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Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.
Subject(s)
Animals , Mice , Drugs, Chinese Herbal , Network Pharmacology , Orthomyxoviridae , Pneumonia/genetics , PulsatillaABSTRACT
Objective To investigate the relationship between hepatitis B surface antigen (HBsAg) levels and liver pathology at different phases of natural history in chronic hepatitis B (CHB) patients, and to establish a non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Methods A total of 145 CHB patients were enrolled and underwent liver biopsy from January 2013 to January 2015, among which 73 patients were hepatitis B e antigen (HBeAg) positive.HBsAg levels and HBV DNA levels were compared between patients at different phases of natural history and between patients with different HBeAg statuses.Logistic analysis was used to analyze the risk factors associated with fibrosis in HBeAg-positive patients, and to evaluate the predictive value of non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Analysis of variance was used for statistical analysis, and t test analysis was used for the comparison between two independent samples.Results The serum HBsAg levels at the immunologic tolerance phase, immunologic clearance phase, low copy phase and reactivation phase of CHB patients were (4.29±0.69), (3.56±0.61), (3.22±0.64), and (3.54±0.50) lg IU/mL, respectively (F=16.72, P<0.01), and the HBV DNA levels were (8.48±0.58), (6.69±1.44), (3.80±0.59), and (6.21±1.06) lg IU/mL, respectively (F=76.73, P<0.01).In HBeAg-positive CHB patients with liver inflammation stage (G)≤G1, G2, G3 and G4, the serum HBsAg levels were (4.44±0.65), (4.00±0.72), (3.74±0.62), and (3.28±0.50) lg IU/mL, respectively (F=9.198, P<0.01).In HBeAg-positive CHB patients with liver fibrosis stage (S)≤S1, S2, S3, and S4, the serum HBsAg levels were (4.55±0.54), (4.04±0.89), (3.59±0.63), and (3.34±0.50) lg IU/mL, respectively (F=10.66, P<0.01).Logistic analysis showed that age (OR=1.091, 95%CI: 1.013-1.175) and HBsAg level (OR=0.190, 95%CI: 0.066-0.542) were independent factors for predicting fibrosis stage.The area under receiver operating characteristic curve of the non-invasive fibrosis model based on age and HBsAg level was 0.849, which was higher than aspartate aminotransferase to platelet ratio index (0.749) and fibrosis index based on the 4 factors (0.763).Conclusions The serum HBsAg levels are significantly different among the different phases of natural history in CHB patients.The serum HBsAg levels decline with the progression of liver fibrosis in HBeAg-positive CHB patients.The non-invasive diagnostic model that based on HBsAg quantification could be used to evaluate the stage of liver fibrosis.
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Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.
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Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.
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Tetramethylpyrazine(TMP)is a main active alkaloid ingredient of Traditional Chinese Medicine Ligusticum chuanqiong Hort. The article reviews the protection of TMP against pathological damage and nervous retardation disease in central nervous and peripheral nervous system and summarizes the mechanisms in basic research,clinical practice and so on.