International journal of molecular medicine最新文献

{"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}

{"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":"","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":"","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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] miR‑378a‑3p exerts tumor suppressive function on the tumorigenesis of esophageal squamous cell carcinoma by targeting Rab10.","authors":"Naixin Ding, Xiujin Sun, Tingting Wang, Lei Huang, Jing Wen, Yiqin Zhou","doi":"10.3892/ijmm.2025.5640","DOIUrl":"10.3892/ijmm.2025.5640","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 3 on p. 385 were strikingly similar to data which had been already been submitted for publication to several other journals that were written by different authors at different research institutes. In addition, overlapping data panels were noted with the EdU assay experiments in Fig. 2C, with the scratch‑wound assay experiments in Fig. 10A, and with the cell invasion assay experiments in Fig. 10B, and the Rab10 western blot data in Fig. 9B for the EC109 cell line were strikingly similar to data that appeared in another journal by different authors at different research institutes. Owing to the fact that the contentious flow cytometric and western blot data in the above article were found to be strikingly similar to data that had already been submitted for publication elsewhere, 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 42: 381‑391, 2018; DOI: 10.3892/ijmm.2018.3639].</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/PMC12459917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086113","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] miR‑760 mediates hypoxia‑induced proliferation and apoptosis of human pulmonary artery smooth muscle cells via targeting TLR4.","authors":"Yu-Zhong Yang, Yun-Feng Zhang, Lei Yang, Jing Xu, Xu-Ming Mo, Wei Peng","doi":"10.3892/ijmm.2025.5642","DOIUrl":"10.3892/ijmm.2025.5642","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, in addition to the duplication of data comparing Fig. 4B with Fig. 6F (showing the results of Transwell assay experiments) and within Fig. 6C (showing the results of scratch‑wound assay experiments), a data panel in Fig. 2C was also featured in a paper written by different authors that had already been submitted to the journal <i>Cancer Science</i>. Owing to the fact that the contentious data in the above article were found to be strikingly similar to data that had already been submitted for publication elsewhere, 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 42: 2437‑2446, 2018; DOI: 10.3892/ijmm.2018.3862].</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/PMC12488201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148962","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":"Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review).","authors":"Di Cheng, Nan Li, Qian Sun, Kun Wang, Fengchun Gao","doi":"10.3892/ijmm.2025.5644","DOIUrl":"10.3892/ijmm.2025.5644","url":null,"abstract":"<p><p>Preterm birth (PTB) is a global maternal and neonatal health challenge, affecting ~15 million infants each year. Despite advances in obstetric and neonatal care, PTB‑related morbidity and mortality remain high. Emerging evidence implicates dysbiosis of the vaginal microbiota (VMB) as a key contributor to PTB. A healthy VMB is typically dominated by <i>Lactobacillus</i> spp., which maintain an acidic vaginal environment and inhibit pathogen colonization. Conversely, reduced Lactobacilli abundance alongside overgrowth of anaerobic taxa such as <i>Gardnerella</i>, <i>Atopobium</i> and <i>Mycoplasma</i> is strongly associated with spontaneous PTB and preterm premature rupture of membranes. Excessive proliferation of vaginal pathogens may lead to ascending infection and intra‑amniotic inflammation via activation of host Toll‑like receptor signaling and induction of pro‑inflammatory cytokines IL‑1β, IL‑6 and IL‑8. Moreover, VMB‑derived metabolites such as lactate play important roles in immunomodulation and inflammation. Although antibiotics remain the mainstay for treating bacterial vaginosis, their non‑specific effects often disrupt microbial balance and predispose to recurrence. Recently, probiotic therapies and VMB transplantation have emerged as promising alternative or adjunctive strategies for PTB prevention and management. However, variability in probiotic efficacy and lack of standardized intervention protocols remain significant challenges. The present review examined pregnancy‑associated VMB dynamics, the mechanisms linking dysbiosis to PTB risk and future microbiome‑based intervention strategies, with the aim of informing theoretical and practical approaches to reduce the global burden of preterm birth.