Life sciences最新文献

{"title":"Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.","authors":"Xiaoxiao Cheng, Jie Yang, Zhijie Wang, Kefan Zhou, Xuejiao An, Zhenjiang Zech Xu, Hui Lu","doi":"10.1016/j.lfs.2024.123309","DOIUrl":"10.1016/j.lfs.2024.123309","url":null,"abstract":"<p><p>The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123309"},"PeriodicalIF":5.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mitochondrial dynamics: A promising approach for intracerebral hemorrhage therapy.","authors":"Mengnan Liu, Binru Li, Zhixue Yin, Lu Yin, Ye Luo, Qi Zeng, Dechou Zhang, Anguo Wu, Li Chen","doi":"10.1016/j.lfs.2024.123317","DOIUrl":"10.1016/j.lfs.2024.123317","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a major global health issue with high mortality and disability rates. Following ICH, the hematoma exerts direct pressure on brain tissue, and blood entering the brain directly damages neurons and the blood-brain barrier. Subsequently, oxidative stress, inflammatory responses, apoptosis, brain edema, excitotoxicity, iron toxicity, and metabolic dysfunction around the hematoma further exacerbate brain tissue damage, leading to secondary brain injury (SBI). Mitochondria, essential for energy production and the regulation of oxidative stress, are damaged after ICH, resulting in impaired ATP production, excessive reactive oxygen species (ROS) generation, and disrupted calcium homeostasis, all of which contribute to SBI. Therefore, a central factor in SBI is mitochondrial dysfunction. Mitochondrial dynamics regulate the shape, size, distribution, and quantity of mitochondria through fusion and fission, both of which are crucial for maintaining their function. Fusion repairs damaged mitochondria and preserves their health, while fission helps mitochondria adapt to cellular stress and removes damaged mitochondria through mitophagy. When this balance is disrupted following ICH, mitochondrial dysfunction worsens, oxidative stress and metabolic failure are exacerbated, ultimately contributing to SBI. Targeting mitochondrial dynamics offers a promising therapeutic approach to restoring mitochondrial function, reducing cellular damage, and improving recovery. This review explores the latest research on modulating mitochondrial dynamics and highlights its potential to enhance outcomes in ICH patients.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123317"},"PeriodicalIF":5.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine N-oxide in cardiovascular disease: Pathophysiology and the potential role of statins.","authors":"Fakhar Latif, Ayesha Mubbashir, Muhammad Sohaib Khan, Zain Shaikh, Aaima Memon, Jenelle Alvares, Ayesha Azhar, Hritvik Jain, Raheel Ahmed, Sai Gautham Kanagala","doi":"10.1016/j.lfs.2024.123304","DOIUrl":"10.1016/j.lfs.2024.123304","url":null,"abstract":"<p><p>Cardiovascular diseases are one of the leading causes of mortality and morbidity worldwide, with the total number of cases increasing to 523 million in 2019. Despite the advent of new drugs, cardiovascular mortality has increased at an alarming rate of 53.7 % from 12.1 million deaths in 1990. Recently, the role of gut microbiome metabolites, such as Trimethylamine N-Oxide (TMAO), in the pathogenesis of cardiovascular disease (CVD) has attracted significant attention. The gut microbiome is critical in various physiological processes including metabolism, immune function, and inflammation. Elevated TMAO levels are associated with atherosclerosis, heart failure, arrhythmia, and atrial fibrillation. TMAO accelerates atherosclerosis by promoting vascular inflammation and reducing reverse cholesterol transport, which leads to lipid accumulation and vessel narrowing. Previous research has indicated that a Mediterranean diet rich in fiber and phytochemicals can reduce TMAO levels by limiting precursors and fostering beneficial gut microbiota. Prebiotics and probiotics also decrease TMAO, while drugs such as meldonium, aspirin, and antibiotics have shown promise. However, recent studies have demonstrated major potential for the use of statins in reducing TMAO levels. Statin therapy can significantly reduce TMAO levels independent of their cholesterol-lowering effects. This reduction may involve direct interactions with the gut microbiome, changes in cholesterol metabolism, and changes in bile acid composition. This review aims to comprehensively evaluate the therapeutic potential of statins in reducing TMAO levels to improve CV outcomes.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123304"},"PeriodicalIF":5.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulated DKK2 may serve as a molecular mechanism of high-fat diet-induced myocardial injury via Wnt/β-catenin pathway.","authors":"Yixuan Wang, Di Chen, Ye Pu, Jiahao Shi, Congxiang Yi, Jie Chen, Guangxiang Yang, Yang Cui, Yu Nie, Liyuan Zhang, Xiaowei Wei, Qin Yu","doi":"10.1016/j.lfs.2024.123306","DOIUrl":"10.1016/j.lfs.2024.123306","url":null,"abstract":"<p><strong>Objective: </strong>High-fat diet could induce structural and functional disorders of the heart, but the underlying mechanism remains elusive. This study aimed to explore related mechanism of obesity cardiomyopathy.