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Mishra R, Singh TG, Bhatia R, Awasthi A. Unveiling the therapeutic journey of snail mucus in diabetic wound care. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:6531-6560. [PMID: 39869187 DOI: 10.1007/s00210-024-03657-9] [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: 10/01/2024] [Accepted: 11/19/2024] [Indexed: 01/28/2025]
Abstract
A diabetic wound (DW) is an alteration in the highly orchestrated physiological sequence of wound healing especially, the inflammatory phase. These alterations result in the generation of oxidative stress and inflammation at the injury site. This further leads to the impairment in the angiogenesis, extracellular matrix, collagen deposition, and re-epithelialization. Additionally, in DW there is the presence of microbial load which makes the wound worse and impedes the wound healing cycle. There are several treatment strategies which have been employed by the researchers to mitigate the aforementioned challenges. However, they failed to address the multifactorial pathogenic nature of the disease. Looking at the severity of the disease researchers have explored snail mucus and its components such as achacin, allantoin, elastin, collagen, and glycosaminoglycan due to its multiple therapeutic potentials; however, glycosaminoglycan (GAGs) is very important among all because they accelerate the wound-healing process by promoting reepithelialization, vascularization, granulation, and angiogenesis at the site of injury. Despite its varied applications, the field of snail mucus in wound healing is still underexplored. The present review aims to highlight the role of snail mucus in diabetic wound healing, the advantages of snail mucus over conventional treatments, the therapeutic potential of snail mucus, and the application of snail mucus in DW. Additionally, clinical trials, patents, structural variations, and advancements in snail mucus characterization have been covered in the article.
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Affiliation(s)
- Ritika Mishra
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, 142001, Punjab, India
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Rohit Bhatia
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
| | - Ankit Awasthi
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
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Musialek P, Bonati LH, Bulbulia R, Halliday A, Bock B, Capoccia L, Eckstein HH, Grunwald IQ, Lip PL, Monteiro A, Paraskevas KI, Podlasek A, Rantner B, Rosenfield K, Siddiqui AH, Sillesen H, Van Herzeele I, Guzik TJ, Mazzolai L, Aboyans V, Lip GYH. Stroke risk management in carotid atherosclerotic disease: a clinical consensus statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases. Cardiovasc Res 2025; 121:13-43. [PMID: 37632337 DOI: 10.1093/cvr/cvad135] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 08/28/2023] Open
Abstract
Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded the knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (i) establishing a unified knowledge foundation and (ii) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailors personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology, and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promoting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management including statins, novel lipid-lowering and antithrombotic strategies, and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multi-morbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for inter-disciplinary collaboration and prioritized patient-centric decision-making.
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Affiliation(s)
- Piotr Musialek
- Jagiellonian University Department of Cardiac and Vascular Diseases, St. John Paul II Hospital, ul. Pradnicka 80, 31-202 Krakow, Poland
| | | | - Richard Bulbulia
- Medical Research Council Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | - Alison Halliday
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | | | - Laura Capoccia
- Department of Surgery 'Paride Stefanini', Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy
| | - Hans-Henning Eckstein
- Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Iris Q Grunwald
- Department of Radiology, Ninewells Hospital, University of Dundee, Dundee, UK
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
| | | | - Andre Monteiro
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, NY, USA
| | | | - Anna Podlasek
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
- Division of Radiological and Imaging Sciences, University of Nottingham, Nottingham, UK
| | - Barbara Rantner
- Vascular Surgery Department, Ludwig Maximilian University Hospital, Campus Grosshadern, Munich, Germany
| | | | - Adnan H Siddiqui
- Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, and Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY, USA
- Jacobs Institute, Buffalo, NY, USA
| | - Henrik Sillesen
- Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Isabelle Van Herzeele
- Department of Thoracic and Vascular Surgery, Ghent University Hospital, Ghent, Belgium
| | - Tomasz J Guzik
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Department of Internal Medicine, Jagiellonian University Collegium Medicum, Krakow, Poland
| | - Lucia Mazzolai
- Department of Angiology, University Hospital Lausanne, Lausanne, Switzerland
| | - Victor Aboyans
- Department of Cardiology, CHRU Dupuytren Limoges, Limoges, France
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Yu Q, Mao H, Vijayalakshmi A, Zhou M. Acacetin Prevents Renal Damage Induced by Streptozotocin via Altering the NF-κB/ASC/NLRP3 and AMPK/SIRT1 Pathways in Mice. Biotechnol Appl Biochem 2025:e2753. [PMID: 40150865 DOI: 10.1002/bab.2753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 03/11/2025] [Indexed: 03/29/2025]
Abstract
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Its pathogenesis includes inflammation, an excess of reactive oxygen species, and kidney damage. The present study intended to explore the nephroprotective effects of acacetin (ACN) in streptozotocin-induced diabetic animals. The following are the experimental groups: One millilitre of 0.9% saline was given to Group I (control), Streptozotocin (STZ) (diabetic animals) + 0.9% saline to Group II (DN group) (negative control), DN + ACN (15 mg/kg body weight [bw]) to Group III, and DN + Valsartan (150 mg/kg bw) to Group IV. According to the findings, ACN decreased the levels of glucose, serum creatinine (Scr), blood urea nitrogen (BUN), malondialdehyde (MDA), and proinflammatory cytokines while increasing the bw, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in comparison to the DN animals. The histopathological analysis revealed that the animals treated with ACN showed recovery of renal damage in the tissues caused by STZ. In the STZ-induced DN mice, ACN reduced renal damage by upregulating the proteins of 5' adenosine monophosphate-activated protein kinase (AMPK), p-AMPK, and SIRT1 and downregulating the proteins of TGF-β, COL-1, COL-IV, NF-κB, ASC, NLRP3, and GSDMD, according to western blot analysis. Hence, the current study demonstrated that the regulation of the AMPK/SIRT1 and NF-κB/ASC/NLRP3 inflammasome pathways in DN mice was responsible for the protective effects of ACN. ACN may therefore be a viable treatment option for DN.
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Affiliation(s)
- Qingfei Yu
- Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Hongyan Mao
- Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Annamalai Vijayalakshmi
- Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India
| | - Meilan Zhou
- Department of Nephrology, Xijing Hospital, Air Force Military Medical University, Xi'an, China
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Sarlak Z, Naderi N, Amidi B, Ghorbanzadeh V. Sodium Butyrate, A Gut Microbiota Derived Metabolite in Type 2 Diabetes Mellitus and Cardiovascular Disease: A Review. Cardiovasc Hematol Agents Med Chem 2025; 23:1-10. [PMID: 39206487 DOI: 10.2174/0118715257307380240820052940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 06/13/2024] [Accepted: 07/03/2024] [Indexed: 09/04/2024]
Abstract
Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.
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Affiliation(s)
- Zeynab Sarlak
- Department of Biology, Khorramabad branch, Islamic Azad University, Khorramabad, Iran
| | - Narges Naderi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Bardia Amidi
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Vajihe Ghorbanzadeh
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
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Singh U, Sharma R, Kumar R. An Overview on Diabetic Neuropathy. Curr Diabetes Rev 2025; 21:29-42. [PMID: 38919000 DOI: 10.2174/0115733998295741240606104106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/09/2024] [Accepted: 05/30/2024] [Indexed: 06/27/2024]
Abstract
The term "Diabetic neuropathy" refers to a collection of clinical and subclinical symptoms caused by problems with the peripheral nervous system. Diabetes, which affects approximately 381 million people worldwide, is the source of dysfunction due to the emergence of microvascular complications. It is anticipated that in the next ten years, Diabetic neuropathy will manifest in about 50% of patients who are currently diagnosed with diabetes. Clinical diagnosis can be established by getting a thorough patient history and exploring the symptoms to rule out alternative causes. Although distal symmetrical polyneuropathy, or just, is the most common and well-researched variant of the disorder, this review will concentrate on it. The multifactorial pathogenesis is linked to various inflammatory, vascular, metabolic, and neurodegenerative illnesses. The three fundamental molecular alterations that lead to the development of diabetic neuropathic pain are oxidative stress, endothelial dysfunction, and chronic inflammation. These three elements are crucial in the development of polyneuropathy because their combination might result in direct axonal damage and nerve ischemia. The purpose of this article was to provide a narrative review of diabetic neuropathy. We provide an overview of the most recent data on biomarkers, the pathogenesis of the illness, the most recent epidemiology of diabetic neuropathy, and the existing screening and diagnosis outcome measures used in both clinical and research contexts.
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Affiliation(s)
- Ujjawal Singh
- Department of Pharmacy Practice, ISF College of Pharmacy, Moga, India
| | - Ramsha Sharma
- Department of Pharmacy Practice, ISF College of Pharmacy, Moga, India
| | - Ranjeet Kumar
- Department of Pharmacy Practice, ISF College of Pharmacy, Moga, India
- Narayan Institute of Pharmacy, Gopal Narayan Singh University, Sasaram, Rohtas, Bihar, 821305, India
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Wen S, Xu D, Yuan Y, Xu Z, Li Y, Gong M, Yuan X, Zhou L. The Effect of Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic on the Metabolic Tumor Markers: A Real-World Retrospective Study. Diabetes Metab Syndr Obes 2024; 17:4115-4133. [PMID: 39502450 PMCID: PMC11537188 DOI: 10.2147/dmso.s487398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 10/26/2024] [Indexed: 11/08/2024] Open
Abstract
Objective Serum tumor markers have been discovered to be elevated in individuals with diabetes mellitus (DM); however, their significance in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia (HHS) is unknown. We evaluated these indicators in the patients with DKA and HHS. Materials and Methods We retrospectively collected the laboratory data of 565 diabetic patients from Shanghai Pudong Hospital between Jan, 2019 and May, 2023, including 300 patients with type 2 diabetes mellitus (T2DM), 206 with DKA, and 59 with HHS. Serum tumor biomarkers and further clinical laboratory tests were compared among the three groups. Patients with conspicuous tumor evidence were excluded from the study. Results We found significantly higher levels of carbohydrate antigen 199 (CA199) in DKA (p<0.01), carcinoembryonic antigen (CEA), complex prostate specific antigen (CPSA) (p<0.01), prostate specific antigen (PSA) (p<0.05) in HHS, as well as the plasma lipid profile, iron, and electrolytes, in addition to decreased thyroid function, hepatic and renal function, and cardiac function (p<0.05). A Spearman correlational study revealed that osmolar levels were significantly positively correlated with myoglobin (MYO) and cardiac troponin I (cTNI), whereas serum iron concentration (r=0.520) was positively correlated with CEA levels in HHS. pH was negatively correlated with CA199 (r=-0.195), while HbA1c (r=0.22), globin (r=0.341), and total cholesterol (TC) (r=0.191) were positively correlated with elevated CA199 levels. Moreover, the multilinear regression investigation identified osmolarity as a significant determinant for CEA, as well as other parameters, and all proved to be proper predictors for CEA in HHS via ROC curve establishment. Conclusion Elevated CA199 levels in DKA were associated with acidosis, whereas HHS with elevated CEA levels may be related to iron homeostasis and could be predicted via the osmolar degree and other predictors.
