To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.
Method
Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.
Results
Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.
Conclusion
Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.
Key Points
• Antigen processing and presentation and leukocyte transendothelial migration may play key roles in the pathogenesis of SLE.
Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM. 相似文献
Objective:To study the effect of Tiantai No.1(天泰1号) on gene expression profile in hippocampus of Alzheimer's disease(AD) rat,molecular genetic target points of the effect of this drug were defined,its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level,and a scientific basis was provided for its clinical availability and promotion.Methods:Thirty male SpragueDawley rats were divided into three groups with 10 rats per group:sham-operation group,model group and Tiantai No.1 group.Sterile surgical procedure was applied,the model group with bilateral hippocampal injection of Aβ_(1-40) was established,and normal saline was used instead of Aβ_(1-40)in the sham-operation group.One week after the models was made,rats were administered by gastric lavage once every day for three consecutive weeks.The rats of the sham-operation group and the model group were daily fed with purified water by lavage;the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage.Total RNAs of hippocampus tissues were extracted with Trizol,the changes of hippocampus gene expression profiles in the above three groups were analyzed by using Affymetrix rat whole genome expression profile microarray.Results:Microarray analysis showed that,compared with the sham-operation group,the hippocampus of the model group had 50 up-regulated genes with significant difference(fold change 2),and 21 down-regulated genes with significant difference(fold change 0.5);compared with the hippocampus of the model group,the hippocampus of the Tiantai No.1 group was found to have 5 up-regulated genes with significant difference(fold change 2) and 20down-regulated genes with significant difference(fold change 0.5).The functions of differentially expressed genes of the groups were involved in nervous system's development,neuronic differentiation and function-regulation,cellular growth and differentiation and apoptosis,synaptic occurrence and plasticity,inflammation and immune response,ion channels/transporters,cellular signal transduction,cellular material/energy metabolism and so on.Conclusion:Tiantai No.1 can regulate hippocampal function,and further regulate the brain function of animals in multiple gene target points by a number of ways. 相似文献
BackgroundHepatic fibrosis is attributed to an imbalance of extracellular matrix production and lysis. Human hepatic stellate cells (HSCs) have been uncovered to converge through complex interactions with hepatocytes and immune cells, causing scarring in liver damage.AimsWe aimed to investigate the expression status of ubiquitin specific peptidase 1 (USP1) and its potential mechanisms on HSCs and hepatic fibrosis.MethodsHepatic fibrosis animal and cell models were generated using mice with carbon tetrachloride (CCl4) treatment and HSCs LX-2 with TGF-β1 treatment. Relationships among USP1, SNAIL, and CXCL1 were identified via dual-luciferase reporter gene assay, co-immunoprecipitation, and chromatin immunoprecipitation. With gain- and loss-of-experiments, CCK-8 and flow cytometry assays were employed for cell proliferation and apoptosis.ResultsUSP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression. USP1 downregulation decreased expressions of fibrosis-related genes, suppressed proliferation, and promoted apoptosis in TGF-β1-induced LX-2 cells, which were reversed by SNAIL overexpression. The pro-fibrosis role caused by SNAIL upregulation was abolished by CXCL1 reduction. Promotive function of USP1/SNAIL/CXCL1 axis in hepatic fibrosis was further confirmed in vivo.ConclusionThese data supported siRNA-mediated silencing of USP1 improved hepatic fibrosis through inhibition of SNAIL and CXCL1, which yields a new therapeutic target for hepatic fibrosis treatment. 相似文献