</p><p><strong>Methods: </strong>Obesity model was established by feeding rats with a high-fat diet, and H9c2 cells were stimulated with palmitic acid to mimic high-fat stimulation. Whole transcriptome analysis results showed that the expression of Dickkopf-2 (DKK2) in obesity cardiomyopathy group was significantly lower than that in control group and simple obesity group. Overexpression and knockdown of DKK2 was achieved by infection with lentivirus. Weight, blood glucose, lipids, blood pressure, and insulin, HE staining, Sirius red staining and echocardiography results were analyzed in rats at 8 and 16 weeks after various interventions. qRT-PCR and western blots were used to detect the expression of RNAs and proteins.</p><p><strong>Results: </strong>High-fat diet-induced obese rats presented with changes in serum lipid, insulin, and increases in myocardial inflammation and fibrosis. Protein and mRNA expression levels of DKK2 were significantly decreased in the obesity cardiomyopathy group compared with the obesity and control group. In vitro, knockdown of DKK2 activated β-catenin/Wnt3a pathway, while overexpress of DKK2 inhibited β-catenin/Wnt3a expression.</p><p><strong>Conclusion: </strong>Activating DKK2 may serve as a novel therapeutic intervention option for obesity cardiomyopathy and obesity-related metabolic disorders, and future studies are needed to validate this hypothesis.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123306"},"PeriodicalIF":5.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitazoxanide alleviates experimental pulmonary fibrosis by inhibiting the development of cellular senescence.","authors":"Xianzhe Wang, Yanyan Zhu, Huilin Liu, Xiangchuan Wang, Hongjie Zhang, Xiuping Chen","doi":"10.1016/j.lfs.2024.123302","DOIUrl":"10.1016/j.lfs.2024.123302","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by irreversible lung scarring with a poor prognosis. Emerging evidence has revealed that IPF is an aging-related disease, and the development of cellular senescence plays a pivotal role in persistent remodeling and fibrotic scarring, acting as a key mechanism in the pathophysiology of IPF. Exploring therapeutic strategies for modulating cellular senescence can provide crucial insights into unraveling IPF processes. Here, we have identified Nitazoxanide (NTZ), an FDA-approved antiprotozoal agent, has specific effects on inhibiting cellular senescence development. In the bleomycin and D-galactose-induced senescence model, NTZ effectively inhibits senescence associated-β-gal staining and preserves cell proliferation ability. We also found that NTZ effectively impedes senescence progression in the bleomycin-induced pulmonary fibrosis model, while mitigating the release of senescence-associated secretory phenotype and alleviating pulmonary fibrosis. The anti-senescence effect of NTZ is mechanistically dependent on the preservation of nuclear SIRT1 expression. We observed that PI3K induces a WIPI1-mediated nucleophagic degradation of SIRT1, while NTZ effectively inhibits PI3K and suppresses WIPI1 expression, thereby maintaining SIRT1 expression in the nucleus and exerting its anti-senescence function. Collectively, our research has shown that NTZ can inhibit PI3K in senescence progression, leading to the inhibition of WIPI1-mediated SIRT1 nucleophagic degradation. As a result, NTZ alleviates fibrosis by inhibiting senescence development.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123302"},"PeriodicalIF":5.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alogliptin attenuates STZ-induced diabetic nephropathy in rats through the modulation of autophagy, apoptosis, and inflammation pathways: Targeting NF-κB and AMPK/mTOR pathway.","authors":"Salma M Selim, Hassan M El Fayoumi, Norhan M El-Sayed, Eman T Mehanna, Reem M Hazem","doi":"10.1016/j.lfs.2024.123307","DOIUrl":"10.1016/j.lfs.2024.123307","url":null,"abstract":"<p><strong>Aim: </strong>Diabetic nephropathy (DN) is a type of microvascular complication that arises from diabetes mellitus and leads to further health issues. Most importantly, the prevalence of DN is steadily rising in developed countries. This research explored the therapeutic benefits of alogliptin, a dipeptidyl peptidase IV (DPP-4) inhibitor, on streptozotocin (STZ)-induced DN and its underlying mechanisms in rats.