International journal of molecular medicine最新文献

{"title":"Nitric oxide‑mediated S‑Nitrosylation contributes to signaling transduction in human physiological and pathological status (Review).","authors":"Yan Xu, Xuesong Wang, Xiaolei Zhou, Lulu Peng, Jiayi Yuan, Yichi Zhang, Nan Wu, Junsong Ye","doi":"10.3892/ijmm.2025.5593","DOIUrl":"10.3892/ijmm.2025.5593","url":null,"abstract":"<p><p>In the complex development of various diseases, nitric oxide‑mediated S‑nitrosylation is increasingly recognized for its distinct regulatory function. Recent research has advanced our knowledge of how this nitric oxide‑dependent modification is dynamically controlled under both physiological and pathological conditions. S‑nitrosylation plays a key role in regulating mitochondrial function, gene transcription, cellular homeostasis and metabolism and it is also involved in the pathogenesis of cardiovascular disorders, neurological conditions and cancer. The present review outlined the signaling pathways driven by nitric oxide and describes the formation, specificity and factors that influence S‑nitrosylation levels. It also compared the strengths and limitations of different detection methods for S‑nitrosation reactions. The present review discussed the cellular regulatory mechanisms affected by S‑nitrosylation to clarify how certain major diseases are connected to specific S‑nitrosylated proteins. These insights may guide the development of targeted repair strategies for malfunctioning proteins by focusing on defined S‑nitrosylation sites, offering theoretical support for disease intervention and treatment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707444","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":"High‑dose X‑ray irradiation induces NETosis via the eCIRP/TREM‑1 axis in mouse neutrophils.","authors":"Satoshi Yamaga, Atsushi Murao, Monowar Aziz, Ping Wang, Max Brenner","doi":"10.3892/ijmm.2025.5598","DOIUrl":"10.3892/ijmm.2025.5598","url":null,"abstract":"<p><p>High‑dose ionizing radiation induces multiple types of tissue injuries, including hematopoietic dysfunction characterized by neutropenia. Neutrophil extracellular traps (NETs) released during NETosis may contribute to the neutropenia, and subsequent infection and inflammation. Triggering receptor expressed on myeloid cells‑1 (TREM‑1) is one of receptors responsible for NET formation and extracellular cold‑inducible RNA‑binding protein (eCIRP) is a ligand for the TREM‑1 receptor. The present study aimed to investigate NET formation after exposure to high‑dose ionizing radiation and to explore the underlying role of the eCIRP/TREM‑1 axis as its mechanism. Bone marrow‑derived neutrophils (BMDNs) isolated from C57BL/6 mice were exposed to 5 to 15 Gy irradiation. C57BL/6 wild‑type (WT), CIRP^‑/‑ and TREM‑1^‑/‑ mice were exposed to 10 Gy total body irradiation (TBI). NET formation was analyzed 24 h after irradiation using flow cytometry and fluorescence microscopy, and also after treatment with eCIRP. TREM‑1 cell surface expression on neutrophils was assessed using flow cytometry. Peptidyl arginine deiminase 4 (PAD4) protein expression levels in BMDNs were evaluated using western blotting. TREM‑1 and PAD4 mRNA expression levels in BMDNs were assessed using reverse transcription‑quantitative PCR. In vitro irradiation of neutrophils resulted in a dose‑dependent increase in NET formation, as assessed using flow cytometry and validated using fluorescence microscopy, which demonstrated the characteristic long extracellular DNA structures of NETs in irradiated neutrophils. The <i>in vivo</i> mouse model of TBI exhibited similar results. Furthermore, TREM‑1 expression in BMDNs was significantly increased after irradiation. Protein and mRNA levels of PAD4 were significantly upregulated after irradiation. The addition of eCIRP to BMDNs further increased NET formation post‑irradiation <i>in vitro</i>. Conversely, knockout of CIRP and TREM‑1 <i>in vivo</i> significantly attenuated radiation‑induced NET formation compared with that of WT mice. High‑dose ionizing radiation induced NET formation through the eCIRP/TREM‑1 pathway and may contribute to early neutropenia post‑irradiation.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760055","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":"SDF2 promotes glioma progression via GRP78‑mediated ERAD and copper homeostasis disruption.","authors":"Aoxiang Li, Xiaolong Li, Tuo Wang, Jinning Song","doi":"10.3892/ijmm.2025.5595","DOIUrl":"10.3892/ijmm.2025.5595","url":null,"abstract":"<p><p>Stromal cell‑derived factor 2 (SDF2) is an endoplasmic reticulum chaperone protein crucial for protein folding. Its role in gliomas is poorly understood. The present study investigated SDF2 expression and function in glioma progression. Our data revealed that the expression of SDF2 was upregulated in glioma tissues. In glioma cell lines, SDF2 promoted cell proliferation and migration, whereas the knockdown of SDF2 (Ad‑shSDF2) induced cell death. Further investigations revealed that the copper chelator tetrathiomolybdate (TTM) could reverse the reduction in cell viability caused by Ad‑shSDF2. Upon SDF2 knockdown, the expression of ATP7A and ATP7B was decreased in glioma cells, whereas the expression of glucose‑regulated protein 78 (GRP78) was increased. Moreover, the proteasome inhibitor MG132 and the silencing of GRP78 effectively blocked the Ad‑shSDF2‑mediated decrease in ATP7A and ATP7B expression, as well as the accumulation of dihydrolipoamide S‑acetyltransferase in mitochondria. <i>In vivo</i>, SDF2 promoted subcutaneous tumor growth in nude mice, an effect that could be reversed by overexpression of GRP78. This reversal was accompanied by an increase in the intra‑tumoral copper ion concentration. In gliomas, SDF2 promotes tumor growth by inhibiting the GRP78‑mediated endoplasmic reticulum‑associated degradation pathway, thereby increasing the expression of ATP7A and ATP7B. This results in reduced intracellular accumulation of copper ions, facilitating tumor progression.