NEK2 plays an active role in Tumorigenesis and Tumor Microenvironment in Non-Small Cell Lung Cancer

Abnormal expression and dysfunction of Never-in-mitosis-A-related kinase 2 (NEK2) result in tumorigenesis. High levels of NEK2 are related to malignant progression, drug resistance, and poor prognosis. However, the relationship between NEK2 levels and the occurrence of non-small cell lung cancer (NSCLC) remains unknown. This study aimed to explore the impacts of NEK2 on the oncogenesis of NSCLC and the tumor microenvironment. Downregulation of NEK2 inhibited A549 and H1299 cell proliferation, migration, and invasion, blocking cell cycle at the G0/G1 phase. Loss of NEK2 inhibited the release of IL-10 from tumor cells, M2-like polarization of macrophages, angiogenesis, and vascular endothelial cell migration. Furthermore, NEK2 deficiency inhibited tumor growth in vivo. Taken together, NEK2 knockdown inhibited the occurrence and development of NSCLC, M2 polarization of macrophages, and angiogenesis. The abnormal expression of NEK2 might not only indicate tumor progression and patient prognosis but also serve as a potential molecular therapeutic target with great development prospects.     

蓝光对保护地蔬菜烟粉虱的控制作用

[目的]研究蓝光开灯时段、蓝光光强对烟粉虱Bemisia tabaci (Gennadius)的驱避作用,以及蓝光照射对保护地辣椒和黄瓜上烟粉虱的控制作用,为利用驱虫灯实施对蔬菜烟粉虱的绿色防控提供科学依据.[方法]在蔬菜上用蓝光(波长为470 nm)照射,设置照射时间段17:00-18:00、18:00-19:00、19:00-20:00、20:00-21:00和21:00-22:005个处理、光照强度1、2、6、8、10、20、30、70、1501x9个处理,分别研究不同开灯时段和光强对烟粉虱的驱避作用,以不用蓝光处理为对照;分别在保护地黄瓜和辣椒上放置蓝色灯带,每天18:00-20:00开灯,每3d一次,分别调查黄瓜和辣椒上烟粉虱的虫量.[结果]18:00-19:00时间段蓝光照射对蔬菜烟粉虱的驱避作用最强,虫口减退率占试验总时段的50.94％;17:00-18:00次之,占22.29％;烟粉虱的虫口减退率与光照强度呈正相关(P＜0.05),其回归方程为)y=3.0297x+ 12.508 (R2=0.981).蓝光对保护地辣椒和黄瓜上烟粉虱有较好的驱避作用,辣椒上蓝光处理10d后烟粉虱的虫口减退率达到85.73％,上部叶片和中部叶片上虫口减退率之间没有显著差异(P＞0.05);蓝光处理黄瓜12d后烟粉虱的虫口减退率达90.33％,在光照的前期上部叶片的虫口减退率高于中部叶片,处理9d后上部叶片和中部叶片上虫口减退率之间没有显著差异(P＞0.05).[结论]蓝光对蔬菜烟粉虱具有较强的驱避作用,在18:00-19:00使用蓝光对保护地蔬菜上的烟粉虱的控制效果较好.     

实时定量PCR构建法夫酵母内参基因β-actin、 gpd、18S rRNA标准品质粒和标准曲线

为建立检测法夫酵母JMU-MVP14中虾青素合成相关基因在不同生长时期表达水平的实时定量PCR方法,构建法夫酵母JMU-MVP14的管家基因β-actin、gpd、18S rRNA的标准质粒,进行实时定量PCR,制作标准曲线及回归方程.β-actin基因标准曲线相关系数（R2）=0.9956,扩增效率（E） =96.93％;gpd基因标准曲线相关系数（R2） =0.9901,扩增效率（E） =93.78％;18S rRNA基因标准曲线相关系数（R2） =0.9981,扩增效率（E）=98.76％.3个基因片段的熔解曲线均呈单峰;扩增曲线呈典型的S型动力学曲线,指数期和平台期明显,为理想的熔解曲线和扩增曲线.用geNorm软件对三个管家基因的稳定性进行分析,三个基因的稳定性排序为β-actin＞ 18S rRNA＞ gpd,故β-actin和18S rRNA较适合作为研究法夫酵母JMU-MVP14定量实验的内参基因.     

