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.

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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.

AimTo study the effect of weaning biscuits supplementation of the nutritional parameters and cognitive performance of the selected children.MethodsThree primary schools situated in Salem District, Tamilnadu, India were selected. A total number of 150 school children, 61 from primary school I, 46 from primary school II and 43 from primary school III comprised the study sample. About 80 primary school children with Grade II malnutrition were selected for the experimental study. Home diet without any supplementation was followed by Group I (n = 20, control group), potato flour biscuit was supplemented to Group II (n = 20), wheat biscuits was given to Group III (n = 20) and ragi biscuits were given to Group IV (n = 20) for the period of 3 months. Parameters like anthropometric measurements, hemoglobin content clinical picture and cognitive performance were analyzed before and after supplementation.ResultsResults about Group I (control group) showed no significant difference in height, weight and clinical picture and cognitive performance after three months on their home diet. In Group II, III and IV significant increase in all the above parameters was noticed. More increase was found in Group II children supplemented with potato flour biscuits for a period of 3 months. About cognitive performance better results was obtained in Group II followed by Group III (supplemented with wheat biscuits) and Group IV (supplemented with ragi biscuits). Least was obtained by control group children who are in their home diet.ConclusionAll these observations evident that if such weaning biscuits made with potato flour, wheat and Ragi can form a daily ingredient in their diets, it will bring out better all round development of the children.

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The usage of BLDC motors in the low-power range is increasing rapidly in home appliances such as ceiling fans. This has necessitated the development of reliable, compact and efficient AC-DC power supplies for motor drive circuitry. This paper presents a power supply design consisting of an AC-DC isolated PFC Cuk converter with integrated magnetics that supplies a single-shunt voltage source inverter for the sensorless drive of the BLDC fan motor. The proposed power supply design is comprised of an integrated magnetics structure in which the two inductors and the transformer windings share the same core. The zero input and output ripple current conditions have been derived from the reluctance model of the magnetic assembly. Smooth operation of the motor by minimizing the motor torque ripples is evident from the results. The Cuk converter operates in continuous conduction mode (CCM), employing the current multiplier method. The CCM-based current multiplier control loop ensures a near-unity power factor as well as low total harmonic distortion in the supply current. The current loop also provides over-current protection, enhancing reliability of the system. Moreover, the speed of the BLDC motor is controlled by the field oriented control (FOC) algorithm, which enables direct operation with alternate energy sources such as batteries and solar photovoltaic panels. The performance of the proposed supply is validated: motor torque ripple is reduced to only 2.14% while maintaining 0.999 power factor and only 4.72% THD at full load. Failure modes analysis has also been performed through software simulations, using the PLECS simulation environment. Due to the reliable power supply design with low ripples, it is well suited for low-power BLDC motors in home appliances and small power tools, in addition to ceiling fans.