Life sciences最新文献

{"title":"Expression of Concern: Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway [Life Sci. 193 (2018) 159-170].","authors":"","doi":"10.1016/j.lfs.2026.124675","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124675","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"404 ","pages":"124675"},"PeriodicalIF":6.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One protein, many faces: TRAF1 from signaling hub to disease diversity.","authors":"Yu-Hang Liu, Run-Shi Xu, Jin-Qiang Hu, Xin Tong, Cong-Cong He, Xing-Hua Gao","doi":"10.1016/j.lfs.2026.124744","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124744","url":null,"abstract":"<p><p>Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a unique member of the TRAF family, distinguished by its lack of an N-terminal RING domain. At the transcriptional level, TRAF1 expression is regulated by diverse mechanisms, including methylation, RNA-binding domain (RBD) proteins, and microRNAs. Post-translationally, TRAF1 undergoes modifications such as M1-linked ubiquitination and phosphorylation. In immune signaling pathways, TRAF1 usually displays functional duality: it activates the canonical NF-κB pathway by enhancing cIAP recruitment downstream of TNFR1, whereas at death domain-lacking TNFR superfamily members (NDDTNFRs), it drives the non-canonical NF-κB pathway through TRAF3 degradation. Conversely, TRAF1 often acts as a negative regulator in Toll-like receptor (TLR) signaling. Within the MAPK pathway, TRAF1 participates in modulating multiple cascades, including ASK1/B-Raf(BRAF)/ERK1. In immune-mediated diseases, TRAF1 contributes to disease pathogenesis by regulating inflammatory cytokines, matrix metalloproteinase (MMP) expression, synovial cell apoptosis and tissue destruction. In infectious diseases, the anti-apoptotic effect of TRAF1 downstream of the 4-1BB signaling pathway serves as a host strategy to combat viral infections by preserving CD8+ T cell survival. However, Helicobacter pylori exploits TRAF1 upregulation to inhibit apoptosis in gastric epithelial cells, facilitating its persistent colonization. This contrast highlights TRAF1's functional diversity across infections. This review summarizes the post-translational regulation of TRAF1, its dual roles in signaling pathways, and its contributions to immune-related and infectious diseases, aiming to clarify its mechanistic complexity within the existing biological framework.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124744"},"PeriodicalIF":6.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimal essentials for humanized vessel-on-a-chip model for vascular research.","authors":"Amparo Romero-Picó, Laura Vázquez-Vázquez, Diana Rodríguez-Suárez, Simón Rodríguez-Moar, Bruno K Rodiño-Janeiro, Carmen Bao-Varela, Sonia Eiras, José R González-Juanatey, Rosa M Agra-Bermejo, Ezequiel Álvarez","doi":"10.1016/j.lfs.2026.124745","DOIUrl":"10.1016/j.lfs.2026.124745","url":null,"abstract":"<p><strong>Aims: </strong>During the last decade, in vitro 3D models based on organ-on-a-chip technology have been developed, representing a biotechnology research advance towards more physiologically relevant models that aim to provide more predictable and less costly preclinical models. We aimed to develop a vessel-on-a-chip using a biocompatible microfluidic device co-cultured with human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC).</p><p><strong>Materials and methods: </strong>VSMC and HUVEC were isolated from umbilical cords and co-cultured in a polydimethylsiloxane (PDMS) chip using specific growth media and tropoelastin-enriched media to favour extracellular matrix (ECM) synthesis, which was measured by gene expression (quantitative polymerase chain reaction) and deposition (immunofluorescence), to establish an organized structure. Then, using a microfluidic pump system, the functional relevance of the model was evaluated by fluidic and permeability studies after a 9-day- cell growth period.</p><p><strong>Key findings: </strong>Our vessel-on-a-chip model showed a bilayer structure, cell specific morphology and biomarkers phenotypes, and cell integrity. Gene and protein expression demonstrated the presence of ECM components, providing structural support and microenvironment control. It was observed that shear stress closer to the physiological range provided stability to the model and control of the permeability function.</p><p><strong>Significance: </strong>Our 3D model may serve as a promising preclinical research tool that closely mimics the structural conformation of blood vessels and reflects essential physiological parameters, including cell maturity, shear stress, and functional permeability. Consequently, it could potentially be applied to cellular and molecular research to further elucidate vascular biology in cardiovascular diseases.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124745"},"PeriodicalIF":6.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and mechanism of ATF6-mediated endoplasmic reticulum stress in ITLN-1 against cerebral ischemia-reperfusion injury.","authors":"Yanqing Liu, Lu Xu, Zhe Zhang, Caiqin Zhang, Peijie Liu, Pan Li, Shuya Wang, Ye Tian, Yang Yang, Xiaochen Niu","doi":"10.1016/j.lfs.2026.124746","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124746","url":null,"abstract":"<p><strong>Aims: </strong>Intelectin-1 (ITLN-1), a novel adipocytokine, exerts neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI), yet its molecular mechanisms remain unclear. This study focused on activating transcription factor 6 (ATF6), a key endoplasmic reticulum stress sensor, to explore its role in CIRI-induced neuronal injury and determine whether ITLN-1 mediates neuroprotection through ATF6 regulation.</p><p><strong>Materials and methods: </strong>We established an N2a cell hypoxia/reoxygenation (H/R) model and a mouse middle cerebral artery occlusion (MCAO) model. Using protein molecular docking, situ proximity ligation assay, Western blotting, mitochondrial membrane potential assays, and TUNEL staining, we investigated ATF6 activation in neuronal apoptosis and its upstream regulatory mechanisms.</p><p><strong>Key findings: </strong>H/R injury markedly induced ATF6 activation in N2a cells, triggering mitochondrial dysfunction and promoting apoptosis. ATF6 overexpression further aggravated these effects, confirming its critical pathogenic role in CIRI. Mechanistic analyses revealed that ITLN-1 physically associates with ATF6. Both ITLN-1 overexpression and exogenous recombinant ITLN-1 administration significantly suppressed excessive ATF6 activation, modulated the JNK signaling pathway, improved cell viability, reduced intracellular calcium overload and reactive oxygen species accumulation, and attenuated neuronal apoptosis. In vivo, ITLN-1 ameliorated neurological deficits, reduced neuronal damage, and alleviated demyelination, whereas ITLN-1 knockdown produced opposite effects.</p><p><strong>Significance: </strong>Excessive ATF6 activation underlies CIRI-induced neuronal injury. ITLN-1 exerts neuroprotection by inhibiting ATF6 and modulating JNK signaling, thereby alleviating mitochondrial dysfunction and reducing apoptosis. These findings highlight the ITLN-1/ATF6 axis as a promising therapeutic target for ischemic stroke.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124746"},"PeriodicalIF":6.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin alleviates CYH33-induced hyperglycemia and preserves antitumor immunity against ovarian cancer in type 1 diabetic mice.","authors":"Jiaqi Sun, Lan Xu, Hui Qu, Xi Zhang, Xiaoyu Ma, Ying Leng, Linghua Meng","doi":"10.1016/j.lfs.2026.124743","DOIUrl":"10.1016/j.lfs.2026.124743","url":null,"abstract":"<p><p>PI3K is frequently hyperactivated in ovarian cancer and has emerged as a promising therapeutic target. CYH33 is a novel PI3Kα-selective inhibitor that has been approved in Japan for the treatment of ovarian clear cell carcinoma harboring PIK3CA mutations. However, its on-target adverse effect of hyperglycemia limits its clinical application, particularly in patients susceptible to diabetes, underscoring the urgent need to optimize therapeutic strategies to improve both safety and efficacy. In this study, we employed an ID8 syngeneic murine ovarian cancer model and demonstrated that CYH33 significantly inhibited tumor growth with a modest effect on glucose homeostasis. We then established mouse models of type 1 (T1D) and type 2 diabetes (T2D) to expose hyperglycemia induced by PI3K inhibition and identified that dapagliflozin effectively alleviated CYH33-induced hyperglycemia while preserving its antitumor activity in T1D mice. Mechanistically, the combination of CYH33 and dapagliflozin may improve the immunosuppressive tumor microenvironment in T1D mice, as evidenced by upregulation gene sets involved in interferon-α and interferon-γ response, as well as significantly enhanced infiltration of CD8⁺ T-cell in ID8 tumors. Furthermore, this combination synergized with anti-PD-1 antibody to further enhance antitumor efficacy. These findings provide a potential strategy for optimizing the clinical use of PI3K inhibitors and shed light on metabolic interventions to modulate tumor immune microenvironment.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124743"},"PeriodicalIF":6.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian system and human health: From molecular mechanisms to clinical integration.","authors":"Tao Fan, Xing Wei, Ping Lin, Yinggao Liu, Yuan Tian","doi":"10.1016/j.lfs.2026.124742","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124742","url":null,"abstract":"<p><p>The circadian system, an evolutionarily conserved endogenous oscillator coordinating physiological adaptation to geophysical cycles, coordinates hierarchical gene regulatory networks, metabolic pathways, and physiological functions to maintain organismal homeostasis. Circadian disturbances caused by modern lifestyle are recognized as key etiological factors in complex multisystem disorders, including neurodegenerative, cardiovascular, metabolic, and oncogenic pathologies. The review synthesizes current evidence to delineate that organ-specific physiological programs across the human body are under circadian clock, and chronic desynchronization of system drives a broad spectrum of clinical disorders. Moreover, the review critically assesses state-of-the-art therapeutic modalities, and identifies promising technological innovations. It advances precision chronomedicine by proposing public health interventions, such as environmental modification combined with behavioral education, offering a roadmap for clinical implementation of circadian restoration therapies.