International journal of molecular medicine最新文献

{"title":"Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment.","authors":"Ying Yang, Lulu Song, Liping Yu, Jinping Zhang, Bo Zhang","doi":"10.3892/ijmm.2025.5497","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5497","url":null,"abstract":"<p><p>The aim of the present study was to investigate the neuroprotective effects of semaglutide in diabetes‑associated cognitive decline (DACD), while also exploring the underlying mechanisms targeting anti‑oxidative effects. The present study evaluated the antioxidant properties of semaglutide using a DACD model of inflammation. To investigate the underlying mechanisms, omics technologies were employed. Comprehensive transcriptomic and proteomic analysis of the cells was conducted to identify the pathways responsible for the observed antioxidant effects. Semaglutide demonstrated the potential to enhance learning and memory functions while mitigating hippocampal pathological damage. RNA‑sequencing and data‑independent acquisition proteomics analyses identified 13,511 differentially expressed genes and 588 differentially expressed proteins between the control and type 2 diabetes mellitus (T2DM) groups. In addition, 1,378 genes and 2,394 proteins exhibited a differential expression between the T2DM and semaglutide (10 µg/kg) treatment groups. A combined transcriptomic and proteomic analysis unveiled 40 common pathways. Acyl‑CoA oxidase 1 (ACOX1) was observed to be activated during oxidative stress and subsequently suppressed by semaglutide. Of note, the antioxidant and anti‑apoptotic properties of semaglutide in high glucose (HG) conditions were partially reversed upon ACOX1 overexpression. Overall, the present data provided molecular evidence to elucidate the physiological connections between semaglutide and neuronal function, and contribute to clarifying the role of semaglutide in combating oxidative stress and HG‑induced cognitive impairment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065474","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":"Remimazolam alleviates myocardial ischemia/reperfusion injury and inflammation via inhibition of the NLRP3/IL‑1β pathway in mice.","authors":"Xueru Liu, Guojing Shui, Yan Wang, Tangting Chen, Peng Zhang, Li Liu, Chunhong Li, Tao Li, Xiaobin Wang","doi":"10.3892/ijmm.2025.5498","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5498","url":null,"abstract":"<p><p>Remimazolam (Rema) is a novel anesthetic that is widely used in anesthesia and sedation in critically ill patients. Notably, Rema exerts effects in patients through activation of the γ‑aminobutyric acid (GABA) receptor. GABA may alleviate myocardial ischemia/reperfusion (I/R) injury; however, the impact of Rema and underlying molecular mechanism in myocardial I/R injury remain to be fully understood. Therefore, the present study aimed to investigate the effects of Rema on cardiac I/R injury and to determine the underlying mechanisms. An acute myocardial I/R model was established by ligating the left anterior descending artery in adult male C57BL/6 mice (8‑10 weeks). Cultured Raw264.7 cells treated with lipopolysaccharide (LPS) were also used to investigate the effect of Rema on macrophages. The results of the present study revealed that Rema improved I/R‑induced cardiac dysfunction by increasing the ejection fraction value and reducing the myocardial infarction area. In addition, Rema also alleviated I/R‑induced cardiac inflammatory cell infiltration based on H&E and immunofluorescence staining. Transmission electron microscopy and ROS measurements showed that Rema improved I/R‑induced mitochondrial structural disruption and oxidative stress in cardiomyocytes. Transcriptomics analysis and reverse transcription‑quantitative PCR revealed that Rema alleviated I/R‑induced release of inflammatory factors and cytokines by inhibiting the expression of IL‑1β, IL‑6, C‑C chemokine receptor 2 and C‑X‑C motif chemokine ligand 5. Rema also inhibited I/R‑induced CD68+ cell proliferation, IL‑1β release, and NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and IL‑1β expression. The results of <i>in vitro</i> assays revealed that Rema inhibited LPS‑induced increases in IL‑1β, IL‑6 and TNF‑α expression and release in cultured RAW264.7 macrophages. In conclusion, the present study revealed that Rema may alleviate I/R‑induced cardiac dysfunction and myocardial injury by inhibiting oxidative stress and inflammatory responses via the NLRP3/IL‑1β pathway.