</p><p><strong>Main methods: </strong>Ten rats were allocated to group 1, served as the normal group; and received saline. To develop diabetes, thirty rats were administered a single intraperitoneal dose of STZ (45 mg/kg). STZ-induced diabetic rats were randomly assigned to three groups: group 2 diabetic control; was given saline, groups 3 and 4 received alogliptin (10 mg/kg) and (20 mg/kg), respectively. The treatment began 8 weeks after diabetes onset and continued for four weeks. Histopathological alterations in the kidney were detected. Serum was collected to measure blood glucose levels (BGL), renal function, and lactate dehydrogenase (LDH). Tissue samples were collected to detect changes in oxidative stress (OS), inflammation, 5' adenosine monophosphate-activated protein kinase (AMPK), and the mammalian target of Rapamycin (mTOR) signaling pathways in addition to apoptotic and autophagy changes.</p><p><strong>Key findings: </strong>Alogliptin reduced STZ-induced histological changes in the kidney as well as OS, and inflammation. Alogliptin also ameliorated the AMPK/mTOR signaling pathways, enhanced autophagy, and reduced apoptosis.</p><p><strong>Significance: </strong>These results demonstrate that alogliptin ameliorates inflammation and OS and consequently modulates the AMPK/mTOR axis along with targeting autophagy and apoptosis, leading to the alleviation of DN.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123307"},"PeriodicalIF":5.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficacy of intra-articular polydioxanone (PDO) injections as a novel viscosupplement in osteoarthritis treatment.","authors":"Linh Thi Thuy Le, Pham Ngoc Chien, Thuy-Tien Thi Trinh, Ji-Won Seo, Nguyen Ngan Giang, Pham Thi Nga, Xin Rui Zhang, Yong Xun Jin, Sun-Young Nam, Chan-Yeong Heo","doi":"10.1016/j.lfs.2024.123303","DOIUrl":"10.1016/j.lfs.2024.123303","url":null,"abstract":"<p><strong>Aims: </strong>Osteoarthritis (OA) is a chronic joint disorder marked by cartilage breakdown, bone alterations, and inflammation, leading to significant pain and disability. Current therapeutic strategies, ranging from lifestyle interventions to pharmacological and surgical treatments, offer limited efficacy and are often accompanied by side effects. This study investigates the potential of Polydioxanone (PDO), a biocompatible synthetic polymer, as a novel intra-articular (IA) viscosupplement in OA.</p><p><strong>Materials and methods: </strong>A validated rabbit model of OA was employed to compare the therapeutic effects of IA injections of PDO against established viscosupplements like hyaluronic acid (HA) and Conjuran (CJR). Sixty rabbits with collagenase-induced OA were randomized into four groups, receiving respective treatments over 12 weeks. The effect of PDO was analyzed by histopathological examination, immunofluorescence staining (IF), immunoblotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Key findings: </strong>The histopathological examination revealed substantial improvements in the PDO group's cartilage structure and matrix composition. qRT-PCR, IF staining, and Western Blot showed significant downregulation of matrix metalloproteinases (MMPs) and upregulation of type II collagen (COL II) and aggrecan (ACAN). ELISA results corroborated decreased inflammatory mediators- interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the PDO-treatment group.</p><p><strong>Significance: </strong>Preliminary results indicate that PDO may enhance cartilage regeneration and reduce inflammation, suggesting it is a viable and superior treatment option for OA. These findings merit further investigation to translate into clinical applications.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123303"},"PeriodicalIF":5.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of acetylation-mediated fusion of lysosomes with autophagosomes in neurons after ischemic stroke.","authors":"Yu Meilin, Xiong Yajie, He Hongyun, Deng Yihao","doi":"10.1016/j.lfs.2024.123305","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123305","url":null,"abstract":"<p><p>Ischemic stroke is a serious cerebrovascular disease that brings a significant threat to human health [5]. Considerable factors are involved in occurrence of cerebral ischemia. Among them, autophagy is an important intracellular process that is activated after ischemic stroke, which plays a crucial role in maintaining homeostasis and survival of neurons [10]. The fusion of lysosomes with autophagosomes is a key step in autophagic processes [1]. In recent decades, investigations have found that acetylation, a common post-translational modification of proteins, has an important regulatory effect on autophagy [7]. The present article focuses on elucidating mechanism and roles of acetylation in fusion of lysosomes with autophagosomes in neurons after ischemic stroke, to seek novel targets and strategies for deeper understanding of the pathogenesis of ischemic stroke [8]. This review is also to provide clues for clinical treatment of ischemic stroke [9].</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123305"},"PeriodicalIF":5.