International journal of molecular medicine最新文献

{"title":"Lactate and lactylation in the kidneys: Current advances and prospects (Review).","authors":"Xu Li, Lan Hu, Qin Hu, Hua Jin","doi":"10.3892/ijmm.2025.5562","DOIUrl":"10.3892/ijmm.2025.5562","url":null,"abstract":"<p><p>Lactate, traditionally overlooked as a glycolytic byproduct, has recently been recognized for its significant biological roles. The normal kidney plays an essential role in maintaining systemic glucose and lactate homeostasis. Lactylation, as a new epigenetic modification, influences the initiation and progression of kidney diseases through the regulation of gene transcription and cellular metabolism. The present review summarizes current perspectives on the physiological functions of lactate and its renal metabolism, analyzes the roles of lactate and lactylation in acute kidney injury, diabetic nephropathy and chronic kidney disease, and proposes that targeted modulation of lactate metabolism may represent a promising therapeutic strategy for kidney disorders, thereby providing a foundation for future investigations.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234031","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 and mechanisms of cuproptosis in the pathogenesis of Wilson's disease (Review).","authors":"Hong Chen, Xie Wang, Jin Xing, Yue Pu, Hao Ye, Ying Ma, Juan Zhang","doi":"10.3892/ijmm.2025.5558","DOIUrl":"10.3892/ijmm.2025.5558","url":null,"abstract":"<p><p>Copper, an indispensable trace element in living organisms, plays a pivotal role in human physiological processes. Wilson's disease (WD), an inherited disorder of copper metabolism, is caused by mutations in the ATP7B gene. This genetic malfunction disrupts the dynamics of copper transport and metabolism, thereby impairing ceruloplasmin synthesis and copper excretion. The resultant accumulation of copper in various tissues and organs precipitates a cascade of cellular demise and functional impairment. Notably, cuproptosis, a recently discovered copper‑dependent regulated cell death mechanism, distinctly deviates from conventional cell death paradigms. This novel mode of cell death involves the interaction of copper with lipoacylated proteins within the tricarboxylic acid cycle, leading to proteinotoxic stress and culminating in cell death. In the realm of pathophysiology, cuproptosis has emerged as a pivotal player in a spectrum of diseases, with WD standing as a paradigm closely intertwined with the dysregulation of copper metabolism. This study aimed to encapsulate the pivotal molecular underpinnings of cuproptosis and delve into its crucial involvement in the etiopathogenesis of WD. By elucidating these mechanisms, the present analysis contributes significantly to the nuanced understanding of the pathological underpinnings of WD, thereby providing fresh insights and evidence that may direct innovative therapeutic strategies for this condition.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234033","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":"[Corrigendum] miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease.","authors":"Xinrong Li, Wenwen Si, Zhan Li, Ye Tian, Xuelei Liu, Shanyu Ye, Zifeng Huang, Yichun Ji, Caiping Zhao, Xiaoqian Hao, Dongfeng Chen, Meiling Zhu","doi":"10.3892/ijmm.2025.5565","DOIUrl":"10.3892/ijmm.2025.5565","url":null,"abstract":"<p><p>Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the JC‑1 staining experiments shown in Fig. 5F on p. 9, the 'mimic NC' and 'inhibitor' panels appeared to show the same cells, even though the green/red ratio was different comparing between the two data panels. In addition, two further instances of duplicated data panels were identified in Figs. S2 and S3, such that data that were allegedly obtained under different experimental conditions appeared to have been derived from the same original sources. After having asked the authors to explain the errors that had occurred in assembling these figures, they responded to explain that the error in Fig. 5F resulted from the incorrect selection of source images for the channels during the image merging process, whereas the errors in Figs. S2 and S3 occurred due to mistakes made in the naming and management of image files during storage. This led to the unintentional use of incorrect images during the process of figure assembly. Moreover, the authors were able to present to the Editorial Office the original data from the JC‑1 staining experiments belonging to Fig. 5F. The Editor of <i>International Journal of Molecular Medicine</i> has agreed that a corrigendum may be published to account for the errors made in assembling Figs. 5, S2 and S3, and the corrected versions of these figures are shown on the next page. All the authors agree with the publication of this corrigendum, and are thankful to the Editor for giving them the opportunity to present this; moreover, the Editor and the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 61, 2021; DOI: 10.3892/ijmm.2021.4894].