International journal of molecular medicine最新文献

{"title":"Function of epigenetic modifications in wound healing and potential therapies (Review).","authors":"Jing Cheng, Weiwei Qian, Fang Chen, Xingqin Liu, Min Fu, Wei Cao, Yue Zhou","doi":"10.3892/ijmm.2025.5631","DOIUrl":"10.3892/ijmm.2025.5631","url":null,"abstract":"<p><p>Wound healing is a highly coordinated physiological process, which is essential for restoring the structural and functional integrity of damaged tissues. The present review explores the multifaceted roles of epigenetic modifications in wound healing and their potential as therapeutic targets. Epigenetic mechanisms, including DNA methylation, histone modifications, regulation by non‑coding RNAs (ncRNAs) and RNA methylation, influence the speed and quality of wound repair by regulating gene expression, cell function and intercellular signaling. During the hemostasis phase, DNA methylation of genes such as platelet endothelial aggregation receptor 1 can impact platelet function, while histone methylation and acetylation serve critical roles in modulating inflammation and fibroblast activation. ncRNAs, such as microRNAs and long ncRNAs, regulate cell proliferation, collagen deposition and scar formation. N6‑methyladenosine modifications, a type of RNA methylation, impact autophagy and fibrosis through their interaction with YTH domain family proteins. Key epigenetic regulators influence wound healing outcomes, providing valuable insights for the development of novel therapeutic strategies. However, challenges remain in translating these findings into clinical applications due to the complexity of epigenetic networks and the need for precise regulatory tools. Future research should focus on elucidating the cell‑specific and spatiotemporal regulatory mechanisms of epigenetic modifications in wound healing, and exploring their potential as therapeutic targets for reducing scar formation and preventing chronic wounds.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040185","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":"Copper homeostasis and cuproptosis in Alzheimer's disease (Review).","authors":"Chao Cong, He Cong, Yuan Yao, Yuquan Bai, Lianwei Xu","doi":"10.3892/ijmm.2025.5613","DOIUrl":"10.3892/ijmm.2025.5613","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuroinflammation, synaptic dysfunction and neuronal loss. Research has revealed a connection between copper metabolism and the pathophysiology of AD, particularly through a newly identified form of copper‑dependent cell death referred to as cuproptosis. Cuproptosis is driven by the aggregation of lipoylated proteins and proteotoxic stress caused by excessive copper accumulation, leading to cellular demise, which is a key event in AD. While studies on copper levels in the brain in AD remain inconclusive, there is mounting evidence suggesting that an imbalance in copper homeostasis, particularly elevated labile copper levels, contributes to oxidative damage and neurodegeneration in patients with AD. The present review examines the role of cuproptosis in AD and discusses how targeting this pathway may provide novel therapeutic opportunities. By investigating the underlying mechanisms and potential clinical implications, the present review highlights that regulation of cuproptosis provides a promising approach for modulating disease progression and developing personalized treatment strategies for AD.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953316","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":"Takotsubo syndrome: Unraveling the mystery behind its triggers (Review).","authors":"Xuehui Fan, Yanlin Yuan, Zuchuan Huang, Liulu Zhang, Binyi Zhao, Dechou Zhang, Yong Liu, Guiquan Chen, Ping Liu, Guoqiang Yang","doi":"10.3892/ijmm.2025.5615","DOIUrl":"10.3892/ijmm.2025.5615","url":null,"abstract":"<p><p>Takotsubo syndrome (TTS) is a clinical condition characterized by left ventricular dysfunction, clinically mimicking acute coronary syndrome. Despite significant advancements in understanding TTS, more questions about its underlying pathological mechanisms remain unresolved. The present review offered current data on the underlying pathological mechanisms of TTS, including central nervous system structural and functional alterations, sympathetic nervous system overstimulation, excessive catecholamine secretion, shifts in