Cell Biology and Toxicology最新文献

{"title":"FBXO39 knockdown promotes spermatogenesis impairment by inducing mitochondrial dysfunction and ferroptosis via inhibiting KDM5A ubiquitination and regulating H3K4me3 demethylation.","authors":"Tao Li, Kun Wang, Yuxiang Chen, Zhuocheng Li, Shanda Li, Yu Zhang, Xuyuan Zhu, Haoran Shi, Liang Gao, Hongtao Jiang","doi":"10.1007/s10565-026-10167-2","DOIUrl":"10.1007/s10565-026-10167-2","url":null,"abstract":"<p><p>The global decline in male fertility highlights the need to understand the mechanisms of spermatogenesis. Mitochondrial dysfunction and ferroptosis have emerged as key contributors to spermatogenic impairment, although the molecular basis of this process is still poorly defined. F-Box Protein 39 (FBXO39), a testis-enriched F-box protein, has been preliminarily associated with cell survival. However, whether FBXO39 participates in mitochondrial functional regulation or ferroptosis signaling during spermatogenesis remains largely unexplored. In our study, FBXO39 knockdown resulted in abnormal testicular development, impaired spermatogenesis, abnormal sperm morphology, and reduced testicular cell viability. Further analysis revealed that FBXO39 deficiency caused mitochondrial dysfunction and ferroptosis, as reflected by decreased ATP production, reduced mitochondrial DNA content, elevated eactive oxygen species (ROS) levels, diminished expression of key mitochondrial proteins, and elevated lipid peroxidation. Mechanistically, FBXO39 maintains mitochondrial homeostasis by targeting lysine-specific demethylase 5A (KDM5A) for ubiquitination-dependent degradation. Conversely, the accumulation of KDM5A upon FBXO39 loss suppressed single-stranded DNA-binding protein 1 (SSBP1) levels through demethylation of Histone H3 lysine 4 trimethylation (H3K4me3) at the SSBP1 promoter. Importantly, restoration of SSBP1 expression functionally ameliorated mitochondrial dysfunction induced by FBXO39 knockdown. Overall, FBXO39 regulates mitochondrial function and ferroptosis in testicular cells through ubiquitinating KDM5A, which affects SSBP1 expression by modulating H3K4me3 demethylation at the SSBP1 promoter. This study elucidates the role of FBXO39 in spermatogenesis and suggested that targeting this regulatory axis may offer novel therapeutic strategies for male infertility.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene Nanoplastics induced placental toxicology by activating Keap1-mediated ferroptosis via METTL3-dependent m6A methylation.","authors":"Yujiao Chen, Yifan Liu, Meng Zhang, Shanshan Li, Yousheng Yan, Chenghong Yin","doi":"10.1007/s10565-026-10152-9","DOIUrl":"10.1007/s10565-026-10152-9","url":null,"abstract":"<p><p>Polystyrene nanoplastics (PS-NPs) exposure can induce placental toxicity, but the molecular mechanism of PS-NP-induced placental toxicity is poorly understood. We selected PS-NPs (80 nm) as a model of plastic particles and treated the human trophoblast cell line JEG3 (6.25, 12.5, 25, 50, and 100 mg/L) and pregnant mice with PS-NPs (15, 30 and 60 mg/kg·bw). These results found that PS-NPs regulated key ferroptosis-associated proteins (GPX4, ACSL4, and FTH1), indicating that PS-NPs induced ferroptosis. Here, we show for the first time that PS-NPs trigger placental ferroptosis by disrupting the p62-Keap1 interaction, thereby blocking Nrf2 degradation. Although m6A modification of the p62-Keap1-Nrf2 axis has been described in other models, its involvement in nanoplastic-induced placental injury remains unexplored. Here, we showed that PS-NPs induce ferroptosis by promoting METTL3 expression in JEG cells and placental tissues. Furthermore, knockdown of METTL3 inhibited PS-NP-induced ferroptosis by regulating Keap1 m6A, which inhibited the p62-Keap1-Nrf2 pathway in vitro. PS-NP-induced ferroptosis was attenuated by METTL3 knockdown via the inhibition of Keap1 m6A, which regulates the p62-Keap1-Nrf2 pathway. Collectively, these findings indicate thatMETTL3-mediated m6A methylation induced by PS-NPs may represent a previously unrecognized molecular basis for placental injury.