Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis

Introduction

Metabolic syndrome is associated with increased risk of cardiovascular events, which contributes to the elevated mortality rate among liver transplant recipients. The objective of this systematic review and meta-analysis was to assess the prevalence and risk factors for metabolic syndrome after liver transplantation.

A quantitative structure-activity approach for lipophilicity estimation of antitumor complexes of different metals using microemulsion electrokinetic chromatography

Microemulsion electrokinetic chromatography (MEEKC) offers a valuable tool for the rapid and highly productive determination of lipophilicity for metal-based anticancer agents. In this investigation, the MEEKC technique was applied for estimation of n-octanol-water partition coefficient (logP(oct)) of a series of antiproliferative complexes of gallium(III) and iron(III) with (4)N-substituted α-N-heterocyclic thiosemicarbazones. Analysis of relationships between the experimental logP(oct) and the retention factors of compounds showed their satisfactory consistency in the case of single metal sets, as well as for both metals. Since none of available calculation programs allows for evaluating the contribution of central metal ion into logP(oct) (i.e. ΔlogP(oct)) of complexes of different metals, this parameter was measured experimentally, by the standard 'shake-flask' method. Extension of the logP(oct) programs by adding ΔlogP(oct) data resulted in good lipophilicity predictions for the complexes of gallium(III) and iron(III) included in one regression set. Comparison of metal-thiosemicarbazonates under examination in terms of logP(oct) vs. antiproliferative activities (i.e. 50% inhibitory concentration in cancer cells) provided evidence that their cytotoxic potency is associated with the ability to cross the lipid bilayer of the cell-membrane via passive diffusion.     

Cyr61在人肿瘤组织中的表达

目的观察分析富含半胱氨酸61(cysteine-rich61,Cyr61)在人类肿瘤组织中的表达情况。方法采用HE染色、免疫组化的方法检测多组织肿瘤组织芯片和30例肿瘤组织标本(包括食管癌、胃癌、直肠癌、肺癌、乳腺癌和肝癌组织标本各5例)中Cyr61的表达。结果组织芯片中79%(38/48)的肿瘤组织Cyr61表达阳性,93%(28/30)肿瘤组织标本中Cyr61表达阳性。其中神经、食管和甲状腺等肿瘤组织中呈强阳性表达,胃、肝、结肠、直肠、肺、肾、子宫、皮肤、卵巢、乳腺等组织的肿瘤呈阳性表达,在膀胱、前列腺和胰腺等肿瘤组织中表达较弱。结论Cyr61在多数肿瘤组织中均过表达,在不同肿瘤组织中表达程度不同,Cyr61可能成为新的肿瘤标志物应用于多种肿瘤的诊断。     

CCN family proteins and angiogenesis: from embryo to adulthood

The CCN family is a novel class of extracellular signal modulators that has been recently established. Typical members are composed of four conserved modules connected tandem, each of which is rich in cysteines and highly interactive with other molecules. The mammalian CCN family consists of six members, most of which have been described as multifunctional factors for the developmental process of mesenchymal tissue including blood vessel formation/induction. Particularly, the angiogenic properties of the three classical members, CCN1, 2 and 3 have so far been characterized, and their physiological and pathological significance has thus been indicated. Recent research has uncovered a unique mechanism regarding these proteins in promoting and/or modulating developmental, physiological and pathological angiogenic events. Namely, CCN proteins exert their ability to drive angiogenesis, not by stimulating a particular behavior of a particular type of cells, but by manipulating the cell communication networks that integrate most of the associated molecules/cells toward angiogenesis. In this article, the role of the CCN proteins in a variety of angiogenic events as an organizer of microenvironmental cell society is comprehensively described, together with a brief summary of the recent findings on each CCN family member relevant to angiogenesis including cardiovascular development and diseases.     

Levofloxacin pharmacokinetics in adult cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. METHODS: Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. RESULTS: When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC(24)), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 microg x h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 microg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC(24)/MIC ratio. CONCLUSION: CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (>/= 750 mg); and establish PK/PD targets for managing PA pulmonary infections.     

Arecoline stimulated Cyr61 production in human gingival epithelial cells: inhibition by lovastatin

Cyr61 is associated with growth and progression of many types of tumors and is an independent poor prognostic indicator for oral cancer patients. Areca nut (AN) chewing is the most important etiological factor in the pathogenesis of oral cancer in India and many Southeast Asian countries. Yet, the molecular mechanisms involved in the AN-induced oral cancer remain largely unknown. In this study, we show that arecoline, a main alkaloid found in AN, stimulated Cyr61 synthesis in human gingival epithelial S-G cells. Constitutive overexpression of Cyr61 protein in oral epithelial cells during AN chewing may play a role in the pathogenesis of oral cancer. ERK inhibitor PD98059, N-acetyl-L-cysteine, Rho-associated protein kinase (ROCK) selective inhibitor Y-27632 and a geranylgeranyltransferase inhibitor reduced the arecoline-stimulated levels of Cyr61 protein by ～31%, 47%, 65% and 100%, respectively. Lovastatin also completely inhibited arecoline-induced Cyr61 synthesis and the inhibition is dose-dependent. Decreased of geranylgeranylated proteins could be the mechanism that lovastatin regulates Cyr61 synthesis and lovastatin could serve as a useful agent in controlling AN-induced oral cancer.     

细胞基质蛋白Cyr61和CTGF在子痫前期发病中的作用

目的:检测细胞基质蛋白Cyr61和CTGF在重度子痫前期患者胎盘组织中的定位及表达,研究它们在子痫前期发病中的作用。方法:采用免疫组化SP法和实时荧光定量聚合酶链式反应(quantitative real time polymerase chain reaction,real-time PCR)方法检测胎盘组织中Cyr61和CTGF的表达,其中重度子痫前期患者34例,正常妊娠16例。结果:(1)细胞基质蛋白Cyr61和CTGF在正常妊娠孕妇及重度子痫前期患者胎盘组织中均有表达;(2)Cyr61在重度子痫前期患者胎盘组织的表达水平低于正常妊娠孕妇胎盘(P<0.01);(3)CTGF在重度子痫前期患者胎盘组织的表达水平高于正常妊娠孕妇胎盘(P<0.05);(4)Cyr61和CTGF mRNA在重度子痫前期患者胎盘组织的表达水平呈负相关(P<0.01)。结论:Cyr61表达下调和CTGF过度表达与子痫前期的发病有关,并在该病的发病过程中起到一定的作用。     

Breaking Barriers: Mobile Health Interventions for Cardiovascular Disease

Cardiovascular disease (CVD) is a leading global cause of death and morbidity and prevention needs to be strengthened to tackle this. Mobile health (mHealth) might present a novel and effective solution in CVD prevention, and interest in mHealth has grown dramatically since the advent of the smartphone. In this review, we discuss mHealth interventions that target multiple cardiovascular risk factors simultaneously in the context of primary as well as secondary prevention. There is some evidence that mHealth interventions improve a range of individual CVD risk factors, but a relative paucity of evidence on mHealth interventions improving multiple CVD risk factors simultaneously. The existing data suggest mHealth programs improve overall CVD risk, at least in the short term. Interpretation of the evidence is difficult in the context of poor methodology and mHealth modalities often being a part of large complex interventions. In this review we identify a number of unanswered questions including: which mode of mHealth (or combination of interventions) would be most effective, what is the durability of intervention effects, and what degree of personalization and interactivity is required.