Neuroprotective effect of resveratrol against radiation after surgically induced brain injury by reducing oxidative stress, inflammation, and apoptosis through NRf2/HO-1/NF-κB signaling pathway.

The impact of resveratrol (RSV) on radiation (RAD)-induced brain injury in rats' brains was investigated. A total of 40 male Wistar Albino rats were randomly divided into four groups (control, RAD, RAD + RSV, and RSV groups, with 10 rats in each group). The results revealed a significant decrease in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, as well as glutathione (GSH) content. Further, a significant elevation in malondialdehyde, nitric oxide, interleukin-1-beta (IL-1ß), IL-6, and transforming growth factor-ß1 levels were observed. Furthermore, decreased B-cell lymphoma 2 (Bcl-2), increased Bcl-2-associated X, and tumor necrosis factor-α genes expression, decreased nuclear factor erythroid-related factor 2, heme oxygenase-1, and increased nuclear factor-κB protein levels were noticed. Also, an apoptosis marker, caspase-3-positive cells, was seen in the hippocampus. Those effects were observed in the RAD group of rats. The treatment of RSV displayed a significant amendment of the studied parameters in the brain tissues of the RAD group of animals. This effect is interrelated to the ability of RSV to scavenge the free radicals, enhance the activity of the antioxidant enzymes, increase GSH contents, and downregulate the inflammatory responses and apoptosis markers in the brain tissues of RAD animals. In conclusion, this study demonstrated that the potent antioxidant, anti-inflammatory, and antiapoptotic activities of RSV can improve the antioxidant status and suppress the inflammatory responses and apoptosis in the brain tissues of RAD animals.

Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved. METHODS: Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo. RESULTS: We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain-derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence. CONCLUSION: Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.

Effects of perfluorooctane on the retina as a short-term and small amounts remnant in rabbits.

AIM: To investigate changes in the rabbit retina after short-term and small amounts tamponade of perfluorooctane (PFO). METHODS: New Zealand rabbits were used, and 48 eyes were randomly and evenly assigned into four different groups. The PFO groups received a residue of 0.1 mL of PFO for ophthalmic surgery or 0.1 mL of F-Octane at the end of surgery; eyes from the pars plana vitrectomy (PPV) group were filled with balanced salt solution and those having not received surgical intervention served as controls. Eyes were collected at 1, 4 and 12wk and studied. RESULTS: Under a microscope, nuclear counts of the inner nuclear layer (INL) and outer nuclear layer (ONL) did not differ among the four groups at all time points; however, slight disarrangement of the ONL and occasional vacuolization of the INL were found in the inferior retina only at 12wk in two PFO groups. Four of the groups had similar results of Caspase-3 and TNF-α staining at all time points. Alternatively, IL-8 was increased in PFOa and PPV control groups at 4wk and in all three PPV groups at 12wk; also, the apoptotic index (%) was similarly increased in all three PPV groups at 4 and 12wk. CONCLUSION: Both PFOs are well tolerated in rabbit eyes for up to 12wk, which suggests that they can be used safely as intraoperative tools or for short-term and small amounts tamponade after surgery.

Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice.

Tris (2-ethylhexyl) trimellitate (TOTM) is commonly used as an alternative plasticizer for medical devices. But very little information was available on its biological effects. In this study, we investigated toxicity effects of TOTM on hepatic differential gene expression analyzed by using high-throughput sequencing analysis for over-represented functions and phenotypically anchored to complementary histopathologic, and biochemical data in the liver of mice. Among 1668 candidate genes, 694 genes were up-regulated and 974 genes were down-regulated after TOTM exposure. Using Gene Ontology analysis, TOTM affected three processes: the cell cycle, metabolic process and oxidative activity. Furthermore, 11 key genes involved in the above processes were validated by real time PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these genes were involved in the cell cycle pathway, lipid metabolism and oxidative process. It revealed the transcriptome gene expression response to TOTM exposure in mouse, and these data could contribute to provide a clearer understanding of the molecular mechanisms of TOTM-induced hepatotoxicity in human.