Chemopreventive Herbal Anti-Oxidants: Current Status and Future Perspectives

Cancer chemoprevention is fast becoming a lucrative approach for controlling cancer. Carcinogenesis being a complex multi-step, multi-factorial process, a number of chemopreventive interventions can be employed. These strategies are generally directed against two broad events of carcinogenesis viz., initiation and promotion/progression. Anti-initiation interventions principally involve inhibition of carcinogen activation, scavenging of free radicals and reactive carcinogen metabolites along with enhanced detoxification of carcinogens by modulating cellular metabolism. Anti-promotion strategies involve attenuation of enhanced cellular proliferation along with induction of cellular apoptosis and differentiation. Dietary agents or herbal anti-oxidants due to low toxicity and relative safety are promising chemopreventive agents. These agents after emerging successful through a series of in vitro and in vivo assays enter clinical trials. Many dietary compounds have emerged as promising chemopreventive agents in empirical experiments. However, in clinical trials these compounds have met with limited success. This emphasizes the need for further detailed research on the mechanisms of observed chemoprevention and choice, dose, duration and bioavailability of chemopreventive agent used. Complex issues such as choice and nutritional status of target population, genetic variation, gene-environment interactions and relevance of biomarkers analyzed also warrant further research and analyses

Abnormal semen parameters among males in infertile couples: a cross sectional study from a tertiary care centre

Background: In India, the prevalence of primary infertility ranges from 3.9% to 16.8%. Male factor contributes 40-50% of this. Male factor infertility is indicated by decreased sperm concentration, reduced motility, vitality or abnormal sperm morphology. Semen analysis is the single most important investigation to detect male factor infertility. The aim of this study was to analyse the prevalence of abnormal semen parameters among males in infertile couples and their association with contributing factors.Methods: This cross-sectional hospital-based study was carried out in the Department of Pathology at Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital. A total of 400 cases were analyzed during a period of 6 months. Detailed history of the couple was taken. Semen analysis was done using automated semen analyzer (SQA-vision) after 3 days of abstinence according to the WHO 5th edition 2010 guidelines. The results were analysed using excel sheet and SPSS software.Results: In the present study, 122 cases (30.5%) out of 400 cases had abnormal semen parameters. Most common abnormality detected was asthenozoospermia (14.3%) followed by oligozoospermia (13.8%), azoospermia (10.5%) and teratozoospermia (10.5%). There was significant association of alcohol intake, obesity and trauma with abnormal semen parameters.Conclusions: Asthenozoospermia was the most common abnormality noted in this study. Lifestyle modifications along with timely medical attention in male partners of infertile couples can improve the semen quality

Characterization of a P-Rex1 gene signature in breast cancer cells

The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their coexpression is indicative of poor prognosis.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Characterization of a P-Rex1 gene signature in breast cancer cells

The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their coexpression is indicative of poor prognosis.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins

Overexpression of PKCε, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCε expression and its up-regulation in cancer, we cloned an ∼1.6-kb promoter segment of the human PKCε gene (PRKCE) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and-105 bp (region A) and-921 and-796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and-269/-247 as well as STAT1 sites in positions -880/-869 and- 793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCε mRNA and protein expression, as well as PRKCE promoter activity. Moreover, a strong correlation was found between PKCε and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCε and its effectors in cancer therapeutics.Centro de Investigaciones Inmunológicas Básicas y AplicadasFacultad de Ciencias Médica

Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins

Overexpression of PKCε, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCε expression and its up-regulation in cancer, we cloned an ∼1.6-kb promoter segment of the human PKCε gene (PRKCE) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and-105 bp (region A) and-921 and-796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and-269/-247 as well as STAT1 sites in positions -880/-869 and- 793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCε mRNA and protein expression, as well as PRKCE promoter activity. Moreover, a strong correlation was found between PKCε and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCε and its effectors in cancer therapeutics.Centro de Investigaciones Inmunológicas Básicas y AplicadasFacultad de Ciencias Médica

Analysing the impact of various incentives on solar tariff in India

In India, solar tariff has been witnessing a continuous fall since the announcement of revised targets for the National Solar Mission (NSM) in the year 2015. This paper discusses components that decide the solar tariff and demonstrates the role of various incentives being provided in bridging the tariff gap between solar and conventional power. The paper concludes with a comparison of various incentives (viability gap funding (VGF), accelerated depreciation (AD), generation-based incentive (GBI), etc.) based on the cost-effectiveness index. Based on the analysis, it is recommended that as levelised cost of energy (LCOE) is coming down, the government may think of pulling back some of the incentive schemes such as VGF, AD, and GBI while some hidden incentive schemes such as waiver of inter and/or intrastate transmission charges and losses, etc may continue