Molecular Biology Reports最新文献

{"title":"Identification and validation of stable reference genes for RT-qPCR analysis in blood samples from golden Syrian hamsters under different immunological conditions.","authors":"Jady Duarte Nogueira, Tiffany Thurow Bunde, Mara Andrade Colares Maia, Natasha Rodrigues de Oliveira, Odir Antônio Dellagostin, Thaís Larré Oliveira Bohn","doi":"10.1007/s11033-026-12980-8","DOIUrl":"10.1007/s11033-026-12980-8","url":null,"abstract":"<p><strong>Background: </strong>The golden Syrian hamster is the main experimental model for leptospirosis. However, there are no validated reference genes for reverse transcription quantitative PCR (RT-qPCR) analysis of blood samples.</p><p><strong>Methods and results: </strong>The expression stability of 11 candidate reference genes was evaluated in hamster blood under distinct immunological conditions, including Leptospira interrogans infection and different immunization strategies. Stability was assessed using BestKeeper, geNorm, NormFinder, and the comparative ΔCt method, with the consensus ranking calculated using the RefFinder approach implemented in the RefSeeker R package. The most stable reference gene was ppia, followed by gapdh and ppib, whereas actb was the least stable gene in the ranking. Normalization of tnf-α expression using actb resulted in an approximately 10-fold overestimation compared with ppia, demonstrating the impact of reference gene choice on data interpretation.</p><p><strong>Conclusions: </strong>These findings support ppia as a reliable reference gene for RT-qPCR normalization in hamster blood under both infection and vaccination conditions.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13694556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mimosa pudica L. extract attenuates endometrial hyperplasia and proliferation of its malignant cell lines: transcript-level insights from a dual in vivo-in vitro model.","authors":"Chandran Manimegalai Swathi, Kalimuthu Vignesh, Chenniappan Archana Devi, Balamuthu Kadalmani","doi":"10.1007/s11033-026-12910-8","DOIUrl":"10.1007/s11033-026-12910-8","url":null,"abstract":"<p><strong>Background: </strong>Endometrium is the innermost layer of the uterus that respond to and synthesize estrogens in connection with its synchronized thickening and shedding during menstrual cycle. Since its thickening is essential for implantation of the embryo, its hyperplasia at chronicity could lead to uterus-associated infertility. if untreated.</p><p><strong>Methods: </strong>Qualitative and quantitative analysis of phytochemical constituents, antioxidant efficacy, and GC-MS analysis of M. pudica leaf extract were done. The antiproliferative efficacy of the extract was assessed by MTT assay, fluorescent staining, and mRNA studies of apoptotic-related genes in endometrial cancer cells (Ishikawa and AN3CA). About 25 female rats were assigned to five groups, control (Group 1) and DES-induced endometrial hyperplasia (Groups 2-5). in this, Groups 3-5 were treated with M. pudica leaf extract at increasing doses to assess its restorative efficacy in terms of estrous cycle, structure of ovary, and uterine weight adopting quantification of hormones, ROS, and mRNA expression of genes associated with inflammation (IL-6, NCOR1, and DLK1), angiogenesis (VEGF), and progression of endometrial hyperplasia (ARID1A, SMARCA4, PIK3CA and KRAS).</p><p><strong>Results: </strong>Administration of M. pudica leaf extract restored the estrous cycle, bringing to normalcy the structure and function of the ovary and uterus, balancing hormones, and reducing inflammation. The expression of ARID1A and SMARCA4, were enhanced while those of genes associated with proliferation, angiogenesis, and inflammation were mitigated.</p><p><strong>Conclusion: </strong>M. pudica leaf extract is potentially effective as a therapeutic agent against endometrial hyperplasia and its cancer cell proliferation by restoring nearly all the dysregulations up to mRNA expression level.