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065461","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":"The off‑target effect of loratadine triggers autophagy‑mediated apoptosis in lung adenocarcinoma cells by deactivating JNK, p38, and STAT3 signaling through both PP2A‑dependent and independent pathways.","authors":"Ming-Hsien Chien, Wen-Yueh Hung, Tsung-Ching Lai, Ching Han Tsai, Kai-Ling Lee, Feng-Koo Hsieh, Wei-Jiunn Lee, Jer-Hwa Chang","doi":"10.3892/ijmm.2025.5495","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5495","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a typical inflammation‑associated cancer, and anti‑inflammatory medications can be valuable in cancer therapy. Loratadine, a histamine receptor H1 (HRH1) antagonist, shows both anti‑inflammatory and anticancer properties. The present study aimed to evaluate impacts of loratadine on LUAD cells as well as in a LUAD xenograft mouse model, and explore underlying mechanisms. Mechanistic investigations were conducted through using western blotting, flow cytometry, immunohistochemistry, acridine orange staining, TUNEL assays, and <i>in silico</i> analyses of loratadine‑modulated genes in LUAD specimens. It was observed that loratadine inhibited LUAD cell proliferation and colony formation by inducing autophagy‑mediated apoptotic cell death independently of HRH1. In a LUAD xenograft model, loratadine decreased tumor proliferation and angiogenesis while enhancing autophagy and apoptosis. Mechanistically, loratadine induced protein phosphatase 2A (PP2A) activation to deactivate c‑Jun N‑terminal kinase (JNK)1/2 and p38 in H23 and PC9 LUAD cells. Additionally, loratadine inhibited signal transducer and activator of transcription 3 (STAT3) activation via a PP2A‑independent pathway. Furthermore, the combination of loratadine with inhibitors for JNK, p38 and STAT3 all enhanced proliferation inhibition of loratadine alone in both cell lines. In the clinic, patients with LUAD expressing high PP2A had favorable prognoses. The present study suggests that loratadine can be used as a PP2A activator for LUAD treatment, and the combination of repurposing loratadine with inhibitors of STAT3, JNK and p38 would be an effectively strategy for inhibiting LUAD growth.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065472","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":"Alda‑1 restores ALDH2‑mediated alcohol metabolism to inhibit the NF‑κB/VEGFC axis in head and neck cancer.","authors":"Yu-Hsuan Lin, Yi-Chen Lee, Jia-Bin Liao, Pei-Lun Yu, Chih-Yu Chou, Yi-Fang Yang","doi":"10.3892/ijmm.2025.5496","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5496","url":null,"abstract":"<p><p>The adaptation of cancer cells to hostile environments often necessitates metabolic pathway alterations to sustain proliferation and invasion. Head and neck cancer (HNC) has unfavorable outcomes. Therefore, elucidating the functional effects and molecular mechanisms underlying metabolic changes is key. Ingenuity Pathway Analysis identified 'ethanol degradation pathway II and IV' was consistently downregulated in tumor tissue, with aldehyde dehydrogenase 2 (<i>ALDH2</i>) emerging as a key prognostic gene among the top‑ranked differentially expressed metabolic pathways. Immunohistochemistry (IHC) of HNC specimens revealed significant downregulation of ALDH2 expression in tumor tissue, which was inversely correlated with T classification, overall stage, recurrence rate and independently predicted poor prognosis. Functional assays showed that ALDH2 knockdown enhanced HNC cell migration, invasion and colony formation, while ALDH2 overexpression attenuated these processes. Mechanistically, ALDH2 downregulation and subsequent reactive oxygen species (ROS) production in cells activated NF‑κB, upregulating vascular endothelial growth factor C (<i>VEGFC</i>) expression. ALDH2 overexpression inhibited ROS production and the NF‑κB/VEGFC oncogenic pathway, with pharmacological inhibition of NF‑κB and VEGFC mitigating the enhanced migration and invasion of ALDH2‑knockdown HNC cells. IHC and transcriptome analysis further highlighted an inverse association between ALDH2 and VEGFC, with the ALDH2^high/VEGFC^low profile predicting the most favorable survival outcome. Inhibition of ALDH2 with Daidzin increased <i>VEGFC</i> and phosphorylated NF‑κB levels, restoring the migration and invasion of ALDH2‑overexpressing HNC cells by enhancing the effects of VEGFC. Notably, modulating ALDH2 activity using Alda‑1 ameliorated NF‑kB/VEGFC axis upregulation following acetaldehyde treatment, aligning with the aforementioned alterations in alcohol metabolisms. These findings emphasize the key role of ALDH2 in influencing HNC progression and patient outcome, suggesting that targeting the ALDH2/NF‑κB/VEGFC pathway may represent a potential therapeutic strategy for HNC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065459","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":"Recent insights and perspectives into the role of the miRNA‑29 family in innate immunity (Review).","authors":"Xing-Chen Yao, Jun-Jie Wu, Sheng-Tao Yuan, Feng-Lai Yuan","doi":"10.3892/ijmm.2025.5494","DOIUrl":"10.3892/ijmm.2025.5494","url":null,"abstract":"<p><p>Innate immunity is the first line of defence against pathogenic microorganisms and is nearly universal among eukaryotes. The innate immune system is composed of various organs, cells and immune molecules. MicroRNAs (miRs) are a class of small non‑coding RNAs (~22 nucleotides) that are widely involved in post‑transcriptional regulation of proteins within the innate immune system through the recognition of seed sequences. The present review summarizes the role of the miR‑29 family in innate immunity, with a focus on its specific functions in the differentiation of T cells, B cells, natural killer cells and macrophages, as well as the mechanisms by which the miR‑29 family participates in innate immune signalling. Additionally, this review discusses how the miR‑29 family helps the host combat infections by hepatitis B and C viruses, human immunodeficiency virus and influenza A virus through the regulation of specific signalling molecules. This comprehensive analysis of existing studies emphasizes the importance of the miR‑29 family in maintaining immune balance and defence against pathogens.