The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

No abstract

Anterior cerebral artery A1 segment hypoplasia is an uncommon fetal variant of the circle of Willis. The frequency of this congenital variation is 1–13% as derived from angiograms and autopsy reports. Impaired collateral blood flow through the circle of Willis is a recognized risk factor for ischemic stroke. The A1 segment of the anterior cerebral artery is a principal supplier of anterior collateral blood flow. The aim of our study was to determine whether A1 segment hypoplasia may be responsible for acute ischemic stroke. We consecutively examined 280 acute ischemic stroke patients (aged 66.9 ± 14.2 years). Cerebral magnetic resonance angiography was performed within 72 h of ischemic stroke onset. The overall incidence of A1 variation in our experimental group was 15.0% (n = 42, agenesis/hypoplasia = 18/24), which was statistically higher than in the control group (n = 12). The majority (n = 30, 71.42%) had ipsilateral striatal lacunar infarctions. Based on our results, A1 agenesis/hypoplasia appears to be a risk factor contributing to ischemic stroke, especially to strokes in arteries penetrating the striatal area.

No abstract

Weak grip strength is associated with subsequent mortality in elderly populations. the normative data and associated factors of HGS in community-dwelling elderly taiwanese populations require further evaluation. From February 2012 until the end of 2016, all residents of Yilan City, Taiwan aged 65 years or older were randomly selected for a population-based community health survey. A total of 2,470 older adults were enrolled in this study. the relationships between HGS and various anthropometric and sociodemographic correlates were examined. the results showed that HGS was higher in men than in women. the mean HGS exhibited a decreasing trend with advanced age in both men and women. HGS was significantly associated with height, weight, and exercise habits. The physical as well as the mental component summary measures of health-related quality of life (HRQoL) were positively associated with HGS. After HRQoL was integrated into the regression model, female sex, age, waist circumference, and diabetes mellitus were significantly negatively associated with HGS. In conclusion, HGS significantly decreased with advanced age. among community-dwelling taiwanese elderly people, Various factors had different effects on HGS.