Aging-Us最新文献

{"title":"Proteomic and secretomic comparison of young and aged dermal fibroblasts highlights cytoskeleton as a key component during aging.","authors":"Françoise Boismal, Sandy Peltier, Sophie Ly Ka So, Guillaume Chevreux, Loïse Blondel, Kévin Serror, Niclas Setterblab, Elina Zuelgaray, David Boccara, Maurice Mimoun, Christelle Guere, Armand Benssussan, Marie Dorr, Gallic Beauchef, Katell Vie, Laurence Michel","doi":"10.18632/aging.206055","DOIUrl":"10.18632/aging.206055","url":null,"abstract":"<p><p>Crucial for skin homeostasis, synthesis and degradation of extracellular matrix components are orchestrated by dermal fibroblasts. During aging, alterations of component expression, such as collagens and enzymes, lead to reduction of the mechanical cutaneous tension and defects of skin wound healing. The aim of this study was to better understand the molecular alterations underwent by fibroblasts during aging by comparing secretomic and proteomic signatures of fibroblasts from young (<35years) and aged (>55years) skin donors, in quiescence or TGF-stimulated conditions, using HLPC/MS. The comparison of the secretome from young and aged fibroblasts revealed that 16 proteins in resting condition, and 11 proteins after a 24h-lasting TGF-β1-treatment, were expressed in significant different ways between the two cell groups (fold change>2, <i>p-value</i> <0.05), with a 77% decrease in the number of secreted proteins in aged cells. Proteome comparison between young and aged fibroblasts identified a significant change of 63 proteins in resting condition, and 73 proteins in TGF-β1-stimulated condition, with a 67% increase in the number of proteins in aged fibroblasts. The majority of the differentially-expressed molecules belongs to the cytoskeleton-associated proteins and aging was characterized by an increase in Coronin 1C (CORO1C), and Filamin B (FLNB) expression in fibroblasts together with a decrease in Cofilin (CFL1), and Actin alpha cardiac muscle 1 (ACTC1) detection in aged cells, these proteins being involved in actin-filament polymerization and sharing co-activity in cell motility. Our present data reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-424-5p suppresses the proliferation and immigration of oral squamous cell carcinoma via down-regulation of KDR.","authors":"Junqing Zhang, Zhangui Tang, Guanghui Bao","doi":"10.18632/aging.206083","DOIUrl":"https://doi.org/10.18632/aging.206083","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this research was to investigate the part played by KDR and miRNAs in the development and prognosis of oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>The gene and protein expression of KDR in OSCC cell lines and a normal human oral epithelial keratinocyte cell line were detected using real-time PCR and western blot analysis. We evaluated the impact of KDR on the proliferation, metastasis, and migration of OSCC cells using the MTT assay and colony formation assay in the CAL27 cell line. Data on OSCC were retrieved from the TCGA-HNSC and GEO databases, and we identified miRNAs that were differentially expressed between OSCC and normal tissue samples. Furthermore, we predicted their potential target mRNAs. miR-424-5p was identified as a regulator upstream of KDR expression, and dual luciferase reporter assays confirmed binding between KDR and miR-424-5p.</p><p><strong>Results: </strong>KDR overexpression was observed in OSCC samples from various databases. These findings were further validated through <i>in vitro</i> experiments, which established that elevated KDR levels enhance the proliferative potential of OSCC cells. Moreover, miR-424-5p was found to counteract the tumorigenic effects of KDR in OSCC cells, suppressing their proliferation, invasion, and metastasis capabilities.</p><p><strong>Conclusions: </strong>Our research suggests that miR-424-5p and KDR might serve as valuable diagnostic and prognostic markers, as well as potential therapeutic targets, in OSCC.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeic acid derivative MPMCA suppresses osteoclastogenesis and facilitates osteoclast apoptosis: implications for the treatment of bone loss disorders.","authors":"Le Huynh Hoai Thuong, Chin-Jung Hsu, Hsien-Te Chen, Yueh-Hsiung Kuo, Chih-Hsin Tang","doi":"10.18632/aging.206067","DOIUrl":"10.18632/aging.206067","url":null,"abstract":"<p><p>Osteoclast activity plays a crucial role in the pathological mechanisms of osteoporosis and bone remodeling. The treatment of these disorders involves the use of pharmacological medicines that work by inhibiting the activity of osteoclasts. Nevertheless, the prevalent and infrequent negative consequences of current antiresorptive and bone anabolic treatments pose significant drawbacks, hence restricting their prolonged administration in patients, particularly those who are elderly and/or suffer from many medical conditions. We are currently in the process of creating a new molecule called N-(4-methoxyphen) methyl caffeamide (MPMCA), which is a derivative of caffeic acid. This compound has shown potential in preventing the production of osteoclasts and causing existing osteoclasts to undergo cell apoptosis. Our investigation discovered that MPMCA hinders osteoclast function via suppressing the MAPK pathways. The expectation is that the findings of this study will stimulate the advancement of a novel approach to treating anti-resorption.