{"title":"<i>miR-199a-3p</i> suppresses <i>Vldlr</i> expression to promote cardiomyocyte proliferation.","authors":"Rui Jiang, Lijuan Pei, Hongjie Zhang, Fenglian He, Yuhan Min, Xinhang Li, Ke Wei","doi":"10.3724/abbs.2024240","DOIUrl":"https://doi.org/10.3724/abbs.2024240","url":null,"abstract":"<p><p>The proliferative capacity of cardiomyocytes is limited in adult mammals, and replacing lost tissue following acute ischemic injury is challenging. Previous studies have demonstrated that <i>miR-199a-3p</i> can promote cardiomyocyte proliferation, but the exact mechanism by which this occurs remains unclear, although multiple targets of <i>miR-199a-3p</i> have been identified. We recently showed that very-low-density-lipoprotein receptor (Vldlr) inhibits cardiomyocyte proliferation, and in this study we aim to test whether <i>Vldlr</i> is a functional target gene of <i>miR-199a-3p</i>. 3'UTR reporter assays demonstrate that <i>miR-199a-3p</i> directly binds to the 3'UTR of <i>Vldlr</i> and inhibits its translation. Overexpressing <i>Vldlr</i> blunts the pro-proliferative effect of <i>miR-199a-3p</i> on cardiomyocytes, suggesting that <i>Vldlr</i> is indeed a functional target of <i>miR-199a-3p</i>. Mechanistically, Vldlr reduces S807/811 phosphorylation of RB1, and inhibiting CDK4/6 to prevent RB1 phosphorylation can block the pro-proliferative effect of both <i>Vldlr</i> knockdown and <i>miR-199a-3p</i>, suggesting that RB1 phosphorylation is required for the cardiomyocyte proliferation induced by <i>miR-199a-3p</i> and <i>Vldlr</i> knockdown. The findings of this study reveal <i>Vldlr</i> as a novel functional target of <i>miR-199a-3p</i> in cardiomyocytes and identify RB1 as a downstream effector of cardiomyocyte proliferation. The identification of the role of the <i>miR-199a-3p</i>- <i>Vldlr</i>-RB1 axis in cardiomyocyte proliferation may provide potential therapeutic targets for cardiac regenerative medicine.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389839","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":"Proline/serine-rich coiled-coil protein 1 alleviates pyroptosis in murine bone marrow-derived macrophages.","authors":"Qiao Wu, Qianqian Wang, Kexin Hu, Tiantian Luo, Jichen Liu, Yazhi Xue, Ling Li, Cuiqi Yang, Rongzhan Lin, Hangyu Pan, Jinhao Wang, Zhigang Guo","doi":"10.3724/abbs.2025012","DOIUrl":"https://doi.org/10.3724/abbs.2025012","url":null,"abstract":"<p><p>Pyroptosis is a regulated inflammatory cell death process that plays an essential role in various diseases. This study investigates the role of proline/serine-rich coiled-coil protein 1 (PSRC1) in pyroptosis and inflammation in macrophages. This study reports that PSRC1 expression is decreased in pyroptotic macrophages and that knockout of <i>PSRC1</i> exacerbates pyroptosis and inflammation. <i>PSRC1</i> overexpression alleviates pyroptosis and inflammation in macrophages. RNA-seq analysis reveals that PSRC1 regulates the expression of genes involved in the extracellular matrix (ECM). Specifically, PSRC1 downregulates the expression of periostin (POSTN), an ECM component. Knockdown of <i>POSTN</i> suppresses macrophage pyroptosis mediated by low expression of PSRC1. These findings suggest that PSRC1 can alleviate pyroptosis and inflammation in bone marrow-derived macrophages (BMDMs) by regulating the ECM and negatively regulating POSTN. This study provides insights into the role of PSRC1 in macrophage pyroptosis and identifies a potential target for the treatment of inflammatory diseases. Further research is needed to confirm these findings <i>in vivo</i> and in various disease models.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397584","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}
Yan Cao, Hengxi Li, Jiali Li, Tenghan Ling, Aiping Yin, Xinyuan Luo, Ying Zhou, Jinghui Li, Hongyan Jiang, Huawei Wang, Li Yang, Haiying Wu, Ping Li
{"title":"Cannabidiol alleviates the inflammatory response in rats with traumatic brain injury through the PGE <sub>2</sub>-EP2-cAMP-PKA signaling pathway.","authors":"Yan Cao, Hengxi Li, Jiali Li, Tenghan Ling, Aiping Yin, Xinyuan Luo, Ying Zhou, Jinghui Li, Hongyan Jiang, Huawei Wang, Li Yang, Haiying Wu, Ping Li","doi":"10.3724/abbs.2024183","DOIUrl":"https://doi.org/10.3724/abbs.2024183","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed. Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist. Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE. Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE <sub>2</sub>-EP2-cAMP-PKA signaling pathway. Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373457","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":"Safari in the RNA world: a special issue focused on RNA biogenesis, functions, and technologies.","authors":"Ya-Nan Chang, Hong Cheng","doi":"10.3724/abbs.2024234","DOIUrl":"10.3724/abbs.2024234","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1-2"},"PeriodicalIF":3.