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High-yield dairy cows are usually subject to high-intensive cell metabolism and produce excessive reactive oxygen species (ROS). Once ROS is beyond the threshold of scavenging ability, it can induce oxidative stress, imperilling the reproductive performance of cows. The study was to investigate the effects of vitamin E (VE) on H 2 O 2 -induced proliferation and apoptosis of bovine granulosa cells and the underlying molecular mechanism. Granulosa cells were pretreated with VE for 24 hr and then treated with H 2 O 2 for 6 hr. The results showed that VE treatment decreased the intracellular ROS levels, increased the MDA content, and improved the antioxidant enzyme activity in a dose-dependent manner. Furthermore, VE treatment promoted the proliferation and inhibited apoptosis in granulosa cells by up-regulation of CCND1 and BCL2 levels and down-regulation of P21, BAX, and CASP3 levels. The cytoprotective effects of VE were attributed to the activation of the NRF2 signalling pathway. Knockdown of the NRF2 impaired the cytoprotective effects of VE on granulosa cells. Besides, the PI3K/AKT and ERK1/2, but not the p38 signalling pathway is involved in the regulation of VE-mediated cell proliferation and apoptosis. The PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited the VE-induced granulosa cell proliferation and promoted apoptosis, whereas the p38 inhibitor SB203580 had the opposite effects. These results were confirmed by proliferation and apoptosis-related gene expression at mRNA and protein levels. The results also showed that the PI3K/AKT inhibitor LY294002 and ERK1/2 inhibitor SCH772984 inhibited VE-induced NRF2, GCLC, GCLM, and HO-1 expression, whereas the p38 inhibitor SB203580 not. Overall, the results demonstrated that VE-regulated granulosa cell proliferation and apoptosis via NRF2-mediated defence system by activating the PI3K/AKT and ERK1/2 signalling pathway., (© 2021 Wiley-VCH GmbH.)

Endosulfan as a new member of persistent organic pollutants has been shown to induce reproductive dysfunction in various animal models. However, the action mechanism of endosulfan-produced reproductive toxicity remains largely unknown. This study was focused on investigating the reproductive toxicity induced by α-endosulfan and clarifying the role of mitochondria and genotoxic response genes in germ cell apoptosis of Caenorhabditis elegans. Our data showed that endosulfan induced a dose-dependent decrease of life span, fecundity, and hatchability, whereas the germ cell apoptosis was dose-dependently increased. The mitochondria membrane potential was disrupted by endosulfan, leading to a significant increase of germ cell apoptosis in mev-1(kn-1) mutant. However, the apoptotic effects of endosulfan were blocked in mutants of cep-1(w40), egl-1(n487), and hus-1(op241), indicating conserved genotoxic response genes played an essential role in endosulfan-induced germ cell apoptosis. Furthermore, exposure to endosulfan induced the accumulation of HUS-1::GFP foci and the germ cell cycle arrest. These findings provided clear evidence that endosulfan caused significant adverse effects on the reproduction system of C. elegans and increased germ cell apoptosis, which was regulated by mitochondrial dysfunction and DNA damage response genes. This study may help to understand the signal transduction pathways involved in endosulfan-induced reproductive toxicity., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study is aimed at separating and identifying a new glycoprotein from sweet potato (SPG) and detecting its anti-colon cancer bioactivity. The SPG-56 was obtained by water extraction, isoelectric precipitation, chromatography and electrophoresis. The compositions of sugar and protein in SPG-56 were identified with high performance liquid chromatography and amino acid analyzer, and the antitumor activities were explored using BALB/c nude mice and human colon cancer cells (HCT-116). Results showed that the molecular weight of SPG-56 is 56 KD. Relative sugar and protein contents of SPG-56 are 2.9% and 97.1%, comprising more than 6 types of sugars and 15 kinds of amino acids. Animal experiments showed that orally administrated SPG-56 could obviously suppress the tumor growth. Results from flow cytometry, western blotting and immunohistochemistry indicated that SPG-56 inhibits cancer by inducing apoptosis. These results suggest that SPG-56 would potentially delay the development of colon cancer. [ABSTRACT FROM AUTHOR]

Aims This study is aimed at detecting the anti-tumor efficacy of a new berberine (BBR) derivative 8-cetylberberine (HBBR), which has a significant improvement in hydrophobicity and pharmacological effects compared to BBR. Main methods The human non-small lung cancer cell line A549 and normal human lung epithelial cells (MRC-5) were cultured to observe inhibition in vitro . Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of HBBR on cell cycle arrest and apoptosis were assessed by flow cytometry and western blotting. In animal studies, BALB/c nude mice were subcutaneously injected with A549 cells in the armpit and administrated with different dose of HBBR and BBR. The body weight, organ coefficient and tumor inhibitory rate were recorded to evaluate the effect of HBBR in vivo . Key findings The data showed that HBBR induced G1-phase cycle arrest by interfering with the expression of Cyclins D1 and Cyclin E1, increased apoptosis by inducing caspase pathway, and probably inhibited the PI3K/Akt pathway in A549 cells. In addition, animal experiments proved that oral administration of HBBR at a dose of 10 mg/kg could significantly inhibit tumor growth, which is stronger than the 120 mg/kg dose of BBR treatment. Significance Our results suggest that HBBR showed a significantly higher anti-tumor efficacy than BBR in vitro and in vivo and could be a potential therapy for lung cancers. [ABSTRACT FROM AUTHOR]