Acta biochimica et biophysica Sinica最新文献_第7页

EHDPP has the potential to impair mitochondrial fatty acid oxidation through inhibition of Cpt1A expression in mice. EHDPP有可能通过抑制小鼠Cpt1A的表达而损害线粒体脂肪酸氧化。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-08-06 DOI: 10.3724/abbs.2026103

Shiyi Hu, Zhiwei Bao, Juntao Wang, Mingrong Qian, Yuanxiang Jin

{"title":"EHDPP has the potential to impair mitochondrial fatty acid oxidation through inhibition of Cpt1A expression in mice.","authors":"Shiyi Hu, Zhiwei Bao, Juntao Wang, Mingrong Qian, Yuanxiang Jin","doi":"10.3724/abbs.2026103","DOIUrl":"10.3724/abbs.2026103","url":null,"abstract":"2-Ethylhexyl diphenyl phosphate (EHDPP), an aromatic organophosphate flame retardant (OPFR), is widely used in electronics, plastics, and textiles. While previous research has primarily focused on in vitro assays, the hepatotoxicity of EHDPP in mammals remains unclear. In the present study, six-week-old C57BL/6 mice are administered EHDPP via oral gavage for 28 days. First, EHDPP exposure leads to decreased body weights and significant hepatic accumulation of EHDPP (23.1 ng/g). Hepatic H&E staining, coupled with significantly elevated serum AST and ALT levels, demonstrates that the accumulation of EHDPP induces liver injury and inflammation. Targeted metabolomic analysis indicates reduced levels of free carnitine and acyl-carnitines in blood. RT-qPCR results confirm the marked suppression of key genes involved in hepatic lipid metabolism. Transmission electron microscopy (TEM) further reveals mitochondrial ultrastructural alterations following EHDPP exposure. Hepatic transcriptomic analysis identifies 79 and 579 differentially expressed genes (DEGs) in the EH-L and EH-H groups, respectively. Notably, Cyp2b10 displays a markedly high fold change in both the EH-L and EH-H groups. Furthermore, KEGG pathway enrichment and protein-protein interaction (PPI) analyses both exhibit that EHDPP exposure mainly affects lipid metabolism and drug metabolism. Within the PPI network modules, Cpt1a is identified as a critical hub protein. Molecular docking analysis predicts a potential interaction between EHDPP and the Cpt1A protein, and hepatic Cpt1A protein levels are significantly decreased after EHDPP exposure. Collectively, these findings provide novel insights into the mammalian health risks associated with EHDPP exposure.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Signal peptide-mediated endoplasmic reticulum targeting enhances antigen expression and secretion to improve mRNA vaccine efficacy. 信号肽介导的内质网靶向增强抗原表达和分泌，提高mRNA疫苗效力。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-08-03 DOI: 10.3724/abbs.2026115

Zijia Guo, Luna Ran, Jiayan Fu, Nengcheng Bao, Han Hu, Zimo Wu, Haiyang Dong, Yuanhui Mao, Yongfeng Jin

{"title":"Signal peptide-mediated endoplasmic reticulum targeting enhances antigen expression and secretion to improve mRNA vaccine efficacy.","authors":"Zijia Guo, Luna Ran, Jiayan Fu, Nengcheng Bao, Han Hu, Zimo Wu, Haiyang Dong, Yuanhui Mao, Yongfeng Jin","doi":"10.3724/abbs.2026115","DOIUrl":"10.3724/abbs.2026115","url":null,"abstract":"The expression and secretion levels of antigenic proteins are critical determinants of mRNA vaccine efficacy. Signal peptides, which direct protein translocation into the endoplasmic reticulum (ER), have the potential to significantly enhance protein expression and immunogenicity, highlighting their value as engineering tools for mRNA vaccine design. This study adopts the SARS-CoV-2 RBD as a model antigen to screen a panel of signal peptides derived from common secretory proteins. The signal peptides from C3, IL-12, and IL-20 are identified as candidates capable of significantly promoting antigen expression and secretion. Fluorescence confocal microscopy reveals that these signal peptides enhance the targeting of mRNA to the ER at the subcellular level. In vivo experiments demonstrate that mRNA vaccines incorporating these engineered signal peptides induce stronger humoral and cellular immune responses. This study confirms that signal peptide replacement can enhance antigen expression, offering a potential strategy for improving the efficacy of mRNA vaccines.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Taraxasterol alleviates liver fibrosis by suppressing hepatic stellate cell activation via the HSD11B1-ERK MAPK signaling axis. taraxastrol通过HSD11B1-ERK MAPK信号轴抑制肝星状细胞活化，减轻肝纤维化。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-08-03 DOI: 10.3724/abbs.2026089

