RESUMO
The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.
Assuntos
2',5'-Oligoadenilato Sintetase/genética , Variação Genética , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/genética , Hepatite B Crônica/patologia , Adulto , Povo Asiático , Etnicidade , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNAAssuntos
DNA/genética , Sequenciamento do Exoma/métodos , Proteínas de Transporte de Ácido Graxo/genética , Síndrome de Melkersson-Rosenthal/genética , Mutação , Biópsia , Análise Mutacional de DNA , Exoma , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Humanos , Masculino , Síndrome de Melkersson-Rosenthal/diagnóstico , LinhagemRESUMO
16 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-substituted phenylacetamide derivatives were synthesized. The chemical structures of the compounds were proved by IR, 1H-NMR, 13C-NMR, Mass spectrometric data and microanalyses. The antidepressant activities of the compounds were investigated by Porsolt's behavioural despair (the forced swimming test) in mice. 2-(5-bromo-2,3-dioxoi-ndolin-1-yl)-N-(2-fluorophenyl)acetamide(4f), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(3-chlorophenyl)acetamide(4j), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(4-bromophenyl)acetamide(4m) reduced 54.9-44.6% duration of immobility times at 100 mg · kg-1 dose level. Anticonvulsant activities were determined by substances pentylenetetrazloe(metrazol)(anti-PTZ) test, and neurotoxicities were determined by the rotarod toxicity test in mice. 12 synthesized compounds were found protective against PTZ at 100 mg â kg-1 dose level.
Assuntos
Acetanilidas/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Acetanilidas/síntese química , Acetanilidas/química , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Antidepressivos/síntese química , Antidepressivos/química , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Convulsões/tratamento farmacológico , Espectrofotometria Infravermelho , Relação Estrutura-Atividade , Testes de Toxicidade/métodosRESUMO
In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system.
Assuntos
Antidepressivos/síntese química , Chalconas/síntese química , Animais , Antidepressivos/farmacologia , Chalconas/farmacologia , Masculino , CamundongosRESUMO
In this study, a series of new 5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine derivatives was synthesized and their anticonvulsant activity and neurotoxicity was evaluated with the maximal electroshock and rotarod tests, respectively. The most promising compounds, 3p (5-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridine) and 3r (5-(4-bromophenoxy)-[1,2,4]triazolo[4,3-a]pyridine), showed a median effective dose of 13.2 and 15.8 mg/kg and had a protective index value of 4.8 and 6.9, respectively. For exploring the putative mechanism of action, compounds 3n, 3p and 3r were tested in chemically induced models.