Cell and Bioscience细胞与生物科学
Cell and Bioscience(英文缩写 CELL BIOSCI),ISSN 2045-3701,eISSN 2045-3701,中文译名:细胞与生物科学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
Cell and Bioscience 最新收录文献
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1. ROCK2 inhibition suppresses cytotoxic T lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.
PMID:日期:2026-07-20Cytotoxic T lymphocyte (CTL)-mediated platelet destruction represents an important pathogenic mechanism in primary immune thrombocytopenia (ITP) patients. Rho-associated coiled-coil kinase 2 (ROCK2) is an emerging regulator of immune balance, but its role in pathogenic CTL activation in ITP remains undefined. Here, we demonstrated that selective ROCK2 inhibition with KD025 potently suppressed CTL-mediated platelet destruction. In vitro, KD025 treatment of CTLs from ITP patients suppressed key effector functions, reducing degranulation as measured by CD107a expression, diminishing the secretion of cytotoxic molecules such as granzyme B and perforin, and decreasing CTL-platelet conjugate formation, resulting in reduced platelet apoptosis and activation. RNA-sequencing revealed downregulation of cytotoxic and glycolytic programs, with enrichment of JAK-STAT signaling. Mechanistically, KD025 reversed the pathogenic metabolic shift in ITP CTLs by lowering glycolytic flux and restoring mitochondrial respiration, accompanied by decreased STAT3 phosphorylation. IL-6-mediated STAT3 activation largely reversed these effects, indicating a ROCK2-STAT3-dependent mechanism. In vivo, both daily KD025 administration to an active ITP mouse model and transplantation of KD025-pretreated CD8 T cells into irradiated Rag1 mice alleviated CTL-mediated platelet apoptosis and increased platelet counts. Collectively, these findings supported a model in which ROCK2 contributed to STAT3-associated transcriptional and metabolic regulation of CTL pathogenicity, providing a rationale for further preclinical and translational evaluation of ROCK2 inhibition in ITP.
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2. Finding functional gaps: integrative analysis of VPAC1- and VPAC2-mediated signalling pathways in human lymphocytes.
PMID:日期:2026-07-19Vasoactive Intestinal Peptide (VIP) is a pleiotropic neuropeptide regulating diverse cellular and physiological processes. Its functions are primarily mediated through two G protein-coupled receptors, VPAC1 and VPAC2. The aim of this study was to perform an integrative analysis of VPAC receptor signalling, encompassing receptor-G protein coupling, second messenger production, kinase activation and transcriptional responses in T cells. Receptor interactions with Gα subunits were analysed using BRET assays. Stable Jurkat T-cell lines overexpressing VPAC1 (J-OEV1) or VPAC2 (J-OEV2) were generated. VPAC-dependent intracellular signalling in these cells was assessed by measuring cAMP and Ca levels, performing phospho-kinase arrays and Western blot analyses, and evaluating immune mediator expression, cell viability, and proliferation. VPAC1 showed interaction with both Gαs and Gαq subunits, whereas VPAC2 preferentially interacted with Gαs. In Jurkat cells, both receptors overexpression enhanced cAMP signalling, while increased Ca responses were restricted to VPAC1. In both J-OEV1 and J-OEV2 cells, VIP treatment reduced phosphorylation of inflammatory kinase-associated proteins. Overexpression of either receptor induced distinct basal transcriptional profiles of transcription factors and cytokines, which were further modulated by CD3/CD28-activation and VIP. While proliferation was not altered with overexpression, J-OEV2 showed a reduced redox metabolism at 72 h. This study aimed to identify functional differences between VPAC1 and VPAC2 signalling and reveals reproducible subtype-specific differences at early signalling. In Jurkat cells, both receptors induce a shift in its basal state; however, changes do not persist during TCR-driven activation, resulting in largely convergent effector responses.
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4. Macrophage Notch1 drives hepatocyte ferroptosis via the exosomal miR-142a-3p/TIPE2 axis to promote MASH progression.
PMID:日期:2026-07-12Metabolic dysfunction-associated steatohepatitis (MASH) is a serious chronic liver disease, in which ferroptosis has been identified as a crucial triggering event. However, the precise mechanisms of ferroptosis activation in MASH have not been fully disclosed. Herein, we found a positive association between macrophage Notch1 activation and hepatocyte ferroptosis in MASH patients and mice. Further, macrophage-specific Notch1 knockout (Notch1) mice showed ameliorative MASH symptoms, including less liver injury, lipid accumulation, inflammation, and collagen deposition. These mice also exhibited reduced hepatocyte ferroptosis, evidenced by decreased Fe levels and expression of pro-ferroptosis genes (Hamp and Ptgs2) and higher expression of anti-ferroptosis genes (Gpx4 and Slc7a11), as well as improved mitochondrial structure. Moreover, hepatocytes that received exosomes from Notch1-deficient macrophages exhibited decreased ferroptosis, while the tail vein infusion of Notch1-activated macrophage exosomes aggravated ferroptosis and MASH symptoms, identifying the role of macrophage Notch1-exosomes in promoting hepatocyte ferroptosis under MASH. Mechanistically, we discovered that macrophage Notch1 activation increased the level of exosomal miR-142a-3p by miRNA sequencing and decreased its target gene TIPE2, and confirmed that the inhibition of miR-142a-3p upregulated the Notch1 activation-induced TIPE2 decrease. Besides, overexpression of TIPE2 in hepatocytes inhibited ferroptosis. Collectively, our findings uncover a novel mechanism by which Notch1 activation in hepatic macrophages promotes hepatocyte ferroptosis through the exosomal miR-142a-3p/TIPE2 axis in MASH. We revealed a novel insight into hepatocyte ferroptosis activation from the perspective of macrophage, and discovered a pivotal role of macrophage Notch1 in hepatocyte ferroptosis during MASH progression, highlighting a potential therapeutic target for MASH treatment.
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5. The diversity of STING in regulating immune cell function and its role in liver diseases: from bench to bedside.
5. STING在调节免疫细胞功能方面的多样性及其在肝脏疾病中的作用：从实验室到床边PMID:日期:2026-07-10The cyclic guanosine monophosphate-adenylate synthase (cGAS)-stimulator of interferon genes (STING) pathway is a critical innate immune signaling pathway that recognizes and transmits cytoplasmic DNA signals, triggering interferon and inflammatory responses. Immune cells enriched in the liver participate in the development of various liver diseases through the STING pathway; however, the precise regulatory mechanisms of this pathway within the immune cells remain poorly integrated. Elucidating these mechanisms holds promise for developing novel therapeutic strategies to address related clinical challenges. This review systematically elucidates the mechanisms by which immune cells from both innate and adaptive immune systems influence liver diseases via the STING pathway, viewed through the lens of immune cell classification. Considering the differential expression of STING across immune cell types and their cross-regulatory interactions, the review categorizes STING's impact on liver diseases into two patterns: direct regulation by endogenous STING (intracellular STING) and indirect regulation by exogenous STING (STING originating from other cells). The diseases discussed encompass common liver disorders, such as viral hepatitis, metabolic dysfunction-associated steatotic liver disease(MASLD), hepatocellular carcinoma(HCC), and autoimmune hepatitis (AIH),among others.Integrating the latest preclinical research findings, the review thoroughly explores the potential feasibility and research progress of targeting the STING pathway to modulate the progression of liver diseases, including traditional STING agonist/antagonist, and novel approaches such as targeted delivery systems and microbiotherapy in STING drug development, along with their therapeutic potential in liver diseases. The cGAS-STING pathway serves as a pivotal signaling axis linking innate and adaptive immunity, playing a crucial role in the immune regulation of liver diseases. In-depth investigation of this pathway provides theoretical and translational foundations for elucidating the mechanisms underlying immune-metabolic dysregulation in the liver and developing precision immunotherapy strategies, thereby facilitating its transition from basic research to clinical treatment.
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6. Genome-wide association and polygenic risk score analyses of MASLD-related hepatic steatosis severity in a Taiwanese Han population.
PMID:日期:2026-07-10Hepatic steatosis is a highly prevalent metabolic condition and a major contributor to chronic liver disease, particularly in Asian populations. This study was conducted to identify genetic variants associated with the severity of ultrasound-defined hepatic steatosis in a Taiwanese Han population and evaluate the variants' biological relevance through cross-ancestry meta-analysis and functional validation. We conducted a genome-wide association study (GWAS) of 133,895 individuals with data in the Genetic Biobank of China Medical University Hospital. Hepatic steatosis severity was graded on an ordinal scale (0-3) using standardised ultrasonographic criteria. The polygenic risk score (PRS) under continuous shrinkage (CS) approach was used to construct a PRS for genetic risk stratification across severity grades. In the GWAS, we identified 1,229 single-nucleotide polymorphisms associated with hepatic steatosis severity (P < 1 × 10⁻), with the strongest signals discovered at the PNPLA3 locus (rs738408 and rs738409). The PRS-CS model exhibited strong discriminative performance (area under the receiver operating characteristic curve = 0.875) and a clear dose-response relationship with ultrasound-defined steatosis severity, substantially outperforming the risk model based on body mass index only. In vitro assays confirmed significantly increased lipid accumulation and intracellular triglyceride content in I148M-expressing hepatocytes under lipid-loading conditions. This study delineates the genetic landscape of ultrasound-defined hepatic steatosis severity in a large Taiwanese Han population and demonstrates the robust ability of the PRS to predict disease stage.
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7. Core binding factor β preserves early chondrogenic identity and prevents hypertrophic transition in cartilage organoids formation.
PMID:日期:2026-07-08Human-induced pluripotent stem cells (hiPSCs) represent a promising cell source for cartilage regeneration because of their self-renewal capacity and chondrogenic potential. However, the propensity of hiPSC-derived chondrocytes to undergo hypertrophic maturation remains a major obstacle to generating stable articular cartilage. Here, we identified core binding factor β (CBFβ) as a critical regulator of early chondrogenic identity and a suppressor of hypertrophic transition during hiPSC-derived cartilage organoid formation. CBFβ expression was markedly diminished in degenerative articular cartilage from both human osteoarthritis (OA) specimens and mouse OA models, and cartilage-specific ablation of Cbfβ accelerated cartilage structural deterioration and matrix loss. Notably, CBFβ was secreted by non-mineralizing cells, including chondrocytes and vascular smooth muscle cells, suggesting an autocrine/paracrine regulatory role. Pharmacological inhibition with Brefeldin A reduced extracellular CBFβ levels, whereas blockade of exosome release by GW4869 had minimal effect, indicating a secretion-associated mechanism independent of exosomes. Recombinant human CBFβ (rhCBFβ) treatment enhanced the chondrocyte phenotype by upregulating early chondrogenic markers (SOX9, COL2A1) while suppressing hypertrophic and catabolic markers ( RUNX2, MMP13). In hiPSC-derived cartilage organoids, rhCBFβ enhanced matrix deposition and increased COL2A1 and SOX9 expression. Transcriptomic profiling and qRT-PCR validation further demonstrated that rhCBFβ activated cartilage matrix-associated and anti-hypertrophic transcriptional programs, including upregulation of PTHRP, HIF1α, HDAC4, MGP, CILP, and ALK5, together with suppression of RUNX2.Collectively, these findings establish CBFβ as a key regulator of articular cartilage homeostasis and highlights its therapeutic potential for cartilage regeneration in OA. The ability of rhCBFβ to preserve early chondrogenic identity while preventing hypertrophic maturation offers a promising strategy for cartilage tissue engineering. Further preclinical studies are warranted to evaluate its efficacy and accelerate clinical translation for OA therapy.
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8. α-Synuclein triggers intercellular nanotubes formation to prevent apoptosis in astroglia by promoting stemness.
8. α-突触核蛋白通过促进干性触发细胞间纳米管形成以防止星形胶质细胞凋亡PMID:日期:2026-07-05Astrocytes play a significant role in neuroprotection by internalizing neurodegenerative aggregates and facilitating their degradation. Recent studies indicate that α-Synuclein (α-SYN) protofibrils promote the transfer of pathogenic aggregates and dysfunctional mitochondria between astroglia via tunneling nanotubes (TNTs), which enhances cell survival and resistance to apoptosis. However, the underlying mechanism of TNT-driven apoptosis resistance remains unclear. We find that α-SYN protofibrils induce aberrant mitochondria with decreased membrane potential (Ψm) and promote dynamic actin remodeling by relocating phosphorylated focal adhesion kinase (pFAK) to the nucleus, which triggers TNT formation in human astrocytoma cell lines and primary murine astrocytes. The important novel finding of this study is that pFAK in the nucleus co-localizes with Nanog, a crucial transcription factor for preserving stemness, and the interaction between pFAK and Nanog is critical for promoting p53 degradation via Mdm2-mediated ubiquitination and upregulating autophagy, thereby supporting the survival of astroglia exposed to toxic α-SYN protofibrils. ROCK inhibitor y-27632 also drives TNT-formation via pFAK translocation to the nucleus, colocalizes with Nanog, and enhances stemness-related gene expression. Inhibiting TNT with the actin depolymerizing agent cytochalasin-D prevents pFAK co-localization with Nanog in the nucleus and fails to protect cells from α-SYN-induced apoptosis. Nanog knockdown does not degrade p53 and hinders cell rescue from apoptosis. Furthermore, these transient TNTs transfer mitochondria to adjacent cells, potentially helping maintain metabolic stability. This study reveals that the TNT formation pathway promotes pFAK-Nanog interaction in the nucleus, leading to p53 degradation, which protects astroglia against α-SYN proteotoxicity and prevents apoptosis.
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9. Dual repression modes triggered by constitutively stabilized beta-catenin in the dorsal neural tube underlie cell fate alterations of the roof plate, neural crest, and dorsal interneurons.