Peng Wang, Haoxiong Zhou, Yuming Ding, Yan Chen, Huiling Liu, Jie Jiang, Bin Wu

{"title":"Taraxasterol alleviates liver fibrosis by suppressing hepatic stellate cell activation via the HSD11B1-ERK MAPK signaling axis.","authors":"Peng Wang, Haoxiong Zhou, Yuming Ding, Yan Chen, Huiling Liu, Jie Jiang, Bin Wu","doi":"10.3724/abbs.2026089","DOIUrl":"10.3724/abbs.2026089","url":null,"abstract":"Taraxasterol (TAR) exerts therapeutic effects on various liver diseases via its inherent hepatoprotective and anti-inflammatory properties. However, the mechanism by which TAR treats hepatic fibrosis remains unclear. This study aims to identify the potential targets and specific molecular mechanisms underlying the therapeutic effects of TAR on hepatic fibrosis. DDC- and CCl 4-induced mouse models of hepatic fibrosis are established. The human hepatic stellate cell (HSC) line LX-2 and primary mouse HSCs are used for in vitro experiments. Transcriptomics, network pharmacology, single-cell transcriptomics, and molecular docking are employed to identify potential therapeutic targets of TAR for hepatic fibrosis. Functional validation is performed via HSD11B1 overexpression and knockdown experiments, and the regulatory role of the ERK MAPK pathway is verified using the specific inhibitor U0126. Histological staining results show that TAR significantly alleviates DDC- and CCl 4-induced hepatic fibrosis in mice and reduces associated liver injury. In vitro assays reveal that TAR effectively reverses TGF-β-induced activation of LX-2 cells and primary mouse HSCs. Multi-omics and docking analyses identify HSD11B1 as a direct target of TAR, whose downregulation in activated HSCs is restored by TAR treatment. Functional experiments demonstrate that overexpression of HSD11B1 attenuates TGF-β-induced HSC activation, while HSD11B1 knockdown abolishes the therapeutic effects of TAR. Subsequent transcriptomic analysis confirms that HSD11B1 suppresses the ERK MAPK pathway, and knockdown of HSD11B1 compromises the therapeutic efficacy of the ERK MAPK inhibitor U0126. In summary, TAR alleviates liver fibrosis by inhibiting HSC activation through the HSD11B1-ERK MAPK axis.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellpose-based autonomous high-throughput atomic force microscopy for single-cell nanomechanical measurements. 用于单细胞纳米力学测量的基于细胞的自主高通量原子力显微镜。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-08-03 DOI: 10.3724/abbs.2026137

Haodong Huang, Meini Li, Lianqing Liu, Mi Li

引用次数: 0

Spatiotemporal orchestration of macrophage heterogeneity by cell adhesion molecules. 细胞粘附分子对巨噬细胞异质性的时空调控。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-07-16 DOI: 10.3724/abbs.2026127

