南方医科大学学报杂志最新文献

{"title":"[Hepatocellular carcinoma-derived lactate-mediated histone H3K18 lactylation modifies S100A2 transcription to promote proliferation, migration, invasion and epithelial-mesenchymal transition of hepatocellular carcinoma cells].","authors":"Liping Huang, Yu Shao, Wanbing Zhou, Jingping He","doi":"10.12122/j.issn.1673-4254.2026.09.06","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.06","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of histone H3 lysine 18 lactylation (H3K18la) regulating the transcription of S100 calcium-binding protein A2 (S100A2) in the development of hepatocellular carcinoma (HCC) and its molecular mechanism.</p><p><strong>Methods: </strong>HCC single-cell transcriptome sequencing data were used to screen the differentially expressed genes and pathways. Intracellular lactate and histone lactylation were measured in HCC and normal hepatocyte cell lines. The effects of glycolysis inhibitors (2-DG/Oxamate) on proliferation, migration, and invasion of the cells were evaluated, and ChIP-qPCR was used to detect the enrichment of H3K18la at the <i>S100A2</i> promoter. TCGA database was used to analyze the association of S100A2 expression with the prognosis of HCC patients. <i>S100A2</i> overexpression and knockdown cell models were established, and rescue experiments using 2-DG or lactate were performed to validate the role of H3K18la in mediating the effects of S100A2. The interaction between S100A2 and KRT6A proteins was validated by STRING, molecular docking, and Co-IP. Western blotting was performed to determine the nuclear expression of β‑catenin and the EMT markers (vimentin and E‑cadherin) in HCC cells, and to elucidate the regulatory effect of H3K18la on the Wnt/β‑catenin pathway.</p><p><strong>Results: </strong>Glycolysis and pyruvate metabolism pathways were upregulated in HCC, and lactate levels was elevated in HCC cells. Pan-Kla and H3K18la were significantly overexpressed in HCC cell lines, especially under hypoxia. Glycolysis inhibitors dose-dependently reduced H3K18la and suppressed malignant phenotypes of HCC cells. S100A2 mRNA and protein levels were upregulated in HCC, and its high expression was correlated with poor prognosis. S100A2 promoted HCC cell proliferation, migration, and invasion, which were reversed by 2‑DG. S100A2 directly interacted with KRT6A, the expression of nuclear β‑catenin was reduced after <i>KRT6A</i> knockdown and increased after <i>KRT6A</i> overexpression; exogenous lactate reversed <i>KRT6A</i> overexpression‑induced inhibition of β‑catenin, which was blocked by XAV939. Treatment with 2‑DG lowered the expressions of β‑catenin and EMT markers, which were reversed by <i>S100A2</i> or <i>KRT6A</i> overexpression.</p><p><strong>Conclusions: </strong>HCC-derived lactate enhances H3K18la modification, which activates <i>S100A2</i> transcription to positively regulate the Wnt/β‑catenin pathway, ultimately promoting the proliferation, migration, invasion and EMT of HCC cells.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2056-2068"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Social isolation induces social avoidance in mice: the mediating role of the medial prefrontal cortex glutamatergic neurons].","authors":"Quan Yuan, Dongdong Zhang, Jingtao Wang, Hanjun Song","doi":"10.12122/j.issn.1673-4254.2026.09.01","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.01","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate social isolation (SI)-induced abnormal behaviors and changes in neuronal activity in the medial prefrontal cortex (mPFC) of mice.</p><p><strong>Methods: </strong>Male C57BL/6J mice kept under normal conditions or SI mice housed in individual cages for 2 weeks were subjected to intracerebral microinjection of a control virus, a chemogenetic activation virus, or an optogenetic activation virus (<i>n</i>=8). The mice were assessed for behavioral changes and examined for neuronal changes in mPFC using c-fos immunofluorescence staining and co-staining with specific antibodies against CaMKIIα (for excitatory neurons) and GABA (for inhibitory neurons). <i>In vivo</i> optical fiber recording was used to detect real-time neuronal changes in the mice during behavioral assessment. The effects of chemogenetics and optogenetics for modulating activities of glutamatergic neurons in the mPFC were observed on social behaviors of both the control and SI mice.