RESUMO
OBJECTIVE: To investigate the effects of Salvianolic-acid B on p38MAPK signaling pathway and its transcriptional factor activated by Transforming growth factor b1 in rat hepatic stellate cells. METHODS: Hepatic stellate cells were isolated from normal rat by in situ perfusion and Nycodenz density-gradient centrifugation method.TGFb1 (10 ng/ml), PD98059(50 mumol/L), SB203580(10 mumol/L) and SA-B (10-6 mol/L) were directly added to the medium of the isolated HSCs. Groups: (1)The detection of total p38, MKK3/6, MEF2A and MEF2C induced by TGFb1 in HSC: include control group, SA-B group, SA-B+TGFb1 group and TGFb1 group. (2)The detection of the phosphorylation of p38, MKK3/6 and a-SMA induced by TGFb1 in HSC: include control group, SA-B group, SA-B+TGFb1 group, TGFb1 group, PD98059 group, PD98059+SA-B group, PD98059+TGFb1 group and SA-B+PD98059+TGFb1 group. (3)The effects of SA-B on activity of MEF2 reporter and collagen a 1(I) reporter induced by TGFb1 in HSC: include mt group, wt group, TGFb1 group, SA-B+TGFb1 group, SA-B group, SB203580+TGFb1 group and SB203580 group. Total and phosphorylated p38 and MKK3/6, MEF2A, MEF2C and a-SMA were assayed by Western blot. HSCs were transfected with either MEF2 or collagen a1(I) luciferase reporter gene by Lipofectamine 2000 transfection method, Cellular extracts were assayed for both MEF2 and collagen a1(I) luciferase activities. Comparisons between groups were performed with Student-Newman-Keuls test. RESULTS: The relative expression level of the phosphorylation of p38 of SA-B group is 0.33+/-0.05,obviously lower than control group(q=7.08, P less than 0.01); SA-B+TGFb1 group is 0.46+/-0.04, obviously lower than TGF b1 group(q=10.45, P less than 0.01); The relative expression level of the phosphorylation of MKK3/6 of SA-B group is 0.11+/-0.07, obviously lower than control group(q=3.944, P less than 0.05); SA-B+TGF b1 group is 0.28+/-0.07, obviously lower than TGFb1 group (q=7.91, P less than 0.01); The relative luciferase activity of MEF2 reporter of SA-B+TGFb1 group and SB203580+TGF b1 group is 2.93+/-0.09 and 2.50+/-0.05 respectively, both obviously lower than TGFb1 group(q=35.35 and 37.2, P less than 0.01); The relative expression level of MEF2C and MEF2A of SA-B group is 15.82+/-0.97 and 13.00+/-0.40 respectively, obviously lower than control group(q is 5.18 and 13.32, both P less than 0.01); SA-B+TGF b1 group is 13.40+/-0.72 and 20.47+/-0.83 respectively, obviously lower than TGFb1 group(q is 43.93 and 12.52,both P less than 0.01); The relative expression level of a-SMA of SA-B+TGFb1 group is 8.76+/-0.44, obviously lower than TGFb1 group(q=20.35, P less than 0.01); SA-B+SB203580+TGFb1 group is only 3.57+/-0.49, obviously lower than TGFb1 group(q=39.78, P less than 0.01); The relative luciferase activity of collagen a1(I) reporter of SA-B+TGF b1 group and SB203580+TGFb1 group is 1.61+/-0.05 and 1.42+/-0.07 respectively, obviously lower than TGFb1 group(q=26.4 and 27.62, both P less than 0.01). CONCLUSION: SA-B could inhibit activation of HSC induced by TGFb1 through inhibiting p38MAPK signaling pathway in hepatic stellate cells.
Assuntos
Benzofuranos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Animais , Células Cultivadas , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract. METHODS: Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants. RESULTS: A rare mutation, c.563G > A, in CRYBB2 gene was found in the proband that showed symptom of non-syndromic congenital autosomal dominant cataract. This mutation had been found in all affected individuals and in one healthy infant, but it did not exist between two individuals who did not develop such disease in that family, as well as in 100 healthy subjects who showed no relation with that family. Cataracts in this family varied with different severity of lens opacities and elongation of axial length. CONCLUSION: One missense mutation c.563G > A is reported in the CRYBB2 gene among one Chinese family suffering from early-onset cataract, and associated novel phenotypes are the elongation of axial length and the types of cataract. Our results expand the spectrum of associated phenotypes of CRYBB2 mutation.
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Catarata , Cadeia B de beta-Cristalina , Povo Asiático/genética , Catarata/genética , China/epidemiologia , Análise Mutacional de DNA , Genes Dominantes , Humanos , Mutação , Mutação de Sentido Incorreto , Linhagem , Cadeia B de beta-Cristalina/genéticaRESUMO
OBJECTIVE: The deletion of the short arm of chromosome 18 is thought to be one of the rare chromosomal aberrations. Here, we report a case to review this disease. CASE REPORT: The proband is a five-and-a-half-year-old girl who has had phenotypes manifested mainly by ptosis, broad face, broad neck with low posterior hairline, mental retardation, short stature, and other malformations. Chromosomal analysis for her mother showed a normal karyotype. Her father and younger brother were phenotypically normal. RESULT: Phenotypical features were quite similar throughout other cases and in accordance with the usual phenotype of del(18p) suggested within the same cases and among the del(18p) cases described. She underwent blepharoplasty, which improved her appearance. CONCLUSION: 18p deletion syndrome is diagnosed by gene analysis. Plastic surgeries for improving the appearance might be an option for these patients.
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BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma. METHODS: The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival. RESULTS: Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92-1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR = 1.84, 95% CI: 1.02-3.34), but not with survival of patients with Hodgkin disease (HD) (HR = 1.03, 95% CI: 0.74-1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value. CONCLUSIONS: This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression.
Assuntos
Linfoma/metabolismo , Linfoma/virologia , Proteínas da Matriz Viral/metabolismo , Intervalos de Confiança , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação , Análise de RegressãoRESUMO
We investigated the role of histone H3 phosphoacetylation in the nucleus accumbens (NAc) in heroin-conditioned place preference paradigm. Heroin could dose-dependently increase histone H3 phosphoacetylation specifically in the NAc and could enhance heroin place preference. Injection of trichostatin A into the NAc significantly augmented heroin-induced histone H3 phosphoacetylation and enhanced heroin place preference. Conversely, injection of MK-801 into the NAc attenuated histone H3 phosphoacetylation and reduced heroin place preference. These data suggest that histone H3 phosphoacetylation in the NAc may play a critical role in heroin addiction.