Jing Yu, Chen Li, Hanlin Qiao, Jinrong Suo, Danting Yang, Changdong Lin

{"title":"Spatiotemporal orchestration of macrophage heterogeneity by cell adhesion molecules.","authors":"Jing Yu, Chen Li, Hanlin Qiao, Jinrong Suo, Danting Yang, Changdong Lin","doi":"10.3724/abbs.2026127","DOIUrl":"10.3724/abbs.2026127","url":null,"abstract":"Monocyte-derived macrophages (mo-macs) are central regulators of innate immunity and are essential for maintaining physiological homeostasis and host defense. Their functional efficacy relies on precisely coordinated transendothelial migration (TEM) and phenotypic polarization into classically activated (M1) or alternatively activated (M2) macrophages. This review delineates how cell adhesion molecules (CAMs), including integrins, selectins, the immunoglobulin superfamily (IgSF), and cadherins, act as pivotal sensors that orchestrate these spatiotemporal dynamics. CAMs facilitate the multi-step TEM of mo-macs and trigger intracellular signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT), to dictate macrophage plasticity in response to inflammation and the tumor microenvironment (TME). We highlight the dual role of CAMs in driving the pathogenesis of atherosclerosis and cancer while also exploring their potential in bioengineering for regenerative medicine. Elucidating these CAM-dependent regulatory networks not only helps to explain the intrinsic mechanisms underlying immune regulation but also provides a theoretical framework for designing next-generation targeted immunotherapies and personalized clinical interventions for inflammatory diseases and malignancies.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 8","pages":"1703-1718"},"PeriodicalIF":4.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ciclopirox suppresses melanoma growth by activating ER stress-driven apoptosis and disrupting Src/STAT3 signaling. 环匹罗通过激活内质网应激驱动的细胞凋亡和破坏Src/STAT3信号传导抑制黑色素瘤生长。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-07-13 DOI: 10.3724/abbs.2026088

Ziwei Zhang, Junwan Lu, Zheng Ouyang, Yi Huang, Bin Lu

{"title":"Ciclopirox suppresses melanoma growth by activating ER stress-driven apoptosis and disrupting Src/STAT3 signaling.","authors":"Ziwei Zhang, Junwan Lu, Zheng Ouyang, Yi Huang, Bin Lu","doi":"10.3724/abbs.2026088","DOIUrl":"https://doi.org/10.3724/abbs.2026088","url":null,"abstract":"Ciclopirox (CPX), an FDA-approved antifungal drug, exhibits promising antitumor activity. This study investigates its efficacy and mechanisms against melanoma. Here, we find that CPX potently inhibits melanoma cell proliferation, migration, and invasion in vitro and significantly suppresses xenograft tumor growth in vivo (20 mg/kg body weight, i.p.). Mechanistically, CPX induces mitochondrial dysfunction and a reactive oxygen species burst, activating PERK-dependent endoplasmic reticulum stress and ultimately triggering apoptosis via Caspase-3 activation. This apoptotic process is rescued by the antioxidant N-acetylcysteine, supporting a causative role of oxidative stress in CPX-induced cytotoxicity. Furthermore, CPX directly binds to the Src kinase domain, inhibiting its autophosphorylation and subsequently mediating a concentration-dependent reduction in STAT3 phosphorylation at Tyr705. It also downregulates total STAT3 protein levels and Ser727 phosphorylation, indicating multi-level disruption of STAT3 signaling. In conclusion, our findings reveal that CPX suppresses melanoma through dual mechanisms: activating ROS/ER stress-mediated apoptosis and disrupting the Src/STAT3 signaling pathway, supporting its therapeutic repurposing for melanoma.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of high-efficiency ( S)- N-methylcoclaurine 3'-hydroxylase involved in the biosynthesis of benzylisoquinoline alkaloids in Berberidaceae. 小檗科植物苯基异喹啉生物碱合成中高效(S)- n -甲基氯嘌呤3′-羟化酶的发现。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-07-13 DOI: 10.3724/abbs.2026113

Lingzhe Kong, Xiao He, Chenghua Gong, Maolun Gao, Ziyan Xie, Ruibing Chen, Zhichao Xu, Lei Zhang