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers and future directions for immunotherapy in microsatellite-stable colorectal cancer: a systematic review.","authors":"Jiaju Xu, Chunxiao Ni, Ping Wang, Lidong Qin","doi":"10.1007/s11033-026-13054-5","DOIUrl":"10.1007/s11033-026-13054-5","url":null,"abstract":"<p><p>The mechanisms of resistance to immune checkpoint inhibitors (ICIs) in microsatellite-stable (MSS) colorectal cancer (CRC) have 3 interconnected levels, which provide information to guide different biomarker strategies. There is a critical clinical need, as objective response rates continue to be < 10%. We suggest a biomarker stratification model on the basis of clinical actionability. POLE/POLD1 mutations, recommended by the NCCN Clinical Practice Guidelines in Oncology for Colon Cancer (Version 1.2025), represent true genomic \"hard\" indicators. While the benefit of ICI-containing combination regimens was predicted by the Immunoscore-IC in the AtezoTRIBE trial, the ANICCA-class II study recently questioned the value of anti-PD-1 monotherapy. Defects in homologous recombination repair HRR), ctDNA kinetics and subtyping of CMS1 show promise but need to be prospectively validated. TMB, however, has shown no consistent value as a single biomarker, and MSIs, such as transcriptomic signatures or PD-L1 combined positive scores, have not been proven to be useful. Future prospects involve multiomics algorithms that integrate immune profiling and stromal determinants, liver-directed sensitizing approaches and serial ctDNA monitoring of acquired resistance as viable strategies for further patient selection. These data collectively pave the way toward moving away from the \"cold tumor\" paradigm and toward dynamic, host-integrated testing for precision immunotherapy in MSS CRC.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of tert-butylhydroquinone on cisplatin-induced neurotoxicity in rats.","authors":"Serdar Yigit, Soner Bitiktas, İsa Yeşilyurt, Huseyin Fatih Gul, Başak Gulakar, Zeynep Cansu Aydın, Ali Alper Kahraman","doi":"10.1007/s11033-026-12986-2","DOIUrl":"10.1007/s11033-026-12986-2","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (Cis) is a potent chemotherapy agent with limited clinical use due to serious side effects, including neurotoxicity. This study investigated the neuroprotective effects of tert-butylhydroquinone (TBHQ) against Cis-induced neurotoxicity.</p><p><strong>Materials and methods: </strong>Rats were randomly divided into five groups (n = 6 per group): Control, Cis, Vehicle, TBHQ, and Cis+TBHQ. Cognitive and behavioral changes were assessed using the Morris Water Maze (MWM) and the Open Field Test. Serum samples were analyzed for antioxidant/oxidant markers (SOD, CAT, GSH, and MDA), and hippocampal tissues were evaluated histopathologically and immunohistochemically (TNF-α, IL-6, and neurogranin).</p><p><strong>Results: </strong>In the MWM test, escape latency to the hidden platform on day 2 of training was significantly longer in the Cis group than in the control group (38.63 ± 15.77 s vs. 14.25 ± 5.82 s, p = 0.014). In contrast, TBHQ co-administration (Cis+TBHQ) alleviated these cognitive deficits, particularly during early learning, significantly reducing day 2 escape latency to 19.04 ± 7.77 s compared with the Cis group (38.63 ± 15.77 s, p = 0.044). Biochemically, Cis was associated with decreased serum SOD, CAT, and GSH and increased serum MDA (p < 0.05). Histopathologically, hemorrhagic foci were observed in the Cis group. Furthermore, immunohistochemical analysis revealed that Cis was associated with increased TNF-α and IL-6 immunoreactivity (p < 0.0001) and decreased neurogranin immunoreactivity (p < 0.0001).</p><p><strong>Conclusion: </strong>Collectively, Cis administration causes potent neurotoxicity, severely impairs spatial learning, and alters plasticity-associated marker neurogranin and inflammatory markers. Specifically, TBHQ administration was associated with the attenuation of Cis-induced cognitive deficits and biochemical alterations. Given its defined profile, TBHQ may warrant further investigation for mitigating chemotherapy-induced neurotoxicity.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM27 enhances NF-κB/MAPK activation by ubiquitinating and degrading TRAF3 to drive asthma-induced airway inflammation.","authors":"Juan Xie, Cheng Guo, Yang Li, Hong Lu, Yuanyuan Wen, Kai Liu","doi":"10.1007/s11033-026-12999-x","DOIUrl":"10.1007/s11033-026-12999-x","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic inflammatory airway disease, and airway epithelial cell injury is closely associated with disease progression. TRIM27, as an E3 ubiquitin ligase, plays a significant role in immune-inflammatory responses. This study aims to investigate the role of TRIM27 in airway epithelial cell injury and inflammation.