Facile synthesis, ex-vivo and in vitro screening of 3-sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716) a potent CB1 receptor antagonist

Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the –CO group in the compound 1 by the –SO₂ group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism.     

Somatic Embryogenesis and Plant Regeneration in Kinnow Mandarin

Somatic embryogenesis and plant regeneration from stem explants of kinnow mandarin, a hybrid of king and willow mandarins, are reported. It is an economically important cash crop of India with great deal of production and export. This is for the first time that callus induction and internodal regeneration has been successfully achieved in this citrus cultivar. Callus was induced from nodal segment (1-2 cm) of kinnow mandarin on Murashige and Skoog (MS) medium supplemented with α-naphthaleneacetic acid (NAA) and benzyl amino purine (BAP). Cotyledonary stage somatic embryos with regenerated shoots were induced on BAPenriched medium. Roots developed when regenerated shoots were excised and cultured on half strength MS medium supplemented with NAA only.     

The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin

Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate (EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h (P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly (P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour cell sensitivity to therapy.     

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.     

EvaGreen-based Multiplex Real-time PCR Assay for Rapid Differentiation of Wild-Type and Glycoprotein E-Deleted Bovine Herpesvirus-1 Strains

Bovine herpesvirus-1 (BoHV-1) is an important viral pathogen causing significant economic losses to the cattle industry. Glycoprotein E-deleted marker vaccines form the basis for BoHV-1 control programs widely, wherein detection and differentiation of wild-type and gE-deleted vaccine strains is of crucial importance for proper disease management. In the present study, we report an EvaGreen-based multiplex real-time polymerase chain reaction (EGRT-PCR) assay for rapid differentiation of wild-type and glycoprotein E-deleted strains of BoHV-1. The EGRT-PCR assay could simultaneously detect two viral genes (glycoprotein B and E) and an internal positive control gene (bovine growth hormone- bGH), in a single-tube reaction. The analytical sensitivity of the EGRT-PCR assay was as little as 10 copies of the BoHV-1 DNA per reaction. The modified real-time PCR assay could successfully differentiate wild-type and gE-deleted BoHV-1 strains based on gene specific melting temperatures (T_m) peaks. Our results have shown that the EGRT-PCR developed in this study might prove to be a promising tool in disease management by enabling rapid differentiation of wild-type and gE-deleted strains of BoHV-1.     

Correlation between interaction strengths drives stability in large ecological networks

Food webs have markedly non‐random network structure. Ecologists maintain that this non‐random structure is key for stability, since large random ecological networks would invariably be unstable and thus should not be observed empirically. Here we show that a simple yet overlooked feature of natural food webs, the correlation between the effects of consumers on resources and those of resources on consumers, substantially accounts for their stability. Remarkably, random food webs built by preserving just the distribution and correlation of interaction strengths have stability properties similar to those of the corresponding empirical systems. Surprisingly, we find that the effect of topological network structure on stability, which has been the focus of countless studies, is small compared to that of correlation. Hence, any study of the effects of network structure on stability must first take into account the distribution and correlation of interaction strengths.     

Auxin-like activity of extract from hypertrophied tissue of <Emphasis Type="Italic">Acacia eburnea</Emphasis> infected with <Emphasis Type="Italic">Ravenelia esculenta</Emphasis>

Ravenelia esculenta Naras. and Thirum. is a rust, pathogenic to Acacia eburnea Willd. The infection leads to hypertrophy changing the morphology with bizarre shapes of plant organs. Healthy and infected tissues were subjected to extraction of IAA and indole derivatives and were estimated by spectrophotometric methods. The hypertrophy produced was presumed to be due to increase in the indole-3-acetic acid (IAA) content in the infected tissue, however, the amount of IAA in infected tissues decreased with the progression of disease. Concomitantly, the infected tissue showed the presence of a novel, slow migrating, indole derivative on TLC. Cultured shoot tips of Withania somnifera were dosed with the methanolic extract of the infected hypertrophied tissue (MEHT) (0.25, 0.5, 0.75, 1.00 and 1.25 mg/l). The stimulation in shoot growth along with profuse rooting was observed in a dose dependent manner with maximum at 1.00 and 1.25 mg/l concentration.     

Influence of Nutrient Availability and Quorum Sensing on the Formation of Metabolically Inactive Microcolonies Within Structurally Heterogeneous Bacterial Biofilms: An Individual-Based 3D Cellular Automata Model

The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity. Cell death occurred preferentially in layers in close proximity to the substratum, resulting in increased heterogeneity in this section of the biofilm; the thickness and heterogeneity of this lowermost layer increased with time, ultimately leading to sloughing. The model predicted the formation of metabolically dormant cellular microniches embedded within faster-growing cell clusters. Biofilms utilizing quorum sensing were more heterogeneous compared to their non-quorum sensing counterparts, and resisted sloughing, featuring a cell-devoid layer of EPS atop the substratum upon which the remainder of the biofilm developed. Overall, our study provides a computational framework to analyze metabolic diversity and heterogeneity of biofilm-associated microorganisms and may pave the way toward gaining further insights into the biophysical mechanisms of antibiotic resistance.     

Chrysin and Capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in Cervical cancer cells

Current studies are focusing on the anti-cancerous properties of natural bioactive compounds, primarily those included in the human diet. These compounds have the potential to alter the redox balance that can hinder cancer cell's growth. In cancer cells, an abnormal rate of ROS production is balanced with higher antioxidant activities, which if not maintained, results in cancer cells being prone to cell death due to oxidative stress. Here, we have analyzed the effects of Chrysin and Capsaicin on the HeLa cells viability and cellular redox signaling. Both these compounds stimulate cellular and mitochondrial ROS overproduction that perturbs the cellular redox state and results in mitochondrial membrane potential loss. Apart from this, these compounds induce cell cycle arrest and induce premature senescence, along with the overexpression of p21, p53, and p16 protein at lower concentration treatment of Chrysin or Capsaicin. Moreover, at higher concentration treatment with these compounds, pro-apoptotic activity was observed with the high level of Bax and cleaved caspase-3 along with suppression of the Bcl-2 protein levels. In-Silico analysis with STITCH v5 also confirms the direct interaction of Chrysin and Capsaicin with target protein p53. This suggests that Chrysin and Capsaicin trigger an increase in mitochondrial ROS, and p53 interaction leading to premature senescence and apoptosis in concentration dependent manner and have therapeutic potential for cancer treatment.     

A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting

Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.