以整合素αvβ3为靶点的RGD配体在抗肿瘤血管新生中的应用

整合素αvβ3是一种能特异性识别RGD序列的膜受体蛋白,其与含RGD（Arg-Gly-Asp）模体的蛋白质结合的特异性在肿瘤细胞的粘附、迁移、浸润及肿瘤血管新生中起重要作用.由于整合素αvβ3在多种肿瘤细胞表面高表达而在正常细胞中低表达或不表达,因此其成为肿瘤治疗的理想靶点.肿瘤新生血管为肿瘤的生长提供营养,因此近年来抑制肿瘤血管新生也成为肿瘤治疗的重要途径.有研究显示,几种RGD毒素蛋白不但以整合素αvβ3为靶点靶向结合到肿瘤部位从而具有直接抗肿瘤细胞增殖、黏附、迁移及浸润功能,而且它们还具有抗肿瘤血管新生的作用,因此RGD毒素蛋白可从上述两方面抑制肿瘤生长与转移.本文就整合素αvβ3为靶向的RGD配体结构特点及其在肿瘤治疗中的靶向治疗和抗血管新生应用及前景加以综述.     

Bone morphogenetic protein 9 overexpression reduces osteosarcoma cell migration and invasion

Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9.     

Identification of a complete set of functional markers for the selection of er1 powdery mildew resistance in Pisum sativum L.

Powdery mildew is the most widespread disease of pea (Pisum sativum L.) and causes severe economic losses worldwide. Recessively inherited er1 powdery mildew resistance, successfully used for decades in pea breeding programs, has recently been shown to originate from the loss of function of the PsMLO1 gene. Five er1 alleles, each corresponding to a different PsMLO1 null mutation, have been characterized to date in pea germplasm. In order to aid er1 selection, we aimed to identify functional markers which target PsMLO1 polymorphisms directly responsible for the resistant phenotype. Highly informative cleaved amplified polymorphic sequence (CAPS), derived cleaved amplified polymorphic sequence (dCAPS), sequence tagged site (STS) and high-resolution melting (HRM) markers were developed which enable the selection of each of the five er1 alleles. Taken together, the results described here provide a powerful tool for breeders, overcoming limitations of previously reported er1-linked markers due to the occurrence of recombination with the resistance locus and/or the lack of polymorphism between parental genotypes. The HRM marker er1-5/HRM54 reported here, targeting a mutagenesis-induced er1 allele recently described by us, does not require manual processing after PCR amplification, and is therefore suitable for large-scale breeding programs based on high-throughput automated screening.     

Involvement of and Interaction between WNT10A and EDA Mutations in Tooth Agenesis Cases in the Chinese Population

Background

Dental agenesis is the most common, often heritable, developmental anomaly in humans. Although WNT10A gene mutations are known to cause rare syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia (OODD), Schöpf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia (HED), and more than half of the cases of isolated oligodontia recently, the genotype-phenotype correlations and the mode of inheritance of WNT10A mutations remain unclear. The phenotypic expression with WNT10A mutations shows a high degree of variability, suggesting that other genes might function with WNT10A in regulating ectodermal organ development. Moreover, the involvement of mutations in other genes, such as EDA, which is also associated with HED and isolated tooth agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR, and EDARADD encode signaling molecules in the Eda/Edar/NF-κB signaling pathways, we also checked EDAR and EDARADD in this study.

Methods

WNT10A, EDA, EDAR and EDARADD were sequenced in 88 patients with isolated oligodontia and 26 patients with syndromic tooth agenesis. The structure of two mutated WNT10A and two mutated EDA proteins was analyzed.

Results

Digenic mutations of both WNT10A and EDA were identified in 2 of 88 (2.27%) isolated oligodontia cases and 4 of 26 (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was found.

Conclusions

WNT10A and EDA digenic mutations could result in oligodontia and syndromic tooth agenesis in the Chinese population. Moreover, our results will greatly expand the genotypic spectrum of tooth agenesis.     

Effects of Remifemin Treatment on Bone Integrity and Remodeling in Rats with Ovariectomy-Induced Osteoporosis

This study aims to evaluate the effects of Remifemin (isopropanolic extract of Cimicifuga Racemosa) on postmenopausal osteoporosis. 120 female Sprague-Dawley rats were randomly assigned to four groups: sham surgery with vehicle, ovariectomy with vehicle, ovariectomy with estradiol valerate, or ovariectomy with Remifemin. Daily oral administrations of the vehicle, estradiol valerate, or Remifemin began 2 weeks after surgery and lasted to 4, 8, or 12 weeks. Ten rats in each group were sacrificed at each timestep with assessment of bone mineral density, trabecular bone structure, and biomechanical parameters of the femur and lumbar vertebra. Bone turnover markers were evaluated 12 weeks after surgery. Both drugs prevented bone density loss in the distal end of the femur and preserved the trabecular bone structure in both the lumbar vertebra and distal end of the femur following ovariectomy. Both drugs protected bone stiffness at the tested regions and reduced bone reabsorption in ovariectomized rats. The preventive effects of Remifemin against bone-loss can rival those of estradiol valerate if treatment duration is adequately extended. In conclusion, Remifemin may demonstrate equivalent effects to estradiol valerate in terms of preventing postmenopausal osteoporosis.