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FGF21 is recently discovered with pleiotropic effects on glucose and lipid metabolism. However, the potential protective effect of FGF21 against D-gal-induced injury in the liver has not been demonstrated. The aim of this study is to investigate the pathophysiological role of FGF21 on hepatic oxidative injury and apoptosis in mice induced by D-gal. The 3-month-old Kunming mice were subcutaneously injected with D-gal (180 mg kg(-1) d(-1)) for 8 weeks and administered simultaneously with FGF21 (5 or 1 mg kg(-1) d(-1)). Our results showed that the administration of FGF21 significantly alleviated histological lesion including structure damage, degeneration, and necrosis of hepatocytes induced by D-gal, and attenuated the elevation of liver injury markers, serum AST, and ALP in a dose-dependent manner. FGF21 treatment also suppressed D-gal-induced profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level in the liver, and restored the activities of antioxidant enzymes SOD, CAT, GSH-Px, and T-AOC. Moreover, FGF21 treatment increased the nuclear abundance of Nrf2 and subsequent up regulation of several antioxidant genes. Furthermore, a TUNEL assay showed that D-gal-induced apoptosis in the mouse liver was significantly inhibited by FGF21. The expression of caspase-3 was markedly inhibited by the treatment of FGF21 in the liver of D-gal-treated mice. The levels of PI3K and PBK/Akt were also largely enhanced, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 and Bax proteins in the liver of D-gal-treated mice. In conclusion, these results suggest that FGF21 protects the mouse liver against D-gal-induced hepatocyte oxidative stress via enhancing Nrf2-mediated antioxidant capacity and apoptosis via activating PI3K/Akt pathway.

Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, many researchers have reported that lentogenic NDV is a safe and effective agent for human cancer therapy. It had been demonstrated that the amino acid sequence of the fusion protein cleavage site is a major factor in the pathogenicity and anti-tumor efficacy of rNDV. However, the role of Hemagglutinin-Neuraminidase (HN) gene that contributes to virulence and anti-tumor efficacy remains undefined. To assess the role of HN gene in virus pathogenicity and anti-tumor efficacy, a reverse genetic system was developed using the lentogenic NDV Clone30 strain to provide backbone for gene exchange. Chimeric virus (rClone30-Anh(HN)) created by exchange of the HN gene of lentogenic strain Clone30 with HN gene of mesogenic strain produce no significant changes in virus pathogenicity as assessed by conducting the mean death time (MDT) and intracerebral pathogenicity index (ICPI) assays. In vitro , infection with chimeras could induce the formation of syncytium relative significantly in HepG2 cells. Furthermore, chimeras was shown to induce the cell apoptosis via MTT and Annexin V-PI assays, reduce mitochondrial membrane potential and increase the mRNA transcription level of caspase 3. In vivo , ICR mice carrying tumor of hepatoma H22 cells were treated via intratumoral injection of chimeric virus. The treatment of chimera shows an obvious suppression in tumor volume. These results suggest that it could be an ideal approach to enhance the antitumor ability of Newcastle disease virus and highlighted the potential therapeutic application of rClone30-Anh(HN) as a viral vector to deliver foreign genes for treatment of cancers. [ABSTRACT FROM AUTHOR]

• BAAPE induced developmental defects in zebrafish embryos at early stages. • Embryos exposure to BAAPE with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). • BAAPE caused cardiotoxicity and changed the expression levels of key genes in cardiac development in zebrafish larvae. • BAAPE exposure induced production and accumulation of ROS and enhanced oxidative stress levels. • BAAPE caused mitochondria-mediated apoptosis in zebrafish larvae. Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects. [ABSTRACT FROM AUTHOR]