Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans

Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited.     

The role of human rhinovirus in immunology, COPD, and corresponding treatments

The common cold is most often a result of human rhinovirus (HRV) infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conversely, HRV may also infect the epithelial cells of the lower respiratory tract. Symptom severity associated with HRV infection ranges from mild to potentially serious depending on a person’s susceptibility and pre-existing condition, such as chronic obstructive pulmonary disease. An over active host immune response is believed to be the primary contributor to HRV pathogenesis. Enhanced activity of various host cell cytokines and granulocytes mediate specific cellular pathways inducing many of the symptoms associated with HRV infection. There are over 100 serotypes of HRV which can be further categorized based on the specific characteristics of each type. The two main categories of HRV consist of the major and minor groups. The unique host cell receptor is the distinguishing factor between these two groups. Yet, these viruses may also differ in mechanism of infection and replication. Due to the high frequency of hospital and clinical visits and the corresponding economic burden, novel therapies are of interest. Several different treatment options varying from herbal remedies to anti-viral drugs have been studied. However, the vast number of HRV serotypes complicates the progress of developing a universal treatment for attenuating HRV infection.     

Regulation of mitochondrial NAD pool via NAD+ transporter 2 is essential for matrix NADH homeostasis and ROS production in Arabidopsis

Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1), a plastid-localized enoyl-ACP reductase essential for de novo fatty acid biosynthesis in Arabidopsis thaliana, leads to the increased malate export from chloroplasts to mitochondria, and the subsequent accumulation of mitochondria-generated ROS and PCD. In this study, we report the identification and characterization of a mod1 suppressor, som592. SOM592 encodes mitochondrion-localized NAD~+ transporter 2(NDT2). We show that the mitochondrial NAD pool is elevated in the mod1 mutant. The som592 mutation fully suppressed mitochondrial NADH hyper-accumulation, ROS production, and PCD in the mod1 mutant, indicating a causal relationship between mitochondrial NAD accumulation and ROS/PCD phenotypes. We also show that in wild-type plants, the mitochondrial NAD+uptake is involved in the regulation of ROS production in response to continuous photoperiod. Elevation of the alternative respiration pathway can suppress ROS accumulation and PCD in mod1, but leads to growth restriction. These findings uncover a regulatory mechanism for mitochondrial ROS production via NADH homeostasis in Arabidopsis thaliana that is likely important for growth regulation in response to altered photoperiod.     

Design,synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers

A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.     

Effect of different iron loads on serum and tissue biochemical parameters and liver hepcidin mRNA abundance of neonatal piglets

Iron (Fe) is an essential and important trace element for animals. In order to study its metabolism and relationship with hepcidin, piglet models of Fe-deficiency and Fe-overload were established by intramuscular injection with different doses of Fe-dextran (150 mg Fe/ml) within 1 week of age. Twelve piglets were divided into three groups of four animals: deficiency, regular and overload group, receiving 0 ml, 1 ml and 6 ml Fe-dextran, respectively. The piglets were euthanised at the age of 7 days for analysis. The results showed that the Fe-concentrations in liver, spleen and serum of piglets in the overload group were higher than in the regular and deficiency groups (p < 0.05). In the overload group, several serum biochemical parameters, e.g. globulin, total bilirubin, total cholesterol, high density lipoprotein (HDL), malondialdehyde, glutathione peroxidase (GPx), peroxidase and xanthine oxidase were higher, while alkaline phosphatase (AKP) and triglycerides were lower, compared with the regular group (p < 0.05). The serum concentrations of AKP, total bilirubin and peroxidase in the deficiency group were lower, while HDL and GPx were higher, compared with the regular group (p < 0.05). Hepcidin mRNA abundance was 131 times lower in the liver of piglets with Fe-deficiency, and 7 times higher in the overloaded group than that in the regular group (p < 0.05). In conclusion, Fe-overload and deficiency would influence Fe-metabolism, serum biochemical indexes, oxidation state and hepcidin mRNA abundance in piglet liver.