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Grants
- Integrated Traditional Chinese and Western Medicine (YC-2023-0404), Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118), Fudan Good Practice Program of Teaching and Learning (FD2023A227), Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY- ZXYJHZX-2-201712), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), Shanghai Natural Science Foundation (19ZR1447500), Pudong New Area Clinical Characteristic Discipline Project (PWYts2021-11), Pudong New Area Clinical Characteristic Discipline Project (PWYts2021-01), Wenzhou Medical University Education Grant (JG2021197)
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Affiliation(s)
- Song Wen
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Dongxiang Xu
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Yue Yuan
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Zhimin Xu
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Yanyan Li
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Min Gong
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Xinlu Yuan
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
| | - Ligang Zhou
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China
- Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China
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Das J, Roy Sarkar S, Das A, Barui A, Mitra Mazumder P. Assessment of efficacy of chrysin in diabetes-associated cardiac complications in chick embryo and murine model. J Pharm Pharmacol 2024; 76:1225-1235. [PMID: 38989974 DOI: 10.1093/jpp/rgae088] [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: 12/21/2023] [Accepted: 06/14/2024] [Indexed: 07/12/2024]
Abstract
OBJECTIVES Patients with type 2 diabetes or prolonged diabetic condition are webbed into cardiac complications. This study aimed to ascertain the utility of chick embryo as an alternative to the mammalian model for type 2 diabetes-induced cardiac complications and chrysin as a protective agent. METHODS Diabetes was activated in ovo model (chick embryo) using glucose along with β-hydroxybutyric acid. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Alamar, and Kenacid blue assay were used to compare with chrysin-administered group. Blood glucose level, total cholesterol, triglyceride, and high-density lipoprotein were considered as endpoints. Diabetes was induced in Wistar albino rats by administering a high-fat diet and a subdued dose of streptozotocin (35 mg/kg, b.w). Percentage of glycated hemoglobin, creatinine kinase-MB, tumor necrosis factor-α, and C-reactive protein were evaluated and compared with chrysin administered group. KEY FINDINGS Chrysin treatment improved elevated blood glucose levels and dyslipidemia in a diabetic group of whole embryos. Condensed cellular growth and protein content as well as enhanced cytotoxicity in ovo were shielded by chrysin. Chrysin reduced cardiac and inflammatory markers in diabetic rats and provided cellular protection to damage the heart of diabetic rats. CONCLUSION The protective action of chrysin in ovo model induced a secondary complication associated with diabetes, evidenced that the ovo model is an effective alternative in curtailing higher animal use in scientific research.
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Affiliation(s)
- Joyani Das
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
| | - Suparna Roy Sarkar
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
| | - Ankita Das
- Centre for Health Care Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur 711103, India
| | - Ananya Barui
- Centre for Health Care Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur 711103, India
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
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Mirzavi F, Rajabian A, Hosseini H. The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress-related organ damage. Food Sci Nutr 2024; 12:6108-6122. [PMID: 39554322 PMCID: PMC11561782 DOI: 10.1002/fsn3.4289] [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: 01/10/2024] [Revised: 05/16/2024] [Accepted: 06/08/2024] [Indexed: 11/19/2024] Open
Abstract
The anticancer, antioxidant, and immunomodulatory properties of carotenoids from saffron or apocarotenoids (e.g., crocin, safranal, crocetin, and picrocrocin) have prompted research into their benefits. Apocarotenoids seem to be effective compound for the treatment of chronic diseases, such as neurodegenerative, cardiovascular, cancer, respiratory, and metabolic disorders. Endoplasmic reticulum (ER) is an essential organelle found in the cytoplasm of eukaryotic cells that participates in the biosynthesis of proteins, lipids, and steroid hormones. Given the role of the ER in the regulation of several fundamental biological processes, including metabolic pathways and immune responses, aberrant ER function can have a significant influence on these vital processes and result in serious pathological consequences. Exposure of cell to adverse environmental challenges, such as toxic agents, ischemia, and so on, causes accumulation of unfolded or misfolded proteins in the ER lumen, also called ER stress. There is a growing evidence to suggest that ER disturbance in the form of oxidative/nitrosative stress and subsequent apoptotic cell death plays major roles in the pathogenesis of many human diseases, including cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and liver diseases. Apocarotenoids with their unique properties can modulate ER stress through PERK/eIF2α/ATF4/CHOP (protein kinase R (PKR)-like ER kinase/eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP /homologous protein) and X-Box Binding Protein 1/activating transcription factor 6 (XBP1/ATF6) pathways. In addition, they suppress apoptosis through inhibition of endoplasmic and mitochondrial-dependent caspase cascade and can stimulate SIRT1 (silent information regulator 1) and Nrf2 (nuclear factor erythroid 2-related factor 2) expression, thereby leading to protection against oxidative stress. This review summarizes the potential benefits of apocarotenoids in various ER-stress-related disorders.
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Affiliation(s)
- Farshad Mirzavi
- Cardiovascular Diseases Research CenterBirjand University of Medical SciencesBirjandIran
| | - Arezoo Rajabian
- Neuroscience Research CenterMashhad University of Medical SciencesMashhadIran
- Department of NeuroscienceFaculty of Medicine, Mashhad University of Medical SciencesMashhadIran
| | - Hossein Hosseini
- Department of Clinical BiochemistryFaculty of Medicine, Mashhad University of Medical SciencesMashhadIran
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Zhang Y, Zheng P, Shi J, Ma Y, Chen Z, Wang T, Jia G. The modification effect of fasting blood glucose level on the associations between short-term ambient air pollution and blood lipids. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:2998-3010. [PMID: 37975287 DOI: 10.1080/09603123.2023.2283048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/09/2023] [Indexed: 11/19/2023]
Abstract
The association between short-term ambient air pollution (AAP) exposure and blood lipids is inconsistent across populations. This study aimed to investigate the modifying effects of fasting blood glucose (FBG) levels on the associations between short-term AAP exposure and blood lipids in 110,637 male participants from Beijing, China. The results showed that FBG modified the association between short-term AAP exposure and blood lipids, especially low-density lipoprotein cholesterol (LDL-C). In the hyperglycemia group, a 10-μg/m3 increase in particles with diameters ≤ 2.5 μm (PM2.5), particles with diameters ≤ 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), or a 1-mg/m3 increase in carbon monoxide (CO) was associated with a 0.454%, 0.305%, 1.507%, 0.872%, or 3.961% increase in LDL-C, respectively. In the nonhyperglycemic group, short-term increases in air pollutants were even associated with small decreases in LDL-C. The findings demonstrate that lipids in hyperglycemic individuals are more vulnerable to short-term AAP exposure than those in normal populations.
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Affiliation(s)
- Yi Zhang
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
| | - Pai Zheng
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
| | - Jiaqi Shi
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
| | - Ying Ma
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
| | - Zhangjian Chen
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
| | - Tiancheng Wang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Guang Jia
- Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China
- Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University, Beijing, China
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10
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Stanek A, Mikhailidis DP, Paraskevas KI, Jawien A, Antignani PL, Mansilha A, Blinc A, Poredoš P. Specificities of primary and secondary prevention of lower extremity artery disease in patients with diabetes mellitus. INT ANGIOL 2024; 43:367-373. [PMID: 39041784 DOI: 10.23736/s0392-9590.24.05260-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Diabetes mellitus (DM) is a major risk factor for lower extremity arterial disease (LEAD) and about 20% of symptomatic patients with LEAD have DM. In subjects with DM, LEAD is a cause of morbidity and mortality. DM typically causes complications in the form of macro- and microangiopathy. In these patients, macroangiopathy manifests as atherosclerosis like in non-diabetic patients. However, its course is accelerated due to accompanying risk factors like hyperlipidemia and hypertension, with cumulative effects. Other factors are also relevant such as inflammation, endothelial dysfunction, platelet activation, blood rheological properties, hypercoagulability, and factors stimulating vascular smooth muscle cell proliferation. Additionally, DM is a risk factor for restenosis and amputation. DM is strongly associated with femoral-popliteal and tibial LEAD, which manifests earlier in patients with DM and may progress more rapidly to critical limb ischemia. Diabetic microangiopathy is characterized by arteriolosclerosis and interstitial fibrosis which additionally affects progression and outcomes of angiopathy of lower limbs. Glycemic control particularly decreases microangiopathic complications, while prevention of macrovascular complications requires treatment of accompanying risk factors like hypertension and dyslipidemia.
