Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells.

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

Global occurrence of deoxynivalenol in food commodities and exposure risk assessment in humans in the last decade: a survey.

Preventing food from fungal infestation has become a cause of great concern as food safety is of particular importance to public health globally. Recently International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in its 2016 press release has urged to take action against widespread mycotoxin contamination in developing countries. Deoxynivalenol (DON) is a group B trichothecene mycotoxin, produced by common field pathogens such as Fusarium graminearum and Fusarium culmorum, and reported to be the predominant contaminant of food commodities. At present, no detailed/systematic review regarding the global occurrence of DON in various food and grain samples is available in the literature. Considering DON's cosmopolitan behavior and toxicological manifestations, the present review summarizes the region-wise reports and surveys conducted across the globe during the last decade, on the occurrence of DON in the food commodities intended for human consumption. Studies conducted on DON metabolites either in food, urine or blood samples from humans have also been reviewed. The present review indicates that the current exposure levels of DON might pose a health risk for the consumers, especially in growing children, necessitating to take vigilant steps to guarantee food safety.

Estrogen receptor potentiates mTORC2 signaling in breast cancer cells by upregulating superoxide anions.

The estrogen receptor (ER) plays a cardinal role in estrogen-responsive breast carcinogenesis. It is, however, unclear as to how estrogen-ER interaction potentiates breast cancer progression. Compelling evidence supports estrogen-induced redox alterations, such as augmented reactive oxygen species (ROS) levels, as having a crucial role in breast carcinogenesis. Despite ER being a biological mediator of the majority of estrogen-induced cellular responses; its role in estrogen-induced tissue-specific ROS generation remains largely debatable. We examined a panel of human breast cancer specimens and found that ER-positive breast cancer specimens exhibited a higher incidence of augmented O(2)(•-) levels compared to matched normal tissue. ROS are known to function as signal transducers and ROS-mediated signaling remains a key complementary mechanism that drives carcinogenesis by activating redox-sensitive oncogenic pathways. Additional studies revealed that augmented O(2)(•-) levels in breast cancer specimens coincided with mammalian target of rapamycin complex 2 (mTORC2) hyperactivation. Detailed investigations using in vitro experiments established that 17ß-estradiol (E2)-stimulated breast cancer cells exhibited transiently upregulated O(2)(•-) levels, with the presence of ER being a crucial determinant for the phenomenon to take place. Gene expression, ER transactivation, and confocal studies revealed that the E2-induced transient O(2)(•-) upregulation was effected by ER through a nongenomic pathway possibly involving mitochondria. Furthermore, E2 treatment activated mTORC2 in breast cancer cells in a characteristically ER-dependent manner. Interestingly, altering O(2)(•-) anion levels through chemical/genetic methods caused significant modulation of the mTORC2 signaling cascade. Taken together, our findings unravel a novel nongenomic pathway unique to estrogen-responsive breast cancer cells wherein, upon stimulation by E2, ER may regulate mTORC2 activity in a redox-dependent manner by transiently modulating O(2)(•-) levels particularly within mitochondria. The findings suggest that therapies aimed at counteracting these redox alterations and/or resultant signaling cascades may complement conventional treatments for estrogen-responsive breast cancer.

Mutagenicity of leachates from industrial solid wastes using Salmonella reverse mutation assay.

Leachates derived from dry wastes of the metal, tannery, and dye industries of the state of Uttar Pradesh (India) were analyzed for their mutagenic potential using reverse mutation assay. Both the spot and plate incorporation assays were conducted with four tester strains of Salmonella typhimurium (TA97a, TA98, TA100, and TA102). The metal concentrations in the samples were also determined. The result suggests that leachates derived from metal and tannery wastes possess mutagenic properties. The findings are indicative of the type of environmental and health risks posed by improper waste disposal.