Overexpression of JAM-A in Non-Small Cell Lung Cancer Correlates with Tumor Progression

The objective of the current study was to determine the clinical significance of junctional adhesion molecule A (JAM-A) in patients with non-small cell lung cancer (NSCLC) and the biological function of JAM-A in NSCLC cell lines. We showed that JAM-A is predominantly expressed in cell membranes and high expression of JAM-A occurred in 37% of lung tumor specimens compared to corresponding normal tissues. High expression of JAM-A was significantly correlated with TNM stage (P = 0.021), lymph node metastasis (P = 0.007), and decreased overall survival (P = 0.02), In addition, we observed that silencing JAM-A by small interfering RNA inhibited tumor cell proliferation and induced cell cycle arrest at the G1/S boundary. Western blotting analysis revealed that knockdown of JAM-A decreased the protein levels of cyclin D1, CDK4, 6, and P-Rb. Thus, JAM-A plays an important role in NSCLC progression.     

Wnt5a抑制Wnt3a促黑素细胞黑素生成的作用探究

目的：研究WntSa对Wnt3a处理过的melan—a细胞分泌黑色素的影响。方法：体外培养黑色素细胞（melan-a细胞）,分别进行GFP、Wnt3a、Wnt3a＋WntSa处理,比较细胞的突起,酪氨酸酶的活性以及黑素合成相关基因（TYR、TRP2、MITF）表达情况。结果：Wnt3a促进黑色素细胞突起的生长和TYR、TRP2、MITF的表达,而Wnt5a逆转了Wnt3a对黑色素细胞的作用。结论：Wnt5a抑制Wnt3a促黑素细胞黑素生成的作用,表明在melan．a黑素细胞中Wnt5a可有效抑制wnt经典通路。     

Triterpenoids from the Stem Bark of Melia toosendan and Determination of Their Absolute Configurations at C(24)

Six new triterpenoids, meliasenins S–X ( 1 – 6 , resp.), were isolated from the stem bark of Melia toosendan. Their structures were elucidated by mass spectrometry, NMR experiments, and comparison with the known compounds. Particularly, the absolute configuration at C(24) in new compounds was determined through their CD spectra of the [Pr(FOD)₃] complex (fod=1,1,1,2,2,3,3,7,7,7‐decafluoroheptane‐4,6‐dione) in CCl₄, as well as by using Mosher's method.     

类风湿性关节炎伴间质性肺病中肿瘤标志物对肺功能的影响分析

目的：探究类风湿性关节炎伴间质性肺病中肿瘤标志物对肺功能的影响。方法：选取2011年3月至2013年3月我院收治的类风湿性关节炎患者88例,根据其是否伴有ILD,分为RA组53例和RA-ILD组35例。检测两组肺功能指标用力肺活量（FVC）、1s用力呼气容积（FEV1）、最大通气量百分比（MVV）、一氧化碳弥散量（DLCO）,肿瘤标志物癌胚抗原CEA、癌抗原125（CA125）、癌抗原199（CA199）及抗环胍氨酸肽抗体（抗CCP抗体）的值,并利用统计学方法分析肿瘤标记物与肺功能指标、抗CCP抗体的相关性。结果：RA．ILD组FVC、FEV1、MVV、DLCO均比RA组低,CEA、CA125、CA199均比RA组高,结果比较差异显著具有统计学意义（P〈0．05）。但两组抗CCP抗体含量相比却无明显差异,不具有统计学意义（P〉0．05）。相关性分析显示,CEA与FVC、FEV1、MVV、DLCO呈负相关（P〈0．05）,而CA125、CA199却与肺功能指标无相关性,CEA、CA125、CA199与抗CCP抗体均无相关性（P〉0．05）。结论：RA-ILD的肺功能指标均有明显下降,而肿瘤标志物表达水平却明显增高,CEA对肺功能损害影响较大,却与关节损害的关系不大,这为临床对类风湿性关节炎伴间质性肺病早诊断、早治疗提供了依据。     

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.     

Properties of MHC Class I Presented Peptides That Enhance Immunogenicity

T-cells have to recognize peptides presented on MHC molecules to be activated and elicit their effector functions. Several studies demonstrate that some peptides are more immunogenic than others and therefore more likely to be T-cell epitopes. We set out to determine which properties cause such differences in immunogenicity. To this end, we collected and analyzed a large set of data describing the immunogenicity of peptides presented on various MHC-I molecules. Two main conclusions could be drawn from this analysis: First, in line with previous observations, we showed that positions P4–6 of a presented peptide are more important for immunogenicity. Second, some amino acids, especially those with large and aromatic side chains, are associated with immunogenicity. This information was combined into a simple model that was used to demonstrate that immunogenicity is, to a certain extent, predictable. This model (made available at http://tools.iedb.org/immunogenicity/) was validated with data from two independent epitope discovery studies. Interestingly, with this model we could show that T-cells are equipped to better recognize viral than human (self) peptides. After the past successful elucidation of different steps in the MHC-I presentation pathway, the identification of variables that influence immunogenicity will be an important next step in the investigation of T-cell epitopes and our understanding of cellular immune responses.     

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

Background

Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90–1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91–1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73–4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38–3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk.

Conclusions

This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.     

A new species of Hiptage (Malpighiaceae) from Nujiang Gorge,southwest China

Hiptage lushuiensis, a new species from the Hengduan Mountains, northwestern Yunnan Province, China, is described and illustrated here. This species was found growing at the margin of an open forest in the Nujiang Gorge of Lushui City. Hiptage lushuiensis is distinctive for its pink petals, 2 or more calyx glands, and large and pink samara with white hairs. This species is isolated in the deep gorge (25°51′N, 98°51′E, altitude 917 m), at the northern edge distribution range of the genus. These distinctive morphological differences and the geographic isolation suggest a history of long-distance dispersal and allopatric speciation. Hiptage lushuiensis has a shorter filament but larger herkogamy than related species, suggesting that H. lushuiensis may have adapted to other pollinators with short but fat body such as Amegilla or Bombus spp.     

Analyzing the action of evolutionarily conserved modules on HMW-GS 1Ax1 promoter activity

Key message

The specific and high-level expression of 1Ax1 is determined by different promoter regions. HMW-GS synthesis occurs in aleurone layer cells. Heterologous proteins can be stored in protein bodies.

Abstract

High-molecular-weight glutenin subunit (HMW-GS) is highly expressed in the endosperm of wheat and relative species, where their expression level and allelic variation affect the bread-making quality and nutrient quality of flour. However, the mechanism regulating HMW-GS expression remains elusive. In this study, we analyzed the distribution of cis-acting elements in the 2659-bp promoter region of the HMW-GS gene 1Ax1, which can be divided into five element-enriched regions. Fragments derived from progressive 5′ deletions were used to drive GUS gene expression in transgenic wheat, which was confirmed in aleurone layer cells, inner starchy endosperm cells, starchy endosperm transfer cells, and aleurone transfer cells by histochemical staining. The promoter region ranging from ??297 to ??1 was responsible for tissue-specific expression, while fragments from ??1724 to ??618 and from ??618 to ??297 were responsible for high-level expression. Under the control of the 1Ax1 promoter, heterologous protein could be stored in the form of protein bodies in inner starchy endosperm cells, even without a special location signal. Our findings not only deepen our understanding of glutenin expression regulation, trafficking, and accumulation but also provide a strategy for the utilization of wheat endosperm as a bioreactor for the production of nutrients and metabolic products.