Acta biochimica et biophysica Sinica最新文献

{"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":"<p><p>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 <i>in vitro</i> 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 <i>in vitro</i>. 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 <i>FoxO3</i> 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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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 <i>in vivo</i> and <i>in vitro</i>. 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 <i>in vivo</i> and <i>in vitro</i>. 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.</p>","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}

{"title":"Phillyrin protects against myocardial ischemia/reperfusion injury by promoting KNL1 K605 acetylation to inhibit the p53/p21 pathway.","authors":"Dongsheng He, Zhipeng Ren, Shangxuan Li, Ziqiang Dai, Gen Zhang, Huan Wang, Guanzheng Cui, Dianyuan Li","doi":"10.3724/abbs.2026104","DOIUrl":"https://doi.org/10.3724/abbs.2026104","url":null,"abstract":"<p><p>Reperfusion therapy is critical for acute myocardial infarction but is often accompanied by myocardial ischemia/reperfusion injury (MIRI). Phillyrin, a natural lignan from <i>Forsythia suspensa</i>, exerts anti-inflammatory and antioxidant effects; however, its role and mechanism in MIRI remain unclear. In this study, HL-1 cardiomyocytes are subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Cell viability, apoptosis, oxidative stress, and inflammation are measured after phillyrin treatment. Multiomics (mRNA-seq, proteomics, and acetylproteomics) is used to identify key targets and pathways. Molecular docking, co-immunoprecipitation, site-directed mutagenesis, and western blot analysis are used to validate posttranslational regulation. A mouse MIRI model is established to confirm the <i>in vivo</i> cardioprotective effects of phillyrin. Phillyrin preserves cell viability and reduces apoptosis, oxidative stress, and inflammation in OGD/R-injured HL-1 cells. Multiomics integration reveals that phillyrin acts primarily through posttranslational regulation and highlights kinetochore scaffold 1 (KNL1) as the only protein that is both upregulated and hyperacetylated at lysine 605 (K605). Mechanistically, phillyrin may bind to the KNL1 C-terminus and enhance the interaction between KNL1 and acetyltransferase p300/CBP. KNL1 K605R mutation and <i>Knl1</i> knockdown reduce KNL1 protein expression and reverse the inhibitory effects of phillyrin on p53 pathway-mediated apoptosis, oxidative stress, and inflammation. In mouse MIRI models, phillyrin reduces infarct size, myocardial damage, and cardiomyocyte apoptosis; these effects are abolished by knockdown of <i>Knl1</i>. Therefore, phillyrin promotes KNL1 acetylation at K605 to increase KNL1 protein expression, thereby inhibiting p53 signaling and alleviating apoptosis, oxidative stress, and inflammation in MIRI. This study identifies KNL1 acetylation at K605 as a novel posttranslational modification target for cardioprotection.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366584","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}

{"title":"The USP46-MCM7-RAD51 axis confers oxaliplatin resistance in colon cancer by augmenting homologous recombination repair capacity.","authors":"Changlei Wu, Wenjie Zhu, Zitao Liu, Taifu Xiao, Cheng Zuo, Zhengming Zhu, Jun Huang","doi":"10.3724/abbs.2026060","DOIUrl":"10.3724/abbs.2026060","url":null,"abstract":"<p><p>Chemoresistance remains a critical barrier to the efficacy of oxaliplatin in colon cancer treatment. While the deubiquitinating enzyme USP46 is implicated in multiple tumor progression pathways, its specific role in oxaliplatin resistance remains undetermined. Our analysis reveals that USP46 is significantly overexpressed in colon cancer tissues, with its elevated expression correlating with poor clinical outcomes in colon cancer patients. Silencing USP46 suppresses both the proliferation and metastatic potential of colon cancer cells while simultaneously enhancing cellular sensitivity to the DNA-damaging agent oxaliplatin. Mechanistically, overexpression of USP46 leads to upregulation of nuclear RAD51 expression and facilitates the assembly of RAD51 foci, thereby increasing homologous recombination repair (HRR) capacity and contributing to oxaliplatin resistance in colon cancer cells. MCM7 is identified as a bona fide substrate of USP46 by LC-MS/MS profiling. Subsequent experiments confirm that USP46 specifically removes K48-linked polyubiquitin chains from MCM7, thereby stabilizing its protein expression. Rescue assays validate that USP46 modulates RAD51 expression and HRR function in an MCM7-dependent manner. Collectively, our study uncovers a novel USP46-MCM7-RAD51 signaling cascade that confers oxaliplatin resistance in colon cancer via augmentation of HRR-dependent DNA repair, thereby establishing this axis as a promising therapeutic target for overcoming oxaliplatin resistance.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597457","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}

