3 times in comparison to the assay with only one SERS-active substrate. It is also shown that the proper readout of the true-positive signal can be achieved in assays with two Raman tags, and this approach also improves LOD. For the optimal combination of the metal–metal junction and Raman tags, a linear relationship between the Raman signal and the concentration of IL-6 is obtained in the range 0–1000 pg⋅mL−1with LOD of 25.2 pg mL−1and RSD < 10%. The presented proof-of-concept of the SERS immunoassay with the dual-enhancement and dual-tag opens additional opportunities for engineering reliable SERS biosensing.
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Ling Y, Weng H, Tang S. The relationship between IL-6 levels and the angiographic severity of coronary artery disease following percutaneous coronary intervention in acute coronary syndrome patients. BMC Cardiovasc Disord 2021; 21:578. [PMID: 34861824 PMCID: PMC8642871 DOI: 10.1186/s12872-021-02406-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 11/26/2021] [Indexed: 12/27/2022] Open
Abstract
Background The present investigation was developed for the exploration of the association between IL-6 levels and acute coronary syndrome (ACS) findings upon angiographic evaluation. Methods A retrospective review of 346 patients suffering from chest discomfort that underwent coronary angiography was performed. The SYNergy between Percutaneous Coronary Intervention with TAXus and cardiac surgery (SYNTAX) score (SS) and SS II were used to gauge ACS severity, with ACS patients being stratified into two groups based on an SS value of 22 and the median SS II value. Associations between IL-6 levels and SS or SS II values were assessed through Spearman's correlation analyses, and independent predictors of intermediate-high SS or high SS II were identified via a multivariate logistic regression approach. A receiver operating characteristic (ROC) curve was employed to explore of the predictive value of IL-6 levels. Results IL-6 was positively correlated with both SS (r = 0.479, P < 0.001) and SS II (r = 0.305, P < 0.001). Moreover, IL-6 levels were independently predictive of intermediate-high SS and high SS II values. ROC curves further demonstrated that IL-6 was able to predict intermediate-high SS and high SS II, with area under the curve (AUC) values of 0.806 and 0.624, respectively. Conclusion IL-6 levels are closely linked to the extent of coronary artery disease in ACS patients undergoing percutaneous coronary intervention. IL-6 levels may thus serve as a valuable and non-invasive biomarker of high-risk ACS patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02406-7.
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Affiliation(s)
- Yang Ling
- Department of Cardiology, Yijishan Hospital Affiliated To Wannan Medical College, 2# West Zhe Shan Road, Wuhu, 241000, China
| | - Hairong Weng
- Department of Emergency Intensive Care Unit, Yijishan Hospital Affiliated To Wannan Medical College, 2# West Zhe Shan Road, Wuhu, 241000, China
| | - Shengxing Tang
- Department of Cardiology, Yijishan Hospital Affiliated To Wannan Medical College, 2# West Zhe Shan Road, Wuhu, 241000, China.
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Dastar S, Gharesouran J, Mortazavi D, Hosseinzadeh H, Kian SJ, Taheri M, Ghafouri-Fard S, Jamali E, Rezazadeh M. COVID-19 pandemic: Insights into genetic susceptibility to SARS-CoV-2 and host genes implications on virus spread, disease severity and outcomes. Hum Antibodies 2021; 30:1-14. [PMID: 34864654 DOI: 10.3233/hab-211506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The outbreak of the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world has caused global public health emergencies, international concern and economic crises. The systemic SARS-CoV-2 disease (COVID-19) can lead to death through causing unrestrained cytokines-storm and subsequent pulmonary shutdown among the elderly and patients with pre-existing comorbidities. Additionally, in comparison with poor nations without primary health care services, in developed countries with advanced healthcare system we can witness higher number of infections per one million people. In this review, we summarize the latest studies on genes associated with SARS-CoV-2 pathogenesis and propose possible mechanisms of the virus replication cycle and its triggered signaling pathways to encourage researchers to investigate genetic and immune profiles of the disease and try strategies for its treatment. Our review shows that immune response in people with different genetic background might vary as African and then Asian populations have lowest number of affected cases compared with European and American nations. Considering SARS-CoV-2 pathogenesis, we put forward some potentially important genetic gateways to COVID-19 infection including genes involved in the entry and replication of SARS-CoV-2 and the regulation of host immune response which might represent explanation for its spread, severity, and morality. Finally, we suggest that genetic alterations within these gateways could be critical factors in influencing geographical discrepancies of the virus, so it is essential to fully study them and design appropriated and reliable therapeutic agents against COVID-19.