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Affiliation(s)
- Agata Stanek
- Department of Internal Medicine, Angiology and Physical Medicine, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Bytom, Poland -
| | - Dimitri P Mikhailidis
- Division of Surgery and Interventional Science, Department of Surgical Biotechnology, University College London Medical School, London, UK
- Department of Clinical Biochemistry, University College London (UCL), Royal Free Hospital Campus, London, UK
| | | | - Arkadiusz Jawien
- Collegium Medicum, Department of Vascular Surgery and Angiology, Nicolaus Copernicus University, Bydgoszcz, Poland
| | | | - Armando Mansilha
- Department of Angiology and Vascular Surgery, Faculty of Medicine, Sao Joao University Hospital, University of Porto, Porto, Portugal
| | - Ales Blinc
- Department of Vascular Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
- Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Pavel Poredoš
- Department of Vascular Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
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11
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Zhang Q, Hu S, Jin Z, Wang S, Zhang B, Zhao L. Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application. Front Pharmacol 2024; 15:1339148. [PMID: 38510656 PMCID: PMC10953506 DOI: 10.3389/fphar.2024.1339148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/31/2024] [Indexed: 03/22/2024] Open
Abstract
Objective: Affected by aging, the elderly diabetes patients have many pathological characteristics different from the young people, including more complications, vascular aging, cognitive impairment, osteoporosis, and sarcopenia. This article will explore their pathogenesis and the mechanism of Traditional Chinese medicine (TCM) intervention, and use the method of systematic review to evaluate the clinical application of TCM in elderly diabetes. Method: Searching for randomized controlled trials (RCTs) published from January 2000 to November 2023 in the following databases: Web of Science, Pubmed, Embase, Cochrane Library, Sinomed, China National Knowledge Internet, Wanfang and VIP. They were evaluated by three subgroups of Traditional Chinese Prescription, Traditional Chinese patent medicines and Traditional Chinese medicine extracts for their common prescriptions, drugs, adverse reactions and the quality of them. Results and Conclusion: TCM has the advantages of multi-target and synergistic treatment in the treatment of elderly diabetes. However, current clinical researches have shortcomings including the inclusion of age criteria and diagnosis of subjects are unclear, imprecise research design, non-standard intervention measures, and its safety needs further exploration. In the future, the diagnosis of elderly people with diabetes needs to be further clarified. Traditional Chinese patent medicines included in the pharmacopoeia can be used to conduct more rigorous RCTs, and then gradually standardize the traditional Chinese medicine prescriptions and traditional Chinese medicine extracts, providing higher level evidence for the treatment of elderly diabetes with traditional Chinese medicine.
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Affiliation(s)
- Qiqi Zhang
- Institute of Metabolic Diseases, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China
| | - Shiwan Hu
- Institute of Metabolic Diseases, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zishan Jin
- Institute of Metabolic Diseases, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Sicheng Wang
- Institute of Metabolic Diseases, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China
| | - Boxun Zhang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang’anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China
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12
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Guo Y, Guo Q, Guo R, Yan Y, Gong W, Zheng W, Wang H, Xu L, Wang X, Nie S. Glycemic Status and Myocardial Strain by Cardiac MRI in Patients With ST-Segment Elevation Myocardial Infarction. J Magn Reson Imaging 2024; 59:548-560. [PMID: 37222658 DOI: 10.1002/jmri.28794] [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: 02/21/2023] [Revised: 05/04/2023] [Accepted: 05/05/2023] [Indexed: 05/25/2023] Open
Abstract
BACKGROUND It is uncertain how various degree of glycemic status affect left ventricular (LV) myocardial strain in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). PURPOSE To investigate the relationship of glycemic status and myocardial strain in STEMI patients. STUDY TYPE Prospective cohort study. POPULATION 282 STEMI patients with cardiac magnetic resonance imaging 5 ± 2 days post-PPCI. Patients were divided into three groups based on the level of glycated hemoglobin A1c (HbA1c) (group 1: HbA1c < 5.7%; group 2: 5.7% ≤ HbA1c < 6.5%; group 3: HbA1c ≥ 6.5%). FIELD STRENGTH/SEQUENCE 3.0-T; late gadolinium enhancement, balanced steady-state free precession cine sequence, black blood fat-suppressed T2-weighted. ASSESSMENT LV function, myocardial strain, and infarct characteristics (infarct size, microvascular obstruction, and intramyocardial hemorrhage) were compared among the three groups by one-way analysis of variance (ANOVA) or Wilcoxon rank sum test. Intraobserver and interobserver reproducibility of LV myocardial strain was evaluated. STATISTICAL TESTS ANOVA or Wilcoxon rank sum test, Pearson chi-square or Fisher's exact test, Spearman's correlation analyses and multivariable linear regression analysis. A two-tailed P value <0.05 was considered statistically significant. RESULTS Infarct characteristics were similar among the three groups (P = 0.934, P = 0.097, P = 0.533, respectively). Patients with HbA1c ≥ 6.5% had decreased LV myocardial strain compared with HbA1c 5.7%-6.4%, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strain. However, no significant differences in myocardial strain were observed between patients with HbA1c 5.7%-6.4% and HbA1c < 5.7% (P = 0.716; P = 0.294; P = 0.883, respectively). After adjustment for confounders, HbA1c as a continuous variable (beta coefficient [β] = -0.676; β = 0.172; β = 0.205, respectively) and HbA1c ≥ 6.5% (β = -3.682; β = 0.552; β = 0.681, respectively) were both independently associated with decreased GRS, GCS, and GLS. DATA CONCLUSION Patients with uncontrolled blood glucose (categorized in group HbA1c ≥ 6.5%) had worse myocardial strain. The level of HbA1c appeared to be independently associated with decreased myocardial strain in STEMI patients. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Yingying Guo
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Qian Guo
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ruifeng Guo
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yan Yan
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Wei Gong
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Wen Zheng
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hui Wang
- Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Lei Xu
- Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xiao Wang
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Shaoping Nie
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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13
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Asante DB, Wiafe GA. Therapeutic Benefit of Vernonia amygdalina in the Treatment of Diabetes and Its Associated Complications in Preclinical Studies. J Diabetes Res 2023; 2023:3159352. [PMID: 38033739 PMCID: PMC10686711 DOI: 10.1155/2023/3159352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 10/31/2023] [Accepted: 11/02/2023] [Indexed: 12/02/2023] Open
Abstract
Diabetes mellitus (DM), a complex heterogeneous metabolic disorder characterized by a defect in the function of insulin, is on the rapid rise globally. Sustained hyperglycemia which is a major sign of DM is linked to the generation of reactive oxygen species which promotes adverse complications of the disorder. Traditional herbal treatment of DM is a common practice in Africa and other tropical parts of the world. Vernonia amygdalina (VA), one of the highly researched species in the Asteraceae family, has proven to possess potent antidiabetic properties. Several phytochemicals identified in multiple extracts from VA are purported to be responsible for the antidiabetic potential of the plant. In this review, we discuss the therapeutic potential of VA in diabetes and its associated complications. We appraise the current evidence and further suggest potential areas that could be effectively exploited in future VA research on diabetes.
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Affiliation(s)
- Du-Bois Asante
- Department of Biomedical Sciences, University of Cape Coast, Ghana
- Department of Forensic Science, University of Cape Coast, Ghana
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14
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Rotaru L, Groppa L, Russu E, Chișlari L, Codreanu C, Spinei L, Arnaut O, Cornea C. Diabetes mellitus as a risk factor and comorbidity in gout. Folia Med (Plovdiv) 2023; 65:770-774. [PMID: 38351759 DOI: 10.3897/folmed.65.e91075] [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: 07/30/2022] [Accepted: 08/12/2022] [Indexed: 02/16/2024] Open
Abstract
INTRODUCTION Metabolic disorders are a public health issue because of the complications they cause, but they are also a major risk factor for the onset of gout.
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Affiliation(s)
- Larisa Rotaru
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Liliana Groppa
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Eugeniu Russu
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Lia Chișlari
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Cătălin Codreanu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Larisa Spinei
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Oleg Arnaut
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
| | - Cornelia Cornea
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova, Republic of
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15
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Liu QJ, Yuan W, Yang P, Shao C. Role of glycolysis in diabetic atherosclerosis. World J Diabetes 2023; 14:1478-1492. [PMID: 37970130 PMCID: PMC10642412 DOI: 10.4239/wjd.v14.i10.1478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/16/2023] [Accepted: 09/14/2023] [Indexed: 10/09/2023] Open
Abstract
Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels. Atherosclerosis (AS) is one of the most common complications of diabetes. Modern lifestyles and trends that promote overconsumption and unhealthy practices have contributed to an increase in the annual incidence of diabetic AS worldwide, which has created a heavy burden on society. Several studies have shown the significant effects of glycolysis-related changes on the occurrence and development of diabetic AS, which may serve as novel thera-peutic targets for diabetic AS in the future. Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall. In particular, it plays a vital role in the physiological and pathological activities of the three important cells, Endothelial cells, macrophages and vascular smooth muscle cells. There are lots of similar mechanisms underlying diabetic and common AS, the former is more complex. In this article, we describe the role and mechanism underlying glycolysis in diabetic AS, as well as the therapeutic targets, such as trained immunity, microRNAs, gut microbiota, and associated drugs, with the aim to provide some new perspectives and potentially feasible programs for the treatment of diabetic AS in the foreseeable future.
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Affiliation(s)
- Qian-Jia Liu
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Wei Yuan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Ping Yang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Chen Shao
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
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16
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Yang C, Qiu H, Lv M, Yang J, Wu K, Huang J, Jiang Q. Gastrodin protects endothelial cells against high glucose-induced injury through up-regulation of PPARβ and alleviation of nitrative stress. Microvasc Res 2023; 148:104531. [PMID: 36963481 DOI: 10.1016/j.mvr.2023.104531] [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: 02/07/2023] [Revised: 03/11/2023] [Accepted: 03/20/2023] [Indexed: 03/26/2023]
Abstract
In diabetes mellitus (DM), high glucose can result in endothelial cell injury, and then lead to diabetic vascular complications. Gastrodin, as the mainly components of Chinese traditional herb Tianma (Gastrodia elata Bl.), has been widely used for cardiovascular diseases. However, the known of the effect of gastrodin on endothelial cell injury is still limited. In this study, we aimed to investigate the effect and possible mechanism of gastrodin on high glucose-injured human umbilical vein endothelial cells (HUVEC). High glucose (30 mmol/L) treatment caused HUVEC injury. After gastrodin (0.1, 1, 10 μmol/L) treatment, compared with the high glucose group, the cell proliferation ability increased in a dose-dependent manner. Meanwhile, gastrodin (10 μmol/L) up-regulated the mRNA and protein expressions of PPARβ and eNOS, decreased the expressions of iNOS, also reduced the protein expression of 3-nitrotyrosine, and lowed the level of ONOO-, increased NO content. Both the PPARβ antagonist GSK0660 (1 μmol/L) and the eNOS inhibitor L-NAME (10 μmol/L) were able to block the above effects of gastrodin. In conclusion, gastrodin protectes vascular endothelial cells from high glucose injury, which may be, at least partly, mediated by up-regulating the expression of PPARβ and negatively regulating nitrative stress.
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Affiliation(s)
- Chuang Yang
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China
| | - Hongmei Qiu
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China
| | - Mingqi Lv
- Experimental Teaching Management Center, Chongqing Medical University, Chongqing 400016, PR China
| | - Junxia Yang
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China
| | - Ke Wu
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China
| | - Jiajun Huang
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China
| | - Qingsong Jiang
- Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
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17
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Tikhonova IV, Tankanag AV, Guseva IE, Grinevich AA. Analysis of interactions between cardiovascular oscillations for discrimination of early vascular disorders in arterial hypertension and type 2 diabetes. Biomed Signal Process Control 2023. [DOI: 10.1016/j.bspc.2022.104222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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18
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Role of cerebral microbleeds in acute ischemic stroke and atrial fibrillation. J Thromb Thrombolysis 2022; 55:553-565. [PMID: 36571659 DOI: 10.1007/s11239-022-02761-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2022] [Indexed: 12/27/2022]
Abstract
Cerebral microbleeds (CMBs) are commonly detected in the brains of patients with acute ischemic stroke (AIS). With the development of neuroimaging, clinicians are paying more attention to the presence of CMBs. CMBs were found to significantly increase the risk of intracranial hemorrhagic transformation and hemorrhage in patients with AIS, especially in patients with concurrent atrial fibrillation (AF). Additionally, the presence of CMBs is thought to be a symbol of a high risk of recurrent ischemic stroke (IS). A few researchers have found that the presence of CMBs has no significant effect on the prognosis of patients with AIS. Therefore, the current views on the role of CMBs in the prognoses of patients with IS are controversial. The use of anticoagulants and other drugs has also become a dilemma due to the special influence of CMBs on the prognosis of these patients. Due to the large number of patients with AF and CMBs, many studies have been conducted on the effects of CMBs on these patients and subsequent pharmacological treatments. However, at present, there are no relevant guidelines to guide the secondary preventive treatment of patients with stroke, CMBs, and AF. In this paper, we summarized the role of CMBs in AIS combined with AF and relevant preventive measures against the recurrence of stroke and the occurrence of intracerebral hemorrhage to help clarify the specifics of drug therapies for this group of patients.
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19
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Tikhonova IV, Grinevich AA, Tankanag AV, Safronova VG. Skin Microhemodynamics and Mechanisms of Its Regulation in Type 2 Diabetes Mellitus. Biophysics (Nagoya-shi) 2022; 67:647-659. [PMID: 36281313 PMCID: PMC9581453 DOI: 10.1134/s0006350922040200] [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: 04/26/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 11/07/2022] Open
Abstract
The review presents modern ideas about peripheral microhemodynamics, approaches to the ana-lysis of skin blood flow oscillations and their diagnostic significance. Disorders of skin microhemodynamics in type 2 diabetes mellitus (DM) and the possibility of their interpretation from the standpoint of external and internal interactions between systems of skin blood flow regulation, based on a comparison of couplings in normal and pathological conditions, including models of pathologies on animals, are considered. The factors and mechanisms of vasomotor regulation, among them receptors and signaling events in endothelial and smooth muscle cells considered as models of microvessels are discussed. Attention was drawn to the disturbance of Ca2+-dependent regulation of coupling between vascular cells and NO-dependent regulation of vasodilation in diabetes mellitus. The main mechanisms of insulin resistance in type 2 DM are considered to be a defect in the number of insulin receptors and impaired signal transduction from the receptor to phosphatidylinositol-3-kinase and downstream targets. Reactive oxygen species plays an important role in vascular dysfunction in hyperglycemia. It is assumed that the considered molecular and cellular mechanisms of microhemodynamics regulation are involved in the formation of skin blood flow oscillations. Parameters of skin blood microcirculation can be used as diagnostic and prognostic markers for assessing the state of the body.
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Affiliation(s)
- I. V. Tikhonova
- Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow oblast Russia
| | - A. A. Grinevich
- Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow oblast Russia
| | - A. V. Tankanag
- Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow oblast Russia
| | - V. G. Safronova
- Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow oblast Russia
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20
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Froldi G, Djeujo FM, Bulf N, Caparelli E, Ragazzi E. Comparative Evaluation of the Antiglycation and Anti-α-Glucosidase Activities of Baicalein, Baicalin (Baicalein 7- O-Glucuronide) and the Antidiabetic Drug Metformin. Pharmaceutics 2022; 14:pharmaceutics14102141. [PMID: 36297576 PMCID: PMC9612222 DOI: 10.3390/pharmaceutics14102141] [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: 07/14/2022] [Revised: 10/03/2022] [Accepted: 10/04/2022] [Indexed: 11/05/2022] Open
Abstract
The discovery of new oral antidiabetic drugs remains a priority in medicine. This research aimed to evaluate the activity of the flavonoid baicalein and its natural glucuronide baicalin, compared to the antidiabetic drug metformin, as potential antiglycation, anti–radical, and anti-α–glucosidase agents, in order to assess their potential role in counteracting hyperglycemia-induced tissue damage. The study considered: (i) the BSA assay, to detect the formation of advanced glycation end products (AGEs), (ii) the GK peptide–ribose assay, which evaluates the cross–linking between the peptide and ribose, and (iii) the carbonyl content assay to detect the total carbonyl content, as a biomarker of tissue damage. In addition, to obtain a reliable picture of the antiglycation capacity of the investigated compounds, DPPH scavenging and oxygen radical absorbance capacity (ORAC) assays were performed. Furthermore, the anti–α–glucosidase activity of baicalein and baicalin was detected. Furthermore, to estimate cell permeability, preliminarily, the cytotoxicity of baicalein and baicalin was evaluated in HT–29 human colon adenocarcinoma cells using the MTT assay. Successively, the ability of the compounds to pass through the cytoplasmic membranes of HT–29 cells was detected as a permeability screen to predict in vivo absorption, showing that baicalein passes into cells even if it is quickly modified in various metabolites, being its main derivative baicalin. Otherwise, baicalin per se did not pass through cell membranes. Data show that baicalein is the most active compound in reducing glycation, α-glucosidase activity, and free radicals, while baicalin exhibited similar activities, but did not inhibit the enzyme α–glucosidase.
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21
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El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines 2022; 10:1507. [PMID: 35884812 PMCID: PMC9312797 DOI: 10.3390/biomedicines10071507] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.
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Affiliation(s)
- Racha El Hage
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
| | - Uwe Knippschild
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Tobias Arnold
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Irene Hinterseher
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
- Berlin Institute of Health, Vascular Surgery Clinic, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Fakultät für Gesundheitswissenschaften Brandenburg, Gemeinsame Fakultät der Universität Potsdam, der Medizinischen Hochschule Brandenburg Theodor Fontane und der Brandenburgischen Technischen Universität Cottbus—Senftenberg, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
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22
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White saffron (Curcuma mangga Val.) attenuates diabetes and improves pancreatic β-cell regeneration in streptozotocin-induced diabetic rats. Toxicol Rep 2022; 9:1213-1221. [DOI: 10.1016/j.toxrep.2022.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 11/24/2022] Open
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Méndez-Morales S, Pérez-De Marco J, Rodríguez-Cortés O, Flores-Mejía R, Martínez-Venegas M, Sánchez-Vera Y, Tamay-Cach F, Lomeli-Gonzaléz J, Emilio Reyes A, Lehman-Mendoza R, Martínez-Arredondo H, Vazquez-Dávila R, Torres-Roldan J, Correa-Basurto J, Arellano-Mendoza M. Diabetic neuropathy: Molecular approach a treatment opportunity. Vascul Pharmacol 2022; 143:106954. [PMID: 35063655 DOI: 10.1016/j.vph.2022.106954] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/15/2022]
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Hallström S, Svensson AM, Pivodic A, Ólafsdóttir AF, Löndahl M, Wedel H, Lind M. Risk factors and incidence over time for lower extremity amputations in people with type 1 diabetes: an observational cohort study of 46,088 patients from the Swedish National Diabetes Registry. Diabetologia 2021; 64:2751-2761. [PMID: 34494137 PMCID: PMC8563633 DOI: 10.1007/s00125-021-05550-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 06/14/2021] [Indexed: 01/30/2023]
Abstract
AIMS/HYPOTHESIS The aim of this work was to study the incidence over time of lower extremity amputations and determine variables associated with increased risk of amputations in people with type 1 diabetes. METHODS Individuals with type 1 diabetes registered in the Swedish National Diabetes Registry with no previous amputation from 1 January 1998 and followed to 2 October 2019 were included. Time-updated Cox regression and gradient of risk per SD were used to evaluate the impact of risk factors on the incidence of amputation. Age- and sex-adjusted incidences were estimated over time. RESULTS Of 46,088 people with type 1 diabetes with no previous amputation (mean age 32.5 years [SD 14.5], 25,354 [55%] male sex), 1519 (3.3%) underwent amputation. Median follow-up was 12.4 years. The standardised incidence for any amputation in 1998-2001 was 2.84 (95% CI 2.32, 3.36) per 1000 person-years and decreased to 1.64 (95% CI 1.38, 1.90) per 1000 person-years in 2017-2019. The incidence for minor and major amputations showed a similar pattern. Hyperglycaemia and renal dysfunction were the strongest risk factors for amputation, followed by older age, male sex, cardiovascular comorbidities, smoking and hypertension. Glycaemic control and age- and sex-adjusted renal function improved during the corresponding time period as amputations decreased. CONCLUSIONS/INTERPRETATION The incidence of amputation and of the most prominent risk factors for amputation, including renal dysfunction and hyperglycaemia, has improved considerably during recent years for people with type 1 diabetes. This finding has important implications for quality of life, health economics and prognosis regarding CVD, indicating a trend shift in the treatment of type 1 diabetes.
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Affiliation(s)
- Sara Hallström
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
| | - Ann-Marie Svensson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Center of Registers in Region Västra Götaland, Gothenburg, Sweden
| | - Aldina Pivodic
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Statistiska Konsultgruppen, Gothenburg, Sweden
| | - Arndís F Ólafsdóttir
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
| | - Magnus Löndahl
- Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden
- Department of Endocrinology, Skane University Hospital, Lund, Sweden
| | - Hans Wedel
- Department of Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
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Samocha-Bonet D, Wu B, Ryugo DK. Diabetes mellitus and hearing loss: A review. Ageing Res Rev 2021; 71:101423. [PMID: 34384902 DOI: 10.1016/j.arr.2021.101423] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/26/2021] [Accepted: 08/05/2021] [Indexed: 12/17/2022]
Abstract
Diabetes (type 2) and sensorineural hearing loss are common health problems manifested with ageing. While both type 1 and type 2 diabetes have been associated with hearing loss, a causal link has been difficult to establish. Individuals with diabetes have twice the incidence of hearing loss compared to those without diabetes and those with prediabetes have a 30% higher rate of hearing loss. Whether hearing loss is associated with diabetes independent of glycemic control remains to be determined. Hearing loss has its own set of risk factors and shares others with diabetes. This review will summarize the complex relationship between diabetes and sensorineural hearing loss.
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Affiliation(s)
- Dorit Samocha-Bonet
- Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW, 2010, Australia.
| | - Buffy Wu
- Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia; School of Medical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia
| | - David K Ryugo
- Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia; School of Medical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia; Department of Otolaryngology Head and Neck and Skull Base Surgery, St. Vincent's Hospital, Darlinghurst, NSW, 2010, Australia
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26
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Medjiofack Djeujo F, Cusinato F, Ragazzi E, Froldi G. α-Glucosidase and advanced glycation end products inhibition with Vernonia amygdalina root and leaf extracts: new data supporting the antidiabetic properties. J Pharm Pharmacol 2021; 73:1240-1249. [PMID: 33779755 DOI: 10.1093/jpp/rgab057] [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] [Received: 01/14/2021] [Accepted: 03/11/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVE This study aims to investigate antidiabetic activity of several Vernonia amygdalina extracts to study their potential use in medicine. METHODS Aqueous and ethanol extracts were obtained by maceration and Soxhlet extraction from roots and leaves of V. amygdalina. The extracts were tested as inhibitors of α-glucosidase activity and of advanced glycation end products (AGEs) formation. Further, radical scavenging activity was examined detecting the oxygen radical absorbance capacity, while the potential cytotoxicity of extracts was estimated with MTT assay. KEY FINDINGS In aqueous and ethanol extracts, several polyphenolic compounds were identified; in detail, (-)-catechin and luteolin were found in leaf extracts, while caffeic acid, chlorogenic acid and the terpenoid vernodalol were recognized in root extracts. Regarding antidiabetic activity, the aqueous root extracts efficiently inhibited α-glucosidase activity in a concentration-dependent manner (IC50 = 5.6 µg/ml and 39.8 µg/ml, respectively of macerated and Soxhlet extracts), whereas those obtained from leaves exhibited lower potency. Furthermore, AGEs formation was reduced by all V. amygdalina extracts starting from 10 µg/ml. CONCLUSIONS The aqueous extracts of V. amygdalina roots obtained by maceration and Soxhlet extraction show remarkable anti-α-glucosidase activity, and all extracts have favourable antiglycation and antioxidant activities.
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Affiliation(s)
| | - Federico Cusinato
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Eugenio Ragazzi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Guglielmina Froldi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
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27
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Guan Y, Wang X. Salvianic Acid A Regulates High-Glucose-Treated Endothelial Progenitor Cell Dysfunction via the AKT/Endothelial Nitric Oxide Synthase (eNOS) Pathway. Med Sci Monit 2021; 27:e928153. [PMID: 33770068 PMCID: PMC8008975 DOI: 10.12659/msm.928153] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The primary cause of death in patients with diabetes mellitus (DM) is diabetic macroangiopathy, a complication that related to the function and number of endothelial progenitor cells (EPCs). Salvianic acid A (SAA) is a water-soluble active ingredient of Salvia miltiorrhiza, a traditional Chinese medicine used to treat cardiovascular diseases. The purpose of this study was to explore the effects of SAA on the function of rat EPCs cultured in vitro in a high-glucose environment. MATERIAL AND METHODS Bone marrow-derived EPCs from 40 Sprague-Dawley rats were identified by fluorescence staining. Cell viability, apoptosis, tube formation, lactated dehydrogenase (LDH) release, and nitric oxide (NO) production were detected by 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay, flow cytometry, tube formation, LDH, and 3-amino,4-aminomethyl-2',7'-difluorescein, and diacetate assays, respectively. The expression levels of proteins were examined by western blotting. RESULTS Cultured EPCs showed a cobblestone morphology and positive expression of Dil-ac-LDL and FITC-UEA-1. High glucose impaired cell viability. Different concentrations of SAA had no significant effect on EPC viability. SAA reduced the apoptosis rate and LDH release, but promoted tube formation, viability, and NO production in high-glucose-treated EPCs. The ratios of p-AKT/AKT and p-eNOS/eNOS in high-glucose-treated EPCs were elevated by SAA. Phosphoinositide 3-kinase inhibitor LY294002 blocked the rescue effects of SAA on high-glucose-treated EPCs. CONCLUSIONS SAA protected EPCs against high-glucose-induced dysfunction via the AKT/eNOS pathway.
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Affiliation(s)
- Yanhua Guan
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland).,Department of Endocrinology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland)
| | - Xu Wang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland).,Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland)
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Fu X, Zong T, Yang P, Li L, Wang S, Wang Z, Li M, Li X, Zou Y, Zhang Y, Htet Aung LH, Yang Y, Yu T. Nicotine: Regulatory roles and mechanisms in atherosclerosis progression. Food Chem Toxicol 2021; 151:112154. [PMID: 33774093 DOI: 10.1016/j.fct.2021.112154] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/22/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023]
Abstract
Smoking is an independent risk factor for atherosclerosis. The smoke produced by tobacco burning contains more than 7000 chemicals, among which nicotine is closely related to the occurrence and development of atherosclerosis. Nicotine, a selective cholinergic agonist, accelerates the formation of atherosclerosis by stimulating nicotinic acetylcholine receptors (nAChRs) located in neuronal and non-neuronal tissues. This review introduces the pathogenesis of atherosclerosis and the mechanisms involving nicotine and its receptors. Herein, we focus on the various roles of nicotine in atherosclerosis, such as upregulation of growth factors, inflammation, and the dysfunction of endothelial cells, vascular smooth muscle cells (VSMC) as well as macrophages. In addition, nicotine can stimulate the generation of reactive oxygen species, cause abnormal lipid metabolism, and activate immune cells leading to the onset and progression of atherosclerosis. Exosomes, are currently a research hotspot, due to their important connections with macrophages and the VSMC, and may represent a novel application into future preventive treatment to promote the prevention of smoking-related atherosclerosis. In this review, we will elaborate on the regulatory mechanism of nicotine on atherosclerosis, as well as the effects of interference with nicotine receptors and the use of exosomes to prevent atherosclerosis development.
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Affiliation(s)
- Xiuxiu Fu
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Tingyu Zong
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Panyu Yang
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Lin Li
- Department of Vascular Surgery, The Qingdao Hiser Medical Center, Qingdao, Shandong Province, China
| | - Shizhong Wang
- The Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 66000, People's Republic of China
| | - Zhibin Wang
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Min Li
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao, 266021, People's Republic of China
| | - Xiaolu Li
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Yulin Zou
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Ying Zhang
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China
| | - Lynn Htet Htet Aung
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao, 266021, People's Republic of China
| | - Yanyan Yang
- Department of Immunology, School of Basic Medicine, Qingdao University, No. 308 Ningxia Road, Qingdao, 266021, People's Republic of China.
| | - Tao Yu
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao, 266021, People's Republic of China.
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Penna C, Femminò S, Alloatti G, Brizzi MF, Angelone T, Pagliaro P. Extracellular Vesicles in Comorbidities Associated with Ischaemic Heart Disease: Focus on Sex, an Overlooked Factor. J Clin Med 2021; 10:327. [PMID: 33477341 PMCID: PMC7830384 DOI: 10.3390/jcm10020327] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/11/2021] [Accepted: 01/14/2021] [Indexed: 02/07/2023] Open
Abstract
Extracellular vesicles (EV) are emerging early markers of myocardial damage and key mediators of cardioprotection. Therefore, EV are becoming fascinating tools to prevent cardiovascular disease and feasible weapons to limit ischaemia/reperfusion injury. It is well known that metabolic syndrome negatively affects vascular and endothelial function, thus creating predisposition to ischemic diseases. Additionally, sex is known to significantly impact myocardial injury and cardioprotection. Therefore, actions able to reduce risk factors related to comorbidities in ischaemic diseases are required to prevent maladaptive ventricular remodelling, preserve cardiac function, and prevent the onset of heart failure. This implies that early diagnosis and personalised medicine, also related to sex differences, are mandatory for primary or secondary prevention. Here, we report the contribution of EV as biomarkers and/or therapeutic tools in comorbidities predisposing to cardiac ischaemic disease. Whenever possible, attention is dedicated to data linking EV to sex differences.
