Vesicular trafficking–related proteins as the potential therapeutic target for breast cancer

Protoplasma - Vesicular trafficking between endoplasmic reticulum and Golgi plays a major role in the growth and proliferation of breast cancer cells. Various proteins regulate this ER-Golgi...     

Peripartum Cardiomyopathy Presenting With Ventricular Tachycardia: A Rare Presentation

A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia.     

Discovery of conformationally rigid 3-azabicyclo[3.1.0]hexane-derived dipeptidyl peptidase-IV inhibitors

The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P₂ region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure–activity relationship, and selectivity against related proteases are delineated.     

Polymorphisms in vitamin D receptor,toll-like receptor 2 and Toll-Like receptor 4 genes links with Dengue susceptibility

Host genetic factors are known to determine disease susceptibility in dengue virus infection. Therefore, in this study association of gene polymorphisms of Vitamin D Receptor [rs731236 (Taq) and rs7975232 (Apa1)], Toll-like receptor 2 [rs5743708 (Arg735Gln) and rs5743704 (Pro631His)] and Toll-like receptor 4 [rs4986790A/G(Asp299Gly13843) and rs4986791 C/T(Thr399Ile)] were studied in cases with dengue as compared to controls. Total 98 cases of confirmed dengue virus infection and 98 age, sex and geographically matched healthy controls were enrolled and their genetic polymorphisms for the above mentioned regions were studied by Sanger sequencing. Mutant genotypes CC of VDR rs731236 (Taq1) [(OR 3.808, p value =0.02, CI 1.160-12.498)], GG of VDR rs7975232 (Apa1) [(OR 3.485, p value =0.02, CI 1.162-10.45)] and heterozygous genotypes of TLR4 rs4986790 A/G Asp299Gly [OR 2.40, p value= 0.02, CI 1.12-5.14], TLR4 rs4986791 C/T Thr399Ile [OR 2.09, p value=0.02, CI 1.12-5.14] were found to be significantly more in cases with dengue virus infection as compared to the controls. Also, at these positions mutant alleles were observed in significantly higher number of cases than controls. The values for C allele at VDR rs731236 (Taq1) were OR 1.86, p value 0.009, CI 1.162-3.001; for allele G at rs7975232( Apa1) were OR 2.71, p value 0.006, CI 1.196-2.98 for allele G at TLR4s rs4986790 A/G Asp299Gly were OR 2.35, p value 0.009, CI 1.23-4.50 and for allele T at rs4986791 C/T Thr399Ile were OR 2.36, p value=0.006, CI 1.28-4.38. VDR and TLR4 but not TLR2 gene polymorphisms were found to be associated with dengue susceptibility in Indian population.     

Investigation of the efficacy of paclitaxel on some miRNAs profiles in breast cancer stem cells

Understanding of the functions of microRNAs in breast cancer and breast cancer stem cells have been a hope for the development of new molecular targeted therapies. Here, it is aimed to investigate the differences in the expression levels of let-7a, miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-200c, miR-221, miR-222 and miR-335, which associated with gene and proteins in MCF-7 (parental) and MCF-7s (Mammosphere/stem cell-enriched population/CD44+/CD24-cells) cells treated with paclitaxel. MCF-7s were obtained from parental MCF-7 cells. Cytotoxic activity of paclitaxel was determined by ATP assay. Total RNA isolation and cDNA conversion were performed from the samples. Changes in expression levels of miRNAs were examined by RT-qPCR. Identified target genes and proteins of miRNAs were analyzed with RT-qPCR and western blot analysis, respectively. miR-125b was significantly expressed (2.0946-fold; p = 0.021) in MCF-7s cells compared to control after treatment with paclitaxel. Downregulation of SMO, STAT3, NANOG, OCT4, SOX2, ERBB2 and ERBB3 and upregulation of TP53 genes were significant after 48 h treatment in MCF-7s cells. Protein expressions of SOX2, OCT4, SMAD4, SOX2 and OCT4 also decreased. Paclitaxel induces miR-125b expression in MCF-7s cells. Upregulation of miR-125b may be used as a biomarker for the prediction of response to paclitaxel treatment in breast cancer.     

Role of antioxidant and anaerobic metabolism enzymes in providing tolerance to maize (Zea mays L.) seedlings against waterlogging

The present investigation was undertaken to identify the possible mode of mechanism that could provide tolerance to maize (Zea mays L.) seedlings under waterlogging. Using cup method, a number of maize genotypes were screened on the basis of survival of the seedlings kept under waterlogging. Two tolerant (LM5 and Parkash) and three susceptible (PMH2, JH3459 and LM14) genotypes were selected for the present study. Activities of antioxidant and ethanolic fermentation enzymes and content of hydrogen peroxide (H2O2), glutathione and ascorbic acid were determined in roots of these genotypes after 72 h of waterlogging. Waterlogging treatment caused decline in activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) in all the genotypes. However, only susceptible genotypes showed slight increase in glutathione reductase (GR) activity. Significant reduction in APX/GR ratio in susceptible genotypes might be the cause of their susceptibility to waterlogging. The tolerant seedlings had higher GR activity than susceptible genotypes under unstressed conditions. Stress led to decrease in H202 and increase in glutathione content of both tolerant and susceptible genotypes, but only tolerant genotypes exhibited increase in ascorbic acid under waterlogging conditions. In the tolerant genotypes, all the enzymes of anaerobic metabolism viz. alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and pyruvate decarboxylase (PDC) were upregulated under waterlogging, whereas in susceptible genotypes, only ADH was upregulated, suggesting that efficient upregulation of entire anaerobic metabolic machinery is essential for providing tolerance against waterlogging. The study provides a possible mechanism for waterlogging tolerance in maize.     

Plasmid-mediated drug resistance of shigellae in Kuwait

Of 153 clinical isolates of shigellae examined, 64.7% belonged toShigella flexneri, 18.9% toSh. sonnei, 11.8% toSh. boydii and 4.6% toSh. dysenteriae. Part of these isolates were resistant to sulfamethoxazole and streptomycin (88.2% each), ampicillin (66.70, tetracycline (63.40 and co-trimoxazole (43.10, with levels of resistance (MIC₅₀ and MIC₉₀) being invariably high. Resistance to three or more drugs (multidrug resistance) was seen in 77.8% of the isolates. All the 25 strains examined for transfer of resistance contained R-plasmids, both autotransferable and non-autotransferable (mobilized by transfer factor X). The frequency of transfer of different r-determinants varied from 2.7 · 10^–8 to 1.4 · 10.