摘要：
Inflammation and immunity play a major role in the development of hypertension, and a potential correlation between host mucosal immunity and inflammatory response regulation. We explored the changes of intestinal mucosal microbiota in hypertensive rats induced by high-salt diet and the potential link between the intestinal mucosal microbiota and inflammation in rats. Therefore, we used PacBio (Pacific Bioscience) SMRT sequencing technology to determine the structure of intestinal mucosal microbiota, used enzyme-linked immunosorbent assay (ELISA) to determined the proinflammatory cytokines and hormones associated with hypertension in serum, and used histopathology methods to observe the kidney and vascular structure. We performed a potential association analysis between intestinal mucosal characteristic bacteria and significantly different blood cytokines in hypertensive rats induced by high-salt. The results showed that the kidney and vascular structures of hypertensive rats induced by high salt were damaged, the serum concentration of necrosis factor-alpha (TNF-alpha), angiotensin II (AngII), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly increased (p < 0.05), and the coefficient of immune organ spleen was significantly changed (p < 0.05), but there was no significant change in serum lipids (p > 0.05). From the perspective of gut microbiota, high-salt diet leads to significant changes in intestinal mucosal microbiota. Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were the dominant differential bacteria in intestinal mucosal, with the AUC (area under curve) value of Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were 1 and 0.875 according to ROC (receiver operating characteristic) analysis. Correlation analysis showed that Bifidobacterium animalis subsp. was correlated with IL-6, IL-8, TNF-alpha, and Ang II. Based on our results, we can speculated that high salt diet mediated chronic low-grade inflammation through inhibited the growth of Bifidobacterium animalis subsp. in intestinal mucosa and caused end-organ damage, which leads to hypertension.
通讯作者：
Liming Zhu<&wdkj&>Yongliang Jiang<&wdkj&>Aiguo Dai
作者机构：
[Li, Guang; Peng, Yanping; Zhu, Liming; Dai, Aiguo; Jiang, Yongliang; Meng, Fang; Li, San; Zhu, Hao; Zhang, Shaoze; Li, Cheng; Gu, Jing] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Resp & Crit Care Med, Changsha, Hunan, Peoples R China.;[Liu, Pingping] Hunan Childrens Hosp, Dept Emergency, Key Lab Pediat Emergency Med Hunan Prov, Changsha, Hunan, Peoples R China.;[Yao, Huiling] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Gen Med, Changsha, Hunan, Peoples R China.;[Dai, Aiguo] Hunan Univ Chinese Med, Med Sch, Dept Resp Dis, Changsha, Hunan, Peoples R China.;[Dai, Aiguo] Hunan Prov Key Lab Vasc Biol & Translat Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Liming Zhu; Yongliang Jiang; Aiguo Dai] D;Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P.R. China<&wdkj&>Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, P.R. China<&wdkj&>Hunan Province Key Laboratory of Vascular Biology and Translational Medicine, Changsha, Hunan, P.R. China<&wdkj&>Department of Respiratory and Critical Care Medicine, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P.R. China
关键词：
Tfh/Tfr;hypoxia;pulmonary hypertension;regulatory B cells
摘要：
Chronic hypoxia promoted Breg cells differentiation in the early stage of HPH, which significantly decreased in the late stage. Insufficient Breg cells exacerbated pulmonary vascular remodelling and dysregulated Tfh/Tfr cells in HPH. Adoptive transfer of Breg cells ameliorated pulmonary vascular remodelling and dysregulated Tfh/Tfr cells in HPH. Abstract Hypoxia‐induced pulmonary hypertension (HPH) is a progressive and lethal disease characterized by the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) and obstructive vascular remodelling. Previous research demonstrated that Breg cells were involved in the pathogenesis of pulmonary hypertension. This work aimed to evaluate the regulatory function of Breg cells in HPH. HPH mice model were established and induced by exposing to chronic hypoxia for 21 days. Mice with HPH were treated with anti‐CD22 or adoptive transferred of Breg cells. The