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283853","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":"Lobetyolin alleviates IMQ‑induced psoriasis‑like skin inflammation by maintaining the homeostasis of the skin and inhibiting the inflammatory cytokines in dendritic cells.","authors":"Jianping He, Chenxi Feng, Yaohan Xu, Siji Chen, Jie Chen, Jingying Pan, Yinjing Song, Hao Cheng, Jiang Zhu, Jie Zhu","doi":"10.3892/ijmm.2025.5563","DOIUrl":"10.3892/ijmm.2025.5563","url":null,"abstract":"<p><p>Psoriasis, the most common inflammatory skin disease, is marked by excessive proliferation of keratinocytes and infiltration of immune cells into the epidermis. Current treatments, particularly biologics targeting the IL‑23/IL‑17 axis, demonstrate excellent efficacy, but issues of recurrence and side effects persist. Therefore, it is essential to identify safer and more effective alternatives. Lobetyolin (LBT), a key component of polyacetylenes in <i>Codonopsis pilosula</i>, exhibits potent antioxidant and antitumor properties, yet its potential for treating psoriasis remains unexplored. In the present study, it was found that topical treatment with LBT significantly inhibits psoriasis in mice and maintains skin homeostasis during disease progression by regulating genes associated with keratinocyte proliferation and differentiation, enhancing the PPAR signaling pathway, and upregulating genes and metabolites involved in linoleic acid metabolism. Additionally, LBT suppressed gene expression linked to cytokine activity as well as the <i>Il17</i>, Tnf and MAPK signaling pathways in IMQ‑treated dendritic cells (DCs). These findings underscored LBT's efficacy in reducing IMQ‑induced psoriasis‑like skin inflammation by preserving skin homeostasis and inhibiting inflammatory cytokines in DCs. The present results suggested that topically applied LBT could serve as a promising drug candidate for psoriasis treatment or as an adjunct to biologic therapies to prevent disease relapse.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283854","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 status and future perspectives of IL‑27 in the treatment of stroke (Review).","authors":"Weiqin Liu, Zhenyou Zou, Wenyang Li, Guang Yang, Jie Zhang, Zhenyu Zhang, Hua Yao","doi":"10.3892/ijmm.2025.5557","DOIUrl":"10.3892/ijmm.2025.5557","url":null,"abstract":"<p><p>Stroke is a life‑threatening cerebrovascular disorder categorized into two major subtypes: Ischemic and hemorrhagic. Characterized by high morbidity and mortality rates, its clinical management remains challenging due to limited therapeutic options. Interleukin (IL)‑27, a pleiotropic cytokine with demonstrated neuroprotective potential, has emerged as a promising candidate for stroke intervention. IL‑27 exerts immunomodulatory effects within the central nervous system, including suppression of proinflammatory T‑cell proliferation and induction of regulatory T‑cell differentiation. These mechanisms collectively attenuate neuroinflammation, mitigate neuronal apoptosis and prevent neurodegenerative processes. The efficacy of IL‑27 in reducing cerebral damage in both ischemic and hemorrhagic stroke models has been validated, although clinical translation remains to be achieved. The present review summarizes: i) The epidemiology of stroke; ii) the immunoregulatory functions of IL‑27 and its neuroprotective mechanisms across stroke subtypes; iii) innovative brain‑targeted delivery approaches; iv) IL‑27 clinical applicability with supporting evidence; and v) possible risks and solutions in clinical applications. By collating the current knowledge, the present study provides a translational framework for advancing IL‑27‑based therapies in stroke management.