Fucoxanthin Enhances Cisplatin-Induced Cytotoxicity via NFκB-Mediated Pathway and Downregulates DNA Repair Gene Expression in Human Hepatoma HepG2 Cells

Cisplain, a platinum-containing anticancer drug, has been shown to enhance DNA repair and to inhibit cell apoptosis, leading to drug resistance. Thus, the combination of anticancer drugs with nutritional factors is a potential strategy for improving the efficacy of cisplatin chemotherapy. In this study, we investigated the anti-proliferative effects of a combination of fucoxanthin, the major non-provitamin A carotenoid found in Undaria Pinnatifida, and cisplatin in human hepatoma HepG2 cells. We found that fucoxanthin (1–10 μΜ) pretreatment for 24 h followed by cisplatin (10 μΜ) for 24 h significantly decreased cell proliferation, as compared with cisplatin treatment alone. Mechanistically, we showed that fucoxanthin attenuated cisplatin-induced NFκB expression and enhanced the NFκB-regulated Bax/Bcl-2 mRNA ratio. Cisplatin alone induced mRNA expression of excision repair cross complementation 1 (ERCC1) and thymidine phosphorylase (TP) through phosphorylation of ERK, p38 and PI3K/AKT pathways. However, fucoxanthin pretreatment significantly attenuated cisplatin-induced ERCC1 and TP mRNA expression, leading to improvement of chemotherapeutic efficacy of cisplatin. The results suggest that a combined treatment with fucoxanthin and cisplatin could lead to a potentially important new therapeutic strategy against human hepatoma cells

Violations of the weak cosmic censorship conjecture in the higher dimensional f(R)f(R) black holes with pressure

We adopt the energy momentum relation of charged particles to study the thermodynamics laws and weak cosmic censorship conjecture of $D$-dimensional $f(R)$ AdS black holes in different phase spaces by considering charged particle absorption. In the normal phase space, it turns out that the laws of thermodynamic and the weak cosmic censorship conjecture are valid. In the extended phase space, though the first law of thermodynamics is valid, the second law of thermodynamics is invalid. More interestingly, the weak cosmic censorship conjecture is shown to be violated only in higher-dimensional near-extremal $f(R)$ AdS black holes. In addition, the magnitudes of the violations for both the second law and weak cosmic censorship conjecture are dependent on the charge $Q$, constant scalar curvature $f'(R_0)$, AdS radius $l$, dimension parameters $p$, and their variations.Comment: Accepted by Eur. Phys. J.

Transient analysis for hypersonic inlet accelerative restarting process

A three-dimensional computational fluid dynamics code that solves the unsteady compressible Reynolds-averaged Navier–Stokes equations was used to investigate the transient accelerative restarting processes of a planar hypersonic inlet. The characteristics of the accelerative restarting process were analyzed, and they revealed that the wall pressure time histories could be used to monitor whether the hypersonic inlet restarted. In addition, the effects of acceleration and flight trajectories on the transient accelerative process were studied. The results showed that the process of the disappearance of the separation bubble was delayed as the acceleration was increased. As a result, the corresponding flight Mach number at which the inlet restarted increased accordingly. The unsteady simulation results also indicated that the trajectory had great impact on the accelerative restarting process

Psychosocial determinants of depression in the community of the elderly with cardiovascular disease

The co-morbidity of cardiovascular disease (CVD) and depression is quite frequent in old people, and some potential biological and behavioural mechanisms linking them have been reported. Yet the impact of psychosocial factors on depression in the elderly with CVD remains unclear. This study aimed to analyze the psychosocial determinants of depression in the elderly with CVD. Using the Geriatric Mental Status-Automated Geriatric Examination for Computer Assisted Taxonomy, a community-based household survey was performed in 2,199 elderly people from the Anhui cohort third-wave survey from 2007 to 2009 and an extended study in Hubei from 2010 to 2011. Multiple logistic regression analyses were employed to assess the influence of psychosocial factors on depression. Among them, the prevalence of depression was 4.77%. Three factors were associated with depression in elderly in the community: self-assessed physical health status, anything else severely upsetting and unpleasantness with relatives, friends, or neighbors. In particular, associations of psychosocial factors with depression were more evident in individuals with CVD. This study confirms several psychosocial determinants of depression and the impact of CVD on the associations among the elderly, which provides some clues for interventional strategies of late-life depression

Cigarette Smoke Extract Stimulates Rat Pulmonary Artery Smooth Muscle Cell Proliferation via PKC-PDGFB Signaling

Accumulating evidence suggests a direct role for cigarette smoke in pulmonary vascular remodeling, which contributes to the development of pulmonary hypertension. However, the molecular mechanisms underlying this process remain poorly understood. Platelet-derived growth factor (PDGF) is a potential mitogen and chemoattractant implicated in several biological processes, including cell survival, proliferation, and migration. In this study, we investigated the effect of cigarette smoke extract (CSE) on cell proliferation of rat pulmonary artery smooth muscle cells (rPASMCs). We found that stimulation of rPASMCs with CSE significantly increased cell proliferation and promoted cell cycle progression from G1 phase to the S and G2 phases. CSE treatment also significantly upregulated the mRNA and protein levels of PDGFB and PDGFRβ. Our study also revealed that Rottlerin, an inhibitor of PKCδ signaling, prevented CSE-induced cell proliferation, attenuated the increase of S and G2 phase populations induced by CSE treatment, and downregulated PDGFB and PDGFRβ mRNA and protein levels in rPASMCs exposed to CSE. Collectively, our data demonstrated that CSE-induced cell proliferation of rPASMCs involved upregulation of the PKCδ-PDGFB pathway