Acta Pharmacologica Sinica最新文献

{"title":"TSG attenuated NAFLD and facilitated weight loss in HFD-fed mice via activating the RUNX1/FGF21 signaling axis.","authors":"Zhen-Lin Huang, Shao-Bo Zhang, Shang-Fu Xu, Xin-Nan Gu, Ze-Qi Wu, Yue Zhang, Jian Li, Li-Li Ji","doi":"10.1038/s41401-025-01568-w","DOIUrl":"https://doi.org/10.1038/s41401-025-01568-w","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by steatosis in hepatocytes and is now becoming the major cause of liver-related mortality. Fibroblast growth factor 21 (FGF21) is an endocrine hormone mainly secreted by the liver, which can bind to its receptor (FGFR) and co-receptor beta klotho (KLB) to form a receptor complex, exerting its lipid-lowering function. 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG), a natural compound isolated from Polygonum multiflorum Thunb, has shown excellent activity in lowering lipid content and efficacy in improving NAFLD. In this study we investigated whether FGF21 was implicated in the therapeutic effect of TSG in NAFLD mice. NAFLD was induced in mice by feeding with a high-fat diet (HFD) for 12 weeks, and treated with TSG (20, 40 mg·kg^-1·d^-1, i.g.) during the last 4 weeks. We showed that TSG treatment significantly alleviated NAFLD in HFD-fed mice evidenced by reduced hepatic triglyceride (TG) and non-esterified fatty acids (NEFA), diminished lipid droplets and decreased NAFLD activity score (NAS) in liver tissues. We demonstrated that TSG treatment significantly increased the mRNA and protein levels of FGF21 in vitro and in vivo, and reduced lipid accumulation in both the liver and adipose tissues. Transcriptomics analysis revealed that TSG treatment significantly increased the nuclear translocation of a transcription factor RUNX1. Knockdown of Runx1 in HFD-fed mice eliminated the efficacy of TSG in alleviating NAFLD, reducing hepatic lipid accumulation and regulating FGF21 signaling pathway in liver and adipose tissues. In conclusion, TSG alleviates NAFLD by enhancing the FGF21-mediated lipid metabolism in a RUNX1-dependent manner.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.","authors":"Ying-Juan Liu, Guo-Rui Jia, Sheng-Han Zhang, Yun-Liang Guo, Xi-Zhen Ma, Hua-Min Xu, Jun-Xia Xie","doi":"10.1038/s41401-025-01560-4","DOIUrl":"https://doi.org/10.1038/s41401-025-01560-4","url":null,"abstract":"<p><p>Iron plays a pivotal role in numerous fundamental biological processes in the brain. Among the various cell types in the central nervous system, microglia are recognized as the most proficient cells in accumulating and storing iron. Nonetheless, iron overload can induce inflammatory phenotype of microglia, leading to the production of proinflammatory cytokines and contributing to neurodegeneration. A growing body of evidence shows that disturbances in iron homeostasis in microglia is associated with a range of neurodegenerative disorders. Recent research has revealed that microglia are highly sensitive to ferroptosis, a form of iron-dependent cell death. How iron overload influences microglial function? Whether disbiosis in iron metabolism and ferroptosis in microglia are involved in neurodegenerative disorders and the underlying mechanisms remain to be elucidated. In this review we focus on the recent advances in research on microglial iron metabolism as well as ferroptosis in microglia. Meanwhile, we provide a comprehensive overview of the involvement of microglial ferroptosis in neurodegenerative disorders from the perspective of crosstalk between microglia and neuron, with a focus on Alzheimer's disease and Parkinson's disease.