不同浓度异氟醚对小鼠肺表面活性蛋白A表达的影响

目的 探讨异氟醚对小鼠肺表面活性蛋白A表达的影响。方法 将雄性昆明小鼠随机分为5组,吸入空气组、吸入1.0MAC异氟醚5min组、吸入3.0MAC异氟醚5min组、吸入1.0MAC异氟醚2h组、吸入3.0MAC异氟醚2h组;RT-PCR方法检测小鼠肺内SP-A mRNA的表达;免疫组化方法检测小鼠肺内SP-A蛋白的表达。结果 吸入异氟醚5min对小鼠肺内SP-A表达无影响,吸入异氟醚2h能降低小鼠肺内SP-A表达,而且随吸入浓度升高,SP-A表达呈负相关。结论 吸入高浓度异氟醚长时间能够降低小鼠肺内SP-A的表达。     

Memory T-cell-specific therapeutics attenuate allograft rejection via mediation of alloreactivity in memory cells

Many means in inbred rodent models promoted long-term graft survival or donor-specific tolerance, but less so in nonhuman primates, outbred rodents or human patients. A diverse repertoire of memory T cells, derived from heterologous immunity or prior to exposure to alloantigen, has been believed to be an important part of this barrier. Memory T cells have a unique capacity to generate effector functions quickly upon re-exposure to antigen, and this capacity is achieved by reduced activation thresholds, and expressed high level trafficking and adhesion molecules, which is likely responsible for their exhibiting differential susceptibility to immune therapeutics compared with na?ve T cells. This review outlines recent progress on characteristics of memory T cells and focuses on these potential therapies targeting memory T cells which are likely to ameliorate allograft rejection by inducing transplant tolerance.     

Pre‐ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress‐dependent autophagy via PERK and IRE1 signalings

Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre‐ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR)‐related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion mouse model. Pre‐ischemia melatonin treatment was able to attenuate IR‐induced ER stress and autophagy. In addition, with tandem RFP‐GFP‐LC3 adeno‐associated virus, we demonstrated pre‐ischemic melatonin significantly alleviated IR‐induced autophagic flux. Furthermore, we showed that IR induced neuronal apoptosis through ER stress related signalings. Moreover, IR‐induced autophagy was significantly blocked by ER stress inhibitor (4‐PBA), as well as ER‐related signaling inhibitors (PERK inhibitor, GSK; IRE1 inhibitor, 3,5‐dibromosalicylaldehyde). Finally, we revealed that melatonin significantly alleviated cerebral infarction, brain edema, neuronal apoptosis, and neurological deficiency, which were remarkably abolished by tunicamycin (ER stress activator) and rapamycin (autophagy activator), respectively. In summary, our study provides strong evidence that pre‐ischemia melatonin administration significantly protects against cerebral IR injury through inhibiting ER stress‐dependent autophagy. Our findings shed light on the novel preventive and therapeutic strategy of daily administration of melatonin, especially among the population with high risk of cerebral ischemic stroke.     

Discovery of Hydroxyamidine Derivatives as Highly Potent,Selective Indoleamine-2,3-dioxygenase 1 Inhibitors

In this study, a series of novel hydroxyamidine derivatives were identified as potent and selective IDO1 inhibitors by structure-based drug design. Among them, compounds 13–15 and 18 exhibited favorable enzymatic and cellular activities. Compound 18 showed improved bioavailability in mouse, rat, and dog (F% = 44%, 58.8%, 102.1%, respectively). With reasonable in vivo pharmacokinetic properties, compound 18 was further evaluated in a transgenic MC38 xenograft mouse model. The combination of compound 18 with PD-1 monoclonal antibody showed a synergistic antitumor effect. These data indicated that compound 18 as a potential cancer immunotherapy agent should warrant further investigation.     

微重力对血管内皮细胞生物学特性的影响

微重力状态下,人体将表现出一系列的心血管去适应性反应.由于血管内皮细胞是血管壁最重要的组成部分,因此血管内皮细胞生物学特性的改变将与去适也性反应直接相关.研究微重力状态下血管内皮细胞生物学特性的改变对预防和治疗航天员心血管的去适应性反应尤为重要.     

