Acta biochimica et biophysica Sinica最新文献

{"title":"Puerarin prevents cadmium-induced endoplasmic reticulum stress via SIRT1-dependent PERK-CHOP pathway in HepG2 cells.","authors":"Di Huang, Mengqi Qiu, Kuanhong Luo, Yanzhe Zhu, Siyu Zhang, Zhen He, Xiaobo Hu, Zhaohui Cao","doi":"10.3724/abbs.2025039","DOIUrl":"https://doi.org/10.3724/abbs.2025039","url":null,"abstract":"<p><p>Cadmium (Cd) is a high-risk heavy metal that induces oxidative stress, endoplasmic reticulum (ER) stress and inflammation, damaging organs such as the liver. Puerarin (PUE) has been shown to treat liver injury and especially prevent Cd-induced hepatic damage via its antioxidant activity. Sirtuin 1 (SIRT1), a histone deacetylase, is a key protector against various stress insults. However, its role in the protection of PUE against Cd-induced liver damage has not been clarified. Thus, this study is designed to elucidate the molecular mechanism in the human hepatoma cell line HepG2. The results first reveal that Cd-induced apoptosis is significantly restored by PUE pretreatment, as confirmed by the CCK-8, flow cytometric, Hoechst 33258 and TUNEL assays. Mechanistically, PUE significantly decreases ROS production and increases SOD levels in Cd-treated HepG2 cells. Moreover, PUE pretreatment alleviates ER stress by inhibiting the PERK-eIF2α-ATF4-CHOP axis and subsequently partially restores ER function as revealed by decreased Ca ²⁺ release from the ER. In addition, further study demonstrates that PUE upregulates SIRT1 expression, which suppresses the PERK signaling cascade and reduces CHOP levels. Collectively, our results first demonstrate that PUE protects HepG2 cells from Cd-induced apoptosis at least partially by inhibiting the PERK-eIF2α-ATF4-CHOP pathway in a SIRT1 expression-dependent manner. Puerarin appears to have great potential as a hepatoprotective agent.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958203","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":"Withaferin A combined with ricolinostat: a potent synergistic therapy for cervical cancer through regulating p53 ubiquitination and acetylation.","authors":"Tian Chen, Yiting Xu, Kunming Yang, Yutong Du, Zhuan Zhu, Lingling Xu, Xinrong Wang, Yi Yin, Yu Hu, Chengcheng Wang, Ronggui Hu, Chuanyin Li","doi":"10.3724/abbs.2025048","DOIUrl":"https://doi.org/10.3724/abbs.2025048","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965687","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":"Reduced expression of the PER2 protein contributes to β ₁-AA-induced cardiac autophagy rhythm disorders.","authors":"Pengjia Li, Jiayan Feng, Jiao Guo, Jin Xue, Yang Li, Shiyuan Wen, Xiaohui Wang, Huirong Liu, Li Wang","doi":"10.3724/abbs.2025023","DOIUrl":"https://doi.org/10.3724/abbs.2025023","url":null,"abstract":"<p><p>Heart failure may be linked to fluctuations in the rhythm of autophagy in cardiomyocytes throughout the day. Circadian rhythms depend on the regulation of core biological clock proteins, with PER2 playing a crucial role. Our previous research confirmed that the presence of β ₁-adrenergic receptor autoantibodies (β ₁-AAs) could inhibit myocardial autophagy, leading to cell death and heart failure. However, it remains unclear whether β ₁-AA induces cardiac autophagy rhythm disorders by affecting PER2 expression. In this study, we find that β ₁-AA disrupts the autophagy rhythm in cardiomyocytes, which is primarily indicated by decreased expression of the autophagy marker protein LC3. β ₁-AA disrupts the rhythmic expression of the PER2 protein in myocardial cells, which is manifested mainly by a decrease in PER2 protein expression. Metoprolol is used to verify that the β ₁-adrenergic receptor contributes to the reduction in the Per2 protein caused by β ₁-AA. Knockdown of <i>Per2</i> with lentivirus reduces the inhibition of LC3 expression caused by β ₁-AA, whereas overexpression of Per2 in cardiomyocytes using lentivirus significantly restores the β ₁-AA-induced decrease in LC3 expression. Moreover, mTORC1 activation is found to participate in β ₁-AA-induced autophagy inhibition in cardiomyocytes after pretreatment with the mTORC1 inhibitor rapamycin. Furthermore, the decreased expression of the PER2 protein caused by β ₁-AA disrupts the myocardial autophagy rhythm by promoting mTORC1 activation through lentiviruses that knock down or overexpress the <i>Per2</i> gene. This study provides an experimental basis for the precise treatment of cardiovascular diseases from the perspective of biological rhythm.