{"title":"Discovery of high-efficiency ( S)- N-methylcoclaurine 3'-hydroxylase involved in the biosynthesis of benzylisoquinoline alkaloids in Berberidaceae.","authors":"Lingzhe Kong, Xiao He, Chenghua Gong, Maolun Gao, Ziyan Xie, Ruibing Chen, Zhichao Xu, Lei Zhang","doi":"10.3724/abbs.2026113","DOIUrl":"https://doi.org/10.3724/abbs.2026113","url":null,"abstract":"Benzylisoquinoline alkaloids (BIAs) represent a class of plant-derived compounds with significant pharmacological importance. The biosynthesis of most BIAs originates from a common precursor ( S)-reticuline. ( S)- N-methylcoclaurine 3'-hydroxylase (NMCH), encoded by CYP80B members, has always been regarded as a rate-limiting step that restricts the efficient synthesis of ( S)-reticuline, thereby leading to the low accumulation of BIAs. The highly-efficiency NMCH still needs to be further explored. Species within the Berberidaceae family are known to accumulate diverse BIAs at relatively high levels, making them an ideal plant resource for exploring highly active enzymes involved in BIA synthesis. Here, by integrating transcriptome and metabolite analysis across 11 Berberidaceae plants, we mine and characterize candidate genes involved in ( S)-reticuline biosynthesis. We further establish an engineered yeast platform for functional screening of NMCH genes and evaluate the catalytic activity of all CYP80B candidates. Among these, MbNMCH, isolated from Mahonia bealei, exhibits significantly higher catalytic activity for ( S)-reticuline production in yeast compared to previously reported NMCH enzymes. Our findings provide abundant genetic and metabolic information on Berberidaceae plants and identify a highly efficient enzymatic tool for BIA production in microbial cell factories, facilitating the sustainable manufacturing of diverse valuable alkaloids.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artesunate protects against sepsis-induced cardiomyopathy by reducing Akt/FoxO3-mediated apoptosis and inflammation. 青蒿琥酯通过减少Akt/ foxo3介导的细胞凋亡和炎症来预防败血症诱导的心肌病。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-07-01 DOI: 10.3724/abbs.2026108

Xi Jiang, Yankun Chen, Yalin Zeng, Yanghao Chen, Dan Yang, Zhiyu Ling

{"title":"Artesunate protects against sepsis-induced cardiomyopathy by reducing Akt/FoxO3-mediated apoptosis and inflammation.","authors":"Xi Jiang, Yankun Chen, Yalin Zeng, Yanghao Chen, Dan Yang, Zhiyu Ling","doi":"10.3724/abbs.2026108","DOIUrl":"https://doi.org/10.3724/abbs.2026108","url":null,"abstract":"Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication of sepsis characterized by acute and reversible myocardial dysfunction, for which effective targeted therapies remain limited. Artesunate (ART), a well-established first-line antimalarial agent, has attracted increasing attention for its anti-inflammatory, antioxidant, and cytoprotective properties. However, its role in SICM has not been fully elucidated. In this study, a murine SICM model is established using lipopolysaccharide (LPS) to evaluate the effects of ART on animal mortality, cardiac function, histopathology, and biomarkers of myocardial injury. In parallel, the in vitro study is performed using neonatal rat cardiomyocytes and H9c2 cells exposed to LPS in the presence or absence of ART. Transcriptomic and metabolomic analyses are used to elucidate the molecular mechanisms underlying ART-mediated cardioprotection. ART administration significantly improves cardiac function, attenuates myocardial injury, alleviates the inflammatory response, and reduces cardiomyocyte apoptosis in LPS-challenged mice. Consistent results are observed in vitro. Integrated multi-omics analyses identify the Akt/FoxO3 signaling pathway as a critical target of ART. ART treatment contributes to increased Akt phosphorylation and subsequent suppression of FoxO3 nuclear translocation and its transcriptional activity. Pharmacological inhibition of Akt using MK2206 or genetic knockdown of FoxO3 by siRNA abolishes the cardioprotective effects of ART. In addition, molecular docking analysis suggests a potential interaction between ART and Akt isoforms. Collectively, these findings demonstrate that ART possesses significant cardioprotective effects in experimental SICM through modulation of the Akt/FoxO3 signaling axis, leading to reduced apoptosis and inflammation. ART may serve as a therapeutic candidate for the management of SICM.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CX3CR1 promoter methylation impairs immune cell migration and exacerbates bacterial pneumonia. CX3CR1启动子甲基化损害免疫细胞迁移并加剧细菌性肺炎

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-07-01 DOI: 10.3724/abbs.2026116

