International journal of molecular medicine最新文献

{"title":"Developments in the connection between epithelial‑mesenchymal transition and endoplasmic reticulum stress (Review).","authors":"Hongyu Chai, Shun Yao, Ya Gao, Qian Hu, Wei Su","doi":"10.3892/ijmm.2025.5543","DOIUrl":"10.3892/ijmm.2025.5543","url":null,"abstract":"<p><p>Endoplasmic reticulum stress (ERS) and epithelial‑mesenchymal transition (EMT) have important roles in fibrosis and tumour development. Moderate ERS activates cellular defence mechanisms in response to noxious stimuli; however, sustained or overly strong ERS induces apoptosis. In this disease process, EMT induces epithelial cells to acquire the ability to migrate and invade. Reportedly, ERS directly or indirectly regulates EMT processes through multiple mechanisms (such as key transcription factors, signalling pathways, ferroptosis, autophagy and oxidative stress), and both processes form a complex network of interactions. Given the critical roles of ERS and EMT in disease, targeted intervention of these two processes has emerged as a potential therapeutic strategy. In the present study, the molecular interaction mechanism of ERS and EMT was systematically explored, research progress in fibrotic and neoplastic diseases was reviewed and the potential application prospects of related targeted therapies were examined, which may provide new ideas for the development of drugs to reverse fibrosis and treat tumours.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993352","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":"Precision oncolytic viral therapy in colorectal cancer: Genetic targeting and immune modulation for personalized treatment (Review).","authors":"Muhammad Haris Sultan, Qi Zhan, Yigang Wang, Yulong Xia, Xiaoyuan Jia","doi":"10.3892/ijmm.2025.5545","DOIUrl":"10.3892/ijmm.2025.5545","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading health issue and treatments to eradicate it, such as conventional chemotherapy, are non‑selective and come with a number of complications. The present review focuses on the relatively new area of precision oncolytic viral therapy (OVT), with genetic targeting and immune modifications that offer a new future for CRC treatment. In the present review, an overview of the selection factors that are considered optimal for an oncolytic virus, mechanisms of oncolysis and immunomodulation applied to the OVT, as well as new strategies to improve the efficacy of this method are described. Additionally, cause‑and‑effect relationships are examined for OVT efficacy, mediated by the tumor microenvironment, and directions for genetic manipulation of viral specificity are explored. The possibility of synergy between OVT and immune checkpoint inhibitors and other treatment approaches are demonstrated. Incorporating the details of the present review, biomarker‑guided combination therapies in precision OVT for individualized CRC care, significant issues and future trends in this required area of medicine are highlighted. Increasingly, OVT is leaving the experimental stage and may become routine practice; it provides a new perspective on overcoming CRC and highlights the importance of further research and clinical work.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999498","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":"Curcumenol inhibits malignant progression and promotes ferroptosis via the SLC7A11/NF‑κB/TGF‑β pathway in triple‑negative breast cancer.","authors":"Feifei Li, Qin Qi, Yu Qiao, Yan Huang, Yuan Lu, Kan Gu, Huirong Liu, Chunfang Gao, Sheng Liu, Huangan Wu","doi":"10.3892/ijmm.2025.5552","DOIUrl":"10.3892/ijmm.2025.5552","url":null,"abstract":"<p><p>Triple‑negative breast cancer (TNBC) exhibits a high degree of malignancy and a propensity for metastasis, ultimately resulting in unfavorable patient outcomes. <i>Curcuma phaeocaulis</i> Valeton is a common herb used in traditional Chinese medicine to treat TNBC. Curcumenol (Cur) is a natural compound derived from <i>C. phaeocaulis</i> Valeton, the effects of which on breast cancer remain under‑reported. The present study elucidated that Cur could effectively inhibit the survival ability of TNBC cells and enhance their sensitivity to paclitaxel. Western blotting (WB) further revealed that Cur modulated apoptosis and epithelial‑mesenchymal transition (EMT) in TNBC. Findings from animal experiments further validated these observations. In the established TNBC mouse model, Cur was shown to exert an inhibitory effect on tumor growth, effectively