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707445","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":"How lactate and lactylation shape the immunity system in atherosclerosis (Review).","authors":"Yan Xiong, Jie Zhou, Junru Wang, Hui Huang","doi":"10.3892/ijmm.2025.5604","DOIUrl":"10.3892/ijmm.2025.5604","url":null,"abstract":"<p><p>Atherosclerosis is a leading cause of cardiovascular diseases, causing significant morbidity and mortality. This review article examines the role of lactate and lactylation in atherosclerosis, a chronic inflammatory disease closely linked to lipid metabolism and immune system activation. Lactate, a metabolic byproduct and signaling molecule, has emerged as a key regulator of immune cell functions and epigenetic modifications. The article explores the mechanisms through which lactate and lactylation influence macrophage polarization, T‑cell differentiation and B‑cell metabolism, highlighting their complex dual roles in the progression of atherosclerosis. By modulating metabolic reprogramming, functional polarization and epigenetic regulation, lactate and lactylation significantly impact plaque formation and stability. These findings provide a foundation for developing novel therapeutic strategies targeting lactate metabolism and lactylation pathways.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760057","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 role of AhR in ischemia‑reperfusion injury and cancers: Focus on ferroptosis and lipid peroxidation signaling pathways (Review).","authors":"Zhihong Liao, Mingzhang Huang, Yuanqi Zhang, Siqi Huang, Wei Lei, Xiaorong Shui","doi":"10.3892/ijmm.2025.5597","DOIUrl":"10.3892/ijmm.2025.5597","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a pivotal ligand‑activated transcription factor that plays a crucial role in maintaining cellular redox homeostasis. The disruption of redox homeostasis in the etiology of numerous diseases primarily manifests as the accumulation of reactive species and the attenuation of the antioxidant defenses, leading to the progressive buildup of lipid peroxides. This phenomenon significantly contributes to the initiation and progression of diseases, such as atherosclerosis, cancer, diabetes and ischemia‑reperfusion injury. Ferroptosis is a form of cell death characterized by iron dependency and lipid peroxidation. The regulation of ferroptosis presents a promising therapeutic target for anticancer therapy and the prevention of neurodegenerative and cardiovascular diseases. AhR transcriptionally regulates downstream target genes, thereby modulating the biosynthesis and accumulation of bioactive compounds and the antioxidant defense mechanism. This process is intricately linked to lipid peroxide accumulation and subsequent ferroptosis. The present review provides an overview of the influence of AhR on lipid peroxidation and ferroptosis, the potential therapeutic targets, and the prospective application value of targeting the AhR to influence lipid peroxidation‑ferroptosis processes in tumor cells and ischemia‑reperfusion injury.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760058","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":"Emerging threat of environmental microplastics: A comprehensive analysis of hepatic metabolic dysregulation and hepatocellular damage (Review).","authors":"Siqing Yue, Siyu Chen, Yu Zhang, Bangjie Chen, Tao Xu","doi":"10.3892/ijmm.2025.5584","DOIUrl":"10.3892/ijmm.2025.5584","url":null,"abstract":"<p><p>The substantial rise in global plastic production has led to the widespread accumulation of microplastics (MPs) in the soil, water and atmosphere. Inevitably, animals and humans have ingested these MPs through environmental contact, resulting in their accumulation within the liver. The elucidation of the hepatotoxic effects of MPs in animals, and in particular on human liver pathophysiology, is now a central topic of investigation in the study of environmental particulate toxicology. The present review summarised existing studies on how MPs damage the liver, and in particular, highlighted the mechanisms of action and the key influencing factors. There is evidence that indicates that MPs can damage the liver tissue structure, induce liver cell death and disrupt lipid metabolism, and that particle size and exposure time are important factors influencing the adverse effects of MPs on the liver. However, further research is required to comprehensively elucidate the mechanisms by which MPs induce liver injury and the long‑term health risks they pose.