The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism

The nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also called Nfe2l2) and its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (KEAP1), are major regulators of redox homeostasis controlling a multiple of genes for detoxification and cytoprotective enzymes. The NRF2/KEAP1 pathway is a fundamental signaling cascade responsible for the resistance of metabolic, oxidative stress, inflammation, and anticancer effects. Interestingly, a recent accumulation of evidence has indicated that NRF2 exhibits an aberrant activation in cancer. Evidence has shown that the NRF2/KEAP1 signaling pathway is associated with the proliferation of cancer cells and tumerigenesis through metabolic reprogramming. In this review, we provide an overview of the regulatory molecular mechanism of the NRF2/KEAP1 pathway against metabolic reprogramming in cancer, suggesting that the regulation of NRF2/KEAP1 axis might approach as a novel therapeutic strategy for cancers.

Impact of IL10, MTP, SOD2, and APOE Gene Polymorphisms on the Severity of Liver Fibrosis Induced by HCV Genotype 4

Complications of hepatitis C virus (HCV) chronic infection cause ~400,000 deaths worldwide annually. One complication, liver fibrosis, is influenced by host genetic factors. Genes influencing fibrosis include immune, metabolic, oxidative stress, and viral entry genes, such as interleukin 10 (IL10), microsomal triglyceride-transfer protein (MTP), superoxide dismutase-2 (SOD2), and apolipoprotein E (APOE)-encoding genes, respectively. Thus, correlating variations in these genes with HCV-induced fibrosis represents an attractive biomarker for the prognosis of fibrosis severity in chronically infected patients. Here, we aimed to test whether polymorphisms in IL10, MTP, SOD2, and APOE genes correlated with the severity of fibrosis induced by HCV genotype 4 (HCV-gt4) in a cohort of chronically infected Egyptian patients. Our results demonstrate a significant association between the severity of fibrosis and specific SNPs in IL-10, SOD2, and ApoE-encoding genes. Haplotype-combination analysis for IL10, MTP, SOD2, and APOE showed statistically significant associations between specific haplotype combinations and fibrosis severity. Identifying biomarkers correlating with the severity of HCV-gt4-induced fibrosis would significantly impact precision prophylaxis and treatment of patients at risk.

Biomarkers for grain yield stability in rice under drought stress

The metabolic-oxidative stress profile of the rice flag leaf during drought stress in the reproductive stage is highly predictive for grain yield loss sensitivity of 292 accessions at harvest time.