CD4+ CD25+ GARP+ regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4⁺ T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4⁺   CD25⁺ GARP⁺ regulatory T (Treg) cells in DCM. Forty‐five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon‐γ (IFN‐γ), interleukin (IL‐17)], and an obvious decrease in Treg number, transforming growth factor‐β₁ (TGF‐β₁) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4⁺ CD25⁺ GARP⁺ Treg cells was impaired in DCM patients upon T‐cell receptor stimulation detected using CFSE dye. Lower level of TGF‐β₁ and higher levels of IFN‐γ and IL‐17 detected using ELISA were found in supernatants of the cultured CD4⁺ CD25⁺ GARP⁺ Treg cells in DCM patients compared with controls. Together, our results indicate that CD4⁺ CD25⁺ GARP⁺ Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.     

The effect of combined CJZ3, a lomerizine derivative,with verapamil on P‐glycoprotein efflux function in vitro

In the effort to inhibit P‐glycoprotein (P‐gp) efflux function with greater activity and less side effect, the combined effect of pair CJZ3 and verapamil (Ver) was evaluated isobolographically in numerous fixed‐ratio combinations of 1:1, 1:2, 1:4, 1:8, 1:10 in doxorubicin‐resistant human myelogenous leukemia (K562/ DOX) cells and in rat brain microvessel endothelial cells (RBMEC). The results displayed that mixtures of both drugs at the fixed‐ratios of 1:2, 1:4, 1:8, 1:10 exerted synergistic interactions, indicating that when the two reversers that bind P‐gp on separated sites were combined, each can contribute to the overall interaction with P‐gp, leading to the greater effect than that given by either agent alone. Drug Dev Res 72: 305–309, 2011. © 2010 Wiley‐Liss, Inc.     

Protective effect of Tanreqing injection on axon myelin damage in the brain of mouse model for experimental autoimmune encephalo- myelitis

OBJECTIVE： To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis（EAE）.METHODS： An EAE model was established by myelin oligodendrocyte glycoprotein（MOG）35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups： normal, model,prednisone acetate（PA）（6 mg/kg）, Tanreqing high dose（5.14 m L/kg）, Tanreqing low dose（2.57 m L/kg）. On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy（TEM）. Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS： Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION： Tanreqing injection alleviates EAE symptoms.     

血小板特异性受体糖蛋白Ⅰb与Ⅳ的研究进展

血小板于机体止凝血过程中发挥至关重要作用.随着对出凝血疾病相关研究的逐步深入,大量相关研究结果证实,血小板特异性受体糖蛋白(GP)Ⅵ与GPⅠb-Ⅸ-Ⅴ复合物中的主要配体结合亚基GPⅠb,在血小板生理功能,如血栓与止凝血过程中起重要调节作用,其表达水平或功能异常与诸多出凝血疾病发生相关.深入研究血小板特异性受体GPⅠ b与GPⅥ的调节机制,有助于评估或预测相关疾病患者出凝血倾向,对指导临床治疗具有重要现实意义.笔者拟就血小板特异性受体GPⅠ b与GPⅥ结构、功能、调节机制及其在出凝血疾病中的临床意义进行综述.     

Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy

Transforming growth factor β (TGF- β) signaling pathway has pleiotropic effects on cell proliferation, differentiation, adhesion, senescence, and apoptosis. TGF-β can be widely produced by various immune or non-immune cells and regulate cell behaviors through autocrine and paracrine. It plays essential roles in biological processes including embryological development, immune response, and tumor progression. Few cell signalings can contribute to so many pleiotropic functions as the TGF- β signaling pathway in mammals. The significant function of TGF-β signaling in tumor progression and evasion leading it to draw great attention in scientific and clinical research. Understanding the mechanism of TGF- β signaling provides us with chances to potentiate the effectiveness and selectivity of this therapeutic method. Herein, we review the molecular and cellular mechanisms of TGF-β signaling in carcinomas and tumor microenvironment. Then, we enumerate main achievements of TGF-β blockades used or being evaluated in cancer therapy, providing us opportunities to improve therapeutical approaches in the tumor which thrive in a TGF-β-rich environment.