加味小柴胡汤对肝癌患者栓塞化疗后脂质过氧化反应的影响

[目的]探讨原发性肝癌患者介入栓塞化疗(TACE)导致肝损害等不良反应的过氧化损伤机制,观察加味小柴胡汤的抗氧化作用.[方法]将56例肝癌患者随机分2组(TACE后均行水化治疗),各28例.对照组口服肌苷、肝泰乐、胃复安、维生素B6等;观察组给予加味小柴胡汤.观测TACE前、后2、7、14、21、28 d肝功能及过氧化指标的动态变化.[结果]TACE后2 d肝功能异常加重,过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性、谷胱甘肽(GSH)水平明显降低,丙二醛(MDA)水平增加,以对照组变化显著.观察组肝功能及氧化指标恢复较快,均优于对照组(P＜0.01).[结论]肝癌TACE引起的不良反应及肝损害,与化疗药诱致的脂质过氧化反应有关.加味小柴胡汤有明显的抗氧化作用.     

四川省媒介按蚊地理分布与疟疾流行的关系

本文根据历年来媒介按蚊调查结果和疟疾流行情况，将四川省疟疾流行区划分为：①中华按蚊分布区；②中华接蚊、嗜人按蚊分布区；③嗜人按蚊分布争议区。讨论了媒介披蚊不同地理分布、喀人按蚊在人房中所占不同比例对疟疾流行程度和防治效果的影响。     

白纹伊蚊β-肌动蛋白基因片段的克隆及其

目的获取白纹伊蚊β-肌动蛋白基因序列并探讨其作为基因表达内参照的作用。方法根据昆虫β-肌动蛋白核苷酸序列的高度保守区设计引物，通过PCR的方法从白纹伊蚊C6／36细胞中扩增获得白纹伊蚊β-肌动蛋白基因片段，进一步通过RT—PCR的方法验证其在稳定转染空载体和40S核糖体蛋白S4（RPS4）基因的白纹伊蚊C6／36细胞中的表达。结果获得白纹伊蚊β-肌动蛋白基因片段，长911bp，与其他几种蚊β-肌动蛋白基因对应序列的相似性在89％以上。在稳定转染空载体和RPS4基因的C6／36细胞中，均可稳定地扩增出目的基因。结论成功获得了白纹伊蚊β-肌动蛋白基因片段，并且该片段完全可以用作基因表达差异分析时的内参照基因。     

Targeted disruption of LH receptor gene revealed the importance of uterine LH signaling

Numerous previous studies have demonstrated that LH and hCG can directly regulate several uterine functions. We investigated in the present study, whether uterine phenotype in LH receptor knockout animals resulted also from the absence of direct actions of LH in the uterus. The phenotype consisted of marked growth reduction of uterus, decreased thickness of endometrial and myometrial layers, number of endometrial glands, height of luminal epithelium and vascular space. Analysis of uterine gene expression by mouse genome U74Av2 Affymetrix genechips revealed a differential expression of 155 genes by more than 3-fold (range 3-53-fold) between null and wild-type animals. Of these, 89 genes decreased and 66 increased in uterus of null animals. Semi-quantitative RT-PCR confirmed the differential expression of several selected genes. The decreased genes can be clustered into 18 functional families and the increased into 15 functional families. Semi-quantitative RT-PCR, Western blotting and immunocytochemistry demonstrated a decreased expression of ERbeta, PR-A, PR-B and AR in uterus of null animals as compared with wild-type siblings. Twenty-one-day estradiol and progesterone replacement therapy did not normalize the decrease in the number of endometrial glands and several genes that either decreased or increased in expression. The partial success of therapy suggests that direct LH actions could be required to completely normalize the uterus. In summary, findings on the knockout model reaffirm that LH and hCG control uterine functions directly as well as indirectly through increasing ovarian synthesis of steroid hormones and both actions are required for normal uterine biology.