Molecular medicine reports最新文献

{"title":"Chimeric PD‑1 receptor redirects primary T cells against childhood solid tumors but not to PD‑1 ligand‑positive CD80‑coexpressing cells.","authors":"Chansu Shin, Masaru Imamura, Yasushi Kasahara, Yuko Suzuki, Minori Baba, Nobuhiro Kubo, Ryosuke Hosokai, Haruko Iwabuchi, Yudai Murayama, Hiroyuki Kawashima, Akira Ogose, Keichiro Mihara, Akihiko Saitoh, Chihaya Imai","doi":"10.3892/mmr.2025.13608","DOIUrl":"10.3892/mmr.2025.13608","url":null,"abstract":"<p><p>The clinical application of T cells engineered with chimeric antigen receptors (CARs) for solid tumors is challenging. A major reason for this involves tumor immune evasion mechanisms, including the high expression of immune checkpoint molecules, such as the programmed death 1 (PD‑1) ligands PD‑L1 and PD‑L2. The inducible expression of PD‑L1 in tumors has been observed after CAR‑T‑cell infusion, even in tumors natively not expressing PD‑L1. Furthermore, numerous types of pediatric cancer do not have suitable targets for CAR‑T‑cell therapy. Therefore, the present study aimed to develop novel CAR‑T cells that target PD‑L1 and PD‑L2, and to evaluate their efficacy against pediatric solid tumors. A novel CAR harboring the immunoglobulin V‑set domain of the human PD‑1 receptor as an antigen binding site (PD‑1 CAR‑T) was developed without using a single‑chain variable fragment. PD‑1 CAR‑T cells were successfully manufactured by adding an anti‑PD‑1 antibody, nivolumab, to the ex vivo expansion culture to prevent fratricide during the manufacturing process due to the inducible expression of PD‑L1 in activated human T cells. The expression of PD‑L1 (and PD‑L2 to a lesser extent) was revealed to be highly upregulated in various pediatric solid tumor cells, which displayed no or very low expression initially, on <i>in vitro</i> exposure to interferon‑γ and/or tumor necrosis factor‑α, which are cytokines secreted by tumor‑infiltrating T cells. Furthermore, PD‑1 CAR-T cells exhibited strong cytotoxic activity against pediatric solid tumor cells expressing PD‑L1 and PD‑L2. Conversely, the effect of PD‑1 CAR‑T cells was significantly attenuated against PD‑L1‑positive cells coexpressing CD80, suggesting that the toxicity of PD‑1 CAR‑T cells to normal immune cells, including antigen presenting cells, can be minimized. In conclusion, PD‑1 ligands are promising therapeutic targets for pediatric solid tumors. PD‑1 CAR‑T cells, either alone or in combination with CAR‑T cells with other targets, represent a potential treatment option for solid tumors.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608841","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":"Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway.","authors":"Yan Qu, Wei Xiong, Rui Zhou, Ning Song, Jinqiao Qian","doi":"10.3892/mmr.2025.13616","DOIUrl":"10.3892/mmr.2025.13616","url":null,"abstract":"<p><p>Dexmedetomidine (Dex) is a selective α2‑adrenergic receptor agonist used for its sedative effects in anesthesia and critical care. Although Dex exhibits cardioprotective effects, to the best of our knowledge, the mechanisms underlying these effects, particularly in a high‑glucose (HG) environment, remain unclear. Research into the role of Dex in alleviating oxidative stress injury in cardiac myoblasts through the PI3K/AKT signaling pathway may reveal novel cardioprotective mechanisms, enhance the understanding of cell survival and metabolic regulation, and offer potential clinical applications in cardiac surgery and critical care. The aim of the present study was to assess the protective effect and mechanism of Dex preconditioning (DP) against hydrogen peroxide (H₂O₂)‑induced H9C2 cardiac myoblast injury under HG conditions. H9C2 cardiac myoblasts were either untreated or pretreated with 10 nM Dex and the PI3K inhibitor LY294002 before exposure to H₂O₂ to induce oxidative cellular damage in the presence of HG culture medium. Cell viability assays were carried out, and apoptosis was evaluated using flow cytometry, TUNEL assays and western blotting. Additionally, the relative levels of oxidative stress indicators, including superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA), were determined. Exposure to H₂O₂ significantly decreased cell viability and increased apoptosis in H9C2 cardiac myoblasts cultured in HG conditions. Treatment with Dex significantly mitigated H₂O₂‑induced apoptosis, as evidenced by reduced