Yanrui Jia, Qi Cao, Yanping Zhang, Yuanyuan Zhang, Xianjin Xie, Shi Zhang

{"title":"CX3CR1 promoter methylation impairs immune cell migration and exacerbates bacterial pneumonia.","authors":"Yanrui Jia, Qi Cao, Yanping Zhang, Yuanyuan Zhang, Xianjin Xie, Shi Zhang","doi":"10.3724/abbs.2026116","DOIUrl":"https://doi.org/10.3724/abbs.2026116","url":null,"abstract":"Severe pneumonia remains a major contributor to infection-related deaths globally, often driven by inadequate pathogen clearance. Impaired immune cell trafficking to infected sites critically contributes to this outcome, yet the underlying regulatory mechanisms remain incompletely understood. Here, we analyze peripheral blood transcriptomic data from a public cohort of 184 pneumonia patients to identify prognosis-related genes, followed by prospective enrollment of 38 patients for integrated multi-omics profiling. Low CX3CR1 expression is associated with 28-day mortality and correlates with hypermethylation at the promoter CpG site cg00262061. Mechanistically, this methylation modification impedes RNA polymerase II recruitment to the CX3CR1 promoter, thereby suppressing transcription. CRISPR-dCas9-based targeted methylation or demethylation at cg00262061 in primary human CD14+ monocytes directly manipulates endogenous CX3CR1 expression, establishing causality. Notably, cg00262061 hypermethylation is detected exclusively in the CX3CR1- subset of patient peripheral blood mononuclear cells, indicating selective epigenetic silencing. Functionally, this methylation or direct CX3CR1 knockdown markedly impairs monocyte and T cell migration. In a murine bacterial pneumonia model, systemic CX3CR1 inhibition reduces pulmonary immune cell infiltration, increases bacterial burden, exacerbates lung injury, and decreases survival. Competitive adoptive transfer confirms a cell-intrinsic migration defect of CX3CR1-deficient immune cells. These findings delineate a pathogenic pathway wherein promoter hypermethylation silences CX3CR1, compromises immune cell homing, and aggravates disease severity, offering a mechanistic basis for prognostic assessment and a conceptual framework for host-directed therapies, although clinical translation warrants further investigation.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIM3 alleviates microglia-mediated neuroinflammation in neuropathic pain by negatively regulating glycolysis-driven NLRP3 inflammasome activation. TIM3通过负调控糖酵解驱动的NLRP3炎性体激活，减轻神经性疼痛中小胶质细胞介导的神经炎症。

IF 4.5 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2026-06-30 DOI: 10.3724/abbs.2026034

Jinhong Jiang, Yeqi Li, Mengyu Zhang, Cui Yin, Zhi Qi, Jie Xu, Chen Lu

{"title":"TIM3 alleviates microglia-mediated neuroinflammation in neuropathic pain by negatively regulating glycolysis-driven NLRP3 inflammasome activation.","authors":"Jinhong Jiang, Yeqi Li, Mengyu Zhang, Cui Yin, Zhi Qi, Jie Xu, Chen Lu","doi":"10.3724/abbs.2026034","DOIUrl":"https://doi.org/10.3724/abbs.2026034","url":null,"abstract":"Microglia-mediated neuroinflammation has emerged as a potential therapeutic target for neuropathic pain. T-cell immunoglobulin domain and mucin domain-3 (TIM3), which is expressed on various immune cells, has been implicated in inflammation-related diseases. However, its role in neuropathic pain remains unclear. Here, we show that following chronic constriction injury, TIM3 expression is significantly upregulated and plays a protective role by limiting the development and progression of neuropathic pain. Specifically, TIM3 upregulation attenuates neuropathic pain progression and microglia-mediated neuroinflammation, whereas pharmacological inhibition of TIM3 exacerbates pain hypersensitivity. Mechanistically, TIM3 negatively regulates glycolysis, thereby suppressing NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and preventing further microglia-driven inflammatory responses in vivo and in vitro. Furthermore, both glycolysis and the glycolysis-associated NLRP3 inflammasome are essential for TIM3-mediated neuropathic pain development. Additionally, TIM3 inhibits nuclear factor-kappa B (NF-κB) activation by downregulating glycolysis in vivo and in vitro. Our findings identify TIM3 as a negative regulator of the glycolysis/NLRP3 inflammasome pathway in inflammatory microglia, highlighting its protective role against neuropathic pain. These results suggest that TIM3 is a promising therapeutic target for preventing neuropathic pain.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0