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Physiological and cellular mechanisms of ischemic preconditioning microRNAs-mediated in underlying of ischemia/reperfusion injury in different organs

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年第2期480卷 855-868页

作者： Gheitasi, Izadpanah Akbari, Ghaidafeh savari, feryal Yasuj Univ Med Sci Fac Med Dept Physiol Yasuj Iran Shoushtar Fac Med Sci Dept Med Basic Sci Shoushtar Iran

Ischemia-reperfusion (I/R) injury, as a pathological phenomenon, takes place when blood supply to an organ is disrupted and then aggravated during restoration of blood flow. Ischemic preconditioning (IPC) is a potent method for attenuating subsequent events of IR damage in numerous organs. IPC protocol is determined by a brief and sequential time periods of I/R before the main ischemia. MicroRNAs are endogenous non-coding RNAs that regulate post-transcriptionally target mRNA translation via degrading it and/or suppressing protein synthesis. This review introduces the physiological and cellular mechanisms of ischemic preconditioning microRNAs-mediated after I/R insult in different organs such as the liver, kidney, heart, brain, and intestine. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2023. Based on these literature studies, IPC/IR intervention can affect cellular mechanisms including oxidative stress, apoptosis, angiogenesis, and inflammation through up-regulation or down-regulation of multiple microRNAs and their target genes.

关键词： Ischemia/reperfusion injury Ischemic preconditioning MicroRNAs

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Corrigendum to "Nonalcoholic steatohepatitis: A comprehensive updated review of risk factors, symptoms, and treatment" [Heliyon Volume 10, Issue 7, April 15, 2024, Article e28468]

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Heliyon 2025年第4期11卷 e42893页

作者： feryal savari Seyed Ali Mard Department of Medical Basic Sciences Shoushtar Faculty of Medical Sciences Shoushtar Iran. Clinical Sciences Research Institute Alimentary Tract Research Center Department of Physiology The School of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran.

[This corrects the article DOI: 10.1016/***.2024.e28468.].

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Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis

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FREE RADICAL RESEARCH 2019年第5期53卷 486-496页

作者： savari, feryal Badavi, Mohammad Rezaie, Anahita Gharib-Naseri, Mohammad Kazem Mard, Seyyed Ali Ahvaz Jundishapur Univ Med Sci PRC Sch Med Dept Physiol Ahvaz Iran Shahid Chamran Univ Ahvaz Sch Vet Med Dept Pathobiol Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Alimentary Tract Res Ctr Sch Med Persian Gulfs Physiol Res Ctr PRCDept Physiol Ahvaz Iran

Aim: Stimulation of Fas death receptor is introduced as a major cause of non-alcoholic steatohepatitis (NASH) progression through suppression of cell viability. Therefore, the blocking of death pathways is hypothesised to be express new approaches to NASH therapy. For this purpose, current experiment applied synthetic small interference RNA (SiRNA) to trigger Fas death receptor and to show its potential therapeutic role in designed NASH model. Methods: Male mice were placed on a western diet (WD) for 8 weeks and exposed to cigarette smoke during the last 4 weeks of feeding to induce NASH model. In the next step, Fas SiRNA was injected to mice aiming to examine specific Fas gene silencing, after 8 weeks. As a control, mice received scrambled SiRNA. Reversible possibility of disease was examined by 3 weeks of recovery. Results: Analysis of data is accompanied with the significant histopathological changes (steatosis, ballooning and inflammation), increased lipid profile and hepatic enzyme activities (AST, ALT, ALP) plus TBARS as well as decreased antioxidants levels in NASH model. Upon Fas-SiRNA injection, almost all measured parameters of NASH such as overexpression of Fas receptor, caspase3, NF-kB genes and marked increase of hepatic TNF-alpha were significantly restored and were remained nearly unchanged following recovery liking as scrambled groups. Conclusions: The suppression of Fas receptor signalling subsequent RNAi therapy may represent an applicable strategy to decline hepatocyte damages and so NASH progression in mice.

关键词： Apoptosis cigarette smoke Fas receptor inflammation NASH SiRNA western diet

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The hepato-protective effect of H2S-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice: The role of MALAT

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2022年 635卷 194-202页

作者： Sameri, Maryam J. savari, feryal Hoseinynejad, Khojasteh Danyaei, Amir Mard, Seyed Ali Ahvaz Jundishapur Univ Med Sci Med Basic Sci Res Inst Persian Gulf Physiol Res Ctr Ahvaz Iran Shoushtar Fac Med Sci Dept Basic Sci Shoushtar Iran Ahvaz Jundishapur Univ Med Sci Sch Med Dept Med Phys Ahvaz Iran

Introduction: Ischemia-reperfusion injury (IRI) by causing histopathological changes is considered one of the most important causes of liver failure and dysfunction after surgery which affect graft outcomes. Stem cells are new promising approaches to treating different diseases. One of the critical strategies to improve their function is the preconditioning of their culture medium. This study compared the effect of NaHS-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice. Methods: Human umbilical cord-derived MSC (MSC) cultured in a 75 cm(3) flask and when confluency reached about 80%, the culture medium replaced with a serum-free medium, and 48 h later supernatants collected, concentrated, and then MSC-Exo extracted. To obtain H2S-Exo, MSC was treated with NaHS (1 mmol),the supernatant collected after 48 h, concentrated and exosomes extracted. Twenty-four male mice were randomly divided into four groups (n 1/4 6) including: 1-ischemia, 2-sham-operated, 3-MSC-Exo, and 4-H2S-Exo. To induce ischemia, the hepatic artery and portal vein clamped using an atraumatic clip for 60 min followed by 3 h of reperfusion. Just upon ending the time of ischemia (removal of clamp artery), animals in MSC-Exo, and H2S-Exo groups received 100 mg exosomes in 100 ml PBS via tail vein. At the end of reperfusion, blood, and liver samples were collected for further serological, molecular, and histological ***: Administration of both MSC-Exo and H2S-Exo improved liver function by reducing inflammatory cytokines, cellular apoptosis, liver levels of total oxidant status, and liver aminotransferases. The results showed that protecting effect of MSC exosomes enhanced following NaHS preconditioning of cell culture ***: MSC-Exo and H2S-Exo had hepato-protective effects against injuries induced by ischemia-reperfusion in mice. NaHS preconditioning of mesenchymal stem cells could enhance the therapeutic effects of MSC-derive

关键词： Exosomes Huc-MSC Sodium hydrosulfide (NaHS) H2S Apoptosis Liver injury

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Nonalcoholic steatohepatitis: A comprehensive updated review of risk factors, symptoms, and treatment

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HELIYON 2024年第7期10卷 e28468页

作者： savari, feryal Mard, Seyed Ali Shoushtar Fac Med Sci Dept Med Basic Sci Shoushtar Iran Ahvaz Jundishapur Univ Med Sci Clin Sci Res Inst Alimentary Tract Res Ctr Sch MedDept Physiol Ahvaz Iran

Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a significant risk for the development of liver-related morbidity and mortality. The complex and multifaceted pathophysiology of NASH makes its management challenging. Early identification of symptoms and management of patients through lifestyle modification is essential to prevent the development of advanced liver disease. Despite the increasing prevalence of NASH, there is no FDA-approved treatment for this disease. Currently, medications targeting metabolic disease risk factors and some antifibrotic medications are used for NASH patients but are not sufficiently effective. The beneficial effects of different drugs and phytochemicals represent new avenues for the development of safer and more effective treatments for NASH. In this review, different risk factors, clinical symptoms, diagnostic methods of NASH, and current treatment strategies for the management of patients with NASH are reviewed.

关键词： NASH NAFLD MASLD Diagnosis Management Treatment

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Molecular Mechanisms of Hawthorn Extracts in Multiple Organs Disorders in Underlying of Diabetes: A Review

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INTERNATIONAL JOURNAL OF ENDOCRINOLOGY 2022年第0期2022卷 2002768页

作者： Gheitasi, Izadpanah savari, feryal Akbari, Ghaidafeh Mohammadi, Jamshid Fallahzadeh, Ali Reza Sadeghi, Hossein Yasuj Univ Med Sci Med Plants Res Ctr Yasuj Iran Shoushtar Fac Med Sci Dept Basic Sci Shoushtar Iran Yasuj Univ Med Sci Cellular & Mol Res Ctr Yasuj Iran

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-kappa B) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collec

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A new method to induce nonalcoholic steatohepatitis (NASH) in mice

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BMC GASTROENTEROLOGY 2019年第1期19卷 125-125页

作者： savari, feryal Mard, Seyyed Ali Badavi, Mohammad Rezaie, Anahita Gharib-Naseri, Mohammad Kazem Ahvaz Jundishapur Univ Med Sci Sch Med Dept Physiol PRC Ahvaz Iran Ahvaz Jundishapur Univ Med Sci Persian Gulfs Physiol Res Ctr PRC Res Ctr Infect Dis Digest Syst Alimentary Tract Res CtrDept PhysiolSch Med Ahvaz Iran Shahid Chamran Univ Ahvaz Sch Vet Med Dept Pathobiol Ahvaz Iran

BackgroundGeneral overnutrition is one of the key factors involved in the development of nonalcoholic fatty liver disease (NAFLD) as the most common liver disease occur by two steps of liver injury ranges from steatosis to nonalcoholic steatohepatitis (NASH). Here the effect of fructose, fat-rich and western diet (WD) feeding was studied along with aggravative effect of cigarette smoking on liver status in ***-four male NMRI mice were included in this study and assigned into 4 groups that fed standard, fructose-rich, high fat-, and western-diet for 8weeks and then each group divided in two smoker and nonsmoker subgroups according to smoke exposing in the last 4weeks of feeding time (n=8). Histopathological studies, serum biochemical analyses and hepatic TNF-alpha level were evaluated in mice to compare alone or combination effects of dietary regimen and cigarette *** liver enzymes and lipid profile levels in WD fed mice were significantly higher than in other studied diets. Exposing to cigarette smoke led to more elevation of serum biochemical parameters that was also accompanied by a significant increase in hepatic damage shown as more severe fat accumulation, hepatocyte ballooning and inflammation infiltrate. Elevated TNF-alpha level confirmed incidence of liver *** finding of this study demonstrated that a combination of cigarette smoke exposure and WD (rich in fat, fructose, and cholesterol) could induce a more reliable mouse model of NASH.

关键词： NAFLD NASH Fructose High fat diet Western diet Cigarette smoke Mice

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