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic study of PD-L1 regulation of metastatic proliferation in non-small cell lung cancer through modulation of IRE1α/XBP-1 signaling pathway in tumor-associated macrophages.","authors":"Yi Wang, Lei Yang, Zezheng Liang, Ming Liu","doi":"10.18632/aging.206082","DOIUrl":"10.18632/aging.206082","url":null,"abstract":"<p><strong>Objective: </strong>To explore the related research of PD-L1 in IRE1α/XBP-1 signaling pathway on non-small cell lung cancer.</p><p><strong>Methods: </strong>The tumor model of mice was established and divided into four groups; after successful modeling, the tumor tissue of mice was removed for subsequent experiments; the bought THP-1 cells were grouped into four different groups, a control group, nivolumab intervention group, IRE1α inhibition group, and nivolumab intervention + IRE1α inhibition group; after co-culture of the four groups of THP-1 cells with A549, THP-1 cell protein levels in the four groups were analyzed using Western blot; A549 cell migration, invasion and proliferation were assessed using the scratch assay, Transwell method, monoclonal experiment and CCK-8 method.</p><p><strong>Results: </strong><i>In vivo</i> studies indicated that the stimulation of nivolumab could strongly check the progress of NSCLC (non-small cell lung); two groups treated with 4 μ8c showed obvious effects on check point of NSCLC; <i>In vitro</i> experiments including Western-blot experiment, Scratch experiment, Transwell method, Monoclonal experiment and CCK-8 experiment suggest that nivolumab could inhibit migration, invasion and proliferation of NSCLC tumor cells and it.</p><p><strong>Conclusion: </strong>PD-L1 is capable of controlling metastatic and proliferative potential of NSCLC by the way of the modification of IRE1α/XBP-1 signaling in tumor-associated macrophages.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophils and drugs for eosinophilia are associated with the risk of colorectal cancer: a Mendelian randomization study.","authors":"Yuan-Yuan Wang, Zhi-Han Jia, Qing-Jun Wang, Zhi-Tu Zhu","doi":"10.18632/aging.206081","DOIUrl":"10.18632/aging.206081","url":null,"abstract":"<p><p>Eosinophils have the potential to exhibit both anti-tumor properties and tumor-promoting effects. However, the impact of eosinophil levels in the bloodstream on tumorigenesis risk remains inadequately explored. Furthermore, investigations regarding the association between drugs regulating eosinophils and cancer risk are currently absent. In this study, we conducted a Mendelian randomization (MR) analysis utilizing eosinophil count and eosinophil percentage as exposures. In both cohorts, a significant association was observed between eosinophil count and the risk of colorectal cancer and skin malignancies. However, upon conducting a sensitivity analysis, heterogeneity was detected specifically in relation to skin malignancies. Subsequent reverse Mendelian randomization analysis did not indicate any evidence of reverse causality. Furthermore, the multivariate Mendelian randomization analysis results suggested that eosinophils act as a mediating factor in reducing the risk of colorectal cancer and skin malignancies in individuals with asthma. And the use of drugs that modulate eosinophilia may increase the risk of colorectal cancer. It is evident that the statistical evidence supporting a negative correlation between eosinophils count and the susceptibility to colorectal cancer is particularly robust. And, it is plausible to suggest that pharmaceutical interventions aimed at modulating eosinophilia may potentially heighten the risk of colorectal cancer. Hence, it is imperative to exercise caution and remain mindful of the potential risk of colorectal cancer when employing these medications.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Bromopalmitate treatment attenuates senescence phenotype in human adult cells - possible role of palmitoylation.","authors":"Adam Krzystyniak, Agata Gluchowska, Agata Pytyś, Magdalena Dudkowska, Tomasz Wójtowicz, Alicja Targonska, Dorota Janiszewska, Ewa Sikora, Grazyna Mosieniak","doi":"10.18632/aging.206080","DOIUrl":"10.18632/aging.206080","url":null,"abstract":"<p><p>Cells may undergo senescence in response to DNA damage, which is associated with cell cycle arrest, altered gene expression and altered cell morphology. Protein palmitoylation is one of the mechanisms by which the DNA damage response is regulated. Therefore, we hypothesized that protein palmitoylation played a role in regulation of the senescent phenotype. Here, we showed that treatment of senescent human vascular smooth muscle cells (VSMCs) with 2-bromopalmitate (2-BP), an inhibitor of protein acyltransferases, is associated with changes in different aspects of the senescent phenotype, including the resumption of cell proliferation, a decrease in DNA damage markers and the downregulation of senescence-associated β-galactosidase activity. The effects were dose dependent and associated with significantly decreased total protein palmitoylation level. We also showed that the senescence-modifying properties of 2-BP were at least partially mediated by the downregulation of elements of DNA damage-related molecular pathways, such as phosphorylated p53. Our data suggest that cell senescence may be regulated by palmitoylation, which provides a new perspective on the role of this posttranslational modification in age-related diseases.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer.","authors":"Weiwei Yuan, Jianye Han, Chen Chen, Yue Qiu, Yuanmin Xu, Yang Huang, Zhangming Chen, Aman Xu, Minzhi Sun","doi":"10.18632/aging.206079","DOIUrl":"10.18632/aging.206079","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes a protein that binds to unstable N-terminal residues of substrate proteins and contributes to the formation of substrate-linked polyubiquitin chains. However, the function and cellular pathways of UBR1 in tumors have received inadequate attention. This study aimed to investigate the potential of UBR1 as a prognostic biomarker and immunotherapy target for stomach adenocarcinoma (STAD) as well as its biological function and molecular mechanism in relation to the disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Differential expression and pan-cancer gene set enrichment analysis (GSEA) were conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx) datasets. The Human Protein Atlas (HPA) database was utilized to identify UBR1-enriched pathways in AGS cells and to compare immunohistochemical differences between cancerous and adjacent non-cancerous tissues in gastric cancer. Quantitative Polymerase Chain Reaction (QPCR) and Western blot (WB) analyses were employed to validate these findings in both cancerous and adjacent non-cancerous tissues of gastric cancer. UBR1 expression in GES-1 and four gastric cancer cell lines was assessed using QPCR and WB. Kaplan-Meier curves, univariate and multivariate Cox regression analyses, and receiver operating characteristic (ROC) curve analyses were performed to evaluate the prognostic and diagnostic roles of UBR1. Additionally, the correlation between UBR1 expression and clinical parameters was analyzed using TCGA and GEO databases. UBR1 mutation data were obtained from the cBioPortal database. The mutation landscape, mutation-associated genes, protein structure, tumor mutation burden (TMB), and microsatellite instability (MSI) correlations were analyzed and illustrated. The biological functions of UBR1 were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The correlation between UBR1 and immune infiltration was assessed using TIMER and EPIC computational methods. Protein expression levels of UBR1 in gastric cancer cell lines were determined by immunohistochemistry (IHC) and WB analysis. Quantitative real-time PCR (qRT-PCR) was employed to analyze mRNA expression. Immunoprecipitation (IP) assays were conducted to detect protein-protein interactions between UBR1 and PDL1, while cellular immunofluorescence was used to observe the co-localization of these proteins. Cell proliferation was evaluated using CCK8 and colony formation assays. Cell migration was assessed using Transwell and wound healing assays. Finally, apoptosis was analyzed using flow cytometry, and WB was used to detect changes in apoptotic proteins and NF-κB P65 pathway proteins.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;UBR1 was upregulated in 28 cancer types, including STAD, and its overexpression was validated in","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson's disease among patients with diabetes mellitus: a retrospective cohort study.","authors":"Kuang-Hua Huang, Yih Yang, Shuo-Yan Gau, Tung-Han Tsai, Chien-Ying Lee","doi":"10.18632/aging.206074","DOIUrl":"10.18632/aging.206074","url":null,"abstract":"<p><strong>Background: </strong>How a person's Parkinson disease (PD) risk is affected by dipeptidyl peptidase-4 (DPP-4) inhibitors remains unclear. We evaluated the association of PD risk with use of these inhibitors in individuals diagnosed as having diabetes mellitus (DM).</p><p><strong>Methods: </strong>Individuals diagnosed as having new-onset DM were enrolled into the case group and comparison group, comprising patients who received a DPP-4 inhibitor and a sulfonylurea, respectively. These groups were matched through propensity score matching on the basis of income level, gender, urbanization level, enrollment year, age, and diabetes complications severity index score. The case group was divided into subgroups on the basis of whether they had a cumulative defined daily dose (cDDD) of <75, 75-150, or >150. The DPP-4 inhibitor-PD risk association was evaluated through a Cox proportional hazards model. The Bonferroni adjustment test was employed to adjust <i>P</i>-values and reduce the false positive rate.