expression of caspase‑3 and BAX, and increased levels of BCL‑2. In addition, oxidative stress was elevated in the HG + H₂O₂ group, as indicated by increased levels of the oxidative stress marker MDA, and reduced levels of the antioxidant enzymes SOD and CAT compared with those in the HG group. By contrast, DP in the DP + HG + H₂O₂ group reduced MDA levels, and increased SOD and CAT levels, indicating improved oxidative stress regulation. Treatment with the PI3K/AKT inhibitor LY294002 in the LY294002 + HG + DP + H₂O₂ group prevented these effects, further increasing MDA levels, and decreasing SOD and CAT levels compared with the DP + HG + H₂O₂ group, suggesting that the protective effects of Dex were abrogated by inhibition of the PI3K/AKT pathway. The present study revealed that Dex pretreatment attenuated H9C2 cardiac myoblast injury via the PI3K/AKT signaling pathway under HG conditions. Its protective effects may be achieved by reducing oxidative stress damage to cardiac myoblasts.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608842","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 role of circular RNAs in gastric cancer: From basic biology to clinical applications (Review).","authors":"Linkun Wang, Peng Zhou, Huiheng Qu, Zhihui Yang, Yuyang Li, Nan Wang, Jiazeng Xia","doi":"10.3892/mmr.2025.13617","DOIUrl":"10.3892/mmr.2025.13617","url":null,"abstract":"<p><p>Despite considerable advances in cancer treatment, gastric cancer (GC) remains a formidable challenge for oncologists worldwide, especially due to the poor survival rates associated with advanced‑stage cases. Circular RNAs (circRNAs) stand out as potential targets for more effective therapeutic strategies. The present review synthesizes insights into the roles of circRNAs in GC, highlighting their multifaceted influence on cancer progression and behaviors. circRNAs can regulate gene expression at multiple levels through modulating transcription, affecting alternative splicing, acting as molecular sponges for microRNAs, serving as RNA‑protein complexes and even encoding functional proteins. The marked stability of circRNAs in bodily fluids has also positioned them as promising diagnostic biomarkers, with some circRNA‑based tests demonstrating high accuracy. Furthermore, emerging evidence indicates that circRNAs carry out a key role in therapy resistance, affecting the therapeutic responses of patients to chemotherapy, targeted therapy and immunotherapy. Collectively, circRNA‑based therapeutic strategies, even with existing challenges in delivery methods, hold considerable promise, particularly when integrated with conventional treatment modalities, offering new avenues for improving GC management.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608844","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":"Roles of human SPATA3 in cell proliferation and expression pattern of <i>Spata3</i> in mouse testis.","authors":"Li Fu, Baixu Zhou, Xia Jiang, Jingliang Cheng, Qiang Wu, Junjiang Fu","doi":"10.3892/mmr.2025.13620","DOIUrl":"10.3892/mmr.2025.13620","url":null,"abstract":"<p><p>Male infertility predominantly manifests as abnormal spermatogenesis and maturation, abnormal semen quality, chromosomal abnormalities, and endocrine dysfunction. The present study aimed to explore the role, expression pattern and localization of spermatogenesis‑associated protein 3 (SPATA3) in the testis, and to analyze its spatiotemporal expression and function. Using previously acquired plasmids as templates, recombinant plasmids of different SPATA3 isoforms were constructed. Cell Counting Kit‑8 assay was used to analyze cell proliferation. Reverse transcription‑PCR and western blotting were used to determine the mRNA and protein expression levels, respectively. Different SPATA3 isoforms were induced to be overexpressed, among which SPATA3‑I1 and SPATA3‑I2 promoted cell proliferation. The subcellular localization results indicated that the green fluorescent protein fusion proteins of various isoforms were mainly localized in the nucleus. However, the fluorescence of the fusion proteins pEGFP‑C3‑SPATA3‑I3 and pEGFP‑C3‑SPATA3‑I4 tended to be distributed in the cytoplasm, accompanied by a decrease in nuclear fluorescence. Additionally, the SPATA3‑I2 isoform protein displayed notable tissue‑specific expression in testes. Notably, the SPATA3‑I2 isoform protein was not expressed in embryos or during the early development stage of the mice, yet it was highly expressed in the testes of mice aged 23‑57 days (3‑8 weeks). Immunohistochemistry revealed that the SPATA3‑I2 isoform protein was located mainly in round and elongated spermatids within the spermatogenic epithelial cells. In conclusion, the findings highlighted that SPATA3 isoforms had differential subcellular localizations and that SPATA3‑I2 exhibited a specific spatiotemporal expression pattern, suggesting its association with spermatogenesis and sperm maturation.