{"title":"Exportin 1 inhibitor KPT‑330 reverses oxaliplatin resistance via p53 nuclear retention in colorectal cancer.","authors":"Chuanxi Lai, Xiya Jia, Yiyi Chen, Kangke Chen, Fei Wang, Qiqi Zhang, Xiaonan Xiang, Zhe-Sheng Chen, Lingna Xu, Sheng Dai","doi":"10.3892/ijmm.2025.5675","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5675","url":null,"abstract":"<p><p>Despite the established clinical efficacy of oxaliplatin in colorectal cancer (CRC), resistance to this platinum‑based agent continues to pose a significant therapeutic challenge. Increased exportin 1 (XPO1) expression in CRC has been linked to chemoresistance, while KPT‑330, a selective XPO1 inhibitor, has exhibited potential in enhancing platinum drug effectiveness in other cancer types. The present study explored the synergistic effects of KPT‑330 and oxaliplatin in oxaliplatin‑resistant CRC models. Oxaliplatin‑resistant cell lines (HCT116/L‑OHP and HCT8/L‑OHP) were developed, exhibiting elevated XPO1 expression as demonstrated by western blotting. A range of <i>in vitro</i> assays (Cell Counting Kit‑8 assays, ethynyldeoxyuridine assays, crystal violet staining, transmission electron microscopy and flow cytometry) and an in vivo subcutaneous xenograft model in nude mice were used to evaluate the combination therapy. Co‑treatment with KPT‑330 and oxaliplatin induced G2/M phase arrest and mitochondrial dysfunction, thereby triggering apoptosis and ferroptosis. Mechanistically, the combination therapy of KPT‑330 and oxaliplatin promoted the nuclear retention of p53, which in turn upregulated p21 and downregulated solute carrier family 7 member 11. <i>In vivo</i>, the combination therapy significantly enhanced tumor sensitivity to oxaliplatin. These results suggested that KPT‑330 restored oxaliplatin sensitivity in resistant CRC by facilitating p53 nuclear retention, presenting a promising approach to overcome chemoresistance through dual modulation of cell cycle arrest and ferroptosis pathways.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiming Shao, Ke Song, Ruixin Yu, He Xiao, Chengjun Li, Yuling Deng, Yuan Zhang, Yixing Ren
{"title":"Immune and metabolic remodeling following bariatric surgery: Implications for targeted immunotherapy (Review).","authors":"Yiming Shao, Ke Song, Ruixin Yu, He Xiao, Chengjun Li, Yuling Deng, Yuan Zhang, Yixing Ren","doi":"10.3892/ijmm.2025.5676","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5676","url":null,"abstract":"<p><p>Over the past few years, bariatric surgery has emerged as a potent remedy for obesity and its related metabolic issues, with its effects on peripheral immune cells garnering considerable attention. Obesity, recognized as a chronic metabolic condition, is intricately connected to dysfunctions spanning a range of immune cell types. Among peripheral immune cells, T cells, B cells and monocytes, obesity markedly alters their counts and functions, driving the inflammation and metabolic dysfunction characteristic of the condition. The modifications in these immune cell cohorts are inextricably intertwined with the augmentation of postoperative metabolic functions and have the potential to exert a salutary effect on complications associated with obesity. The present review primarily examined the latent influence of bariatric surgery on the number and function of peripheral immune cells, thereby offering novel perspectives and therapeutic targets for the immunotherapy of obesity.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Retracted] Hypoxic preconditioned bone mesenchymal stem cells ameliorate spinal cord injury in rats via improved survival and migration.","authors":"Weiheng Wang, Xiaodong Huang, Wenbo Lin, Yuanyuan Qiu, Yunfei He, Jiangming Yu, Yanhai Xi, Xiaojian Ye","doi":"10.3892/ijmm.2025.5672","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5672","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the data panels (namely, three of the six panels) in Fig. 3 showing the results of migration assay experiments were strikingly similar to data in a paper which was submitted for publication at around the same time by the same research group to the journal <i>Stem Cells International</i>, where the results were described differently. Upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that data included in Figs. 1C, 6D and 7B‑D were also strikingly similar to data appearing in a few other articles written by the same research group, one of which had already been published and one of which was submitted for publication at around the same time as the above paper. Moreover, two pairs of data panels in Fig. 3 also contained overlapping sections of data, such that data which were intended to show the results of differently performed experiments had apparently been derived from a smaller number of original sources. Given the apparent re‑use of a large number of the data featured in the above paper in other articles by the same research group, and in view of the overlapping data identified in Fig. 3, the Editor of <i>International Journal of Molecular Medicine</i> has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply.The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2538‑2550, 2018; DOI: 10.3892/ijmm.2018.3810].