Long noncoding RNA growth arrest-specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR-dependent manner

Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest-specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy-related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin-inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5-mediated depression in cisplatin-evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5-increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.     

B(a)P暴露干扰细胞周期调控蛋白影响孕早期小鼠卵巢黄体功能

该研究旨在探讨苯并(a)芘[Benzo(a)pyrene,B(a)P]对孕早期小鼠卵巢黄体功能的影响及机制.体内模型:将昆明小鼠每晚按雌雄3∶1的比例合笼,次晨查得阴栓记为孕第1天(d1);将其随机分为对照组和B(a)P处理组,每日早晨称重后以0.1 mL/10 g动物体质量灌胃给予0.2 mg/(kg·d)的B(a)...     

Influence of cycle exercise on acetone in expired air and skin gas

Abstract

This study investigated the influence of cycle exercise on acetone concentration in expired air and skin gas. The subjects for this experiment were eight healthy males. Subjects performed a continuous graded exercise test on a cycle ergometer. The workloads were 360 (1.0 kg), 720 (2.0 kg), 990 (2.75 kg) kgm/min, and each stage was 5 min in duration. A pedaling frequency of 60 rpm was maintained. Acetone concentration was analyzed by gas chromatography. The acetone concentration in expired air and skin gas during exercise at 990 kgm/min intensity was significantly increased compared with the basal level. The skin-gas acetone concentration at 990 kgm/min significantly increased compared with the 360 kgm/min (P < 0.05). The acetone excretion of expired air at 720 kgm/min and 990 kgm/min significantly increased compared with the basal level (P < 0.05). Acetone concentration in expired air was 4-fold greater than skin gas at rest and 3-fold greater during exercise (P < 0.01). Skin gas acetone concentration significantly related with expired air (r = 0.752; P < 0.01). This study confirmed that the skin-gas acetone concentration reflected that of expired air.     

Integrated analysis of DNA methylation and mRNA expression profiling reveals candidate genes associated with cisplatin resistance in non-small cell lung cancer

DNA methylation plays a critical role during the development of acquired chemoresistance. The aim of this study was to identify candidate DNA methylation drivers of cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). The A549/DDP cell line was established by continuous exposure of A549 cells to increasing concentrations of DDP. Gene expression and methylation profiling were determined by high-throughput microarrays. Relationship of methylation status and DDP response was validated in primary tumor cell culture and the Cancer Genome Atlas (TCGA) samples. Cell proliferation, apoptosis, cell cycle, and response to DDP were determined in vitro and in vivo. A total of 372 genes showed hypermethylation and downregulation in A549/DDP cells, and these genes were involved in most fundamental biological processes. Ten candidate genes (S100P, GDA, WISP2, LOXL1, TIMP4, ICAM1, CLMP, HSP8, GAS1, BMP2) were selected, and exhibited varying degrees of association with DDP resistance. Low dose combination of 5-aza-2′-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) reversed drug resistance of A549/DDP cells in vitro and in vivo, along with demethylation and restoration of expression of candidate genes (GAS1, TIMP4, ICAM1 and WISP2). Forced expression of GAS1 in A549/DDP cells by gene transfection contributed to increased sensitivity to DDP, proliferation inhibition, cell cycle arrest, apoptosis enhancement, and in vivo growth retardation. Together, our study demonstrated that a panel of candidate genes downregulated by DNA methylation induced DDP resistance in NSCLC, and showed that epigenetic therapy resensitized cells to DDP.     

Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development

Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR, GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho > 0.9; P < 0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.     

Fatty acid composition of muscle and heart tissue of Nile perch,Lates niloticus,and Nile tilapia,Oreochromis niloticus,from various populations in Lakes Victoria and Kioga,Uganda

The fatty acid composition in the heart tissue and muscle tissue of the Nile perch, Lates niloticus, and Nile tilapia, Oreochromis niloticus populations from Lakes Kioga and Victoria was determined by methanolysis and gas chromatography of the resulting fatty acid methyl esters. The analytical data were treated by multivariate principal component analysis. The most abundant individual fatty acids were palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1n9), vaccenic acid (18:1n7), arachidonic acid (20:4n6) and docosahexaenoic acid (22:6n3). Due to high levels of both n6 and n3 fatty acids, the ratios of n3 to n6 were between 1 and 2, typical for freshwater fish species. Two Lake Victoria and one Lake Kioga populations of Nile tilapia and Nile perch were distinguished by the fatty acid profiles in their heart and muscle tissue. The heart tissue showed better separation than muscle tissue, due to dominance of polar phospholipids. It is rationalised that genetics are more important than diet in determining the fatty acid composition of the tissues.