Cathepsin S deficiency results in abnormal accumulation of autophagosomes in macrophages and enhances Ang II-induced cardiac inflammation

Background

Cathepsin S (Cat S) is overexpressed in human atherosclerotic and aneurysmal tissues and may contributes to degradation of extracellular matrix, especially elastin, in inflammatory diseases. We aimed to define the role of Cat S in cardiac inflammation and fibrosis induced by angiotensin II (Ang II) in mice.

Methods and Results

Cat S-knockout (Cat S^−/−) and littermate wild-type (WT) C57BL/6J mice were infused continuously with Ang II (750 ng/kg/min) or saline for 7 days. Cat S^−/− mice showed severe cardiac fibrosis, including elevated expression of collagen I and α-smooth muscle actin (α-SMA), as compared with WT mice. Moreover, macrophage infiltration and expression of inflammatory cytokines (tumor necrosis factor α, transforming growth factor β and interleukin 1β) were significantly greater in Cat S^−/− than WT hearts. These Ang II-induced effects in Cat S^−/− mouse hearts was associated with abnormal accumulation of autophagosomes and reduced clearance of damaged mitochondria, which led to increased levels of reactive oxygen species (ROS) and activation of nuclear factor-kappa B (NF-κB) in macrophages.

Conclusion

Cat S in lysosomes is essential for mitophagy processing in macrophages, deficiency in Cat S can increase damaged mitochondria and elevate ROS levels and NF-κB activity in hypertensive mice, so it regulates cardiac inflammation and fibrosis.     

Levels of Hexachlorocyclohexanes and Dichloro-Dipheny-Trichloroethanes in Penguin Droppings Collected from Ardley Island,Maritime Antarctic

This article reports the concentrations of hexachlorocyclohexanes (HCHs) and dichloro-diphenyl-trichloroethanes (DDTs) in fresh Gentoo penguin (Pygoscelis Papua) droppings deposited on the Ardley Island (62°13′S, 58°56′W), West Antarctica, and those in the island's two lake cores. In the fresh penguin droppings, metabolites were the predominant constituents of the DDT group, most likely due to the ban on DDT use in agriculture and the higher stability of the metabolites in the environment. In contrast, γ-HCH comprised 66% of the total HCHs, apparently due to the continuous use of Lindane in the Southern Hemisphere. The concentrations of HCHs and DDTs in the fresh droppings are many times higher than those in penguin plume, the latter currently being used as biomaterial for monitoring coastal contaminations in Antarctica. Results of this study indicate that penguin droppings have a good potential for use as another biomonitoring material in detecting the organochlorine pesticides and other contaminants in the maritime Antarctic. Because penguin droppings can be well preserved in lake sediments, they also provide a good and continuous historical record of these contaminants. The slight increase of DDTs since the 1990s, as observed in the aged penguin droppings in the sediment cores, suggests there have been new inputs of DDT into the Antarctic coastal ecosystem, probably from the illegal use of DDT in the Southern Hemisphere.     

Clinical,Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

BackgroundThe second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.MethodsFive patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.ResultsFour patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).ConclusionExpectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.     

应用生物法合成内酯化合物

内酯是广泛存在于自然界中具有生物活性的一类化合物。由于大多数内酯化合物具有手性,用化学方法合成不仅过程复杂,而且产率也不高。利用酶反应的特异性,应用生物法合成内酯化合物具有很好的应用前景,其中包括微生物次生代谢合成内酯,脂肪酸生物转化合成内酯和脂肪酶在有机相中催化羟基脂肪酸形成内酯。本文报道这些领域的进展。     

The myocardial response to adrenomedullin involves increased cAMP generation as well as augmented Akt phosphorylation

