Experimental antioxidant therapy in toxic liver damage from CCl4 and chloxyl

The authors studied the pharmacotherapeutic efficacy of antioxidants vitamin E, sodium selenite, and their combination in damage to rat liver by CCl4 and the anthelmintic agent chloxyl. Changes of the intensity of peroxidation of biological membrane lipids, the activity of enzymes-markers of hepatocyte cytolysis--alanine aminotransferase and aspartate aminotransferase--in blood serum, and changes in the structure of the liver were studied. Antioxidants and their combination blocked lipid peroxidation, reduced the activity of alanine aminotransferase and aspartate aminotransferase in blood serum considerably, and caused a protective effect on the structure of rat liver in its damage by CCl4 and chloxyl.     

Geroprotective effect of Ala-Glu-Asp-Gly peptide in male rats exposed to different illumination regimens

Exposure of male rats to permanent or natural illumination of North-Western Russia accelerated their death in comparison with animals exposed to standard (12 h) light. Permanent illumination promoted the development of spontaneous tumors in comparison with the standard photoregimen. Injection of epithalone (synthetic Ala-Glu-Asp-Gly peptide; subcutaneously 0.1 μg/rat 5 times a week from the age of 4 months until natural death) virtually did not change the mean lifespan of male rats, but was associated with a significant (p<0.05) normalization of population aging rate and hence, time of mortality rate doubling in groups exposed to natural or constant illumination. Epithalone injected to rats exposed to any photoregimen significantly inhibited the development of spontaneous tumors, primarily testicular leydigomas and leukemias. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 455–460, April, 2008     

LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway

BackgroundLINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague.MethodsLINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time‐quantitative polymerase chain reaction (RT‐qPCR). Besides, the five‐year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan–Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation‐associated proteins, migration‐associated proteins, glycolysis‐associated proteins, and phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway‐associated proteins were detected by Western blot.ResultsIn laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5‐year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell‐cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki‐67, PCNA, MMP2, N‐Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E‐Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes.ConclusionLINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.     

男性乳腺癌特异性生存率预测模型的构建

目的:构建男性乳腺癌特异性生存(BCSS)生存率预测模型.方法:选取SEER数据库中诊断时间为2010年1月1日至2015年12月31日的2226名男性乳腺癌病例,按7:3的比例随机分为训练集(n=1558)和验证集(n=668).在训练集中,使用Cox比例风险回归模型筛选与BCSS相关的变量,构建BCSS生存率多因素...     

Prkdc和Il2rg双敲除免疫缺陷小鼠的构建和初步应用

目的：构建NOD背景免疫缺陷小鼠,作为新的人源肿瘤异种移植(patient?derived xenograft,PDX)模型。方法：利用 CRISPR/Cas9技术获得NOD背景Prkdc和Il2rg双基因敲除小鼠,通过正常繁育得到能够稳定遗传的纯合子后代(命名为NYG 小鼠),流式细胞术检测小鼠外周血免疫细胞比例,移植接种新鲜肿瘤组织,观察记录肿瘤生长状况及HE染色观察传代PDX 肿瘤形态学特点。结果：NYG小鼠外周血小鼠无成熟的T细胞、B细胞和NK细胞表达,对移植的患者肿瘤组织几乎没有排斥反应,组织病理学表型及免疫系统未见明显异常。结论：成功构建NYG小鼠免疫缺陷小鼠,为肿瘤学基础理论及应用研究提供了新的PDX动物模型。     

儿童脊肌萎缩症运动神经元生存基因缺失分析

目的评价聚合酶链反应-限制性片段长度多肽性（PCR-RFLP）分析技术在脊肌萎缩症（SMA）临床诊断中的价值，分析端粒侧运动神经元生存基因（SMNt）表达与SMA临床分型之间的关系。方法对临床拟诊为SMA的23例患儿同时采用临床诊断标准和PCR-RFLP分析技术进行诊断，两种结果对比，分析灵敏度、特异度、Kappa值及P值。结果（1）临床诊断与PCR-RFLP基因诊断结果比较：23例拟诊患儿中临床确诊为SMA者18例，非SMA者5例。PCR-RFLP技术检测结果：5例非SMA者，SMNt基因检测均无缺失；18例确诊SMA者，SMNt基因缺失者15例，无SMNt基因缺失者3例，缺失频率为83．3％。此方法的灵敏度为83．3％，特异度为100％，阳性预测值100％，阴性预测值62．5％，真实性为86．96％，Kappa值为0．685。（2）SMA不同临床分型中SMNt基因7、8号外显子缺失检测结果：Ⅰ型患者以7、8号外显子缺失为主，SMNt基因缺失频率100．0％；Ⅲ型患者以7号外显子缺失为主，SMNt基因缺失频率为66．7％；Ⅰ型患者7、8号外显子联合缺失频率较Ⅲ型高（P〈0．05）。结论（1）PCR-RFLP分析技术简便、快捷、特异性高，敏感性好，适用于临床儿童型SMA的基因诊断，尤其对于SMAI型患者。（2）SMNt基因7、8号外显子联合缺失常常提示病情严重，预后不良；单独缺失提示病情较轻，预后较好。     

Adult stem cells and other cancer residents. Part II

In this review, we have attempted to generalize recent data on adult stem cells as the most likely cells, according to the current dominant paradigm, in which a predisposition to malignant degeneration occurs or, in other words, where cancer is initiated.     

Expression of Progastrin-Derived Peptides and Somatostatin in Fundus and Antrum of Nonulcer Dyspepsia Subjects With and Without Helicobacter pylori Infection

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine–extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.     

Control of Aβ release from human neurons by differentiation status and RET signaling

Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer's disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid β (Aβ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased Aβ secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered Aβ release was associated with rapid upregulation of the GDNF coreceptor “rearranged during transfection” (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased Aβ, whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and Aβ increase. This suggests that RET signaling affects Aβ release from aging neurons.