</p><p><strong>Results: </strong>Compared with those in the comparison group (treatment with a sulfonylurea), patients with a DPP-4 inhibitor cDDD of >150 had a hazard ratio (HR) of 1.30 for PD development (95% confidence interval [CI]: 0.97-1.73; adjusted <i>P</i> = .263); the HRs for patients with a cDDD of <75 or 75-150 were 0.95 (95% CI: 0.71-1.27; adjusted <i>P</i> = .886) and 1.06 (95% CI: 0.75-1.50; adjusted <i>P</i> = .886), respectively. We noted nonsignificant differences regarding the associations between the use of the various DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) and PD risk after adjustment for any individual inhibitor (adjusted <i>P</i> > .05).</p><p><strong>Conclusions: </strong>DPP-4 inhibitors were discovered in this study to not be associated with increased PD risk. This result was confirmed when the analysis was conducted individually for the 4 investigated DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and vildagliptin).</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between <i>Helicobacter pylori</i> infection and digestive tract diseases and analysis of risk factors: a cross-sectional study based on 3867 Chinese patients.","authors":"Wang Zhao, Yanzhi Han, Yizhi Xiao, Yuan Liu, Zhenling Zhang, Lijuan Liao, Jinqi Wei, Xiaofeng Li, Minzhao Gao, Jing Lu","doi":"10.18632/aging.206065","DOIUrl":"10.18632/aging.206065","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infect nearly half of the global population, contributing to upper digestive tract diseases. This 2019 cross-sectional study included 3,867 patients undergoing esophagogastroduodenoscopy (EGD) and 2,875 undergoing both colonoscopy and EGD. Subjects were categorized into <i>H. pylori</i> positive and negative groups by rapid urease test (RUT). In addition to exploring the relationship between <i>H. pylori</i> infection and upper gastrointestinal diseases, this study further revealed that <i>H. pylori</i> infection was closely related to lower digestive tract diseases, including colorectal polyp (63.28%) and colorectal cancer (75.76%), as well as upper and lower gastrointestinal comorbidities, including chronic atrophic gastritis with colorectal polyp (79.85%), peptic ulcer with colorectal polyp (79.72%), gastric polyp with colorectal polyp (66.24%), and chronic atrophic gastritis with colorectal cancer (92.86%). Besides, a univariate logistic regression analysis was conducted to compare the differences between the two groups (including gender, nationality, marital status, smoking history, drinking history, living area, age, BMI, glycosylated hemoglobin, fasting blood glucose, total cholesterol, and triglyceride levels), the results identified marital status and age as independent risk factors for <i>H. pylori</i> infection (OR, 1.435; 95% CI, 1.042 to 1.977; OR, 1.007; 95% CI, 1.001 to 1.013). Further clarification of the correlation between the prevalence of gastrointestinal diseases and <i>H. pylori</i> infection will be important for <i>H. pylori</i> infection management strategies and the treatment and prevention of gastrointestinal diseases.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulating miR-432-5p exacerbates adriamycin-induced cardiotoxicity via activating the RTN3 signaling pathway.","authors":"Wei Geng, Shaohua Yan, Dasen Sang, Jie Tao, Xuefei Zhang, Xinshun Gu, Xiangyu Zhang","doi":"10.18632/aging.206062","DOIUrl":"10.18632/aging.206062","url":null,"abstract":"<p><strong>Background: </strong>Adriamycin (ADR) is a widely used chemotherapy drug in clinical practice and it causes toxicity in the myocardium affecting its clinical use. miR-432-5p is a miRNA primarily expressed in myocardial cells and has a protective effect in the myocardium. We aim to explore the protective effect of miR-432-5p on ADR-caused impaired mitochondrial ATP metabolism and endoplasmic reticulum stress (ERs).</p><p><strong>Method: </strong>The primary cardiomyocytes were obtained from neonatal mice and the ADR was added to cells, meanwhile, a mice model was constructed through intravenous ADR challenge, and expression levels of miR-432-5p were examined. Subsequently, the miR-432-5p was introduced <i>in vitro</i> and <i>in vivo</i> to explore its effect on the activity of mitochondrial ATP synthesis, autophagy, and ER stress. The bioinformatics analysis was performed to explore the target of miR-432-5p.</p><p><strong>Results: </strong>ADR decreased the expression of miR-432-5p in cardiomyocytes. It also decreases mitochondrial ATP production and activates the ER stress pathway by increasing the expression of LC3B, Beclin 1, cleaved caspase 3, and induces cardiac toxicity. miR-432-5p exogenous supplementation can reduce the cardiotoxicity caused by ADR, and its protective effect on cardiomyocytes depends on the down-regulation of the RTN3 signaling pathway in ER.</p><p><strong>Conclusion: </strong>ADR can induce the low expression of miR-432-5p, and activate the RTN3 pathway in ER, increase the expression of LC3B, Beclin 1, cleaved caspase 3, CHOP, and RTN3, and induce cardiac toxicity.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}