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608849","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":"MicroRNAs: Novel clinical biomarkers for cancer radiotherapy (Review).","authors":"Junseok Park, Mi Eun Kim, Jun Sik Lee","doi":"10.3892/mmr.2025.13619","DOIUrl":"10.3892/mmr.2025.13619","url":null,"abstract":"<p><p>MicroRNAs (miRNAs/miRs) have attracted increasing attention as biomarkers and therapeutic agents for cancer treatment, particularly in the context of radiotherapy. Originally identified >30 years ago, miRNAs are short, non‑coding RNA molecules that regulate gene expression by binding to target mRNAs. Their involvement in physiological processes such as cell cycle regulation, DNA repair, apoptosis and signal transduction makes them essential for modulating cancer cell responses to therapeutic interventions. Recent research has explained the dual role of miRNAs in tumorigenesis. Some miRNAs function as oncogenes, promoting tumor growth and resistance to treatment, while others act as tumor suppressors, enhancing radiosensitivity and promoting apoptosis in cancer cells. Because of their stability, specificity and presence in bodily fluids, miRNAs are promising non‑invasive biomarkers for the diagnosis, prognosis and monitoring of therapeutic responses in cancer. Furthermore, miRNAs such as miR‑144, miR‑200c and let‑7 have demonstrated potential in guiding radiotherapy for breast, prostate, lung and other cancers, modulating treatment outcomes by enhancing radiosensitivity or contributing to radioresistance. Despite the early challenges of miRNA‑based therapies, advancements in miRNA delivery systems, including TargomiR‑ and liposome‑based approaches, offer promising avenues for clinical applications. The present review highlights the role of miRNAs as biomarkers and modulators in cancer radiotherapy and discusses ongoing research on miRNA delivery mechanisms to improve therapeutic outcomes. Future studies are needed to address the challenges of miRNA pleiotropy and safety in clinical applications, to advance miRNA‑based interventions in precision oncology, and to enhance the efficacy of radiotherapy across various cancer types.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of lipid mediators, obtained from docosahexaenoic acid via soybean lipoxygenase, on lipopolysaccharide‑induced acute lung injury through the NF‑κB and Nrf2/HO‑1 signaling pathways.","authors":"Yan Su, Hack Sun Choi, Soon Kyu Kwon, Yunjon Han, Soon-Chang Cho, Jin Hyuk Shin, Yong-Suk Jang, Jong Hyun Choi, Jeong-Woo Seo","doi":"10.3892/mmr.2025.13598","DOIUrl":"10.3892/mmr.2025.13598","url":null,"abstract":"<p><p>Acute lung injury (ALI), marked by acute and chronic inflammation, causes damage to alveolar epithelial and capillary endothelial cells. The present study investigated lipid mediators (LM) effects on lipopolysaccharide (LPS)‑induced RAW264.7 cells and ALI mice. LM, comprising 17S‑monohydroxy docosahexaenoic acid (DHA), resolvin D5 and protectin DX (in a 3:47:50 ratio), were derived from DHA via soybean lipoxygenase and demonstrated anti‑inflammatory properties. <i>In vitro</i> experiments revealed that LM decreased nitric oxide (NO) and prostaglandin E2 (PGE2) levels caused by LPS via downregulating inducible nitric oxide synthase and cyclooxygenase‑2. Additionally, LM inhibited the inflammation by suppressing NF‑κB signaling. The results also indicated that LM reduced oxidative stress by lowering reactive oxygen species and malondialdehyde (MDA) levels while enhancing glutathione (GSH) content and superoxide dismutase (SOD) activities, probably through activation of nuclear factor erythroid 2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) signaling pathway. Moreover, the benefits of LM on inflammation and oxidative stress were reversed when pretreated with ML385, an Nrf2 inhibitor. <i>In vivo</i> studies revealed that LM reduced the lung wet/dry ratio, increased GSH, catalase and SOD activities, along with lowered myeloperoxidase and MDA levels. In addition, LM reduced inflammatory cytokine levels in serum and bronchoalveolar lavage fluid. Mechanistically, LM inhibited NF‑κB signaling and activated Nrf2/HO‑1 signaling pathways.