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Affiliation(s)
- Claudia Penna
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), Italy;
| | - Saveria Femminò
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), Italy;
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy;
| | - Giuseppe Alloatti
- Uni-Astiss, Polo Universitario Rita Levi Montalcini, 14100 Asti, Italy;
| | - Maria F. Brizzi
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy;
| | - Tommaso Angelone
- Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, E. and E.S. (Di.B.E.S.T.), University of Calabria, 87036 Rende (CS), Italy;
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), Italy;
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30
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Yang C, Xie Z, Yang Q, Su M, Yan R, Cai X, Fu X, Gao H, Du L, Zhong W, Xie C. Characterization of lncRNA and mRNA profiles in rats with diabetic macroangiopathy. PLoS One 2020; 15:e0243987. [PMID: 33378343 PMCID: PMC7773178 DOI: 10.1371/journal.pone.0243987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 12/02/2020] [Indexed: 11/18/2022] Open
Abstract
Diabetic macroangiopathy is part of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat of 16weeks. A total of 15 GK rats were constructed as a test group, along with 15 Wistar rats set as control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue; 3223 novel lncRNAs and 20367 annotated lncRNAs were indemnified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy. The results of the present study indicated that lncRNAs, especially Nrep. bSep08, Col5a1, aSep0, soygee.aSep08-unspliced, NONRATT013247.2, votar.aSep08-unspliced, etc, both participate in and mediate the process of inflammatory response, cell apoptosis. What’s more. Our research provides further insights into understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.
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Affiliation(s)
- Chan Yang
- Hospital of Chengdu, University of Traditional Chinese Medicine, Chengdu, China
| | - Ziyan Xie
- Chengdu University of Traditional Chinese Medicine Clinical Medical College, Chengdu, China
| | - Qiangfei Yang
- Department of Orthopaedics, The People’s Hospital of Jianyang city, Chengdu, China
| | - Min Su
- Chengdu University of Traditional Chinese Medicine Clinical Medical College, Chengdu, China
| | - Ran Yan
- Chengdu University of Traditional Chinese Medicine Clinical Medical College, Chengdu, China
| | - Xueqin Cai
- Chengdu University of Traditional Chinese Medicine Clinical Medical College, Chengdu, China
| | - Xiaoxu Fu
- Chengdu University of Traditional Chinese Medicine Clinical Medical College, Chengdu, China
| | - Hong Gao
- Hospital of Chengdu, University of Traditional Chinese Medicine, Chengdu, China
| | - Lian Du
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen Zhong
- Hospital of Chengdu, University of Traditional Chinese Medicine, Chengdu, China
| | - Chunguang Xie
- Hospital of Chengdu, University of Traditional Chinese Medicine, Chengdu, China
- * E-mail:
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Han WM, Chen XC, Li GR, Wang Y. Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals. Front Pharmacol 2020; 11:607796. [PMID: 33519472 PMCID: PMC7844858 DOI: 10.3389/fphar.2020.607796] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/25/2020] [Indexed: 12/16/2022] Open
Abstract
The strategy of decreasing atherosclerotic cardiovascular disorder is imperative for reducing premature death and improving quality of life in patients with diabetes mellitus. The aim of this study was to investigate whether the natural flavone acacetin could protect against endothelial injury induced by high glucose and attenuate diabetes-accelerated atherosclerosis in streptozotocin-(STZ) induced diabetic ApoE−/− mice model. It was found that in human umbilical vein endothelial cells (HUVECs) cultured with normal 5.5 mM or high 33 mM glucose, acacetin (0.3–3 μM) exerted strong cytoprotective effects by reversing high glucose-induced viability reduction and reducing apoptosis and excess production of intracellular reactive oxygen species (ROS) and malondialdehyde in a concentration-dependent manner. Acacetin countered high glucose-induced depolarization of mitochondrial membrane potential and reduction of ATP product and mitoBcl-2/mitoBax ratio. Silencing Sirt3 abolished the beneficial effects of acacetin. Further analysis revealed that these effects of acacetin rely on Sirt1 activation by increasing NAD+ followed by increasing Sirt3, pAMPK and PGC-1α. In STZ-diabetic mice, acacetin significantly upregulated the decreased signaling molecules (i.e. SOD, Bcl-2, PGC-1α, pAMPK, Sirt3 and Sirt1) in aorta tissue and attenuated atherosclerosis. These results indicate that vascular endothelial protection of acacetin by activating Sirt1/Sirt3/AMPK signals is likely involved in alleviating diabetes-accelerated atherosclerosis by preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorder in patients with diabetes.
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Affiliation(s)
- Wei-Min Han
- Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Xu-Chang Chen
- Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Gui-Rong Li
- Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, China.,Nanjing Amazigh Pharma Limited, Nanjing, China
| | - Yan Wang
- Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, China
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Combination of Astragalus membranaceous and Angelica sinensis Ameliorates Vascular Endothelial Cell Dysfunction by Inhibiting Oxidative Stress. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:6031782. [PMID: 33293989 PMCID: PMC7714576 DOI: 10.1155/2020/6031782] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/24/2020] [Accepted: 09/05/2020] [Indexed: 12/24/2022]
Abstract
Vascular endothelial dysfunction is an essential and early sign of diabetic macroangiopathy, a primary complication of diabetes mellitus. Astragalus membranaceous-Angelica sinensis is a classic medical combination applied in China to treat diabetes mellitus. The aim of this study was to investigate the effect of the granule form of the extract produced from the dried root of Astragalus membranaceous (AM) combination with the granule form of the extract produced from the dried Angelica sinensis (AS) on diabetic macroangiopathy and its underlying mechanism. Herein, rats were treated by AM-AS at a ratio of 3 : 2 via intragastric administration. High glucose-induced human umbilical vein vascular endothelial cells (HUVECs) were then treated with drug-containing serum collected from the rats. In high glucose-treated HUVECs, AM-AS combination increased cell viability (P < 0.05), decreased the percentage of apoptotic cells (P < 0.05) and the expression of the proapoptosis protein caspase 3 (P < 0.05), reduced the proportion of cells in the G0/G1 phase (P < 0.05), decreased reactive oxygen species level (P < 0.05), enhanced cell migration and invasion (P < 0.05), and reduced the level of 8-iso-prostaglandin F2alpha. These results indicate that AM-AS combination at the ratio of 3 : 2 ameliorated HUVEC dysfunction by regulating apoptosis, cell migration, and invasion, which might be mediated by their regulatory effect on reactive oxygen species production. The current study provides a theoretical basis for the treatment of diabetic macroangiopathy using AM-AS.
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Cai H, Wang P, Zhang B, Dong X. Expression of the NEK7/NLRP3 inflammasome pathway in patients with diabetic lower extremity arterial disease. BMJ Open Diabetes Res Care 2020; 8:8/2/e001808. [PMID: 33323459 PMCID: PMC7745315 DOI: 10.1136/bmjdrc-2020-001808] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 11/04/2020] [Accepted: 11/11/2020] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION The NLRP3 inflammasome is closely related to diabetes and atherosclerosis. Recent studies suggest NIMA-related kinase 7 (NEK7) is necessary for NLRP3 inflammasome activation during potassium efflux. However, the expression of the NEK7/NLRP3 inflammasome pathway in diabetic lower extremity arterial disease (DLEAD) is unclear. The present study aimed to explore whether the NEK7/NLRP3 inflammasome pathway is involved in the pathogenesis of DLEAD. RESEARCH DESIGN AND METHODS The serum levels of interleukin-1β (IL-1β) and IL-18 in the control group (n=39), diabetes without lower extremity artery diseases group (n=39) and DLEAD group (n=85) were measured. H&E and Von Kossa staining were used to observe the vasculature of amputated feet from patients with diabetic foot. Furthermore, immunohistochemical staining, immunofluorescence and western blot were used to detect the expression of NEK7 and the NLRP3 inflammasome. RESULTS The serum IL-1β level in the DLEAD group was significantly increased compared with that in the control group and diabetes without lower extremity artery disease group. The serum IL-18 level was significantly higher in the DLEAD group and diabetes without lower extremity artery disease group than in the control group. H&E staining showed that the subintimal tissue of the arteries of patients with diabetic foot were highly thickened and exhibited irregular atherosclerotic plaques, and the arterial lumen was nearly occluded. Von Kossa staining showed dense brown-black calcium salt deposits in the vascular mesangium. Moreover, the expression of NEK7 and the NLRP3 inflammasome was significantly increased in the vascular cells of patients with diabetic foot, especially in vascular smooth muscle cells. CONCLUSION The NEK7/NLRP3 inflammasome pathway might be involved in the pathogenesis of DLEAD.
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Affiliation(s)
- HuaiQiu Cai
- Department of Ultrasonography, Fourth Hospital of Harbin Medical University, Harbin, China
| | - Peng Wang
- Department of Orthopeadic Surgery, Fourth Hospital of Harbin Medical University, Harbin, China
| | - Bo Zhang
- Department of Cardiology, Fourth Hospital of Harbin Medical University, Harbin, China
| | - XiaoQiu Dong
- Department of Ultrasonography, Fourth Hospital of Harbin Medical University, Harbin, China
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Hanna RM, Ferrey A, Rhee CM, Kalantar-Zadeh K. Renal-Cerebral Pathophysiology: The Interplay Between Chronic Kidney Disease and Cerebrovascular Disease. J Stroke Cerebrovasc Dis 2020; 30:105461. [PMID: 33199089 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105461] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/01/2020] [Accepted: 11/03/2020] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVES Cerebrovascular disease has increasingly been linked to overall vascular health. Pathologic conditions like diabetes, hypertension, and kidney disease have been shown to affect brain health and cerebrovascular and nervous systems. Acute kidney injury (AKI) and chronic Kidney Disease (CKD) represent a variety of vascular insults that can adversely affect cerebral health. Hypertension, fluctuations in blood pressure, and diabetic vasculopathy are known risk factors for cerebrovascular disease associated with CKD. Other emerging areas of interest include endothelial dysfunction, vascular calcification due to calcium and phosphorus metabolism dysregulation, and uremic neuropathy present the next frontier of investigation in CKD and cerebrovascular health. METHODS It has become apparent that the interrelation of AKI and CKD with vascular health, chemical homeostasis, and hormonal regulation upset many aspects of cerebral health and functioning. Stroke is an obvious connection, with CKD patients demonstrating a higher proclivity for cerebrovascular accidents. Cerebral bleeding risk, uremic neuropathies, sodium dysregulation with impacts on nervous system, vascular calcification, and endothelial dysfunction are the next salient areas of research that are likely to reveal key breakthroughs in renal-cerebral pathophysiology. RESULTS In this review nephrological definition are discussed in a neuro-centric manner, and the areas of key overlap between CKD and cerebrovascular pathology are discussed. The multifaceted effects of renal function on the health of the brain are also examined. CONCLUSION This review article aims to create the background for ongoing and future neurological-nephrological collaboration on understanding the special challenges in caring for patients with cerebrovascular disease who also have CKD.
