Silver nanoparticles (AgNPs) were synthesized using Artemisia oliveriana extract, and their physicochemical characteristics were studied. The antioxidant and antimicrobial activities of the AgNPs, as well as their anticancer effects on the lung cancer cell line (A549), using 1,1-diphenyl-2-picrylhydrazyl (DPPH), MIC and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) techniques respectively demonstrated that the synthesized AgNPs mainly affected the gram-positive bacteria rather than the gram-negative bacteria, and exhibited significant cellular toxicity on the A549 cell line. Further, the cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell. Moreover, their impact on the expression of apoptotic genes including Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9) and miR-192 using real-time PCR demonstrated substantial increase in the expression of all mentioned genes (p<.001). Finally, the apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line. The results revealed that the AgNPs synthesized using A. oliveriana extract have potential biological applications.
In the current study, niosome‐encapsulated tobramycin based on Span 60 and Tween 60 was synthesized and its biological efficacies including anti‐bacterial, anti‐efflux, and anti‐biofilm activities were investigated against multidrug resistant (MDR) clinical strains of Pseudomonas aeruginosa. The niosomal formulations were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering measurement. The encapsulation efficiency was found to be 69.54% ±; 0.67. The prepared niosomal formulations had a high storage stability to 60 days with small changes in size and drug entrapment, which indicates that it is a suitable candidate for pharmaceutical applications. The results of biological study showed the anti‐bacterial activity via reduction of antibiotic resistance, enhanced anti‐efflux and anti‐biofilm activities by more folds in comparison to free tobramycin. In addition, niosome encapsulated tobramycin down‐regulated the MexAB‐OprM efflux genes, pslA and pelA biofilm related genes in MDR P. aeruginosa strains. The anti‐proliferative activity of formulation was evaluated against HEK293 cell lines, which exhibited negligible cytotoxicity against HEK293 cells. The finding of our study shows that encapsulation of tobramycin in niosome enhanced the antibacterial activity and reduced antibiotic resistance in MDR strains of P. aeruginosa comparing to free tobramycin and it can be considered as a favorable drug delivery system.
Background: Asparginase is known to be one of the most important bedrocks of acute lymphoblastic leukemia (ALL) treatment in almost all pediatric regimens in treatment protocols. Escherichia coli L-Asparginase (EC 3.5.1.1) is one of the most common resources to produce this enzyme. One of the affordable methods to overcome the side effects of drug is utilizing bioinformatic tools in the form of In silico study. In this study we designed a new structure of L-Asparginase to decrease its toxicity, reduce some side effects and increase the stability. Methods: We used some bioinformatics software and servers like Toxin red, Popmusic, kobami and I-TASSER server to reduce toxicity level of enzyme, and to increase stability and enzyme half-life. Results: We obtained 6 protein sequences in which the best was Mut 6 with four changes in structure: L23G, K129L, S263C and R291F. In contrast to the wild type, the new predicted protein is not toxic and has 25 hours more half-life and 600 kcal/mol more stable with no significant change in protein secondary, tertiary structure, antigenicity and allergenicity. Conclusions: Finally, sequence number 6 was the only sequence with all distinct characteristics: non-toxic, more stability and more half life.
Declaration of interests: The authors declare that they have no conflict of interests. Authors' contribution: All the authors had substantial contributions to the conception of the work. Drafting of the work was done by NS and NR; the remaining authors did critical revision. All approved the final draft and agree to be accountable for all aspects of the work.
The emergence of extended-spectrum beta-lactamases (ESBL) producing strains become a great concern, because few antimicrobial agents remain active against them. Due to the lack of data on the genotyping characteristics and antibiotics resistance of clinical isolates of Klebsiella pneumoniae in the north of Iran, this study aimed to determine the occurrence of ESBL-producing isolates and their molecular characteristics in order to analyses their epidemiological relationships. This cross-sectional study performed on 60 K. pneumoniae isolates which were recovered from different clinical specimens within May and November 2016. Isolates were identified by standard microbiologic tests and confirmed by API 20E strip. Antimicrobial susceptibility testing was carried out by disk diffusion method. The genetic relatedness among the isolates was assessed by RAPD-PCR. Totally, the lowest level of susceptibility was toward amoxicillin/clavulanat, and nalidixic acid. On the other hand, the highest level of susceptibility was toward imipenem (86.7%). The rate of ESBL-producing isolates was 45% (27/60). There was a significant association between production of ESBLs and higher antibiotic resistance in tested isolates. The RAPD-PCR dendrogram revealed 5 major clusters with a similarity of 80% which indicates the high relatedness of the studied isolates. Twenty-one isolates out of the 27 ESBL-producing isolates were clustered in cluster A. In summary, results showed the high prevalence of multiple-drug resistant and ESBL-producing K. pneumoniae isolates in our ICUs. Also, results revealed a significant similarity between ESBL-producing isolates that necessitate restricted infection control policies and rational prescription and use of antibiotics.
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