An immunoinformatic approach employing molecular docking and molecular dynamics simulation for evaluation of l-asparaginase produced by Bacillus velezensis.

l-Asparaginase is one of the most important treatments for acute lymphoblastic leukemia. In this study, l-asparaginase-producing bacteria were isolated from the effluent and soil of the Isfahan slaughterhouse using M9 specific medium. Isolates were identified by 16SrRNA phylogenetic analysis. The immune characteristics were predicted. Molecular docking was performed between l-asparaginase and l-asparagine substrate using AutoDock tools 4.2 and AutoDock Vina. Molecular dynamics simulation studies were fulfilled using GROMACS. Five l-asparaginase-producing bacteria isolated that belonging to Stenotrophomonas maltophilia, Chryseobacterium sp. Chryseobacterium indologenes, Bacillus velezensis and Bacillus safensis. Predictions showed B. velezensis has better immune characteristics than B. safensis. The binding energies of the docked complex were calculated to be -4.34 and -4.9 kcal/mol. Molecular docking confirmed the interaction of l-asparaginase with its substrate. It was observed that the residues Thr36, Tyr50, Ala47, Thr116, Asp117, Met142, Thr193 and Thr192 were fundamental in protein-ligand complexation. Also, RMSD, RMSF, Rg, DSSP, SASA and MM-PBSA analysis showed that when l-asparaginase is bound to l-asparagine, it did not lose stability, secondary structure and compactness. Slaughterhouse soils and effluents are a potential source of l-asparaginase-producing bacteria that probably can probably produce l-asparaginase with more favorable immune properties than commercial enzymes.Communicated by Ramaswamy H. Sarma.

Evaluation antibiotic resistance and presence of blaOXA-51, blaOXA-58 and blaOXA-23 genes in Acinetobacter baumannii strains via multiplex PCR.

The resistance of Acinetobacter baumannii to most antibiotics is increasing. The presence of metallo-beta-lactamase and carbapenemase enzymes has led to the resistance of these bacteria to carbapenems as one of the major classes of broad-spectrum antibiotics and has raised concerns in human societies. This research evaluated the presence of blaOXA-51, blaOXA-58 and blaOXA-23 genes in A. baumannii strains during a 12 months period. One hundred strains were isolated from the patients hospitalized in ICU of Ali Asghar and Shahid Rajaee trauma hospitals in Shiraz. Bacterial identity was determined by biochemical tests and antibiotic resistance was determined by disk diffusion method. The isolated strains were then evaluated in terms of carrying blaOXA-23, blaOXA-51 and blaOXA-58 genes, using the multiplex PCR method. The results showed that A. baumannii was resistant to carbapenems but most strains were susceptible to tigecyclin and colistin. The majority of strains carried the blaOXA-23 and blaOXA-51 genes, but very few carried the bla OXA-58 gene. The results revealed that the antibiotic resistance of A. baumannii is increasing, which causes a more outbreak of this organism.

The effect of Ficus carica latex on 7, 12-dimethylbenz (a) anthracene-induced breast cancer in rats.

OBJECTIVE: In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. Recently, in vitro studies have reported the anticancer effect of this latex on cancer cell lines. This study evaluated the effect of this latex on breast cancer growth, hematological parameters, and histopathology in rats. MATERIALS AND METHODS: Twenty-four female rats were randomly divided into 3 groups. In cancerous group, 0.5 ml 7, 12-dimethylbenz (a) anthracene was injected to nipple for breast cancer induction. The control group received sesame oil at the same volume through similar route. In fig latex treated group (Fle), breast cancer was induced and then 0.5 ml of fig latex was intratumorally injected on a daily basis for 4 weeks. Tumor size was measured at the 2nd, 4th and 6th weeks of the experiment. Blood samples were used for investigation of the hematological parameters and livers, kidneys and tumor tissues were removed for histopathological analysis. RESULTS: The tumor size in Fle group was significantly decreased compared to the cancerous group. Haematocrit, hemoglobin, RBC and their indices were significantly decreased, whereas platelet, leukocyte and white blood cell numbers were significantly increased in cancerous group compared to the control group. There were no changes in these parameters in the Fle group compared to the control group. There were severe pathological changes in the livers and kidneys of cancerous group, but not in Fle group. CONCLUSION: These results suggest that fig latex could decrease tumor growth without having any adverse effect on hematological and histological factors. However, further investigation is required in this field.

In silico and in vitro studies of cytotoxic activity of different peptides derived from vesicular stomatitis virus G protein.

OBJECTIVES: This study aims at exploring cytotoxic activity of different peptides derived from VSVG protein against MCF-7 and MDA-MB-231 breast cancer cell lines and human embryonic kidney normal cell (HEK 293). MATERIALS AND METHODS: The ANTICP web server was used to predict anticancer peptides. The cytotoxic activity of peptides with high score (P26, P7) and low score (P19) was examined by MTT and DNA fragmentation assays. RESULTS: The results obtained from ANTICP web server demonstrated that 4 out of 48 peptides (P26, P7, P10, and P16) had anticancer activity. P26 and P7 peptides of these 4 peptides were detected to have high cytotoxic activity against MCF-7 cells with CC50 values of 98,280 µg/ml and MDA-MB231 cells with CC50 100,550 µg/ml, respectively. In addition, the results showed that amino acid residues of these 4 peptides were located near fusion domain. CONCLUSION: The results confirmed that P26 and P7 peptides might induce membrane damage and initiate apoptosis. The present study suggested that P26 and P7 peptides could be appropriate candidates for further studies as cytotoxic agents and modifications in the residue at positions 70-280 might potentially produce a more efficient VSVG protein in gene therapy.