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Objective:To study the mechanism of Herba Hedyotidis against liver fibrosis based on network pharmacology. Methods:Based on TCMSP database and Uniprot database, the effective components and target genes of Herba Hedyotidis were screened. Target genes of liver fibrosis were screened by GeneCards and OMIM database, and the "disease-component-target" network map was constructed by Cytoscape 3.8.2 software. Protein interaction network was constructed by STRING database, and the Cytoscape 3.8.2 software was used to screen the core target out. The core targets were analyzed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Experimental verification was performed to the analysis results. A hepatic fibrosis model was established by intraperitioneal imjection of 40% carbon tetrachloride oil solution in rats that were then divided into the model control group and the Herba Hedyotidis group by randomized number table table, with 10 rats in each group. Ten normal rats were used as the normal control group. The Herba Hedyotidis group were injected 2.7 g/kg herb aqueous extract by intragastric administration, once a day, for 4 weeks; and the normal and model control group were given the same volume distilled water for gavage. The serum GPT, GOT, Alb and liver pathologic changes were observed. The serum expressions of IL-6, IL-1β and TGF-β1 were detected by ELISA. The expressions of PI3K, Akt, HIF-1α and VEGF were detected by Western blot. Results:5 effective components and 118 targets of Herba Hedyotidis in the treatment of hepatic fibrosis were obtained. Stigmasterol, β-sitosterol and quercetin were the most effective components with high moderate value. The moderate targets were VEGF, EGFR, HIF-1α and IL-6. The core genes of PPI network were HIF-1α, IL-6, etc. GO enrichment analysis showed that RNA transcription, protein binding and other processes may be affected. KEGG pathway enrichment analysis showed that significant enrichment pathways were cancer pathway, hepatitis B pathway, PI3K/Akt, HIF pathway and so on. Animal experimental results showed that compared with model group, liver histopathology was improved significantly, the content of GPT, GOT, IL-6, IL-1β and TGF-β1 decreased ( P<0.01), the content of Alb increased ( P<0.01), and the protein expressions of PI3K, Akt, HIF-1α and VEGF in liver tissue were down-regulated ( P<0.01). Conclusion:The Herba Hedyotidis exerts functions of anti-hepatic fibrosis through acting on the targets of VEGF, EGFR, HIF-1α and IL-6, regulating the PI3K/Akt, HIF-1 pathways, and has anti-inflammatory, anti-angiogenesis, anti-tumor and other biological functions.
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@#Management of complicated massive infective endocarditis (IE) in patients who are contraindicated for surgical valve replacement has long been a dilemma for many clinicians. Studies have shown that massive IE patients who were treated conservatively generally result in poorer prognosis. We report two cases of massive native valve infective endocarditis with severe mitral valve regurgitation and septic emboli that has been successfully treated conservatively. Interestingly, despite having a large vegetation and multiple septic emboli complications, none of these two cases had any positive culture or serology. Managing culture negative IE without surgical intervention pose an even greater challenge to the choice and duration of antibiotics with further long-term plans. We hope to share these case series to aid in the management dilemma of similar cases in the future.
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OBJECTIVE@#To explore the mechanism of catgut embedding at back- points on nonalcoholic steatohepatitis (NASH) in rats based on IKK/IKB/NF-κB signaling pathway and downstream inflammatory factors.@*METHODS@#Eighty SPF SD rats were selected, among them 10 rats were selected divided into a normal group (group A), and the remaining 70 rats were fed with high-fat diet to establish NASH model. At the end of 12 weeks, 10 rats were randomly selected to verify whether the model establishment was successful. Then the remaining 60 rats were randomly divided into a model group (group B), a catgut embedding at back- points group (group C), a catgut embedding at abdominal points group (group D), an acupuncture at back- points group (group E), a sham catgut embedding group (group F) and a western medication group (group G), 10 rats in each group. The rats in the group C were treated with catgut embedding at "Ganshu" (BL 18), "Pishu" (BL 20), "Weishu" (BL 21) and "Shenshu" (BL 23); the rats in the group D were treated with catgut embedding at "Daheng" (SP 15), "Fujie" (SP 14), "Huaroumen" (ST 24) and "Tianshu" (ST 25); the rats in the group E were treated with acupuncture at the same acupoints as the group C; the rats in the group F were treated with catgut embedding at back- points but the needle did not enter subcutaneous tissue gamma; the rats in the group G were treated with intragastric administration of vitamin E capsule. All the treatment was given for 4 weeks. The rats in the group A were fed with normal diet until the end of 16 weeks without any intervention. The rats in the group B continued to be fed with high-fat diet until the end of 16 weeks. After the intervention, the liver index was calculated; the liver histomorphology was observed by HE staining; the liver function [alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GGT), alkaline phosphatase (ALP)] and blood lipid [serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)] were measured by serum biochemistry. The serum levels of TNF-α, IL-6 and IL-1βwere detected by ELISA, and the expressions of IKK-α, NF-κBp65, IL-6, IL-1β and TNF-α proteins in liver tissue were detected by Western blot. The temperature of the conception vessel and the governor vessel was measured by infrared thermography.@*RESULTS@#Compared with the group A, the obvious steatosis and inflammatory cell infiltration were observed in the group B, and the body weight, liver wet-weight and liver index were all increased (0.05), while the temperature of the governor vessel in the group C was superior to that in the group D (<0.05).@*CONCLUSION@#The catgut embedding at back- points might inhibit the activation of IKK/IKB/NF-κB signaling pathway to interrupt the inflammatory cascade, and reduce the "second hit" of inflammatory factors on liver, which could slow down NASH progress and prevent and treat NASH.
Subject(s)
Animals , Rats , Acupuncture Points , Catgut , NF-kappa B , Non-alcoholic Fatty Liver Disease , Rats, Sprague-Dawley , Signal TransductionABSTRACT
To investigate the effects and mechanism of andrographolide(Andro)on type II diabetic nephropathy in Leprdb/dbmice,levels of urinary protein,serum creatinine and blood urea nitrogen after 24 h of Andro(1 mg/kg,ip)treatment on Leprdb/dbmice were measured by kit.The changes on renal pathology and sugar levels in diabetic mice treated by Andro were observed by HE staining and PAS staining.The expression of fibronectin (FN)and NOX-4 protein were analyzed by immunofluorescence.Results showed that levels of urinary protein, serum creatinine and blood urea nitrogen in Leprdb / dbmice after Andro treatment for 24 h were significantly lower than those of the control group. Kidney pathologic change was inhibited, and FN and NOX-4 expression were markedly decrease in the Andro group.In conclusion,Andro can significantly reduce the diabetic nephropathy in Leprdb/dbmice with spontaneous type II diabetes mellitus.
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<p><b>OBJECTIVE</b>This investigation aimed to examine how buccal mucosa microbiome succeeds in a healthy population with different ages and dentition stages.</p><p><b>METHODS</b>Twenty-five subjects were recruited and subdivided into five groups: primary dentition group, mixed dentition group, adolescent group, adult group, and elderly group. Individual mucosal microbiota was obtained by gently scraping both sides of the buccal mucosa with a cotton swab. Microbial diversity was analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE).</p><p><b>RESULTS</b>1) The composition of buccal mucosa microbiota has great intra-individual divergence. 2) The average band numbers of the primary dentition group, mixed dentition group, adolescent group, adult group, and elderly group were 21.2 +/- 4.0, 17.8 +/- 3.9, 15.8 +/- 4.3, 16.8 +/- 3.7, and 22.2 +/- 6.5, respectively. No between-group differences was observed (P > 0.05), indicating that predominant strains in the oral cavity may be stable throughout an individual's lifetime. 3) The Shannon indices of primary dentition group, mixed dentition group, adolescent group, adult group, and elderly group were 1.73 +/- 10.2, 1.43 +/- 0.1, 1.05 +/- 0.2, 1.45 +/- 0.2, and 1.63 +/- 0.3, respectively. A significant between-group difference was observed (P = 0.003), indicating that the microbial diversity of the buccal mucosa decreases from childhood through adolescence, but increases from adult through senescence. 4) The clustering analysis showed that most of the samples in the same group clustered together, indicating higher intra-group community structure similarity.</p><p><b>CONCLUSION</b>Composition of the buccal mucosa microbiota was different among age groups. Adolescence may be an essential turning point of microbial ecology succession throughout life.</p>
Subject(s)
Adolescent , Adult , Aged , Humans , DNA, Bacterial , Microbiota , Mouth Mucosa , Polymerase Chain Reaction , RNA, Ribosomal, 16SABSTRACT
Children, especially those younger than 5 years of age and those with chronic medical conditions, such as respiratory diseases, neurological diseases, immunosuppression, receiving longterm aspirin therapy, obesity or co-infection with bacteria, are at an increased risk of pandemic H1N1 infection-related complications. This paper reviews the underlying medical conditions associated with death or complications of pandemic H1N1 infection in children.