Cadmium modulates intestinal Wnt/ß-catenin signaling ensuing intestinal barrier disruption and systemic inflammation.

The intricate architecture of the intestinal epithelium, crucial for nutrient absorption, is constantly threatened by environmental factors. The epithelium undergoes rapid turnover, which is essential for maintaining homeostasis, under the control of intestinal stem cells (ISCs). The central regulator, Wnt/ß-catenin signaling plays a key role in intestinal integrity and turnover. Despite its significance, the impact of environmental factors on this pathway has been largely overlooked. This study, for the first time, investigates the influence of Cd on the intestinal Wnt signaling pathway using a mouse model. In this study, male BALB/c mice were administered an environmentally relevant Cd dose (0.98 mg/kg) through oral gavage to investigate the intestinal disruption and Wnt signaling pathway. Various studies, including histopathology, immunohistochemistry, RT-PCR, western blotting, ELISA, intestinal permeability assay, and flow cytometry, were conducted to study Cd-induced changes in the intestine. The canonical Wnt signaling pathway experienced significant downregulation as a result of sub-chronic Cd exposure, which caused extensive damage throughout the small intestine. Increased intestinal permeability and a skewed immune response were also observed. To confirm that Wnt signaling downregulation is the key driver of Cd-induced gastrointestinal toxicity, mice were co-exposed to LiCl (a recognized Wnt activator) and Cd. The results clearly showed that the harmful effects of Cd could be reversed, which is strong evidence that Cd mostly damages the intestine through the Wnt/ß-catenin signalling axis. In conclusion, this research advances the current understanding of the role of Wnt/ß catenin signaling in gastrointestinal toxicity caused by diverse environmental pollutants.

Antimicrobial activity of different plants extracts against Staphylococcus aureus and Escherichia coli.

BACKGROUND: Microbial pathogens, mainly bacteria, are a major cause of food spoilage resulting in several foodborne diseases. Food spoilage can be prevented by the application of chemical preservatives in the food industry but such process has harmful effects on human health and causes the introduction of chemicals in several food chains, leading to toxicity and long-term complications. Due to such adverse effects, the need to find natural preservatives that are safer to use, effective and less complicated is increasing. OBJECTIVES: This study is based on plant extracts that play a major role in microbicidal action (the use of natural preservatives is preferred over chemical ones). Antimicrobial action of different plant extracts was assessed using Staphylococcus aureus and Escherichia coli as experimental bacterial strains. MATERIAL AND METHODS: Ethanolic extracts of different plants like Punica granatum, Acacia catechu and Phyllanthus emblica were highly effective against the both analyzed bacterial strains at a dosage of 10 mg/mL, while the extracts of Ocimum bacilicum and Quercus infectoria were effective only against S. aureus and E. coli, respectively. RESULTS: Punica granatum and Phyllanthus emblica extracts were found to be the most effective and exhibited bacteriostatic and bactericidal activities against the highly infectious strains of pathogenic bacteria causing food spoilage, with minimum inhibitory concentration (MIC) of 2.5 mg/mL and minimum bactericidal concentration (MBC) of 5 mg/mL. CONCLUSIONS: The plant extracts used in the study were highly effective in reducing bacterial contamination and can be used as an alternative to chemical preservatives to avoid and control foodborne diseases and for preservation of food with no health-related hazards caused by chemicals.

NF-κB p65 regulates hepatic lipogenesis by promoting nuclear entry of ChREBP in response to a high carbohydrate diet.

Overconsumption of sucrose and other sugars has been associated with nonalcoholic fatty liver disease (NAFLD). Reports suggest hepatic de novo lipogenesis (DNL) as an important contributor to and regulator of carbohydrate-induced hepatic lipid accumulation in NAFLD. The mechanisms responsible for the increase in hepatic DNL due to overconsumption of carbohydrate diet are less than clear; however, literatures suggest high carbohydrate diet to activate the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP), which further transcribes genes involved in DNL. Here, we provide an evidence of an unknown link between nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and increased DNL. Our data indicates high carbohydrate diet to enforce nuclear shuttling of hepatic NF-κB p65 and repress transcript levels of sorcin, a cytosolic interacting partner of ChREBP. Reduced sorcin levels, further prompted ChREBP nuclear translocation, leading to enhanced DNL and intrahepatic lipid accumulation both in vivo and in vitro. We further report that pharmacological inhibition of NF-κB abrogated high carbohydrate diet-mediated sorcin repression and thereby prevented ChREBP nuclear translocation and this, in turn, attenuated hepatic lipid accumulation both in in vitro and in vivo. Additionally, sorcin knockdown blunted the lipid-lowering ability of the NF-κB inhibitor in vitro. Together, these data suggest a heretofore unknown role for NF-κB in regulating ChREBP nuclear localization and activation, in response to high carbohydrate diet, for further explorations in lines of NAFLD therapeutics.