International journal of molecular medicine最新文献

{"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}

{"title":"Advancements in omics technologies: Molecular mechanisms of acute lung injury and acute respiratory distress syndrome (Review).","authors":"Zhihuan Zheng, Xinyu Qiao, Junhao Yin, Junjie Kong, Wanqing Han, Jing Qin, Fanda Meng, Ge Tian, Xiujing Feng","doi":"10.3892/ijmm.2024.5479","DOIUrl":"10.3892/ijmm.2024.5479","url":null,"abstract":"<p><p>Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an inflammatory response arising from lung and systemic injury with diverse causes and associated with high rates of morbidity and mortality. To date, no fully effective pharmacological therapies have been established and the relevant underlying mechanisms warrant elucidation, which may be facilitated by multi‑omics technology. The present review summarizes the application of multi‑omics technology in identifying novel diagnostic markers and therapeutic strategies of ALI/ARDS as well as its pathogenesis.</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/PMC11722059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921588","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":"Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice.","authors":"Tao Wang, Mengzhou Wang, Wuming Liu, Lin Zhang, Jia Zhang, Junzhou Zhao, Zheng Wu, Yi Lyu, Rongqian Wu","doi":"10.3892/ijmm.2025.5483","DOIUrl":"10.3892/ijmm.2025.5483","url":null,"abstract":"<p><p>Cold‑inducible RNA‑binding protein (CIRP) is a cold shock protein implicated in the regulation of multiple biological processes depending on its cellular localization. However, to the best of our knowledge, the role of CIRP in liver regeneration and injury after hepatectomy has not been investigated. The present study was therefore designed to explore whether CIRP is involved in liver regeneration after hepatectomy and its specific role and underlying molecular mechanism. The overall involvement of CIRP in liver regeneration and injury after hepatectomy was evaluated in CIRP‑deficient mice. C23, an antagonist of extracellular CIRP, was used to assess the effect of extracellular CIRP on liver regeneration and injury after hepatectomy. CIRP overexpression and short hairpin RNA plasmids were transfected into HepG2 cells to study the effect of intracellular CIRP on cell proliferation. The effects of extracellular CIRP on cell proliferation and injury were determined via the use of recombinant CIRP protein to stimulate HepG2 cells <i>in vitro</i>. The results indicated that both hepatic and serum CIRP levels significantly increased after partial hepatectomy. Additionally, CIRP deficiency impaired liver regeneration but alleviated liver injury after partial hepatectomy in mice. C23 administration attenuated liver injury and suppressed endoplasmic reticulum (ER) stress and oxidative stress. Loss‑ and gain‑of‑function analyses in HepG2 cells indicated that an increase in intracellular CIRP promoted cell proliferation via signal transducers and activation of transcription 3 (STAT3) signaling pathway activation. Moreover, recombinant CIRP had no effect on cell proliferation or STAT3 phosphorylation but induced ER stress, which was blocked by TAK242, an inhibitor of Toll‑like receptor 4 (TLR4), in HepG2 cells. Taken together, the results of the present study demonstrated that intracellular CIRP promotes liver regeneration by activating the STAT3 pathway, whereas extracellular CIRP induces ER stress possibly via the TLR4 signaling pathway after hepatectomy.</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/PMC11758893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948021","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":"Potential and challenges of utilizing exosomes in osteoarthritis therapy (Review).","authors":"Xuesong Chen, Bin Tian, Yiqun Wang, Jiang Zheng, Xin Kang","doi":"10.3892/ijmm.2025.5484","DOIUrl":"10.3892/ijmm.2025.5484","url":null,"abstract":"<p><p>Exosomes are integral to the pathophysiology of osteoarthritis (OA) due to their roles in mediating intercellular communication and regulating inflammatory processes. Exosomes are integral to the transport of bioactive molecules, such as proteins, lipids and nucleic acids, which can influence chondrocyte behavior and joint homeostasis. Given their properties of regeneration and ability to target damaged tissues, exosomes represent a promising therapeutic avenue