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667607","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":"Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review).","authors":"Yunnan Liu, Haimei Yang, Jian Xiong, Ying Wei, Chen Yang, Qianhua Zheng, Fanrong Liang","doi":"10.3892/ijmm.2025.5589","DOIUrl":"10.3892/ijmm.2025.5589","url":null,"abstract":"<p><p>Ischemic heart disease (IHD), mainly due to atherosclerosis and coronary microvascular dysfunction, continues to be a major cause of mortality worldwide. This condition can escalate to severe complications, including heart failure, arrhythmias and sudden cardiac mortality. In advanced stages, treatments such as coronary artery bypass grafting or percutaneous coronary intervention may be necessary. The brain‑heart axis, which facilitates the interaction between the central nervous system and the cardiovascular system via the autonomic nervous system, is crucial in the management of IHD. An imbalance in autonomic function, marked by increased sympathetic activity and diminished parasympathetic influence, can worsen cardiovascular conditions by promoting inflammation, vasoconstriction and myocardial ischemia. Innovative treatments such as spinal cord stimulation and vagus nerve stimulation show potential in re‑establishing autonomic equilibrium and improving cardiovascular function by influencing the neurocardiac interface. The present review discussed the pathophysiology of IHD and methodically examined the role of the nervous system in this disease. It emphasized the possibilities of neural modulation therapy, while identifying ongoing challenges and areas lacking in current knowledge.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667606","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":"Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review).","authors":"Shuang Lv, Chunxia Luo","doi":"10.3892/ijmm.2025.5594","DOIUrl":"10.3892/ijmm.2025.5594","url":null,"abstract":"<p><p>The present review explored the emerging role of blood‑brain barrier (BBB) dysfunction in schizophrenia. Findings from biochemical markers, neuroimaging, genetic studies and experimental models are integrated to examine the impact of BBB dysfunction on the development and progression of schizophrenia. Additionally, the mechanisms by which BBB dysfunction exacerbates the schizophrenia were examined, including disruptions in cerebral blood flow, the facilitation of neuroinflammation and alterations in neurotransmitter systems. Finally, the potential for integrating BBB‑targeted interventions into broader therapeutic strategies for schizophrenia were discussed, with the goal of improving drug efficacy and minimizing side effects in clinical practice.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707336","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":"m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).","authors":"Qian Yi, Yi Liao, Wei Sun, Jiachen Li, Dahang Yang, Hongxi Shang, Weichao Sun","doi":"10.3892/ijmm.2025.5605","DOIUrl":"10.3892/ijmm.2025.5605","url":null,"abstract":"<p><p>N6‑methyladenosine (m6A) RNA modification represents a pivotal and novel post‑transcriptional modification in eukaryotic RNAs. Initially identified in messenger RNAs (mRNAs), m6A modification on these transcripts regulates a spectrum of essential cellular processes, including mRNA splicing, subcellular localization, stability and translation. Recent studies have highlighted the involvement of m6A methylation in both biological and pathological processes, particularly in cancer. Non‑coding RNAs (ncRNAs), a diverse class of RNA molecules that do not encode proteins, encompass microRNAs, long ncRNAs and circular RNAs. Notably, m6A has been recognized as a reversible epigenetic modification within ncRNAs, a discovery that has garnered considerable attention. This modification not only influences the stability of ncRNAs but also endows them with the novel capacity for peptide translation. The differential and specific expression pattern in diseases give these m6A‑modified ncRNAs potential as biomarkers for molecular diagnostics and targeted therapy, and using ncRNA‑encoded peptides as a target for immunotherapy has also been attempted. This review synthesizes the current understanding of m6A modifications in ncRNAs, explores the effects of m6A on ncRNA function and presents the latest insights into the role of ncRNA m6A modifications in disease progression.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799038","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":"[Expression of Concern] Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.","authors":"Xueling Guo, Jin Shang, Yan Deng, Xiao Yuan, Die Zhu, Huiguo Liu","doi":"10.3892/ijmm.2025.5600","DOIUrl":"10.3892/ijmm.2025.5600","url":null,"abstract":"<p><p>Following the publication of this paper, for the histopathological data shown in Fig. 2A, it was drawn to the Editor's attention by a concerned reader that, in the 'OGT' row of data panels, the 'Week  0' and 'Week 1' panels appeared to show an overlapping section of data, such that data which were intended to have shown the results of differently performed experiments appeared to have been derived from the same original source. Moreover, the OGT western blots shown in Fig. 4B were strikingly similar to the blots shown for the p-p38 MAPK experiment in this figure. The authors were contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal Of Molecular Medicine 36: 150-158, 2015; DOI: 10.3892/ijmm.2015.2198].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760054","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}