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962722","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":"CRATS: a one-pot CRISPR-Cas12b and RPA combined assay with a temperature switchcong for highly sensitive detection of monkeypox virus.","authors":"Guangxi Yu, Yue Wang, Yukang Chen, Jiangyuan Liu, Hongtao Kang, Xiaodong Luan, Song Gao, Pei Wang","doi":"10.3724/abbs.2025016","DOIUrl":"https://doi.org/10.3724/abbs.2025016","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794363","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":"miR-32-5p suppresses the progression of hepatocellular carcinoma by regulating the GSK3β/NF-κB signaling.","authors":"Guangzhi Wang, Qianqian Yang, Yaqi Han, Yunlong Zhang, Wei Pan, Zhongliang Ma, Hui Tian, Xudong Qu","doi":"10.3724/abbs.2025038","DOIUrl":"https://doi.org/10.3724/abbs.2025038","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly fatal form of malignancy that seriously threatens patient survival. The global 5-year survival rate for HCC patients ranges from 15% to 19%, and nearly 80% of patients are diagnosed at an advanced stage. Therefore, exploring the mechanism of HCC development and identifying biomarkers and therapeutic targets for HCC are vital. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs, are 20-24 nucleotides (nt) long. They play pivotal roles in modulating the progression of diverse diseases. The specific role of miR-32-5p in the development of HCC remains unclear. In this study, qRT-PCR is utilized to precisely determine the downregulated expression levels of miR-32-5p in HCC. Subsequently, functional analysis reveals the suppressive role of miR-32-5p in modulating the proliferative and migratory capabilities of HCC cells. Glycogen synthase kinase 3β (GSK3β) has emerged as a potential target of miR-32-5p, which is confirmed through a dual-luciferase reporter assay. Notably, the expression of GSK3β in HCC tissue specimens is negatively correlated with the abundance of miR-32-5p, and patients with high GSK3β expression have shorter survival time. Furthermore, the targeted downregulation of GSK3β remarkably impedes the proliferation and migration of tumor cells. This study suggests that miR-32-5p inhibits the proliferation and migration of HCC through regulating the GSK3β/NF-κB signaling pathway. Therefore, this study reveals that miR-32-5p exerts its suppressive effect on HCC progression, suggesting that it is a promising target for both diagnostic and targeted therapeutic interventions against HCC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762648","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":"TLR4 mediates lipotoxic β-cell dysfunction by inhibiting the TMEM24/PI3K/AKT pathway.","authors":"Chao Lan, Yan Li, Zhiyan Weng, Wei Pan, Wanxin Lin, Zhen Jiang, Liyong Yang, Ximei Shen","doi":"10.3724/abbs.2025045","DOIUrl":"https://doi.org/10.3724/abbs.2025045","url":null,"abstract":"<p><p>Immune imbalance is the core pathophysiological mechanism of the deterioration of β-cell function driven by lipid metabolism disorders. Toll-like receptor 4 (TLR4) inflammatory signaling is a key pathway that mediates lipotoxic injury in β-cells, but the underlying mechanism needs to be further elucidated. Transmembrane protein 24 (TMEM24) is a key transporter that regulates pulsatile insulin secretion, but its pathophysiology in lipotoxicity remains unclear. In this study, we investigate whether TLR4-mediated lipotoxicity is affected by the inhibition of TMEM24 expression. The PPI network shows that TLR4 is associated with both insulin secretion and ER