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the role of GDF15 in atherosclerosis in mouse and human.","authors":"Mo-Nan Liu, Zheng-Hong Liu, Rui-Xue Leng, Hans Strijdom, Jian-Ping Weng, Suo-Wen Xu","doi":"10.1038/s41401-025-01561-3","DOIUrl":"https://doi.org/10.1038/s41401-025-01561-3","url":null,"abstract":"<p><p>Growth differentiation factor 15 (GDF15) is a key regulator of food intake and energy metabolism. GDF15 mimetic drugs for the treatment of metabolic syndrome and obesity are under clinical development. While GDF15 presents a promising target for weight management, its potential cardiovascular actions remain elusive. In this study we investigated the role of GDF15 in macrophage function and atherosclerosis pathogenesis and whether GDF15 acts both as a biomarker and mediator of atherosclerosis severity. ApoE^-/- mice were fed a high-cholesterol diet (HCD, 1.25% cholesterol) for 6, 12 or 18 weeks to establish atherosclerotic models. We showed that serum levels of GDF15 were elevated in ApoE^-/- mice with atheroprogression; increased serum levels of GDF15 were also observed in patients with coronary artery disease. Enlightened by this finding, we established atherosclerotic model in Gdf15^-/- mice by injecting with AAV8-PCSK9^D377Y virus and feeding HCD for 12 or 16 weeks. We showed that global Gdf15 knockout, whether in male or female mice, did not alter plaque size in en face aorta, lesion in aortic sinus, size of necrotic core or plaque composition. In macrophage-derived foam cells isolated from atherosclerotic mice, neither Gdf15 deletion nor the treatment with recombinant GDF15 protein (1, 10, 100 ng/mL) affected lipid deposition or macrophage polarization. To translate this finding into a clinically relevant scenario, we performed Mendelian randomization (MR) analysis, and found no significant causal association between circulating GDF15 levels and the incidence of cardiovascular diseases. Furthermore, MR studies suggest that genetic associations between GDF15 and factors such as BMI, ApoB, LDL and HDL were not significant in plasma data from the UK Biobank and the deCODE cohort. In summary, this study demonstrates that global Gdf15 deficiency does not affect the development of atherosclerosis in male or female mice despite the positive association between circulating GDF15 levels and disease progression in mice and human. Thus, GDF15 in circulation is a potential biomarker, but not a causal mediator, of atherosclerosis. Long-term cardiovascular safety of GDF15-targeted therapies warrants further investigation.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursolic acid derivative UA312 ameliorates ionizing radiation-induced cardiotoxicity and neurodevelopmental toxicity in zebrafish via targeting chrna3 and grik5.","authors":"Fei-Fei Xu, Yue Shang, Hui-Qiang Wei, Wei-Ying Zhang, Li-Xing Wang, Tong Hu, Shu-Qin Zhang, Yan-Li Li, Hai-Hua Shang, Wen-Bin Hou, Wen-Feng Gou, Sai-Jun Fan, Yi-Liang Li","doi":"10.1038/s41401-025-01564-0","DOIUrl":"https://doi.org/10.1038/s41401-025-01564-0","url":null,"abstract":"<p><p>The biological damage caused by ionizing radiation (IR) depends not only on the time and doses of exposure to tissue components but also on the developmental state of the cells. Currently, amifostine is the only radiation-protective agent used for clinical indications related to radiation therapy, but this compound has multiple drawbacks including high toxicity, short half-life and no protective effect on the nervous system. Ursolic acid (UA), a natural pentacyclic triterpenoid that exhibits multiple protective effects including anti-inflammatory, anticarcinogenic, and antioxidant effects. Due to its poor solubility and bioavailability, UA is mostly administered with liposomes. In this study we investigated the impact of UA312, an optimized derivative of UA, on radiation-induced developmental toxicity in zebrafish embryos and larvae. Embryo and larvae survival were observed at 4, 24, 48, and 72 hpf. UA312 was administered at 3 hpf, while embryos were irradiated with 6 Gy of γ-irradiation (dose rate: 0.88 Gy/min) at 4 hpf, then the embryos were moved to a fresh buffer. We determined that 40 µM of UA312 was a safe concentration for zebrafish embryos and larvae. We found that treatment with UA312 (40 µM) restored IR-induced early developmental dysplasia of the zebrafish embryos and larvae. Transcriptomic analysis revealed that exposure to IR inhibited multiple pathways related to neurodevelopment and cardiomyocyte function in zebrafish, which were validated by assessing abnormal cardiac morphology, variations in neurotransmitter levels and alterations in locomotor behavior; and that UA312 treatment ameliorated these alterations. We demonstrated that UA312 treatment significantly reversed the related signaling pathways by targeting chrna3 and grik5. In conclusion, this study identified a promising radioprotective drug, UA312, which alleviates IR-induced cardiotoxicity and neurodevelopmental toxicity in zebrafish by targeting chrna3 and grik5. UA312 may be developed as a novel radioprotective agent against acute IR damage in humans.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol inhibits the DPYSL2-JAK/STAT pathway by targeting mito-IDHs mediated mitochondrial metabolism to exhaust breast cancer.","authors":"Qiao-Li Shi, Chen-Ran Feng, Hui-Ying Li, Pei-Li Wang, Peng Chen, Xu Wei, Wen-Hua Kuang, Guan-Jun Li, Shi-Jie Qin, Rui Liu, Rui-Xing Chen, Jun-Zhe Zhang, Ping Song, Yuan Yuan, Ji-Gang Wang, Ling Huang","doi":"10.1038/s41401-025-01548-0","DOIUrl":"https://doi.org/10.1038/s41401-025-01548-0","url":null,"abstract":"<p><p>Targeting mitochondrial metabolism represents a novel approach in the discovery and development of anti-tumor drugs. Celastrol (Cel) is a naturally-derived small molecule from Tripterygium wilfordii with significant anticancer activities. In this study, we investigated the anti-tumor mechanisms involving mitochondrial metabolic reprogramming regulated by Cel in breast cancer (BRCA). We showed that Cel potently inhibited the proliferation of triple-negative breast cancer cells (MDA-MB-231) and ER⁺ breast cancer cells (MCF-7) with IC₅₀ values of 2.15 μM and 2.29 μM, respectively. Administration of Cel (5, 2, 2 mg/kg, i.p. for three times after tumor formation) significantly suppressed the tumor growth in syngeneic allograft and CDX breast cancer mouse models. Using activity-based protein profiling (ABPP) technology, we identified mitochondrial isocitrate dehydrogenases (including IDH2 and IDH3A, collectively referred to as mito-IDHs) as direct targets of Cel. We demonstrated that Cel significantly inhibited mito-IDHs mediated mitochondrial metabolism to induce the accumulation of metabolites α-ketoglutaric acid, and that Cel enhanced the interaction between DPYSL2 with IDH3A while promoting the accumulation of DPYSL2 within mitochondria of BRCA cells resulting in inactivation of JAK/STAT pathway and ultimately induced ferroptosis and apoptosis in cancer cells. Collectively, this study elucidates a pharmacological mechanism by which Cel exerts its tumor-inhibiting effects through modulation of mitochondrial metabolism. Furthermore, it provides compelling evidence supporting Cel as a promising candidate for development as a small-molecule inhibitor targeting mitochondrial metabolism.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fangchinoline-mediated autophagy inhibition amplifies antigen presentation and PD-1 blockade efficacy in lung cancer.","authors":"Yue Song, Yu-Xiao Jiang, Jie-Ying Guan, Jun-Bo Jiang, Man-Si Xu, Xue-Ying Zhong, Li-Na He, Zhen-Yang Ren, Yuan Liao, Fang Liu, Yan-Jun Jiang, Shan Hu, Wei Guo, Ting-Xiu Zhao, Xiao-Yi Liu, Jiang-Yong Gu, Ya-Fei Shi, Huan-Huan Luo, Kun Wang, Jian-Yong Xiao","doi":"10.1038/s41401-025-01541-7","DOIUrl":"https://doi.org/10.1038/s41401-025-01541-7","url":null,"abstract":"<p><p>Cancer cells frequently exhibit MHC-I deficiency, impairing immune-mediated cytotoxicity even in the presence of PD-1 checkpoint inhibition. To date, no clinically approved therapies exist that can upregulate MHC-I expression to boost immune responses against cancer cells. Emerging evidence has shown that autophagy plays a role in MHC-I molecule degradation, contributing to reduced recognition of cancer cells by CD8⁺ T cells. We previously report that fangchinoline, a bisbenzylisoquinoline alkaloid derived from Chinese herb, is a novel autophagy inhibitor with an adjuvant of chemotherapy against lung cancer. In this study we investigated the modulatory effects of PD-1 blockade combined with fangchinoline on CD8⁺ T cells within the tumor microenvironment of lung cancer. We showed an inverse correlation between elevated autophagic activity and decreased MHC-I surface expression-a phenomenon often associated with poor clinical efficacies-in various human lung cancer cell lines (NCI-H1299, NCI-H1975, A549, NCI-H1650 and NCI-H446) compared with normal bronchial epithelial cells lung cancer. Knockdown of ATG4 and ATG5 resulted in increased MHC-I expression and enhanced tumor antigen presentation in NCI-H1975, NCI-H1299 and A549 cells. As autophagy receptors were crucial for transporting proteins to autophagosomes for degradation, we sequentially silenced various autophagy receptors and found that NDP52 knockdown specifically restored MHC-I expression, suggesting that NDP52-mediated autophagy might contribute to MHC-I degradation, and autophagy inhibition might enhance immune-mediated cancer cell death. We showed that pretreatment of LLC-OVA cells with the autophagy inhibitor fangchinoline (1.25, 2.5, 5 μM) followed by coculture with CD8⁺ T cells, dose-dependently enhanced immune killing. In both in vitro and in vivo experiments, we showed that fangchinoline combined with anti-PD-1 therapy significantly increased CD8⁺ T cell-mediated cytotoxicity. In conclusion, this study highlights NDP52 as a key autophagy receptor involved in MHC-I degradation and provides a new insight into tumor immune evasion. Combining autophagy inhibition with immunotherapy may be a promising therapeutic strategy for anticancer immunity enhancement.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway.","authors":"Xia-Yun Ni, Xiao-Jun Feng, Zhi-Hua Wang, Yang Zhang, Peter J Little, Yang Cao, Suo-Wen Xu, Li-Qin Tang, Jian-Ping Weng","doi":"10.1038/s41401-025-01559-x","DOIUrl":"https://doi.org/10.1038/s41401-025-01559-x","url":null,"abstract":"","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rh2 in combination with IFNγ potentiated the anti-cancer effect by enhancing interferon signaling response in colorectal cancer cells.","authors":"Mu-Yang Huang, Chun-Cao Xu, Qian Chen, Yan-Ming Zhang, Wen-Yu Lyu, Zi-Han Ye, Ting Li, Ming-Qing Huang, Jin-Jian Lu","doi":"10.1038/s41401-025-01557-z","DOIUrl":"https://doi.org/10.1038/s41401-025-01557-z","url":null,"abstract":"<p><p>Interferon gamma (IFNγ) can amplify immune cell-mediated anti-tumor immunity, as well as directly kill cancer cells. Ginsenoside Rh2 (Rh2), a bioactive compound in traditional Chinese medicine, exhibits anti-cancer effects such as inhibiting proliferation and metastasis. Our earlier research found that Rh2 combined with IFNγ enhanced CXCL10 secretion in cancer cells. Here, we explored whether Rh2 and IFNγ exerted more potent anti-cancer activity in vitro and in vivo, along with its mechanisms and clinical value. Our data showed that Rh2 in combination with IFNγ resulted in a remarkably increased cytotoxicity in colorectal cancer cells including HT29, LoVo and T84 cell lines. Consistently, intratumoral injection with Rh2 plus IFNγ further restricted the HT29 tumor growth in vivo, and importantly, it was demonstrated to be safe for mice. Meanwhile, the combo treatment activated the stimulator of interferon genes (STING) pathway in cancer cells, promoting the transcription of downstream type I interferon. RNA sequencing revealed a dramatically transcriptional alteration in cancer cells with combo treatment and indicated that Rh2 