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179893","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":"Molecular mechanisms and intervention approaches of heart failure (Review).","authors":"Shuang Guo, Yingqing Hu, Li Ling, Zhuangzhuang Yang, Luxuan Wan, Xiaosong Yang, Min Lei, Xiying Guo, Zhanhong Ren","doi":"10.3892/ijmm.2025.5566","DOIUrl":"10.3892/ijmm.2025.5566","url":null,"abstract":"<p><p>Heart failure is a major health issue that threatens life and health. Previous studies have shown that heart failure is the terminal stage of arrhythmia, dilated cardiomyopathy, hypertension, hypertrophic cardiomyopathy and myocardial infarction. The pathological mechanisms through which cardiovascular diseases result in heart failure include myocardial fibrosis and hypertrophy, myocardial cell death, mitochondrial dysfunction, vascular remodeling and calcium dysregulation. However, the detailed molecular mechanisms of heart failure remain elusive because of its complexity, hindering the development of intervention approaches for heart failure. The present study reviewed recent research progress on heart failure and provided references and strategies for the prevention and treatment of heart failure.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283855","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":"Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).","authors":"Hiroshi Kobayashi, Shogo Imanaka","doi":"10.3892/ijmm.2025.5559","DOIUrl":"10.3892/ijmm.2025.5559","url":null,"abstract":"<p><p>Mitochondria and mitochondrial DNA (mtDNA) are crucial for cellular energy metabolism and the adaptive response to environmental changes. mtDNA collaborates with the nuclear genome to regulate mitochondrial function. Dysfunctional mitochondria and mutations in mtDNA are implicated in a wide range of diseases, including mitochondrial disorders, neurodegenerative conditions, age‑associated pathologies and cancer. While the nuclear genome has been extensively studied for its role in driving the clonal expansion of oncogenes and other aging‑related genetic alterations, knowledge regarding mtDNA remains comparatively limited. However, advances in quantitative analysis have provided information regarding the complex patterns of mtDNA mutations. The present review offers a detailed examination of mtDNA mutations and their classifications in the contexts of aging and cancer, and elucidates the role of mtDNA mutations in these processes. Mutations in mtDNA can be detected as early as the neonatal stage, yet most transition mutations retain a normal cellular phenotype. In contrast to mutations in oncogenes and tumor suppressor genes within the nuclear genome, mtDNA exhibits conserved mutational signatures, irrespective of cancer tissue origin. To adapt to the aging process, mitochondria undergo clonal expansion of advantageous mtDNA mutations, maintaining a dynamic equilibrium among various mitochondrial clones. Over time, however, the loss of strand bias can disrupt this equilibrium, diminishing the pool of adaptive clones. This breakdown in mitochondrial homeostasis may contribute to tumorigenesis. In conclusion, the heterogeneity of mtDNA mutations and the collapse of its homeostasis are pivotal in the progression of age‑related diseases, including cancer, underscoring the importance of mtDNA mutations in health and disease.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234034","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":"Epigenetic roles of chromatin remodeling complexes in bone biology and the pathogenesis of bone‑related disease (Review).","authors":"Wenxiao Wu, Yinxing Cui, Yuqi Wu, Yan Ni, Chunling Zhao, Weichao Sun, Qian Yi","doi":"10.3892/ijmm.2025.5556","DOIUrl":"10.3892/ijmm.2025.5556","url":null,"abstract":"<p><p>Chromatin remodeling complexes are essential regulators of chromatin architecture, facilitating critical processes such as nucleosome sliding, eviction, histone exchange and post‑translational modifications. By providing an additional layer of epigenetic regulation beyond the canonical genetic code, these complexes significantly influence bone biology and health. Epigenetic regulation through chromatin remodeling complexes is crucial in modulating gene expression and cellular behavior in bone cells. However, alterations in the activity of chromatin remodeling complexes can also contribute to the progression of various bone diseases. Emerging evidence suggests that specific chromatin remodeling factors may serve as potential biomarkers for diagnosing bone‑related conditions and as therapeutic targets for intervention. The present review aims to elucidate the intricate relationship between chromatin remodeling complexes and bone‑related diseases, including osteoporosis, osteoarthritis and osteosarcoma. The present review discusses the diverse subunits of these complexes and their multifaceted roles in regulating key cellular processes such as stemness, differentiation, proliferation, senescence and apoptosis in bone cells. Notably, the present review provides a comprehensive overview of the roles of