LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2

Long non-coding RNA HOTAIR predicts negative tumor prognosis and exhibits oncogenic activity. Herein, we demonstrate HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Mechanistically, HOTAIR reduces the recuritment of the CREB, P300, RNA polII onto the SETD2 promoter region that inhibits SETD2 expression and its phosphorylation. Thereby, the SETD2 binding capacity to substrate histone H3 is weakened, triggering a reduction of trimethylation on histone H3 thirty-sixth lysine, and thereby the H3K36me3–hMSH2-hMSH6-SKP2 complex is also decreased. Strikingly, the complex occupancy on chromosome is depressed, preventing from mismatch DNA repair. While reducing the degradation capacity of Skp₂ for aging histone H3 bound to damaged DNA, the aging histone repair is impaired. Furthermore, that the damaged DNA escaped to repair can causes microsatellite instability(MSI) and abnormal expression of cell cycle related genes that may trigger the hepatocarcinogenesis. This study provides evidence for HOTAIR to promote tumorigenesis via downregulating SETD2 in liver cancer stem cells.     

miR-140靶向PD-L1在小鼠脓毒症免疫抑制中的作用

【摘要】 目的 探讨miR-140靶向PD-L1在小鼠脓毒症免疫抑制中的作用。 方法 取90只小鼠随机分成对照组（Control组）、脓毒症模型组（CLP组）和CLP+miR 140组，每组30只。盲肠结扎穿孔法（CLP法）建立小鼠脓毒症模型，尾静脉注射转染miR-140 agomir，记录30天生存率，ELISA法检测血清肿瘤坏死因子（TNF-α）、白细胞介素2（IL-2）表达，流式细胞术检测血清CD4+T和CD8+T细胞百分率，提取腹膜巨噬细胞，流式细胞术分析PD L1阳性百分率，实时荧光定量PCR（RT-qPCR）检测miR-140和PD-L1基因表达，蛋白印迹（Western blot）检测PD-L1蛋白表达，荧光素酶报告实验检测miR-140和PD-L1靶向作用关系。 结果 与control组相比，CLP组在1 、7、14 d的TNF α、IL-2水平升高（P＜0.01），而TNF-α、IL-2水平呈时间依赖性降低（P＜0.05）；CLP组较control组小鼠生存率降低（P＜0.01），CD4+和CD8+细胞百分比升高（P＜0.01），巨噬细胞PD-L1阳性细胞率升高（P＜0.01），miR-140表达水平降低（P＜001），PD-L1基因和蛋白表达水平升高（P＜0.01）；与CLP组比较，CLP+miR-140组小鼠生存率升高（P＜0.01），CD4+和CD8+细胞百分比升高（P＜0.01），巨噬细胞PD-L1阳性细胞率下降（P＜0.01），miR-140表达水平升高（P＜0.01），PD-L1基因和蛋白表达水平降低（P＜0.01）；荧光素酶报告实验结果显示miR-140和PD-L1存在靶向作用关系。 结论 miR-140可靶向作用于PD-L1，从而改善小鼠脓毒症引起的免疫抑制。     

Elevated troponin I levels on admission predict long-term mortality in patients with acute cerebral infarction following thrombolysis

Neurological Sciences - Cardiac diseases are frequently accompanied by elevated levels of biomarkers, among which, troponin is commonly investigated. The levels of plasma cardiac troponin I (cTnI),...     

胃泌素瘤的诊断及治疗

胃泌素瘤是一种神经内分泌肿瘤, 异位分泌胃泌素, 导致卓-艾综合征。大部分胃泌素瘤为散发病例, 20%～25%患者作为多发性内分泌腺瘤综合征1型(MEN1)临床表现之一存在。因为散发胃泌素瘤及MEN1治疗策略不同, 所以临床上需要将其加以区分。胃泌素瘤药物治疗主要分为控制高胃泌素血症相关症状和控制肿瘤生长两类。散发病例的手术治愈率为20%～40%, 而对于MEN1人群是否进行手术治疗尚存在争议。本文对近年来胃泌素瘤诊断及治疗相关临床进展进行阐释, 以期为临床工作提供参考。     

Hyperspectral classification using an adaptive spectral-spatial kernel-based low-rank approximation

