L-Carnitine inhibits the senescence-associated secretory phenotype of aging adipose tissue by JNK/p53 pathway.

Senescence-associated secretory phenotype (SASP) plays a role in aging adipose tissue dysfunction by directly promoting chronic inflammation. The JNK/p53 pathway was reported as a potential mechanism that mediates SASP. In this study, we investigated the effects of L-carnitine, an inhibitor of the JNK/p53 pathway in adipose tissue SASP and dysfunction. Young and aging rat were given L-carnitine by gavage. Next, we detected the senescence, cytokines expression, chronic inflammation and insulin resistance of adipose tissue. Additionally, JNK/p53 pathway was estimated. Our results show a significant increase expression of SASP components in the adipose tissue of aging rats compared to young rats. Further, we found that infiltration of immune cells and the expression of pro-inflammatory cytokines were enhanced in aging adipose tissue while insulin signaling activity was reduced in aging adipose tissue. Interestingly, L-carnitine markedly reduced the expression of SASP factors. L-Carnitine could significantly reduce chronic inflammation, improving insulin resistance. Further, L-carnitine inhibited SASP by inhibiting JNK/p53 pathway. L-Carnitine inhibited SASP by JNK/p53 pathway and attenuated adipose tissue dysfunction of aging.

Role of the CHADS2 Score in the Evaluation of Carotid Atherosclerosis in Patients with Atrial Fibrillation Undergoing Carotid Artery Ultrasonography.

OBJECTIVE: This study investigated the characteristics of carotid atherosclerosis in patients with atrial fibrillation (AF) and determined the feasibility and significance of the CHADS2 score in predicting the degree of carotid atherosclerosis. METHODS: Consecutive patients (n = 109) with nonvalvular AF were registered and classified into two groups, the paroxysmal AF group (n = 59) and persistent AF group (n = 50). Fifty healthy patients, matched by sex and age, were considered the control group. All patients were examined using carotid ultrasound and velocity vector imaging (VVI). RESULTS: Compared with the control group, the mean intimal-medial thickness in the paroxysmal AF group (0.56 ± 0.11 versus 0.61 ± 0.10, respectively, P < 0.05) and the persistent AF group (0.56 ± 0.11 versus 0.64 ± 0.13, respectively, P < 0.001) was significantly increased. The plaque index (PI) in the persistent AF group was significantly higher than that observed in the paroxysmal AF group (1.05 ± 1.33 versus 1.42 ± 1.47, respectively, P < 0.001). Regarding the VVI indices, those reflecting the long-axis longitudinal motion function of carotid arteries were significantly decreased in both AF groups. Compared with the control group, a significantly lower total longitudinal displacement (tLoD) index was observed in the persistent AF group (0.73 ± 0.66 versus 0.31 ± 0.23, respectively, P < 0·0001) and the paroxysmal AF group (0.73 ± 0.66 versus 0.34 ± 0.17, P < 0·0001). The CHADS2 score was related to indicators reflecting the structure and function of the carotid artery. CONCLUSIONS: Carotid arterial structure and function were significantly altered in patients with AF. The degree of carotid atherosclerosis depended on the duration of AF. The CHADS2 score may be useful as a predictor of the extent of carotid atherosclerosis in patients with AF.

RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.

BACKGROUND: Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application. RESULTS: Forty short hairpin RNA (shRNA) expression plasmids were constructed to target conserved regions among nine HBV genotypes. HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with shRNA plasmids into either Huh7 cells or mice. The levels of various viral markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376, B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA, surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in mice. No unusual cytotoxicity or off-target effects were noted. CONCLUSIONS: Such siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising advances in the treatment of HBV.