In this work we aimed to observe (1) the changes in adrenomedullin (AM) and its receptor system - calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) - in myocardial ischemic injury and (2) the response of injuried myocardia to AM and the phosphorylation of Akt to illustrate the protective mechanism of AM in ischemic myocardia. Male SD rats were subcutaneously injected with isoproterenol (ISO) to induce myocardial ischemia. The mRNA levels of AM, CRLR, RAMP1, RAMP2 and RAMP3 were determined by RT-PCR. Protein levels of Akt, phosphor-Akt, CRLR, RAMP1, RAMP2 and RAMP3 were assayed by Western blot. Results showed that, compared with that of the controls, ISO-treated rats showed lower cardiac function and myocardial injury. The mRNA relative amount of AM, CRLR, RAMP1, RAMP2 and RAMP3 in the myocardia of ISO-treated rats was increased. The elevated mRNA levels of CRLR, RAMP1, RAMP2 and RAMP3 were positively correlated with AM content in injured myocardia. The protein levels of CRLR, RAMP1, RAMP2 and RAMP3 in injured myocardia were increased compared with that of control myocardia. AM-stimulated cAMP generation in myocardia was elevated in the ISO group, and was antagonized by AM(22-52) and CGRP(8-37). Western blot analyses revealed that AM significantly enhanced Akt phosphorylation in injured myocardia, which was blocked by pretreatment with AM(22-52) or CGRP(8-37). Ischemia-injured myocardia hyper-expressed AM and its receptors - CRLR, RAMP1, RAMP2 and RAMP3 - and the response of ischemic myocardia to AM was potentiated, and the level of Akt phosphorylation was also increased, which suggests that changes in cardiac AM/AM receptor might play an important role in the pathogenesis of myocardial ischemic injury.     

Diagnostic Performance of Echocardiography for the Detection of Acute Cardiac Allograft Rejection: A Systematic Review and Meta-Analysis

Objective

Many studies have addressed the diagnostic performance of echocardiography to evaluate acute cardiac allograft rejection compared with endomyocardial biopsy. But the existence of heterogeneity limited its clinical application. Thus, we conducted a comprehensive, systematic literature review and meta-analysis for the purpose.

Methods

Studies prior to September 1, 2014 identified by Medline/PubMed, EMBASE and Cochrance were examined by two independent reviews. We conducted meta-analysis by using Meta-DiSc 1.4 software. An assessment tool of QUADAS-2 was applied to evaluate the risk of bias and applicability of the studies.

Results

Thirty studies met the inclusion criteria of meta-analysis. The four parameters of pressure half time, isovolumic relaxation time, index of myocardial performance and late diastolic mitral annular motion velocity were included in the meta-analysis, with a pooled diagnostic odds ratio of 10.43, 6.89, 15.95 and 5.68 respectively, and the area under the summary receiver operating characteristic curves value of 0.829, 0.599, 0.871 and 0.685 respectively.

Conclusion

The meta-analysis and systematic review demonstrate that no single parameter of echocardiography showed a reliable diagnostic performance for acute cardiac allograft rejection. A result of echocardiography for ACAR should be comprehensively considered by physicians in the context of clinical presentations and imaging feature.     

双季稻田冬季种植模式对土壤有机碳和碳库管理指数的影响

为探讨冬季覆盖作物还田对稻田土壤碳库的影响,通过冬季种植油菜、紫云英、黑麦草、马铃薯,并以冬闲为对照进行大田试验,测定了不同冬季作物模式下早稻和晚稻的土壤有机碳、活性有机碳含量,并计算了稳态碳、碳库活度、活度指数、碳库指数和土壤碳库管理指数.结果表明:冬季作物还田增加了土壤有机碳含量,早稻和晚稻后的土壤有机碳含量比对照分别提高了1%～8%和3%～18%;油菜、黑麦草和紫云英还田均促进了土壤活性有机碳含量的增加,早稻后增加16.2%～84.2%,晚稻后增加24.4%～28.1%;冬季作物还田增加了土壤碳库管理指数,增加幅度为1.4%～41.8%.综上所述,冬种作物还田有利于提高土壤的固碳效应,并提升土壤质量,以种植黑麦草、紫云英的综合效果较佳.