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Affiliation(s)
- Ramy M Hanna
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Antoney Ferrey
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Connie M Rhee
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA.
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Fang Z, Hu X, Chen Z, Xie J, Wu D, Yin Y, You L. Radix pseudostellariae of Danzhi Jiangtang capsule relieves oxidative stress of vascular endothelium in diabetic macroangiopathy. Saudi Pharm J 2020; 28:683-691. [PMID: 32550799 PMCID: PMC7292866 DOI: 10.1016/j.jsps.2020.04.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 04/17/2020] [Indexed: 10/30/2022] Open
Abstract
AIM Medicinal plants act as an alternative source of anti-diabetic agents. Recently, Danzhi Jiangtang capsule (DJC) has been clinically used for treatment of diabetes, but the effect of DJC on diabetic macroangiopathy remained unclear. The present study investigates the therapeutic role of DJC in diabetic macroangiopathy and elucidates the underlying mechanisms. METHODS Diabetes patients were treated with DJC for 20 weeks. Blood glucose and serum parameters (insulin, FFA, SOD, GSH-Px, MDA, NO) were determined before and after treatment. Streptozotocin -induced diabetic rat model and human HUVECs cells were applied to assess the anti-oxidative capacity of DJC and its bioactive constituents. The expression levels of eNOS, JNK, GRP78, CHOP, Bcl2, and BAX were measured by qPCR and/or immunoblotting. RESULTS Diabetic macroangiopathy were ameliorated by DJC administration. Radix pseudostellariae (RP) mediated the anti-oxidative stress capacity of DJC, which improved insulin resistance (p < 0.01) and relieved oxidative stress (p < 0.01) of vascular endothelium through oxidative stress signaling and apoptosis pathway. The ability of DJC to ameliorate diabetic macroangiopathy and relieve oxidative stress was mainly mediated by its bioactive constituent RP. CONCLUSION This study would provide experimental evidence for DJC in the prevention and treatment of diabetes and diabetic macroangiopathy.
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Affiliation(s)
- Zhaohui Fang
- Department of Endocrine, the First Hospital Affiliated to Anhui University of Chinese Medicine, No. 117 Meishan Road, Hefei 230038, Anhui, China
- Anhui Provincial Academy of Science of Chinese Medicine, No. 117 Meishan Road, Hefei 230038, Anhui, China
| | - Xiu Hu
- Graduate Institute, Anhui University of Chinese Medicine, No. 103 Meishan Road Hefei 230038, Anhui, China
| | - Zhi Chen
- Department of Endocrine, Taizhou Hospital of Traditional Chinese Medicine, No. 86 Jichuandong Road, Taizhou 225300, China
| | - Jing Xie
- Graduate Institute, Anhui University of Chinese Medicine, No. 103 Meishan Road Hefei 230038, Anhui, China
| | - Di Wu
- Graduate Institute, Anhui University of Chinese Medicine, No. 103 Meishan Road Hefei 230038, Anhui, China
| | - Yundong Yin
- Graduate Institute, Anhui University of Chinese Medicine, No. 103 Meishan Road Hefei 230038, Anhui, China
| | - Liangzhen You
- Graduate Institute, Anhui University of Chinese Medicine, No. 103 Meishan Road Hefei 230038, Anhui, China
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Biscetti F, Rando MM, Nardella E, Cecchini AL, Pecorini G, Landolfi R, Flex A. High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives. Int J Mol Sci 2019; 20:ijms20246258. [PMID: 31835864 PMCID: PMC6940913 DOI: 10.3390/ijms20246258] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 12/08/2019] [Accepted: 12/09/2019] [Indexed: 12/17/2022] Open
Abstract
Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.
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Affiliation(s)
- Federico Biscetti
- U.O.C. Clinica Medica e Malattie Vascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (G.P.); (R.L.); (A.F.)
- Laboratory of Vascular Biology and Genetics, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
- Correspondence: ; Tel.: +39-06-3015-4335; Fax: +39-06-3550-7232
| | | | - Elisabetta Nardella
- Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (M.M.R.); (E.N.); (A.L.C.)
| | | | - Giovanni Pecorini
- U.O.C. Clinica Medica e Malattie Vascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (G.P.); (R.L.); (A.F.)
- Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (M.M.R.); (E.N.); (A.L.C.)
| | - Raffaele Landolfi
- U.O.C. Clinica Medica e Malattie Vascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (G.P.); (R.L.); (A.F.)
- Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (M.M.R.); (E.N.); (A.L.C.)
| | - Andrea Flex
- U.O.C. Clinica Medica e Malattie Vascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (G.P.); (R.L.); (A.F.)
- Laboratory of Vascular Biology and Genetics, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
- Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (M.M.R.); (E.N.); (A.L.C.)
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Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:9570616. [PMID: 31885827 PMCID: PMC6925928 DOI: 10.1155/2019/9570616] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 11/25/2019] [Indexed: 01/08/2023]
Abstract
The occurrence and development of cardiovascular complications are predominantly responsible for the increased morbidity and mortality observed in patients with diabetes. Oxidative stress under hyperglycemia is currently considered the initial link to diabetic cardiovascular complications and a key node for the prevention and treatment of diabetes-related fatal cardiovascular events. Numerous studies have indicated that the common upstream pathway in the context of oxidative stress in the cardiovascular system under diabetic conditions is the interaction of advanced glycation end products (AGEs) with their receptors (RAGEs). Therefore, a further understanding of the relationship between oxidative stress and AGEs is of great significance for the prevention and treatment of cardiovascular complications in patients with diabetes. In this review, we will briefly summarize the recent research advances in diabetes with an emphasis on oxidative stress and its association with AGEs in diabetic cardiovascular complications.
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Xiong Q, Liu J, Xu Y. Effects of Uric Acid on Diabetes Mellitus and Its Chronic Complications. Int J Endocrinol 2019; 2019:9691345. [PMID: 31737070 PMCID: PMC6815590 DOI: 10.1155/2019/9691345] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 05/26/2019] [Accepted: 09/06/2019] [Indexed: 02/07/2023] Open
Abstract
With the deepening of the researches on uric acid, especially in the study of metabolic diseases, uric acid has been found to be closely related to obesity, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, and other metabolic diseases. Uric acid causes a series of pathophysiological changes through inflammation, oxidative stress, vascular endothelial injury, and so on and thus subsequently promotes the occurrence and development of diseases. This review confirmed the positive correlation between uric acid and diabetes mellitus and its chronic complications through the pathogenesis and clinical studies aspects.
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Affiliation(s)
- Qing Xiong
- Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
- Department of Endocrinology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan 570208, China
| | - Jie Liu
- Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Yancheng Xu
- Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
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Hallström S, Pivodic A, Rosengren A, Ólafsdóttir AF, Svensson AM, Lind M. Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry. Diabetes Care 2019; 42:1530-1538. [PMID: 31171564 DOI: 10.2337/dc18-2457] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 05/08/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. RESULTS In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA1c, coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m2), and elevated levels of HbA1c (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. CONCLUSIONS The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.
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Affiliation(s)
- Sara Hallström
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden .,Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Aldina Pivodic
- Department of Ophthalmology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Statistiska Konsultgruppen, Gothenburg, Sweden
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Arndís F Ólafsdóttir
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
| | - Ann-Marie Svensson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Center of Registers in Region Västra Götaland, Gothenburg, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
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Froldi G, Baronchelli F, Marin E, Grison M. Antiglycation Activity and HT-29 Cellular Uptake of Aloe-Emodin, Aloin, and Aloe arborescens Leaf Extracts. Molecules 2019; 24:molecules24112128. [PMID: 31195732 PMCID: PMC6600357 DOI: 10.3390/molecules24112128] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 05/23/2019] [Accepted: 06/03/2019] [Indexed: 12/14/2022] Open
Abstract
Aloe arborescens is a relevant species largely used in traditional medicine of several countries. In particular, the decoction of leaves is prepared for various medicinal purposes including antidiabetic care. The aim of this research was the study of the antiglycation activity of two A. arborescens leaf extracts and isolated compounds: aloin and aloe-emodin. These phytoconstituents were quantitatively assessed in methanolic and hydroalcoholic extracts using high performance liquid chromatography (HPLC) analysis. In addition, the total phenolic and flavonoid contents were detected. In order to study their potential use in diabetic conditions, the antiglycation and antiradical properties of the two extracts and aloin and aloe-emodin were investigated by means of bovine serum albumin (BSA) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays; further, their cytotoxicity in HT-29 human colon adenocarcinoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, the ability of aloin and aloe-emodin to permeate the cellular membranes of HT-29 cells was determined in order to estimate their potential in vivo absorption. This assessment indicated that aloe-emodin can substantially pass through cell membranes (~20%), whereas aloin did not permeate into HT-29 cells. Overall, the data show that both the methanolic and the hydroalcoholic A. arborescens extracts determine significant inhibition of glycation and free-radical persistence, without any cytotoxic activity. The data also show that the antiglycation and the antiradical activities of aloin and aloe-emodin are lower than those of the two extracts. In relation to the permeability study, only aloe-emodin is able to cross HT-29 cellular membranes, showing the attitude to pass through the intestinal layer. Overall, the present data surely support the traditional use of A. arborescens leaf extracts against hyperglycemic conditions, while aloin and aloe-emodin as potential drugs need further study.