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333533","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":"miR‑145 and miR‑23b co‑transfection decreases proliferation, migration, invasion and protein levels of c‑MYC, ZEB1 and ABCB1 in epithelial ovarian cancer cell lines.","authors":"Allison Fredes-Garrido, Álvaro Armijo Cruz, Gloria M Calaf, Maritza P Garrido, Carmen Romero","doi":"10.3892/mmr.2025.13611","DOIUrl":"10.3892/mmr.2025.13611","url":null,"abstract":"<p><p>MicroRNAs (miRs) are non‑coding RNAs that prevent the translation of mRNAs. miRs participate in cellular processes such as cell proliferation, migration and invasion, acting as oncogenes or tumor suppressors. In epithelial ovarian cancer (EOC), a decrease in tumor suppressor miRs, such as miR‑145 and miR‑23b, regulates the mRNAs of oncogenic proteins. The present study aimed to determine whether the co‑transfection of two oncosuppressor miRs (miR‑145‑5p and miR‑23b‑3p) decreased the proliferation, migration, invasion, and protein levels of c‑MYC, zinc finger E‑box binding homeobox 1 (ZEB1) and ATP binding cassette subfamily B1 (ABCB1) in EOC cell lines (A2780, SKOV‑3 and OV‑90). Reverse transcription‑quantitative PCR was employed to determine miR expression after co‑transfection. Cell proliferation was evaluated by Ki‑67 immunofluorescence staining and Ki‑67 positive cell counting. Transwell inserts, both with and without Matrigel, were used to assess invasion and migration, respectively. c‑MYC, ZEB1 and ABCB1 protein expression was determined by western blot analysis. The co‑transfection of miR‑145 and miR‑23b resulted in decreased proliferation, migration and invasion, along with reduced protein expression levels of c‑MYC, ZEB1 and ABCB1 in EOC cells. The combination of miR‑23b and miR‑145 transfection in EOC cells exhibited good antitumor effects, thus supporting the design of future complementary therapies for EOC.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608848","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":"Mechanisms and interventions in aneurysmal subarachnoid hemorrhage: Unraveling the role of inflammatory responses and cell death in early brain injury (Review).","authors":"Rijin Lin, Sheng Guan, Jian Wang, Mingyang Han, Mengyan Fan, Jiaxin Wan, Xiaowen Zhang, Nan Zhang, Jing Li","doi":"10.3892/mmr.2025.13621","DOIUrl":"10.3892/mmr.2025.13621","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of stroke associated with high morbidity and mortality rates worldwide, posing challenges in developing effective treatment strategies. The present review aimed to summarize the role of inflammation and pyroptosis in early brain injury (EBI), a key determinant of outcomes in aSAH, the interplay between oxidative stress, neuroinflammation and cell death and the immune‑inflammatory response and oxidative stress as central components in the pathogenesis of aSAH. Key signaling pathways include toll‑like receptor 4/NF‑κB and NLR family pyrin domain‑containing 3/gasdermin D pathways, which regulate inflammatory responses and pyroptotic cell death. Additionally, current and traditional Chinese therapeutic approaches to mitigating EBI and improving patient outcomes are summarized, demonstrating the potential roles of salvianolic acid B, pterostilbene, luteolin and electro‑acupuncture. The findings of the present review underscore the necessity for continued research into the molecular mechanisms underlying aSAH to translate these insights into clinical practice, enhancing patient survival and recovery.