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-derived mesenchymal stromal cells stimulate neovascularization less than their primary counterparts.","authors":"Julian Gonzalez-Rubio, Kira Zeevaert, Eva Miriam Buhl, Michaela Schedel, Stefan Jockenhoevel, Christian G Cornelissen, Wolfgang Wagner, Anja Lena Thiebes","doi":"10.1016/j.lfs.2024.123298","DOIUrl":"10.1016/j.lfs.2024.123298","url":null,"abstract":"<p><strong>Aims: </strong>Mesenchymal stromal cells (MSCs) are being tested and accepted as a source for cell therapy worldwide. However, the advanced age of the patients, together with the difficulties in achieving the required cell amounts, impede autologous treatments. Reprogramming of MSCs into induced pluripotent stem cells (iPSCs), followed by re-differentiation to MSCs has emerged as a promising and safe method to facilitate the cell expansion and the removal of aging-associated characteristics. However, the effect of reprogramming on the MSC's pro-angiogenicity is poorly understood.</p><p><strong>Materials and methods: </strong>In this study, we use a microfluidic organ-on-a-chip platform designed for vascularization assays to study and compare the effects of bone marrow MSCs (BM-MSCs) and iPSC-derived MSCs (iMSCs) in stimulating the formation of vessels by endothelial cells. Cells were loaded in fibrin hydrogels, injected into the microfluidic channel, and grown for ten days.</p><p><strong>Key findings: </strong>Fluorescence microscopy revealed that BM-MSCs promote the formation of long and interconnected endothelial vessels, while iMSCs barely stimulate neoangiogenesis. This was further confirmed and explained by bulk RNA sequencing, showing a decrease of pro-angiogenic agents in both of the iMSCs co-cultures. Furthermore, transmission electron microscopy revealed that BM-MSCs closely associate with the new vessels as perivascular cells, while iMSCs just remain in proximity.</p><p><strong>Significance: </strong>These results highlight iMSCs as a promising substitute for BM-MSCs in the treatment of diseases with pernicious vascularization, such as osteoarthritis, ocular degeneration, and cancer.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123298"},"PeriodicalIF":5.2,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic exercise training attenuates ischemia-reperfusion injury in mice by decreasing the methylation level of METTL3-associated m6A RNA in cardiomyocytes.","authors":"Xinmin Zhang, Dong-Xu Huang, Chengluan Xuan, Yanhui Li, Yuting Jiang, Xuehan Wu, Wenqian Zhou, Yang Lei, Fan Yang, Haichun Ma, Kun Hou, Xue Han, Guichen Li","doi":"10.1016/j.lfs.2024.123294","DOIUrl":"10.1016/j.lfs.2024.123294","url":null,"abstract":"<p><strong>Background and aims: </strong>Ischemic heart disease (IHD) presents a significant global health challenge, with myocardial ischemia-reperfusion injury (MIRI) being a major pathophysiological contributor and lacking effective interventions. While aerobic exercise training (AET) enhances cardiovascular health, its protective mechanism in MIRI remains elusive. This study aims to elucidate the protective effect of AET in MIRI and its underlying mechanism.</p><p><strong>Methods: </strong>A mouse model of AET and MIRI was established to evaluate basic indices, cardiac ultrasound, and myocardial injury markers. Dot Blot, qRT-PCR, and Western blot were employed to assess m⁶A RNA methylation levels and related protein expression in myocardial tissue. In vitro, primary cardiomyocyte culture was utilized to mimic MIRI, evaluating cell viability, mitochondrial membrane potential, etc. Finally, myocardial tissues of MIRI mice were immunoprecipitated for m⁶A RNA methylation and sequenced to analyze related signaling pathways.</p><p><strong>Key results: </strong>AET significantly improved cardiac function and mitigated myocardial injury and fibrosis. Moreover, AET protected myocardium from MIRI by reducing m⁶A RNA methylation levels and modulating METTL3 expression. In vitro experiments demonstrated that the decrease in m⁶A RNA methylation levels and METTL3 expression conferred resistance to hypoxia/reoxygenation-induced injury. Furthermore, sequencing results indicated elevated myocardial tissue m⁶A RNA methylation levels during MIRI, activation of the Nrf2-related signaling pathway, and AET-mediated regulation of the Nrf2/HO-1 signaling pathway, thereby attenuating MIRI through modulation of METTL3-related m⁶A methylation.</p><p><strong>Conclusion and significance: </strong>AET attenuates MIRI by reducing the level of METTL3-related m⁶A RNA methylation in cardiomyocytes and activating the Nrf2/HO-1 antioxidant signaling pathway. This finding provides a novel insight and strategy for the prevention and treatment of IHD, holding significant clinical implications.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123294"},"PeriodicalIF":5.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}