</p><p><strong>Results: </strong>Behavioral tests showed that two weeks of SI did not cause obvious anxiety or depression-like behaviors or impair object recognition memory, working memory, social ability or social memory, but induced social avoidance behaviors in the mice. Immunofluorescence staining revealed significantly increased c-fos-positive neurons in the mPFC of SI mice, consisting mostly of excitatory glutamatergic neurons. <i>In vivo</i> optical fiber recording showed that during the second stage of social interaction test (SIT), the activity of mPFC glutamatergic neurons increased significantly in SI mice. Chemogenetic and optogenetic activation of mPFC glutamatergic neurons induced obvious social avoidance in the control mice, and inhibition of these neurons significantly alleviated social avoidance in SI mice.</p><p><strong>Conclusions: </strong>Two weeks of SI can induce social avoidance behaviors in mice and enhances the activity of mPFC glutamatergic neurons.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"1993-2005"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[CHIR99021 alleviates neuroinflammation in a mouse model of Parkinson's disease by inhibiting the GSK-3β/NF-κB pathway].","authors":"Kelin Shi, Xiaochuan Qi, Shixiang Xu, Yuanyuan Gao, Mingzhe Fang, Juncheng Hu, Chunjing Wang, Changqing Liu, Yu Guo","doi":"10.12122/j.issn.1673-4254.2026.07.13","DOIUrl":"10.12122/j.issn.1673-4254.2026.07.13","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of CHIR99021 for improving neuroinflammation in a mouse model of Parkinson's disease (PD) and the role of the GSK-3β/NF-κB pathway in mediating this effect.</p><p><strong>Methods: </strong>In the cell experiment, induced SH-SY5Y cells were pretreated with 3 μmol/L CHIR99021 for 2 h prior to MPP+ treatment. In a male C57BL/6 mouse model of MPTP-induced PD, the effect of intraperitoneal injection of CHIR99021 for 7 days on motor function of the mice were assessed using behavioral tests. Western blotting and immunofluorescence staining were used to detect the changes in the GSK-3β/NF-κB pathway, NLRP3 inflammasome and autophagy in both SH-SY5Y cells and the mouse models.</p><p><strong>Results: </strong>MPP+-treated SH-SY5Y cells showed significantly downregulated expression of p-GSK-3β protein and upregulated expressions of p-NF-κB p65, ASC, NLPR3, and caspase-1, and these changes were obviously attenuated by pretreatment with CHIR99021. Compared with normal mice, the PD mouse models showed significantly decreased motor function and reduced TH neurons in the brain with lowered expression of p-GSK-3β, increased expression of p-NF-κB p65 (Ser536), and upregulated ASC, NLPR3, and caspase-1 expressions. Treatment with CHIR99021 significantly increased the expression of p-GSK-3β, and reduced the expression of p-NF‑κB p65 (Ser536), ASC, NLPR3, and caspase-1.</p><p><strong>Conclusions: </strong>CHIR99021 inhibits the GSK-3β/NF‑κB signaling pathway to improve motor function of PD mice, reduce neuroinflammation, and activate autophagy to maintain the homeostasis of intracellular environment, suggesting that targeting GSK-3β, a potential multifunctional therapeutic target, can simultaneously regulate multiple key pathological links in PD.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 7","pages":"1593-1600"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Jianwei Shoutai</i> Pill reduces spontaneous abortion in mice by inhibiting Exo-miR-410-3p uptake and promoting trophoblast epithelial-mesenchymal transition, migration, and invasion].","authors":"Zhanfa Xu, Zhenyue Chen, Liping Xie, Xinyi Li, Genggeng Qin, Jie Gao","doi":"10.12122/j.issn.1673-4254.2026.09.02","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.02","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the therapeutic effect of <i>Jianwei Shoutai</i> Pill (JSP) on spontaneous abortion (SA) in mice and explore its therapeutic mechanism.</p><p><strong>Methods: </strong>The miR-410-3p mimic was electroporated into milk exosomes to prepare exosomal miR-410-3p (Exo-miR-410-3p), which was characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. CCK-8, scratch wound healing, and Transwell assays were used to test the effects of control and JSP-medicated rat serum on proliferation, migration, and invasion of trophoblast HTR-8/Svneo cells. Female C57BL/6 mice were divided into SA model group, Model+Exo-miR-410-3p group, Model+Exo-miR-410-3p+P group, and Model+Exo-miR-410-3p+JSP group. The fluorescently labeled exosomes was tracked using <i>in vivo</i> and <i>ex vivo</i> imaging and embryo resorption rate was calculated. RT-qPCR, Western blotting, <i>in situ</i> hybridization, and immunohistochemical studies were carried out for further <i>in vivo</i> verification.</p><p><strong>Results: </strong>Treatment with Exo-miR-410-3p significantly reduced migration and invasion capacities of HTR-8/Svneo cells, and these inhibitory effects were effectively reversed by JSP intervention. In pregnant C57BL/6 mouse models, JSP treatment prevented Exo-miR-410-3p from reaching the maternal-fetal interface. Consistently, the embryo resorption rate was significantly lower in Exo-miR-410-3p+JSP group than in Exo-miR-410-3p alone group [(20.73±3.77)% <i>vs</i> (74.95±10.09)%, <i>P</i><0.01]. JSP treatment significant reduced miR-410-3p level and upregulated TRAF6 expression in the female mouse models.</p><p><strong>Conclusions: </strong>JSP inhibits Exo-miR-410-3p uptake by trophoblast cells, thereby promoting trophoblast EMT, migration, and invasion and reducing embryo resorption in mouse models of spontaneous abortion.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2006-2022"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Dual inhibition of PSME2 and STAT3 induces ferroptosis in esophageal squamous cell carcinoma cells by regulating the SLC7A11/GPX4 axis].","authors":"Chunhui Qi, Heqian Zhang, Xiaoshuang Wu, Yongan Kang, Jingyi Yang, Di Zhao, Shegan Gao, Yijun Qi","doi":"10.12122/j.issn.1673-4254.2026.09.21","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.21","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the form of cell death induced by PSME2 silencing combined with the STAT3 inhibitor WP1066 in esophageal squamous cell carcinoma (ESCC) cells and explore the underlying mechanism.</p><p><strong>Methods: </strong>ESCC cell lines KYSE30 and NE6-T with PSME2 silencing were treated with WP1066. Phenotypic rescue experiments were performed to determine the predominant form of cell death using different cell death-related inhibitors. Western blotting was used to detect the expressions of the protein markers of ferroptosis, apoptosis, pyroptosis and necroptosis. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation were assessed using DCFH-DA and C11-BODIPY fluorescent probes, respectively. Mitochondrial ultrastructural changes were observed by transmission electron microscopy (TEM). mRNA transcriptomic analysis was performed to identify differentially expressed genes in cells treated with PR171 or siPSME2 combinedwith WP1066. Gene set enrichment analysis to analyze the enriched biological functions.</p><p><strong>Results: </strong>Dual inhibition of PSME2 and STAT3 induced obvious ESCC cell death. This lethal effect was markedly reversed by the ferroptosis inhibitor ferrostatin-1 and attenuated by the apoptosis inhibitor Z-VAD-FMK, whereas 2-bromohexadecanoic acid or necrosulfonamide did not show significant inhibitory effects. The combined treatment with siPSME2 and WP1066 significantly downregulated SLC7A11 and GPX4 protein expressions and increased intracellular ROS levels and lipid peroxide accumulation in ESCC cells. The ESCC cells with dual inhibition showed obvious mitochondrial shrinkage, reduced cristae, and increased membrane density. mRNA transcriptomic analysis identified 45 overlapping differentially expressed genes between the PR171 plus WP1066 group and the siPSME2 plus WP1066 group, enriched in pathways related to stress response, redox imbalance, protein translation/ribosomal function, metabolism, and cell cycle regulation.</p><p><strong>Conclusions: </strong>Dual inhibition of PSME2 and STAT3 promotes lipid peroxide accumulation and induces ferroptosis in ESCC cells possibly by regulating the SLC7A11/GPX4 antioxidant axis, indicating a therapeutic strategy targeting both PSME2 and STAT3 for ESCC.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2230-2241"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Natural bear bile powder attenuates lipopolysaccharide-induced acute lung injury in mice by regulating the NF-κB and Nrf-2/HO-1 signaling pathways].","authors":"Yuhang Sun, Xingzhen Lu, Xinyue Zhang, Jianpeng Guo, Xin Jin","doi":"10.12122/j.issn.1673-4254.2026.07.16","DOIUrl":"10.12122/j.issn.1673-4254.2026.07.16","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism that mediates the protective effect of bear bile powder (BBP) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.</p><p><strong>Methods: </strong>Cultured RAW264.7 cells were pretreated with, different concentrations of BBP, or dexamethasone (Dex) for 1 h before LPS challenge. Sixty male C57BL/6 mice were randomized into 5 groups (<i>n</i>=12), including a control group, a LPS-induced ALI model group, a Dex treatment group, and two BBP treatment groups treated with low- (30 mg/kg) or high-dose (120 mg/kg) BBP. The levels of inflammatory factors and oxidative stress-related indicators in the cells and mouse lung tissues were determined, and mouse lung histopathology, wet/dry weight ratio, and BALF cell count were examined; the expressions of NF-κB and Nrf-2/HO-1 pathways were detected using qPCR, Western blotting, and immunohistochemistry.</p><p><strong>Results: </strong>In LPS-stimulated RAW264.7 cells, BBP (12.5 μg/mL) significantly reduced the levels of TNF-α, COX-2, IL-1β, IL-6, MDA, NO and ROS, enhanced SOD activity, increased mRNA expressions of IκB-α, Nrf-2, and HO-1, and lowered mRNA expressions of TNF-α, IL-1β, Keap-1, and NF-κB (p65). The ALI mouse models showed severe lung pathologies and edema, increased BALF cell counts, and increased levels of TNF‑α, COX-2, IL-1β, IL-6, MDA, and NO, lowered SOD activity with reduced protein expressions of IκB-α, Nrf-2, and HO-1 and increased expressions of Keap-1 and p65. Treatment with high-dose BBP significantly ameliorated lung pathologies in the mouse models and improved the aberrant alterations in pulmonary expressions of inflammatory factors, oxidative stress-related indicators and the NF-κB and Nrf-2/HO-1 pathways.</p><p><strong>Conclusions: </strong>BBP protects against LPS-induced ALI in mice possibly by targeting the Nrf-2/HO-1 and NF-κB pathways, suggesting its potential as a therapeutic agent for ALI.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 7","pages":"1622-1633"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Qihuang Jianpi Zishen</i> Granule ameliorates renal injury in patients with systemic lupus erythematosus by regulating immunometabolic reprogramming of macrophages].","authors":"Ai Qian, Chuanbing Huang, Yawen Zhu, Kexin Hu, Xinran Song, Yuxiang Xu","doi":"10.12122/j.issn.1673-4254.2026.09.11","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.11","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism of <i>Qihuang Jianpi Zishen</i> Granule (QJZG) for regulating macrophage polarization in renal damage in patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>Public databases were used to screen the targets of QJZG, SLE and renal damage. An active ingredient-target network and a protein-protein interaction network were constructed followed by molecular docking. Sixty-two SLE patients were randomized into QJZG treatment group and control group (<i>n</i>=31), with 30 healthy individuals as the normal control group. Macrophage polarization markers (iNOS and Arg-1) and AMPK/ULK1 pathway molecules were detected using Western blotting and RT-qPCR, and the changes in renal function, immune indicators, and TCM syndrome scores of the participants were evaluated.</p><p><strong>Results: </strong>Three key active ingredients of QJZG (quercetin, kaempferol, and 7-O-methylisoflavanone) and 9 core targets were identified, and the target genes were enriched in the TNF, HIF-1, and mTOR pathways. Molecular docking showed strong binding of the active compounds of QJZG with HIF-1α and mTOR. In SLE patients, QJZG treatment significantly improved their renal function, regulated the immune function (increasing CD4⁺/CD8⁺ ratio and reducing CD8⁺ T cells), and reduced TCM syndrome scores. QJZG treatment also significantly downregulated iNOS, mTOR, and HIF-1α expressions and upregulated Arg-1, AMPK, and ULK1 expression in SLE patients.