Elucidating novel antibacterial compounds from the NPASS database against the FimH lectin domain for the treatment of urinary tract infections: an in-silico study.

The increase in multidrug-resistant pathogens in urinary tract infections (UTIs) among communities and hospitals threatens our ability to treat these common pathogens. Uropathogenic Escherichia coli (UPEC) strains are the most frequent uropathies linked to the development of UTIs. This work aims to introduce bioactive natural products via virtual screening of small molecules from a public database to prevent biofilm formation by inhibiting FimH, a type 1 fimbriae that plays a crucial role in UPEC pathogenicity. A total of 30926 small molecules from the NPASS database were subjected to screening via molecular docking. Followed by performing in silico ADME studies, seven molecules showed promising docking results ranging from -6.8 to -8.7 kcal/mol. As a result of the docking score findings, 100 ns Molecular dynamics (MD) simulations were performed. Based on MM-PBSA analysis, NPC313334 ligand showed high binding affinity -42 and stability with the binding pocket of FimH protein during molecular dynamic simulations. DFT calculations were also performed on the ligands to calculate the HOMO-LUMO energies of the compounds in order to an idea about their structure and reactivity. This research suggests that NPC313334 may be a possible antibacterial drug candidate that targets FimH to reduce the number of UPEC-related urinary tract infections.Communicated by Ramaswamy H. Sarma.

Pharmacokinetic Effect of MDR Gene Polymorphism rs2032582 on the Therapeutic Response in Iraqi Patients with Acute Myeloid Leukemia.

BACKGROUND: The main problem in treatment of leukemia patients is the chemotherapy resistance which is a main concern in recent years. The cause of chemotherapy drug resistance is related to MDR gene which is located on chromosome 7 (7q21-31) and it is mainly connected with energy-dependent efflux (P-glycoprotein). This study was conducted to assess the correlation between MDR polymorphism and chemotherapy efficiency with Vincristine in a sample of Iraqi Acute Myeloid Leukemia (AML) patients. METHODS: The blood sample of 200 AML patients and 200 controls were collected and the frequency of rs2032582 was calculated through sequencing and then the role of different genetic patterns was evaluated on cancer cells by MTT assay. RESULTS: The results indicate that GG and TT genotypes (20 and 20.5% from total patients count) are more frequent in Iraqi AML patients than other genetic patterns in MDR gene and also the genotype TA is more sensitive to Vincristine chemotherapy than other genotypes. CONCLUSION: It seems that genetic pattern is the main factor in determination of chemotherapy of AML patients, and patients should not undergo chemotherapy with such drugs, especially Vincristine.

Association study of two single nucleotide polymorphisms rs10757278 and rs1333049 with atherosclerosis, a case-control study from Iraq.

Atherosclerosis is one of the most important coronary artery disease (CAD) caused by lipid accumulation, hypertension, smoking, and many other factors such as environmental and genetic factors. It has been recorded that genetic variations in rs10757278 and rs1333049 are correlated with CAD. In the present study, 100 blood samples were collected (50 CAD patients and 50 appeared to be healthy controls), who referred to Ibn-Albytar general hospital/in Bagdad city for heart disease from February to March 2019. Genotyping for two SNPs rs10757278 and rs1333049, were done by Tetra ARMS method. For the rs10757278 polymorphism, the GG genotype verses to AA genotype was significantly associated with the risk of CAD (OR=5.16, 95% CI:1.02-26.0, P=0.047). For the rs10757278 polymorphism, there was no significant associatin between genotypes and the susceptibiulity to CAD. In the present study, the rs10757278 polymorphism showed an association with CAD.