coculture systems of Breg cells with CD4+ T cells and Breg cells with PASMCs in vitro were constructed. Lung pathology was evaluated by HE staining and immunofluorescence staining. The frequencies of Breg cells, Tfh cells and Tfr cells were analysed by flow cytometry. Serum IL‐21 and IL‐10 levels were determined by ELISA. Protein levels of Blimp‐1, Bcl‐6 and CTLA‐4 were determined by western blot and RT‐PCR. Proliferation rate of PASMCs was measured by EdU. Compared to the control group, mean PAP, RV/(LV + S) ratio, WA% and WT% were significantly increased in the model group. Anti‐CD22 exacerbated abnormal hemodynamics, pulmonary vascular remodelling and right ventricle hypertrophy in HPH, which ameliorated by adoptive transfer of Breg cells into HPH mice. The proportion of Breg cells on day 7 induced by chronic hypoxia was significantly higher than control group, which significantly decreased on day 14 and day 21. The percentage of Tfh cells was significantly increased, while percentage of Tfr cells was significantly decreased in HPH than those of control group. Anti‐CD22 treatment increased the percentage of Tfh cells and decreased the percentage of Tfr cells in HPH mice. However, Breg cells restrained the Tfh cells differentiation and expanded Tfr cells differentiation in vivo and in vitro. Additionally, Breg cells inhibited the proliferation of PASMCs under hypoxic condition in vitro. Collectively, these findings suggested that Breg cells may be a new therapeutic target for modulating the Tfh/Tfr immune balance in HPH.
作者机构：
[Chen, Kaiqin; Chen, Chunjing; Lu, Fangguo; Ye, Chun; Hu, Jue; Wei, Ke; Gao, Zihan; Xiao, Rong] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.
通讯机构：
[Wei, Ke] M;Medical School, Hunan University of Chinese Medicine, Changsha 410208,China. Electronic address:
关键词：
Immune infiltration;GDF10;NCKAP5;RTKN2;Non-small cell lung cancer
摘要：
This study aimed to identify potential biomarkers for non-small cell lung cancer (NSCLC) and analyze the role of immune cell infiltration in NSCLC. R software was used to screen differentially expressed genes (DEGs) from NSCLC datasets obtained from the Gene Expression Omnibus (GEO) database, and functional correlation analysis was performed. The machine learning algorithms were used to screen the potential biomarkers of NSCLC. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. The protein and mRNA expression levels of potential biomarkers were verified based on the Human Protein Atlas (HPA) database and qRT-PCR. CIBERSORT was used to evaluate the infiltration of immune cells in NSCLC tissues, and the correlation between potential biomarkers and infiltrated immune cell was analyzed. Finally, specific siRNAs were utilized to reduce the GDF10, NCKAP5, and RTKN2 expression in A549 and H1975 cells. The proliferation ability of A549 and H1975 cells was detected by MTT assay. A total of 848 upregulated DEGs and 1308 downregulated DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were mainly related to cell division. Disease ontology (DO) enrichment analysis showed that the diseases with these DEGs were mainly lung diseases, including NSCLC. In addition,three potential biomarkers were identified: GDF10, NCKAP5, and RTKN2. Immune cell infiltration analysis showed that resting NK cells, activated dendritic cells, and Tregs may be involved in the pathogenesis of NSCLC. Meanwhile, GDF10, NCKAP5, and RTKN2 were negatively correlated with Tregs and naïve B cells but were positively correlated with activated dendritic cells and resting NK cells. Immunohistochemical staining showed that the expression of GDF10, NCKAP5, and RTKN2 in the lung tissue of patients with NSCLC was lower than that of normal lung tissue. qRT-PCR also confirmed that the mRNA expression of three biomarkers in NSCLC cell lines A549 and H1975 were significantly lower than those in human normal lung epithelial cells BEAS-2B. An MTT assay showed that GDF10, NCKAP5, and RTKN2 knockdown significantly promoted the proliferation of A549 and H1975 cells. The in vitro experiments showed that GDF10, NCKAP5, and RTKN2 played the inhibitory effects on NSCLC cell lines proliferation. Hence, GDF10, NCKAP5, and RTKN2 can be used as diagnostic biomarkers for NSCLC.
作者机构：
[Chen, Kaiqin; Liang, Junjie; Lu, Fangguo; Wei, Ke; Ye, Chun; Gao, Zihan] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;[Wei, Ke] Hunan Univ Chinese Med, Hunan Prov Key Lab Integrat Pathogen Biol, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wei, K ] H;Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Key Lab Integrat Pathogen Biol, Changsha 410208, Hunan, Peoples R China.
关键词：
miRNA;lncRNA;circRNA;Breast cancer cells;Glucose metabolism
摘要：
Breast cancer is the tumor with the highest incidence in women worldwide. According to research, the poor prognosis of breast cancer is closely related to abnormal glucose metabolism in tumor cells. Changes in glucose metabolism in tumor cells are an important feature. When sufficient oxygen is available, cancer cells tend to undergo glycolysis rather than oxidative phosphorylation, which promotes rapid proliferation and invasion of tumor cells. As research deepens, targeting the glucose metabolism pathway of tumor cells is seen as a promising treatment. Non-coding RNAs (ncRNAs), a recent focus of research, are involved in the regulation of enzymes of glucose metabolism and related cancer signaling pathways in breast cancer cells. This article reviews the regulatory effect and mechanism of ncRNAs on glucose metabolism in breast cancer cells and provides new ideas for the treatment of breast cancer.
摘要：
Objective To investigate the correlations between intestinal flora,plasma metabolites,and blood stasis syndrome in coronary heart disease(CHD),and the mechanisms of Yangxin Tongmai Formula(养心通脉方,YXTMF)for blood stasis syndrome in CHD rats.Methods A total of 18 specific ...MORE Objective To investigate the correlations between intestinal flora,plasma metabolites,and blood stasis syndrome in coronary heart disease(CHD),and the mechanisms of Yangxin Tongmai Formula(养心通脉方,YXTMF)for blood stasis syndrome in CHD rats.Methods A total of 18 specific pathogen free(SPF)male Sqrague-Dawley(SD)rats were used to establish CHD rat models with blood stasis syndrome,which were then randomized into model,YXTMF,and atorvastatin calcium(AVT)groups,with six rats in each group,and were intervened through gavage for two weeks.Subsequently,additional six rats that received normal diet were included as normal group.The pathological changes in the CHD rat models were identified by hematoxylin-eosin(HE)staining.The electrocardiogram,hemodynamics,and lipid profiles of the rats were detected as well.The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry(LC-MS/MS),their ileal mucosal flora by 16S rRNA sequencing,and the correlation between the two results were also analyzed.Results The whole blood viscosity,total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)of rats in the model group increased compared with those in the control group(P<0.05).In the model group,the proliferation of endothelial cells in the coronary artery of rats was damaged,with quite a few vacuolated pathological changes observed.However,the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups(YXTMF and AVT groups).With the use of LC-MS/MS,a total of 33 potential endogenous metabolites were identified in plasma,among which 1-methylhistidine,N-acetylhistamine,progesterone,and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome.The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group.The correlation