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate Dehydrogenase B delactylation promotes gastric cancer metastasis via enhancing glutathione-mediated resistance to ferroptosis.","authors":"Xun Xiao, Yan Yang, Yunchao Yang, Gaoping Zhao","doi":"10.1007/s10565-026-10165-4","DOIUrl":"10.1007/s10565-026-10165-4","url":null,"abstract":"<p><strong>Purpose: </strong>To elucidate the role of protein lactylation in gastric adenocarcinoma progression, focusing on lactate dehydrogenase B (LDHB) delactylation at K58 and its effects on metastasis, glutathione (GSH) metabolism, and ferroptosis resistance.</p><p><strong>Methods: </strong>Quantitative proteomics profiled lactylation in gastric adenocarcinoma versus adjacent normal tissues. Bioinformatics and Kaplan-Meier analyses assessed differentially lactylated genes and survival correlations. LDHB lactylation sites were validated via immunoprecipitation and Western blotting in lactate-stimulated cells. Functional assays evaluated LDHB-K58R (delactylation mimic) effects on proliferation, invasion, GSH levels, cystine uptake, STAT1/SLC7A11/GPX4 expression, and RSL3-induced ferroptosis in vitro. EMT markers were examined by immunofluorescence and Western blotting. In vivo lung metastasis was assessed in nude mice injected with modified AGS cells, treated with RSL3 or DMSO.</p><p><strong>Results: </strong>Proteomics identified 121 upregulated and 53 downregulated lactylation sites in tumors, with LDHB as a key differentially lactylated protein. High LDHB expression correlated with poor progression-free and disease-specific survival. LDHB was primarily lactylated at K58; K58R delactylation enhanced proliferation, colony formation, invasion, cystine uptake, and SLC7A11-dependent GSH synthesis by suppressing STAT1 and downregulating GPX4, without affecting EMT or lactate release. K58R conferred robust resistance to RSL3-induced ferroptosis, reducing lipid ROS and preserving malignant phenotypes in vitro. In vivo, K58R promoted lung metastasis and suppressed RSL3-induced ferroptosis and lipid peroxidation (4-HNE).</p><p><strong>Conclusion: </strong>LDHB-K58 delactylation drives gastric cancer metastasis via SLC7A11-mediated GSH synthesis and ferroptosis resistance, suggesting therapeutic targeting of this axis for overcoming therapy resistance.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic cadmium exposure promotes TRPM7-dependent acquisition of a myofibroblast-like phenotype in pancreatic stellate cells.","authors":"Mathilde Fourgeaud, Julie Auwercx, Alexis Lalot, Laure Noé, Belinda Duchêche, Anthony Verdin, Sara Agrane, Frédéric Hague, Stéphanie Guénin, Nour Jaber, Aurélie Dupont-Deshorgue, Laurent Gutierrez, Denis Chatelain, Frédéric Ledoux, Isabelle Dhennin-Duthille, Bertrand Brassart, Sylvie Brassart-Pasco, Nicolas Jonckheere, Mathieu Gautier","doi":"10.1007/s10565-026-10169-0","DOIUrl":"10.1007/s10565-026-10169-0","url":null,"abstract":"<p><p>Cadmium (Cd) is a metallic pollutant which has been classified as a possible pancreatic carcinogen. Cd uses similar ion channels than divalent cations to accumulate into the cells. These include the Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) which has been also shown as a biomarker of pancreatic cancer. Pancreatic carcinogenesis is associated with the establishment of a fibrous stroma induced by pancreatic stellate cell (PSC) activation. Although several stress factors have been identified as activators of PSCs, the impact of pollutants, particularly Cd, is still unknown. Here, we chronically exposed human PSCs to Cd and we observed that Cd-exposed cells acquired a myofibroblast-like phenotype. Moreover, TRPM7 expression and activity were upregulated following Cd exposure. Both TRPM7 inhibition by silencing or NS8593 treatment prevented the Cd-induced PSC cell migration indicating that TRPM7 regulated PSC activation. We used a model of indirect co-culture to study the impact of PSC on MIA PaCa-2 cancer cell migration. Interestingly, we showed that Cd-exposed PSCs stimulated MIA PaCa-2 cancer cell migration to a greater extent than non-exposed PSCs. TRPM7 inhibition in PSCs abolished the migration of cancer cells. Finally, in a mouse model with the KRAS^G12D mutation inducing spontaneous pancreatic intraepithelial neoplasia, Cd exposure aggravates collagen deposition in fibrotic areas showing high α-SMA and TRPM7 expressions. In summary, our study showed that Cd exposure upregulates TRPM7 leading to PSC activation and aggravation of precancerous pancreatic fibrosis in vivo.