various chromatin remodeling subunits, such as BRG1, BAF47 and chromodomain‑helicase‑DNA binding 7 (CHD7), in bone metabolism, highlighting their disease‑specific mechanisms, including bromodomain‑containing protein (BRD)9‑mediated pyroptosis in intervertebral disc degeneration and CHD7‑driven bone‑fat imbalance. Furthermore, the present review highlights the therapeutic potential of targeting dysfunctional subunits (such as BRD7 in osteosarcoma and SS18 in synovial sarcoma) and propose AI‑driven structural biology approaches to design chemical modulators. The understudied impact of aging on chromatin remodeling activity in bone homeostasis is also underscored, advocating for longitudinal studies to address this gap. Finally, the distinct functions of each chromatin remodeling complex and its specific subunits in the context of bone‑related diseases were also explored, providing a comprehensive understanding of their contributions to both normal bone physiology and pathological conditions.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180502","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":"The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).","authors":"Feifan He, Qiuchen Zhang, Yunjie Chen, Suli Ge, Yidai Xie, Ruihong Sun, Yuqing Wu, Jian Xu","doi":"10.3892/ijmm.2025.5564","DOIUrl":"10.3892/ijmm.2025.5564","url":null,"abstract":"<p><p>Cyclin‑dependent kinase (CDK)4/6 inhibitors regulate the cell cycle by binding to CDK4/6, thus exerting an inhibitory effect, and they have a notable impact on tumor immunity. CDK4/6 inhibitors have been demonstrated to modulate the immune microenvironment by affecting immune cells and immune escape phenomena in the tumor microenvironment. T cells, natural killer cells and macrophages are all regulated by CDK4/6 inhibitors, thereby acting on cancer cells. In addition, these inhibitors modulate immune checkpoints, enhancing antitumor immune responses when combined with immune checkpoint inhibitors, such as programmed death‑ligand 1 and programmed death‑1. However, these inhibitors are not without limitations, as they can enhance tumor immune evasion. Therefore, combination therapies to improve efficacy are being investigated, including immunotherapy, targeted therapy, chemotherapy and radiation therapy. In addition, challenges associated with the widespread use of CDK4/6 inhibitors, such as the emergence of tumor resistance, underscore the necessity for further research to enhance the clinical applicability of these inhibitors.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283856","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":"Insight into microbial extracellular vesicles as key communication materials and their clinical implications for lung cancer (Review).","authors":"Jeong Yun Jang, Ji Hoon Seo, Jae Jun Choi, Hyun Jin Ryu, Hyunjun Yun, Dong Myeong Ha, Jinho Yang","doi":"10.3892/ijmm.2025.5560","DOIUrl":"10.3892/ijmm.2025.5560","url":null,"abstract":"<p><p>The complexity of lung cancer, driven by multifactorial causes such as genetic, environmental and lifestyle factors, underscores the necessity for tailored treatment strategies informed by recent advancements. Studies highlight a significant association between the lung microbiome and lung cancer, with dysbiosis potentially contributing to disease development via inflammation, immune response alterations and bacterial metabolite production. Furthermore, exposure to airborne bacteria may influence lung health by introducing pathogenic species or altering the human microbiome, thereby implicating certain dominant airborne bacteria in lung diseases, including the exacerbation of lung cancer. Extracellular vesicles (EVs) facilitate cell‑to‑cell communication, penetrating mucosal barriers to impact various organs, notably the lung. Epidemiological evidence suggests a strong relationship between the presence of microbial EVs (MEVs) in the air and chronic pulmonary diseases, with indications of a potential risk for lung cancer. MEVs play a significant role in pulmonary disease development by inducing airway inflammation and affecting lung function. The microbiome and MEVs offer considerable potential as novel tools in precision medicine for lung cancer. Biological data analysis and artificial intelligence technology advancements are pivotal for fully realizing their diagnostic and therapeutic capabilities. These developments can potentially shape the future landscape of lung cancer diagnostics, therapeutics and prevention strategies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234030","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}