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Affiliation(s)
- Guglielmina Froldi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
| | - Federica Baronchelli
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
| | - Elisa Marin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
| | - Margherita Grison
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
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Froldi G, González DL, Rosteghin F, Grison M, Sut S, Dall’Acqua S, Sánchez-Mateo CDC. α-Glucosidase and glycation inhibitory activities of Rumex lunaria leaf extract: a promising plant against hyperglycaemia-related damage. Nat Prod Res 2019; 34:3418-3422. [DOI: 10.1080/14786419.2019.1569655] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Guglielmina Froldi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Diana Luján González
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Francesca Rosteghin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Margherita Grison
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Stefania Sut
- Department of Agronomy, Food, Natural Resources, Animals and the Environment, University of Padova, Padova, Italy
| | - Stefano Dall’Acqua
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
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Abstract
We begin this chapter by describing normal characteristics of several pertinent connective tissue components, and some of the basic changes they undergo with ageing. These alterations are not necessarily tied to any specific disease or disorders, but rather an essential part of the normal ageing process. The general features of age-induced changes, such as skin wrinkles, in selected organs with high content of connective or soft tissues are discussed in the next part of the chapter. This is followed by a section dealing with age-related changes in specific diseases that fall into at least two categories. The first category encompasses common diseases with high prevalence among mostly ageing populations where both genetic and environmental factors play roles. They include but may not be limited to atherosclerosis and coronary heart disease, type II diabetes, osteopenia and osteoporosis, osteoarthritis, tendon dysfunction and injury, age-related disorders of spine and joints. Disorders where genetics plays the primary role in pathogenesis and progression include certain types of progeria, such as Werner syndrome and Hutchinson-Gilford progeria belong to the second category discussed in this chapter. These disorders are characterized by accelerated signs and symptoms of ageing. Other hereditary diseases or syndromes that arise from mutations of genes encoding for components of connective tissue and are less common than diseases included in the first group will be discussed briefly as well, though they may not be directly associated with ageing, but their connective tissue undergoes some changes compatible with ageing. Marfan and Ehlers-Danlos syndromes are primary examples of such disorders. We will probe the role of specific components of connective tissue and extracellular matrix if not in each of the diseases, then at least in the main representatives of these disorders.
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Affiliation(s)
- Carolyn Ann Sarbacher
- Department of Pathology, College of Veterinary Medicine, The University of Georgia and AU/UGA Medical Partnership, Athens, GA, USA
| | - Jaroslava T Halper
- Department of Pathology, College of Veterinary Medicine, The University of Georgia and AU/UGA Medical Partnership, Athens, GA, USA.
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Sharma G, Ashhar MU, Aeri V, Katare DP. Development and characterization of late-stage diabetes mellitus and -associated vascular complications. Life Sci 2018; 216:295-304. [PMID: 30408473 DOI: 10.1016/j.lfs.2018.11.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/28/2018] [Accepted: 11/03/2018] [Indexed: 02/07/2023]
Abstract
Preclinical investigation is the key mark of medical research, as the major breakthroughs including treatment of devastating diseases in biomedical research have been led by animal studies. Type 2 diabetes mellitus (T2DM) is a predominant metabolic disorder having high prevalence of morbidity worldwide which create an urgent need to understand the pathogenesis, complication and other possible influences by development of appropriate animal model. High-fat diet (HFD) fed animals (21 days) were treated with single cycle of repetitive dose (SCRD) of streptozotocin (STZ; 40, 30 and 20 mg/kg/per day in three respective group at 1st, 3rd, and 5th day) and double cycle of repetitive dose (DCRD) of streptozocin (STZ) (20, 10 and 5 mg/kg/per day in three respective group at 1st, 3rd, and 5th day in one cycle and 21st, 23rd, 25th day in second cycle of treatment) to induce late-stage diabetic complications. Induction of hyperglycemia was assessed by fasting and postprandial blood glucose, HbA1c, insulin, C-peptide, pancreatic β-cells and dyslipidaemia up to 12 weeks. Combined treatment of HFD and STZ (20 mg/kg) in the DCRD manner were significantly induced late-stage diabetic complication with sustained hyperglycaemia, no mortality, increased HbA1c and dyslipidaemia, reduced insulin, C-peptide and beta cells. Moreover, biochemical and histological assessment of micro and macrovascular tissues confirmed the significant cardio-renal injury, endothelial and hepatic damage. The study confirmed the development of chronic diabetic model in rat mimicked to clinical pathology with associated micro and macrovascular abnormalities which can further explore the molecular aspects of diseases.
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Affiliation(s)
- Gunjan Sharma
- Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh 201303, India
| | - Md Umama Ashhar
- Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh 201303, India
| | - Vidhu Aeri
- Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India
| | - Deepshikha Pande Katare
- Proteomic & Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida 201313, India.
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Wu C, Wu D, Lin M, Zhong Y. The Associations between Paraoxonase 1 L55M/Q192R Genetic Polymorphisms and the Susceptibilities of Diabetic Macroangiopathy and Diabetic Microangiopathy: A Meta-Analysis. Diabetes Ther 2018; 9:1669-1688. [PMID: 29987647 PMCID: PMC6064588 DOI: 10.1007/s13300-018-0466-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Plenty of studies have focused on the associations of paraoxonase 1 Q192R and L55M genetic polymorphisms with diabetic macroangiopathy and microangiopathy susceptibility, but these associations remain controversial. Therefore, this meta-analysis was conducted to demonstrate these relationships. METHODS Relevant studies published in English or Chinese were identified in PubMed, Embase, Wanfang Database, and CNKI by applying specific inclusion and exclusion criteria. Statistical analyses were performed using the STATA 12.0 statistical software. RESULTS 25 Case-control studies were included in the meta-analyses: six on the association between paraoxonase 1 L55M genetic polymorphism and diabetic macroangiopathy risk, nine on the association between L55M and diabetic microangiopathy risk, 12 on the association between Q192R and diabetic macroangiopathy risk, and 12 on the association between Q192R and diabetic microangiopathy risk. Paraoxonase 1 L55M genetic polymorphism was significantly associated with diabetic microangiopathy susceptibility in the dominant model [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.33-0.83, P = 0.006], the homozygous model (OR 0.37, 95% CI 0.16-0.86, P = 0.021), the allelic contrast model (OR 0.62, 95% CI 0.43-0.90, P = 0.011), the recessive model (OR 12.04, 95% CI 8.02-18.06, P = 0.000), and the heterozygous model (OR 0.57, 95% CI 0.38-0.85, P = 0.006), but L55M was not significantly associated with macroangiopathy susceptibility. Paraoxonase 1 Q192R genetic polymorphism was significantly associated with diabetic macroangiopathy susceptibility in the homozygous model (OR 1.88, 95% CI 1.06-3.32, P = 0.030), the allelic contrast model (OR 1.31, 95% CI 1.02-1.69, P = 0.038), and the recessive model (OR 1.55, 95% CI 1.11-2.16, P = 0.010), but not in the dominant and heterozygous models. Meanwhile, there was no significant association between paraoxonase 1 Q192R genetic polymorphism and diabetic microangiopathy susceptibility. CONCLUSION Paraoxonase 1 L55M and Q192R genetic polymorphisms play important roles in diabetic macroangiopathy and microangiopathy susceptibility. Further well-designed studies based on large samples are needed to confirm these results.
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Affiliation(s)
- Chenfang Wu
- ICU Center, The Second Xiangya Hospital, Central South University, Furong, Changsha, China
| | - Diling Wu
- ICU Center, The Second Xiangya Hospital, Central South University, Furong, Changsha, China
| | - Minjie Lin
- Clinical Skills Training Center, The Second Xiangya Hospital, Central South University, Furong, Changsha, China
| | - Yanjun Zhong
- ICU Center, The Second Xiangya Hospital, Central South University, Furong, Changsha, China.
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Guo D, Xiao L, Hu H, Liu M, Yang L, Lin X. FGF21 protects human umbilical vein endothelial cells against high glucose-induced apoptosis via PI3K/Akt/Fox3a signaling pathway. J Diabetes Complications 2018; 32:729-736. [PMID: 29907326 DOI: 10.1016/j.jdiacomp.2018.05.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/01/2018] [Accepted: 05/18/2018] [Indexed: 12/19/2022]
Abstract
AIMS Diabetic macroangiopathy is the main cause of morbidity and mortality in patients with diabetes. Endothelial cell injury is a pathological precondition for diabetic macroangiopathy. Fibroblast growth factor 21 (FGF21) is a key metabolic regulator which has recently been suggested to protect cardiac myocytes and vascular cells against oxidative stress-induced injury in vitro and vivo. In this study, we aimed to investigate the protective capacity of FGF21 in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced apoptosis via phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway. METHODS The cell viability was examined by CCK-8 assay, Intracellular ROS levels were measured by the detection of the fluorescent product formed by the oxidation of DCFH-DA, Apoptosis was analyzed using Hoechst 33258 nuclear staining and Flow Cytometry Analysis (FCA), the expression of protein were detected by Western blot. RESULTS Results show that pretreating HUVECs with FGF21 before exposure to HG increases cell viability, while decreasing apoptosis and the generation of reactive oxygen species. Western blot analysis shows that HG reduces the phosphorylation of Akt and FoxO3a, and induces nuclear localization of FoxO3a. The effects were significantly reversed by FGF21 pre-treatment. Furthermore, the protective effects of FGF21 were prevented by PI3K/Akt inhibitor LY294002. CONCLUSIONS Our data demonstrates that FGF21 protects HUVECs from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.
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Affiliation(s)
- Dongmin Guo
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang City, Hunan Province 421001, China
| | - Lele Xiao
- Huzhou University, Huzhou City, Zhejiang Province 313000, China
| | - Huijun Hu
- Department of Pathology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou City, Guangdong Province 516001, China
| | - Mihua Liu
- Centre for Lipid Research & Key Laboratory of Molecular Biology for infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of infectious Disease, The Second Affiliated Hospital, Chongqing Medical University, Chongqing City 400016, China
| | - Lu Yang
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang City, Hunan Province 421001, China.
| | - Xiaolong Lin
- Department of Pathology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou City, Guangdong Province 516001, China.
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