Astragaloside IV attenuates inflammatory response mediated by NLRP-3/calpain-1 is involved in the development of pulmonary hypertension

Inflammation eventually leads to pulmonary arterial hypertension (PAH). Astragaloside IV(AS-IV) has a protective effect on pulmonary hypertension, but the specific protective mechanism has been unclear until now. Therefore, in this study, our aim was to investigate the mechanisms underlying the effects of AS-IV on PAH. In vivo, male Sprague-Dawley (SD) rats were injected intraperitoneally with monocrotaline (MCT, 60 mg/kg) and treated with AS-IV (40 mg/kg, 80 mg/kg), MCC950 and MDL-28170. In vitro, human pulmonary artery endothelial cells (HPAECs) were treated with monocrotaline pyrrole (MCTP, 60 μg/mL). The protein expression levels of NLRP-3, caspase-1, ASC, IL-18, IL-1β and calpain-1 were measured in vivo and/or in vitro. The results showed that AS-IV decreased the protein expression levels of NLRP-3, caspase-1, ASC, IL-18, IL-1β and calpain-1 in vivo and/or vitro. In conclusion, in this study the results suggested that AS-IV could inhibit monocrotaline-induced pulmonary arterial hypertension via the NLRP-3/calpain-1 pathway.     

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.     

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.     

ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition

Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a potential target for improving radiosensitivity.Materials and Methods: The radiosensitivity of NSCLC cells was evaluated by flow cytometry, colony formation assays, immunofluorescence, and Western blotting. Bioinformatics assay was used to identify the effect of ITGB1 and YAP1 expression in NSCLC tissues.Results: ITGB1 mRNA and protein expression levels were higher in H460R than in the parental H460 cells. We observed lower clonogenic survival and cell viability and a higher rate of apoptosis of ITGB1-knockdown A549 and H460R cells than of wild type cells post-irradiation. Transfection with an ITGB1 short hairpin (sh) RNA enhanced radiation-induced DNA damage and G2/M phase arrest. Moreover, ITGB1 induced epithelial-mesenchymal transition (EMT) of NSCLC cells. Silencing ITGB1 suppressed the expression and intracellular translocation of Yes-associated protein 1 (YAP1), a downstream effector of ITGB1.Conclusions: ITGB1 may induce radioresistance via affecting DNA repair and YAP1-induced EMT. Taken together, our data suggest that ITGB1 is an attractive therapeutic target to overcome NSCLC cell radioresistance.     

Nuclear-localized eukaryotic translation initiation factor 1A is involved in mouse preimplantation embryo development

Journal of Molecular Histology - Preimplantation embryo development is characterized by drastic nuclear reprogramming and dynamic stage-specific gene expression. Key regulators of this earliest...     

干旱对不同花椒种植模式下土壤微生物和线虫群落的影响

随着全球气候变暖, 我国岷江上游干旱区面积呈现增加的趋势。花椒(Zanthoxylum bungeanum)是岷江上游重要的经济树种之一, 对当地经济和社会发展起着重要作用, 提高花椒生态系统应对干旱干扰已成为迫切的问题。本研究设置了花椒单作、花椒-苜蓿(Medicago sativa)间作和花椒-大豆(Glycine max)间作3种种植模式, 在2015年8月对每种种植模式模拟干旱30 d, 每种种植模式包括干旱和对照处理, 在模拟干旱结束后、恢复15 d、30 d和45 d后分别采集土壤样品, 分析土壤化学性质、土壤微生物和线虫群落, 以探究花椒林下豆科植物能否缓和干旱的遗留效应对土壤化学性质和土壤生物的影响。重复测量方差分析表明: 在花椒单作模式下, 干旱恢复45 d后土壤硝态氮含量显著高于对照, 微生物量和真菌/细菌比与对照无显著差异, 线虫密度与对照无显著差异, 但线虫功能团没有恢复到对照水平; 在花椒-苜蓿间作模式下, 干旱恢复45 d后土壤含水量、铵态氮、硝态氮、溶解性有机碳、溶解性有机氮、微生物量、真菌/细菌比、线虫密度和线虫功能团组成与对照无显著差异, 但植食性线虫属Boleodorus相对多度显著高于对照; 在花椒-大豆间作模式下, 干旱恢复45 d后土壤含水量、铵态氮、硝态氮、溶解性有机碳、溶解性有机氮、微生物量和真菌/细菌比与对照无显著差异, 但线虫密度和功能团组成与对照有显著差异。在3种花椒种植模式中, 花椒-苜蓿间作模式下干旱的遗留效应对土壤养分和生物的影响最小。因此, 在干旱背景下, 花椒林下间作豆科植物可以加快土壤养分、土壤微生物和线虫群落的恢复, 进而有利于目标作物生长。     

隆水蚤科多样性与生态学研究进展

隆水蚤科以其丰富的个体数和多样性成为海洋水体生态系统中极为重要的小型桡足类, 但其分类学和多样性研究仍有较大不足, 其生态功能及在生态系统中的地位存在被低估的可能。为了提升对隆水蚤科的认识, 本文对国际隆水蚤科分类学和物种多样性研究进展、隆水蚤科的物种多样性研究难点和技术发展趋势、隆水蚤科的分布和生态等方面研究进行概述。19世纪末Giesbrecht创建隆水蚤科, 随后该科的新物种不断被发现和描述, 目前已描述115种。中国海仅记录到隆水蚤科物种11种, 相关生态学研究较薄弱。隆水蚤科由于个体小, 许多物种间具有高度的形态相似性, 并且包含很多姐妹种及种内分型, 因此许多研究将传统分类鉴定手段与分子生物学技术相结合, 以提高物种的发现和描述效率。随着研究的不断深入, 有关隆水蚤科物种的分布特征、食性特征、种群特征和行为学特征等均得到不同程度的关注, 这都将提高隆水蚤科研究的广度和深度。随着研究技术的迅速发展以及许多设备先进的科学考察船和载人潜水器被用于海洋研究, 从近海、边缘海到深远海研究的协同发展, 海洋生物样品资源不断丰富, 这将带动我国分类和多样性研究快速发展, 使隆水蚤科的分类学研究不断深入。