Molecular modelling studies and identification of novel phytochemical inhibitor of DLL3.

Prostate cancer has been recently considered the most diagnosed cancer in male. DLL3 is overexpressed in CRPC-NE but not in localised prostate cancer or BPH. There are no effective treatments for neuroendocrine differentiated prostate cancer due to a lack of understanding of DLL3 structure and function. The structure of DLL3 is not yet determined using any experimental techniques. Hence, the structure-based drug discovery approach against prostate cancer has not shown great success. In present study, molecular modelling techniques were employed to generate three-dimensional structure of DLL3 and performed its thorough structural analysis. Further, all-atom molecular dynamics simulation was performed to obtain energetically favourable conformation. Further, we used a virtual screening using a library of >13800 phytochemicals from the IMPPAT database and other literature to select the best possible phytochemical inhibitor for DLL3 and identified the top five compounds. Relative binding affinity was calculated using the MM-PBSA approach. ADMET properties of the screened compounds reveal the toxic effect of Gnemonol C. We believe these studied physicochemical properties, functional domain identification, and binding site identification would be very useful to gain more structural and functional insights of DLL3; also, it can be used to infer their pharmacodynamics properties of DLL3 which was recently reported as an important prostate cancer target. The current study also proposes that Ergosterol Peroxide, Dioslupecin A, Mulberrofuran K, and Caracurine V have strong affinities and could serve as plausible inhibitors against DLL3. We believe this study would further help develop better drug candidates against neuroendocrine prostate cancer.Communicated by Ramaswamy H. Sarma.

Listeria ilorinensis sp. nov., isolated from cow milk cheese in Nigeria.

During microbial assessment of cow milk cheese products in the city of Ilorin, Nigeria, a Listeria-like isolate was detected that could not be assigned to any known species. Whole-genome sequence analyses against all currently known 26 Listeria species confirmed that this isolate constitutes a new taxon within the genus Listeria, with highest similarity to Listeria costaricensis (average nucleotide identity blast of 82.66%, in silico DNA-DNA hybridization of 28.3%). Phenotypically, it differs from L. costaricensis by the inability to ferment sucrose, l-fucose and starch. The absence of haemolysis and Listeria pathogenic islands suggest that this novel species is not pathogenic for humans and animals. The name Listeria ilorinensis sp. nov. is proposed, with the type strain CLIP 2019/01311T (=CIP 111875T=DSM 111566T).

Effect of co-administration of metformin and extracts of Costus pictus D.Don leaves on alloxan-induced diabetes in rats.

Background and aim: The present study evaluates the antidiabetic effects of aqueous (CPAQ) and methanolic (CPME) extract of Costus pictus D. Don singly and/or in combination with metformin in alloxan-induced diabetic rats. Experimental procedure: CPAQ and CPME (400 mg/kg dose), metformin (120 mg/kg) and two different combinations of plant extracts and metformin (200 + 60 mg/kg and 400 mg/kg + 60 mg/kg) were orally given to alloxan-induced diabetic rats for 21 days. At 0, 7, 14, and 21 days, body weight and blood glucose levels were measured. Results and conclusion: After 21 days of treatment, biochemical profiling and histopathology analysis were carried out. CPAQ and CPME, when administrated separately, could decrease blood glucose levels (P ≤ 0.05). CPME showed more promising results (P ≤ 0.05) compared to the diabetic control group. Extracts co-administrated with metformin showed dose-dependent significant recovery of hypoglycemic activity of metformin. Fasting blood glucose levels, body weight, protein, and lipid profile of the treatment group were compared to the diabetic and normal control groups. Animal groups co-administered with CPME and metformin showed more significant effects on the recovery of tissue damages. The synergistic effect of plant extracts with metformin has positive effects on all the parameters and enhanced the efficiency and reduction of blood glucose levels.

Isolation and characterization of Lactococcus garvieae from the fish gut for in vitro fermentation with carbohydrates from agro-industrial waste.

This study focused on agro-industrial waste such as fruit peels by extracting prebiotics as a carbon source for lactic acid bacteria (LAB). Four strains of LAB were selected from Oreochromis niloticus (B2 and B3) and Nemipterus japonicas (R4 and R5), and identified as Lactococcus garvieae through 16S rRNA gene sequencing. The analysis of probiotic characteristics revealed that all four strains were able to tolerate sodium chloride (up to 7 %), bile salt (up to 3 %), and broad range of pH (2-9). Further, analysis of polysaccharide contents in the agro-industrial waste materials such as peels of pineapple, orange, lemon, sugarcane, pomegranate, and sweet lemon revealed that the concentration ranged from 3.91-163.85 mg/g. It was observed that orange peels (20.38-140.99 mg/g), sweet lemon peels (22.03-161.93 mg/g), and pomegranate peels (38.19-163.85 mg/g) yielded maximum indigestible polysaccharide. Evaluation of synbiotic combination of probiotic and prebiotic revealed that L. garvieae strains had better fermentation efficiency with orange, sweet lemon, and pineapple compared to lemon, sugarcane, and pomegranate. In nutshell, different types of agro-industrial waste evaluated in this research were found to be a cheap and fermentable carbon sources for LAB. Further study should be conducted to analyze this symbiotic combination as feed supplements for fish in aquaculture as well as various fermentation industries.