Life sciences最新文献

{"title":"PLAC1 augments the malignant phenotype of cervical cancer through the mTOR/HIF-1α/snail signaling pathway.","authors":"Rujun Chen, Yue Hou, Jina Chen, Fuyun Dong, Xiaoqin Wang, Junhua Guan, Liwen Zhang, He Fei, Lina Yang","doi":"10.1016/j.lfs.2024.123242","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123242","url":null,"abstract":"<p><strong>Aims: </strong>This study investigated the molecular mechanisms of placenta-specific protein 1 (PLAC1) in cervical cancer (CCa), aiming to elucidate its role in tumorigenesis through in vitro and in vivo experiments.</p><p><strong>Materials and methods: </strong>CCa cell lines with overexpressed or silenced PLAC1 were established to evaluate its impact on cell cycle, apoptosis and the expression of key proteins in the PLAC1/mTOR/HIF-1α/Snail signaling pathways. Functional assays were conducted to assess the influence of the PLAC1/mTOR/HIF-1α/Snail regulatory pathway on cell proliferation, migration and invasion. The role of the mTOR signaling pathway in PLAC1-mediated modulation of CCa characteristics was validated using a mTOR activator (MHY1485) and a mTOR inhibitor (Rapamycin) respectively. HIF1A siRNA was introduced to confirm the role of HIF1A. Furthermore, an in vivo nude mouse model was constructed to confirm PLAC1's influence on tumorigenesis and metastasis in CCa.</p><p><strong>Key findings: </strong>PLAC1 upregulated hypoxia-inducible factor (HIF)-1α and Snail, promoting CCa cell proliferation, migration, and invasion via the mTOR/HIF-1α/Snail pathway. Enrichment analysis of PLAC1-associated differentially expressed genes implicated their involvement in CCa and tumor promotion. In a xenograft mouse model, PLAC1 exhibited a pro-tumorigenic effect, which can be reversed by siRNA targeting HIF1A.</p><p><strong>Significance: </strong>This study enhances our understanding of PLAC1's role and molecular mechanisms in CCa progression, highlighting its potential as a diagnostic, prognostic, and therapeutic marker for the management of CCa.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123242"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644418","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":"SIRT7 stabilizes β-catenin and promotes canonical Wnt activation via upregulating FZD7","authors":"Yiying Gu ,&nbsp;Zhiqiang Wang ,&nbsp;Gaoshuang Liang ,&nbsp;Jinying Peng ,&nbsp;Xiangwen Zhang ,&nbsp;Tingzi Yu ,&nbsp;Cong Ding ,&nbsp;Zhuan Li","doi":"10.1016/j.lfs.2024.123240","DOIUrl":"10.1016/j.lfs.2024.123240","url":null,"abstract":"<div><h3>Aims</h3><div>The dysregulated Wnt/β-Catenin signaling pathway leads to occurrence of various diseases, and abnormal activation of β-Catenin is a major characteristic of human HCC. FZD7 is a positive regulator of the Wnt/β-catenin signaling pathway, and its upregulation is related to increase of β-catenin expression and carcinogenesis in human HCC. However, mechanisms underlying FZD7 upregulation in HCC remain elusive.</div></div><div><h3>Main methods</h3><div>Nuclear cytosol fractionation, immunofluorescence and Top-Flash were used to detect the activation of β-Catenin. Protein half-life and ubiquitination assays were applied to evaluate protein stability. RNA-seq combined with qRT-PCR was used to evaluate differential gene expressions after SIRT7 knockdown. Wound healing and transwell assays were used to measure cancer cell migration.</div></div><div><h3>Key findings</h3><div>SIRT7-mediated FZD7 expression is essential for stability and activation of β-catenin. Knockdown SIRT7 in HCC cells resulted in enhanced binding of β-catenin to the DC, decreased its stability, nuclear localization and activation. Knockdown FZD7 reversed SIRT7 overexpression mediated β-catenin stabilization and impairment of binding of β-catenin to the DC. At molecular level, SIRT7 promotes FZD7 expression via upregulating transcription factor PU.1, knockdown PU.1 abolished SIRT7-mediated upregulation of FZD7. Finally, we confirmed that FZD7 was responsible for SIRT7-mediated β-catenin stabilization and HCC cells migration. By using clinical samples, we observed strong positive correlations between SIRT7 and PU.1, FZD7, p-GSK3β and β-Catenin in human HCC.</div></div><div><h3>Significance</h3><div>Our results thus revealed a previously undisclosed role of SIRT7 in regulating the canonical Wnt/β-catenin signaling pathway, thereby offering additional evidence that SIRT7 holds promise as a novel therapeutic target for human HCC.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123240"},"PeriodicalIF":5.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623315","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":"Transient cerebral ischaemia alters mesenteric arteries in hypertensive rats: Limited reversal despite suberoylanilide hydroxamic acid cerebroprotection","authors":"Andrea Díaz-Pérez ,&nbsp;Silvia Lope-Piedrafita ,&nbsp;Belén Pérez ,&nbsp;Paula Vázquez-Sufuentes ,&nbsp;Maria Rodriguez-Garcia ,&nbsp;Ana M. Briones ,&nbsp;Xavier Navarro ,&nbsp;Clara Penas ,&nbsp;Francesc Jiménez-Altayó","doi":"10.1016/j.lfs.2024.123247","DOIUrl":"10.1016/j.lfs.2024.123247","url":null,"abstract":"<div><div>Stroke induces brain injury, especially severe in hypertensive patients, and elevates mortality rates through non-neurological complications. However, the potential effects of a transient ischaemic episode on the peripheral vasculature of hypertensive individuals remain unclear. We investigated whether transient cerebral ischaemia (90 min)/reperfusion (1 or 8 days) induces alterations in mesenteric resistance artery (MRA) properties in adult male spontaneously hypertensive rats (SHR). In addition, we assessed whether the reported cerebroprotective effects of suberoylanilide hydroxamic acid (SAHA; 50 mg/kg; administered intraperitoneally at 1, 4, or 6 h after reperfusion onset) extend over several days and include beneficial effects on MRAs. Functional and structural properties of MRAs were examined at 1- and 8-days post-stroke. Nuclei distribution, collagen content, and oxidative stress were assessed. Ischaemic brain damage was evaluated longitudinally using magnetic resonance imaging. Following stroke, MRAs from SHR exhibited non-reversible impaired contractile responses to the thromboxane A₂ receptor agonist U46619. Stroke increased the MRA cross-sectional area, wall thickness, and wall/lm ratio due to augmented collagen deposition. These changes were partially sustained 8 days later. SAHA did not improve U46619-induced contractions but mitigated stroke-induced oxidative stress and collagen deposition, preventing MRA remodelling at 24 h of reperfusion. Furthermore, SAHA induced sustained cerebroprotective effects over 8 days, including reduced brain infarct and oedema, and improved neurological scores. However, SAHA had minimal impact on chronic MRA contractile impairments and remodelling. These findings suggest that stroke causes MRA changes in hypertensive subjects. While SAHA treatment offers sustained protection against brain damage, it cannot fully restore MRA alterations.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123247"},"PeriodicalIF":5.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling","authors":"Manar M. Esmail ,&nbsp;Noha M. Saeed ,&nbsp;Diana M.F. Hanna ,&nbsp;Haidy E. Michel ,&nbsp;Reem N. El-Naga ,&nbsp;Samar S. Azab","doi":"10.1016/j.lfs.2024.123229","DOIUrl":"10.1016/j.lfs.2024.123229","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling.</div></div><div><h3>Materials and methods</h3><div>Five groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days.</div></div><div><h3>Key findings</h3><div>Results showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP.</div></div><div><h3>Significance</h3><div>These findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123229"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of pyroptosis in the pathogenesis of autoimmune diseases","authors":"Yingqiu Song ,&nbsp;Yanhui Peng ,&nbsp;Bing Wang ,&nbsp;Xinyue Zhou ,&nbsp;Yikang Cai ,&nbsp;Haiyong Chen ,&nbsp;Chenggui Miao","doi":"10.1016/j.lfs.2024.123232","DOIUrl":"10.1016/j.lfs.2024.123232","url":null,"abstract":"<div><div>The occurrence of autoimmune diseases is a result of the immune system's immune response against healthy components of the body. Pyroptosis is an innovative form of programmed cell death dependent on inflammatory caspases, leading to the release of cytokines. Excessive pyroptosis can lead to a sustained inflammatory response, which may aggravate the development of autoimmune diseases. In rheumatoid arthritis (RA), tumor necrosis factor (TNF) and NLRP3 enhance pyroptosis, exacerbating the disease. In systemic lupus erythematosus (SLE), the release of nuclear antigen promotes the development of SLE. In multiple sclerosis (MS), elevated active caspase-11 in primary astrocytes induces oligodendrocyte pyroptosis, advancing MS progression. This review outlines the mechanisms of pyroptosis in autoimmune diseases. Meanwhile, we elaborated the possible therapeutic targets from the perspective of pyroptosis. We conclude that pyroptosis is expected to be a therapeutic target for autoimmune diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123232"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623318","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":"Total minor ginsenosides exert anti-fatigue effects via antioxidant, anti-inflammatory, regulating gut microbiota and serum metabolism","authors":"Yuhang Zhang ,&nbsp;Ge Yang ,&nbsp;Yansong Gao ,&nbsp;Lei Gao ,&nbsp;You Kang ,&nbsp;Yujuan Zhao ,&nbsp;Lei Zhao ,&nbsp;Shengyu Li","doi":"10.1016/j.lfs.2024.123231","DOIUrl":"10.1016/j.lfs.2024.123231","url":null,"abstract":"<div><div>Minor ginsenosides have demonstrated notable anti-fatigue capabilities. The aim of this study was to investigate the anti-fatigue mechanisms of total minor ginsenosides (TMGs) derived from a process involving probiotic fermentation and high-pressure steam treatment. The fatigue model was established in BALB/c male mice