Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAM^high cells compared to the cisplatin sensitive counterpart. EpCAM^high populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAM^high populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAM^high populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAM^high populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAM^high populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAM^high populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAM^high populations.

Community managed Village Common Forest (VCF) in Chittagong Hill Tracts (CHTs) in Bangladesh is an example of sustainable forest management under non-governmental customary rules and regulations. This study explored the diversity of medicinal plants and their therapeutic uses by ethnic communities at two VCFs in Rangamati hill district. A total of 30 square plots of $10m\times 10m$size was selected by stratified random sampling from the two VCFs. All medicinal plants of different habits were recorded to calculate phytosociological attributes and diversity indices. A semi-structured questionnaire was used to survey the community and local herbalists to list the ethno-medicinal uses of available plant species. A total 204 species belonging to 160 genera and 76 families used by the communities in CHTs for treating about 197 diseases/ailments were recorded. Leaves were the most used part (145 species) followed by roots (119 species) and stem (53 species). In terms of habit form, herbs were the highest percentage (44%) followed by trees (26%) and shrubs (16%). The diversity indices indicated the presence of diverse medicinal plants.

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). Methods: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. Results: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. Conclusions: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.

Background: There is evidence that oxidative stress plays an important role in autoimmune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. A study was designed to determine the potential beneficial effects of antioxidant intervention on clinical parameters of RA.Methods: Randomized clinical trial of 152 patients with positive rheumatoid factor (RF) and a Disease Activity Score (DAS 28) higher than 3.2 were enrolled in the study. Patients were divided into two groups (Group A and Group B) randomly and group A received methotrexate and antioxidant vitamins (A, C and E in a fixed dose) and group B methotrexate only. They were followed up for three visits (baseline, 10th week and 14th week). The intervention was stopped after 10 weeks and was followed by a ‘wash-out’ period of 4 weeks. At baseline, 10th week and 14th week patient’s condition were assessed by means of DAS-28 score. P- Value less than <0.05 was considered significant.Results: The numbers of swollen and tender joints were significantly reduced and general health was improved reflected by improved DAS-28 score at 10th week.The antioxidant effect was considered beneficial as compared to the scores of 1st visit at baseline; the DAS-28 score was significantly reduced at 2nd visit at 10th week. Increment of the DAS-28 score among the group A patients who were on antioxidant up to10 weeks, after the “wash-out period” of four weeks i.e. at 14th week confirmed a significant relation between changes in clinical condition and antioxidants.Conclusion: This study was designed to assess the potential beneficial effect of antioxidants (Vitamin A, C and E) in combination with methotrexate in the treatment of RA.

Chronic kidney disease (CKD) is a serious condition associated with premature mortality, decreased quality of life, and increased health-care expenditures. A failure to produce sufficient Erythropoietin (EPO) accounts for the moderate to severe anemia observed in chronic kidney disease. Decreased EPO production is attributed to destruction of renal production sites. A cross-sectional descriptive study was designed for determination of erythropoietin level in chronic kidney disease patients with anemia. At the same time measurement of serum iron and serum ferritin to establish anemia. Serum concentration of erythropoietin was the parameter taken to evaluate the kidney status. This study was carried out in the Nephrology ward, Chittagong Medical College Hospital (CMCH), Chittagong, Bangladesh during the period of January 2012 to December 2012. Total Sixty Patients having hemoglobin level < 11 gm/dl and serum creatinine > 3 mg/dl taken as a case of chronic kidney disease with anemia. Mean Hemoglobin level found 8.67gm/dl [± 1.39SD(standard deviation), Serum creatinine level found 8.21 mg/dl (±3.25 SD), Serum erythropoietin level found 2.67 miu (mili international unit)/ml (± 2.36 SD), Serum iron level found 13.78 µg/dl (±2.58 SD). Serum ferritin level found 73.35ng/mL (± 26.81SD). It is also observed that Pearson’s correlation coefficient (r) between erythropoietin and hemoglobin is – 0.190 (r=0.036, p value=0.145), which is not significant. Correlation coefficient between erythropoietin and creatinine is – 0.082 (r=0.007 p value = 0.532), which is not significant. Correlation coefficient between erythropoietin and iron is 0.021 (r=4.549, p value =0.872), which is not significant but shows weakly positive correlation. Correlation coefficient between erythropoietin and ferritin is 0.005 (r=2.723 p value=0.968) which is not significant but also shows weakly positive correlation.