Tanshinone IIA protects rat primary hepatocytes against carbon tetrachloride toxicity via inhibiting mitochondria permeability transition

Tanshinone IIA (Tan IIA), one of the key components of Salvia milthorrhiza Bunge (Lamiaceae), is used to treat liver disease. The present study was carried out to investigate the possible mechanisms involved in the hepatoprotective effects of Tan IIA on carbon tetrachloride (CCl₄)-induced hepatocyte toxicity. In cultures treated with 1 or 2 μM CCl₄, Tan IIA (10–75 μM) significantly increased hepatocyte survival rates. However, only at a concentration of 75 μM could Tan IIA partially reverse the CCl₄ (3 μM)-induced decrease of survival rate (34?±?3% vs. 18?±?3%, n?=?8, p?<?0.01). In isolated mitochondria energized with succinate, Tan IIA could inhibit the large swelling effect induced by CCl₄ (1 and 2 μM). Base on these results, Tan IIA could protect rat primary cultured hepatocytes from CCl₄-induced toxicity partially by the inhibitory effect on the opening of mitochondrial permeability transition (MPT).     

Exploring the longitudinal association between interventions to support the transition to secondary school and child anxiety

School transition at around 11-years of age can be anxiety-provoking for children, particularly those with special educational needs (SEN). The present study adopted a longitudinal design to consider how existing transition strategies, categorized into cognitive, behavioral or systemic approaches, were associated with post-transition anxiety amongst 532 typically developing children and 89 children with SEN. Multiple regression analysis indicated that amongst typically developing pupils, systemic interventions were associated with lower school anxiety but not generalized anxiety, when controlling for prior anxiety. Results for children with SEN differed significantly, as illustrated by a Group × Intervention type interaction. Specifically, systemic strategies were associated with lower school anxiety amongst typically developing children and higher school anxiety amongst children with SEN. These findings highlight strategies that schools may find useful in supporting typically developing children over the transition period, whilst suggesting that children with SEN might need a more personalized approach.     

Hemodynamic support of the micropreemie: Should hydrocortisone never be left out?

Hemodynamic support for a micropreemie is critically important for preventing mortality and morbidity. An essential consideration in hemodynamic support is insufficient transition from fetal to neonatal circulation and inadequate cortisol production. The first 72 h of life are the most critical, especially when myocardial function is immature and impaired. Therefore, there is a need to determine and adjust preload, myocardial contractility, and afterload appropriately using repeated functional echocardiography. In addition, if myocardial function is not responsive to these attempts at hemodynamic management, hydrocortisone must be used to minimize the suboptimal perfusion burden. Fetal cortisol production is supported by a supply of progesterone from the placenta, and postnatally, adrenal cortisol production in the extremely preterm infant may be inadequate if the infant is placed under excessive stress. This leads to relative adrenal insufficiency which may last for up to several weeks after birth and lead to late-onset circulatory collapse, necessitating treatment with physiological doses of hydrocortisone.     

The Impact of Age of Transfer on Outcomes in the Transition From Pediatric to Adult Health Systems: A Systematic Review of Reviews

PurposeInternational guidance on health-care transition has existed for over a decade; however, many unanswered questions remain. This systematic review of reviews aimed to answer the question: is a later age of transfer from pediatric to adult health care associated with improved health and health service outcomes?MethodsWe included systematic reviews which considered at least one long-term condition and provided outcome data from adult services. Methodology of primary studies was not an exclusion criterion. We searched multiple databases and conducted an initial search in May 2015 which was repeated in May 2017. All reviews were assessed for quality using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) tool. Reviews that scored less than 22 were excluded.ResultsInitial searches identified 6,149 papers. Forty-three reviews met exclusion and inclusion criteria, and 15 reviews also met quality criteria. With one exception, primary studies from reviews which only considered quantitative evidence found that a delayed age of transfer resulted in improved outcomes. Qualitative and mixed-methods evidence supported the view that age 18 was an appropriate time of transfer.ConclusionWe found moderate evidence that models of transition which transfer young people in late adolescence or early adulthood can improve transition outcomes and patient satisfaction.     

LncRNA Linc00152靶向miR-193a-3p对胃癌细胞增殖、侵袭和迁移的影响

目的 探讨LncRNA Linc00152靶向调控miR-193a-3p对胃癌细胞增殖、侵袭和迁移的影响。方法 采用qRT-PCR法检测正常胃黏膜细胞GES-1及4种胃癌细胞(MGC803、BGC803、SGC7901、AGS)中Linc00152的表达水平。MGC-803细胞分为pcDNA3.1-GFP-Linc00152组、pcDNA3.1-GFP组;AGS细胞分为si-Linc00152组、si-NC组,分别转染相应的Linc00152过表达和抑制载体。qRT-PCR法检测Linc00152、细胞周期素D1(cyclin D1,CCND1)和miR-193a-3p基因的表达水平,CCK-8检测细胞的活性,细胞克隆试验检测细胞的克隆能力,Annexin VFITC/PI染色后采用流式细胞术检测转染细胞凋亡率,Transwell法检测细胞侵袭,荧光素酶报告试验检测Linc00152和miR-193a-3p靶向关系,Western blotting检测Bcl-2、Bax、CCND1、E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)的蛋白表达水平。并将si-Linc00152组、si-NC组细胞接种裸鼠,观察裸鼠体质量和一般状态,处死后称重记录肿瘤体积、质量,qRT-PCR法测定肿瘤组织Linc00152、CCND1和miR-193a-3p的表达水平。结果 与GES-1细胞相比,胃癌细胞MGC803、BGC803、SGC7901、AGS中Linc00152的表达升高,其中Linc00152在胃癌MGC803细胞中表达较低,而在胃癌AGS细胞中的表达较高,选用胃癌MGC803、AGS细胞进行后续试验。与pcDNA3.1-GFP组相比,pcDNA3.1-GFP-Linc00152组细胞的活性显著升高,克隆能力增强,细胞凋亡减少,侵袭能力显著上升,CCND1、Bcl-2、波形蛋白的表达显著升高,miR-193a-3p和E-钙黏蛋白的表达显著降低。双荧光素酶报告基因系统检测结果显示,Linc00152可直接调控miR-193a-3p的转录活性,且Linc00152可显著上调MGC-803细胞CCND1蛋白表达。与si-NC组相比,si-Linc00152组的裸鼠体内的异种移植瘤体积和体质量显著下降,CCND1和Linc00152的表达显著下降,miR-193a-3p的表达显著上升。结论 Linc00152可靶向作用于miR-193a-3p促进胃癌细胞增殖、侵袭和迁移,其作用机制与细胞周期、上皮细胞间充质转化以及细胞凋亡有关。     

Targeting the MET pathway for potential treatment of NSCLC

Introduction: The mesenchymal-epithelial transition (MET) protein is the only known receptor for hepatocyte growth factor and has recently been identified as a novel promising target in several human cancers, including NSCLC. Activation of the MET signaling pathway can occur via different mechanisms. A number of compounds targeting MET have been evaluated in clinical trials, and recent clinical data have begun to afford some insight into the tumor types and patient populations that might benefit from treatment with MET pathway inhibitors.

Areas covered: We review recent publications and information disclosed at public conferences and summarize the epidemiology of dysregulation of MET signaling, and the associations thereof with other driver genes and therapeutic inhibitors useful to treat NSCLC.

Expert opinion: The MET pathway is emerging as a target for advanced NSCLC that is either resistant to EGFR tyrosine kinase inhibitors or that arises de novo. MET inhibitors currently being evaluated in clinical trials have yielded compelling evidence of clinical activities when used to treat various solid tumors, especially NSCLC. Remaining challenges are the identification of patient populations who might benefit from the use of MET inhibitors, and the most effective diagnostic methods for such patients.