Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity.

The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested-PD-1, PD-L1, PD-L2 and CTLA-4-remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

Effect of Ocimum basilicum leaves extract on acetaminophen-induced nephrotoxicity in BALB/c mice.

Background Acetaminophen (APAP) is one of the most widely used drugs to treat pain. Its overdose is lethal causing liver and kidney failure. Nephrotoxicity and hepatotoxicity are mostly due to the overproduction of reactive oxygen species. Ocimum basilicum, known as basil, is a commonly used medicinal plant due to its versatile role as antibacterial, antifungal, and anti-oxidative. We aim in this study to investigate the preventive and protective effect of basil leaves aqueous extract against APAP-induced hepatorenal toxicity in BALB/c mice. Methods Acute kidney injury (AKI) was induced in mice using APAP. Mice were treated with basils extract pre and post AKI induction. Kidney and liver functions were assessed by measuring creatinine, urea, alanine transaminase, and aspartate transaminase levels in serum. Superoxide dismutase, catalase (CAT), and malondialdehyde levels of renal and hepatic tissues were assayed using Elisa. Kidney injury molecule (KIM-1) was quantified in kidney homogenate. Histopathological analysis of kidney and liver were examined. Results Significant increase in all serum parameters, in hepatic and renal MDA, and in renal KIM-1 levels was observed post AKI induction. Treatment with basils post AKI induction minimized APAP damage by reducing serum markers and MDA in both organs and by increasing SOD and CAT. However, pretreatment with basils extract caused additional increase in serum ALT and AST and MDA in liver, with a significant increase in renal antioxidant enzymes. These results were confirmed by histopathological examination. Conclusion Basil extract may act as a natural antioxidant to treat APAP-induced acute hepato-renal toxicity when used as a post-treatment.