Biology subjects

Chowdhury, D.

Publications and source records attributed to Chowdhury, D..

22 records · Page 2Linked to original sources

bioRxiv2022

Optimization of conditions for conjugation of outer membrane vesicles of Salmonella Typhimurium with oral delivery systems using response surface method

BackgroundOuter membrane vesicles (OMVs) released from Salmonella Typhimurium can become the effective vaccine candidate. For efficient delivery through oral route, the OMVs are conjugated with some delivery systems. The current study was aimed at optimization of conditions required for conjugation of OMVs with nano- or microparticles for maximum entrapment of OMV in terms of protein concentration. MethodsThe OMVs of Salmonella Typhimurium were conjugated under three optimum conditions of pH, temperature and ratio (nanoparticles or microparticles: OMVs) predicted by response surface method. The efficiency of conjugation was determined by entrapment of OMVs in nano/microparticles. ResultThe pH and temperature were not influential conditions in case of conjugation of OMVs with chitosan nanoparticles (Ch-NP) and poly-lactide co-glycolide microparticles (PLG-MP) while they had influence in case of poly(anhydride) nanoparticles. In case of Ch-NP and PLG-MP, the optimum ratio for maximum entrapment was found to be 1:10 and 1:9 respectively. The optimum pH and temperature was found to be 7 and 24{degrees}C respectively for conjugation of poly(anhydride) nanoparticles. The optimized conditions did not alter the protein profile and immunogenic potential of conjugated vaccines.

biochemistry↗

bioRxiv2021

A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pathway for pyrimidine biosynthesis. A clinical stage inhibitor of DHODH (rate limiting enzyme in the de novo pathway) diminishes UMP pools, generates DNA damage, and induces apoptosis through suppression of replication forks--an "on target" effect, as shown by uridine rescue. MALDI mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.

cancer biology↗

bioRxiv2021

Metallothionein 3-zinc axis suppresses caspase-11 inflammasome activation and impairs antibacterial immunity

Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE- 4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (M{phi}) is negatively controlled by the zinc (Zn2+) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), M{phi} increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1{beta}. Mechanistically, MT3 increased intramacrophage Zn2+ to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram- negative bacteria. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=149 HEIGHT=200 SRC="FIGDIR/small/454033v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@15070f1org.highwire.dtl.DTLVardef@27174forg.highwire.dtl.DTLVardef@6b48beorg.highwire.dtl.DTLVardef@174b850_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Effect of Leaf Aqueous Extract of Manilkara hexandra on Digestive and Glucose Metabolic Enzymes, and Serum Glucose Level in Labeo rohita Fingerlings

Manilkara hexandra (Roxb.) Dubard (common name Khirni, family: Sapotaceae) is an evergreen traditionally used medicinal plant. The present study aimed to see the effects of leaf aqueous extract of M. hexandra (LAEMH) on digestive and glucose metabolic enzyme action and serum glucose level in rohu, Labeo rohita, fingerlings. Experimental fish were fed a basal diet (Group I), and diets supplemented with LAEMH at 300 mg (Group II) and 600 mg (Group III) kg-1body weight. A significant reduction in serum glucose was noticed in the treated groups when compared with the control group. The reduced amylase activity was noticed in the treated fingerlings in a dose-dependent manner. However, lipase and protease activities didnt differ significantly among the experimental groups. Reduced serum glucose level might be correlated with the decline in the activity of digestive amylase in fish. Group II (3.35{+/-}0.19 U) and Group III (3.49{+/-}0.13 U) were recorded with reduced glucose-6-phosphatase activities than the control group (4.4{+/-}0.39 U). Moreover, the study revealed a decline in fructose-1,6-phosphatase activities in the treated groups in comparison to the control group. The decline in the activities of the metabolic enzymes might be associated with the non-availability of glucose owing to reduced activity of the digestive amylase in the treated groups. In conclusion, the present study established the hypoglycaemic effect of the leaf aqueous extract of M. hexandra in a fish model.

pharmacology and toxicology↗