心脏特异性高度表达的抗凋亡蛋白——ARC

与凋亡(apoptosis)相关的许多心脏疾病如心肌梗死、心肌病及心衰等严重威胁着人类的健康和生命.寻找有效手段防治这些心脏病是当前医学研究的热点.ARC(带有caspase富集功能域的凋亡抑制因子)是新近发现的唯一在心脏大量且特异表达的抗凋亡蛋白,其全称是带有caspase富集功能域的凋亡抑制因子.ARC可被持续性磷酸化并参与阻断凋亡发生途径的多个层面.因此,ARC是一种强大的抗心肌凋亡蛋白.     

Severe fever with thrombocytopenia syndrome and its pathogen SFTSV

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne bunyavirus. In endemic area in China 1%–3% population was infected with SFTSV, but age is critical risk factor for hospitalization and death of SFTS patients.     

Consequences of Domain Insertion on the Stability and Folding Mechanism of a Protein

SlyD, the sensitive-to-lysis protein from Escherichia coli, consists of two domains. They are not arranged successively along the protein chain, but one domain, the “insert-in-flap” (IF) domain, is inserted internally as a guest into a surface loop of the host domain, which is a prolyl isomerase of the FK506 binding protein (FKBP) type. We used SlyD as a model to elucidate how such a domain insertion affects the stability and folding mechanism of the host and the guest domain. For these studies, the two-domain protein was compared with a single-domain variant SlyDΔIF, SlyD* without the chaperone domain (residues 1-69 and 130-165) in which the IF domain was removed and replaced by a short loop, as present in human FKBP12. Equilibrium unfolding and folding kinetics followed an apparent two-state mechanism in the absence and in the presence of the IF domain. The inserted domain decreased, however, the stability of the host domain in the transition region and decelerated its refolding reaction by about 10-fold. This originates from the interruption of the chain connectivity by the IF domain and its inherent instability. To monitor folding processes in this domain selectively, a Trp residue was introduced as fluorescent probe. Kinetic double-mixing experiments revealed that, in intact SlyD, the IF domain folds and unfolds about 1000-fold more rapidly than the FKBP domain, and that it is strongly stabilized when linked with the folded FKBP domain. The unfolding limbs of the kinetic chevrons of SlyD show a strong downward curvature. This deviation from linearity is not caused by a transition-state movement, as often assumed, but by the accumulation of a silent unfolding intermediate at high denaturant concentrations. In this kinetic intermediate, the FKBP domain is still folded, whereas the IF domain is already unfolded.     

Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV-1-infected children

Background

Variability in MDR1 and PXR has been associated with differences in drug plasma levels and response to antiretroviral therapy. We investigated whether polymorphisms in MDR1 (T-129C, C1236T and C3435T) and PXR (C63396T) affect lopinavir plasma concentration and the virological or immunological response to HAART in HIV-1-infected children.

Methods

Genotypes were identified in 100 blood donors and 38 HIV-1-infected children. All children received HAART with lopinavir boosted with ritonavir (LPV/r) at the time of LPV plasma level quantification, before (C_trough) and between 1 and 2 h after (C_post-dose) the administration of the next dose of drug. CD4⁺ T-cell counts and plasma viral load were analyzed before and after the initiation of LPV/r.

Results

MDR1 1236T, MDR1 3435T and PXR 63396T alleles showed a frequency of ~ 50% while the MDR1 -129C allele only reached 5%. Children heterozygotes 1236CT showed a significantly lower LPV C_post-dose than homozygotes 1236TT (median C_post-dose = 3.04 μg/ml and 6.50 μg/ml, respectively; p = 0.016). Children heterozygotes 1236CT also had a lower decrease of viral load after 36 weeks of LPV/r exposure compared with homozygotes 1236CC (median viral load changes = − 0.50 log₁₀ copies/ml and − 2.08 log₁₀ copies/ml, respectively; p = 0.047). No effect on the immunological response was observed for polymorphisms of MDR1 or PXR.

Conclusions

Our results suggest that the MDR1 C1236T SNP significantly reduces LPV plasma concentration affecting the virological response to HAART. Heterozygotes 1236CT might have an altered level of P-gp expression/activity in enterocytes and CD4⁺ T lymphocytes that limits the absorption of LPV leading to an impaired virological suppression.     

抗HSV-IICP22蛋白抗原多肽抗体对ICP22定位的检测分析

ICP22作为单纯疱疹病毒进入细胞后最早表达的蛋白之一,对于病毒的复制具有重要的调节功能,由于抗原表位的同源性,使用完整的ICP22蛋白作为抗原难以获得特异性的抗体.通过氨基酸序列预测,ICP22蛋白1～36位氨基酸具有较强的抗原性,将ICP22蛋白1-36位氨基酸偶联于GTS蛋白作为抗原免疫小鼠,所制备抗体能够特异性识别具有正常生理构象的ICP22蛋白.抗体检测结果显示,ICP22不但定位于细胞核内,而且还能够形成特殊的点状结构.     

关于三氧化二砷（As2O3）联合药物治疗肝癌的研究进展

实验与临床研究已证实,As2O3能有效治疗急性早幼粒细胞性白血病（APL）。在此基础上．As2O3抗肝癌作用的研究报告日益增多。研究表明As2O3的抗肝癌效力呈剂量一时间效应关系,但作用时间越长及药物浓度越大,As2O3的毒副作用越大。为实现As2O3低毒高效的抗肿瘤目的,联合用药引起关注。本文通过查阅94年至今国内外有关As2O3药物联合治疗肝癌的文献,对As2O3联合药物治疗肝癌予以综述。