stress proteins in islets from obese rats. Using <i>in vitro</i> lipotoxic β-cell models, we found that TMEM24 is the target signal of palmitic acid (PA)-induced insulin secretion impairment in islet β-cells, and TLR4 plays a mediating role in this process. Mechanistically, TLR4 mediates lipotoxicity by binding to TMEM24 and downregulating its protein expression to suppress PI3K/AKT signaling, leading to β-cell dysfunction. <i>TLR4</i> knockout ameliorates islet function impairment through TMEM24/PI3K/AKT signaling in HFD-induced obese rats. Taken together, our results show that TLR4 mediates lipotoxicity in islet β-cells by inhibiting the TMEM24/PI3K/AKT pathway, and the mechanism of TLR4-mediated lipotoxicity is elucidated from the perspective of insulin vesicular secretion.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762697","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":"<i>In vitro</i> and <i>in vivo</i> efficacy of aurintricarboxylic acid against <i>Neospora caninum</i> infection.","authors":"Zhengkai Wei, Yuxiao Qian, Xi Jiang, Yuqian Jiang, Rongsheng Huang, Kaifeng He, Jing Huang, Jiaxuan Wang, Xin Guo, Wenlong Huang, Dezhi Zhang, Zhengtao Yang, Quan Liu, Qianyong Li","doi":"10.3724/abbs.2025006","DOIUrl":"https://doi.org/10.3724/abbs.2025006","url":null,"abstract":"<p><p>Bovine neosporosis, a protozoal disease caused by <i>Neospora caninum</i> ( <i>N</i>. <i>caninum</i>), poses a significant threat to the global cattle industry, resulting in substantial economic losses that are difficult to quantify. The current lack of effective commercial vaccines and specific treatments highlights the urgent need for the development of potent drugs against <i>N</i>. <i>caninum</i>. In this study, we investigate the efficacy of aurintricarboxylic acid (ATA), a derivative of polyaromatic carboxylic acid, against <i>N</i>. <i>caninum</i> both <i>in vitro</i> and <i>in vivo</i>. Cell cytotoxicity is evaluated using CCK-8 kits. <i>N</i>. <i>caninum</i> proliferation within cells is assessed by qPCR analysis. Transmission electron microscopy (TEM) is employed to examine the ultrastructures of <i>N</i>. <i>caninum</i> tachyzoites. The efficacy of ATA against <i>N</i>. <i>caninum</i> infection is validated in a mouse model. Our findings indicate that ATA not only inhibits <i>N</i>. <i>caninum</i> proliferation but also reduces parasite loads within individual cells. Furthermore, ATA (20 and 40 μM) has immunomodulatory effects by downregulating the mRNA expressions of <i>N</i> . <i>caninum</i>-induced cytokines, including tumor necrosis factor-α (TNF-α), interferon (IFN-α, -β, and -γ), and β-defensin 5 (BNBD5). ATA treatment directly targets and eliminates <i>N</i>. <i>caninum</i> by disrupting its ultrastructure. The <i>in vivo</i> study confirms the potential of ATA to increase body weight, decrease parasite loads in the lungs and duodenum, and ameliorate the pathological effects induced by <i>N</i> . <i>caninum</i> infection in mice. In conclusion, this study represents the first evidence of the anti- <i>N</i>. <i>caninum</i> ability of ATA and provides compelling data to support its potential as a candidate for developing anti- <i>N</i>. <i>caninum</i> drugs.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750539","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":"TRIM21 promotes type I interferon by inhibiting the autophagic degradation of STING via p62/SQSTM1 ubiquitination in systemic lupus erythematosus.","authors":"Chen Li, Ang Ma, Yu Bai, Zitao Liu, Linghan Tian, Ziyuan Wang, Huaishun Ma, Zhengpu Chen, Zhengheng Gao, Shijie Feng, Ping Fu","doi":"10.3724/abbs.2025046","DOIUrl":"10.3724/abbs.2025046","url":null,"abstract":"<p><p>The cGAS-STING signaling pathway serves as a pivotal surveillance mechanism for cytosolic double-stranded DNA (dsDNA) detection in mammalian systems. While STING-mediated type I interferon production is crucial for host defense, sustained activation of this pathway contributes to autoimmune pathologies, including systemic lupus erythematosus (SLE). Maintaining