Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Objective To investigate the relationship of interleukin-18(IL-18) and IL-18 antibody(IL-18Ab) in the adriamycin(ADR)-induced model of minimal change nephritic syndrome(MCNS).Methods Thirty rats were divided randomly into 3 groups:normal control group,non-treatment group and treatment group.Wistar rats were induced to the model of MCNS by single injection of ADR(6.5 mg·kg-1) though tail vena.The rats in non-treatment group and normal control group were induced by injection of equal volume of physiological saline solution.Urine protein was measured on the 1st,14th,28th and 42nd day.Serum total cholesterol(TC),triacylglycerol(TG),serum total protein(TP),albumin(Alb),urea nitrogen(BUN),creatinine(SCr),IL-18,interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α) were analyzed when all rats were sacrificed on the 42nd day after the first injection of ADR.Expressions of IL-18,IFN-γ and TNF-α in kidney were analyzed with immunohistochemistry and the renal histological changes were observed under light microscope and electron microscope.Results Proteinuria appeared in the second week and had peak concentration in the fourth week.Proteinuria in control group was significantly low on the 14th,28th,42nd day(Pa0.05),and that in treatment group was lower than non-treatment group on the 28th,42nd day(Pa0.05).Serum TC and TG in non-treatment group and treatment group were significantly higher than those in normal control group(Pa0.05),whereas those in treatment group were significantly lower than those in non-treatment group(P0.05).However,serum TP and Alb in non-treatment group and treatment group were significantly lower than those in normal control group(Pa0.05),whereas those in treatment group were significantly higher than those in non-treatment group(Pa0.05).In addition,the expressions of IL-18,IFN-γ and TNF-α in nephridial tissue and peripheral blood in non-treatment group and treatment group were markedly increased(Pa0.05),and those in treatment group were significantly decreased than those in non-treatment group(Pa0.05).Three groups had no obvious differences under light microscope.However,under electron microscope,non-treatment group had the prominent lesions while treatment group showed minimal change.Conclusions IL-18 may parti-cipate in the pathogenesy of proteinuria in the rats model of MCNS.The action was mediated by production of IFN-γ,TNF-α and IL-18Ab may have therapeutical effect to a certain degree.
Abstract Background: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. Methods: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein–protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues. Results: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan–Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results. Conclusion: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.
Our study was undertaken to evaluate the important role that a disintegrin and metalloproteinase 9 (ADAM9) regulates IL-6 trans-signaling in carbon tetrachloride (CCl4)-induced liver injury in mice. Mice were divided into four groups. Each group respectively received mineral oil injection, CCl4 injection, anti-ADAM9 monoclonal antibody (mAb) pretreatment and CCl4 injection, anti-ADAM9 mAb and recombinant mouse ADAM9 molecules pretreatment with CCl4 injection. Our results showed that anti-ADAM9 mAb pretreatment significantly aggravated liver injury, inhibited IL-6 trans-signaling, which led to downregulation of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), upregulation of Caspase3, cytochrome P450 2E1 (CYP2E1), and hepatocytes apoptosis at 24 h after CCl4 injection. Recombinant ADAM9 molecules pretreatment reversed the impact of anti-ADAM9 mAb pretreatment in mice. In conclusion, our study suggested that ADAM9 could regulate the hepatocytes proliferation, apoptosis, angiogenesis, and CYP2E1 expression by activating IL-6 trans-signaling and play important protective roles during CCl4-induced liver injury in mice.
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