adrenergic receptors (ARs) distribution and balance, hormone influences, epicardial vasospasm, endothelial dysfunction and genetic predispositions. For example, stressors from physical or emotional triggers induce central neurohumoral activation by influencing the hippocampus and amygdala, which results in excessive local or systemic secretion. This catecholamine surge affects the myocardium by altering cellular metabolism, disrupting signaling pathways and impairing endothelial function. The regional myocardial effects are influenced by the modified ARs distribution and the density of autonomic innervation, which are pivotal in the onset of TTS. These insights suggest potential therapeutic strategies, including cognitive behavioral therapy, endothelin A antagonists and β‑blockers. However, the complex interplay of these factors in TTS onset remains poorly understood. Further research is essential to elucidate the intricate mechanisms and interactions underlying this syndrome, paving the way for improved prevention and treatment approaches.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953324","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":"Role of cellular senescence in hepatic diseases (Review).","authors":"Yunqi Xing, Junfeng Zhu","doi":"10.3892/ijmm.2025.5623","DOIUrl":"10.3892/ijmm.2025.5623","url":null,"abstract":"<p><p>Cellular senescence, a hallmark of aging, is characterized by irreversible, permanent cell cycle arrest accompanied by halted proliferation triggered by endogenous or exogenous stimuli. The accumulation of senescent cells in tissues or organs elicits detrimental effects on adjacent normal cells through their pathogenic senescence‑associated secretory phenotype (SASP), driving secondary senescence, disrupting tissue homeostasis and ultimately exacerbating age‑related pathologies such as types of cancer and neurodegenerative disorders. Hepatic disorders constitute a leading cause of global mortality, imposing considerable healthcare burdens. Robust clinical evidence has now demonstrated a strong correlation between cellular senescence and poor clinical outcomes in various hepatopathies. This intricate yet critical signaling network is dynamically regulated in both physiological homeostasis and chronic hepatic inflammatory conditions. Notably, recent years have witnessed extensive research into pharmacological strategies to deplete senescent cells, inhibit SASP, and target other senescence markers across diverse contexts, thereby establishing the field of senotherapeutics. The present review systematically summarized key molecular pathways and biomarkers of hepatic senescence, while outlining the emerging role of cellular senescence in inflammatory liver disorders. It also discussed the therapeutic potential of senescence‑regulating drugs for liver disease, which could alleviate hepatic inflammation and enhance clinical outcomes.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000547","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":"Piezo knockdown reduces 5‑hydroxytryptamine release from enterochromaffin cells and exacerbates intestinal dyskinesia in mice with functional constipation.","authors":"Xiangyun Yan, Peitao Ma, Wen Wang, Weijian Zeng, Yanqiu Li, Yujun Hou, Jiangnan Ye, Qianhua Zheng, Wei Zhang, Junpeng Yao, Ying Li","doi":"10.3892/ijmm.2025.5619","DOIUrl":"10.3892/ijmm.2025.5619","url":null,"abstract":"<p><p>Enterochromaffin (EC) cell dysfunction decreases 5‑hydroxytryptamine (5‑HT) secretion, contributing to functional constipation (FC). However, the underlying mechanisms remain unclear. Piezo ion channels mediate 5‑HT release from EC cells. The present study investigated the roles and mechanisms of Piezo1 and Piezo2 in the pathogenesis of FC and explored possible interactions. In a loperamide‑induced FC mouse model, Piezo1 and Piezo2 were singly or simultaneously knocked down using adeno‑associated viruses. In vitro, their function in EC cells was assessed via lentiviral‑mediated knockdown in the QGP‑1 cell line. In FC mice, the expression of Piezo1 and Piezo2, along with their colocalization with EC cells, was significantly reduced. Knockdown of either channel impaired intestinal motility, prolonged gastrointestinal transit time, delayed gastric emptying and reduced small intestinal propulsion. Correspondingly, 5‑HT, 5‑HT₃ receptor and tryptophan hydroxylase‑1 (TPH‑1) levels were decreased. Dual knockdown exacerbated these effects, resulting in colon structural abnormalities, decreased substance P expression and increased serotonin transporter levels. Knockdown of Piezo1 or Piezo2 reduced ERK and protein kinase C (PKC) phosphorylation in colonic tissues, with combined knockdown producing a more pronounced suppression of PKC phosphorylation. Consistently, dual knockdown in EC‑like cells led to more pronounced reductions in intracellular calcium, 5‑HT and TPH‑1 compared with single knockdowns. These findings demonstrated that Piezo1 and Piezo2 play critical and cooperative roles in maintaining intestinal homeostasis in FC mice by jointly inducing calcium ion influx in EC cells, thereby coordinating 5‑HT signaling homeostasis. Targeting Piezo channels may offer novel therapeutic avenues for managing functional constipation.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000582","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":"Contribution of insulin‑like growth factor‑1 to tendon repair (Review).","authors":"Yixuan Chen, Yuchen Zhu, Siqi Song, Yushi Hu","doi":"10.3892/ijmm.2025.5636","DOIUrl":"10.3892/ijmm.2025.5636","url":null,"abstract":"<p><p>Tendinopathy is a common musculoskeletal disorder that markedly diminishes both physical performance and overall quality of life across age groups, imposing considerable socio‑economic burdens. Insulin‑like growth factor‑1 (IGF‑1) functions as a protective cytokine with significant involvement in multiple pathological conditions, including tendinopathy. The present review integrated current evidence on the role of IGF‑1 in tendon repair. IGF‑1 actively participates in every phase of tendon repair, making it a central driver of the injury response. When administered for tendon repair, IGF‑1 binds to IGF‑1R on target cell membranes, initiating sequential phosphorylation cascades that transmit signals from the membrane to the nucleus, while IGFBPs finely modulate this process. These intricate signaling pathways ultimately yield beneficial effects such as reduced inflammation, enhanced cell proliferation and migration and increased collagen synthesis, thereby promoting restoration of tendon structure and integrity. IGF‑1 has emerged as one of the most promising growth factors in tendon regenerative strategies. Nevertheless, clarification of critical parameters such as administration dosage and timing remains necessary to optimize its therapeutic value and to fully delineate its contribution to tendon repair.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040162","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":"Noncoding RNAs in periodontitis: Progress and perspectives (Review).","authors":"Yuanyi Feng, Xiaolan Guo, Yumeng Yang, Wei Qiu, Zhao Chen, Fuchun Fang","doi":"10.3892/ijmm.2025.5607","DOIUrl":"10.3892/ijmm.2025.5607","url":null,"abstract":"<p><p>Periodontitis is the sixth most common chronic non‑infectious disease in the world. It mainly leads to the inflammatory destruction of periodontal supporting tissue, which has become the main cause of tooth loss in adults. Periodontitis is also a risk factor for various systemic diseases. Noncoding ribonucleic acids (ncRNAs) are important regulators of normal biological processes and their abnormal expression has been shown to be important to the pathogenesis of inflammatory diseases, including periodontitis. Biologically, they can regulate immune inflammation, bone homeostasis and cell proliferation in periodontitis. Clinically, they are promising diagnostic markers and therapeutic targets. Recent advances in technology have opened up new directions for the study of ncRNAs, including RNA secondary structures, RNA protein interactions, ncRNA‑encoded peptides or proteins and single‑cell RNA sequencing. Therefore, the present study summarized the function and mechanisms of ncRNAs in periodontitis, as well as their clinical potential for diagnosis and treatment and highlight these exciting areas of research.