• Heavy metals effects fishes when its concentration arises from its normal. • Bioaccumulation of manganese and chromium was studied in Cyprinus carpio on hematological and biochemical parameters. • In organ, bioaccumulation is highest in the gills followed by intestine > muscles > skin > bones. • It is concluded that heavy metal can readily bio accumulate in the organs of fish.

Diabetes mellitus, one of the most common endocrine-metabolic disorders, has caused significant morbidity and mortality worldwide. To avoid sugar digestion and postprandial hyperglycemia, it is necessary to inhibit α-glucosidase, a digestive enzyme with an important role in carbohydrate digestion. The criteria for the selection of alkaloids are based on their in vitro and in vivo activities on glucose modulation. The current study assessed the bonding potential of isolated alkaloids with the targeted protein. For this purpose, the 3D structure of the target protein (α-glucosidase) was reproduced using MODELLER 9.20. The modeled 3D structure was then validated and confirmed by using the RAMPAGE, ERRAT, and Verify3D online servers. The molecular docking of 32 alkaloids reported as α-glucosidase inhibitors, along with reference compounds (acarbose and miglitol), was done through MOE-Dock applied in MOE software to predict the binding modes of these drug-like compounds. The results revealed that nummularine-R and vindoline possess striking interactions with active site residues of the target protein, and were analogous to reference ligands. In conclusion, the current study provided a computational background to the α-glucosidase inhibitors tested. This novel information should facilitate the development of new and effective therapeutic compounds for the treatment of diabetes mellitus.

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

Introduction: Brucella melitensis is a facultative intracellular bacterial pathogen that causes abortion in goats and sheep and Malta fever in humans. In humans, chronic infection occurs through contact with infected animals or their waste products. Methods: The subtractive genomic approach is considered as a powerful and useful method for the identification of potential drug and vaccine targets. In this study, an attempt has been made through a subtractive proteomic strategy to identify novel drug targets in Brucella melitensis strains. Total 2604 core proteins of 56 strains of B. melitensis were taken, of which 545 non-human homologs were found to be essential for pathogen growth. Metabolic pathway analysis of these essential proteins revealed that 129 proteins are exclusively involved in 21 unique metabolic pathways in B. melitensis reference strain. Results: Of these, 31 proteins were found to be involved in 10 metabolic pathways that are unique to the pathogen. We selected Nitrate reductase subunit-β, Urease subunit α-2, Pantoate-β-alanine ligase, Isochorismatase, 2-dehydro-3-deoxyphosphooctonate aldolase and Serine O-acetyltransferase as drug targets in Brucella melitensis strains. Among these druggable targets, we selected only Pantoate-β- alanine ligase as high confidence target based on intensive literature curation, which is nonhomologous to the human gut metagenome involved in biosynthesis of secondary metabolites pathway. Pantothenate synthetase is the best chemotherapeutic target to combat Brucellulosis. Conclusion: Furthermore, in vitro and in vivo validation is needed for the evaluation of lead compounds against Brucella melitensis strains.