Targeting the Ubiquitin Proteasome System in Cancer

The ubiquitin proteasome system is involved in a myriad of biological functions including cell cycle progression, intracellular signaling and protein degradation. As such, it is not surprising to find many components of the system misregulated in cancer. The clinical success of Bortezomib for treatment of multiple myeloma proves that targeting the ubiquitin proteasome system is valid and feasible. Here, a detailed examination of the strategies used to target the ubiquitin proteasome system in cancer is discussed. The inhibitors available, its targets, the cancer type and the developmental stage it is in are discussed

Genotoxicity testing of food additives by employing Vicia MN assay

In the present study genotoxic effect induced by two food preservatives viz. ammonium acetate and zinc acetate was evaluated in the root meristem cells of Vicia faba. Genotoxic property was evaluated by scoring micronucleus in the root tip cells of treated roots. Roots were treated with 1, 2.5. 5, and 7.5 g/l of ammonium acetate and zinc zcetate solutions at room temperature in dark for 6, 12, 18 and 24h. The dosages selected for evaluation were below LD50 dose of the compounds. The increase in the concentration and period of treatment of each compound resulted in increase in the frequency of micronuclei. The results indicate that ammonium acetate and zinc acetate induce genotoxic effect in the dose range tested

QUALITATIVE CHARACTERIZATION OF PHYTOCHEMICALS AND IN VITRO ANTIMICROBIAL EVALUATION OF LEAF EXTRACT OF COUROUPITA GUIANENSIS AUBL. - A THREATENED MEDICINAL TREE

Objective: Screening of phytochemicals present in aqueous extract and evaluation of the antibacterial and antifungal activities from different organic extracts of leaf of C. guianensis Aubl.Methods: Antimicrobial activity of different extracts was evaluated by using the disc diffusion assay. Methanolic, ethanolic and chloroform extracts of leaf were tested against fungus and representatives of Gram-positive and Gram-negative bacteria.Results: Presence of alkaloids, flavonoids, glycosides, phlobatannins, steroids, tannins and terpenoids was observed in aqueous extract of leaf. Chloroform extract showed better activity against Gram-positive bacteria in comparison to Gram-negative bacteria. Methanolic extract was more effective on Gram negative bacteria. Leaf extract was also effective against Candida species. Minimum inhibitory concentration was 25 mg/ml for ethanolic, 50 mg/ml for methanolic and 100 mg/ml for chloroform extracts against S. aureus. Conclusion: Present study of C. guianensis seems to be promising for pharmaceutical industries for making an antimicrobial drug or cream especially against S. aureus and provides details of pharmacological investigation, identification, isolation and characterization of novel bioactive compounds

ANTICANCER AND ANTIMICROBIAL POTENTIAL OF BARLERIA PRIONITIS LEAVES ETHANOL EXTRACT

Objective: The present study was focused to screen traditionally used Barleria prionitis for anticancer effects against various cell lines and antimicrobial effect against various pathogenic strains of bacteria and fungi.Methods: Extraction of Barleria prionitis leaves in ethanol was done by the Soxhlet method. After extraction, phytochemical estimation of these seven secondary metabolites like alkaloids, flavonoids, anthraquinones, saponins, terpenoids, tannins, and cardiac glycosides was done as per the protocols of Kokate. Minimum Inhibitory Concentration (MIC) effect of Barleria leaf ethanol (BLE) was done by the dilution method on five bacterial and five fungal strains. Further analysis (anticancer activity) was done with SRB (Sulphorhodamine B) assay. Statistical analysis of antimicrobial and anticancer activity was done by using MS Excel 2007 to±standard deviation and student t-test.Results: Barleria leaf extract with ethanol is a non-polar solvent extract and considered as the best solvent to extract the maximum number of secondary metabolites like alkaloids, saponins, flavonoids, and tannins. BLE extract gave excellent MIC (Minimum Inhibitory Concentration) effects against pathogenic bacteria and pathogenic fungal strains. BLE had highly effective activity against Pseudomonas aeruginosa with 1.25 mg MIC, the OD value of the sample was 0.02±0.0005 (±SD) with 0.0211-0.0245 range. MIC against fungal strains had effective activity against Candida vaginitis with 6.25 mg, the OD value of the sample was 0.02±0.0003 (±SD) with 0.0213-0.0232 range. BLE extract had given more than 70% inhibition against breast cell lines (MCF-7) and 75.16% inhibition of DLD1 cell lines; it was near to Doxorubicin antibiotic (81%). Breast metastatic cell line (MDMAMB-468) was found 60% inhibited with BLE extract and there was a great difference in the results of Doxorubicin. Out of six experimented cell lines, BLE gave very good inhibition for two cell lines, i.e. Breast (MCF-7) and Colon cell lines (DLD-1).Conclusion: BLE extract had shown the best antimicrobial and antifungal effect, against Pseudomonas aeruginosa and Candida vaginitis respectively. BLE also showed an anticancer effect against Lung cell lines (A549), Breast cancer cell line (MCF-7), Breast metastatic cell line (MDMAMB-468), Colon cell line (DLD-1) and lung metastatic cell line (NCIH358) at a statistically significant level (p=<0.05). It did not give any significant results against the colon metastatic cell line (SW620)