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845875","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":"Pathogen virulence genes: Advances, challenges and future directions in infectious disease research (Review).","authors":"Yun Chen, Xiaolong Wu, Chengcheng Xu, Jianxiang Huang, Lingyu Zhang, Peng Qiu, Danling Zheng, Wang Chen, Shuyao Zhang","doi":"10.3892/ijmm.2025.5614","DOIUrl":"10.3892/ijmm.2025.5614","url":null,"abstract":"<p><p>Pathogens, including bacteria, viruses and fungi, employ virulence genes to invade their hosts, circumvent immunity and induce diseases. The present review examines the categorization and regulatory mechanisms of virulence genes and their co‑evolution with antimicrobial resistance. The present review focused on the fimbrial adhesion H adhesion gene of <i>Escherichia coli</i>, the spike protein gene of severe acute respiratory syndrome coronavirus 2 and the enhanced filamentous growth protein 1 (EFG1) morphological transition gene of <i>Candida albicans</i>, as well as their roles in host adhesion, immune evasion and tissue damage. Application of technologies, including multi‑omics integration, artificial intelligence and CRISPR‑based genome editing, is discussed in the context of precision diagnostics, targeted therapy and vaccine development. By elucidating pathogen adaptation dynamics and host‑pathogen interactions, the present review offers a basis for reducing the global burden of drug‑resistant infections through improved surveillance and personalized interventions.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953355","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":"Ferroptosis and head and neck cancer: Mechanisms and therapeutic perspectives (Review).","authors":"Chenglin Kang, Xiaomei Li, Xudong Wei","doi":"10.3892/ijmm.2025.5625","DOIUrl":"10.3892/ijmm.2025.5625","url":null,"abstract":"<p><p>Head and neck cancer (HNC) is a common malignant disease in otorhinolaryngology; however, its pathogenesis remains to be fully elucidated. Currently, the treatment for HNC mainly comprises surgery assisted by other methods, including radiotherapy, chemotherapy and immunotherapy. After surgical treatment, the laryngeal function, and swallowing and breathing abilities of patients can be affected to a certain extent, and the loss of vocal ability can cause daily communication obstacles and affect the physical and mental health of patients. HNC recurrence makes retreatment challenging. Ferroptosis is a type of iron‑dependent regulated cell death caused by plasma membrane rupture and lipid peroxidation, and its occurrence is related to HNC. The present review aimed to describe the organelles that influence ferroptosis, the factors that activate and inhibit ferroptosis, and the role of ferroptosis in the pathogenesis, treatment and prognosis of HNC.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000574","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‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration.","authors":"Qiuwei Li, Chenhao Zhao, Peilin Jin, Cailiang Shen","doi":"10.3892/ijmm.2025.5634","DOIUrl":"10.3892/ijmm.2025.5634","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a major cause of chronic back pain, yet its molecular mechanisms remain poorly understood despite its high prevalence. In the present study, the significant role of microRNA (miR)‑27b‑3p in regulating 731 immune cell types was systematically uncovered utilizing Mendelian randomization (MR) and single‑cell RNA sequencing, with a particular focus on CD4⁺CD39⁺ regulatory T cells (Tregs); and its critical impact on immune‑mediated IVDD progression was highlighted. A total of 76 miRs were screened and, through MR analysis, a significant causal relationship between miR‑27b‑3p and IVDD was identified. Subsequent <i>in vivo</i> and <i>in vitro</i> experiments demonstrated that miR‑27b‑3p overexpression not only promoted apoptosis of nucleus pulposus cells but also accelerated IVDD by modulating the immune functions of CD4+CD39+ Tregs. Single‑cell RNA sequencing further revealed a marked upregulation of immune‑related genes in degenerated discs, particularly those involved in immune cell migration, inflammation and apoptotic regulation pathways. These findings suggest that miR‑27b‑3p plays a pivotal role in IVDD by influencing various immune cells, especially CD4+CD39+ Tregs, underscoring its potential as a therapeutic target with significant clinical implications. Further research into the mechanisms of miR‑27b‑3p could open new avenues for IVDD treatment strategies, offering promising possibilities for future clinical applications.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040194","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}