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.
This study explores the feasibility of using diffusion kurtosis imaging (DKI) in the pelvic floor region and assesses the water diffusivity of the pubovisceral muscle. Twenty-seven healthy young nulliparous females underwent DKI at 3.0 T that included 15 gradient directions and three b values (0, 750, and 1500 s/mm2). The diffusion tensor and diffusion kurtosis metrics values of the pubovisceral muscle were measured after image processing. Two independent sample t-tests, a paired-samples t-test, and a nonparametric hypothesis test were performed as appropriate to compare the differences among different metrics. Twenty-six subjects (mean ± standard deviation age, 25 ± 2 years) were successfully analyzed by measuring the diffusion tensor and diffusion kurtosis metrics of the bilateral pubovisceral muscles. The metrics included mean kurtosis, axial kurtosis, radial kurtosis, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. We found no statistically significant differences for these measurement values between the left and right pubovisceral muscles (p = 0.271–0.931). However, radial kurtosis was greater than axial kurtosis in both pubovisceral muscles (p < 0.001) and axial diffusivity was lower than radial diffusivity in both pubovisceral muscles (p < 0.001). We deem the application of DKI technology to the pelvic floor region to be feasible. 相似文献
Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway. 相似文献
Ecotoxicology - Soil heavy metal pollution evaluations are a necessary measure for mine ecological control projects. In this study, the heavy metals Pb, Zn and Cd were studied in mining areas,... 相似文献