using weight-bearing swimming and TMGs were administered by orally at a dosage of 200 mg/kg for four weeks. The anti-fatigue mechanisms of TMGs were explored by assessing liver oxidative stress, skeletal muscle inflammation markers, as well as their impact on gut microbiota and serum metabolism. The results indicated that TMGs could significantly increase the levels of SOD, CAT, ATP and Na⁺-K⁺-ATPase and enhance the antioxidant capacity by modulating the PGC-1α/KEAP1/NRF2/HO-1 pathway. Meanwhile, TMGs reducing the levels of inflammatory factors TNF-α, IL-1β and IL-6 and inhibited inflammation by modulating the AMPK/TORC2/CREB/PGC-1α pathway. TMGs also regulated the gut microbiota, increasing the abundance of probiotic bacteria and the content of short-chain fatty acids (SCFAs) in the cecum. Serum metabolomics analyses have shown that TMGs can significantly affect the serum metabolic profile of fatigue model mice, regulating metabolic markers through affecting anti-fatigue-related metabolic pathways. In conclusion, TMGs exerted significant anti-fatigue effects through antioxidant and anti-inflammatory effects, and alleviate fatigue by regulating gut microbiota and serum metabolism.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123231"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623319","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":"Glioblastoma therapy: State of the field and future prospects","authors":"Nadia Allahyarzadeh Khiabani ,&nbsp;Mohammad Amin Doustvandi ,&nbsp;Darren Story ,&nbsp;Shima Alizadeh Nobari ,&nbsp;Masoumeh Hajizadeh ,&nbsp;Robert Petersen ,&nbsp;Gary Dunbar ,&nbsp;Julien Rossignol","doi":"10.1016/j.lfs.2024.123227","DOIUrl":"10.1016/j.lfs.2024.123227","url":null,"abstract":"<div><div>Glioblastoma (GB) is a cancerous brain tumor that originates from glial cells and leads to thousands of deaths each year and a five-year survival of only 6.8 %. Treatments for GB include surgery, chemotherapy, radiation, and immunotherapy. GB is an incurable fatal disease, necessitating the development of innovative strategies to find a developing effective therapy. Genetic therapies may be crucial in treating GB by identifying the mutations and amplifications of multiple genes, which drive its proliferation and spread. Use of small interfering RNAs (siRNAs) provides a novel technology used to suppress the genes associated with disease, which forms a basis for targeted therapy in GB and its stem cell population, which are recognized for their ability to develop resistance to chemotherapy and tumorigenic capabilities. This review examines the use of siRNAs in GB, emphasizing their effectiveness in suppressing key oncogenes and signaling pathways associated with tumor development, invasion, stemness, and resistance to standard treatments. siRNA-based gene silencing is a promising approach for developing targeted therapeutics against GB and associated stem cell populations, potentially enhancing patient outcomes and survival rates in this devastating disease.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123227"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623311","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":"Metabolomics for enhanced clinical understanding of inflammatory bowel disease.","authors":"Theresa Louise Boye, Alexander Hammerhøj, Ole Haagen Nielsen, Yulan Wang","doi":"10.1016/j.lfs.2024.123238","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123238","url":null,"abstract":"<p><p>Metabolomics is an emerging field involving the systematic identification and quantification of numerous metabolites in biological samples. Precision medicine applies multiomics systems biology to individual patients for reliable diagnostic classification, disease monitoring, and treatment. Multiomics systems biology encompasses genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Therefore, metabolomic techniques could be highly valuable for future clinical decision-making. This review provides a technical overview of two commonly used techniques for metabolomics measurements: mass spectrometry (MS) and proton nuclear magnetic resonance (¹H NMR) spectroscopy. We also discuss recent clinical advances in these techniques. Individuals with inflammatory bowel disease (IBD) exhibit significant variability in prognosis and response to treatment. Since both genetic predisposition and environmental factors contribute to this condition, targeting the metabolome may provide key insights for distinguishing and profiling patients with different clinical needs. Additionally, the considerable overlap in the clinical presentation of various disease subtypes emphasizes the need for enhanced diagnostic methods to improve patient care.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123238"},"PeriodicalIF":5.