Assessment of postural stability in women with hip osteoarthritis: A case–control study

Objective

The aim of the study was to assessment the impact of hip osteoarthritis on postural stability.

富脯氨酸蛋白11 在食管癌组织中的表达及其对TE-2 细胞恶性生物学行为的影响

目的：探讨富脯氨酸蛋白11（PRR11）在食管癌组织中的表达及其在体外对人食管癌TE-2 细胞侵袭和迁移能力的影响。方法：选取2016 年10 月至2018 年10 月郑州大学第二附属医院胸外科经病理确诊为食管癌患者80 例，收集其手术切除的食管癌组织及相应的癌旁组织标本。用qPCR检测食管癌组织或细胞系中PRR11 mRNA的表达水平，Log-rank Test 法分析食管癌组织中PRR11 mRNA的表达与患者一般资料、组织学分级、淋巴结转移、浸润深度及TNM分期的关系，Kaplan-Meier 曲线分析法分析PRR11 mRNA与食管癌患者预后的关系。以慢病毒shRNA表达载体感染食管癌TE-2 细胞，构建敲低PRR11 的细胞系及相应的对照细胞系作为本研究的shPRR11#1、shPRR11#2 及对照组，qPCR及WB实验分别验证细胞株中PRR11 mRNA及蛋白的表达水平，MTT实验检测感染后细胞的增殖能力，Transwell 实验检测其侵袭和迁移能力。结果：PRR11 mRNA在食管癌组织中的表达高于癌旁组织（P<0.05），PRR11 mRNA的过表达与食管癌的组织学分级、淋巴结转移、浸润深度及TNM分期均显著相关（均P<0.05），PRR11 高表达与食管癌患者预后不良显著相关（P<0.05）；shPRR11#1、shPRR11#2 组细胞中PRR11 mRNA及蛋白表达显著低于对照组细胞（P<0.05 或P<0.01）。shPRR11#1、shPRR11#2 组细胞的增殖能力低于对照组（P<0.05 或P<0.01），Transwell侵袭及迁移实验结果显示，shPRR11#1、shPRR11#2 组平均每个视野内细胞数均显著低于对照组（P<0.01）。结论：PRR11 高表达于食管癌组织中，与食管癌的发生、进展及患者预后密切相关；体外实验也证明了敲低PRR11 表达可以抑制食管癌的增殖、侵袭和迁移能力，是潜在的食管癌靶标。     

Metformin use and endometrial cancer survival

Objective

Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC).

Methods

We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan–Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided.

Results

Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p = 0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p < 0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed.

Conclusion

Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.     

A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein

P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. The diphenylpropylamine opioids methadone and loperamide are structurally similar, but loperamide has about a 4-fold higher Pgp-mediated transport rate. In addition to these differences, they showed significant differences in their effects on Pgp-mediated adenosine triphosphate (ATP) hydrolysis. The activation of Pgp-mediated ATP hydrolysis by methadone was monophasic, whereas loperamide activation of ATP hydrolysis was biphasic implying methadone has a single binding site and loperamide has 2 binding sites on Pgp. Quenching of tryptophan fluorescence with these drugs and digoxin showed competition between the opioids and that loperamide does not compete for the digoxin-binding site. Acrylamide quenching of tryptophan fluorescence to probe Pgp conformational changes revealed that methadone- and loperamide-induced conformational changes were distinct. These results were used to develop a model for Pgp-mediated transport of methadone and loperamide where opioid binding and conformational changes are used to explain the differences in the opioid transport rates between methadone and loperamide.     

The Influence of In Vivo Metabolic Modifications on ADMET Properties of Green Tea Catechins–In Silico Analysis

The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B.     

Electroreduction of methyl viologen in the presence of nitrite. Its influence on enzymatic electrodes

The electroreduction of methyl viologen (MV) in the presence of nitrite was studied by cyclic voltammetry. A catalytic wave for the reduction of MV²⁺ was observed at ?0.740 V for which an EC catalytic mechanism is proposed. The rate constant for this chemical reaction under pseudo-first-order conditions, evaluated using working curves, was employed in the simulation of the voltammetric response. The second-order rate constant was also evaluated. Influences of the reaction at ?0.800 V on enzymatic electrodes employing nitrate reductase (NR) and MV⁺ as mediator were also analysed by chronoamperometry.