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668021","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":"Combination of machine learning and protein‑protein interaction network established one ATM‑DPP4‑TXN ferroptotic diagnostic model with experimental validation.","authors":"Mengze Wu, Zhao Zou, Yuce Peng, Suxin Luo","doi":"10.3892/mmr.2025.13604","DOIUrl":"10.3892/mmr.2025.13604","url":null,"abstract":"<p><p>Ferroptosis and lethal sepsis are interlinked, although this association remains largely unknown to clinical panels. Sepsis is characterized by dysfunction of the inflammatory microenvironment. Most septic biomarkers lack independent validation, and a comprehensive diagnosis comprising biomarker assessment combined with clinical evaluation may improve sepsis management. Targeting ferroptosis regulators may offer new hope for uncovering the inflammatory machinery and for developing novel diagnostic methods for sepsis, and bioinformatics analyses are a valuable tool to investigate this further. In the present study, septic datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were subsequently introduced in enrichment analyses and intersected with ferroptotic genes for acquiring ferroptosis‑related DEGs (FRDEGs). A protein‑protein interaction network (PPIN) was then constructed to retain hub‑FRDEGs, and this was imported into three machine learning algorithms. A nomogram based on the logistic regression model was subsequently built and validated <i>in silico</i>. CIBERSORT and single‑sample gene set enrichment analysis were used to carry out an analysis of the immune microenvironment, and inflammatory associations with the hub‑FRDEGs were examined. A cellular model was subsequently applied to substantiate the results of the bioinformatic analyses. A total of 94 FRDEGs were obtained from the overlap of 4,410 DEGs and 506 ferroptotic genes. One PPIN of FRDEGs was constructed to identify 38 hub‑FRDEGs, and the three machine learning algorithms were subsequently analyzed, which resulted in the identification of three hub‑FRDEGs, namely ataxia telangiectasia mutated, dipeptidyl peptidase 4 and thioredoxin. One diagnostic nomogram was advanced and scrutinized for its diagnostic accuracy. The functions and pathways of the DEGs were revealed to be mainly concentrated on the immune response and cellular transportation. A notably wide discrepancy was demonstrated to exist between the hub‑FRDEGs and the immunocytes. In conclusion, three potential hub‑FRDEGs connected with sepsis were identified in the present study. Their diagnostic accuracy and immune association demonstrated that ferroptosis is implicated in the inflammatory dysfunction of sepsis, and based on these findings, novel strategies for pharmacological interference and improving diagnostic utility may be developed to facilitate improved management of sepsis.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560542","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":"Centrosome‑, mitotic spindle‑ and cytokinetic bridge‑specific compartmentalization of AGO2 protein in human liver cells undergoing mitosis: Non‑canonical, RNAi‑dependent, control of local homeostasis.","authors":"Eleni I Theotoki, Panos Kakoulidis, Konstantinos-Stylianos Nikolakopoulos, Eleni N Vlachou, Ourania E Tsitsilonis, Gerassimos E Voutsinas, Ema Anastasiadou, Dimitrios J Stravopodis","doi":"10.3892/mmr.2025.13609","DOIUrl":"10.3892/mmr.2025.13609","url":null,"abstract":"<p><p>Argonaute RNA‑induced silencing complex catalytic component 2 (AGO2) is an evolutionary conserved protein involved in microRNA‑dependent gene expression regulation via the RNA interference (RNAi) mechanism. Nevertheless, AGO2 may also be involved in other key processes, such as histone modification, DNA methylation and alternative splicing. Its role in the proper development of organisms is key and no homologue is able to compensate for its loss. Therefore, using advanced immunofluorescence, transient transfection and molecular bioinformatics, the present study aimed to investigate novel, non‑canonical, RNAi‑dependent functions of AGO2 protein in mRNA/protein local homeostasis. The data revealed microtubule network‑dependent, localization of AGO2 in both centrosome and mitotic spindle assemblies during cell division and in the cytokinetic bridge formed during the last stage of mitosis (cytokinesis). Detection of AGO2 protein in these mitosis‑specific compartments, regardless of the presence of malignant phenotypes or multiple centrosomes/mitotic spindles in liver cells, indicates the cardinal role of AGO2 in centrosome biosynthesis, mitotic spindle formation and function, potentially controlling locality‑dependent homeostasis, in a novel non‑canonical, RNAi‑dependent manner. This novel AGO2/centrosome/mitotic spindle/cytokinetic bridge pathway may serve as a versatile molecular 'toolbox' for targeted therapy of human malignancy, including liver cancer.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608840","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}