Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.
The purpose of this study was to evaluate the predictors of pregnancy outcome for infertile couples attending in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) programmes. Infertile couples attending IVF or ICSI procedures were included in this study. Related data including semen parameters and male and female age and body mass index were collected and analysed. The main outcome was clinical pregnancy, defined as an ultrasound detection of foetal heartbeat 6 weeks after embryo transfer. A total of 1316 couples who underwent IVF and 266 who underwent ICSI were recruited for this study. A multivariate logistic regression with likelihood ratio test revealed the following predictors of pregnancy outcome: female age and sperm DNA fragmentation index (DFI) and acrosomal activity in IVF procedures (chi-square of likelihood ratio = 26.42, d.f. = 3, P < 0.005) and female age and DFI in ICSI procedures (chi-square of likelihood ratio = 18.88, d.f. = 2, P < 0.005). In conclusion, our study indicated that sperm DFI, female age and acrosomal levels have a significant effect on ART pregnancy outcome.
Identifying the degree of liver inflammation is critical for therapeutic judgement of patients with chronic hepatitis B (CHB). However, we lack indexes which can accurately predict significant liver inflammation in patients with CHB. This study aimed to develop a simple predictive index for liver inflammation in CHB using routine clinical parameters. A total of 519 patients with CHB who underwent liver biopsy were enrolled and randomly divided into training (n = 346) and validation cohorts (n = 173). Based on routine clinical parameters, gamma-glutamyl transpeptidase (GGT; P = 0.031) and platelets (PLT; P < 0.001) were identified as independent predictors of significant inflammation by multivariable analysis in the training cohort. Accordingly, the GGT to PLT ratio (GPR) was developed to amplify the opposing effects for predicting liver inflammation. In the training cohort, the AUCs of GPR in predicting significant inflammation were 0.791 (95% CI: 0.742-0.839), 0.783 (95% CI: 0.717-0.849) and 0.791 (95% CI: 0.716-0.867) in the entire patients with CHB, HBeAg-positive CHB patients and HBeAg-negative CHB patients, respectively. The diagnostic performance of GPR for significant inflammation was significantly superior to that of alanine aminotransferase (ALT), aspartate transaminase (AST) and GGT in all patients with CHB and HBeAg-positive CHB patients, but was comparable with ALT, AST and GGT in HBeAg-negative CHB patients. In the validation cohort, the diagnostic performance of GPR in assessing significant liver inflammation was also superior to other indexes in all patients with CHB and HBeAg-positive CHB patients, but was comparable with GGT in HBeAg-negative CHB patients. Thus, GPR can be a novel and simple index for predicting significant liver inflammation in CHB, especially for HBeAg-positive CHB.
Homocysteine is an amino acid that is produced from the metabolic demethylation of dietary methionine. It has gained arising attention for its association with increased risk of myocardial infarction, stroke and venous thromboembolism. Erectile dysfunction (ED), especially for vasculogenic ED, is a vascular disorder of cavernosal vascular bed. In this prospective pilot case-control study, we investigated plasma homocysteine levels in 32 ED patients and 20 healthy control men. Related patients characteristics including age, weight, height, marital status, smoking and drinking status, level of education were collected and analysed as well as penile colour Doppler ultrasound parameters. ED patients were further categorised into mild, moderate and severe ED based on 5-item of the International Index of Erectile Function. Higher homocysteine levels were observed in ED patients as compared with controls (p < .05). A multivariate logistic regression with likelihood ratio test revealed that homocysteine and penile peak systolic blood flow velocity (PSV) levels posed significant indicators for ED (chi-square of likelihood ratio = 20.42, df = 2, p < .005) as well as moderate and severe ED occurrence (chi-square of likelihood ratio = 28.50, df = 2, p < .005). The threshold value of homocysteine concentration to discriminate ED and control subjects was 12.65 μmol/L by performing receiver operating characteristic curve analyses. These data suggested that elevation of homocysteine levels was associated with an increased risk of ED.
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