GDP Induces PANC-1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway

Pancreatic tumors are hypovascular, which leads to a poor nutrient supply to support the aggressively proliferating tumor cells. However, human pancreatic cancer cells have extreme resistance to nutrition starvation, which enables them to survive under severe metabolic stress conditions within the tumor microenvironment, a phenomenon known as “austerity” in cancer biology. Discovering agents which can preferentially inhibit the cancer cells’ ability to tolerate starvation conditions represents a new generation of anticancer agents. In this study, geranyl 2,4-dihydroxy-6-phenethylbenzoate (GDP), isolated from Boesenbergia pandurata rhizomes, exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition starvation conditions. GDP also possessed PANC-1 cell migration and colony formation inhibitory activities under normal nutrient-rich conditions. Mechanistically, GDP inhibited PI3K/Akt/mTOR/autophagy survival signaling pathway, leading to selective PANC-1 cancer cell death under the nutrition starvation condition. Therefore, GDP is a promising anti-austerity agent for drug development against pancreatic cancer.     

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.     

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。     

Association of genetic variants in enamel-formation genes with dental caries: A meta- and gene-cluster analysis

Previous studies have reported the association between multiple genetic variants in the enamel-formation genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in the enamel-formation genes and the risk of dental caries. We identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR = 1.40, 95% CI: 1.02–1.93, P = 0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR = 1.15, 95% CI: 0.88–1.52, P = 0.310), rs1784418 in MMP20 (OR = 1.07, 95% CI: 0.76–1.49, P = 0.702) and rs3796704 in ENAM (OR = 1.06, 95% CI: 0.96–1.17, P = 0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P < 10⁻⁵), so did genetic variants in MMP13 (3 variants; P = 0.004), MMP2 (3 variants; P < 10⁻⁵), MMP20 (2 variants; P < 10⁻⁵) and MMP3 (2 variants; P < 10⁻⁵). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P < 10⁻⁵). The present meta-analysis revealed that genetic variant rs17878486 in AMELX was associated with dental caries, and multiple genetic variants in the enamel-formation genes jointly contributed to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.