Biochimica et biophysica acta. General subjects最新文献

{"title":"Rapid in vivo loss of non-T-cell binding capacities of ATLG Grafalon® and ATG Thymoglobulin® explains selective effect on T-cell reconstitution after hematopoietic stem cell transplantation","authors":"Lisa V.E. Oostenbrink,&nbsp;Anja M. Jansen-Hoogendijk,&nbsp;Monique M. van Ostaijen-ten Dam,&nbsp;Carly Vervat,&nbsp;Cornelia M. Jol-van der Zijde,&nbsp;Maarten J.D. van Tol,&nbsp;Robbert G.M. Bredius,&nbsp;Arjan C. Lankester,&nbsp;Marco W. Schilham,&nbsp;Gertjan Lugthart","doi":"10.1016/j.bbagen.2026.130904","DOIUrl":"10.1016/j.bbagen.2026.130904","url":null,"abstract":"<div><div>Anti-thymocyte globulin (ATG Thymoglobulin®) and anti-T-lymphocyte globulin (ATLG Grafalon®) are commonly used in hematopoietic stem cell transplantation (HSCT) for <em>in vivo</em> T-cell depletion, aiming to reduce graft failure and graft-<em>versus</em>-host disease (GvHD). Despite their widespread use, the precise mechanisms by which ATG/ATLG affect immune recovery post-transplantation remain partially understood. In this study, in 289 pediatric HSCT patients treated with ATG (<em>n</em> = 213) or ATLG (<em>n</em> = 76), the relationship between longitudinal serum levels of the active T-lymphocyte-binding component of ATG/ATLG and immune reconstitution was evaluated. High levels of active ATG/ATLG did not prevent the recovery of neutrophils or NK-cells; however, T-cell recovery was delayed until active ATG/ATLG concentrations fell below 1 AU/mL. This is in apparent contradiction with the fact that ATG/ATLG are known not only to contain antibodies against antigens present on T-cells but also to antigens present on other immune and non-immune cells, including B-, NK-cells, granulocytes, monocytes and hematopoietic stem and progenitor cells (HSPC). To address this, we assessed the binding capacities of ATG and ATLG to immune cell subsets and HSPC both <em>in vitro</em> directly from the vial and <em>in vivo</em> from patients serum samples taken at multiple time points pre- and post-HSCT. Shortly after infusion, we observed a rapid reduction of ATG and ATLG binding to all cell types except for T-cells. This real-life specificity of ATG and ATLG explains their selective impact on T-cell reconstitution. These findings enhance our understanding of the mechanisms of action of ATG and ATLG and may contribute to optimization of these therapies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130904"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976108","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":"Ectonucleotidases: Possible roles in the tumor microenvironment and influence on tumor progression in breast cancer","authors":"Thaís Cristino Rocha-Vieira ,&nbsp;José Roberto Meyer-Fernandes","doi":"10.1016/j.bbagen.2026.130913","DOIUrl":"10.1016/j.bbagen.2026.130913","url":null,"abstract":"<div><div>Compared with nontumor tissue, the tumor microenvironment has a higher concentration of extracellular ATP. Extracellular ATP is degraded by the cooperative action of CD39 and ecto-5′-nucleotidase (CD73), thus leading to increases in the concentrations of adenosine and phosphate. This cooperative action can convert a proinflammatory environment characterized by a high concentration of ATP into an anti-inflammatory environment characterized by a high concentration of adenosine. In addition to its role in immune suppression, adenosine induces migration, metastasis and angiogenesis in breast cancer. In breast cancer, extracellular Pi plays an important role in tumor progression by increasing metastatic capacity. Studies have demonstrated that ecto-5′-nucleotidases are associated with chemoresistance and immune suppression through adenosine generation. In addition, ecto-5′-nucleotidases play a role in activating the epithelial-mesenchymal transition. Therefore, ectonucleotidase activity may represent a therapeutic target for the treatment of breast cancer.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130913"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091824","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":"Obese serum factors aggravate DNA damage, alter DNA damage response, and promote proliferation in colon cancer cells","authors":"Bhavana Deshmukh,&nbsp;Himanshi Yaduvanshi,&nbsp;Firoz Khan Bhati,&nbsp;Manoj Kumar Bhat","doi":"10.1016/j.bbagen.2026.130911","DOIUrl":"10.1016/j.bbagen.2026.130911","url":null,"abstract":"<div><div>Clinical data indicate a positive association between obesity and DNA damage, which has been implicated in several pathological conditions. Obesity also increases the risk of the development and progression of cancers, including colon cancer. However, the underlying mechanisms linking obesity-induced alterations in the DNA damage response (DDR) to colon cancer remain largely unexplored. The present study aims to investigate the functional status of the cellular DNA damage response in an obese environment and its association with colon cancer. To address this, cells were cultured in media supplemented with serum collected from mice fed a normal-fat diet (ND) and a high-fat diet (HFD). Subsequently, the DNA damage response and associated phenotypic parameters were evaluated.</div><div>Experimental results revealed that cells cultured in HFD serum exhibited increased DNA damage along with reduced levels of DNA repair molecules, together with activation of the DDR, as indicated by elevated levels of pH2AX, P-p53Ser15, and pchk2 proteins. Moreover, cell growth assays demonstrated rapid proliferation of cells cultured in HFD serum. Furthermore, HFD-fed C57BL6/J mice administered with azoxymethane/dextran sodium sulfate (AOM/DSS) exhibited a higher incidence of colon polyps compared to ND-fed mice. Interestingly, in ATM knockout mice (ATM, a key DDR-related molecule), a higher occurrence of polyps was detected compared to ATM wild-type mice, suggesting a potential role of ATM in polyp formation. Thus, by perturbing DDR and DNA repair pathways and promoting cell survival, obesity creates a favorable environment for cell proliferation. Collectively, this pre-clinical study enhances our understanding of obesity-altered DDR and its association with cancer cell proliferation.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130911"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083540","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":"TMED2 promotes thyroid cancer tumorigenesis by being involved in mTORC1-mediated fatty acid metabolism","authors":"Jiajun Yin ,&nbsp;Shiping Wang ,&nbsp;Yang Liu","doi":"10.1016/j.bbagen.2026.130910","DOIUrl":"10.1016/j.bbagen.2026.130910","url":null,"abstract":"<div><h3>Background</h3><div>TMED2, a p24 family member, has been implicated in the progression of multiple cancers. However, its function in thyroid cancer (THCA) is unclear and needs to be clarified.</div></div><div><h3>Methods</h3><div>TMED2 expression was first explored using single-cell datasets and the TCGA database, followed by validation in THCA tissues and cell lines by immunohistochemistry (IHC), western blot, and qRT-PCR. Survival analysis was performed to evaluate the correlation between TMED2 expression and patient survival. The impact of TMED2 on THCA cells was analyzed using CCK-8, EdU staining, wound healing, Transwell, and flow cytometry assays. The lipid droplet accumulation was detected using BODIPY staining. The expression of key enzymes involved in fatty acid (FA) synthesis was assessed using western blot assay. Rescue experiments were conducted to investigate the mechanism of TMED2. Finally, the role of TMED2 <em>in vivo</em> was assessed in a nude mouse model.</div></div><div><h3>Results</h3><div>TMED2 expression was significantly upregulated in THCA tissues and four cell lines and was closely related to worse outcomes. Functional experiments revealed that TMED2 enhanced proliferation, migration, invasion, and FA synthesis in THCA cells, while suppressing cell apoptosis. Mechanistically, TMED2 promoted tumor growth and FA synthesis in THCA by affecting the activation of mTORC1 signaling, which was also observed in a xenograft mouse model.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated that TMED2 may function as an oncogene to support THCA growth by affecting mTORC1-mediated FA synthesis. These findings suggest that TMED2 could serve as a potential target for THCA treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130910"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046055","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":"Involvement of neuropilin-1 in radiation-induced cell death via modulation of DNA double-strand break repair in glioblastoma T98G cells","authors":"Kaori Tsutsumi ,&nbsp;Kouta Kawahara ,&nbsp;Mizuki Kojima ,&nbsp;Ayu Yuasa ,&nbsp;Mitsuki Imazato ,&nbsp;Juri Kidachi ,&nbsp;Nanoha Yamamoto ,&nbsp;Hisashi Nakano","doi":"10.1016/j.bbagen.2026.130906","DOIUrl":"10.1016/j.bbagen.2026.130906","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most malignant form of brain tumor and is characterized by resistance to chemotherapy, radiotherapy, and combined chemoradiotherapy. Neuropilin-1 (NRP1) is a transmembrane receptor known to play critical roles in angiogenesis, tumor progression, and radioresistance. However, its precise role in radiation-induced cellular responses, particularly in GBM, remains unclear. In this study, we aimed to elucidate the mechanism underlying radiation resistance via NRP1 by examining the effects of NRP1 depletion in the p53-mutant GBM T98G cell line. Short interfering RNA-mediated suppression of NRP1 significantly reduced clonogenic survival following irradiation. Although the expression of caspase-3 and p21 was up-regulated in NRP1-suppressed cells, radiation-induced apoptosis and senescence did not significantly increase. γH2AX foci, a marker of radiation-induced DNA double-strand breaks (DSBs), were comparable between control and NRP1-suppressed cells. However, the DSB repair capacity was reduced in NRP1-suppressed cells, as evidenced by a higher number of unrepaired DSBs 24 h after irradiation. The number of 53BP1 foci, one of an important molecule in non-homologous end joining (NHEJ) of the DNA repair pathways, decreased in NRP1 suppression cells 0.5 h after X-ray irradiation. These changes were also observed in another GBM cell line, LN-18. The phosphorylation status of AKT, a key molecule in the survival pathway, remained unchanged in NRP1-suppressed cells compared to control cells. These findings suggest that NRP1 may regulate radiosensitivity by modulating DNA repair pathways in p53-mutated GBM T98G cells. NRP1 could serve as a potential therapeutic target for improving the response of radioresistant tumors such as GBM.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130906"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994077","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":"Targeting the IGF1/Twist1 axis: A novel mechanism for β-elemene-induced anoikis and EMT inhibition in breast cancer cells","authors":"Haibin Yan ,&nbsp;Xinyuan Wang ,&nbsp;Yifei Mo ,&nbsp;Yinan Huang ,&nbsp;Zheng Fu ,&nbsp;Lufan Xie","doi":"10.1016/j.bbagen.2026.130901","DOIUrl":"10.1016/j.bbagen.2026.130901","url":null,"abstract":"<div><h3>Background</h3><div>Anoikis resistance and epithelial-mesenchymal transformation (EMT) promote breast cancer spread. There is a positive correlation between twist family BHLH transcription factor 1 (Twist1) and anoikis resistance. Given the demonstrated therapeutic effect of β-elemene treatment on breast cancer, its effects on Twist1 and anoikis became the focus of our research.</div></div><div><h3>Methods</h3><div>Breast cancer cells, MDA-MB-157 and MDA-MB-231, were treated with 25 and 50 μM concentrations of β-elemene. Breast cancer cell lines with insulin-like growth factor 1 (IGF1) overexpression and Twist1 knockdown were successfully constructed to further explore the relevant mechanisms. Cell viability and apoptosis were detected by cell counting kit 8 (CCK8) method and fluorescent staining, respectively. Scratch assay for the detection of cell migration ability. The expression levels of matrix metalloproteinase (MMP) 9, MMP2, vimentin, N-cadherin, E-cadherin, Twist1, IGF1 and other related proteins were measured by western blot.</div></div><div><h3>Results</h3><div>β-elemene reduced cell viability and produced anoikis in a concentration-dependent manner. β-elemene decreased the expressions of MMP9 and MMP2, inhibited vimentin, N-cadherin, Twist1, IGF1 expressions and cell migration ability, and up-regulated E-cadherin. The overexpression of IGF1 reversed the regulatory effects of β-elemene on cell survival, anoikis, cell migration and associated protein expressions, but the knockdown of Twist1 can counteract the impact of IGF1 overexpression.</div></div><div><h3>Conclusion</h3><div>β-elemene modulates anoikis and EMT in breast cancer cells via the IGF1/Twist1 signaling pathway, offering novel insights for breast cancer therapy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 3","pages":"Article 130901"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905532","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":"Corrigendum to N-glycosylation of CD4+ T cell changes with the development in Graves' disease and is sensitive to methimazole treatment [Biochimica et Biophysica Acta General Subjects 1869 (2025) 130824]","authors":"Sara Trzos ,&nbsp;Marta Szewczyk ,&nbsp;Paweł Link-Lenczowski ,&nbsp;Grzegorz Sokołowski ,&nbsp;Małgorzata Trofimiuk-Müldner ,&nbsp;Katarzyna Bocian ,&nbsp;Ewa Pocheć","doi":"10.1016/j.bbagen.2026.130902","DOIUrl":"10.1016/j.bbagen.2026.130902","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 3","pages":"Article 130902"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948523","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":"Ursolic acid activates SIRT6 by enhancing enzyme-substrate interactions and promoting protein structural rearrangement","authors":"Zohreh Tabatabaian Nimavard ,&nbsp;Nuredin Bakhtiari ,&nbsp;Fereshteh Taghavi ,&nbsp;Sako Mirzaie ,&nbsp;Farangis Ataei ,&nbsp;Hamid-Reza Khaledi","doi":"10.1016/j.bbagen.2025.130890","DOIUrl":"10.1016/j.bbagen.2025.130890","url":null,"abstract":"<div><div>Ursolic acid (UA) has emerged as a promising bioactive compound with potential therapeutic effects, particularly in the upregulation of SIRT6, an important protein involved in various cellular processes, including longevity, stress response, and metabolism. Despite the growing interest in UA and its beneficial biological activities, the precise mechanisms governing its interaction with SIRT6 remain inadequately elucidated. This study aims to conduct a comprehensive investigation into the binding affinity of UA to SIRT6, as well as its effects on the protein's stability, kinetics, and structural characteristics.</div><div>Molecular dynamics simulations using Schrodinger software analyzed parameters such as radius of gyration, RMSD, RMSF, and binding energy. The SIRT6 gene was cloned into the pET28a vector, expressed in <em>Escherichia coli</em>, and purified via affinity chromatography. Kinetic parameters (Km, Vmax, and Kcat) were assessed using fluorescence enzyme assays, while structural modifications were examined via fluorescence spectroscopy, FTIR, and UV–visible spectrophotometry.</div><div>UA significantly enhances SIRT6 stability, reducing its radius of gyration and lowering binding energy from −25.38 to −47.93 kcal/mol. Kinetic analysis revealed a decrease in Km (13 to 10), an increase in Vmax (5013.42 to 9421.48 μM/min), and a rise in Kcat (15.03/s to 281.01/s), improving the Kcat/Km ratio. Structural assessments confirmed UA-induced modifications, increasing alpha-helix content (8.5 % to 26.2 %) and elevating the folding ratio from 0.066 to 14.8. However, it decreased aggregation index from 402.38 to 81.25. This integrative study elucidates UA's molecular influence on SIRT6, underscoring its potential therapeutic relevance across various signaling pathways.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130890"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623196","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":"Spermidine deficiency induces BNIP3/LC3B-mediated mitophagy in the salivary glands of accelerated aging mice","authors":"Nguyen Khanh Toan ,&nbsp;Manh Dat Duong ,&nbsp;Nguyen Duy Phu ,&nbsp;Le Viet Thanh ,&nbsp;Sang-Gun Ahn","doi":"10.1016/j.bbagen.2025.130897","DOIUrl":"10.1016/j.bbagen.2025.130897","url":null,"abstract":"<div><div>Aging is associated with mitochondrial dysfunction and altered autophagic processes, particularly in secretory organs such as the salivary glands. In this study, we investigated metabolic changes and their interactions with mitophagy in primary salivary gland cells (PSGCs) from klotho-deficient (kl−/−) mice, a model of accelerated aging. We observed a significant reduction in both mitochondrial number and mitochondrial DNA copy number in the PSGCs of kl−/− mice compared with those of wild-type (WT) controls. In contrast, lysosomal abundance was markedly increased in PSGCs from kl−/− mice. Moreover, the expression of the autophagy marker LC3B was significantly upregulated in kl−/− PSGCs, and the expression of the mitophagy markers BNIP3 and NIX increased. Our metabolomic profiling revealed disrupted spermidine biosynthesis in the salivary glands of kl−/− mice. Interestingly, spermidine treatment in kl−/− PSGCs increased the number of mitochondria and suppressed mitophagy, as indicated by the reduced expression of BNIP3 and LC3B. Conversely, in WT PSGCs, spermidine induced the expression of autophagy and mitophagy markers, namely, BNIP3 and LC3B. These findings suggest that accelerated aging in mice impairs mitochondrial homeostasis and alters autophagy/mitophagy pathways in salivary gland cells, potentially through the dysregulation of spermidine metabolism. Our results provide insight into the molecular mechanisms of aging in salivary glands and reveal the potential role of polyamine metabolism in maintaining mitophagy during aging.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130897"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780083","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":"Osmotic stress suppresses osteogenic differentiation by inhibiting nuclear translocation of YAP via perinuclear actin accumulation","authors":"Takashi Miyano,&nbsp;Haruka Hasegawa,&nbsp;Toshihiro Sera","doi":"10.1016/j.bbagen.2025.130891","DOIUrl":"10.1016/j.bbagen.2025.130891","url":null,"abstract":"<div><div>Hyperglycemia is a well-recognized cause of osteoblast dysfunction. Recent evidence, however, indicates that elevated extracellular osmolarity associated with hyperglycemia may independently impair osteogenic differentiation. However, the mechanisms underlying these effects remain poorly understood. In this study, we examined how osmotic stress influences osteoblast differentiation, with a focus on actin cytoskeletal remodeling and subcellular localization of the Yes-associated protein (YAP), a mechanosensitive transcriptional coactivator involved in osteogenesis. Using MC3T3-E1 pre-osteoblasts, we found that osteogenic induction enhanced cell proliferation, migration, nuclear deformation, and nuclear translocation of YAP, accompanied by upregulated expression of genes encoding osteogenic markers. In contrast, treatment with either glucose or mannitol, used to isolate the osmotic component of hyperglycemia, preserved nuclear morphology, decreased nuclear localization of YAP, and led to perinuclear actin accumulation, as confirmed by radial profile analysis of actin distribution. These effects were accompanied by downregulation of target genes of YAP and reduction in alkaline phosphatase (ALP)-positive cells. Similar effects observed following treatments with both glucose and mannitol suggest that the impairment arises primarily from osmotic stress rather than from glucose-specific metabolic signaling. Notably, pharmacological inhibition of Rho-associated kinase using Y-27632 attenuated perinuclear actin accumulation, restored nuclear translocation of YAP, and rescued the expression of YAP-dependent osteogenic genes under osmotic conditions. Y-27632 also increased the number of ALP-positive cells after treatment with both glucose and mannitol. These findings underscore cytoskeletal remodeling as a central regulator of YAP activity and osteogenesis under osmotic stress, and propose potential therapeutic targets for skeletal fragility in diabetes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130891"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628462","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}