Progress in neuregulin/Erb B signaling and chronic heart failure

Heart failure is one of the leading causes of death today.It is a complex clinical syndrome in which the heart has a reduced contraction ability and decreased viable myocytes.Novel approaches to the clinical management of heart failure have been achieved through an understanding of the molecular pathways necessary for normal heart development.Neuregulin-1(NRG-1) has emerged as a potential therapeutic target based on the fact that mice null for NRG-1 or receptors mediating its activity,Erb B2 and Erb B4,are embryonic lethal and exhibit severe cardiac defects.Preclinical studies performed with animal models of heart failure demonstrate that treatment with NRG-1 significantly improves heart function and survival.Clinical data further support NRG-1 as a promising drug candidate for the treatment of cardiac dysfunction in patients.Recent studies have revealed the mechanism underlying the therapeutic effects of NRG-1/Erb B signaling in the treatment of heart failure.Through activation of upstream signaling molecules such as phosphoinositide 3-kinase,mitogen-activated protein kinase,and focal adhesion kinase,NRG-1/Erb B pathway activation results in increased c MLCK expression and enhanced intracellular calcium cycling.The former is a regulator of the contractile machinery,and the latter triggers cell contraction and relaxation.In addition,NRG-1/Erb B signaling also influences energy metabolism and induces epigenetic modification in cardiac myocytes in a way that more closely resembles healthy heart.These observations reveal potentially new treatment options for heart failure.

Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults

Objective:To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination. Methods:Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination. Results:A total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoS-mithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ 2 =2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no sta- tistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t= 1.575, P=0.116). Conclusions:Domestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.