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065458","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":"Research progress on the molecular mechanisms of Saikosaponin D in various diseases (Review).","authors":"Simin Gu, Yiyuan Zheng, Chong Chen, Jing Liu, Yanping Wang, Junmin Wang, Yong Li","doi":"10.3892/ijmm.2024.5478","DOIUrl":"10.3892/ijmm.2024.5478","url":null,"abstract":"<p><p>Bupleurum, a Traditional Chinese Medicine (TCM) herb, is widely used in China and other Asian countries to manage chronic liver inflammation and viral hepatitis. Saikosaponin D (SSD), a triterpenoid saponin extracted from Bupleurum, exhibits extensive pharmacological properties, including anti‑inflammatory, antioxidant, anti‑apoptotic, anti‑fibrotic and anti‑cancer effects, making it a therapeutic candidate for numerous diseases. Clarifying the targets and molecular mechanisms underlying TCM compounds is essential for scientifically validating TCM's therapeutic roles in disease prevention and treatment, as well as for identifying novel therapeutic targets and lead compounds. This analysis comprehensively examines SSD's mechanisms across various conditions, such as myocardial injury, pulmonary diseases, hepatic disorders, renal pathologies, neurological disorders, diabetes and cancer. In addition, challenges and potential solutions encountered in SSD research are addressed. SSD is posited as a promising monomer for multifaceted therapeutic applications and this article aims to enhance researchers' understanding of the current landscape of SSD studies, offering strategic insights to guide future investigations.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880955","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":"Protective role of triiodothyronine in sepsis‑induced cardiomyopathy through phospholamban downregulation.","authors":"Qiumin Xie, Qin Yi, Jing Zhu, Bin Tan, Han Xiang, Rui Wang, Huiwen Liu, Tangtian Chen, Hao Xu","doi":"10.3892/ijmm.2025.5488","DOIUrl":"10.3892/ijmm.2025.5488","url":null,"abstract":"<p><p>Sepsis is often a cause of mortality in patients admitted to the intensive care unit. Notably, the heart is the organ most susceptible to the impact of sepsis and this condition is referred to as sepsis‑induced cardiomyopathy (SIC). Low triiodothyronine (T3) syndrome frequently occurs in patients with sepsis, and the heart is one of the most important target organs for the action of T3. Phospholamban (PLN) is a key protein associated with Ca²⁺‑pump‑mediated cardiac diastolic function in the myocardium of mice with SIC, and PLN is negatively regulated by T3. The present study aimed to explore whether T3 can protect cardiac function during sepsis and to investigate the specific molecular mechanism underlying the regulation of PLN by T3. C57BL/6J mice and H9C2 cells were used to establish <i>in vivo</i> and <i>in vitro</i> models, respectively. Myocardial damage was detected via pathological tissue sections, a Cell Counting Kit-8 assay, an apoptosis assay and crystal violet staining. Intracellular calcium levels and reactive oxygen species were detected by Fluo‑4AM and DHE fluorescence. The protein and mRNA expression levels of JNK and c‑Jun were measured by western blotting and reverse transcription‑quantitative PCR to investigate the molecular mechanisms involved. Subsequently, 100 clinical patients were recruited to verify the clinical application value of PLN in SIC. The results revealed a significant negative correlation between PLN and T3 in the animal disease model. Furthermore, the expression levels of genes and proteins in the JNK/c‑Jun signaling pathway and PLN expression levels were decreased, whereas the expression levels of sarcoplasmic reticulum calcium ATPase were increased after T3 treatment. These results indicated that T3 alleviated myocardial injury in SIC by inhibiting PLN expression and its phosphorylation, which may be related to the JNK/c‑Jun signaling pathway. Accordingly, PLN may have clinical diagnostic value in patients with SIC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005158","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":"Iron metabolism and the tumor microenvironment: A new perspective on cancer intervention and therapy (Review).","authors":"Xiaorui Bu, Lufang Wang","doi":"10.3892/ijmm.2024.5480","DOIUrl":"10.3892/ijmm.2024.5480","url":null,"abstract":"<p><p>Iron metabolism plays a crucial role in the tumor microenvironment, influencing various aspects of cancer cell biology and tumor progression. This review discusses the regulatory mechanisms of iron metabolism