Dietary Phytochemicals: As a Natural Source of Antioxidants

Since time immemorial, plants are used as the source of food and medicine. It can be traced back to the start of humanity. Bringing plant-based food, such as fruits, vegetables, and whole grains, rich in phytochemicals, with beneficial nutrients, opens the door for healthy living. The health benefits are partly attributed to the compounds which possess antioxidants. Several epidemiological observations have shown an opposite relationship between consumption of plant-based foods, rich in phytochemicals, and many diseases including cancer. The majority of the ailments are related to oxidative stress induced by free radicals. Free radicals are extremely unstable with a very short half-life, highly reactive molecule which leads to oxidative damage to macromolecules such as proteins, DNA, and lipids. Free radical induced cellular inflammation appears to be a major contributing factor to cause aging, and degenerative diseases such as cancer, cardiovascular diseases, diabetes, hepatic diseases, renal ailments, and brain dysfunction. Free radicals have been caught up in the pathogenesis of several diseases. Providentially, free radical formation is controlled naturally by phytochemicals, through their antioxidant potential which plays a key role in preventing many diseases including cancer by suppressing oxidative stress-induced DNA damage. Keeping these facts in mind, an attempt has been made to highlight the oxidative stress, enzymatic and non-enzymatic antioxidant, dietary phytochemicals and their role of in disease prevention and cure

Oct1 and OCA-B are selectively required for CD4 memory T cell function

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4+ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4+ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4+ T cell memory

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression

Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression of ADAM-12 is very low in adult tissues but rises markedly in response to certain physiological cues, such as during pregnancy in the placenta, during development in neonatal skeletal muscle and bone and in regenerating muscle. Studies on ADAM-12 regulation have identified a highly conserved negative regulatory element (NRE) at the 5′-UTR of human ADAM-12 gene, which acts as a transcriptional repressor. The NRE contains a stretch of dinucleotide-repeat sequence that is able to adopt a Z-DNA conformation both in vitro and in vivo and interacts with hZαADAR1, a bona fide Z-DNA-binding protein. Substitution of the dinucleotide-repeat-element with a non-Z-DNA-forming sequence inhibited NRE function. We have detected a NRE DNA-binding protein activity in several tissues where ADAM-12 expression is low while no such activity was seen in the placenta where ADAM-12 expression is high. These observations suggest that interaction of these proteins with ADAM-12 NRE is critical for transcriptional repression of ADAM-12. We also show that the Z-DNA forming transcriptional repressor element, by interacting with these putative Z-DNA-binding proteins, is involved in the maintenance of constitutive low-level expression of human ADAM-12. Together these results provide a foundation for therapeutic down-regulation of ADAM-12 in cancer, arthritis and cardiac hypertrophy

Oct1 and OCA-B are selectively required for CD4 memory T cell function

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4⁺ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4⁺ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ~50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4⁺ T cell memory