attenuate EMT and substantially reduce the incidence of lung metastasis. Integrated analyses using RNA sequencing, WB and reverse transcription‑quantitative polymerase chain reaction demonstrated that Cur markedly downregulated the expression levels of solute carrier family 7 member 11 (SLC7A11), phosphorylated‑NF‑κB and TGF‑β. Molecular docking studies further validated that Cur can establish stable interactions with SLC7A11. In‑depth bioinformatics analysis revealed a positive association between high SLC7A11 expression and reduced disease‑free survival in patients with breast cancer. Additionally, in TNBC cells, Cur was revealed to reduce the mitochondrial membrane potential and promote the accumulation of lipid reactive oxygen species. Subsequent experimental investigations demonstrated that Cur can counteract the inhibitory influence of ferrostatin‑1 on ferroptosis. These findings strongly implied a potential underlying mechanism, suggesting that Cur may impede the malignant progression of TNBC via the modulation of ferroptosis. In conclusion, the findings of the present study underscore the marked efficacy of Cur in hampering the progression of TNBC by suppressing the SLC7A11/NF‑κB/TGF‑β signaling pathway.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077039","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":"Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).","authors":"Yanning Sun, Kai Sun, Hongju Ling, Qinghua Xia","doi":"10.3892/ijmm.2025.5551","DOIUrl":"10.3892/ijmm.2025.5551","url":null,"abstract":"<p><p>Metabolic reprogramming represents a hallmark of malignant tumors, manifested through progressive alterations in nutrient utilization patterns during oncogenesis. As fundamental constituents of biological membranes, essential components of signaling pathways, and critical energy substrates, lipids undergo comprehensive metabolic restructuring in neoplastic cells. This lipid remodeling confers enhanced adaptability to sustain uncontrolled proliferation while promoting aggressive migratory phenotypes. Farnesoid X receptor (FXR), a ligand‑activated nuclear receptor responsive to bile acid (BA) derivatives and cholesterol metabolites, orchestrates key aspects of lipid homeostasis. Its regulatory network encompasses cholesterol/BA metabolism, fatty acid (FA) metabolism and plasma lipoprotein trafficking pathways. Emerging evidence positions FXR as a pleiotropic modulator in oncogenesis, with dysregulated expression patterns documented across multiple tumor lineages and premalignant lesions. This mechanistic understanding has propelled FXR‑targeted therapeutics into the forefront of precision oncology development. The present review critically examines the FXR‑lipid axis in lipid‑enriched malignancies, with particular emphasis on its regulatory circuitry governing BA flux and FA turnover.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077714","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":"Function and application of brain‑derived neurotrophic factor precursors (Review).","authors":"Risheng Chen, Weixin Chen, Ping Li, Yingchang Zhao, Qianqian Zeng, Wenqing Chen, Dequan Cao","doi":"10.3892/ijmm.2025.5546","DOIUrl":"10.3892/ijmm.2025.5546","url":null,"abstract":"<p><p>Brain‑derived neurotrophic factor precursor (proBDNF) plays a critical role in the pathogenesis and progression of various human diseases. Through its interaction with p75NTR and sortilin receptors, proBDNF promotes apoptosis, impairs synaptic plasticity, and contributes to the regulation of immune system function, inflammatory responses and cellular metabolic processes. proBDNF is widely distributed throughout the body, and as such, extensive research has demonstrated that proBDNF is significantly associated with the pathophysiological mechanisms underlying several diseases. In the present review, the mechanisms by which proBDNF contributes to different diseases are summarized to highlight its potential therapeutic and diagnostic implications. Specifically, the role of proBDNF in cognitive disorders, focusing on its effects on synaptic function and neural network dynamics, while analyzing the cascade reactions involving proBDNF and downstream effector molecules in inflammatory diseases, to elucidate its bidirectional regulatory effects in tumor initiation and progression. Furthermore, the function of proBDNF in neurogenesis, the mechanism by which it regulates the memory of fear, and enhances individual behavioral flexibility is discussed. Finally, the potential of proBDNF as a biomarker for disease diagnosis and the therapeutic prospects of targeting it using monoclonal antibodies are highlighted while also proposing future research directions. The present review can serve as a reference for translational medical research on proBDNF and its receptors.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009585","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 of programmed cell death and potential targeted pharmacotherapy in ischemic stroke (Review).","authors":"Wan-Li Duan, Li-Hui Gu, Ai Guo, Xue-Jie Wang, Yi-Yue Ding, Peng Zhang, Bao-Gang Zhang, Qin Li, Li-Xia Yang","doi":"10.3892/ijmm.2025.5544","DOIUrl":"10.3892/ijmm.2025.5544","url":null,"abstract":"<p><p>Stroke poses a threat to the elderly, being the second leading cause of death and the third leading cause of disability worldwide. Ischemic stroke (IS), resulting from arterial occlusion, accounts for ~85% of all strokes. The pathophysiological processes involved in IS are intricate and complex. Currently, tissue plasminogen activator (tPA) is the only Food and Drug Administration‑approved drug for the treatment of IS. However, due to its limited administration window and the risk of symptomatic hemorrhage, tPA is applicable to only ~10% of patients with stroke. Additionally, the reperfusion process associated with thrombolytic therapy can further exacerbate damage to brain tissue. Therefore, a thorough understanding of the molecular mechanisms underlying IS‑induced injury and the identification of potential protective agents is critical for effective IS treatment. Over the past few decades, advances have been made in exploring potential protective drugs for IS. The present review summarizes the specific mechanisms of various forms of programmed cell death (PCD) induced by IS and highlights potential protective drugs targeting different PCD pathways investigated over the last decade. The present review provides a theoretical foundation for basic research and insights for the development of pharmacotherapy for IS.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017539","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":"Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review).","authors":"Rongqi Guo, Rui Wang, Weisong Zhang, Yangyang Li, Yihao Wang, Hao Wang, Xia Li, Jianxiang Song","doi":"10.3892/ijmm.2025.5554","DOIUrl":"10.3892/ijmm.2025.5554","url":null,"abstract":"<p><p>The early growth response (EGR) family comprises four zinc finger transcription factors: EGR1, EGR2, EGR3 and EGR4. These transcription factors belong to the Cys₂‑His₂‑type zinc finger protein family and are essential in cell differentiation, proliferation, apoptosis and stress response. Initially, EGR1 was recognised for its essential regulatory role in tumourigenesis. Recent studies have identified similarities between other members of the EGR family and EGR1 in tumour regulation and the multifaceted regulatory mechanism employed by the EGR family to affect tumours. Therefore, the present review describes the dual roles of the EGR family in tumours and their regulatory mechanisms in immunity, metabolism and differentiation. Additionally, the present review offers a new perspective on relevant tumour therapeutic studies based on current EGR targeting.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181808","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":"[Retracted] MicroRNA‑7 functions as a tumor‑suppressor gene by regulating ILF2 in pancreatic carcinoma.","authors":"Yiliang Bi, Wei Shen, Min Min, Yan Liu","doi":"10.3892/ijmm.2025.5542","DOIUrl":"10.3892/ijmm.2025.5542","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the Transwell cell migration and invasion assay data shown in Fig. 3C on p. 304 were strikingly similar to data appearing in different form in an article written by different authors at different research institutes that had already been published in the journal <i>Oncotarget</i>. Upon performing an independent analysis of the data in this paper, the data shown in Fig. 2B were also strikingly similar to data that had appeared in another previously published article. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of <i>International Journal of Molecular Medicine</i> has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 39: 900‑906, 2017; DOI: 10.3892/ijmm.2017.2894].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964620","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":"Gossypin induces apoptosis and autophagy via the MAPK/JNK pathway in HT‑29 human colorectal cancer cells.","authors":"Jun-Mo Moon, Sang-Woo Lee, Yun-Seo Jang, Su-A Lee, Soo-Hyun Jung, Sang-Ki Kim, Byung-Kwon Park, Young-Seok Park, Byeong-Soo Kim, Myeon-Sik Yang, Ji-Youn Jung","doi":"10.3892/ijmm.2025.5548","DOIUrl":"10.3892/ijmm.2025.5548","url":null,"abstract":"<p><p>Gossypin, a flavone found in <i>Hibiscus vitifolius</i>, exhibits antioxidant, antidiabetic, anti‑inflammatory and anticancer effects. The present study investigated the potential of gossypin to induce apoptosis and autophagy in HT‑29 human colorectal cancer (CRC) cells, and assessed its association with the MAPK/JNK pathway. Cell viability assays, DAPI staining, flow cytometry, acridine orange staining, western blotting, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and immunohistochemistry were performed. The results revealed an increased number of apoptotic bodies, higher apoptosis rates and enhanced autophagy in gossypin‑treated HT‑29 cells. To investigate autophagy during cell death, the effects of the early autophagy inhibitor 3‑methyladenine (3‑MA) and the late autophagy inhibitor hydroxychloroquine on cell viability and the expression of apoptosis‑related proteins were assessed. Significant increases in cell viability were observed following 3‑methyladenine pretreatment, as well as a decrease in the expression levels of Bcl‑2 and an increase in Bax. The analysis of MAPK pathway proteins following treatment with gossypin revealed that the levels of phosphorylated (p‑)JNK and p‑p38 were significantly increased in a concentration‑dependent manner. The JNK inhibitor SP600125 was used to confirm the role of the JNK pathway in gossypin‑induced apoptosis and autophagy. Moreover, gossypin reduced the volume of HT‑29 tumors in mice, and western blotting indicated the induction of apoptosis and autophagy in these tumors <i>in vivo</i>. Finally, TUNEL and immunohistochemistry experiments confirmed the induction of apoptosis and p‑JNK upregulation in these tumors <i>in vivo</i>. In conclusion, the present study suggested that gossypin may induce MAPK/JNK‑mediated apoptosis and autophagy in HT‑29 CRC cells, highlighting the potential of gossypin as an anticancer agent.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077722","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 vitamins in the development and treatment of osteoporosis (Review).","authors":"Mingze Jiang, Genghan Li, Keda Yang, Lin Tao","doi":"10.3892/ijmm.2025.5550","DOIUrl":"10.3892/ijmm.2025.5550","url":null,"abstract":"<p><p>Osteoporosis has escalated into a pressing public health challenge amidst global demographic aging. Conventional diagnostic approaches and therapeutic interventions demonstrate growing limitations in both risk stratification and epidemiological control. In this context, serological monitoring and targeted nutrient supplementation emerge as promising preventive strategies. Vitamins, fundamental regulators of cellular homeostasis, demonstrate particular significance in bone remodeling processes. The present comprehensive review elucidates the pathophysiological mechanisms through which specific vitamins differentially modulate osteoblastic activity and osteoclastic regulation, summarizing contemporary evidence from the molecular to clinical research levels. While vitamin A exhibits dual effects, other vitamins predominantly show positive impacts on bone homeostasis. Oxidative stress and inflammation are key pathological changes associated with osteoporosis. Vitamins play a protective role by enhancing the expression of antioxidant enzymes, activating antioxidant pathways and inhibiting the secretion of inflammatory cytokines, thereby mitigating these conditions. Serum vitamin concentrations exhibit significant correlations with bone mineral density alterations and osteoporosis progression, providing predictive biomarkers for fracture risk assessment. However, serum vitamin profiles exhibit marked heterogeneity across osteoporosis risk strata, necessitating population‑specific therapeutic protocols. Precision‑adjusted supplementation strategies effectively attenuate pathological bone resorption while preserving physiological remodeling homeostasis. The present review systematically delineates the therapeutic potential of vitamins in osteoporotic management, underscoring the necessity for evidence‑based precision nutrient protocols tailored to at‑risk populations to prevent disease progression.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077730","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}