CDH1 -160C>A gene polymorphism is an ethnicity-dependent risk factor for gastric cancer

The associations between E-cadherin (CDH1) gene polymorphisms and gastric cancer (GC) susceptibility are still controversial. Given this uncertainty, we carried out a meta-analysis of published case-control studies to derive more precise estimations of these relationships. Relevant studies were identified from PubMed and EMBASE up to March 2011. Seventeen studies with 3511 GC cases and 4826 controls were selected. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the associations. No associations between CDH1 (+54T>C, -160C>A, -347G>GA, -616G>C, -2076C>T and -3159T>C) gene polymorphisms and GC risk for all genetic models were found. As for CDH1 -160C>A polymorphism, subgroup analyses by country, gender, study design, smoking status, Helicobacter pylori infection, and the Lauren classification of GC did not change the results. When stratified by ethnicity, we found the A allele carriers had a significantly increased risk of GC among Caucasians (AA vs. CA+CC: OR=1.50, 95% CI=1.03-2.19, P=0.03), but not among Asians (AA vs. CA+CC: OR=0.87, 95% CI=0.56-1.37, P=0.56). No publication bias was found in the present study. This meta-analysis suggests that CDH1 -160C>A gene polymorphism may contribute to increased risk of GC among Caucasians.     

Atomic Layer Deposition of CdS Quantum Dots for Solid‐State Quantum Dot Sensitized Solar Cells

Functioning quantum dot (QD) sensitized solar cells have been fabricated using the vacuum deposition technique atomic layer deposition (ALD). Utilizing the incubation period of CdS growth by ALD on TiO₂, we are able to grow QDs of adjustable size which act as sensitizers for solid‐state QD‐sensitized solar cells (ssQDSSC). The size of QDs, studied with transmission electron microscopy (TEM), varied with the number of ALD cycles from 1‐10 nm. Photovoltaic devices with the QDs were fabricated and characterized using a ssQDSSC device architecture with 2,2',7,7'‐tetrakis‐(N,N‐di‐p methoxyphenylamine) 9,9'‐spirobifluorene (spiro‐OMeTAD) as the solid‐state hole conductor. The ALD approach described here can be applied to fabrication of quantum‐confined structures for a variety of applications, including solar electricity and solar fuels. Because ALD provides the ability to deposit many materials in very high aspect ratio substrates, this work introduces a strategy by which material and optical properties of QD sensitizers may be adjusted not only by the size of the particles but also in the future by the composition.     

Cholinergic Control of Nerve Growth Factor in Adult Rats: Evidence from Cortical Cholinergic Deafferentation and Chronic Drug Treatment

Abstract: It is well documented that nerve growth factor (NGF) plays an important role in maintaining functions of cholinergic basal forebrain neurons. In the present study, we tested the hypothesis that cholinergic activity controls NGF levels in cholinoceptive neurons of the cerebral cortex and hippocampus. To address that question, we used both cholinergic deafferentation of cerebral cortex and hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic pharmacological treatment of sham-treated and immunolesioned rats with the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We observed an increase in NGF protein levels in the cortex and hippocampus after cholinergic immunolesions and also after muscarinic receptor blockade by chronic intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks. There was no further increase in the accumulation of NGF after scopolamine treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced accumulation of NGF. There was no effect of cholinergic lesion and drug treatment on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF retrograde transport as opposed to its de novo synthesis. This study provides strong evidence for the hypothesis that there is cholinergic control of cortical and hippocampal NGF protein but not mRNA levels in adult rats.     

乳链菌肽的作用位点

乳链菌肽 (ｎｉｓｉｎ)是由乳酸乳球菌属乳酸亚种 (Ｌａｃｔｏｃｏｃｃｕｓｌａｃｔｉｓｓｕｂｓｐ .ｌａｃｔｉｓ)的某些菌株产生的一种抗菌多肽 ,对范围广泛的革兰氏阳性菌有极强的抑杀作用。它是一种多肽 ,很容易被人体消化酶分解成氨基酸而被人体吸收和利用 ,因此乳链菌肽作为食品防腐剂具有天然无毒的特点。人们一直都试图将乳链菌肽当做一种抗生素用于医疗方面 ,由于它易被人体消化酶分解和溶解度不高 ,以及在其它方面存在着一些缺陷 ,目前还不适于药用。近年来 ,很多致病菌对常见的抗生素产生了抗性 ,甚至有些菌对人们所能依靠的最后…     

A model study of interactions between TcAChE peripheral site segment Tyr70Val71 and loop 1 of Fasciculin 2

The continuous chain of residues (Thr7 to Ala12) of Loop1 of Fas2 (F1) and its interaction with the peripheral binding sites (Tyr70-Val71) of AChE (P1) has been studied. Our results suggest that the flexibility of Loop1 might be caused by either the partially protonated guanidine group of Arg11 under experimental conditions or by the interaction with the negatively charged center of substrates. The binding energy of F1-P1 is predicted to be -16.6 kcal/mol at the B3LYP/6-311G(d,p) level, which is assumed to originate from one isolated O7...HN10 H-bond, one possible O10...HC71 unconventional O...HC type H-bonding, and the improved pi-bonding cooperativity around the peptide group of the AChE segment Tyr70-Val71. The classical Kitaura-Morokuma energy decomposition analysis, the NPA charge analysis, and the AIM analysis consistently reveal that the peptide group in segment P1 is more polarizable, which might play the key role in the interactions between F1 and P1. The PCM solvent effect corrected results reveal decrease of the interaction energy of the considered model. The importance of Thr8 of Fas2 in the P-site binding of AChE is also concluded. Site-directed mutations on either the Fas2 residue of Thr8 or the AChE residue of Tyr70 are expected to alter the binding behavior of the Loop1 of Fas2 with AChE.     

20(S)-Protopanaxadiol Inhibition of Progression and Growth of Castration-Resistant Prostate Cancer

Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a decline in serum prostate-specific antigen levels as well as a decrease in AR levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were resistant to growth inhibition by the next-generation anti-androgen enzalutamide. The present study represents the first to show the preclinical efficacy of PPD in inhibiting castration-resistant progression and growth of prostate cancer. The findings provide a rationale for further developing PPD or its analogues for prostate cancer therapy.     

Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: A meta-analysis

Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. Results: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR = 1.20, 95% CI = 1.03–1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI = 1.09–1.58) and 1.03 in Asians (95% CI = 0.81–1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR = 1.13, 95% CI = 0.80–1.60, nonsmokers: OR = 0.99, 95% CI = 0.71–1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR = 1.50, 95% CI = 1.09–2.07), but not in colon cancer (OR = 1.33, 95% CI = 0.94–1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. Conclusion: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians.