GLUT3 inhibitor discovery through in silico ligand screening and in vivo validation in eukaryotic expression systems.

The passive transport of glucose and related hexoses in human cells is facilitated by members of the glucose transporter family (GLUT, SLC2 gene family). GLUT3 is a high-affinity glucose transporter primarily responsible for glucose entry in neurons. Changes in its expression have been implicated in neurodegenerative diseases and cancer. GLUT3 inhibitors can provide new ways to probe the pathophysiological role of GLUT3 and tackle GLUT3-dependent cancers. Through in silico screening of an ~ 8 million compounds library against the inward- and outward-facing models of GLUT3, we selected ~ 200 ligand candidates. These were tested for in vivo inhibition of GLUT3 expressed in hexose transporter-deficient yeast cells, resulting in six new GLUT3 inhibitors. Examining their specificity for GLUT1-5 revealed that the most potent GLUT3 inhibitor (G3iA, IC50 ~ 7 µM) was most selective for GLUT3, inhibiting less strongly only GLUT2 (IC50 ~ 29 µM). None of the GLUT3 inhibitors affected GLUT5, three inhibited GLUT1 with equal or twofold lower potency, and four showed comparable or two- to fivefold better inhibition of GLUT4. G3iD was a pan-Class 1 GLUT inhibitor with the highest preference for GLUT4 (IC50 ~ 3.9 µM). Given the prevalence of GLUT1 and GLUT3 overexpression in many cancers and multiple myeloma's reliance on GLUT4, these GLUT3 inhibitors may discriminately hinder glucose entry into various cancer cells, promising novel therapeutic avenues in oncology.

AgNPs Ornamented Modified Bacterial Cellulose Based Self-Healable L-B-L Assembly via a Schiff Base Reaction: A Potential Wound Healing Patch.

A layer-by-layer (L-B-L) bacterial cellulose (BC)-based transdermal patch has been prepared via a Schiff base reaction. The L-B-L assembly consisting of covalently cross-linked ethylene diamine-modified carboxymethylated BC isolated from the Glucanoacetobacter xylinus (MTCC7795) bacterial strain and aldehyde-modified pectin formed via a Schiff base reaction. The presence of the imine bond assists the self-healing process after being scratched in the presence of a pH 7.4 buffer solution monitored via optical microscopy, atomic force microscopy, and tensile strength analyses. The formation of the L-B-L assembly was confirmed using field-emission scanning electron microscopy (FESEM) analysis. Simultaneously, water swelling and deswelling studies were carried out to test its water retention efficiency. The presence of silver nanoparticles (AgNPs) has been confirmed by ultraviolet-visible spectroscopy and FESEM analyses. The antimicrobial activity of the AgNPs-incorporated transdermal patch has been examined over Staphylococcus aureus and Escherichia coli using the zone of inhibition method. Additionally, the cell viability assay was performed using the fluorescent dyes 4',6-diamidino-2-phenylindole and propidium iodide. The AgNPs in the L-B-L assembly showed antimicrobial property against both types of bacteria. The cytotoxicity and wound healing property of the patch system have been studied over NIH 3T3 fibroblast and A549 epithelial cell lines. The L-B-L film also influenced the wound healing process of these two cell lines.

Hydrothermal synthesis of gelatin quantum dots for high-performance biological imaging applications.

In the present study, we are reporting a one-pot synthesis of gelatin quantum dots (GeQDs) by the hydrothermal process. The synthesized GeQDs were characterized by fourier transform infrared spectroscopy, nuclear magnetic resonance, ultraviolet-visible and photoluminescence spectroscopic techniques, and also by using high-resolution transmission electron microscopy. The GeQDs showed a high level of photoluminescence quantum yield (PLQY) with significantly higher stability for up to 6 months and presented similar fluorescent intensity as the initial PLQY without any precipitation and aggregation at ambient condition. The cell imaging ability of synthesized GeQDs was examined using cells belonging to diverse clinical backgrounds like bacterial cells including Escherichia coli and Staphylococcus aureus, yeast cells including Candida albicans, C. krusei, C. parapsilosis, and C. tropicalis, mycelial fungi including Aspergillus flavus and A. fumigatus cells, cancer cell lines A549, HEK293 and L929. The results demonstrated that the GeQDs illuminates the cells and can be utilized as potential cell labeling non-toxic biomarkers. In conclusion, it can be said that the gelatin stabilized QDs are a promising candidate for stable and long-term fluorescent imaging of different types of cells.

