鼻咽癌细胞中上皮细胞钙黏蛋白基因启动子甲基化的研究

目的 探讨鼻咽癌细胞中上皮细胞钙黏蛋白(E-cadherin)启动子甲基化对基因表达的影响,以及经去甲基化药物5-杂氮-2'-脱氧胞苷(5-Aza-dC)作用后肿瘤细胞增殖与侵袭能力的变化.方法采用逆转录(RT)-PCR、Western blot与免疫组织化学(polymer法)检测经5-Aza-dC处理前后HNE1和CNE2细胞中E-cadherin的表达水平,以甲基化特异性PCR(MSP)分析启动子甲基化状态,以四甲基偶氮唑盐(MTT)比色法与侵袭实验测定细胞增殖与侵袭能力的变化.结果 HNE1和CNE2细胞中E-cadherin表达水平减弱,其启动子区域存在部分甲基化现象;经5-Aza-dC作用后可显著上调鼻咽癌细胞E-cadherin的表达水平,降低基因启动子甲基化程度,同时显著抑制肿瘤细胞的增殖能力与侵袭能力.经20 μmol/L 5-Aza-dC作用后,HNE1与CNE2细胞的增殖能力与未处理组相比分别降低27.6%和34.3%,P＜0.05;HNE1与CNE2细胞经5-Aza-dC药物处理后,通过滤膜迁移进至侵袭小室下腔的数量与未处理组相比分别减少37.2%和29.7%,P＜0.05.结论基因启动子区域高甲基化状态是导致E-cadherin表达水平下调的机制之一,应用去甲基化药物可恢复E-cadherin表达并抑制肿瘤细胞的恶性生物学特征.     

维稳形式下新疆高校国防生心理健康与觉察压力及应对方式

目的:探讨维稳形势下新疆高校国防生心理健康状况及相关因素。方法:采用SCL-90症状自评量表、觉察压力量表(PSS-C)和简易应对方式问卷(SCSQ)进行测验。结果:1维稳形势下,国防生觉察压力、应对方式在年级、性别和灾难经历上具有显著差异(P0.01),SCL-90得分与大学生常模相比,除强迫症状和偏执外,其余各因子分和SCL-90总均分显著低于大学生常模(t=-2.14,-2.10,-2.82,-2.49,-2.30,-2.91,-2.71,-2.34;P0.01);2预测感与强迫症状、人际敏感和抑郁呈显著正相关(P0.01);控制感、超载感与躯体化、抑郁、焦虑、敌对、恐怖、精神病性和SCL-90总均分呈显著负相关(P0.01);除人际敏感外,积极应对方式与SCL-90各因子及总均分呈显著负相关(P0.01)。3预测感、超载感和积极应对方式对心理健康有直接效应(路径系数为0.20、-0.22和0.17),控制感对心理健康的间接效应为0.044。结论:觉察压力和积极应对方式是影响维稳形势下新疆高校国防生心理健康的两个重要因素;积极应对方式在控制感和心理健康状况间具有中介作用。     

Senecavirus A Enhances Its Adaptive Evolution via Synonymous Codon Bias Evolution

Synonymous codon bias in the viral genome affects protein translation and gene expression, suggesting that the synonymous codon mutant plays an essential role in influencing virulence and evolution. However, how the recessive mutant form contributes to virus evolvability remains elusive. In this paper, we characterize how the Senecavirus A (SVA), a picornavirus, utilizes synonymous codon mutations to influence its evolution, resulting in the adaptive evolution of the virus to adverse environments. The phylogenetic tree and Median-joining (MJ)-Network of these SVA lineages worldwide were constructed to reveal SVA three-stage genetic development clusters. Furthermore, we analyzed the codon bias of the SVA genome of selected strains and found that SVA could increase the GC content of the third base of some amino acid synonymous codons to enhance the viral RNA adaptive evolution. Our results highlight the impact of recessive mutation of virus codon bias on the evolution of the SVA and uncover a previously underappreciated evolutionary strategy for SVA. They also underline the importance of understanding the genetic evolution of SVA and how SVA adapts to the adverse effects of external stress.     

De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment,Spastic Paraparesis,Axonal Neuropathy,and Cerebellar Atrophy

KIF1A is a neuron‐specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type‐2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.     

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

A morphometric study of the lumbar spinous process in the Chinese population

Our goal was to analyze the anatomical parameters of the lumbar spine spinous processfor an interspinous stabilization device designed for the Chinese population and tooffer an anatomical basis for its clinical application. The posterior lumbar spines(T₁₂-S₁) of 52 adult cadavers were used for measuring thefollowing: distance between two adjacent spinous processes (DB), distance across twoadjacent spinous processes (DA), thickness of the central spinous processes (TC),thickness of the superior margin of the spinous processes (TS), thickness of theinferior margin of the spinous processes (TI), and height of the spinous processes(H). Variance and correlation analyses were conducted for these data, and the datamet the normal distribution and homogeneity of variance. DB decreased gradually fromL_1-2 to L₅-S₁. DA increased fromT₁₂-L₁ to L_2-3 and then decreased fromL_2-3 to L_4-5. The largest H in males was noted atL₃ (25.45±5.96 mm), whereas for females the largest H was noted atL₄ (18.71±4.50 mm). Usually, TS of the adjacent spinous process waslower than TI. Based on the anatomical parameters of the lumbar spinous processesobtained in this study, an “H”-shaped coronal plane (posterior view) was proposed asan interspinous stabilization device for the Chinese population. This study reportsmorphometric data of the lumbar spinous processes in the Chinese population, whichprovides an anatomical basis for future clinical applications.     

MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy

Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR-218 directly binds to the 3’-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma.     

Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease

Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status.     

宫颈癌组织中DCR3表达与外周血T细胞亚群的相关性研究

目的探讨宫颈癌组织中诱骗受体3(DCR3)表达与外周血T细胞亚群之间的相关性。方法免疫组织化学法检测宫颈上皮内瘤变(CIN)、宫颈癌(CC)及正常宫颈组织中DCR3表达情况,并检测宫颈癌组织中实质及间质内T细胞表面抗原CD3、CD4、CD8阳性细胞数量;应用流式细胞术分析患者外周血中CD3+、CD4+、CD8+T数量变化情况,分析研究宫颈癌组织中DCR3表达与患者外周血T细胞亚群之间的相关性。结果 DCR3表达强度与宫颈病变严重程度有关;宫颈癌患者外周血中T细胞数明显降低,且宫颈组织中DCR3表达与患者外周血中CD3+T、CD4+/CD8+呈负相关;宫颈癌变后实质内T细胞数明显减少,T细胞主要聚集于肿瘤间质内。结论 DCR3参与了宫颈癌细胞免疫逃逸,外周血T细胞亚群联合DCR3检测可作为宫颈癌免疫诊断指标,为患者免疫治疗提供基础。