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124742"},"PeriodicalIF":6.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELF1 exacerbates intervertebral disc degeneration by promoting ACSL4-dependent ferro-aging of nucleus pulposus cells through the IFITM3-PTPRO axis.","authors":"Jia-Hao Lu, Shan-Shan Huang, Hao-Wei Xu, Shu-Bao Zhang, Sheng-Jie Chang, Fei-Yang Wu, Xiao-Wei Liu, Shan-Jin Wang","doi":"10.1016/j.lfs.2026.124736","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124736","url":null,"abstract":"<p><strong>Aims: </strong>Intervertebral disc degeneration (IVDD) is a major cause of low back pain and is characterized by nucleus pulposus cell (NPC) senescence and extracellular matrix degradation. Ferro-aging, a chronic iron-dependent lipid peroxidation-associated senescence program, has recently been proposed as a potential mechanism linking metabolic dysregulation with tissue aging. However, whether ferro-aging contributes to IVDD and how it is regulated remain unclear. This study aimed to investigate the role of ferro-aging in IVDD and identify its upstream regulatory network.</p><p><strong>Materials and methods: </strong>Single-cell RNA sequencing analysis, human nucleus pulposus tissue validation, puncture-induced and age-related IVDD animal models, and multiple NPC senescence models were used to investigate IFITM3-associated ferro-aging. Loss- and gain-of-function approaches, RNA sequencing, co-immunoprecipitation, dual-luciferase reporter assays, and chromatin immunoprecipitation assays were performed to investigate the regulatory network involving ELF1, IFITM3, PTPRO, and ACSL4.</p><p><strong>Key findings: </strong>IFITM3 showed increased expression in degenerated NPCs and was associated with ferroptosis-related pathways, inflammatory responses, and extracellular matrix remodeling. IFITM3 promoted NPC ferro-aging by enhancing iron accumulation, ACSL4 expression, lipid peroxidation, oxidative stress, and cellular senescence. Mechanistically, PTPRO was identified as an IFITM3-associated regulatory node that contributes to ACSL4 protein stabilization and lipid peroxidation, while ELF1 transcriptionally activates IFITM3. Genetic inhibition of Ifitm3, Ptpro, or Elf1 alleviated ferro-aging phenotypes and attenuated IVDD progression.</p><p><strong>Significance: </strong>This study identifies ferro-aging as a previously unrecognized mechanism contributing to IVDD and identifies a regulatory network involving ELF1, IFITM3, PTPRO, and ACSL4 as a potential therapeutic framework for delaying disc degeneration.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124736"},"PeriodicalIF":6.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-485-5p targets RGS4 to promote angiogenesis in lower limb ischemia by activating VEGFR-2/AKT/ERK1/2 signaling.","authors":"Mengting Li, Yulin Luo, Yufei Li, Jingcan You, Liqun Wang, Jianbo Wu, Youkun Zheng, Mao Luo","doi":"10.1016/j.lfs.2026.124626","DOIUrl":"10.1016/j.lfs.2026.124626","url":null,"abstract":"<p><p>Angiogenesis is critical for post-ischemic tissue repair. Although miR-485-5p is highly expressed in vascular tissues and RGS4 regulates angiogenesis, their specific roles under hypoxia remain largely unknown. This study aimed to elucidate these functions and underlying mechanisms. Using a CoCl₂-induced hypoxic model in HUVECs, we observed that hypoxia significantly downregulated miR-485-5p expression while concurrently upregulating RGS4 mRNA levels. Notably, either inhibition of RGS4 or overexpression of miR-485-5p markedly enhanced HUVEC proliferation, migration, and tube formation. A luciferase reporter assay further confirmed that miR-485-5p directly targets RGS4. In addition, miR-485-5p overexpression or RGS4 inhibition increased the phosphorylation levels of VEGFR-2, AKT, and ERK1/2. Through co-immunoprecipitation assays, we revealed for the first time a direct interaction between RGS4 and VEGFR-2, which suppresses VEGF signaling and consequently impairs angiogenesis. Conversely, overexpression of RGS4 reversed the pro-angiogenic effects of miR-485-5p, as evidenced by reduced VEGFR-2/AKT/ERK1/2 phosphorylation and decreased proliferation, migration, and tube formation in HUVECs. These findings indicate that miR-485-5p promotes angiogenesis by downregulating RGS4. Consistent with these in vitro results, experiments in vivo using a rat hindlimb ischemia model confirmed that inhibition of RGS4 via si-RGS4 or overexpression of miR-485-5p via agomir-miR-485-5p markedly improved blood perfusion recovery, enhanced vascular angiogenesis, and increased VEGFR-2/AKT/ERK1/2 phosphorylation. Collectively, our study demonstrates that the miR-485-5p/RGS4 axis promotes hypoxia-induced angiogenesis by relieving RGS4-mediated inhibition of VEGFR-2/AKT/ERK1/2 signaling, thereby providing a strong rationale for targeting miR-485-5p as a possible treatment approach for lower extremity arterial disease.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124626"},"PeriodicalIF":6.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis lipopolysaccharide induces osteoblast senescence and defective mineralization associated with indoleamine 2,3-dioxygenase 1-kynurenine-aryl hydrocarbon receptor signaling.","authors":"Shuguang Han, Wenlong Zhang, Xiaoli Zhang, Mingyong Wang, Yu Jiang","doi":"10.1016/j.lfs.2026.124741","DOIUrl":"10.1016/j.lfs.2026.124741","url":null,"abstract":"<p><strong>Aim: </strong>To determine whether Porphyromonas gingivalis-derived lipopolysaccharide (P.g-LPS) is associated with osteoblast senescence and defective mineralization involving inflammation-related indoleamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway and to examine its upstream regulation.</p><p><strong>Methods: </strong>hFOB1.19 human osteoblasts and zebrafish were exposed to P.g-LPS. Osteogenic differentiation, senescence, IDO1/Kyn/AhR signaling, Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/RELA regulation, and rescue by the IDO1 inhibitor epacadostat or AhR inhibitor CH223191 were assessed using staining, qPCR, western blotting, ELISA, gene silencing, and dual-luciferase reporter assays.</p><p><strong>Results: </strong>P.g-LPS reduced osteogenic differentiation and mineralization and increased senescence-associated markers in hFOB1.19 cells and zebrafish. P.g-LPS increased IDO1 expression and Kyn levels; epacadostat attenuated osteogenic impairment and senescence-associated changes. Exogenous Kyn increased AhR-responsive gene expression and produced similar phenotypes, which were attenuated by CH223191. TLR4 knockdown reduced P.g-LPS-induced IDO1, NFKB1, and RELA expression, and RELA overexpression enhanced wild-type IDO1 promoter activity, with loss of this response after mutation of the predicted NF-κB site.</p><p><strong>Conclusion: </strong>P.g-LPS-induced osteogenic impairment and senescence-associated changes involve IDO1-Kyn-AhR-related signaling, alongside TLR4-associated responses and RELA-dependent IDO1 promoter activity. Inhibition of IDO1 or AhR attenuated these phenotypes in the experimental models.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124741"},"PeriodicalIF":6.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Hydroxybutyrate alleviates intestinal aGVHD via remodeling gut microbiota-bile acid axis and inhibiting TLR4-NF-κB-driven Th1/Th17 differentiation.","authors":"Ruixue Tian, Chao Deng, Kexin Liu, Hurong Lai, Caifeng Liao, Huaijun Tu, Jian Li","doi":"10.1016/j.lfs.2026.124737","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124737","url":null,"abstract":"<p><p>The intestine is a major target organ in acute graft-versus-host disease (aGVHD), and its microbial homeostasis critically influences disease pathogenesis and progression. Emerging evidence indicates that beta-hydroxybutyrate (BHB) can remodel the gut microbiota and dampen pro-inflammatory immune activity. To investigate the therapeutic potential of BHB in aGVHD, we first reanalyzed publicly available transcriptomic and single-cell RNA sequencing data from patients with aGVHD, which revealed that genes involved in ketone body metabolism and transport were significantly decreased in intestinal tissues. We then used a murine model of aGVHD to evaluate the therapeutic effects of BHB by clinical scoring and intestinal histopathological examination. To define the immunological and microbial mechanisms, we integrated flow cytometry and ELISA for Th1/Th17, intestinal tissue-resident T and circulating T cells assessment, and with multi-omics analyses, including fecal 16S rRNA sequencing, fecal metabolomics, and intestinal transcriptomics. We further explored whether BHB directly regulates T-cell migration and differentiation and therefore assessed its effects on Th1 and Th17 differentiation in vitro. BHB treatment reduced the clinical score of aGVHD, alleviated intestinal injury in mice, and showed effects similar to those of methotrexate (MTX). BHB also corrected gut microbial dysbiosis, enriched Akkermansia muciniphila, and ameliorated bile acid metabolism dysregulation. Moreover, BHB inhibited intestinal T cell migration and Th1/Th17 differentiation both in vivo and in vitro. Mechanistically, transcriptome sequencing suggested that suppression of the TLR4-NF-κB pathway may underlie these anti-inflammatory effects. In summary, BHB effectively alleviates intestinal damage in aGVHD mice, likely through coordinated microbial, metabolic, and immunological regulation, and may represent a promising therapeutic strategy for aGVHD.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124737"},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}