Novel POMGnT1 mutations cause muscle-eye-brain disease in Chinese patients

Muscle-eye-brain (MEB) disease is a congenital muscular dystrophy (CMD) phenotype characterized by hypotonia at birth, brain structural abnormalities and ocular malformations. To date, few MEB cases have been reported in China where clinical recognition and genetic confirmatory testing on a research basis are recent developments. Here, we report the clinical and molecular genetics of three MEB disease patients. The patients had different degrees of muscle, eye and brain symptoms, ranging from congenital hypotonia, early-onset severe myopia and mental retardation to mild weakness, independent walking and language problems. This confirmed the expanding phenotypic spectrum of MEB disease with varying degrees of hypotonia, myopia and cognitive impairment. Brain magnetic resonance imaging showed cerebellar cysts, hypoplasia and characteristic brainstem flattening and kinking. Four candidate genes (POMGnT1, FKRP, FKTN and POMT2) were screened, and six POMGnT1 mutations (four novel) were identified, including five missense and one splice site mutation. Pathogenicity of the two novel variants in one patient was confirmed by POMGnT1 enzyme activity assay, protein expression and subcellular localization of mutant POMGnT1 in HeLa cells. Transfected cells harboring this patient’s L440R mutant POMGnT1 showed POMGnT1 mislocalization to both the Golgi apparatus and endoplasmic reticulum. We have provided clinical, histological, enzymatic and genetic evidence of POMGnT1 involvement in three unrelated MEB disease patients in China. The identification of novel POMGnT1 mutations and an expanded phenotypic spectrum contributes to an improved understanding of POMGnT1 structure–function relationships, CMD pathophysiology and genotype–phenotype correlations, while underscoring the need to consider POMGnT1 in Chinese MEB disease patients.     

Genome-wide identification and characterisation of F-box family in maize

F-box-containing proteins, as the key components of the protein degradation machinery, are widely distributed in higher plants and are considered as one of the largest known families of regulatory proteins. The F-box protein family plays a crucial role in plant growth and development and in response to biotic and abiotic stresses. However, systematic analysis of the F-box family in maize (Zea mays) has not been reported yet. In this paper, we identified and characterised the maize F-box genes in a genome-wide scale, including phylogenetic analysis, chromosome distribution, gene structure, promoter analysis and gene expression profiles. A total of 359 F-box genes were identified and divided into 15 subgroups by phylogenetic analysis. The F-box domain was relatively conserved, whereas additional motifs outside the F-box domain may indicate the functional diversification of maize F-box genes. These genes were unevenly distributed in ten maize chromosomes, suggesting that they expanded in the maize genome because of tandem and segmental duplication events. The expression profiles suggested that the maize F-box genes had temporal and spatial expression patterns. Putative cis-acting regulatory DNA elements involved in abiotic stresses were observed in maize F-box gene promoters. The gene expression profiles under abiotic stresses also suggested that some genes participated in stress responsive pathways. Furthermore, ten genes were chosen for quantitative real-time PCR analysis under drought stress and the results were consistent with the microarray data. This study has produced a comparative genomics analysis of the maize ZmFBX gene family that can be used in further studies to uncover their roles in maize growth and development.     

金属烤瓷全冠修复老年人活髓隐裂牙适应证及临床疗效

目的：探讨老年人活髓隐裂牙应用金属烤瓷全冠修复临床效果及适应症。方法：选取本院2006年1月至2011年1月期间收治的356例老年活髓隐裂牙合计621颗为研究对象,根据患牙疼痛程度随机将患者分为咬合疼痛组（A组）104例合计215颗患牙,咬合伴过敏性冷热刺激痛组（B组）122例合计232颗患牙,咬合伴延续性冷热刺激疼痛组（C组）130例合计174颗患牙,所有患者均接受金属烤瓷全冠修复,观察患者在治疗后1个月、6个月、12个月、18个月、24个月治愈情况以及牙髓及根尖周病变及牙髓发生情况。结果：与C组相比,A组、B组术后1个月、6个月、12个月、18个月、24个月治愈率以及总有效率较高,差异有统计学意义（P〈0．05）。结论：金属烤瓷全冠修复适合于轻微咬合疼痛以及咬合伴过敏性冷热刺激痛的患者,而对于咬舍伴延续性冷热刺激疼痛的患者则宜先行根管治疗术再进行全冠修复。     

姜黄素诱导人胰腺癌PANC-1细胞凋亡的机制研究

目的：胰腺癌恶性程度高、进展快、预后差,姜黄素对于抑制恶性肿瘤的发生和进程具有广泛的生物学效应。但姜黄素能否诱导人胰腺癌细胞凋亡,其具体作用机制如何？目前仍无报道。本研究拟观察姜黄素对人胰腺癌PANC．1细胞凋亡的影响,探讨姜黄素诱导PANC．1细胞凋亡的机制。方法：不同浓度姜黄素处理人胰腺癌PANC-1细胞,流式细胞仪检测PANC-1细胞凋亡率,并分析Caspase-9和Caspase-3活性的变化,同时通过RT—PCR和Westemblot分析PANC-1细胞中P53表达的变化。结果：PANC-1细胞经不同浓度的姜黄素处理后,可以显著诱导细胞凋亡,并呈现一定的剂量依赖性,提示姜黄素具有一定抗肿瘤活性。姜黄素能够同时增加Caspase-9和Caspase-3的活性,并呈现一定的剂量依赖性,提示姜黄素可能通过Caspase-9和Caspase-3途径来诱导PANC．1细胞凋亡的发生。RT—PCR和westernblot结果显示,姜黄素可以显著增加PANC-1细胞中P53蛋白表达水平。结论：姜黄素可以显著诱导PANC-1细胞凋亡的发生,提高Caspase-9和Caspase-3的活性,同时增加的P53表达,并呈现一定的剂量依赖性,提示姜黄素诱导PANC-1细胞凋亡的过程可能与增加细胞中Caspase-9,Caspase-3以及P53的表达有关。本研究探讨了姜黄素诱导PANC-1细胞凋亡的分子机制,为姜黄素的进一步应用提供了新的思路和理论支持,在人胰腺癌的临床治疗中具有一定的潜在应用价值。     

Reglα蛋白表达在胃癌及癌前病变组织中的变化

目的：观察再生基因1α（Regeneration gene 1α,Regla）在胃癌前病变组织及胃癌组织中的表达变化,探讨Reglot在胃粘膜癌变中发挥的作用,为临床诊治提供理论基础。方法：收集2011年1月-2012年12月在我院接受胃镜活检的患者胃粘膜组织,病理确诊为浅表性胃炎的为正常组,中度以上萎缩及肠化的为癌前病变组及胃腺癌即胃癌组。采用荧光定量PCR的方法检测三组胃粘膜组织中Regla的mRNA表达情况。结果：Reglet的mRNA表达在正常组、癌变组及胃癌组织中呈进行性升高;胃癌组中,低分化及印戒细胞癌和Ⅳ期胃癌患者的Reg1α表达升高最为明显;Regla在不同分化程度的胃癌组织间表达无显著差异;Regla在Ⅳ期胃癌中的表达显著高于I／II期;差异均具有统计学意义（P〈0．05）。结论：作为一种生长因子Regla可能参与了胃粘膜癌变的过程,并且Reglet的高表达可能与胃癌的预后相关。     

SCY1-like 1 binding protein 1 (SCYL1-bp1) interacts with p53-induced RING H2 protein (Pirh2) after traumatic brain injury in rats

Traumatic brain injury (TBI) triggers a complex series of neurochemical and signaling changes that lead to neuronal dysfunction and overreactive astrocytes. In the current study, we showed that interactions between SCYL1-bp1 and Pirh2 are involved in central nervous system (CNS) injury and repair. Western blot and immunohistochemical analysis of an acute traumatic brain injury model in adult rats revealed significantly increased levels of SCYL1-bp1 and Pirh2 in the ipsilateral brain cortex, compared to contralateral cerebral cortex. Immunofluorescence double-labeling analyses further revealed that SCYL1-bp1 is mainly co-expressed with NeuN. Terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling staining data supported the involvement of SCYL1-bp1 and Pirh2 in neuronal apoptosis after brain injury. We additionally examined the expression profiles of active caspase-3, which were altered in correlation with the levels of SCYL1-bp1 and Pirh2. Notably, both SCYL1-bp1 and Pirh2 were colocalized with active caspase-3, and all three proteins participated in neuronal apoptosis. Immunoprecipitation experiments further revealed interactions of these proteins with each other in the pathophysiology process. To our knowledge, this is the first study to report interactions between SCYL1-bp1 and Pirh2 in traumatic brain. Our data collectively indicate that SCYL1-bp1 and Pirh2 play important roles in CNS pathophysiology after TBI.