</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/PMC12488211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148955","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":"Apelin‑13 in the paraventricular nucleus (PVN) attenuates myocardial ischemia through V1a receptors in PVN/nucleus tractus solitarii (NTS) and GARγ2 in NTS.","authors":"Wen Yan, Dan Wang, Xinmin Zhang, Chengluan Xuan","doi":"10.3892/ijmm.2025.5652","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5652","url":null,"abstract":"<p><p>The apelin system plays a significant role in central blood pressure regulation, but its role in the neural control of myocardial protection remains poorly understood. The present study evaluated the effects of apelin‑13 in the paraventricular nucleus (PVN) on myocardial infarction (MI). In a male rat MI model, apelin‑13 expression was decreased in PVN, while Vasopressin 1a (V1a) receptor expression was increased in both PVN and nucleus tractus solitarii (NTS) and GABAA receptor (GAR)γ2 expression was increased in NTS. Cardiac function was assessed after microinjection of apelin‑13 or gene transfer of apelin‑13 into the PVN. Apelin‑13 overexpression in PVN markedly improved MI cardiac function, as evidenced by left ventricular end‑diastolic diameter, left ventricular end‑systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening, along with decreased plasma noradrenaline and increased vasopressin levels. Mechanistically, both TGF‑β/Smad signaling and Bax/Bcl‑2 expression were implicated in heart tissue. Additionally, serum levels of four parasympathetic neuropeptides (somatostatin, cholecystokinin, glucagon‑like peptide‑1 and vasoactive intestinal peptide) were elevated in parallel with cardiac function improvement. Notably, V1a receptor antagonist administration in PVN/NTS or GAR agonist treatment in NTS attenuated the cardioprotective effects of apelin‑13. These findings demonstrated that PVN apelin‑13 overexpression improves cardiac function through V1a receptors (PVN/NTS) and GARγ2 (NTS), involving both parasympathetic neuroendocrine activation and modulation of myocardial apoptotic/inflammatory pathways. The present study provided novel insights into neural mechanisms of cardiovascular regulation.</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":"145212632","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":"CDC5L binds to ELAVL1 to inhibit pyroptosis in hepatocellular carcinoma through the Caspase 3/GSDME signaling pathway.","authors":"Shuai Liang, Zhongcheng Zhu, Yangshuo Tang, Shuhua Zhou, Moyan Xiao, Xuejun Gong, Ke Ye","doi":"10.3892/ijmm.2025.5639","DOIUrl":"10.3892/ijmm.2025.5639","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is associated with elevated rates of illness and mortality, posing a significant challenge to global health. Elevated levels of cell division cycle 5 like (CDC5L) in HCC predict a poor prognosis. The present study aimed to elucidate the role of CDC5L in HCC. First, CDC5L expression was detected using bioinformatics analysis and validated on clinical samples and cells. Next, CDC5L was knocked down and overexpressed. CDC5L and Caspase 3 knockdown was conducted to explore the effect on pyroptosis in HCC. The mechanisms of HCC pyroptosis were investigated by interfering with and overexpressing ELAV like RNA binding protein 1 (ELAVL1), as well as interfering with CDC5L and overexpressing ELAVL1. Finally, the role of CDC5L/ELAVL1 in regulating Caspase 3/Caspase 3‑-gasdermin E (GSDME) in HCC pyroptosis was validated through cellular and animal experiments. It was found that CDC5L expression was increased in HCC. Elevated CDC5L levels were linked to adverse outcomes in HCC. Suppressing CDC5L expression reduced cell viability, curbed cell proliferation and diminished cell migration and invasion capabilities, while simultaneously enhancing pyroptosis. Additionally, CDC5L