Formulation Development & Evaluation of Buffered Tablet of Proton Pump Inhibitors Drug Rabeprazole Sodium

The aim of present study was to prepare buffered tablets of acid labile drug, Rabeprazole sodium for oral administration using buffering agents to protect a drug from gastric fluid. Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+, K+ATPase at the secretory surface of the gastric parietal cell. Rabeprazole blocks the final step of gastric acid secretion. The tablets were prepared by direct compression and wet granulation method. The formulations contain water soluble buffers such as sodium bicarbonate and trisodium phosphate as well as water insoluble buffers as magnesium oxide, magnesium hydroxide and calcium carbonate and crospovidone as superdisintegrant. Preformulation studies like angle of repose, bulk density, tapped density, Carr’s index, hausner’s ratios, DSC and drug/excipient compatibility study were conducted and evaluated for hardness, friability, weight variation, drug content, disintegration and in-vitro dissolution. In the present study, pH of F6 batch was found to be optimum and disintegration time is 42 sec. The drug release was found to show maximum drug release in case of F6 with 99.3% in 60 minutes. In case of stability studies study of the optimized batch, all the results were found to be satisfactory and within limits. There were no significant changes after the period of 1 month study. Keywords: Rabeprazole sodium, Proton-pump inhibitors, Buffered tablet, Superdisintegrants, Buffering agent

Study on the Diversity and seasonal variation of zooplankton in Bhusara maun under Muzaffarpur, Bihar

Diversity of zooplankton in the Bhusara maun was studied during March 2010- Feb 2011. The population of zooplankton consisted of rotifers copepods and cladocerans. Total number of zooplankton recorded were 2335 per litre of which rotifers were 1461 (62.56%), cladocerans 226 (9.67%) and copepods 608 (27.75%). All the dominant groups of zooplankton present throughout the year. Diversity analysis showed that rotifers had 11 species cladoccrans four and copepode four species. High number of zooplankton were recorded in winter season. While low number was recorded in monsoon season. Keyword: Zooplankton, Bimodal distribution, Diversity richnes

Study on Fish Fauna Diversity of Bhusara maun under Muzaaffarpur district of Bihar

The present study has been carried from Bhusara maun under Muzaaffarpur district of Bihar”. Fish diversity on this lentic water body has been studied in detail with its food value and commercial status. Twenty eight Fish species of fishes were recorded, which belonged to 20 genera and 14 families. A classified list of fishes has been given. The Indian major carps and few fresh species are commercially important groups in the Bhusara maun Keywords: Fish species, diversity, food value. Commercially important.&nbsp

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

AIMS:Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. METHODS:Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. RESULTS:The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. CONCLUSIONS:Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C

Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population

Background Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making

c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression

Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFβ receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2. We demonstrate that HGF stimulates TGFβ signalling through c-SRC-mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2-HECT interaction, inhibiting SMURF2 and enhancing TGFβ receptor stabilisation. This upregulation of the TGFβ pathway by HGF leads to TGFβ-mediated EMT and invasion. In vivo we show that TGFβ receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFβ and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers