pppA2’p5’A2’p5’A保护病毒感染细胞的普遍性

pppA2’p5’A2’p5’A(简称2’-5’P_3A_3)是干扰素作用于细胞后诱导产生的物质。干扰素的作用机理很复杂,其中之一是2’-5’寡聚腺苷酸合成酶的活力增加,此酶以ATP为底物合成2’-5’P_3A_3及其同系物2’-5’P_3An。但2’-5’P_3A_3或2’-5’P_3A_n本身是否具有抗病毒作用,干扰素的抗病毒作用是否通过2’-5’P_3A_3或2’-5’P_3An而进行,这是一个很     

pppA2′p5′A2′p5′A保护病毒感染细胞的普遍性

pppA2′p5′A2′p5′A(简称2′-5′P_3A_3)是干扰素作用于细胞后诱导产生的物质。干扰素的作用机理很复杂,其中之一是2′-5′寡聚腺苷酸合成酶的活力增加,此酶以ATP为底物合成2′-5′P_3A_3及其同系物2′-5′P_3An。但2′-5′P_3A_3或2′-5′P_3A_n本身是否具有抗病毒作用,干扰素的抗病毒作用是否通过2′-5′P_3A_3或2′-5′P_3A_n而进行,这是一个很     

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3)

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.     

miR-15a-5p和miR-16-5p在骨肉瘤组织中的表达分析

目的:使用microRNAs基因芯片及实时定量PCR法测定骨肉瘤组织中miR-15a-5p和miR-16-5p的相对表达含量,并与瘤旁组织对比,分析骨肉瘤细胞内miR-15a-5p和miR-16-5p的表达变化。方法:选取34例骨肉瘤组织蜡块样本,使用microRNAs基因芯片观察miR-15a-5p和miR-16-5p在骨肉瘤和瘤旁组织内的表达差异;实时定量PCR法测定骨肉瘤组织和瘤旁组织中miR-15a-5p和miR-16-5p的相对表达含量,并将两种结果对比分析。结果:microRNAs基因芯片结果显示,在骨肉瘤组织中,miR-15a-5p在肿瘤中的表达较瘤旁组织低1.79倍,miR-16-5p较瘤旁组织低1.62倍。实时定量PCR实验结果表明,miR-15a-5p和miR-16-5p表达较瘤旁组织降低,差异有统计学意义(P0.05)。经过统计学计算,miR-15a-5p在肿瘤中的表达较瘤旁组织低3.14倍,miR-16-5p较瘤旁组织低5.65倍。结论:在骨肉瘤中,miR-15a-5p和miR-16-5p表达含量降低,提示这两种microRNAs在骨肉瘤中可能做为抑癌因子存在。     

p,p′-Dichlorodiphenyldichloroethylene Induces Colorectal Adenocarcinoma Cell Proliferation through Oxidative Stress

p, p′-Dichlorodiphenyldichloroethylene (DDE), the major metabolite of Dichlorodiphenyltrichloroethane (DDT), is an organochlorine pollutant and associated with cancer progression. The present study investigated the possible effects of p,p′-DDE on colorectal cancer and the involved molecular mechanism. The results indicated that exposure to low concentrations of p,p′-DDE from 10⁻¹⁰ to 10⁻⁷ M for 96 h markedly enhanced proliferations of human colorectal adenocarcinoma cell lines. Moreover, p,p′-DDE exposure could activate Wnt/β-catenin and Hedgehog/Gli1 signaling cascades, and the expression level of c-Myc and cyclin D1 was significantly increased. Consistently, p,p′-DDE-induced cell proliferation along with upregulated c-Myc and cyclin D1 were impeded by β-catenin siRNA or Gli1 siRNA. In addition, p,p′-DDE was able to activate NADPH oxidase, generate reactive oxygen species (ROS) and reduce GSH content, superoxide dismutase (SOD) and calatase (CAT) activities. Treatment with antioxidants prevented p,p′-DDE-induced cell proliferation and signaling pathways of Wnt/β-catenin and Hedgehog/Gli1. These results indicated that p,p′-DDE promoted colorectal cancer cell proliferation through Wnt/β-catenin and Hedgehog/Gli1 signalings mediated by oxidative stress. The finding suggests an association between p,p′-DDE exposure and the risk of colorectal cancer progression.     

p16INK4a/p19Arf与年龄相关性胰岛β细胞功能

2型糖尿病是一种与年龄密切相关的疾病,随着年龄增加,胰岛β细胞增殖能力和分泌能力下降,糖尿病患病率明显增加,但其机制尚不清楚. 最近研究发现,细胞周期蛋白依赖激酶(cyclin-dependent kinase, CDK)抑制剂p16INK4a是引起胰岛β细胞年龄相关性老化的重要调控因子.研究表明,通过p16INK4a介导的胰岛老化机制可能有如下两个：p38MAPK(mitogen-activated protein kinase)途径和PDGFR(platelet-derived growth factor receptor) 途径,两者均引起p16ink4a及p19ARF表达增加,而损害胰岛细胞增殖.本文综述年龄相关性胰岛β细胞功能下降的潜在机制,从而为改善胰岛β细胞功能提供新的分子靶点.     

5-amino-pyrazoles as potent and selective p38α inhibitors

The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed.     

Down regulation of miR-30a-5p and miR-182–5p in gastric cancer: Clinical impact and survival analysis

Background and aimGastric Cancer (GC) is a leading cause of morbidity and mortality worldwide, particularly in developing nations, only a few suitable gastric cancer serum biomarkers with acceptable sensitivity and specificity exist. This work aims to highlight and uncover miR-30a-5p and miR-182–5p′s diagnostic roles regarding gastric cancer and their roles in predicting prognosis.Methods148 patients participated in this study. Groups I, II, and III had 47 patients with GC, 54 patients with benign gastric lesions, and 47 apparently healthy subjects of coincided age and gender as controls, respectively. All participants were clinically evaluated and subjected to CBC, serum CEA, and CA19-9 by ELISA, and real-time PCR tests of miR-30a-5p and miR-182–5p.ResultsMiR30a-5p and miR-182–5p were down regulated in gastric cancer patients in Group I more than Groups II and III (P < 0.001). ROC curve analysis revealed that miR30a-5p had better AUC, sensitivity, and specificity (0.961%, 93.62%, and 90.74%respectively). When miR-182–5p was gathered with CEA and CA19-9, specificity raised to 98.15% and PPV to 97.6%. Lower miR-30a-5p levels are linked with the presence of distant metastases, advanced TNM stage, and degree of pathological differentiation of tumors in GC patients (p = 0.034, 0.019, 0.049) respectively. According to the multivariate analysis, miR30a-5p expression level could be an independent predictor of GC.ConclusionOur results exhibited that miRNAs, miR-30a-5p and miR182–5p, gene expression have a diagnostic power and can identify patients with GC. MiR-30a-5p displayed the highest diagnostic specificity and sensitivity. Besides other known tumor markers, they could offer simple noninvasive biomarkers that predict gastric cancer.     

miRNA-139-5p与肿瘤

转移和复发是恶性肿瘤的重要特征。肿瘤细胞的增殖、浸润、侵袭能力与肿瘤的复发和转移息息相关。非编码小RNA通过转录后水平参与肿瘤的发生和发展过程。其中,miR-139-5p成为研究热点之一。在许多肿瘤中都发现miR-139-5p的异常表达,它参与了肿瘤细胞的增殖、分化、转移和浸润,调节肿瘤细胞对化疗药物敏感性,并与肿瘤患者的预后相关。因此,miR-139-5p可能成为肿瘤治疗的一个新靶点。本文对miR-139-5p与肿瘤的关系作一综述。系统地了解它在恶性肿瘤进程中的作用,为广大研究者及临床工作者提供新思路新方法。     

miR-196b-5p促进成肌细胞增殖分化

MicroRNA (miRNA)是一类由内源基因编码的长度约为22个核苷酸的非编码单链RNA分子，在动植物中参与转录后基因表达调控。大量研究表明，miRNA调控骨骼肌的发育，主要表现在肌卫星细胞的激活及增殖、分化、肌管的形成等生物学过程。本实验室前期对大白猪背最长肌(longissimus dorsi,LD)和比目鱼肌(soleus muscle,Sol)进行miRNA测序，筛选鉴定到一个在不同骨骼肌中差异表达并且序列高度保守的miR-196b-5p，目前miR-196b-5p在骨骼肌方面的研究尚未见报道。本研究进一步设计合成miR-196b-5p mimics和inhibitor对C2C12细胞进行miR-196b-5p过表达及干扰表达，利用蛋白免疫印迹、实时荧光定量PCR检测、流式细胞术、免疫荧光染色等方法探究miR-196b-5p对成肌细胞增殖分化的影响，并利用生物信息学预测和双荧光素酶报告系统鉴定了miR-196b-5p的靶基因。结果显示，过表达miR-196b-5p显著增加细胞周期基因Cyclin B、Cyclin D和Cyclin E的mRNA和蛋白表达水平(P<0....     

遗传性平衡易位t(3; 22) (p21; q13）家系

本文报道一例t(3; 22) (p21; q13）平衡 相互易位的家系。先证者，男性，一岁半，淋巴 细胞及皮肤成纤维细胞G带分析结果：核型均 为46, XY, t(3; 22)(p21；q13）或46, XY,t(3; 22)(3gter” 3p21：：22813” 22gter；2 2 pter” 22gl3::3p21” 3 pter )；先证者母亲（图1）与 外祖母核型均为46, XX, t(3; 22)(p21; q13) 或46, XX, t(3; 22)(3gter、3p21：:22813一 22gter; 22pter～ 22813：:3p21一3pter)。经银 染与G带复合显示技术，先证者及母亲的22der 可见清晰的AgNOR区。先证者的父亲与舅父 G带分析核型正常。在此情况下，有生育正常 婴儿的可能，但必须作产前诊断。     

Trisomy 6p22→6pter due to familial t(6;13)(p22;q34 or 33) translocation

Summary 235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.     

Plasmodium berghei Δp52&p36 Parasites Develop Independent of a Parasitophorous Vacuole Membrane in Huh-7 Liver Cells

The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Δp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM). However, a small proportion of P. berghei Δp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Δp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Δp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Δp52&p36 parasites were able to fully mature and produced infectious merozoites. These Δp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Δp52&p36 liver stages were infectious for C57BL/6 mice.