Curcumin entrapped gelatin/ionically modified bacterial cellulose based self-healable hydrogel film: An eco-friendly sustainable synthesis method of wound healing patch.

In this context, we have prepared a biocompatible gelatin based polyelectrolyte hydrogel patch that has an inherent ability to self-heal in the presence of physiological pH (pH = 7.4). The gelatin-based hydrogel patch consists of the ionically modified self-assembled bacterial cellulose (iBC), extracted from Glucanoacetobacter xylinus (MTCC7795) bacterial strain. Presence of the iBC provides a sturdy cage to the gelatin matrix and also participates into the self-healing activity via formation of the ionic interlocking system in the presence of buffer solution having a pH of 7.4 after being damaged. The self-healing activity of the patch has been monitored through tensile strength measurement and AFM depth profilometry analyses. Loading of the curcumin in the hydrogel patch system incorporates the wound healing activity, examined over the NIH 3 T3 fibroblast cell line. The patch is also able to show antimicrobial activity which has been assessed via FESEM analysis and live-dead assay using propidium iodide (PI) and 4',6-diamidino-2-phenylindole (DAPI) as a fluorescent indicator. This self-healable, ionically interlocked, mechanically robust, bio-derived smart hydrogel patch system can pave a new direction in the transdermal drug delivery system.

Modified bacterial cellulose based self-healable polyeloctrolyte film for wound dressing application.

In this investigation, we prepare a self-healable polyelectrolyte film via crosslinking the cationically charged chitosan (Cts) with anionically modified bacterial cellulose (BC), which is a green source of nano-filler. This polyelectrolyte film is able to show dynamic self-healing activity at physiological pH condition via adapting ionic interaction, a state of non-covalent bond. BC was prepared using Glucanoacetobacter xylinus (MTCC7795) bacteria and after that its surface was modified with anionic poly(acrylic acid) using "grafting from" technique. It was observed that the notch (single and multiple) created over the composite film was disappeared by showing vibrant diffusion and ionic interlocking in contact with buffer solution having physiological pH. The XTT assay revealed that the composite film is non-toxic in nature and it was witnessed that the composite film was capable of delivering curcumin, a hydrophobic drug that has an ability to show antimicrobial activity and wound healing capability.

Modified chitosan encapsulated core-shell Ag Nps for superior antimicrobial and anticancer activity.

This investigation reports a one pot synthesis of silver nanoparticles (Ag Nps) using aqueous solution of chitosan-graft-poly(acrylamide) (Cts-g-PAAm) as a reducing agent and polyethylene glycol (PEG) as a stabilizing agent. The as synthesized Ag Nps was characterized by ultra violet-visible (UV-vis), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analysis. Field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that Ag Nps, which were stable upto more than 60 days, were spherical in shape and the particle size was in the range of 5-50 nm. Atomic force microscopy (AFM) image also supported the above obtained result. The prepared Ag Nps exhibited strong antimicrobial activity against different gram positive bacteria (Alkaliphilus, Bascillus substillis, Lysinibascillus) and gram negative bacteria (Enterobacter aerogenus, Vivbrio vulnificus and Escherichia coli) and haemolytic assay revealed its blood compatible nature. The synthesized Ag Nps showed significant cytotoxicity over human cervical HeLa cancer cells and it was found that the inhibitory concentration for 50% cell death (IC50) was 8 µg/ml.