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930379","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":"Continuous carbon source supply is essential for high rifamycin productivity of <i>Amycolatopsis mediterranei</i> in nitrate-stimulated fermentation revealed by a metabolomic study.","authors":"Qi Yan, Zhihui Shao, Chen Yang, Guoping Zhao","doi":"10.3724/abbs.2024245","DOIUrl":"https://doi.org/10.3724/abbs.2024245","url":null,"abstract":"<p><p><i>Amycolatopsis</i> <i>mediterranei</i> U32 is an industrial strain capable of producing therapeutically useful rifamycin SV. In early days of fermentation studies, nitrate was found to increase the yield of rifamycin along with globally, affecting both carbon and nitrogen metabolism in favor of antibiotic biosynthesis; thus, the <i>nitrate-stimulating effect</i> (NSE) hypothesis was proposed. Although GlnR is likely the master regulator of the pleotropic effect of NSE, the global metabolism affected by NSE has never been systematically examined. In this study, we use mass spectrometry-based metabolomics to quantitatively monitor the metabolomic responses of <i>A</i>. <i>mediterranei</i> U32 to nitrate supplementation. The concentrations of many metabolites involved in central carbon metabolism, including glucose 6-phosphate, glucose 1-phosphate, UDP-glucose, and acetyl-coenzyme A, decrease significantly after the addition of 80 mM potassium nitrate to the medium. We find that the rifamycin SV production yield could be increased by the addition of glucose during the logarithmic growth phase. Moreover, at multiple time points during glucose supplementation in the mid- and late-exponential phases, the yield of rifamycin SV further increases, reaching 354.3%. Quantitative real-time PCR assays of the key genes corresponding to the synthesis of the rifamycin SV precursor combined with data from metabolomics analysis confirm that carbon source deficiency is compensated for after glucose supplementation and that the expression of genes involved in the pathway of 3-amino-5-hydroxybenzoic acid synthesis by UDP-glucose and glutamine is significantly increased. This preliminary exploration of dynamic metabolomic profiles has the potential to increase our understanding of the NSE.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027691","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":"Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia.","authors":"Yuxin Shu, Linmin Zhou, Jinqin Qian, Wei-Guo Zhu","doi":"10.3724/abbs.2025011","DOIUrl":"https://doi.org/10.3724/abbs.2025011","url":null,"abstract":"<p><p>Relieving hypoxia in the tumor microenvironment (TME) promotes innate and adaptive immunity. Our previous research demonstrated that reoxygenation of the TME promotes the phagocytosis and tumor-killing functions of tumor-associated macrophages (TAMs) by upregulating pyruvate carboxylase (PCB). However, the mechanism remains obscure. In the present study, we find that versican derived from melanoma cells binds to TLR2 and activates the downstream transcription factor RelB, which transcribes PCB under normoxia. Blocking the versican-TLR2-MyD88-RelB axis not only reverses the upregulation of PCB in TAMs but also hinders the clearance of tumor cells by TAMs. Our work suggests a pathway that modulates the functions of TAMs under normoxia, which could be harnessed for strengthening anti-tumor immunity.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035545","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":"mTOR-related linc-PMB promotes mitochondrial biogenesis via stabilizing SIRT1 mRNA through binding to the HuR protein.","authors":"Qian Chen, Huaying Zhang, Daokun Wang, Wenjing Liao, Yazhou Liu, Yurui Cai, Siyou Wang, Mengqian Yu","doi":"10.3724/abbs.2024236","DOIUrl":"https://doi.org/10.3724/abbs.2024236","url":null,"abstract":"<p><p>Mitochondrial dysfunction is implicated in numerous disorders, including type 2 diabetes, Alzheimer's disease and cancer. Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators of cellular energy metabolism, yet their roles remain largely unclear. In this study, we identify an lncRNA named linc-PMB, which is associated with mTOR and promotes mitochondrial biogenesis, through microarray analysis. We demonstrate that the knockdown of <i>linc-PMB</i> results in significantly impaired mitochondrial respiration and biogenesis, along with altered expressions of related genes. Conversely, overexpression of linc-PMB markedly increases mitochondrial function. We further reveal that linc-PMB interacts with the RNA-binding protein HuR, promoting the stabilization of SIRT1 mRNA and a substantial increase in SIRT1 expression, which in turn activates the PGC-1α/mtTFA pathway and mitochondrial biogenesis. Collectively, our findings reveal a novel regulatory pathway in which linc-PMB, through its interaction with HuR, modulates the SIRT1/PGC-1α/mtTFA axis to maintain mitochondrial biogenesis and function.