Nrf2, a redox sensitive transcription factor, plays a pivotal role in redox homeostasis during oxidative stress. Nrf2 is sequestered in cytosol by an inhibitory protein Keap1 which causes its proteasomal degradation. In response to electrophilic and oxidative stress, Nrf2 is activated, translocates to nucleus, binds to antioxidant response element (ARE), thus upregulates a battery of antioxidant and detoxifying genes. This function of Nrf2 can be significant in the treatment of diseases, such as cancer, neurodegenerative, cardiovascular and pulmonary complications, where oxidative stress causes Nrf2 derangement. Nrf2 upregulating potential of phytochemicals has been explored, in facilitating cure for various ailments while, in cancer cells, Nrf2 upregulation causes chemoresistance. Therefore, Nrf2 emerges as a key regulator in oxidative stress-mediated diseases and Nrf2 silencing can open avenues in cancer treatment. This review summarizes Nrf2-ARE stress response mechanism and its role as a control point in oxidative stress-induced cellular dysfunctions including chronic inflammatory diseases.

RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4 + T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type.

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Background: Iodine defi ciency is still a signifi cant public health problem. In the rural plains of Nepal, it remains a mild-to-moderate public health problem among pregnant and lactating women despite the availability of iodized salt. To date, only limited attention has been paid to breast-milk iodine content despite its importance in the intellectual development of infants. Objectives: (i) To determine iodine content in mother's urine, mother's milk and to measure their respective child's TSH level. (ii) To correlate iodine content of mother's urine with child's TSH level and also mother's milk content with child's TSH level. Setting and Design: Cross sectional study in human using consecutive sampling technique. Materials and Methods: Mother's urinary and milk iodine level was measured by Ammonium Persulfate Digestion Microplate method using Sandell-Kolthoff reaction in a sealing cassette (Hitachi, Japan) and child's TSH by ELISA commercial Kit from Eliscan (RFCL, India) based on classical sandwich technique. Statistical Analysis: Spearman's correlation was performed in quantitative variables. A p-value less than 0.05 and 0.001 were considered statistically signifi cant and highly signifi cant respectively. Results: The median mother's urine was 174.96 μg/L (97.39-215.43) and their respective median child TSH level was 3.86 mIU/L (2.66-4.80). Median mother's milk iodine was 129.90 μg/L (94.14-165.94).There was signifi cant negative correlation between mothers' urinary iodine content and their child's TSH (r2= -0.391, p = 0.005) and between mother's urinary iodine and their child's TSH (r2= -0.471, p = 0.001). There was positive correlation between mother's milk iodine and mother urinary iodine but not statistically signifi cant ((r2= 0.261, p = 0.067). Conclusion: Mothers urinary iodine, mother's milk iodine and child TSH are interrelated with each other.

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