immune homeostasis requires precise regulation of STING activity to prevent hyperactivation. Our study identifies TRIM21 as a novel positive regulator of cGAS-STING signaling in SLE pathogenesis. Our results demonstrate that TRIM21 overexpression stabilizes STING by suppressing autophagic degradation, whereas TRIM21 depletion accelerates this clearance process. Mechanistically, TRIM21 catalyzes the K63-linked polyubiquitylation of the selective autophagy receptor p62/SQSTM1, disrupting its interaction with STING. This post-translational modification prevents the sequestration of STING into autophagosomes, thereby stabilizing the adaptor protein and amplifying downstream type I interferon responses. Our findings reveal a previously unrecognized regulatory circuit in which TRIM21 orchestrates cross-talk between ubiquitin signaling and autophagy to control STING turnover. The TRIM21-p62 axis represents a potential therapeutic target for attenuating pathological interferon production in STING-dependent autoimmune disorders. This work advances our understanding of immune regulation by demonstrating how E3 ligase-mediated ubiquitin modifications modulate cargo recognition in selective autophagy pathways. The identified mechanism provides new insights into the molecular interplay between protein ubiquitylation and autophagic degradation in maintaining the innate immune balance, offering novel perspectives for developing targeted therapies against interferonopathies associated with cGAS-STING hyperactivity.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"834-846"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast cancer-derived exosomal miR-105-5p facilitates the transformation of NFs into CAFs through LATS2-NF-κB signaling.","authors":"Xiaodi Ding, Zhimei Sheng, Jiayu Cui, Meimei Cui, Liying Zhang, Ruijun Feng, Yongming Wang, Wei Sun, Xiurong Zhang, Lihong Shi, Baogang Zhang","doi":"10.3724/abbs.2025017","DOIUrl":"https://doi.org/10.3724/abbs.2025017","url":null,"abstract":"<p><p>Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727338","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 positive feedback loop between FOSB and miR-133b controls colon cancer cell proliferation.","authors":"Wanwan Li, Qionggui Hu, Changwei Lin, Xiaorong Li, Yang Bai, Min Ma","doi":"10.3724/abbs.2025041","DOIUrl":"https://doi.org/10.3724/abbs.2025041","url":null,"abstract":"<p><p>FOSB, a member of the FOS gene family, forms heterodimers with JUN family proteins to engage in diverse cellular processes. Its biological impacts vary among different types of tumors, yet its specific function in colon cancer (CC) remains ambiguous. In this study, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) are applied to measure FOSB expression levels, followed by an analysis of the association between FOSB expression and patients' clinical parameters. <i>In vitro</i> experiments are performed to assess cell proliferation, including growth rate, cell cycle distribution, and apoptosis. A subcutaneous xenograft model in nude mice is utilized to monitor tumor growth <i>in vivo</i>. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays are conducted to dissect the interactions among FOSB, miR-133b, and POU2F1. The results indicate that FOSB expression is downregulated in CC tissues relative to normal controls. Overexpression of FOSB suppresses proliferation and promotes apoptosis in CC cells. Mechanistically, FOSB binds to the promoter region of miR-133b, enhancing its transcription and subsequently repressing POU2F1 expression. Notably, decreased POU2F1 expression also alleviates the transcriptional repression of the <i>FOSB</i> promoter region, establishing a FOSB-miR-133b-POU2F1 feedback loop that inhibits CC proliferation. In summary, our findings suggest that FOSB acts as a tumor suppressor gene in CC and may exert its inhibitory effects on CC growth via the FOSB-miR-133b-POU2F1 feedback loop.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727337","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}