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Importance of B cells (Review).","authors":"Zhiyuan Liu, Haoran Dai, Xiaoyu Cui, Yeping Liu, Zhaocheng Dong","doi":"10.3892/ijmm.2025.5673","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5673","url":null,"abstract":"<p><p>As a key component of the immune system, B cells primarily mediate humoral immunity via the synthesis and secretion of antibodies. In addition, B cells contribute to immune responses via antigen presentation and cytokine secretion. B cell‑targeted therapy has potential for the treatment of autoimmune diseases. However, current B cell‑targeted therapies have limited efficacy when used as monotherapies in clinical settings. In an aim to provide in‑depth understanding of this limitation, the present review discusses the developmental and differentiation pathways of B cells and the mechanisms by which various B cell subsets participate in immune responses, as well as randomized controlled trials on B cell‑targeted therapies conducted on lupus nephritis, an autoimmune disease with a notable inflammatory response. The clinical benefits of these therapies remain modest. This suggests that while B cells may serve a pathogenic role, existing therapies fail to address the fundamental mechanisms underlying disease progression. Targeting the interactions between B and T cells, particularly by inhibiting B cell‑mediated antigen presentation, may represent a promising novel direction for B cell‑targeted therapy.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting of CIRP attenuates osteoarthritis progression via suppressing TLR4/NF‑κB/NLRP3 signaling axis.","authors":"Weichao Sun, Yi Liao, Jianguo Feng, Jianhui Liang, Qifei He, Yinxing Cui, Dixi Huang, Houyin Shi, Wei You, Wei Sun, Qian Yi","doi":"10.3892/ijmm.2025.5674","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5674","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the most common joint diseases worldwide. Recently, cold‑inducible RNA binding protein (CIRP), a novel identified pro‑inflammatory cytokine, was reportedly increased in the synovial fluid of OA patients. However, its function and the underlying mechanism in OA progression remains unclear. Therefore, the current study investigated the role of CIRP in the progression of OA. It was observed that CIRP and matrix metalloproteinases were highly expressed in OA chondrocytes, whereas collagen Ⅱ exhibited low expression levels. Additionally, CIRP was found to be secreted by OA human chondrocytes in the form of exosomes. CIRP treatment influenced inflammatory related signaling pathway, which in turn affected inflammatory response and extracellular matrix (ECM) degradation in human chondrocytes. Additionally, CIRP induced the nuclear translocation of p65 and promoted ECM degradation dependent the Toll‑like receptor 4 (TLR4)/NF‑κB signaling. The present study also reported that CIRP increased the IL‑1β secretion via the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, targeting of CIRP by microRNA‑145 or exosome loading with microRNA‑145 attenuated its role in promoting OA both <i>in vitro</i> and <i>in vivo</i>. The findings indicated that CIRP acts as a pro‑inflammatory factor and activates the TLR4/NF‑κB/NLRP3 pathway, which promotes the inflammatory response, ECM degradation and the progression of OA and targeting CIRP could be a novel strategy for OA treatment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Pan, Yiwen Bao, Xiaoping Lu, Qiqun Gu, Yongchao Zhang, Yi Zheng
{"title":"Short‑chain fatty acids regulate hepatocellular carcinoma progression: A metabolic perspective on tumor immunity (Review).","authors":"Dan Pan, Yiwen Bao, Xiaoping Lu, Qiqun Gu, Yongchao Zhang, Yi Zheng","doi":"10.3892/ijmm.2025.5655","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5655","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide and is characterized by complex metabolic and immunological processes throughout its progression. Emerging research has underscored the critical involvement of the gut microbiota and its metabolites, particularly short‑chain fatty acids (SCFAs), in regulating the hepatic immune microenvironment and contributing to the development of HCC. SCFAs play essential roles in the gut‑liver axis by supporting immune homeostasis, modulating lipid metabolism and influencing immune escape mechanisms within the liver. SCFAs are not only products of gut microbiota metabolism but also key regulators of liver metabolism and immune responses. SCFAs play both positive and negative roles in HCC. SCFAs influence T‑cell function and immune responses through the activation of G‑protein‑coupled receptors and the inhibition of histone deacetylases. The present review provided an overview of the current knowledge concerning the regulatory dual effects of SCFAs on the immune microenvironment of HCC, examines their interactions with immune cells via the gut‑liver axis and evaluated their potential as adjuncts in HCC immunotherapy, with the goal of informing future therapeutic strategies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianqin Li, Yan Yang, Lei Wang, Quanli Liu, Xiaohong Kang, Yun Yang