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254216","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":"Head-to-head: IL-21 triumphs over IL-15 in NK cell therapy for glioblastoma.","authors":"Jake C Miller, Bihui Cao, Jia Shen","doi":"10.3724/abbs.2025009","DOIUrl":"https://doi.org/10.3724/abbs.2025009","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021709","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}
Jingran Xu, Li Li, Yaping Zhou, Zulipikaer Abudureheman, Lexin Xue, Chao Wu, Xiaoguang Zou
{"title":"Immunopathological characteristics and therapeutic effects of UC-MSCs in a pigeon breeder's lung mouse model.","authors":"Jingran Xu, Li Li, Yaping Zhou, Zulipikaer Abudureheman, Lexin Xue, Chao Wu, Xiaoguang Zou","doi":"10.3724/abbs.2025010","DOIUrl":"https://doi.org/10.3724/abbs.2025010","url":null,"abstract":"<p><p>Hypersensitivity pneumonitis (HP), including pigeon breeder's lung (PBL), often progresses from acute inflammation to fibrosis, impairing lung function and limiting targeted therapeutic strategies. Mechanistic studies on PBL progression are limited by the lack of preclinical animal models and a predominant focus on patient data. This study explores the immunopathological characteristics of all stages of PBL in mice and evaluates the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) during the non-fibrotic stage. PBL models are created in A/J mice through tracheal instillation of pigeon dropping extract (PDE) protein powder. Different doses (0.4 × 10 <sup>6</sup>, 0.8 × 10 <sup>6</sup>, and 1.6 × 10 <sup>6</sup> cells per animal) and frequencies (1-2 times) are administered to the model. The immunopathological characteristics of <i>PBL</i> and the therapeutic effects of UC-MSCs are assessed using micro-CT, pulmonary function, histopathology, cell counts in BALF, HYP levels, inflammatory factor levels, immunohistochemistry, and fibrosis marker expression in lung tissues. The results show that PDE exposure consistently impairs pulmonary function and increases the levels of inflammation and fibrosis markers as the disease progresses. Model mice experience non-fibrotic stages (acute inflammation) from days 0-36, mild fibrosis from days 37-77, and severe fibrosis from day 78 onwards. UC-MSCs, particularly at the highest dose (1.6 × 10 <sup>6</sup> cells), effectively treat non-fibrotic <i>PBL</i> by improving pulmonary function (lung ventilation area recovers) and reducing inflammation and fibrosis. This study successfully establishes PBL mouse models reflecting both the acute (inflammatory) and chronic (fibrotic) stages, and UC-MSCs have the potential to delay fibrosis, providing new therapeutic options for PBL and other inflammation-induced lung fibrotic diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021711","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":"Daphnetin-mediated mitophagy alleviates intervertebral disc degeneration via the Nrf2/PINK1 pathway.","authors":"Yiting Tu, Jiaping Ren, Weiyuan Fang, Chencheng Zhou, Binli Zhao, Tianyong Hua, Yiqi Chen, Zhenya Chen, Yongzeng Feng, Haiming Jin, Xiangyang Wang","doi":"10.3724/abbs.2025002","DOIUrl":"https://doi.org/10.3724/abbs.2025002","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Reactive oxygen species (ROS) stress induces NLRP3 inflammasome activation, and this, along with extracellular matrix metabolism (ECM) degradation in nucleus pulposus cells (NPCs), plays a crucial role in the progression of IDD. Daphnetin (DAP) is a biologically active phytochemical extracted from plants of the <i>Genus Daphne</i>, which possesses various bioactivities, including antioxidant properties. In the present study, we demonstrate that DAP significantly attenuates tert-butyl hydroperoxide (TBHP)-induced ECM degradation, oxidative stress and NLRP3 inflammasome activation in NPCs. Furthermore, DAP could facilitate mitophagy to increase the removal of damaged mitochondria, consequently reducing mitochondrial ROS accumulation and alleviating NLRP3 inflammasome activation. Mechanistically, we unveil that DAP activates mitophagy by stimulating the Nrf2/PINK1 signaling pathway in TBHP-induced NPCs. <i>In vivo</i> experiments further corroborate the protective effect of DAP against IDD progression in a rat model induced by disc puncture. Accordingly, our findings reveal that DAP could be a promising therapeutic candidate for the treatment of IDD.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998290","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}