{"title":"Metabolic reprogramming-the nexus of cellular adaptations, organ crosstalk, and therapeutic innovations in human diseases.","authors":"Jun Ren, Hartmut Schlüter, Marcel Kwiatkowski, Ling Lin","doi":"10.3724/abbs.2026110","DOIUrl":"https://doi.org/10.3724/abbs.2026110","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 7","pages":"1437-1440"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668030","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}

{"title":"A bifunctional aptamer-siRNA chimera targeting ACE2 for the inhibition of SARS-CoV-2 S pseudovirus entry and replication.","authors":"Tao Jiang, Zhiqiang Chen, Wei Li, Xiaohua Ni, Wen Pan, Qihan Wu","doi":"10.3724/abbs.2026087","DOIUrl":"https://doi.org/10.3724/abbs.2026087","url":null,"abstract":"<p><p>The relentless evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of immune-evasive variants underscore an urgent need for novel therapeutic strategies that are resilient to viral mutations. Targeting conserved host factors essential for viral entry represents a promising approach to overcome this challenge. Here, we report the development of a bifunctional therapeutic platform targeting the primary human receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Using systematic evolution of ligands by exponential enrichment (SELEX), we isolate a high-affinity DNA aptamer, designated AA2, that binds to human ACE2 with a dissociation constant ( <i>K</i>d) of 5.41 ± 1.23 nM. Molecular docking and competitive binding assays confirm that AA2 sterically hinders the interaction between the viral spike receptor-binding domain (RBD) and ACE2. Consequently, AA2 demonstrates potent neutralization of SARS-CoV-2 S pseudovirus entry into host cells. To achieve a synergistic antiviral effect, we engineer an aptamer-siRNA chimera (AsiC) by conjugating AA2 to a short interfering RNA (siRNA) targeting the GFP coding region of the pseudovirus genome. This AsiC construct significantly represses viral replication compared to aptamer or siRNA treatment alone, validating a dual mechanism of action that combines receptor blockade with targeted gene silencing. This study establishes a robust proof-of-concept for an ACE2-targeted AsiC, representing a new class of dual-function antiviral therapeutics with the potential to effectively combat current and future ACE2-dependent coronaviruses.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337421","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}

{"title":"How distinct hormones sculpt a common receptor: ligand-specific conformational pathways of the insulin receptor.","authors":"Di Jiang, Dan Tang, Shiqian Qi","doi":"10.3724/abbs.2026024","DOIUrl":"10.3724/abbs.2026024","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1433-1435"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163428","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}

{"title":"The tRNA landscape in cancer: from pathogenesis to therapeutic interventions.","authors":"Ni Jian, Han Ren, Yingqi Huang, Lijuan Ma, Yingchen Zhou, Libo Yu, Weiren Huang","doi":"10.3724/abbs.2026093","DOIUrl":"10.3724/abbs.2026093","url":null,"abstract":"<p><p>Transfer RNA (tRNA) acts not only as an indispensable adaptor in protein synthesis but also as a key contributor to tumorigenesis when its regulation is disrupted. This review systematically summarizes aberrant tRNA-related mechanisms in cancer, including altered tRNA expression profiles, abnormal post-transcriptional modifications, dysregulated aminoacylation, production of tRNA-derived small RNAs (tdRs), and defects in tRNA trafficking and translational fidelity. Notably, the metabolically abnormal tumor microenvironment actively shapes tRNA reprogramming to facilitate adaptive survival, while dysregulated tRNA elements, such as specific modifications and tdRs, further drive cancer stem cell properties and therapeutic resistance. Collectively, these alterations reprogram the oncoproteome and signaling networks, thereby promoting tumor cell proliferation, metastasis, immune evasion, and drug resistance. Targeting these mechanisms represents a promising strategy for developing novel cancer therapies. Potential approaches include the use of suppressor tRNAs to restore tumor suppressor gene function, the employment of tdRs to modulate oncogenic signaling pathways, or direct inhibition of enzymes involved in tRNA biogenesis. These strategies aim to remodel the dysfunctional tRNA network in cancer and offer new avenues for innovative treatments.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1187-1212"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262735","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}

{"title":"Caught the 'Catch' of midnolin: structural basis for broad substrate specificity in ubiquitin-independent proteasomal degradation.","authors":"Chuanyin Li, Ronggui Hu","doi":"10.3724/abbs.2026006","DOIUrl":"10.3724/abbs.2026006","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":"58 6","pages":"1431-1432"},"PeriodicalIF":4.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262807","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}