胶质母细胞瘤(glioblastoma,GBM)是最常见且恶性程度最高的原发性脑癌,5年生存率低于10%,现有治疗效果有限,其免疫抑制性肿瘤微环境是治疗应答不足的核心原因[1]。星形胶质细胞作为中枢神经系统中数量丰富的细胞,虽具重要免疫调节功能,...胶质母细胞瘤(glioblastoma,GBM)是最常见且恶性程度最高的原发性脑癌,5年生存率低于10%,现有治疗效果有限,其免疫抑制性肿瘤微环境是治疗应答不足的核心原因[1]。星形胶质细胞作为中枢神经系统中数量丰富的细胞,虽具重要免疫调节功能,但其在GBM免疫反应的具体作用长期不明。近期FAUST等[2](QUINTANA团队)通过GBM样本、临床前模型及单细胞测序、多重免疫荧光、CRISPR基因干扰等技术,结合小鼠与人类体外实验,明确揭示肿瘤微环境中星形胶质细胞通过白细胞介素11(interleukin-11,IL-11)-信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)-肿瘤坏死因子相关凋亡诱导配体(TNF-related apoptosis-inducing ligand,TRAIL)通路介导T细胞凋亡,证实其为GBM免疫逃逸的关键“帮凶”,为治疗策略开辟新视角。展开更多
目的:本研究基于“肝与大肠相通”理论,采用网络药理学预测与动物实验验证相结合的策略,探讨赶黄草–炙黄芪–生大黄复方(SHY)干预酒精性肝损伤(ALI)的作用机制。方法:网络药理学获取SHY干预ALI的活性成分及主要靶点,构建PPI网络,进行GO...目的:本研究基于“肝与大肠相通”理论,采用网络药理学预测与动物实验验证相结合的策略,探讨赶黄草–炙黄芪–生大黄复方(SHY)干预酒精性肝损伤(ALI)的作用机制。方法:网络药理学获取SHY干预ALI的活性成分及主要靶点,构建PPI网络,进行GO和KEGG富集分析筛选可能涉及的生物过程和信号通路。利用Lieber-DeCarli酒精液体饲料[5% (vol/vol)乙醇]复制野生型(WT)小鼠ALI模型,通过检测体循环血清ALT、IL-11及肝脏组织IL-11和p-STAT3蛋白表达,验证SHY对ALI的保护作用及机制。结果:通过TCMSP数据库筛选共获得15种活性成分及219个药物靶点,与ALI疾病靶点交集得到106个关键靶点。PPI网络分析显示TNF、IL6、AKT1等为核心节点,GO/KEGG富集提示其通过IL-17、TNF等信号通路调控氧化应激与炎症反应。动物实验证实SHY显著降低模型小鼠血清ALT、IL-11水平(P Objective: Based on the traditional Chinese medicine theory of “liver-intestine correlation,” this study integrated network pharmacology prediction with experimental validation to investigate the mechanism of the Penthorum chinense Pursh-Astragalus membranaceus-Raw Rheum palmatum compound (SHY) in alleviating alcohol-induced liver injury (ALI). Methods: Network pharmacology was employed to identify active components and key targets of SHY against ALI. Protein-protein interaction (PPI) networks were constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate biological processes and signaling pathways. ALI was induced in wild-type (WT) mice using the Lieber-DeCarli ethanol liquid diet (5% ethanol, vol/vol). Serum alanine aminotransferase (ALT) and interleukin-11 (IL-11) levels, along with hepatic IL-11 and phosphorylated STAT3 (p-STAT3) protein expression, were measured to validate SHY’s hepatoprotective effects. Results: Fifteen bioactive components and 219 potential targets of SHY were identified from the TCMSP database, with 106 overlapping targets linked to ALI. PPI network analysis revealed TNF, IL6, and AKT1 as core targets. GO/KEGG enrichment highlighted SHY’s regulation of oxidative stress and inflammation via IL-17 and TNF signaling pathways. Animal experiments demonstrated that SHY significantly reduced serum ALT and IL-11 levels (P < 0.01) and suppressed hepatic p-STAT3 phosphorylation. Western blot confirmed a 1.8-fold downregulation of IL-11 expression in SHY-treated mice. Conclusion: This study is the first to demonstrate that SHY ameliorates ALI by modulating the IL-11R/JAK/STAT axis, providing molecular evidence for the “treating liver diseases through intestinal regulation” theory.展开更多