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Affiliation(s)
- Saba Dastar
- Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Fatih, Istanbul, Turkey
| | - Jalal Gharesouran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Deniz Mortazavi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hassan Hosseinzadeh
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Jalal Kian
- Department of Virology, Iran University of Medical Sciences, School of Medicine, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elena Jamali
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rezazadeh
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks. Int J Mol Sci 2021; 22:ijms222212419. [PMID: 34830301 PMCID: PMC8620086 DOI: 10.3390/ijms222212419] [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] [Received: 10/20/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 12/16/2022] Open
Abstract
Hypoglycemia has been recognized as a risk factor for diabetic vascular complications and cognitive decline, but the molecular mechanisms of the effect of hypoglycemia on target organs are not fully understood. In this work, gene networks of hypoglycemia and cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive decline, and Alzheimer's disease were reconstructed using ANDSystem, a text-mining-based tool. The gene network of hypoglycemia included 141 genes and 2467 interactions. Enrichment analysis of Gene Ontology (GO) biological processes showed that the regulation of insulin secretion, glucose homeostasis, apoptosis, nitric oxide biosynthesis, and cell signaling are significantly enriched for hypoglycemia. Among the network hubs, INS, IL6, LEP, TNF, IL1B, EGFR, and FOS had the highest betweenness centrality, while GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR, and AQP7 demonstrated the highest cross-talk specificity. Hypoglycemia-related genes were overrepresented in the gene networks of diabetic complications and comorbidity; moreover, 14 genes were mutual for all studied disorders. Eleven GO biological processes (glucose homeostasis, nitric oxide biosynthesis, smooth muscle cell proliferation, ERK1 and ERK2 cascade, etc.) were overrepresented in all reconstructed networks. The obtained results expand our understanding of the molecular mechanisms underlying the deteriorating effects of hypoglycemia in diabetes-associated vascular disease and cognitive dysfunction.
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Bioactive Foods and Medicinal Plants for Cardiovascular Complications of Type II Diabetes: Current Clinical Evidence and Future Perspectives. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6681540. [PMID: 34567218 PMCID: PMC8460387 DOI: 10.1155/2021/6681540] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 09/01/2021] [Indexed: 12/14/2022]
Abstract
Cardiovascular diseases (CVDs) are the main cause of mortality in type 2 diabetes mellitus (T2DM); however, not all patients are fully satisfied with the current available treatments. Medicinal plants have been globally investigated regarding their effect in CVD, yet the field is far from getting exhausted. The current paper aims to provide an evidence-based review on the clinically evaluated medicinal plants and their main therapeutic targets for the management of CVD in T2DM. Electronic databases including PubMed, Cochrane, Embase, Scopus, and Web of Science were searched from 2000 until November 2019, and related clinical studies were included. Lipid metabolism, glycemic status, systemic inflammation, blood pressure, endothelial function, oxidative stress, and anthropometric parameters are the key points regulated by medicinal plants in T2DM. Anti-inflammatory and antioxidant properties are the two most important mechanisms since inflammation and oxidative stress are the first steps triggering a domino of molecular pathological pathways leading to T2DM and, subsequently, CVD. Polyphenols with potent antioxidant and anti-inflammatory effects, essential oil-derived compounds with vasorelaxant properties, and fibers with demonstrated effects on obesity are the main categories of phytochemicals beneficial for CVD of T2DM. Some medicinal plants such as garlic (Allium sativum) and milk thistle (Silybum marianum) have strong evidences regarding their beneficial effects; however, others have low level of evidence which reveals the need for further clinical studies with larger sample sizes and longer follow-up periods to confirm the safety and efficacy of medicinal plants for the management of CVD in T2DM.