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicogenomic Characterization of Perfluorooctanoic Acid-Associated Bladder Carcinogenesis.","authors":"Yang Liu, Aifa Tang, Han Wang","doi":"10.1007/s10565-026-10164-5","DOIUrl":"10.1007/s10565-026-10164-5","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to bridge toxicological target prediction and bladder cancer transcriptomics by systematically identifying molecular signatures and pathways that converge between PFOA-associated toxicological effects and bladder cancer biology, using an integrative multi-cohort computational framework.</p><p><strong>Methods: </strong>Bioinformatics strategies were applied to assemble 9,591 putative molecular targets associated with perfluorooctanoic acid (PFOA) from five independent databases. Differential expression analysis and weighted gene co-expression network analysis were then conducted across five bladder cancer cohorts to delineate tumor-related genes. Functional enrichment analyses, machine learning-based modeling with SHAP interpretation, and molecular docking were subsequently employed to explore affected biological pathways and evaluate predictive performance.</p><p><strong>Results: </strong>A total of 69 candidate genes, predominantly associated with cell cycle control and DNA damage-related processes, were delineated. From these, a nine-gene classifier yielded excellent discriminatory performance, achieving an AUC of 0.986 in the training set and maintaining robust accuracy across multiple external cohorts (AUCs: 0.944-1.000). SHAP-based interpretability analyses identified MCM7 as the most influential contributor to bladder cancer classification. In silico docking further suggested a strong predicted interaction between PFOA and IGFBP2, with a binding energy of -13.0 kcal/mol.</p><p><strong>Conclusion: </strong>By integrating toxicological target prediction with large-scale bladder cancer transcriptomic analyses, this study provides a computational bridge between environmental chemical exposure and cancer-related molecular programs. The resulting nine-gene classifier demonstrates strong and consistent performance across independent cohorts and captures transcriptional features that intersect with PFOA-associated toxicological pathways, offering a systems-level, hypothesis-generating perspective on transcriptional programs that overlap between predicted PFOA-associated targets and bladder cancer biology.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain organoids in environmental neurotoxicology: applications, mechanisms, and future perspectives.","authors":"Jiawen Liu, Yanling Xie, Meihui Zhu, Zhiqiu Wang, Yan Huang, Xiaobo Cen, Qian Bu","doi":"10.1007/s10565-026-10161-8","DOIUrl":"10.1007/s10565-026-10161-8","url":null,"abstract":"<p><p>The advent of human induced pluripotent stem cell (hiPSC)-derived brain organoids represents a significant advance in environmental neurotoxicology, propelling the discipline toward human-relevant, mechanistic, and predictive in vitro paradigms. This review explores the utility of brain organoids in environmental neurotoxicology, which uniquely address critical limitations of traditional models by recapitulating key aspects of human brain development, including three-dimensional (3D) cytoarchitecture, multilineage cellular heterogeneity, and functional network activity. This review systematically elaborates on their construction principles, unique advantages in neurotoxicological research, and the significant progress made in elucidating mechanisms of toxicity. Notably, brain organoids exhibit enhanced sensitivity in identifying the subtle adverse outcomes of chronic, low-dose exposures to environmental contaminants, often eluding conventional approaches. Their key advantage lies in the greater capacity to deconstruct complex toxicological pathways, enabling precise tracing of adverse outcome pathways (AOPs). Future development requires enhancing model complexity through vascularization, promoting automation and standardization, and integrating artificial intelligence (AI) for data analysis. Concurrently, establishing sustained ethical oversight and standardized frameworks is essential to ultimately advance the field toward more precise and efficient hazard identification and risk characterization.Highlights1. Human brain organoids