文摘胶质母细胞瘤(glioblastoma,GBM)是最常见且恶性程度最高的原发性脑癌,5年生存率低于10%,现有治疗效果有限,其免疫抑制性肿瘤微环境是治疗应答不足的核心原因[1]。星形胶质细胞作为中枢神经系统中数量丰富的细胞,虽具重要免疫调节功能,但其在GBM免疫反应的具体作用长期不明。近期FAUST等[2](QUINTANA团队)通过GBM样本、临床前模型及单细胞测序、多重免疫荧光、CRISPR基因干扰等技术,结合小鼠与人类体外实验,明确揭示肿瘤微环境中星形胶质细胞通过白细胞介素11(interleukin-11,IL-11)-信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)-肿瘤坏死因子相关凋亡诱导配体(TNF-related apoptosis-inducing ligand,TRAIL)通路介导T细胞凋亡,证实其为GBM免疫逃逸的关键“帮凶”,为治疗策略开辟新视角。
文摘目的:本研究基于“肝与大肠相通”理论,采用网络药理学预测与动物实验验证相结合的策略,探讨赶黄草–炙黄芪–生大黄复方(SHY)干预酒精性肝损伤(ALI)的作用机制。方法:网络药理学获取SHY干预ALI的活性成分及主要靶点,构建PPI网络,进行GO和KEGG富集分析筛选可能涉及的生物过程和信号通路。利用Lieber-DeCarli酒精液体饲料[5% (vol/vol)乙醇]复制野生型(WT)小鼠ALI模型,通过检测体循环血清ALT、IL-11及肝脏组织IL-11和p-STAT3蛋白表达,验证SHY对ALI的保护作用及机制。结果:通过TCMSP数据库筛选共获得15种活性成分及219个药物靶点,与ALI疾病靶点交集得到106个关键靶点。PPI网络分析显示TNF、IL6、AKT1等为核心节点,GO/KEGG富集提示其通过IL-17、TNF等信号通路调控氧化应激与炎症反应。动物实验证实SHY显著降低模型小鼠血清ALT、IL-11水平(P Objective: Based on the traditional Chinese medicine theory of “liver-intestine correlation,” this study integrated network pharmacology prediction with experimental validation to investigate the mechanism of the Penthorum chinense Pursh-Astragalus membranaceus-Raw Rheum palmatum compound (SHY) in alleviating alcohol-induced liver injury (ALI). Methods: Network pharmacology was employed to identify active components and key targets of SHY against ALI. Protein-protein interaction (PPI) networks were constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate biological processes and signaling pathways. ALI was induced in wild-type (WT) mice using the Lieber-DeCarli ethanol liquid diet (5% ethanol, vol/vol). Serum alanine aminotransferase (ALT) and interleukin-11 (IL-11) levels, along with hepatic IL-11 and phosphorylated STAT3 (p-STAT3) protein expression, were measured to validate SHY’s hepatoprotective effects. Results: Fifteen bioactive components and 219 potential targets of SHY were identified from the TCMSP database, with 106 overlapping targets linked to ALI. PPI network analysis revealed TNF, IL6, and AKT1 as core targets. GO/KEGG enrichment highlighted SHY’s regulation of oxidative stress and inflammation via IL-17 and TNF signaling pathways. Animal experiments demonstrated that SHY significantly reduced serum ALT and IL-11 levels (P < 0.01) and suppressed hepatic p-STAT3 phosphorylation. Western blot confirmed a 1.8-fold downregulation of IL-11 expression in SHY-treated mice. Conclusion: This study is the first to demonstrate that SHY ameliorates ALI by modulating the IL-11R/JAK/STAT axis, providing molecular evidence for the “treating liver diseases through intestinal regulation” theory.