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623313","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":"Albumin binding domain fusion improved the therapeutic efficacy of Inhibitor of Differentiation-2 protein in colitis mice","authors":"Lingyun Xu ,&nbsp;Yuxin Wang ,&nbsp;Dong Yan ,&nbsp;Min Li ,&nbsp;Lin Qiao ,&nbsp;Zhiguo Chen ,&nbsp;Minna Wu ,&nbsp;Genshen Zhong","doi":"10.1016/j.lfs.2024.123237","DOIUrl":"10.1016/j.lfs.2024.123237","url":null,"abstract":"<div><h3>Aims</h3><div>The human Inhibitor of Differentiation-2 (hID2) protein is a promising candidate for the treatment of colitis. However, its relatively low molecular weight limits its clinical application. To extend the therapeutic half-life, an albumin-binding domain (ABD), known for its high affinity for human serum albumin (HSA), was fused to hID2, resulting in a recombinant ABD-hID2. The anti-colitis bioactivity of ABD-hID2 than that of hID2 was evaluated in this study.</div></div><div><h3>Main methods</h3><div>Western blotting, size-exclusion high-performance chromatography, HSA binding assay, and pharmacokinetic studies were used to characterise ABD-hID2, which was induced by dextran sulfate sodium salt (DSS), <em>Citrobacter rodentium</em> (<em>CR</em>), and ABD-hID2 and hID2. The Disease Activity Index, histological pathologies, inflammatory response, Alcian blue or tuft cell staining, and tight junction proteins were determined. Alterations in the intestinal microbiota after ABD-hID2 treatment were analysed <em>via</em> 16S rRNA gene sequencing.</div></div><div><h3>Key findings</h3><div>Compared with hID2, ABD-hID2 exhibited a decreased dimer complex, bound to HSA with high affinity, and demonstrated an extended blood retention time <em>in vivo</em>. Consequently, ABD-hID2 exhibited increased therapeutic efficacy in both DSS- and <em>CR</em>-induced colitis mouse models, as evidenced by the alleviation of colitis symptoms, preservation of goblet and tuft cell functions, restoration of the intestinal mucus barrier, and suppression of abnormal immune-inflammatory responses. Additionally, the modulation of the gut microbiota may play a role in the protective effects of ABD-hID2 in mice with <em>CR</em>-induced ulcerative colitis.</div></div><div><h3>Significance</h3><div>ABD-hID2 enhances the bioactivity of hID2 and has the potential for further development as a treatment for colitis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123237"},"PeriodicalIF":5.2,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623320","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 AMPK with Irisin: Implications for metabolic disorders, cardiovascular health, and inflammatory conditions - A systematic review.","authors":"Lucas Fornari Laurindo, Victória Dogani Rodrigues, Lívia Fornari Laurindo, Luana Maria Amaral Cherain, Enzo Pereira de Lima, Beatriz Leme Boaro, Jéssica da Silva Camarinha Oliveira, Eduardo Federighi Baisi Chagas, Vitor Cavallari Strozze Catharin, Jesselina Francisco Dos Santos Haber, Patricia Cincotto Dos Santos Bueno, Rosa Direito, Sandra Maria Barbalho","doi":"10.1016/j.lfs.2024.123230","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123230","url":null,"abstract":"<p><p>Irisin-based interventions have gained attention for their potential to modulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in various diseases. Physiologically, irisin is a myokine released during physical exercise that exerts anti-inflammatory effects and is a metabolic and cardiometabolic enhancer. On the other hand, AMPK is crucial for maintaining energy balance and metabolic homeostasis. Therefore, individuals presenting low blood levels of irisin and AMPK dysregulation are more predisposed to metabolic disorders and cardiovascular health inflammatory conditions since regulating energy balance and metabolic homeostasis are crucial for preventing or treating these disorders. In light of those mentioned above and considering that no review has addressed the intricate relationships between irisin and AMPK regulation in the realm of metabolic disorders, cardiovascular health, and inflammatory conditions, we comprehensively reviewed studies involving irisin's effects on AMPK signaling in different models and interventions. Our systematic analysis involved in vitro studies, animal models, and their relevant clinical implications of irisin targeting AMPK due to the absence of relevant clinical trials. The outcomes and limitations of the included studies were extensively highlighted. Objectively, irisin improved metabolic disorders by enhancing β-cell function and insulin secretion in diabetes, mitigating myocardial injury in cardiovascular conditions, and reducing inflammation and oxidative stress in various injury models by targeting AMPK. However, the lack of clinical trials limits the generalizability of these findings to human subjects. Future research should focus on translating these findings into clinical applications and exploring the broader implications of irisin-based interventions in human health.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123230"},"PeriodicalIF":5.2,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623316","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}