This paper presents a novel adaptive spectral-spatial kernel-based low-rank approximation method for spectral-spatial hyperspectral image (HSI) classification. In the first of three steps of the proposed method, superpixel and image patch are used together to calculate the weights in the homogeneous region. Second, an adaptive spectral-spatial kernel is defined to capture the spectral and spatial feature of HSIs. In the final step, an adaptive spectral-spatial kernel and low-rank approximation are integrated into a decision model to perform HSI classification. Extensive experimental results on Indian Pines and Pavia University demonstrate the superiority of the proposed classifier when compared with other competing classifiers.     

mTORC1 is a target of nordihydroguaiaretic acid to prevent breast tumor growth in vitro and in vivo

Nordihydroguaiaretic acid (NDGA) is a natural phenolic compound isolated from the creosote bush Larrea divaricata, which has anti-tumor activities both in vitro and in vivo. Its analogs are in clinical development for use in refractory solid tumors. But the mechanisms underlying the anti-cancer effect of NDGA are not fully understood. In this study, we identified mammalian target of rapamycin complex 1 (mTORC1) as a target of NDGA both in cultured breast cancer cells and in xenograft models. NDGA effectively inhibited basal level of mTORC1 but not mTORC2 activity in breast cancer cell lines. NDGA also suppressed mTORC1 downstream signaling such as expression of cyclin D1, hypoxia-inducible factor-?? and VEGF, and prevented proliferation in breast cancer cells. Although NDGA stimulated AMP-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) signaling, which negatively regulates mTORC1, AMPK and TSC2 deletion could not diminish the inhibition of mTORC1 by NDGA. Subsequent studies revealed that NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin-stimulated mTORC1 and acted like rapamycin to disrupt mTOR?CRaptor interaction. Most importantly, NDGA repressed breast tumor growth and targeted mTORC1 and its downstream signaling in xenograft models. Together our data provide a novel mechanism for NDGA activity which could help explain its anti-cancer activity. Disruption of mTOR?CRaptor complex and activation of AMPK/TSC signaling may contribute to inhibitory effects of NDGA against mTORC1. Our data also raise the possibility that NDGA, as an mTORC1 inhibitor, may have a broad spectrum of action on breast cancers.     

Computerized image analysis for quantitative neuronal phenotyping in zebrafish

An integrated microscope image analysis pipeline is developed for automatic analysis and quantification of phenotypes in zebrafish with altered expression of Alzheimer's disease (AD)-linked genes. We hypothesize that a slight impairment of neuronal integrity in a large number of zebrafish carrying the mutant genotype can be detected through the computerized image analysis method. Key functionalities of our zebrafish image processing pipeline include quantification of neuron loss in zebrafish embryos due to knockdown of AD-linked genes, automatic detection of defective somites, and quantitative measurement of gene expression levels in zebrafish with altered expression of AD-linked genes or treatment with a chemical compound. These quantitative measurements enable the archival of analyzed results and relevant meta-data. The structured database is organized for statistical analysis and data modeling to better understand neuronal integrity and phenotypic changes of zebrafish under different perturbations. Our results show that the computerized analysis is comparable to manual counting with equivalent accuracy and improved efficacy and consistency. Development of such an automated data analysis pipeline represents a significant step forward to achieve accurate and reproducible quantification of neuronal phenotypes in large scale or high-throughput zebrafish imaging studies.     

中老年男性不同部位骨密度和骨质疏松检出率的对比分析

目的探讨中老年男性在应用双能X线骨密度仪检测不同部位骨密度时应关注检测的部位。方法选取2012年9月至2014年12月在我院行双能骨密度检测的中老年男性,比较腰椎、髋部、前臂桡骨下1/3的骨密度(BMD)和T值。结果中老年男性腰椎、髋部、前臂桡骨下1/3三个部位的BMD和T值比较,P0.001差异有统计学意义。随着年龄逐渐增大,腰椎BMD和T值下降不明显,髋部、前臂BMD和T值60岁以后才逐渐降低,前臂T值下降幅度明显大于腰椎和髋部。随着年龄的增加,髋部及前臂骨质疏松检出率也逐渐增加,但腰椎骨质疏松检出率随年增加反而下降。结论应用双能X线骨密度仪检测腰椎、髋部、前臂3个部位,经比较发现老年男性髋部和前臂BMD和T值明显低于腰椎,而且腰椎BMD和T值相对平稳,提示对老年男性骨质疏松诊断应同时检测髋部和前臂骨密度,以免出现骨质疏松的漏诊。