International journal of molecular medicine最新文献

{"title":"NLRP3 inflammasome in health and disease (Review).","authors":"Haoran Wang, Li Ma, Weiran Su, Yangruoyu Liu, Ning Xie, Jun Liu","doi":"10.3892/ijmm.2025.5489","DOIUrl":"10.3892/ijmm.2025.5489","url":null,"abstract":"<p><p>Activation of inflammasomes is the activation of inflammation‑related caspase mediated by the assembly signal of multi‑protein complex and the maturity of inflammatory factors, such as IL‑1β and IL‑18. Among them, the Nod‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most thoroughly studied type of inflammatory corpuscle at present, which is involved in the occurrence and development of numerous human diseases. Therefore, targeting the NLRP3 inflammasome has become the focus of drug development for related diseases. In this paper, the research progress of the NLRP3 inflammasome in recent years is summarized, including the activation and regulation of NLRP3 and its association with diseases. A deep understanding of the regulatory mechanism of NLRP3 will be helpful to the discovery of new drug targets and the development of therapeutic drugs.</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/PMC11781521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390905","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}

{"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}