Development of Zein-Pectin Nanoparticle as Drug carrier

Recent years have witnessed tremendous growth of nanotechnology based drug delivery system which reduces drug toxicity and side effects and increases the therapeutic index of the drug. Aim of the study is to develop a biodegradable, non-toxic nanoparticle, solely from natural polymers. Zein – pectin nanoparticle comprising of a hydrophobic zein core and a hydrophilic pectin shell was developed by ultrasonication method. SEM images confirm the nanosize of the nanoparticle. UV- Visible and FT-IR spectroscopic results confirm the incorporation of zein, pectin and the encapsulation of the model drug quercetin in the nanoparticle. Zein is a prolamine class of protein found in wheat, maize etc and pectin is a polymer of galacturonic acid units found in plant cell wal

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

Suzuki-Miyaura coupling under microwave enhanced conditions: Synthesis of 2-(hetero)aryl benzimidazoles

An expedient, palladium-mediated cross-coupling approach to functionalize the benzimidazole-based core under microwave-assisted conditions has been developed and is described. This protocol, which incorporates appendage diversity on this potential scaffold, is found to be compatible with a wide range of electronicallyand sterically-divergent (hetero)aryl boronic acids. The use of the PdCl2/(SPhos) catalytic system allows the formation of a stable and highly active LPd(0) species which was found to be critical for the successful synthesis of these novel, pharmacologically-relevant molecules. © AUTHOR(S).Russian Foundation for Basic Research, RFBR: 170300641AThe authors are thankful to SAIF, Indian Institute of Technology, Madras, for providing all the analytical data and spectra. Vasiliy A. Bakulev is thankful to Russian Foundation for Basic Research (Grant # 170300641A)

MUC16-mediated activation of mTOR and c-Myc reprograms pancreatic cancer metabolism.

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global metabolic alterations in MUC16 knockdown pancreatic cancer cells, as compared to the controls. Specifically, glycolytic and nucleotide metabolite pools were significantly decreased. We observed similar metabolic alterations that correlated with MUC16 expression in primary tumor tissue specimens from human pancreatic adenocarcinoma cancer patients. Overall, our results demonstrate that MUC16 plays an important role in metabolic reprogramming of pancreatic cancer cells by increasing glycolysis and enhancing motility and invasiveness

Mass dependence of light nucleus production in ultrarelativistic heavy ion collisions

Light nuclei can be produced in the central reaction zone via coalescence in relativistic heavy ion collisions. E864 at BNL has measured the production of ten light nuclei with nuclear number of A=1 to A=7 at rapidity $y\simeq1.9$ and $p_{T}/A\leq300MeV/c$. Data were taken with a Au beam of momentum of 11.5 A $GeV/c$ on a Pb or Pt target with different experimental settings. The invariant yields show a striking exponential dependence on nuclear number with a penalty factor of about 50 per additional nucleon. Detailed analysis reveals that the production may depend on the spin factor of the nucleus and the nuclear binding energy as well.Comment: (6 pages, 3 figures), some changes on text, references and figures' lettering. To be published in PRL (13Dec1999

Measurements of Light Nuclei Production in 11.5 A GeV/c Au+Pb Heavy-Ion Collisions

We report on measurements by the E864 experiment at the BNL-AGS of the yields of light nuclei in collisions of Au(197) with beam momentum of 11.5 A GeV/c on targets of Pb(208) and Pt(197). The yields are reported for nuclei with baryon number A=1 up to A=7, and typically cover a rapidity range from y(cm) to y(cm)+1 and a transverse momentum range of approximately 0.1 < p(T)/A < 0.5 GeV/c. We calculate coalescence scale factors B(A) from which we extract model dependent source dimensions and collective flow velocities. We also examine the dependences of the yields on baryon number, spin, and isospin of the produced nuclei.Comment: 21 figures-to be published in Phys. Rev.

101 Dothideomycetes genomes: A test case for predicting lifestyles and emergence of pathogens.

Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with &gt;95&nbsp;% accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species

Tunable variation of optical properties of polymer capped gold nanoparticles

Optical properties of polymer capped gold nanoparticles of various sizes (diameter 3-6 nm) have been studied. We present a new scheme to extract size dependent variation of total dielectric function of gold nanoparticles from measured UV-Vis absorption data. The new scheme can also be used, in principle, for other related systems as well. We show how quantum effect, surface atomic co - ordination and polymer - nanoparticle interface morphology leads to a systematic variation in inter band part of the dielectric function of gold nanoparticles, obtained from the analysis using our new scheme. Careful analysis enables identification of the possible changes to the electronic band structure in such nanoparticles.Comment: 13 pages,7 figures, 1 tabl