PMID:日期:2026-06-30The roof plate that covers the dorsal neural tube is a key organizer or signaling center that generates morphogenetic signaling proteins to regulate neural crest cell production and dorsal CNS patterning. However, knowledge remains limited regarding the molecular mechanism regulating roof plate cell fate and function. Loss of function of Wnt/ß-catenin signaling in the roof plate or dorsal neural folds can prevent neural tube closure, neural crest cell production, and dorsal CNS patterning. In this study, we carried out conditional activation of ß-catenin in the dorsal neural folds of mice and found dramatic cell fate alterations, which include anteriorly expressed Cdx2 of the caudal-type homeobox gene in the dorsal neural tube, swapped expression patterns of the roof plate markers Bmp6 and Lmx1a with their respective homologues Bmp4 and Lmx1b, ectopically expressed Msx1 of the neural crest inducer in the migratory stream and dorsal root ganglia, and completely abolished expression of the neural crest cell differentiation marker Sox10 and the dorsal spinal interneuron precursor marker Atoh1. Our in vitro studies using a neural crest cell line demonstrate that the full-length ß-catenin, not the signaling defective ß-catenin significantly upregulates Msx1 and represses Sox10 and Atoh1 expression, which can be rescued by Msx1 knockdown, supporting an indirectly repressive role of the stabilized ß-catenin acting through Msx1 on Sox10 and Atoh1 expression. Intriguingly, Wnt1 and Wnt3a are drastically abolished in the roof plate of the ß-catenin stabilized embryos. However, Msx1 knockdown does not upregulate or rescue Wnt1 and Wnt3a expression when they are repressed by ß-catenin in vitro. Further in vitro studies reveal a direct repression of Wnt1 and Wnt3a by ß-catenin transcriptional complex, implicating a novel negative feedback loop of Wnt/ß-catenin signaling pathway at the ligand level. Together, these results suggest that constitutively stabilized ß-catenin triggers dual repression modes to prevent specification and differentiation of multiple cell lineages derived from the dorsal neural tube, but it may not prevent the presumptively undifferentiated Msx1-expressing neural crest cell precursors migrating out the dorsal neural tube to form the dorsal root ganglia, and that a finely tuned Wnt/ß-catenin signaling level is crucial for proper cell fate determination and functional modulation of the dorsal neural tube and its derivatives.
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10. The ubiquitin E3 ligase TRIM59 in myeloid cell regulates complement C3 through degrading CCAAT/enhancer binding protein β to promote neuron survival after ischemic stroke.
PMID:日期:2026-06-30Ischemic stroke is a cerebrovascular disease that activates the complement system, leading to inflammation and neuronal injury. TRIM59, an E3 ubiquitin ligase, has been extensively studied in cancer, sepsis, and myocardial infarction, and is upregulated in macrophages after ischemic stroke. This study used myeloid cell Trim59 conditional knockout and macrophage-specific Trim59 overexpression mice to investigate the role of macrophage TRIM59 in regulating complement C3 release and neuronal phagocytosis following cerebral ischemia. Myeloid cell Trim59 conditional knockout (Trim59-cKO) mice were generated and bred using the Cre-loxP system, and macrophage-specific Trim59 overexpressing (AAV-Trim59) mice were constructed via intra-bone marrow injection. Middle cerebral artery occlusion/reperfusion (MCAO/R) and photothrombotic (PT) surgery were used to mimic the cerebral ischemia in mice. RT-qPCR, ELISA and immunofluorescence staining were performed to detect the expression of complement molecules and synaptic engulfment. Neurobehavioral tests were performed during recovery phase. Western blot and co-immunoprecipitation (Co-IP) assay were utilized to analyze the effect of TRIM59 on C3 expression and its transcription factor CCAAT/enhancer binding protein β (c/EBPβ). Compared to Trim59 mice, Trim59-cKO promoted excessive expression and release of complement components C3 and C9 in macrophages after cerebral ischemia, resulting in aggravated pathological injury and reduced neuronal survival. In contrast, macrophage-specific TRIM59 overexpression reversed the above results and alleviated acute-phase injury. Furthermore, deficiency of Trim59 led to excessive macrophage-derived C3 deposition around neurons, enhanced phagocytic activity, and aggravated synaptic loss during the acute phase after MCAO/R injury, ultimately causing delayed recovery of cerebral blood flow, impaired learning and memory function, and lower survival rates during the chronic phase after PT induced ischemic stroke. The transcription factor c/EBPβ was identified as a key mediator of macrophage TRIM59-dependent regulation of C3 expression, verified by silencing of c/EBPβ in Trim59 knockout macrophages could attenuate the neuronal C3 deposition and synaptic damage. Further research shows that TRIM59 promotes K48-linked ubiquitination and proteasomal degradation of c/EBPβ through its RING domain. Macrophage TRIM59 is critical for controlling excessive complement C3 activation, release, and phagocytosis after ischemic stroke by promoting ubiquitin-mediated degradation of its transcription factor c/EBPβ, providing a potential therapeutic target for cerebral ischemia.