for OA treatment. Exosomes have potential in promoting cartilage repair, reducing inflammation and improving overall joint function. However, several challenges remain, including the need for standardized isolation and characterization methods, variability in exosomal content, and regulatory hurdles. The present review aims to provide a comprehensive overview of the current understanding of exosome mechanisms in OA and their therapeutic potential, while also addressing the ongoing challenges faced in translating these findings into clinical practice. By consolidating existing research, the present review aims to pave the way for future studies aimed at optimizing exosome‑based therapies for effective OA management.</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/PMC11759586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948158","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":"Recent advances in nanomaterials for the detection of mycobacterium tuberculosis (Review).","authors":"Jianmeng Zhu, Hongqin Wang, Lili Chen","doi":"10.3892/ijmm.2024.5477","DOIUrl":"10.3892/ijmm.2024.5477","url":null,"abstract":"<p><p>The world's leading infectious disease killer tuberculosis (TB) has >10 million new cases and ~1.5 million mortalities yearly. Effective TB control and management depends on accurate and timely diagnosis to improve treatment, curb transmission and reduce the burden on the medical system. Current clinical diagnostic methods for tuberculosis face the shortcomings of limited accuracy and sensitivity, time consumption and high cost of equipment and reagents. Nanomaterials have markedly enhanced the sensitivity, specificity and speed of TB detection in recent years, owing to their distinctive physical and chemical features. They offer several biomolecular binding sites, enabling the simultaneous identification of multiple TB biomarkers. Biosensors utilizing nanomaterials are often compact, user‑friendly and well‑suited for detecting TB on location and in settings with limited resources. The present review aimed to review the advances that have occurred during the last five years in the application of nanomaterials for TB diagnostics, focusing on their detection capabilities, structures, working principles and the significance of key nanomaterials. The current review addressed the limitations and challenges of nanomaterials‑based TB diagnostics, along with potential solutions.</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/PMC11722055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882181","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":"Aquaporin‑1 regulates microglial polarization and inflammatory response in traumatic brain injury.","authors":"Yixuan Ma, Yimin Huang, Xuyang Liu, Liwu Jiao, Hongtao Zhu, Zhiye Chen, Zhuojin Wu, Yuanzhong Shen, Kehan Lin, Feng Hu, Kai Shu","doi":"10.3892/ijmm.2025.5482","DOIUrl":"10.3892/ijmm.2025.5482","url":null,"abstract":"<p><p>The present study investigated the mechanisms by which aquaporin 1 (AQP1) influences microglial polarization and neuroinflammatory processes in traumatic brain injury (TBI). A model of TBI was generated in AQP1‑knockout mice to assess the impact of AQP1 deletion on inflammatory cytokine release, neuronal damage and cognitive function. Immunofluorescence, reverse transcription‑quantitative PCR, western blotting and enzyme‑linked immunosorbent assay were employed to evaluate pro‑inflammatory and anti‑inflammatory markers. Behavioral assessments, including the Barnes maze, were performed to determine cognitive outcomes. Moreover, AQP1 knockout inhibited the activation of inflammation‑related signaling pathways, including nuclear factor‑κB, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3‑kinase/protein kinase B and extracellular signal‑regulated kinase/mitogen‑activated protein kinase pathways. Further studies indicated that the AQP1 inhibitor m‑phenylenediacrylic acid demonstrated significant neuroprotective effects in a mouse model of TBI. These findings suggested that AQP1 may be essential in post‑TBI inflammatory responses and neuronal injury, establishing a theoretical foundation for future therapies aimed at AQP1.</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/PMC11759584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921593","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":"Linking microRNA to metabolic reprogramming and gut microbiota in the pathogenesis of colorectal cancer (Review).","authors":"Wan Muhammad Farhan Syafiq Bin Wan Mohd Nor, Soke Chee Kwong, Afiqah Alyaa Md Fuzi, Nur Akmarina Binti Mohd Said, Amira Hajirah Abd Jamil, Yeong Yeh Lee, Soo Ching Lee, Yvonne Ai-Lian Lim, Ivy Chung","doi":"10.3892/ijmm.2025.5487","DOIUrl":"10.3892/ijmm.2025.5487","url":null,"abstract":"<p><p>Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.</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/PMC11759585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005154","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":"Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR.","authors":"Yu-Hao Huang, Peng-Ju Chien, Wen-Ling Wang, Li-Sung Hsu, Yen-Min Huang, Wen-Wei Chang","doi":"10.3892/ijmm.2025.5485","DOIUrl":"10.3892/ijmm.2025.5485","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a type of head and neck cancer (HNC) with a high recurrence rate, which has been reported to be associated with the presence of cancer stem cells (CSCs). Tribbles pseudokinase 3 (TRIB3) is involved in intracellular signaling and the aim of the present study was to investigate the role of TRIB3 in the maintenance of CSCs. Analysis of The Cancer Genome Atlas database samples demonstrated a positive correlation between TRIB3 expression levels and shorter overall survival rates in patients with HNC. Knockdown of TRIB3 in the SAS and HSC-3 OSCC cell lines reduced cell proliferation through the induction of cell cycle arrest, but not of apoptosis. The population of OSCC-CSCs, defined by a high level of intracellular aldehyde dehydrogenase activity and the ability to form tumorspheres, was also reduced in TRIB3-silenced OSCC cells. The tumorigenicity of tumorspheres derived from the SAS OSCC cell line was reduced following TRIB3 knockdown. These results suggested the potential involvement of TRIB3 in the self-renewal capability of the OSCC CSCs. Mechanistically, TRIB3 was shown to positively regulate SOX2 expression via maintaining both the protein expression level and the SOX2 promoter-binding capability of E2F transcription factor 1 (E2F1). Additionally, TRIB3 also increased the expression level of EGFR through preventing its lysosomal degradation. The significant associations between TRIB3 and E2F1, SOX2 or EGFR expression were also confirmed using a HNC tissue array. Taken together, the findings of the present study may suggest that TRIB3 is an oncogenic protein that supports the stemness of OSCC and that targeting TRIB3 may be a potential strategy for OSCC therapy in the future.</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/PMC11758896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055950","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":"New insights into the role of ubiquitination in angiogenesis (Review).","authors":"Tao Chen, Keyu Wang, Ziqiang Sun","doi":"10.3892/ijmm.2024.5473","DOIUrl":"10.3892/ijmm.2024.5473","url":null,"abstract":"<p><p>Angiogenesis is a dynamic and complex mechanism for generating new blood vessels from existing ones. Angiogenesis occurs through all life stages and involves several physiological processes. It has an important physiological and pathological role including in cancer, wound healing and inflammation. The emerging role of ubiquitination in regulating angiogenesis highlights the importance of studying this pathway in an angiogenic setting. In angiogenic events, imbalances between pro‑ and anti‑angiogenic factors, induction of hypoxic signaling and stimulation of angiogenic signaling pathways play a central role. This review provides a comprehensive overview of the role of ubiquitination in angiogenesis. This includes angiogenic factors [VEGF, platelet‑derived growth factor, (basic) fibroblast growth factor and angiopoietin], vascular cells (pericytes, endothelial cells, vascular smooth muscle cells) and extracellular matrix and cell adhesion molecules, all of which have important roles in angiogenesis, hypoxic signaling (hypoxia‑inducible factor), which induces angiogenesis, and important vascular signaling pathways (Wnt and Notch). In addition, the molecular biological basis of angiogenesis is discussed and the potential therapeutic value of ubiquitination in angiogenesis‑related diseases is highlighted.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 2","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864218","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}