Biochimica et biophysica acta. General subjects最新文献

{"title":"Drought stress induces variation in DNA methylation pattern in a genotype-dependent manner in chickpea","authors":"Khushboo Gupta,&nbsp;Rohini Garg","doi":"10.1016/j.bbagen.2025.130836","DOIUrl":"10.1016/j.bbagen.2025.130836","url":null,"abstract":"<div><div>When plants are exposed to harsh environmental conditions, such as extreme temperatures or drought, certain genes are turned on or off. This process can be controlled by a chemical modification to their DNA called methylation. Here, we examined the impact of DNA methylation during drought stress on two chickpea genotypes, ICC 1882 (drought sensitive, DS) and ICC 4958 (drought tolerant, DT) chickpea genotypes via whole-genome bisulfite sequencing. A higher degree of hypomethylation in the DT genotype and more hypermethylation in the DS genotype were observed. A positive correlation was observed between CG methylation with genes and CHH methylation with TEs. Functional annotation of differentially methylated regions associated with differentially expressed genes revealed distinct pathways enriched in DS, such as enrichment of genes involved in root development, telomere maintenance, ion transport, and regulation of gene expression, while pathways like apoptosis, silencing by miRNAs, programmed cell death and carotenoid metabolic processes were enriched in DT genotype. Further, small RNA distribution and non-CWA context methylation density in TEs suggested the role of the RdDM pathway in mediating CHH hypermethylation in transposable elements. Overall, we observed distinct genes are differentially expressed and differentially methylated under drought stress in sensitive and tolerant genotypes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130836"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neu1 sialidase regulates heterospecific social interaction in zebrafish via D1 dopamine receptor","authors":"Sumomo Tsuji ,&nbsp;Asami Ikeda ,&nbsp;Yurina Kubo ,&nbsp;Toshiki Hyodo ,&nbsp;Mika Ishii ,&nbsp;Masaharu Komatsu ,&nbsp;Kazuhiro Shiozaki","doi":"10.1016/j.bbagen.2025.130839","DOIUrl":"10.1016/j.bbagen.2025.130839","url":null,"abstract":"<div><div>Neu1 sialidase catalyzes the removal of sialic acids from oligosaccharides and glycoproteins in lysosomes and plasma membranes. Recently, the association between Neu1 and psychiatric disorders, such as manic depression and schizophrenia, has attracted attention. <em>neu1</em>^−/− zebrafish (Neu1-KO) exhibit low anxiety, low aggressiveness, and increased social interaction with unfamiliar conspecific and heterospecific groups; however, the underlying mechanisms of action remain unclear. This study investigated alterations in monoamine levels in the Neu1-KO zebrafish brain and their significance in the unique behavioral response toward heterospecifics. The dopamine (DA) and serotonin (5-HT) levels were significantly elevated in the brains of Neu1-KO zebrafish compared with those of wild-type (WT) zebrafish, accompanied by a decrease in noradrenaline (NE). Immunohistochemical (IHC) analysis revealed increased numbers of DA and 5-HT neurons in the Neu1-KO zebrafish brain. Behavioral analysis revealed that treatment with a D1 receptor antagonist significantly suppressed heterospecific interactions in Neu1-KO zebrafish, whereas treatment with D2 and 5-HT receptor antagonists did not. IHC showed that polysialic acid (PSA), a known regulator of DA neuronal function, was predominantly distributed in the hypothalamus of zebrafish, with markedly enhanced signals in Neu1-KO zebrafish. These findings elucidate the role of Neu1 sialidase in regulating social interaction behaviors via DA neurons, potentially as a mechanism for mitigating risks in social environments.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130839"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP33-mediated stabilization of c-Myc drives glycolytic reprogramming and promotes ovarian cancer progression","authors":"Dejia Chen ,&nbsp;Yue Zhao ,&nbsp;Xiaobo Zhang ,&nbsp;Xiaocheng Shi ,&nbsp;Yiming Liu ,&nbsp;Ge Lou","doi":"10.1016/j.bbagen.2025.130830","DOIUrl":"10.1016/j.bbagen.2025.130830","url":null,"abstract":"<div><div>Ovarian cancer (OC) is one of the most lethal gynecological malignancies, characterized by late-stage presentation, high recurrence rates, and a lack of effective early diagnostic markers. Recent evidence suggests that deubiquitinating enzymes (DUBs) play pivotal roles in tumor development and metabolic reprogramming. Here, we identify and characterize the function of the deubiquitinase USP33 in regulating c-Myc stability and glycolytic metabolism in OC. Through quantitative PCR (qPCR) and Western blot analyses, we show that USP33 is significantly upregulated in both OC tissues and cell lines compared to normal controls. Functional assays reveal that USP33 knockdown markedly inhibits cell proliferation, migration, and invasion while promoting apoptosis. Metabolically, USP33 silencing reduces glucose uptake, lactate production, and the extracellular acidification rate, consistent with downregulation of key glycolytic enzymes (LDHA, GLUT1, and PKM2). Mechanistically, co-immunoprecipitation and ubiquitination assays demonstrate that USP33 interacts with and deubiquitinates c-Myc at K48-linked chains, thereby stabilizing c-Myc protein levels and enhancing its transcriptional activity. Moreover, c-Myc overexpression rescues the inhibitory effects of USP33 knockdown on both glycolysis and malignant phenotypes. Clinically, high USP33 expression correlates with poor prognosis, suggesting that the USP33–c-Myc axis may serve as both a prognostic biomarker and a potential therapeutic target. Taken together, our findings highlight a critical role for USP33 in OC pathogenesis by mediating c-Myc-driven glycolytic reprogramming, and they provide new insights for developing targeted treatment strategies aimed at disrupting this pathway.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130830"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of alkaloid-based inhibition of aldose reductase: Computational perspectives and experimental validations","authors":"Emadeldin M. Kamel ,&nbsp;Saleh Maodaa ,&nbsp;Sarah I. Othman ,&nbsp;Adil Abalkhail ,&nbsp;Faris F. Aba Alkhayl ,&nbsp;Al Mokhtar Lamsabhi","doi":"10.1016/j.bbagen.2025.130841","DOIUrl":"10.1016/j.bbagen.2025.130841","url":null,"abstract":"<div><div>Excessive aldose reductase activity drives the polyol-pathway damage that underlies diabetic cataract, neuropathy and nephropathy, yet few safe, potent AR inhibitors have reached the clinic. Here we integrated virtual screening, atomistic simulation and enzymology to evaluate six natural alkaloids—calycanthine, rutaecarpine, glaucine, sparteine, berbamine and tetrandrine—as prospective AR antagonists. A 2500-compound AutoDock Vina screen singled out these scaffolds for high predicted affinity (≤ − 7.0 kcal mol⁻¹), chemotype diversity and favorable <em>in silico</em> developability. Docking located all ligands within the catalytic cleft; 200-ns MD trajectories plus free-energy landscapes revealed that rutaecarpine and the bis-benzylisoquinolines tetrandrine and berbamine clamp the anion-binding and specificity pockets simultaneously, collapsing conformational space into a single deep basin. MM/PBSA analysis ranked tetrandrine highest (ΔG_total = −35.8 ± 2.5 kcal mol⁻¹) followed by rutaecarpine (−23.0 ± 1.3 kcal mol⁻¹) and berbamine (−19.4 ± 2.7 kcal mol⁻¹); per-residue decomposition highlighted Phe122, Trp219 and Leu300 as recurring hot-spots. <em>In vitro</em>, the same hierarchy emerged: tetrandrine inhibited recombinant human AR with an IC₅₀ of 1.56 ± 0.23 μM, outperforming quercetin (2.37 ± 0.27 μM), while rutaecarpine and berbamine yielded IC₅₀ values of 4.84 ± 0.81 and 7.35 ± 0.78 μM, respectively. Lineweaver–Burk and Michaelis–Menten plots demonstrated non-competitive inhibition, aligning with the MD-inferred pocket-clamping mechanism. ADMET profiling identified rutaecarpine as the most balanced lead (Lipinski-compliant, moderate hERG/CYP risk), whereas tetrandrine's hERG liability and low solubility call for scaffold refinement. This study validates bis-benzylisoquinoline and indolo-quinazolinone frameworks as privileged AR inhibitory chemotypes and showcases an end-to-end computational–experimental pipeline that rapidly converts ethnopharmacological molecules into mechanistically characterized leads for managing diabetic complications.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130841"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EP300-mediated H3K18la regulation of METTL3 promotes macrophage ferroptosis and atherosclerosis through the m6A modification of SLC7A11","authors":"Jingquan Chen ,&nbsp;Zongrong Liu ,&nbsp;Zhujun Yue ,&nbsp;Qiang Tan ,&nbsp;Hongshun Yin ,&nbsp;Haifei Wang ,&nbsp;Zhilong Chen ,&nbsp;Yanbing Zhu ,&nbsp;Jianghua Zheng","doi":"10.1016/j.bbagen.2025.130838","DOIUrl":"10.1016/j.bbagen.2025.130838","url":null,"abstract":"<div><div>Macrophages, as the primary immune cell population in atherosclerosis (AS), exhibit complex pathogenic mechanisms that are not fully elucidated. This study aims to explore the interplay between histone lactylation and methyltransferase-like protein 3 (METTL3)-mediated m6A modification and their potential mechanisms in AS. We demonstrate that METTL3 is highly expressed in macrophages in both in vivo and in vitro models of atherosclerosis, and myeloid cell-specific deletion of METTL3 attenuates the progression of atherosclerosis. Furthermore, the accumulation of lactate levels in macrophages promotes METTL3 expression through EP300-mediated histone H3 lysine 18 lactylation (H3K18la) binding to the METTL3 promoter site. We found that METTL3-mediated m6A modifications are enriched in solute carrier family 7 member 11 (SLC7A11) and accelerate its mRNA degradation in a YTH domain family member 2 (YTHDF2)-dependent manner, thereby promoting ferroptosis in macrophages. Additionally, lactate stimulation downregulates SLC7A11 through the METTL3/YTHDF2 pathway, further promoting ferroptosis. Overall, during AS, lipid peroxidation induces an increase in lactate levels within macrophages, which enhances METTL3 expression through EP300-mediated H3K18la. This further accelerates the degradation of SLC7A11 mRNA via the YTHDF2-dependent m6A modification pathway, inducing ferroptosis in macrophages. This discovery provides new insights into the mechanisms of macrophage function in AS and offers a theoretical basis for the development of therapies for AS.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130838"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid virtual screening identifies dipyrazole carboxamide derivatives as novel direct InhA inhibitors with antitubercular activity","authors":"Auradee Punkvang ,&nbsp;Bongkochawan Pakamwong ,&nbsp;Naruedon Phusi ,&nbsp;Paptawan Thongdee ,&nbsp;Kampanart Chayajarus ,&nbsp;Jidapa Sangswan ,&nbsp;Kanjana Pangjit ,&nbsp;Khomson Suttisintong ,&nbsp;Jiraporn Leanpolchareanchai ,&nbsp;Poonpilas Hongmanee ,&nbsp;Pitak Santanirand ,&nbsp;James Spencer ,&nbsp;Adrian J. Mulholland ,&nbsp;Sanya Sureram ,&nbsp;Prasat Kittakoop ,&nbsp;Pornpan Pungpo","doi":"10.1016/j.bbagen.2025.130827","DOIUrl":"10.1016/j.bbagen.2025.130827","url":null,"abstract":"<div><div>Direct inhibitors of <em>M. tuberculosis</em> enoyl-acyl carrier protein reductase (<em>M. tuberculosis</em> InhA) remain effective against variants with mutations associated with isoniazid resistance. In our previous study, structure-based virtual screening was employed to discover such inhibitors. However, most identified hits exhibited limited antimycobacterial activity, with minimum inhibitory concentration (MIC) values of &gt;100 μg/mL. To address this challenge, we refined our virtual screening strategy by integrating ligand- and structure-based virtual screening approaches. The efficacy of this hybrid virtual screening approach was validated through biological assays measuring MIC and half-maximal inhibitory concentration (IC₅₀) for the inhibition of <em>M. tuberculosis</em> growth and InhA activity, respectively. Among 14 identified hits, compounds <strong>3</strong> and <strong>10</strong>, classified as dipyrazole carboxamide derivatives, were validated as promising lead candidates, with MIC values of 25 and 50 μg/mL and IC₅₀ values of 10.60 ± 0.56 and 5.08 ± 0.30 μM, respectively. The relatively low hit-to‑lead conversion rate (14 %) is ascribed to our observation that nine of the identified hits, including compounds <strong>3</strong> and <strong>10</strong>, showed some level of precipitation in the MIC assay medium. Molecular dynamics simulations show that the dipyrazole carboxamide moiety in compounds <strong>3</strong> and <strong>10</strong> forms essential hydrogen bonds with nicotinamide adenine dinucleotide (oxidized form) (NAD⁺) in the InhA binding pocket. Notably, both compounds <strong>3</strong> and <strong>10</strong> exhibit favorable safety profiles, with no toxicity observed in Caco-2 cells at concentrations up to 100 μg/mL. Consequently, we believe that these compounds present promising starting points for further lead optimization and development of novel antitubercular agents.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130827"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants","authors":"Subhash Chandra Bihani ,&nbsp;Tarushi ,&nbsp;Ashish Kumar Srivastava","doi":"10.1016/j.bbagen.2025.130819","DOIUrl":"10.1016/j.bbagen.2025.130819","url":null,"abstract":"<div><div>Calcium (Ca²⁺) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca²⁺ sensors that transduce the Ca²⁺ signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca²⁺ binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca²⁺ sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130819"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual generation of stereo- and linear-specific monoclonal antibodies through B-cell receptors by DNA and cell immunization for therapeutic applications","authors":"Chiho Miyamae ,&nbsp;Yushi Isozaki ,&nbsp;Kanta Tsumoto ,&nbsp;Masahiro Tomita","doi":"10.1016/j.bbagen.2025.130822","DOIUrl":"10.1016/j.bbagen.2025.130822","url":null,"abstract":"<div><div>The optimized stereospecific targeting (SST) technique features selective generation of conformation-specific monoclonal antibodies against membranous proteins with high specificity after DNA and cell immunization. This technology consists of two critical steps, which are specific selection of sensitized B lymphocytes by antigen-expressing myeloma cells through B-cell receptors (BCRs) and selective fusion of B cell-myeloma cell complexes by electrical pulses to produce hybridoma cells secreting stereospecific monoclonal antibodies. Here we were able to verify the critical step for the selection of B lymphocytes by intact antigen-expressing myeloma cells by a double-label immunofluorescence analysis. Interestingly, the cell complex was a single attachment. Furthermore, we newly found the new progress that the optimized SST technique offered dual production of anti-intact and anti-linear specific monoclonal antibodies against a human ephrin type-A receptor 2 (hEphA2). The optimized SST technique may be useful for producing not only stereospecific monoclonal antibodies, but also primary-specific monoclonal antibodies based on the selection of sensitized B lymphocytes by the target intact antigen through BCRs. It would elicit more advanced medical applications by generating dual monoclonal antibodies against the intact antigen.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130822"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalein benefits amyotrophic lateral sclerosis via reduction of Intraneuronal misfolded protein","authors":"Chen-Hung Ting ,&nbsp;Shao-Ting Tai ,&nbsp;Hsiang-Yu Chang ,&nbsp;Po-Ya Huang ,&nbsp;Lo-Fan Cheng ,&nbsp;Hsing-Jung Lai ,&nbsp;Yih-Chih Kuo ,&nbsp;Chia-Hsin Kao ,&nbsp;I-Fan Wang ,&nbsp;Li-Kai Tsai","doi":"10.1016/j.bbagen.2025.130831","DOIUrl":"10.1016/j.bbagen.2025.130831","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by muscle weakness and atrophy, with limited treatment options. The accumulation of misfolded proteins, such as misfolded superoxide dismutase 1 (mSOD1), contributes significantly to neuronal degeneration in ALS. Therapies targeting misfolded proteins represent a promising strategy. Baicalein, a flavonoid compound with neuroprotective properties, has shown efficacy in clearing misfolded proteins and improving behaviors in rodent models of Alzheimer's and Parkinson's diseases. However, its effects in ALS remain largely unexplored. This study demonstrated that baicalein treatment reduced total and misfolded SOD1 protein levels in both soluble and insoluble fractions of a motor neuron cell line overexpressing mutant SOD1. Baicalein also reduced intracellular SOD1 aggregates in cultured motor neurons transfected with <em>SOD1/G93A</em>, preserving neurite length. In an ALS mouse model expressing the <em>SOD1/G93A</em> transgene, baicalein treatment decreased mSOD1 aggregation, increased spinal motor neuron density, and reduced neuromuscular junction denervation. Furthermore, baicalein partially improved motor behaviors, as assessed by the rotarod test. These findings highlight baicalein's potential as a therapeutic agent for ALS, targeting intraneuronal misfolded proteins to ameliorate pathological changes and preserve motor function.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130831"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 mesenchymal stem cells and their exosomes in radiotherapy: A new opportunity or a potential threat","authors":"Fatemeh Zeinalzadeh ,&nbsp;Seyedeh Nasibeh Mousavikia ,&nbsp;Mohammad Taghi Bahreyni Toossi ,&nbsp;Hosein Azimian","doi":"10.1016/j.bbagen.2025.130823","DOIUrl":"10.1016/j.bbagen.2025.130823","url":null,"abstract":"<div><div>Cancer remains a major global health problem characterized by complex biological mechanisms and diverse clinical manifestations. Radiotherapy is a key element in cancer treatment. However, radioresistance is a major obstacle to achieving optimal results. This resistance is associated with several factors, including genetic and epigenetic changes in tumor cells that allow cancer cells to survive and proliferate despite radiation exposure. In this context, mesenchymal stem cells (MSCs) play an important role in the tumor microenvironment. Due to their unique properties such as self-renewal, migration to tumors <em>via</em> the bloodstream and involvement in paracrine signaling, they are important for understanding cancer biology and treatment responses. MSCs can release exosomes that can promote intercellular communication and influence tumor response to radiotherapy. However, the role of MSCs in cancer is complex and sometimes contradictory. In some contexts they may exhibit tumor suppressive effects, while in others they promote tumor growth and metastasis. This duality raises important questions about their overall impact on cancer therapy, particularly in relation to radiotherapy. This review will first explore the multifaceted role of MSCs and their exosomes as key mediators of cellular communication within the tumor microenvironment, and then assess the implications of these interactions for radiotherapy, focusing on how MSCs may influence treatment efficacy and the potential to harness their properties to improve therapeutic outcomes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130823"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}