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.     

miR-301b在调节脂肪细胞分化中的作用

摘要： 目的 研究 miR-301b 在调节间充质干细胞向脂肪细胞分化过程中的作用。方法 对小鼠骨髓基质细胞 ST2 进行脂肪细胞诱导分化, 并利用 qRT-PCR 检测细胞分化过程中成脂分化诱导组相对于阴性对照组的 miR-301b 表达变化。对 ST2 细胞转染 miR-301b mimics 并进行成脂诱导分化, 利用 qRT-PCR 和 Western blot 技术检测 miR- 301b mimics 转染组和阴性对照片段 （NC） 转染组细胞的脂肪特异性基因和蛋白表达水平的变化。结果 成脂分化诱导组 miR-301b 相对表达水平 （0.219±0.021） 较对照组 （1.000±0.425） 减少 （P＜0.05）。miR-301b mimics 转染组的脂肪细胞特异性转录因子过氧化物酶体增殖物激活受体 （PPARγ）、 CCAAT 增强子结合蛋白 （C/EBPα） 和脂肪型脂肪酸结合蛋白 （aP2） 的相对表达量均较 NC 转染组降低 （P＜0.05）。miR-310b mimics 转染组与 NC 转染组相比, 标志基因aP2、 转录因子PPARγ 和C/EBPα 蛋白的表达量均减少 （P＜0.05）。结论 miR-301b可抑制脂肪细胞分化。     

Protein kinase C isoforms in atherosclerosis: Pro- or anti-inflammatory?

Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future.     

Effect of soft tissue mobilization techniques on adhesion-related pain and function in the abdomen: A systematic review

ObjectiveTo systematically review the effects of soft tissue mobilization (STM) on both surgical and non-surgical abdominal adhesion-related symptoms.Study designSystematic Review.BackgroundIt is known that abdominal adhesions can cause a variety of symptoms with one of the most common being abdominal pain. To date, there is no known systematic review that documents the effects of STM on adhesion-related abdominal symptoms.Methods and measuresA systematic review of literature was indexed in the following databases: PubMed, Cochrane, Google Scholar, OVID, and EBSCO. The quality of the studies was assessed using the MINORS scale.ResultsNine studies satisfied the eligibility criteria for this systematic review. The studies' population age ranged from 10.7 to 89.4 years. Four articles were nonrandomized and had scores ranging from 3 to 14 out of 16 total on the MINORS scale. Five articles were randomized controlled trials or comparative studies and scores ranged from 16 to 23 out of 24 total on the MINORS scale. There were five articles that used pain as an objective measure and all of them reported a decrease in pain after treatment. Two studies looked at quality of life and function and both saw objective improvements following abdominal adhesion treatment. Collectively, there were also improvements seen in scar mobility, infertility, posture, a reduction in medication, increased pressure tolerance and decreased postoperative ileus.ConclusionThe results of this review indicate preliminary strong evidence for the benefits of STM on symptoms relating to acute post-surgical adhesions, preliminary moderate evidence for the benefits of STM on symptoms relating to chronic non-surgical related adhesions (fertility and SBO) and moderate evidence for the benefits of STM on symptoms relating to chronic post-surgical adhesions.     

巨噬细胞移动抑制因子的表达与食管癌的临床病理指标的相关性

目的探讨巨噬细胞移动抑制因子（macrophage migration inhibitory factor,MIF）在食管癌组织中的表达与食管癌的临床病理指标的相关性,及其在肿瘤发生中的可能作用。方法收集2010年1月—2012年9月间新疆医科大学第一附属医院经手术切除并存档的食管癌组织标本40例,癌旁组织标本20例。应用s—P免疫组化方法检测食管癌组织及癌旁食管上皮组织中MIF的表达情况。结果组织中MIF阳性表达在食管癌组明显高于癌旁组织组,差异有统计学意义（P〈0．05）;MIF的表达和肿瘤部位、肿瘤直径、病理类型、分化程度等均无明显相关（P〉0．05）,与食管癌患者的肿瘤浸润范围、淋巴结转移、远处转移、TNM分期有关（P〈0．05）。结论MIF在食管癌组织中高表达,与肿瘤的浸润范围、淋巴结转移、远处转移及TNM分期相关,MIF可以作为一种诊断食管黏膜癌变的免疫组织化学检测指标。     

核桃青皮提取物对食管癌细胞增殖的抑制作用及其分子机制的探讨

目的观察核桃青皮提取物对人食管癌细胞增殖的抑制作用.方法：用MTT法分别测定核桃青皮粗提物和核桃青皮提取物没食子酸、乙酸乙酯、紫杉叶素、7-D-芹菜糖-儿茶酚对食管癌细胞EC9706和KYSE150的增殖抑制率,并用Western Blot检测不同药物处理后食管癌细胞中细胞周期相关蛋白CyclinD1的蛋白表达.结果：核桃青皮粗提物、没食子酸和乙酸乙酯能抑制食管癌细胞的增殖,其作用呈明显剂量依赖性,当药物浓度增加至80 μg/mL时,对KYSE150的抑制率分别为82.75% 、90.51%、88.36%,对EC9706的抑制率分别为85.54% 、87.21%、85.17%.与对照组相比,3种药物均会显著抑制KYSE150和EC9706细胞中CyclinD1的表达.结论：核桃青皮提取物对食管癌细胞系的增殖有较强的抑制作用,其机制可能与引起细胞周期阻滞有关.     

The size‐dependent genotoxic potentials of titanium dioxide nanoparticles to endothelial cells

Despite intensive research activities, there are still many major knowledge gaps over the potential adverse effects of titanium dioxide nanoparticles (TiO₂‐NPs), one of the most widely produced and used nanoparticles, on human cardiovascular health and the underlying mechanisms. In the present study, alkaline comet assay and cytokinesis‐block micronucleus test were employed to determine the genotoxic potentials of four sizes (100, 50, 30, and 10 nm) of anatase TiO₂‐NPs to human umbilical vein endothelial cells (HUVECs) in culture. Also, the intracellular redox statuses were explored through the measurement of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. Meanwhile, the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) were also detected by western blot. The results showed that at the exposed levels (1, 5, and 25 μg/mL), all the four sizes of TiO₂‐NPs could elicit an increase of both DNA damage and MN frequency in HUVECs in culture, with a positive dose‐dependent and negative size‐dependent effect relationship (T100 < T50 < T30 < T10). Also, increased levels of intracellular ROS, but decreased levels of GSH, were found in all the TiO₂‐NP‐treated groups. Intriguingly, a very similar manner of dose‐dependent and size‐dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also elevated in the TiO₂‐NP‐exposed HUVECs, with an inversely size‐dependent effect relationship. These findings indicated that induction of oxidative stress and subsequent genotoxicity might be an important biological mechanism by which TiO₂‐NP exposure would cause detrimental effects to human cardiovascular health.