Fatty acid composition and bioactivity of Sesbania sesban seed oil

The aim of this study is to estimate the fatty acid composition and bioactivity of extracted seed oil of Sesbania sesban. S. sesban seeds were separated into two parts germ (42.48%) and endosperm with seed coat by a domestic mixer at medium speed by dry milling process. Endosperm with seed coat was separated by treatment with distilled water: ethanol, kept for 2hours, ground with mixer to obtain pure endosperm(26.22%), seed coat(11.33%) & subjected to extraction process viz. hot and cold method with solvent petroleum ether 40-60οC. Fatty acids composition was analyzed using gas-liquid chromatography for both soxhlet and cold extract that revealed maximum amount of palmitic acid was found in cold extract of endosperm (50.511%) & in seed coat (30.65%). Oleic acid was found to be maximum in cold extract of powder (48.20%) and in germ (48.67%) but in hot lower than cold. Linoleic acid was found to be more hot than cold methods. The antimicrobial activity of seed oil was done by disk diffusion method. Antibacterial activity has been shown more significant by cold in comparison to hot extracts. Hence, the present study revealed the potentiality of seed oil as a bioactive marker for pharmaceuticals, nutraceuticals and cosmetics

Hedgehog Signaling Antagonist GDC-0449 (Vismodegib) Inhibits Pancreatic Cancer Stem Cell Characteristics: Molecular Mechanisms

Recent evidence from in vitro and in vivo studies has demonstrated that aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway regulates genes that promote cellular proliferation in various human cancer stem cells (CSCs). Therefore, the chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for pancreatic cancer. GDC-0449 (Vismodegib), orally administrable molecule belonging to the 2-arylpyridine class, inhibits SHH signaling pathway by blocking the activities of Smoothened. The objectives of this study were to examine the molecular mechanisms by which GDC-0449 regulates human pancreatic CSC characteristics in vitro.GDC-0499 inhibited cell viability and induced apoptosis in three pancreatic cancer cell lines and pancreatic CSCs. This inhibitor also suppressed cell viability, Gli-DNA binding and transcriptional activities, and induced apoptosis through caspase-3 activation and PARP cleavage in pancreatic CSCs. GDC-0449-induced apoptosis in CSCs showed increased Fas expression and decreased expression of PDGFRα. Furthermore, Bcl-2 was down-regulated whereas TRAIL-R1/DR4 and TRAIL-R2/DR5 expression was increased following the treatment of CSCs with GDC-0449. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GDC-0449-treated pancreatic CSCs. Thus, activated Gli genes repress DRs and Fas expressions, up-regulate the expressions of Bcl-2 and PDGFRα and facilitate cell survival.These data suggest that GDC-0499 can be used for the management of pancreatic cancer by targeting pancreatic CSCs

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery

Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum

A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L.) plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV) and Ageratum leaf curl betasatellite (ALCB), respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch’s postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants

Measurement of the νe−\nu_e-Nucleus Charged-Current Double-Differential Cross Section at <Eν>=\left< E_{\nu} \right> = 2.4 GeV using NOvA

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using $8.02\times10^{20}$ protons-on-target (POT) in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by $\simeq$ 17\% systematic rather than the $\simeq$ 7.4\% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on $Q^{2}$ (squared four-momentum transfer) and energy, in the range 1 GeV $\leq E_{\nu} <$6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs. $Q^{2}$

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

Effects of Thyroxine Treatment on the Contractility and Morphometry of Dystrophic Hamster Muscles

The BIO 14.6 dystrophic hamster is a genetically determined animal model which exhibits muscular dystrophy. A possible contribution to this hereditary myopathy is made by an abnormal metabolism of thyroxine hormone which plays an important role in metabolism, neural activity, muscle strength, and lung diffusion capacity. The purpose of this investigation was to test the hypothesis that thyroxine treatment started in young dystrophic hamsters improves skeletal muscle functions by preventing or reducing the development of morphological and contractile degeneration in skeletal muscles. The experimental protocol included 3 test groups of animals: Normal (BIO F 1 B) (placebo treated), dystrophic (placebo treated), and dystrophic (thyroxine treated). Normal and dystrophic placebo groups were implanted s.c. with placebo pellets containing biodegradable carrier-binder, while the dystrophic thyroxine treated group received 90- day, 22 mg L-thyroxine pellets, also s.c; the implantation was repeated after 3 months for the 6-month experimental groups. Various contractile and morphometric characteristics were evaluated on the phrenic nerve-hemidiaphragm preparations and extensor digitorum longus (EDL) muscles isolated from normal and dystrophic hamsters, pretreatment and after 2 months and 6 months post-treatment. After thyroxine supplementation, the body weight gain in DT group was significantly higher (P\u3c0.05) compared to DP group;-from 7 to 18 weeks. Nonsignificant increases in optimal muscle length (Lo) were observed in diaphragm of DT, both after 2 month and 6 month post-treatment; the increase was more after 2 month post-treatment. In contrast, no significant difference (P\u3e0.05) in Lo was observed between DP and DT groups after 2 month and 6 month post-treatment, which is consistent with earlier findings in dystrophic animals that limb muscles are slowly and less affected by muscular dystrophy. A significantly higher (P\u3c0.05) muscle weight of diaphragm for DP compared to NP could be attributed to increased tissue hydration and calcification indystrophic skeletal muscles. The increased tissue hydration was also reflected in terms of lower (P\u3c0.05) % dry-to-wet weight ratios for DP compared to NP. Similar to Lo, a nonsignificant increase (P\u3e0.05) in diaphragm weight was observed in DT group, after 2 month and 6 month post-treatment, the increase being more after 2 month post-treatment. The values of twitch tension (specific force) were significantly lower (P\u3c0.05), both in direct and indirect modes, for DP compared to NP at all the time points. Further, an increase in this force was observed in DT compared to DP; the increase was significant (P\u3c0.05) after 2 month post-treatment (in direct mode) and 6 month post-treatment (in indirect mode). Also, a significant increase (P\u3c0.05) was observed in EDL muscle of DT group after 2 month post-treatment. The maximum tetanic force occurred at frequencies between 80- 100 Hz. Nonsignificant increases (P\u3e0.05) in maximum tetanic force (prefatigue and postfatigue) were observed in DT group after 2 month and 6 month post-treatment, both in DIA and EDL ; the increase was significant for directly stimulated EDL at t=2 months. No significant difference (P\u3e0.05) was observed between twitch contraction times for DIA of DP and DT groups, after 2 month and 6 month post-treatment. On the other hand, twitch half-relaxation times were insignificantly reduced (P\u3e0.05) in dystrophic DIA, both in direct and indirect modes, after 2 month and 6 month post-treatment. The slowing of time course of twitch has been ascribed to the decrease in activity of sarcoplasmic reticulum Ca2+-ATPase by thyroid hormone deficiency, suggesting a slowed Ca2+ re-uptake and therefore a slowed relaxation time course. Similar reductions in fatigue resistance of dystrophic DIA and EDL muscles were observed in DT group after 2 months and 6 months of thyroxine treatment; the reduction was significant (P\u3c0.05) for DIA-direct mode at t=6 months. Our morphometric and contractile data correlate well with the severe and progressive nature of muscular dystrophy, especially after 2 month post-treatment. The results of this study also suggest that thyroxine therapy may be beneficial in dystrophic hamsters, if started early in their life span

Scaffold of selenium nanovectors and honey phytochemicals for inhibition of pseudomonas aeruginosa quorum sensing and biofilm formation

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery