Molecular and Cellular Biochemistry最新文献

{"title":"Phytoestrogens and related microbial metabolites remodel aberrant prostate transcriptomic profiles generated upon exposure to oxidative stress.","authors":"Jiaxi Zhang, Arian Abolhassani, Cayla Boycott, Marco Tello-Palencia, Katarzyna Papierska, Ali Khan, Maidinai Sabier, David D Kitts, Barbara Stefanska","doi":"10.1007/s11010-026-05750-4","DOIUrl":"10.1007/s11010-026-05750-4","url":null,"abstract":"<p><p>Dietary phytoestrogens, including pterostilbene (PTS) from berries and genistein (GEN) from soybeans, exert anti-oxidant and anti-inflammatory effects in prostate cancer. However, the specific actions in regulation of cell biology and homeostasis in normal prostate epithelial cells remain unknown and a prominent research gap refers to the effects of related microbial metabolites of phytoestrogens. We therefore explored effects of distinct phytoestrogens, PTS and GEN, and PTS microbial metabolite, pinostilbene (PNS), in healthy cells with disrupted homeostasis. Human RWPE-1 prostate epithelial cells were treated with 100 µM concentration of hydrogen peroxide (H₂O₂). The H₂O₂-challenged cells were then exposed to phytoestrogens, followed by RNA sequencing. Transcriptomics revealed 1,770 differentially expressed genes (DEGs) upon H₂O₂ exposure. Upregulated genes were functionally implicated in immune signaling and inflammatory pathways, whereas downregulated genes were linked to autophagy, homeostasis, and cellular architecture. A quantitative metric termed the Weighted Recovery Ratio (WRR) was developed to quantify the extent that the treatment reversed gene expression change induced upon H₂O₂ challenge. WRR indicated that PNS recovered the highest number of H₂O₂-responsive genes. Among all PTS and PNS DEGs, 47% and 69%, respectively, constituted partially or fully recovered H₂O₂-responsive genes. This fraction was only 9% for GEN. PTS and PNS, but not GEN, recovered genes involved in DNA methylation/demethylation, which suggests restoration of DNA methylation equilibrium that was disrupted by H₂O₂. Our findings provide a novel tool to quantify the relative efficacy of phytoestrogens in attenuating alterations caused by an oxidative stressor. We present evidence for differential action of phytoestrogens with distinct chemical structures and for more potent action of microbial metabolites derived from phytoestrogens.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5621-5645"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum exosomal miRNA signature in hypertension: an exploratory study integrating with comparative analysis of the GEO database.","authors":"Dongling Zhong, Yue Zhang, Tianyu Liu, Yuxi Li, Xiaobo Liu, Yuan Chen, Qian Liang, Jiayi Chen, Congjie Lei, Rongjiang Jin, Juan Li","doi":"10.1007/s11010-026-05744-2","DOIUrl":"10.1007/s11010-026-05744-2","url":null,"abstract":"<p><p>Essential hypertension (EH) remains a leading cause of mortality worldwide. Exosome-carried microRNAs (miRNAs) play a pivotal role in the pathogenesis of EH. In this exploratory study, we aimed to characterize the serum exosomal miRNA expression profile in patients with EH and to investigate the potential functional relevance of differentially expressed (DE) miRNAs, aiming to provide preliminary evidence for future mechanistic investigations. Serum exosomes were isolated from patients with EH and healthy controls, followed by small RNA sequencing. Differentially expressed (DE) miRNAs were identified and further subjected to bioinformatic target gene prediction. To elucidate the potential biological functions of these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Additionally, a comparative analysis of the DE miRNAs was conducted using an independent dataset from the Gene Expression Omnibus (GEO) database. Six significantly downregulated miRNAs (hsa-miR-16-5p, hsa-miR-652-3p, hsa-miR-93-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-193a-5p) were identified in 20 hypertensive patients compared with 10 healthy controls. GO and KEGG analyses revealed that the predicted target genes of these miRNAs were significantly enriched in biological processes related to neuronal function, protein homeostasis, and cell cycle regulation, and were primarily involved in MAPK, Hippo, p53, and TGF-β signaling pathways. Notably, comparative analysis of the GEO dataset demonstrated a distinct expression profile between exosomal and total plasma miRNAs, underscoring the unique value of exosome-specific analysis. This exploratory study identified six serum exosomal miRNAs as candidate biomarkers for hypertension, with predicted targets enriched in MAPK and TGF‑β pathways. The exosomal signature was distinct from total plasma miRNA profiles, suggesting that exosomal miRNAs may carry disease‑specific signals. However, given the limited sample size and exploratory nature of this study, these findings are preliminary and require validation in larger cohorts.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5667-5677"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANKRD28 interacts with DOCK180 to activate Rac1-STAT3-Myc signaling and sustain stemness of CD34⁺ leukemia stem cells in acute myeloid leukemia.","authors":"Xiaoyan Zheng, Yue Du, Xiaohui Zhang, Huachao Zhu","doi":"10.1007/s11010-026-05749-x","DOIUrl":"10.1007/s11010-026-05749-x","url":null,"abstract":"<p><p>Leukemia stem cell (LSC) stemness maintenance is a core cause of relapse and therapeutic resistance in acute myeloid leukemia (AML). ANKRD28, an ankyrin repeat domain‑containing gene, has been implicated in malignant phenotypes across various tumors, but its role in regulating AML LSC stemness remains unclear. GEO datasets (GSE9476, GSE30029) and public databases (GEPIA2, TIMER, CCLE) were analyzed to characterize ANKRD28 expression and prognostic relevance in AML and LSCs. ANKRD28 expression in CD34⁺ LSCs from newly diagnosed AML patients was assessed by RT‑qPCR and Western blot. Effects on proliferation, cell cycle, apoptosis, and stemness markers were evaluated using colony formation, CCK‑8, EdU incorporation, flow cytometry, and Western blot. A patient‑derived xenograft (PDX) model was used to assess in vivo tumorigenic capacity. Downstream signaling was explored via GEPIA2 correlation analysis, Western blot, and rescue experiments. Co‑immunoprecipitation (Co‑IP), Rac1 activity assays, and nuclear‑cytoplasmic fractionation were performed to elucidate the underlying mechanism. ANKRD28 was overexpressed in AML tissues, CD34⁺ cells, and CD34⁺‑enriched cell lines, and was associated with FLT3 mutations, relapse, and poor prognosis. Its expression was positively correlated with LSC markers. CD34⁺ANKRD28⁺ cells exhibited greater colony‑forming capacity than CD34⁺ANKRD28^- cells. ANKRD28 knockdown inhibited LSC proliferation, induced apoptosis, caused cell cycle arrest, and downregulated stemness markers, whereas overexpression exerted opposite effects. In vivo, ANKRD28 knockdown prolonged survival, reduced LSC infiltration, and alleviated histopathological damage. Mechanistically, ANKRD28 directly bound DOCK180, activated Rac1, promoted STAT3 nuclear translocation and transcriptional activation, and upregulated Myc expression. ANKRD28 is overexpressed in AML CD34⁺ LSCs and sustains stem cell‑like properties via the DOCK180‑Rac1‑STAT3‑Myc axis, serving as a potential therapeutic target for AML.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5679-5695"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF1-IGF1R signaling in tumor-associated macrophages regulates extracellular matrix organization in BRAF inhibitor-targeted melanoma.","authors":"Ya Luo, Linlin Liu, Xing Zhou, Jiao Yang, Min Tang, Wei Feng, Chunlan Du, Xiaobo Liu, Liu Yang, Fei Liu, Liqun Zhang","doi":"10.1007/s11010-026-05673-0","DOIUrl":"10.1007/s11010-026-05673-0","url":null,"abstract":"<p><p>Melanoma, particularly driven by activating mutations in the BRAF gene, has witnessed significant therapeutic advances through targeted therapies such as BRAF and MEK inhibitors. However, the development of acquired resistance remains a major clinical challenge, limiting long-term treatment efficacy. The tumor microenvironment (TME), especially tumor-associated macrophages (TAMs), plays a pivotal role in mediating immune evasion, angiogenesis, and drug resistance. Despite extensive research into TAM polarization and function, the precise molecular mechanisms underlying their contribution to therapy resistance remain incompletely understood. Here, we investigated the regulatory role of IGF1-IGF1R signaling in THP-1-derived macrophages and its impact on the sensitivity of co-cultured melanoma cells to the BRAF inhibitor PLX4032. We observed markedly upregulated IGF1 expression in both melanoma cells and THP-1-derived macrophages. Either IGF1R knockdown or pharmacological blockade of IGF1-IGF1R signaling in macrophages restrained the polarization of THP-1-derived macrophages. Both in vitro cellular assays and in vivo xenograft experiments verified that A375 cells pre-co-cultured with IGF1R-deficient macrophages were more sensitive to PLX4032 relative to those pre-co-cultured with IGF1R-proficient macrophages. Transcriptomic analysis reveals that IGF1-IGF1R signaling in THP-1-derived TAMs significantly regulates extracellular matrix (ECM) organization. Collectively, our results offer a new insight into IGF1-IGF1R signaling in THP-1-derived macrophages regulating ECM organization in TME and its potential role in indirectly modifying the tumor cells responsiveness to PLX4032.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5171-5183"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glyoxal induces arterial injury through the inactivation of receptors and signaling pathways.","authors":"Ming-Zhang Xie, Xue Yang, Zhi-Wei Wu, Lin-Ping Zhou, Hai-Xia Chu, Qun-Mei Zhang, Yu-Chao Zhang, Xiao-Chun Zhou, Meng-Meng Zhao, Qing-Jiang Mo, Xiao-Fang Wang, Wei-Dong Xv, Wen-Yan Bian, Ya-Nan Li","doi":"10.1007/s11010-026-05719-3","DOIUrl":"10.1007/s11010-026-05719-3","url":null,"abstract":"<p><p>Glyoxal exposure is associated with a spectrum of adverse health outcomes, including arterial injury. While existing evidence confirms that glyoxal targets oxidative stress and the mitogen-activated protein kinase pathway, the precise underlying mechanism of glyoxal-induced arterial damage remains elusive. In this study, we aimed to elucidate the molecular mechanism driving glyoxal-induced arterial injury through a combination of in vitro and in vivo experiments. In vitro, we treated human aortic endothelial cells with glyoxal, then performed cell viability assays, tandem mass tag (TMT)-based quantitative proteomics, parallel reaction monitoring (PRM), glutathione quantification for oxidative stress assessment, western blotting, and quantitative polymerase chain reaction (qPCR) analysis. In vivo, we administered glyoxal to C57BL/6 mice, after which we conducted biochemical, histological, and immunohistochemical assays to evaluate arterial pathological changes. In vitro, the proteomic profiling results were further validated via PRM and western blotting, which confirmed that glyoxal exposure induces energy metabolism dysfunction, aberrant vascular endothelial growth factor receptor (VEGF-R) expression, and signaling pathway inactivation. Consistent with the proteomic results, we detected reduced protein levels of VEGF-R (36.4% reduction), insulin-like growth factor receptor (IGF-R, 21.6% reduction ), and insulin receptor (INS-R, 16.4% reduction) relative to control after glyoxal treatment. Compared to the control group, the glyoxal-exposed group exhibited a 48.7% reduction in the phosphorylation levels of ErbB2 and ErbB4, while total protein levels of ErbB2 and ErbB4 (106.0% of the control level) were comparable between the two groups. In addition, the levels of Wnt signaling-related proteins-including β-catenin (52.5% of the control level) and Wnt ligands-were significantly decreased following glyoxal treatment, relative to the control. Consistent with our in vitro results, we observed that the protein levels of VEGF-R (47.7% reduction), β-catenin (25.7% reduction), and INS-R (66.0% reduction) were decreased relative to the control group after in vivo glyoxal treatment. Collectively, our findings outline a comprehensive molecular portrait of glyoxal-induced arterial injury, which provides a foundational framework that may advance the development of precision medicine strategies for glyoxal-related vascular disease.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5287-5300"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itaconate metabolism in regulated cell death.","authors":"Daolin Tang, Rui Kang","doi":"10.1007/s11010-026-05743-3","DOIUrl":"10.1007/s11010-026-05743-3","url":null,"abstract":"<p><p>Itaconate, a metabolite generated from the tricarboxylic acid cycle through aconitate decarboxylase 1 (ACOD1, also known as IRG1), has emerged as a key link between cellular metabolism, immunity, and regulated cell death. Although initially recognized for its anti-inflammatory properties, accumulating evidence indicates that the biological functions of itaconate extend far beyond immunomodulation to encompass multiple forms of regulated cell death. The ACOD1-itaconate axis regulates apoptosis, ferroptosis, pyroptosis, necroptosis, and other emerging cell-death programs through coordinated control of mitochondrial metabolism, redox homeostasis, inflammatory signaling, and covalent protein modification. These effects are context dependent and are further shaped by the distinct biological activities of endogenous itaconate, synthetic derivatives, and the recently recognized itaconate-independent functions of ACOD1. In this review, we summarize recent advances in immunometabolism and regulated cell death, discuss the mechanistic basis by which the ACOD1-itaconate axis governs cell fate, and highlight how intercellular metabolic communication and non-canonical ACOD1 signaling expand its biological functions. We also highlight unresolved