within the tumor microenvironment and highlights how tumor cells and associated stromal cells manage iron uptake, accumulation and regulation. The sources of iron within tumors and the biological importance of ferroptosis in cancer were explored, focusing on its mechanisms, biological effects and, in particular, its tumor‑suppressive properties. Furthermore, the protective strategies employed by cancer cells to evade ferroptosis were examined. This review also delves into the intricate relationship between iron metabolism and immune modulation within the tumor microenvironment, detailing the impact on tumor‑associated immune cells and immune evasion. The interplay between ferroptosis and immunotherapy is discussed and potential strategies to enhance cancer immunotherapy by modulating iron metabolism are presented. Finally, the current ferroptosis‑based cancer therapeutic approaches were summarized and future directions for therapies that target iron metabolism were proposed.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921597","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":"Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.","authors":"Yingle Jiang, Xuewei Wen, Xiaoyu Jian, Qianbo Chen, Yan Li","doi":"10.3892/ijmm.2025.5486","DOIUrl":"10.3892/ijmm.2025.5486","url":null,"abstract":"<p><p>Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis. The aim of the present study was to explore the effects of klotho on subretinal fibrosis induced by laser photocoagulation in mice and EMT induced by TGF‑β1 in RPE cells and the underlying molecular mechanisms. <i>In vitro</i>, klotho overexpression or knockdown was performed in ARPE‑19 cells (adult retinal Pigment Epithelial‑19), then TGF‑β1 treatment was applied. Using western blotting, expression of epithelial markers (zonula occludens‑1), mesenchymal signs (α‑smooth muscle actin, α‑SMA, N‑cadherin, N‑cad and collagen I), and the ERK1/2 and Wnt/β‑catenin signaling pathways were assessed. The proliferative ability of ARPE‑19 cells was examined by CCK‑8 and EdU test, and the migratory ability was examined by wound healing and Transwell assays. Furthermore, to explore the underlying molecular pathway of klotho overexpression, RNA‑sequencing (seq) was performed. <i>In vivo</i>, photocoagulation was used to induce subretinal fibrosis in mice, which occurs as a result of choroidal neovascularization (CNV), then recombinant mouse klotho protein was administered intravitreally. Upregulation of epithelial and downregulation of mesenchymal markers demonstrated that klotho overexpression prevented TGF‑β1‑induced EMT; klotho knockdown resulted in the opposite effects. Additionally, klotho overexpression suppressed cell proliferation and migration and attenuated ERK1/2 and Wnt/β‑catenin signaling activated by TGF‑β1. RNA‑seq results demonstrated that several signaling pathways, including cellular senescence and the TNF signaling pathway, were associated with anti‑fibrotic effects of klotho overexpression. <i>In vivo</i>, subretinal fibrotic areas were attenuated following klotho treatment in laser‑induced CNV lesions, as illustrated by immunofluorescence and Masson staining of the mouse eyes. Western blotting results that the protein levels of mesenchymal markers were significantly downregulated and those of epithelial markers were upregulated. In summary, the present study suggested that klotho may have therapeutic value in management of fibrotic vitreoretinal disorders such as subretinal fibrosis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948113","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":"Mitochondrial calcium uniporter complex: An emerging therapeutic target for cardiovascular diseases (Review).","authors":"Yaling Li, Hongmin Hu, Chun Chu, Jun Yang","doi":"10.3892/ijmm.2024.5481","DOIUrl":"10.3892/ijmm.2024.5481","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is currently a major factor affecting human physical and mental health. In recent years, the relationship between intracellular Ca²⁺ and CVD has been extensively studied. Ca²⁺ movement across the mitochondrial inner membrane plays a vital role as an intracellular messenger, regulating energy metabolism and calcium homeostasis. It is also involved in pathological processes such as cardiomyocyte apoptosis, hypertrophy and fibrosis in CVD. The selective mitochondrial calcium uniporter complex (MCU complex) located in the inner membrane is essential for mitochondrial Ca²⁺ uptake. Therefore, the MCU complex is a potential therapeutic target for CVD. In this review, recent research progress on the pathophysiological mechanisms and therapeutic potential of the MCU complex in various CVDs was summarized, including myocardial ischemia‑reperfusion injury, pulmonary arterial hypertension, other peripheral vascular diseases, myocardial remodeling and arrhythmias. This review contributes to a deeper understanding of these mechanisms at the molecular level and highlights potential intervention targets for CVD treatment in clinical practice.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921606","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}