bridge species gaps for more human-relevant neurotoxicity assessment.2. Brain organoids effectively recapitulate chronic, low-dose and mixture environmental risks.3. Integrating brain organoid data into the AOP frameworks enhances mechanistic understanding.4. Coupling brain organoids with organ-on-a-chip and AI advances next-generation risk assessment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linc-ROR orchestrates autophagy suppression and marks gastric cancer via the miR-145-5p/CARMIL1 axis.","authors":"Juan Ding, Rongshu Cui, Yunyan Teng, Ke Xiao, Zhaogang Dong, Yi Zhang","doi":"10.1007/s10565-026-10163-6","DOIUrl":"10.1007/s10565-026-10163-6","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) have been considered the main regulators of cancer progression through their regulation of diverse cellular processes. Autophagy, which exerts context-dependent dual effects on gastric cancer (GC), remains controversial, and its interplay with lncRNAs has yet to be fully elucidated. Through integrated in vitro and in vivo functional assessments, we illustrate that silencing Linc-ROR markedly inhibits GC cell proliferation, migration, invasion, and xenograft growth. Transmission electron microscopy and mRFP-GFP-LC3 dual-fluorescence reporters revealed that Linc-ROR overexpression suppresses autophagic flux, which was further confirmed by Western blot analysis. Mechanistically, Linc-ROR functions as a competing endogenous RNA (ceRNA) to sequester miR-145-5p, thereby upregulating CARMIL1 and activating ERK/mTOR signaling, leading to autophagy inhibition and promotion of GC cell growth and invasiveness. Notably, pharmacological inhibition of mTOR with Everolimus reversed these malignant phenotypes, highlighting a therapeutically actionable vulnerability. Clinically, serum exosomal Linc-ROR was significantly elevated in GC patients and outperformed carcinoembryonic antigen (CEA) in diagnostic accuracy. Collectively, our findings establish Linc-ROR as a master regulator of autophagy suppression and GC progression via the miR-145-5p/CARMIL1/ERK-mTOR axis, underscoring its potential as a therapeutic target, while serum exosomal Linc-ROR emerges as a promising noninvasive biomarker for GC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ADAMTS1/HDAC6 alleviates TGF-β1/SMAD2-associated cardiac fibrosis in cardiac fibrosis post-myocardial infarction.","authors":"Qiao Jin, Chun Chen, Pengcui Wu, Liang Li, Luping Jiang, Ran Chen, Shanxiang Xu, Yuyan Huang, Haixia Xu, Xiao Long","doi":"10.1007/s10565-026-10159-2","DOIUrl":"10.1007/s10565-026-10159-2","url":null,"abstract":"<p><strong>Background: </strong>A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is involved in the occurrence and development of myocardial fibrosis. Here, we sought to explore the specific regulatory mechanism of ADAMTS1 in cardiac fibrosis post-myocardial infarction (CFPMI).</p><p><strong>Methods: </strong>Blood samples from patients with myocardial fibrosis were collected. A CFPMI mouse model and in vitro models involving human or mouse cardiac fibroblasts treated with TGF-β1 or Ang II were constructed. ChIP was used to confirm that SMAD2 binds to ADAMTS1, and Co-IP was used to verify the interaction between ADAMTS1 and HDAC6. Cellular models with SMAD2 knockdown, ADAMTS1 regulation, and HDAC6 inhibitor treatment were used to study their roles in fibrosis. Finally, AAV-shRNA-HDAC6 and ADAMTS1 inhibitor effects were verified in vivo.</p><p><strong>Results: </strong>ADAMTS1 levels were higher in myocardial fibrosis patients' serum. Increased ADAMTS1 and p-SMAD2 were found in fibrotic mouse hearts and human cardiac fibroblasts stimulated with fibrotic factors. ChIP validated the binding of SMAD2 to ADAMTS1. Mechanistically, SMAD2 regulated ADAMTS1 expression during TGF-β1-induced fibrosis in human and mouse cardiac fibroblasts. Overexpression of ADAMTS1 enhanced the production of collagen fiber proteins in human and mouse cardiac fibroblasts induced by TGF-β1. Moreover, HDAC6 expression was elevated in CFPMI mouse hearts and ADAMTS1 inhibited HDAC6 to regulate fibrosis. ADAMTS1 interacted with HDAC6 during fibrosis. In vivo, shRNA-HDAC6 and ADAMTS1 inhibitor treatment alleviated myocardial fibrosis and improved cardiac function after CFPMI.