questions regarding target selectivity, context-dependent signaling, and therapeutic translation. A deeper understanding of the ACOD1-itaconate network may provide new insights into therapeutic strategies targeting regulated cell death in inflammatory diseases, infection, and cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5145-5169"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic acid partially attenuates thiomersal-associated oxidative, apoptotic, and CREB/BDNF-related alterations in rat hippocampal and prefrontal cortex tissues and systemic inflammatory responses.","authors":"Murat Celebi, Cagla Celebi","doi":"10.1007/s11010-026-05752-2","DOIUrl":"10.1007/s11010-026-05752-2","url":null,"abstract":"<p><p>Thiomersal (THIM), an organomercury preservative, has been associated with oxidative stress-related neurotoxicity. This study investigated the effects of gallic acid (GA) on THIM-associated oxidative, apoptotic, and CREB/BDNF-related molecular alterations in brain tissue and systemic inflammatory responses in rats. Twenty-eight male Wistar albino rats were assigned to Control, THIM, GA, and THIM+GA groups (n = 7/group). THIM (25 µg/kg, intraperitoneally) was administered at 10-day intervals, whereas GA (50 mg/kg/day, oral gavage) was given for 20 consecutive days. MDA, SOD, CAT, and GSH were measured in combined hippocampal and prefrontal cortex homogenates; serum MDA, IL-1β, IL-6, and TNF-α were also assessed. Bax, Bcl-2, Casp-3, CREB, and BDNF mRNA expression was analyzed by RT-qPCR. THIM increased tissue MDA (0.44 ± 0.06 vs. 1.06 ± 0.15 nmol/mg protein, p < 0.0001) and serum TNF-α (93.9 ± 9.6 vs. 171.3 ± 8.8 ng/L, p < 0.0001) and reduced BDNF mRNA expression (1.01 ± 0.15 vs. 0.41 ± 0.17, p = 0.0001). In THIM-exposed animals, GA reduced tissue MDA and serum TNF-α and increased BDNF expression (all p < 0.05). Significant THIM × GA interactions were identified for tissue CAT, GSH, MDA, Bax/Bcl-2 ratio, BDNF, and serum MDA, IL-1β, IL-6, and TNF-α. Simple-effects analyses indicated that GA effects were mainly evident during THIM exposure. These findings suggest that GA partially attenuates THIM-associated oxidative and apoptosis-related molecular alterations, systemic inflammatory responses, and BDNF-related transcriptional changes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5709-5722"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircARHGAP10 inhibits colorectal cancer cell proliferation, migration and invasion by governing the miR-29a-5p/LPP axis and regulating Wnt/β-catenin signaling pathway.","authors":"Liyuan Liu, Yongcun Jia, Dongjie Li, Yuqing Dong, Guangxian Xu, Dan Jiang","doi":"10.1007/s11010-026-05731-7","DOIUrl":"10.1007/s11010-026-05731-7","url":null,"abstract":"<p><p>CircARHGAP10 is significantly downregulated in colorectal cancer (CRC), but its functional role and underlying molecular mechanism in CRC progression remain unelucidated. Here, we first detected circARHGAP10 expression in CRC tissues and adjacent normal tissues, as well as in CRC cell lines and normal intestinal epithelial cells. Functional analyses using CCK-8, EdU, colony formation, wound healing, and transwell assays demonstrated that circARHGAP10 overexpression notably inhibits CRC cell proliferation, migration, and invasion, while circARHGAP10 knockdown promotes these malignant phenotypes. Mechanistically, bioinformatic predictions, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays confirmed that circARHGAP10 acts as a competing endogenous RNA (ceRNA) to sponge miR-29a-5p, thereby upregulating the expression of its downstream target gene LPP. Furthermore, we found that circARHGAP10 modulates LPP, the Wnt/β-catenin signaling pathway and reverses epithelial-mesenchymal transition (EMT) through the miR-29a-5p, as validated by rescue experiments. Collectively, our findings reveal that circARHGAP10 functions as a tumor suppressor in CRC via two independent regulatory branches downstream of the circARHGAP10/miR-29a-5p cascade. On one hand, it restores LPP expression to block the malignant proliferation, migration and invasion of CRC cells; on the other hand, this signaling cascade mitigates excessive Wnt/β-catenin pathway activation and reverses EMT. This newly identified circRNA-centered regulatory network provides a promising novel therapeutic target for CRC intervention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5337-5353"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoplastics as disruptors of microtubule dynamics and intracellular trafficking: implications for cellular senescence and ageing.","authors":"Yun Li, Shanshan Zhu, Shanshan Chen, Xiaodong Mu","doi":"10.1007/s11010-026-05729-1","DOIUrl":"10.1007/s11010-026-05729-1","url":null,"abstract":"<p><p>Nanoplastics (NPs) are increasingly recognized as persistent intracellular cargoes whose long-term effects may depend not only on chemical reactivity, oxidative stress, and inflammation, but also on how particle-containing vesicles are transported, positioned, and cleared. Because the positioning and movement of endosomes, lysosomes, autophagosomes, mitochondria, and NP-containing vesicles are extensively regulated by microtubule-based transport, prolonged NP retention has the potential to disrupt intracellular trafficking and organelle homeostasis. Here, we examine how NPs may influence microtubule dynamics, tubulin post-translational modifications, motor-dependent trafficking, and organelle positioning, with particular emphasis on their relationships to cellular senescence and ageing. We first summarize evidence that senescence and ageing are associated with alterations in microtubule organization, stability, acetylation, intracellular transport capacity, cytoplasmic physical properties, and neuronal microtubule integrity. We then evaluate emerging evidence linking NP exposure to altered microtubule states and trafficking-related dysfunction, while considering particle size, shape, surface chemistry, aggregation, exposure duration, and intracellular burden as important determinants of particle fate and cellular response. We propose microtubule-dependent trafficking congestion as a testable framework in which persistent NP-containing cargo progressively reduces intracellular transport efficiency, while distinguishing this state from simple particle retention or generalized organelle dysfunction. Potential mechanisms include increased cargo loading, altered kinesin-dynein balance, perinuclear lysosomal retention, changes in cytoplasmic crowding or viscosity, and dysregulation of tubulin-modifying enzymes. Direct evidence for NP-induced trafficking congestion remains limited, highlighting the need for quantitative live-cell measurements of vesicle mobility, velocity, run length, pausing, directionality, and recovery after exposure withdrawal. Finally, we discuss human biomonitoring and tissue-distribution evidence and emphasize the distinction between detection of plastic particles in human tissues and demonstration of pathological causality.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5373-5383"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B6 attenuates diabetic cardiomyopathy by targeting CtBP1 and alleviating Golgi stress via the AKT/HO-1 signaling pathway.","authors":"Mo-Li Zhu, Rui Hao, Bing-Yan Mao, Hong-Dou Zhang, Peng Li, Chun-Rui Zhang, Hui-Dan Wang, Xi-Yue Li, Cheng-Zhi Li","doi":"10.1007/s11010-026-05734-4","DOIUrl":"10.1007/s11010-026-05734-4","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a serious complication of diabetes, characterized by the impairment of cardiac structure and function. Increasing evidence suggests that Golgi stress responses are involved in the pathogenesis of DCM. This study investigated the protective effects of vitamin B6 on DCM and explored the potential involvement of Golgi stress responses and the AKT/HO-1 signaling pathway in vitamin B6-mediated cardioprotection. Network pharmacology and molecular docking were used to identify potential targets of vitamin B6. A DCM mouse model was established in C57BL/6 mice using a high-fat diet and streptozotocin, and high-glucose-treated H9c2 cells were used in vitro. Cardiac function was assessed by echocardiography, histopathological changes were evaluated by HE and Masson staining, Golgi morphology was examined by transmission electron microscopy, and the expression of CtBP1, GM130, HO-1, NHE1, and P-AKT was analyzed by immunohistochemistry, immunofluorescence, and Western blotting. DCM mice exhibited increased heart weight-to-body weight ratio (HW/BW), reduced ejection fraction and fractional shortening, disordered myocardial fibers, and marked fibrosis, whereas vitamin B6 treatment significantly improved cardiac function and alleviated myocardial injury and fibrosis. Ultrastructural analysis showed Golgi fragmentation, filamentous disruption, and mitochondrial damage in DCM cardiomyocytes, all of which were ameliorated by vitamin B6. At the molecular level, DCM decreased CtBP1, GM130, HO-1, and P-AKT expression while increasing NHE1, and these changes were reversed by vitamin B6. These findings indicate that vitamin B6 may attenuate DCM through CtBP1-associated regulation and preservation of Golgi homeostasis, highlighting its potential therapeutic value.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5471-5482"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}