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Objective@#To identify the disease-causing mutations in a pedigree with familial hypertrophic cardiomyopathy (HCM) from Yunnan province, and analyze the relationship between the genotype and the phenotype.@*Methods@#The blood samples and the clinical data of the HCM family members were collected.The coding exons and their flanking intronic regions of 28 previously reported genes related to HCM were screened in the proband by high-throughput sequencing. The mutations in proband were confirmed and detected in all family members as well as in 159 healthy controls by Sanger sequencing.The relationship between the genotype and the phenotype was analyzed in this pedigree.@*Results@#Two missense mutations of Arg1045His and Ala26Val in β myosin heavy chain gene(MYH7) were identified. Genetic screening showed that the mother and brother of the proband carried Arg1045His mutation.Both mutations were absent in other family members and in 159 healthy controls.Disease onset age was less than 50 years old in this pedigree, chest pain, exertional dyspnea and syncope were the major symptoms, and all accompanied by severe left ventricular hypertrophy and left ventricular outflow tract stenosis.The grandma of the proband suffered sudden cardiac death. The proband had the worst symptoms and the earliest disease onset in this pedigree.@*Conclusions@#We find a pedigree with familial HCM from Yunnan province carrying MYH7 Arg1045His and Ala26Val mutations. The study suggests that Arg1045His mutation in MYH7 gene caused HCM is malignant with early onset, severe ventricular hypertrophy and poor prognosis. Arg1045His and Ala26Val double-mutant might have dosage effects and aggravate the clinical phenotype of the patient.
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Allergic rhinitis is a kind of nasal mucosal chronic noninfectious inflammatory disease, which is caused by an imbalance in the body cytokine network,a number of intracellular signaling pathways being actived. Many studies have shown that mitogen-activated protein kinase (MAPK) involved in the activation process of allergic rhinitis. p38 mitogen-activated protein kinase (MAPK), as one kind of that, plays a key role in the process of inflammatory cells proliferation and differentiation, as well as production of inflammatory cytokines, and involved in airway inflammatory mechanisms of chronic airway disease. In vitro experiments have confirmed that p38 MAPK inhibitors have anti-inflammatory effect by blocking the downstream related response.
Subject(s)
Humans , Cell Differentiation , Cell Proliferation , Cytokines , Inflammation , MAP Kinase Signaling System , Rhinitis, Allergic , Metabolism , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
Objective To evaluate the effect of total glucosides of paeony (TGP) on the expression of interleukin-18 (IL-18) in human HaCaT keratinocytes,and to explore the roles of extracelluar signal-regulated protein kinase1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) signaling pathways in the effect.Methods Some cultured human HaCaT keratinocytes were classified into three groups:control group treated with dimethyl sulfoxide (0.031％),TGP groups treated with 6 different concentrations (0.5,2.5,12.5,62.5,125.0 and 312.5 mg/L) of TGP respectively,inhibitor groups treated with TGP of 125 mg/L after 2-hour pretreatment with PD98059 (an ERK1/2 inhibitor) and SP600125 (a JNK1/2 inhibitor) of 10 μmol/L respectively.After additional culture for 48 hours,reverse transcription (RT)-PCR was performed to measure the mRNA expression level of IL-18,and enzymelinked immunosorbent assay (ELISA) to determine the level of IL-18 protein in the culture supematant of HaCaT cells.Some HaCaT keratinocytes were classified into two groups to be treated with TGP of 125 mg/L for 15,30 and 60 minutes with or without the pretreatment with PD98059 and SP600125 of 10 μmol/L; then,Western blot was carried out to determine the phosphorylation levels of ERK1/2 and JNK1/2 in HaCaT cells.Results The levels of IL-18 mRNA and protein in culture supernatant were significantly increased by TGP of 0.5 and 2.5 mg/L,but decreased by TGP of 62.5 and 125.0 mg/L,and TGP of 125.0 mg/L showed the strongest inhibitory effect.After treatment with TGP of 125.0 mg/L,the level of phosphorylated ERK1/2 in HaCaT cells peaked at 15 minutes (0.448 ± 0.018),decreased to 0.213 ± 0.005 at 30 minutes and 0.217 ± 0.005 at 60 minutes,with significant differences between TGP-treated and untreated cells at 15 minutes (0.448 ± 0.018 vs.0.204 ± 0.005,P＜ 0.05) but not at 30 or 60 minutes (both P ＞ 0.05).The phosphorylation level of ERK1/2 was 0.237 ± 0.010 in HaCaT cells pretreated with PD98059 prior to the treatment with TGP,significantly different from that in HaCaT cells treated with TGP only (P ＜0.01).TGP of 125.0 mg/L had no obvious effect on JNK phosphorylation,and there was no significant difference in the level of phosphorylated JNK1/2 between HaCaT cells untreated and those treated with TGP of 125.0 mg/L for different durations (all P ＞ 0.05).Conclusions TGP can inhibit the expression of IL-18 mRNA and protein in HaCaT cells,likely through the ERK1/2 signaling pathway.
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Objective To assess the clinical efficacy of direct Stenting (DS) and conventional post-dilation stenting (CS) for A and B1 lesions in Patients with coronary artery disease.Methods Demographic characters, final baloon dilation pressure, instent angiographic results, and long term outcomes were compared between patients receiving DS (n=62) and patients receiving CS(n=51). Results The operation time in DS group was much shorter than that in CS group ( 17.2 ?8.6 min vs 26.3 ?7.1 min, P