further augmented the activation of interferon signaling pathway, compared with the IFNγ alone. Inhibition of janus kinase (JAK) by ruxolitinib could significantly rescue the cell death-triggered by the combo treatment. Then, a gene set named Rh2+IFNγ signature genes (RISG) was defined, which contained top 20 significantly upregulated genes from the combo treatment. Patients who exhibited a favorable response to the immunotherapy had a higher expression of RISG in tumor compared with those who did not respond. And the high expression of RISG was correlated with better clinical outcome in patients with colorectal cancer (CRC) and skin cutaneous melanoma (SKCM). Herein, the combination of Rh2 with IFNγ served as a promising strategy for cancer treatment, and its-derived RISG gene set also exhibited potential value in predicting clinical outcome. Schematic diagram of the anti-cancer effect of Rh2 combined with IFNγ. The schematic diagram illustrated that ginsenoside Rh2 in combination with IFNγ robustly activated the interferon signals in cancer cells, ultimately leading a significant cell death of cancer cells. ISGs, interferon-stimulated genes. Created with BioRender.com.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway.","authors":"Bai-En Liang, Luo-Sha Long, Xin-Yan Wu, Mei-Ying Huang, Ying Lai, Xi Yuan, Ming-Hui Wang, Meng Li, Qi-Qi Zheng, Hai-Ling Zhang, Man-Chun Chen, Zhen-de Liu, Xin Geng, Qian-Qian Lyu, Wei-Dong Wang, Qing-Hua Liu, Wei-Zhi Liu, Chun-Ling Li","doi":"10.1038/s41401-025-01545-3","DOIUrl":"https://doi.org/10.1038/s41401-025-01545-3","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and tubular injury. Alginate oligosaccharide (AOSC), a natural product obtained from alginate by acidolysis and hydrolysis, shows activities of antioxidant, immunomodulation, and anti-inflammation. In this study, we investigated the potential of AOSC in the treatment of AKI. Renal ischemia-reperfusion (I/R) was induced in male rats by clipping both the renal artery and vein for 45 min followed by reperfusion for 24 h. The rats were treated with AOSC (100 mg/kg, i.g.) before surgery. At the end of the experiments, both kidneys were collected for protein, mRNA measurement, or histological analysis. We showed that AOSC pretreatment significantly improved glomerular and tubular function in the kidney of I/R rats. AOSC markedly inhibited I/R-induced activation of TLR4/MyD88/NF-κB/IL-1β inflammatory signaling and prevented apoptosis in the kidney. In HK2 cells subjected to hypoxia/reoxygenation (H/R) stimulation, AOSC (250-1000 μg/ml) dose-dependently prevented pro-inflammatory responses and cell apoptosis. Transcriptomic analysis revealed that I/R increased the expression levels of mannose receptor type C1 (MRC1) in the kidney, which was markedly inhibited by AOSC. Molecular docking showed that AOSC interacted with E725, N727, E733, T743, S745, and N747 of MRC1 through hydrogen bonds. MRC1 gene knockout significantly improved renal function and attenuated I/R-induced kidney inflammation and apoptosis in mice. In line with this, AOSC failed to prevent I/R-induced kidney injury in MRC1 gene knockout mice. UPLC analysis showed that the protection of AOSC in HK2 cells subjected to H/R was likely attributed to MRC1-mediated intracellular endocytosis. In conclusion, AOSC prevents I/R-induced AKI, which is at least partially mediated by MRC1.</p>","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple and efficient method for purification of human pluripotent stem cell-derived cardiomyocytes via activating p53.","authors":"Peng Zhang, Sen-le Rao, Xiao-Chen Wang, Ping Liang, Ji-Zhen Lu, Wen-Wen Jia, Huang-Tian Yang","doi":"10.1038/s41401-025-01543-5","DOIUrl":"https://doi.org/10.1038/s41401-025-01543-5","url":null,"abstract":"","PeriodicalId":6942,"journal":{"name":"Acta Pharmacologica Sinica","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}