</p><p><strong>Conclusions: </strong>Targeting ADAMTS1/HDAC6 alleviated TGF-β1/SMAD2-associated cardiac fibrosis in CFPMI. This study may provide a novel theoretical basis for the treatment of myocardial fibrosis.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA-Seq reveals transcriptional heterogeneity in sepsis and down-regulation of SNHG5/miR-324-5p/CDK16 axis in T cells.","authors":"Jinxin Zhang, Heliang Fu, Shanshou Liu, Jiangang Xie, Shunzhong Zhao, Xianqi Wang, Qianmei Wang, Shanbo Hu, Peng Zhao, Jijun Chen, Junjie Li, Wen Yin","doi":"10.1007/s10565-026-10136-9","DOIUrl":"10.1007/s10565-026-10136-9","url":null,"abstract":"<p><strong>Objective and design: </strong>T lymphopenia is a common phenomenon in the sepsis patients, closely related with secondary infection and patients death, whereas its mechanism is still largely unelucidated. Hence, it is urgent to study the mechanism underlying sepsis induced T lymphopenia and lower morbidity and mortality of septic infection.</p><p><strong>Material and methods: </strong>We performed Single-cell RNA-seq (scRNA-seq) and created an atlas of peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy volunteers (n = 3). To further illustrate mechanisms related to fundamental biological in sepsis, we investigated SNHG5 mediated T cell apoptosis.</p><p><strong>Results: </strong>We collected blood samples of 3 sepsis patients and 3 healthy donors, separated PBMCs, and performed scRNA-seq to create a atlas of PBMCs. 7 cell clusters were identified and annotated, followed by differentially expressed genes and pathway analysis. Then, we systematically discussed the cellular heterogeneity, and generated gene expression patterns of 7 different cellular cluster in sepsis and healthy group. Further analysis DEG and further bioinformatics analysis of different cellular cluster indicated that SNHG5/miR-324-5p/CDK16 axis contributed to inflammatory T cell apoptosis in sepsis. And further inhibitory and functional experiments indicated that SNHG5/miR-324-5p/CDK16 axis contributed to inflammatory T cell apoptosis in sepsis.</p><p><strong>Conclusion: </strong>This study unveiled molecular mechanisms related to T lymphopenia in sepsis, such as cell fate decisions and modulation of SNHG5/miR-324-5p/CDK16 axis, making SNHG5 a promising therapeutic measurement for sepsis.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of acalabrutinib metabolism by finerenone and its molecular docking studies.","authors":"Peiqi Wang, Haoxin Fu, Jun Wu, Ruibin Li, Lu Cao, Ren-Ai Xu, Weihong Lin","doi":"10.1007/s10565-026-10148-5","DOIUrl":"10.1007/s10565-026-10148-5","url":null,"abstract":"<p><p>Acalabrutinib is a frontline agent for chronic lymphocytic leukemia (CLL). The objective of this experiment was to screen 21 cardiovascular drugs with a focus on elucidating the metabolic inhibition of acalabrutinib by finerenone in vitro and in vivo. The ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to quantify acalabrutinib and its major active metabolite ACP-5862 in liver microsomes in vitro and in rats in vivo. The half-maximal inhibitory concentrations (IC₅₀) of finerenone in rat liver microsomes (RLM), human liver microsomes (HLM) and recombinant human CYP3A4 (rCYP3A4) were 7.00, 21.29 and 3.52 μM, respectively. In RLM and rCYP3A4, finerenone inhibited the metabolism of acalabrutinib via mixed-type inhibition (competitive and non-competitive), with a non-competitive inhibition observed in HLM. Compared with the control group, in vivo pharmacokinetic analysis indicated that finerenone co-administration increased acalabrutinib exposure, as reflected by 4.08-, 7.16-, and 3.96-fold increases in AUC_(0-t), AUC_(0-∞), and half-life (t_1/2), respectively, accompanied by an 86.02% reduction in the clearance (CL_z/F). Its metabolite ACP-5862 demonstrated a 57.47% and 65.12% decrease in AUC_(0-t) and the maximum concentration (C_max), respectively, while CL_z/F was increased by 0.79-fold. Finally, acalabrutinib and finerenone were evaluated for binding to cytochrome P450 3A4 (CYP3A4) by molecular docking, yielding binding energies of -2.36 and -2.19 kcal/mol, respectively. Thus, in vivo and in vitro results consistently indicated that finerenone inhibited the metabolism of acalabrutinib, providing the basis for individualized dosing considerations.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}