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BACKGROUND: To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. METHODS: The week 12-34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 µg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. RESULTS: A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. CONCLUSIONS: Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.
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Antivirais/uso terapêutico , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Telbivudina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Estudos de Casos e Controles , DNA Viral/sangue , Feminino , Idade Gestacional , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated. OBJECTIVE: The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation. METHODS: In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting. RESULTS: A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed. CONCLUSION: SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.
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Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Animais , Camundongos , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Simulação de Acoplamento Molecular , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Background: Acute myeloid leukemia (AML) is one of the most common hematologic malignancies with a poor prognosis and high recurrence rate. The discovery of new predictive models and therapeutic agents plays a crucial role. Methods: The differentially expressed gene that was explicitly highly expressed in The Cancer Genome Atlas (TCGA) and GSE9476 transcriptome databases were screened and included in the least absolute shrinkage and selection operator (LASSO) regression model to derive risk coefficients and build a risk score model. Functional enrichment analysis was conducted on the screened hub genes to explore the potential mechanisms. Subsequently, critical genes were incorporated into a nomogram model based on risk scores to analyze prognostic value. Finally, this study combined network pharmacology to find potential natural compounds for hub genes and used molecular docking to verify the binding ability of molecular structures to natural compounds to explore drug development for possible efficacy in AML. Results: A total of 33 highly expressed genes may be associated with poor prognosis of AML patients. After LASSO and multivariate Cox regression analysis of 33 critical genes, Rho-related BTB domain containing 2 (RHOBTB2), phospholipase A2 (PLA2G4A), interleukin-2 receptor-α (IL2RA), cysteine and glycine-rich protein 1 (CSRP1), and olfactomedin-like 2A (OLFML2A) were found to played a significant role in the prognosis of AML patients. CSRP1 and OLFML2A were independent prognostic factors of AML. The predictive power of these 5 hub genes in combination with clinical features was better than clinical data alone in predicting AML in the column line graphs and had better predictive value at 1, 3, and 5 years. Finally, through network pharmacology and molecular docking, this study found that diosgenin in Guadi docked well with PLA2G4A, beta-sitosterol in Fangji docked well with IL2RA, and OLFML2A docked well with 3,4-di-O-caffeoylquinic acid in Beiliujinu. Conclusions: The predictive model of RHOBTB2, PLA2G4A, IL2RA, CSRP1, and OLFML2A combined with clinical features can better guide the prognosis of AML. In addition, the stable docking of PLA2G4A, IL2RA, and OLFML2A with natural compounds may provide new options for treating AML.
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OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.