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Hayes LD, Herbert P, Sculthorpe NF, Grace FM. Short-Term and Lifelong Exercise Training Lowers Inflammatory Mediators in Older Men. Front Physiol 2021; 12:702248. [PMID: 34489725 PMCID: PMC8417555 DOI: 10.3389/fphys.2021.702248] [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] [Received: 04/29/2021] [Accepted: 07/26/2021] [Indexed: 11/23/2022] Open
Abstract
Increased basal low-grade inflammation is observed with advancing age, which is augmented by physical inactivity. However, data regarding the influence of lifelong exercise training and particularly high-intensity interval training (HIIT) on inflammatory mediators in older men are scarce. Therefore, we examined effects of 6weeks of aerobic preconditioning followed by 6weeks of HIIT on inflammatory mediators [interleukin (IL)-6, homocysteine, and high-sensitivity C-reactive protein (hsCRP)] in previously sedentary older men (SED) and masters athletes (LEX). Further, we investigated whether SED exhibited greater basal inflammatory biomarkers compared to LEX. Twenty-two men (aged 62±2years) participated in the SED group, while 17 age-matched LEX men (aged 60±5years) also participated as a positive comparison group. In SED, preconditioning (P=0.030, d=0.34) and HIIT (P=0.030, d=0.48) caused a reduction in IL-6 compared to enrollment. SED homocysteine did not change throughout (P>0.57; d<0.26), while the decrease in hsCRP after preconditioning (P=0.486, d=0.25) and after HIIT (P=0.781, d=0.23) compared to enrollment was small. HIIT did not influence IL-6 or hsCRP in LEX (all P>0.42; d<0.3). Homocysteine increased from enrollment to post-HIIT in LEX (P=0.144, d=0.83), but all other perturbations were trivial. IL-6 and hsCRP were greater in SED than LEX throughout the investigation (all P<0.029; d>0.72), but homocysteine was not different (all P >0.131; d<0.41). Results of this study suggest moderate-intensity aerobic exercise and HIIT lowers IL-6 (and possible hsCRP) in previously sedentary older men. Moreover, lifelong exercise is associated with reduced concentrations of some inflammatory biomarkers in older males, and therefore, physical activity, rather than age per se, is implicated in chronic low-grade inflammation. Moreover, physical inactivity-induced inflammation may be partly salvaged by short-term exercise training.
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Affiliation(s)
- Lawrence D Hayes
- School of Health and Life Sciences, University of the West of Scotland, Glasgow, United Kingdom
| | - Peter Herbert
- School of Sport, Health and Outdoor Education, University of Wales Trinity Saint David, Carmarthen, United Kingdom
| | - Nicholas F Sculthorpe
- School of Health and Life Sciences, University of the West of Scotland, Glasgow, United Kingdom
| | - Fergal M Grace
- Faculty of Health, Federation University, Ballarat, VIC, Australia
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Ibrahim BA, Mohamed SH, Hassaan MMM, Sabbah NA. Associations of galectin-3 expression and LGALS-3 (rs4652) gene variant with coronary artery disease risk in diabetics. J Med Biochem 2021; 40:395-406. [PMID: 34616230 PMCID: PMC8451226 DOI: 10.5937/jomb0-30424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 06/10/2021] [Indexed: 11/26/2022] Open
Abstract
Background Galectin-3 protein encoded by lectin galactoside-binding soluble-3 (LGALS-3) gene is an important genetic factor in type 2 diabetes mellitus (T2DM) and its cardiovascular obstacles in various populations. We aimed to elicit the pro-inflammatory effect of galectin-3 as determined by interleukin-6 (IL-6) serum levels and to explore the relationship between galectin-3 (LGALS-3 rs4652) gene variant and its expression levels with coronary artery disease (CAD) risk among T2DM Egyptian patients. Methods 112 lean subjects were compared to 100 T2DM without CAD and 84 T2DM with CAD. A tetra-primer amplification refractory mutation system polymerase chain reaction was used to test LGALS-3 (rs4652), and galectin3 expression was tested with a quantitative real-time polymerase chain reaction. Serum IL-6 was measured using an enzyme-linked immunosorbent assay. Results We found that the prevalence of LGALS-3 (rs4652) AC genotype and galectin-3 gene expression levels in T2DM with CAD were significantly higher than the additional 2 groups and were correlated positively to IL-6 circulating levels. Also, the C allele carriers (AC+CC) had significantly higher relative Galectin-3 expression levels compared to the A allele carriers (AA). Conclusions We concluded that galectin-3 expression levels and LGALS-3 (rs4652) AC genotype were coronary artery disease risk factors in people with type two diabetes among an Egyptian sample.
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Affiliation(s)
- Basma A Ibrahim
- University of Zagazig, Faculty of Medicine, Medical Biochemistry Department, Zagazig, Egypt
| | - Samy H Mohamed
- University of Zagazig, Faculty of Medicine, Medical Biochemistry Department, Zagazig, Egypt
| | - Mohamed M M Hassaan
- University of Zagazig, Faculty of Medicine, Internal Medicine Department, Zagazig, Egypt
| | - Norhan A Sabbah
- University of Zagazig, Faculty of Medicine, Medical Biochemistry Department, Zagazig, Egypt
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