knockdown resulted in a progressive decline in tumor volume and a decrease in tumor size and weight. CDC5L overexpression exerted an opposite effect. Moreover, regulating pyroptosis in HCC by CDC5L was dependent on Caspase family. Following CDC5L knockdown, tumor volume steadily diminished, tumor mass shrank and tumor weight was correspondingly reduced. ELAVL1 overexpression reversed these effects. CDC5L competitively bound to ELAVL1 to inhibit the binding of ELAVL1 with <i>Caspase 3</i> mRNA, thereby regulating HCC pyroptosis. Finally, cellular and animal experiments confirmed that silencing CDC5L/ELAVL1 regulated Caspase 3/GSDME to promote HCC pyroptosis and inhibit tumor progression. In conclusion, CDC5L bound to ELAVL1 to inhibit pyroptosis in HCC through Caspase 3/GSDME signaling pathway, offering a promising therapeutic strategy for improving the prognosis and treatment of HCC.</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/PMC12459918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040192","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":"PANoptosis: A novel therapeutic target in kidney disease (Review).","authors":"Lianyan Jiang, Liangbin Zhao, Yu Liu, Zhongmei Fu, Mengzhu Wu, Zengyi Mou, Mingquan Li","doi":"10.3892/ijmm.2025.5648","DOIUrl":"10.3892/ijmm.2025.5648","url":null,"abstract":"<p><p>The global prevalence of kidney diseases continues to rise annually, posing a serious public health challenge, and notably contributing to morbidity and mortality rates worldwide. In affected individuals, kidney function progressively declines, ultimately resulting in renal failure. Therefore, elucidating the pathophysiological mechanisms underlying kidney diseases and identifying novel therapeutic targets is of paramount importance. Among these, the regulation of cell death pathways has emerged as a pivotal factor in disease progression. PANoptosis, a recently characterized form of programmed cell death, is activated by diverse stimuli, and involves the integrated activation of pyroptosis, apoptosis and necroptosis, coordinated through the PANoptosome complex. Increasing evidence has suggested that PANoptosis serves an important role in the development of kidney diseases, and further investigation into its regulatory mechanisms may provide valuable insights into disease modulation. The present review summarizes current knowledge regarding the mechanisms of PANoptosis and its involvement in various kidney diseases, offering perspectives for future diagnostic and 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":"145149022","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":"[Corrigendum] Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways.","authors":"Longbin Cao, Yunxiao Yang, Ziyu Ye, Bihua Lin, Jincheng Zeng, Caihong Li, Tong Liang, Keyuan Zhou, Jixia Li","doi":"10.3892/ijmm.2025.5650","DOIUrl":"https://doi.org/10.3892/ijmm.2025.5650","url":null,"abstract":"<p><p>Subsequently to the publication of the above article, the authors drew to the Editor's attention that, for the MCF‑7 cell invasion assay data shown in Fig. 2C on p. 1630, the '10 µM' data panel had been placed incorrectly, and was a duplication of the data panel shown (correctly) for the '20 µM' experiment. Subsequently, upon performing an independent review of the data published in this paper, the Editorial Office alerted the authors to the fact that, in Fig. 2A, the data shown for the MDA‑MB‑231 / 20 µM quercetin‑3‑methyl ester‑0 h and ‑24 h data panels were strikingly similar, such that these were apparently derived from the same original source, where the results of differently performed experiments were intended to have been portrayed. After re‑examining their original data, the authors realized that these data in Fig. 2C had inadvertently been assembled incorrectly. The revised version of Fig. 2, showing the correct data for the MDA‑MB‑231 / 20 µM quercetin‑3‑methyl ester‑24 h experiment in Fig. 2A and the '10 µM' data panel in Fig. 2C, is shown on on the next page. The authors are grateful to the Editor of <i>International</i> <i>Journal of Molecular Medicine</i> for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 1625‑1636, 2018; DOI: 10.3892/ijmm.2018.3741].</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":"145212642","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}