The study aimed to explore the association between psychological stress-related cytokines and essential hypertension to provide the theoretical basis for the prevention and control of the essential hypertension. We sc...The study aimed to explore the association between psychological stress-related cytokines and essential hypertension to provide the theoretical basis for the prevention and control of the essential hypertension. We screened hypertension patients in six communities in Wuzhong City of Ningxia, and chose the healthy people who had lived in the same community for full 5 years as a control group. Finally, we selected 210 pairs of cases and controls randomly, including 108 pairs of Hui and 102 pairs of Han (50% male;age 35 -74). The results showed that the serum TNF alpha levels of hypertension group were higher than the control group (ρ 0.01), and the serum IFN-gamma levels were lower than the control group both in Hui and Han (ρ 0.01). Further analysis showed that the serum TNF alpha level of the Hui hypertension group was higher than the Han hypertension group (ρ 0.01), while the serum IFN-gamma level was lower than Han hypertension group (ρ 0.01). In conclusion, TNF alpha and IFN-gamma were the important related cytokines between psychological stress and hypertension, and taking effective measures to control the level of serum TNF alpha. IFN-gamma may have the vital significance in alleviating or preventing the genesis and development of essential hypertension.展开更多
目的探究摩罗丹浓缩丸(Moluodan concentrated pill,MLD)治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)潜在的分子机制。方法利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database a...目的探究摩罗丹浓缩丸(Moluodan concentrated pill,MLD)治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)潜在的分子机制。方法利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中医药综合数据库(Traditional Chinese Medicine Integrated Database,TCMID)、中医药整合药理学研究平台(Integrative Pharmacologybased Research Platform of Traditional Chinese Medicine,TCMIP)和中药免疫肿瘤学数据库(Traditional Chinese Medicine on Immuno-Oncology,TCMIO)获取MLD的化合物和化合物相关靶点(compound-related target,CRT);DisGeNET和GeneCards数据库获取CAG相关靶点基因(CAG related target gene,CAG-RTG);采用Cytoscape 3.7.2软件构建MLD化合物-CRT网络,并将CRT和CAG-RTG取交集获取MLD相关疾病靶点(MLD-related disease target,MLD-RDT);利用STRING数据库构建MLD-RDT的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并进行拓扑结构分析,筛选重要靶点。采用基因本体论(Gene Ontology,GO)富集分析与京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析探索MLD治疗CAG的主要分子机制。结果MLD中共有259个活性分子,获得961个靶基因,其中179个可能与CAG相关。PPI网络显示,AKT1、TNF、IL-6、TP53、IL-1β等是MLD治疗CAG的关键靶点。富集分析显示,MLD治疗CAG的关键通路为PI3K-AKT信号通路和TNF信号通路。结论MLD可能通过介导TNF/PI3K/AKT信号通路治疗CAG。展开更多
Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,d...Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.展开更多
Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by i...Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.展开更多
文摘The study aimed to explore the association between psychological stress-related cytokines and essential hypertension to provide the theoretical basis for the prevention and control of the essential hypertension. We screened hypertension patients in six communities in Wuzhong City of Ningxia, and chose the healthy people who had lived in the same community for full 5 years as a control group. Finally, we selected 210 pairs of cases and controls randomly, including 108 pairs of Hui and 102 pairs of Han (50% male;age 35 -74). The results showed that the serum TNF alpha levels of hypertension group were higher than the control group (ρ 0.01), and the serum IFN-gamma levels were lower than the control group both in Hui and Han (ρ 0.01). Further analysis showed that the serum TNF alpha level of the Hui hypertension group was higher than the Han hypertension group (ρ 0.01), while the serum IFN-gamma level was lower than Han hypertension group (ρ 0.01). In conclusion, TNF alpha and IFN-gamma were the important related cytokines between psychological stress and hypertension, and taking effective measures to control the level of serum TNF alpha. IFN-gamma may have the vital significance in alleviating or preventing the genesis and development of essential hypertension.
文摘目的探究摩罗丹浓缩丸(Moluodan concentrated pill,MLD)治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)潜在的分子机制。方法利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中医药综合数据库(Traditional Chinese Medicine Integrated Database,TCMID)、中医药整合药理学研究平台(Integrative Pharmacologybased Research Platform of Traditional Chinese Medicine,TCMIP)和中药免疫肿瘤学数据库(Traditional Chinese Medicine on Immuno-Oncology,TCMIO)获取MLD的化合物和化合物相关靶点(compound-related target,CRT);DisGeNET和GeneCards数据库获取CAG相关靶点基因(CAG related target gene,CAG-RTG);采用Cytoscape 3.7.2软件构建MLD化合物-CRT网络,并将CRT和CAG-RTG取交集获取MLD相关疾病靶点(MLD-related disease target,MLD-RDT);利用STRING数据库构建MLD-RDT的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并进行拓扑结构分析,筛选重要靶点。采用基因本体论(Gene Ontology,GO)富集分析与京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析探索MLD治疗CAG的主要分子机制。结果MLD中共有259个活性分子,获得961个靶基因,其中179个可能与CAG相关。PPI网络显示,AKT1、TNF、IL-6、TP53、IL-1β等是MLD治疗CAG的关键靶点。富集分析显示,MLD治疗CAG的关键通路为PI3K-AKT信号通路和TNF信号通路。结论MLD可能通过介导TNF/PI3K/AKT信号通路治疗CAG。
基金Xizang Major Science and Technology Project(XZ202101ZD0005N)Yunnan Major Science and Technology Project(202302AE090015)+1 种基金National Key R&D Program of China(2023ZD04044-04)National Natural Science Foundation of China(32060736)。
文摘Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.
文摘Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.