analysis suggested that Hydrogenophaga,Limnohabitans,and Polaromonas,which were highly related to the formation of blood stasis syndrome in CHD patients,were positively correlated with plasma metabolites such as 5-hydroxyindole,N-acetylhistamine,and progesterone(P<0.01),but were negatively correlated with plasma metabolites such as L-arginine,homoarginine,and Boc-beta-cyano-L-alanine(P<0.01).After YXTMF intervention,Lactobacillus,Corynebacterium,and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine,stachydrine,and naringenin(P<0.05),while negatively correlated with 5-hydroxyindole,N-acetylhistamine,and oleoylethanolamide(P<0.05).Conclusion YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.FEWER
摘要：
目的探索莓茶提取物对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠糖脂代谢及肝脏沉默信息调节因子1(silence information regulator 1,SIRT1)、AMP活化蛋...展开更多 目的探索莓茶提取物对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠糖脂代谢及肝脏沉默信息调节因子1(silence information regulator 1,SIRT1)、AMP活化蛋白激酶(AMP activated protein kinase,AMPK)、过氧化物酶体增殖物激活受体γ辅助活化因子1α(peroxisome proliferator-activated receptor-γcoactivator-1α,PGC-1α)蛋白表达的影响。方法高脂高糖喂养联合链脲佐菌素(35 mg/kg)腹腔注射建立T2DM大鼠模型,建模成功后随机分为模型组、莓茶低剂量组(0.4 g/kg)、莓茶高剂量组(0.8 g/kg),另设普通饲料喂养大鼠为正常组,每组8只。各组灌胃给药6周后,行口服葡萄糖耐量试验计算血糖-时间曲线下面积(area under the curve,AUC),ELISA法检测空腹血胰岛素(fasting insulin,FINS)水平,计算稳态模型以评估胰岛素抵抗指数(homeostatic model assessment for insulin resistance,HOMA-IR),全自动生化分析仪测定血清总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醇(malondialdehyde,MDA)水平,HE染色观察肝脏组织形态学变化,Western blot检测肝脏SIRT1、AMPK、PGC-1α蛋白表达。结果与正常组比较,模型组FBG、AUC、FINS、HOMA-IR、TC、TG、LDL-C、MDA均明显升高(P<0.01),HDL-C、SOD和SIRT1、AMPK、PGC-1α蛋白表达均明显降低(P<0.01),肝脏组织肝索排列紊乱,肝细胞间隙不清晰,呈脂肪变性改变。与模型组比较,莓茶低剂量组、莓茶高剂量组FBG、FINS、HOMA-IR、TG、MDA均明显降低(P<0.05,P<0.01),SOD和SIRT1、AMPK、PGC-1α蛋白表达均明显升高(P<0.05,P<0.01),肝脏组织肝索排列相对整齐,脂肪变性得到改善;莓茶高剂量组AUC、TC均明显降低(P<0.05),HDL-C明显升高(P<0.05)。与莓茶低剂量组比较,莓茶高剂量组FBG、AUC、FINS、TC、MDA均明显降低(P<0.05),SIRT1、AMPK、PGC-1α蛋白表达均明显升高(P<0.05)。结论莓茶提取物能在一定程度上改善T2DM大鼠糖脂代谢,减轻胰岛素抵抗,其机制可能与改善氧化应激,调节肝脏SIRT1、AMPK、PGC-1α蛋白表达有关。收起
摘要：
Ferroptosis has been observed during retinal photoreceptor cell death, suggesting that it plays a role in retinitis pigmentosa (RP) pathogenesis. Qi-Shen-Tang (QST) is a combination of two traditional Chinese medicines used for the treatment of ophthalmic diseases; however, its mechanism of action in RP and ferroptosis remains unclear. Therefore, this study aimed to explore the effect and potential molecular mechanisms of QST on RP. QST significantly improved tissue morphology and function of the retina in the RP model mice. A significant increase in retinal blood flow and normalization of the fundus structure were observed in mice in the treatment group. After QST treatment, the level of iron and the production of malondialdehyde decreased significantly; the levels of superoxide dismutase and glutathione increased significantly; and the protein expression of glutathione peroxidase 4 (GPX4), glutathione synthetase, solute carrier family 7 member 11, and nuclear factor erythroid 2-related factor 2 (NRF2) increased significantly. The molecular docking results demonstrated potential interactions between the small molecules of QST and the key proteins of NRF2/GPX4 signaling pathway. Our results indicate that QST may inhibit ferroptosis by inhibiting the NRF2/GPX4 signaling pathway, thereby reducing RP-induced damage to retinal tissue.