</p><p><strong>Methods: </strong>House dust mite extract (HDM)-induced mouse or 16HBE cell models were constructed to simulate asthma in vivo and in vitro. Lung histopathological injury was assessed via HE and PAS staining. Bronchoalveolar lavage fluid (BALF) inflammatory cell counts and ELISA were used to measure inflammation levels. Cell viability and apoptosis was detected by CCK-8, flow cytometry and TUNEL staining. RT-qPCR and Western blot were employed to detect related gene and protein expression.</p><p><strong>Results: </strong>TRIM27 was upregulated in both in vivo and in vitro asthma models. TRIM27 knockdown alleviated HDM-induced lung histopathological damage in mice, reduced goblet cell hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In vitro experiments showed that TRIM27 knockdown partially restored HDM-induced decline in cell viability, inhibited apoptosis, ROS generation, and inflammatory cytokine release. Mechanistic studies revealed that HDM stimulation activated the NF-κB/MAPK pathway, while TRIM27 knockdown suppressed its activation. Further research demonstrated that TRIM27 activates the NF-κB/MAPK pathway by promoting TRAF3 ubiquitination and degradation. TRAF3 knockdown can weaken the beneficial effects of TRIM27 knockdown.</p><p><strong>Conclusion: </strong>TRIM27 activates the NF-κB/MAPK signaling pathway by promoting TRAF3 ubiquitination and degradation, thereby exacerbating airway epithelial cell injury and inflammatory response, and promoting asthma progression.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospecting for efflux pump and repressor genes in rivers of the Amazon region of Brazil.","authors":"Valéria Alves Chaves, David Tavares Martins, Carlos Willian Dias Dantas, Savia Moreira da Silva, Juliana Araripe Gomes da Silva, Ana Lídia Queiroz Cavalcante, Daralyns Borges Macedo, Ana Luzia Leite Fernandes, Sandeep Tiwari, Rommel Thiago Jucá Ramos, Oscar Victor Cardenas-Alegria","doi":"10.1007/s11033-026-12979-1","DOIUrl":"10.1007/s11033-026-12979-1","url":null,"abstract":"<p><strong>Background: </strong>The spread of multidrug-resistant bacteria in water bodies poses a significant public health concern. Efflux pumps represent critical mechanisms of antimicrobial resistance, regulated by genetic repressors that aid bacterial adaptation to environmental stress. This study profiles the diversity of efflux pump genes and genetic repressors in the surface waters of the Cereja (Bragança) and Uraim (Paragominas) rivers in the Amazon region of Brazil.</p><p><strong>Methods and results: </strong>Surface water samples were collected along a gradient of anthropogenic impact, and environmental DNA was sequenced on the Illumina platform. The resulting sequencing data were subsequently subjected to metagenomic analysis, which identified a higher abundance of efflux pump genes in the Cereja River compared to the Uraim River, dominated by the RND and SMR families. Additionally, two-component system (TCS) repressor genes, particularly cbrB, were successfully recovered and modeled using Swiss-Model homology modeling.</p><p><strong>Conclusions: </strong>The higher coverage of the cbrB repressor gene in anthropogenically impacted sites underscores its regulatory role in bacterial stress responses, suggesting its potential application as a novel biomarker of environmental pollution and antibiotic resistance spread in aquatic ecosystems.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13694302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced GP73 promotes the Warburg effect in hepatocellular carcinoma via HIF-1α.","authors":"Mierkamilijiang Abudureheman, Diwen Zhu, Weixin Ren","doi":"10.1007/s11033-026-12991-5","DOIUrl":"10.1007/s11033-026-12991-5","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE)-induced hypoxia is a key driver of hepatocellular carcinoma (HCC) progression. This study investigated whether Golgi protein 73 (GP73) drives the Warburg effect and epithelial-mesenchymal transition (EMT) via hypoxia-inducible factor-1α (HIF-1α) under hypoxia, thereby promoting HCC malignancy.</p><p><strong>Methods: </strong>HepG2 cells were exposed to hypoxia (1% O₂). Lentivirus-mediated GP73 overexpression (LV-GP73) and siRNA-mediated HIF-1α knockdown (si-HIF-1α) were established. Four groups were compared: H + LV-NC (negative control), H + LV-GP73, H + LV-GP73 + si-NC, and H + LV-GP73 + si-HIF-1α. Cell proliferation, apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, and Transwell assays. Glycolysis and mitochondrial respiration were evaluated by biochemical kits and Seahorse XFe24 Analyzer. Protein levels were detected by Western blotting. Clinical validation was performed in peripheral blood mononuclear cells (PBMCs) from 169 HCC patients who underwent TACE.</p><p><strong>Results: </strong>GP73 overexpression significantly enhanced colony formation, migration, invasion, glucose consumption, lactate production, LDH activity, ATP levels, and extracellular acidification rate, while decreasing apoptosis (P < 0.05). It also showed a decreasing trend in oxygen consumption rate, indicating Warburg effect activation. It also upregulated HIF-1α, glycolytic enzymes (HK2, SLC2A1, LDHA, PGK1), and Vimentin, but downregulated E-cadherin (P < 0.05). Notably, HIF-1α knockdown reversed all these pro-tumorigenic phenotypes, metabolic reprogramming, and molecular changes. Clinical validation further confirmed that PBMCs from TACE-resistant patients exhibited significantly elevated GP73, HIF-1α, and HK2 expression at both mRNA and protein levels (all P < 0.001), consistent with the in vitro findings.</p><p><strong>Conclusions: </strong>Under hypoxia, GP73 promotes the Warburg effect and EMT through HIF-1α stabilization, facilitating HCC progression. The GP73-HIF-1α axis is a critical mediator of TACE resistance and a potential therapeutic target. PBMC-based detection of this pathway may serve as a non-invasive strategy for monitoring TACE resistance risk.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization of Fusobacterium necrophorum subsp. necrophorum strain JKSFn-26 associated with severe ovine footrot in Kashmir, India.","authors":"S Farooq, M A Bhat, M N Hassan, M I Hussain, H M Dar","doi":"10.1007/s11033-026-12996-0","DOIUrl":"10.1007/s11033-026-12996-0","url":null,"abstract":"<p><strong>Background: </strong>Fusobacterium necrophorum is an important anaerobic bacterium associated with the progression and severity of ovine footrot. However, genomic information on footrot associated isolates, particularly those recovered from severe lesions, remains limited. Here, we report the genomic characterization of F. necrophorum subsp. necrophorum strain JKSFn-26, isolated from a severe ovine footrot lesion in Kashmir, India.</p><p><strong>Methods: </strong>The isolate was characterized phenotypically and assigned to the previously identified JKS-F3 leukotoxin (lktA) variant by partial gene sequence analysis. Whole genome sequencing was performed using the Illumina HiSeq platform. The draft genome was subjected to annotation, phylogenomic analysis, and in silico screening for virulence associated genes, toxin-related determinants, antimicrobial resistance associated genes, and adaptive defense elements.</p><p><strong>Results: </strong>JKSFn-26 belonged to the JKS-F3 lktA variant previously associated with severe ovine footrot in Kashmir, and the analyzed lktA gene fragment showed 100% nucleotide identity with the reported JKS-F3 sequence. The draft genome was 2.23 Mb with a G + C content of 34.37% and contained 2,048 predicted coding sequences, 45 tRNAs, five rRNAs, four annotated non-coding RNAs, one tmRNA, two CRISPR arrays, and ten pseudogenes. Phylogenomic analysis placed JKSFn-26 within the F. necrophorum subsp. necrophorum clade. The genome contained the lktBAC locus and predicted virulence associated determinants related to hemolytic activity, adhesion, iron acquisition, and outer membrane proteins. Multiple toxin-antitoxin modules and putative antimicrobial resistance associated determinants were also identified. The deduced LktA amino acid sequence showed 98.0% identity to the corresponding leukotoxin A sequence of Fusobacterium necrophorum subsp. necrophorum strain ATCC 25286 .</p><p><strong>Conclusions: </strong>This study provides genomic information on a JKS-F3 lktA variant associated with severe ovine footrot in Kashmir and expands genomic resources for F. necrophorum.