</p><p><strong>Conclusions: </strong>QJZG alleviated renal damage in SLE patients through a mechanism involving multiple components and targets. The active ingredients of QJZG regulate macrophage polarization possibly by activating the AMPK/ULK1 pathway via binding to their targets including HIF-1α and mTOR.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2113-2122"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genistein alleviates cerebral ischemia/reperfusion-induced inflammatory injury in rats by regulating microglial polarization <i>via</i> the PI3K/AKT/COX-2 signaling pathway].","authors":"Mengjia Li, Mengzhe Wang, Yu Tao, Yixuan Pang, Li Li, Xiaonan Zhang, Shidi Zhao","doi":"10.12122/j.issn.1673-4254.2026.09.13","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.13","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism of genistein for alleviating cerebral ischemia/reperfusion (I/R)-induced neuroinflammation in microglia and its protective effects on co-cultured neurons.</p><p><strong>Methods: </strong>Male SD rats were divided into control group, I/R group, and 3 genistein groups treated with 25, 50 or 100 mg/kg genistein before I/R modeling (<i>n</i>=10), and the expressions of microglial polarization markers CD86 and CD206, inflammatory cytokines, PI3K, AKT, and COX-2 were examined. In cultured BV-2 cells with oxygen-glucose deprivation/reperfusion (OGD/R), the effects of genistein, si‑PI3K, genistein combined with si‑PI3K, 740Y‑P (a PI3K agonist), or 740Y‑P with genistein on microglial polarization, inflammatory factors, and PI3K, AKT and COX-2 expressions were assessed. In a neuron‑microglia co‑culture system, the changes in neuronal apoptosis rate, cell viability, and apoptosis‑related proteins in response to genistein treatment were detected.</p><p><strong>Results: </strong>The rat models of I/R exhibited obvious M1 polarization of the microglia, as shown by upregulated CD86, IL‑6, IL‑8, IL‑1β, TNF‑α, PI3K, AKT, and COX‑2 expressions and downregulated IL‑4 and TGF‑β expressions. Genistein treatment effectively reversed M1 polarization of the microglia, downregulated pro‑inflammatory factors and the PI3K/AKT/COX‑2 pathway, and promoted M2 polarization of the microglia in the mouse models. The COX‑2 inhibitor celecoxib produced similar effects to genistein by decreasing the expressions of M1 markers, TNF‑α, PI3K, AKT, and COX‑2 and increasing M2 markers and TGF‑β expression. In cultured BV-2 cells, genistein significantly inhibited OGD/R‑induced M1 polarization and pro‑inflammatory responses, and such protective effects were mimicked by PI3K knockdown, whereas PI3K activation by 740Y‑P partially counteracted the effects of genistein. In the neuron‑microglia co‑culture system, genistein obviously reduced OGD/R‑induced neuronal apoptosis, enhanced cell viability, decreased cleaved caspase‑3 and Bax expressions, and increased Bcl‑2 and BDNF expressions.</p><p><strong>Conclusions: </strong>Genistein alleviates cerebral I/R-induced neuroinflammatory injury in rats by promoting M2 polarization of the microglia <i>via</i> downregulating the PI3K/AKT/COX‑2 pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2130-2148"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Hepatocellular carcinoma cells induce M2 macrophage polarization through upregulation of ANXA2 and ANXA5 expression].","authors":"Junying Xu, Chenghao Liu, Hao Huang, Huijiao Jiang, Dan Dong, Xiangwei Wu, Xueling Chen","doi":"10.12122/j.issn.1673-4254.2026.09.10","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.10","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the prognostic value of annexins A2 (ANXA2) and A5 (ANXA5) in hepatocellular carcinoma (HCC) and their impact on tumor microenvironment.</p><p><strong>Methods: </strong>Public datasets of HCC transcriptome and clinical data and spatial transcriptomic data were used for survival analysis, correlation analysis, immune microenvironment analysis, and enrichment analysis to explore the effects of annexin A2 (ANXA2) and ANXA5 on patient prognosis and tumor microenvironment and the potential mechanisms. Immunofluorescence assays were performed to detect ANXA2, ANXA5, and ANXA11 expressions in HCC tissues and their co-expression with CD206. THP-1 cells were treated with culture supernatant of human HCC MHCC-97H cells (TCM), and the changes in mRNA levels of IL-10, ANXA2, ANXA5, and ANXA11 and the protein levels of ANXA2, ANXA5, ANXA11, and KLF4 were examined using qRT-PCR and Western blotting. Flow cytometry was used to detect the expression of CD206 and PD-L1 in the macrophages.</p><p><strong>Results: </strong>ANXA2, ANXA5 and ANXA11 expressions were all significantly up-regulated in HCC tissues in correlation with poor patient prognosis. GO and GSEA revealed enrichment of IL-10 and IL-4/IL-13 signaling pathways in tumors overexpressing ANXA2, ANXA5 and ANXA11, whose high expressions were positively correlated with macrophage infiltration. Immunofluorescence staining demonstrated co-expressions of ANXA2 and ANXA5 with M2-macrophage markers in human HCC tissues. The conditioned medium from HCC cells significantly up-regulated the expressions of ANXA2, ANXA5, CD206 and PD-L1 in THP-1 cells, whereas treatment with the recombinant ANXA2 or ANXA5 protein alone increased CD206 expression only. Correlation analysis indicated that KLF4 was positively correlated with both ANXA2 and ANXA5, and inhibition of KLF4 caused significant reduction of ANXA2, ANXA5 and CD206 levels in THP-1 cells.</p><p><strong>Conclusions: </strong>HCC promotes M2 macrophage polarization by up-regulating ANXA2 and ANXA5 expressions, which contribute to an immunosuppressive microenvironment in HCC and potentially serve as molecular targets for HCC immunotherapy.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2101-2112"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Xuebijing</i> Injection ameliorates sepsis-associated acute respiratory distress syndrome in mice by upregulating phospholipid transfer protein to regulate macrophage JNK/c-JUN pathway].","authors":"Lu Xu, Yuanjin Pan, Yuchen Wang, Zhenyu Chen, Wei Jiang, Jiangquan Yu, Ruiqiang Zheng","doi":"10.12122/j.issn.1673-4254.2026.09.04","DOIUrl":"10.12122/j.issn.1673-4254.2026.09.04","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the ameliorative effect of <i>Xuebijing</i> Injection in a mouse model of sepsis-associated acute respiratory distress syndrome (ARDS) and its molecular mechanisms.</p><p><strong>Methods: </strong>In a C57BL/6J mouse model of sepsis-associated ARDS induced by lipopolysaccharide (LPS), the ameliorative effect of pretreatment with <i>Xuebijing</i> injection at low and high doses prior to modeling were evaluated by analyzing survival rates, lung histopathology, levels of inflammatory cytokines, and expressions of phospholipid transfer protein (PLTP) using transcriptomics, qPCR, Western blotting, ELISA, and immunofluorescence staining. In the cell experiment, RAW264.7 macrophages treated with LPS and different concentrations of <i>Xuebijing</i> were examined for changes in cell viability, morphology, inflammatory cytokine levels, and PLTP expression. PLTP overexpression experiment was carried out to verify the function of PLTP, and the changes in expressions of JNK/c-JUN and NF-κB pathway proteins were detected.</p><p><strong>Results: </strong><i>Xuebijing</i> pretreatment, especially at the high dose, significantly increased the 4-day survival rate, reduced lung histopathological injury score, and decreased lung wet/dry weight ratio in mice with sepsis-associated ARDS. High-dose <i>Xuebijing</i> more effectively lowered serum levels of TNF-α, IL-6, and IL-1β than the low dose, while at both doses, <i>Xuebijing</i> significantly decreased IL-1β levels in the bronchoalveolar lavage fluid (BALF); <i>Xuebijing</i> at the high dose, but not the low dose, significantly reduced BALF levels of TNF‑α and IL-6. LPS significantly downregulated PLTP expression in mouse lung tissue, a trend effectively ameliorated by <i>Xuebijing</i> pretreatment. In cultured RAW264.7 cells, <i>Xuebijing</i> dose-dependently inhibited LPS-induced inflammatory cytokine release and upregulated PLTP expression, resulting also in suppressed phosphorylation and activation of the JNK/c-JUN and NF-κB signaling pathways, and this effect was significantly enhanced by PLTP overexpression.</p><p><strong>Conclusions: </strong><i>Xuebijing</i> alleviates sepsis-associated ARDS by upregulating PLTP and inhibiting JNK/c-JUN and NF-κB signaling pathways, suggesting the potential of PLTP as a therapeutic target for this condition.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"46 9","pages":"2035-2045"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}