{"title":"Quinazolinone derivatives as potential anti‑tumor agents: Structural features and molecular mechanisms in inducing cell death (Review).","authors":"Jianqin Li, Yan Yang, Lei Wang, Quanli Liu, Xiaohong Kang, Yun Yang","doi":"10.3892/ijmm.2025.5646","DOIUrl":"10.3892/ijmm.2025.5646","url":null,"abstract":"<p><p>The quinazolinone scaffold is widely present in natural compounds and serves as a core structural unit in various alkaloids. Its structural flexibility is a major advantage in anti‑tumor drug development. Characterized by a fused bicyclic system, this scaffold enables precise pharmacological modulation through targeted chemical modifications, allowing the regulation of multiple cell death pathways, including apoptosis, autophagy, ferroptosis, senescence, pyroptosis and necrosis. This review systematically describes the molecular mechanisms by which quinazolinone derivatives induce tumor cell death and critically evaluates their clinical translation potential. In addition, quinazolinone‑based agents approved by the Food and Drug Administration and those in preclinical development as targeted anti‑tumor therapies are summarized, providing new perspectives and methodological frameworks for advancing oncology drug discovery.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148942","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":"Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).","authors":"Qinge Ma, Kejia Liu, Chenyu Chang, Lei Wang, Zhangyang Shen, Jiaxin Li, Mozili Adu, Qingyuan Lin, Huilian Huang, Xutao Wu, Rongrui Wei","doi":"10.3892/ijmm.2025.5668","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5668","url":null,"abstract":"<p><p>Metabolic dysfunction‑associated steatotic liver disease (MASLD) is caused by multiple factors that lead to the buildup of steatosis and fat deposition in hepatocytes. These changes are the primary hallmarks of the disease and result in significant impairment of liver function. Consequently, the quality of life of patients and their ability to work are adversely affected. The pathogenesis of MASLD involves both Western and Chinese medicines, with these mechanisms markedly influencing the onset and progression of MASLD; they are not independent but rather interrelated. Conducting histopathological diagnosis of MASLD in the liver is challenging in humans. Consequently, both <i>in vivo</i> and <i>in vitro</i> models are essential. Researchers must select appropriate methods and model types to establish MASLD models that most suitably mimic the human body. Currently, both pharmacological and non‑pharmacological treatments have some efficacy in improving the condition of MASLD and the combination of the two is more helpful in providing more effective treatment for patients, but further research and clinical trials are needed to verify in the future. Therefore, the present review comprehensively summarized the pathogenesis, model and treatment of MASLD. It will provide an important basis for subsequent research on MASLD.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).","authors":"Zeyin He, Lili Zhang, Shiyi Gong, Xudan Yang, Guixuan Xu","doi":"10.3892/ijmm.2025.5667","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5667","url":null,"abstract":"<p><p>Cholesterol and its metabolites exert multifaceted and profound effects on cancer initiation, progression and therapeutic response as well as patient prognosis. The present review systematically summarizes the oncogenic role of cholesterol metabolism in malignancies. Cancer cells extensively remodel cholesterol homeostasis through enhanced synthesis, increased uptake and impaired efflux, thereby sustaining proliferative signaling, suppressing ferroptotic cell death, promoting autophagic survival and facilitating epithelial‑mesenchymal transition, collectively fueling tumor invasion and metastasis. Within the tumor immune microenvironment, cholesterol exhibits dual immunoregulatory roles; it potentiates T‑cell antitumor function while its oxidized derivatives contribute to T‑cell exhaustion. Therapeutic targeting of cholesterol metabolism represents a promising strategy to trigger ferroptosis, reverse chemoresistance and reinvigorate antitumor immunity. Nevertheless, epidemiological evidence regarding the correlation between cholesterol levels and cancer risk remains contentious, underscoring the context‑dependent and complex nature of cholesterol in oncology. Targeting cholesterol metabolism may thus offer a novel integrative approach for cancer therapy, meriting further mechanistic and clinical investigation.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aging of the human eye lens: Epigenetic landscape and therapeutic targets in age‑related cataracts (Review).","authors":"Wenxin Yang, Yingying Zheng, Silong Chen, Jiarui Guo, Zicai Pan, Yibo Yu","doi":"10.3892/ijmm.2025.5657","DOIUrl":"10.3892/ijmm.2025.5657","url":null,"abstract":"<p><p>Age‑related cataracts (ARCs) are the predominant cause of blindness globally and are characterized by progressive opacification of the ocular lens. Although oxidative stress, ultraviolet radiation and metabolic dysfunction are well‑documented etiological factors, growing evidence implicates epigenetic dysregulation as a critical pathogenic mechanism in ARCs. Epigenetics refers to heritable changes in gene expression that occur without alterations to the underlying DNA sequence. The primary epigenetic alterations include non‑coding RNAs, DNA methylation, histone modifications, RNA modifications and chromatin remodelling. Epigenetic modifications dynamically regulate gene expression profiles in lens epithelial cells, modulating critical cellular processes such as proliferation, the oxidative stress response and DNA repair, all of which are essential for maintaining lens transparency. Epigenetic research offers novel insights into the molecular mechanisms underlying ARCs and may yield therapeutic strategies targeting dysregulated epigenetic pathways. The present review discusses current evidence on epigenetic mechanisms in ARC pathogenesis, delineating their roles in lens opacity development and highlighting potential targets for clinical intervention.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12530798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212618","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}