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of 2'-5'-oligoadenylate synthetase (OAS) proteins in HIV infection: innate antiviral immunity, viral persistence, and therapeutic opportunities.","authors":"Mohammad Mehdi Akbarin, Zahra Farjami, Mahdieh Soltani, Hugo Ramírez Álvarez","doi":"10.1007/s11033-026-13013-0","DOIUrl":"10.1007/s11033-026-13013-0","url":null,"abstract":"<p><p>Human immunodeficiency virus type 1 (HIV-1) establishes persistent infection despite robust innate immune responses and effective antiretroviral therapy, highlighting the importance of host antiviral mechanisms in regulating viral replication and persistence. Among interferon-stimulated genes, 2'-5'-oligoadenylate synthetase 1 (OAS1) is a key antiviral effector that senses viral double-stranded RNA and activates the OAS-RNase L pathway. Beyond its canonical antiviral activity, emerging evidence implicates OAS1 in immune regulation, viral latency, neuroinflammation, and retroviral disease progression. This review examines the genomic organization, structural diversity, isoform-specific functions, genetic variation, and interferon-mediated regulation of the OAS protein family, emphasizing OAS1 in HIV infection. Experimental and clinical studies indicate that type I and type III interferons induce OAS1 in macrophages, dendritic cells, epithelial and endothelial cells, microglia, and lymphocytes, contributing to HIV restriction through RNase L activation and enhanced innate antiviral responses. OAS signalling may also support mucosal antiviral defence, regulate viral burden and chronic immune activation, influence interferon responsiveness during combination antiretroviral therapy, and contribute to central nervous system protection. Conversely, dysregulated OAS1 expression has been associated with HIV-associated neurocognitive disorders. Genetic polymorphisms and alternative splicing generate functional diversity in OAS1, potentially influencing antiviral activity, individual susceptibility, and clinical outcomes. Collectively, available evidence positions OAS1 as a multifunctional antiviral and immunoregulatory component of host defence that may influence multiple aspects of HIV pathogenesis. Further investigation into OAS1 activation, genetic variation, isoform-specific functions, and immune modulation may facilitate biomarker discovery and support the development of host-directed therapeutic strategies against persistent retroviral infections.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLU attenuates sepsis-associated acute lung injury by inhibiting Bax-mediated mitochondrial damage.","authors":"Song Chen, Fei Zhong, Conghui Fan, Wei Song, Tao Zhang, Yijiong Zhang, Jian Wan, Hu Peng","doi":"10.1007/s11033-026-12794-8","DOIUrl":"10.1007/s11033-026-12794-8","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (ALI) is typified by unchecked inflammation and widespread cell death, yet the underlying molecular pathways are still unclear.</p><p><strong>Methods: </strong>Differentially expressed genes were identified from the GSE10474 dataset. Protein-protein interaction (PPI) network analysis was employed to identify hub genes, and expression validation was carried out. An in vitro model of ALI caused by sepsis was applied to confirm CLU expression. CLU expression was assessed by qRT-PCR and Western blotting. To investigate the function and mechanism of CLU expression, functional assays such as cell viability assays, flow cytometry, co-immunoprecipitation (Co-IP), transmission electron microscopy (TEM), cytochrome c (Cyto c) release, and Reactive Oxygen Species (ROS) assays, ATP content, and mitochondrial membrane potential (ΔΨm) were carried out.</p><p><strong>Results: </strong>Bioinformatics analysis identified six hub genes (CDKN1A, HIST1H3F, HLA-DQB1, CD74, VDAC1, and CLU) as downregulated in sepsis-induced ALI. The reduction of CLU expression in the ALI model was validated by experimental validation, whereas its overexpression decreased apoptosis and restored cell viability. Mechanistically, CLU interacted with Bax and inhibited its translocation to mitochondria, which may contribute to Cyto c release, preserving ATP content and ΔΨm, maintaining mitochondrial morphology, and reducing ROS accumulation. Crucially, the protective effect of CLU was attenuated by overexpressing Bax, which resulted in increased apoptosis, lower cell viability, increased reactive oxygen species, and worsened mitochondrial damage.</p><p><strong>Conclusion: </strong>Our in‑vitro findings suggest that CLU could mitigate apoptosis in the sepsis‑induced ALI cell model, at least partly through modulating Bax‑dependent mitochondrial damage. These results point to CLU as a possible treatment target for ALI caused by sepsis.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}