No abstract

ObjectiveThe objective of this study was to investigate the antibiotic susceptibility, virulence factors and clonal relationship among Pseudomonas aeruginosa isolated from environmental sources, hospitalized patients and the surfaces of cockroaches in the ICUs of four hospitals in Hamadan, west of Iran. A total of 237, 286 and 156 bacterial isolates were collected from clinical, environmental and cockroach sources respectively from May to September, 2017. The antimicrobial susceptibility was determined using disk diffusion method. The virulence factors, exotoxins A, S and U were detected by PCR. The genetic linkage of P. aeruginosa isolates were analyzed by Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR.ResultsAccording to our findings, 58 (24.4%), 46 (16%) and 5 (3.25) P. aeruginosa were isolated from clinical, environmental and cockroach samples respectively. The MDR phenotypes were detected in 18 (45%) and 15 (37.5%) of clinical and environmental strains. The environmental isolates harbored more exoA and exoS than did clinical isolates. Genetic diversity was established among P. aeruginosa isolates as 14 different ERIC fingerprints were detected. The clonal relationships was detected among clinical, environmental and cockroach isolates. Our results highlighted the importance of identifying and controlling the potential sources of P. aeruginosa infections in hospitals.

Histamine H3 receptors (H3R), belonging to G‐protein coupled receptors (GPCR) class A superfamily, are responsible for modulating the release of histamine as well as of other neurotransmitters by a negative feedback mechanism mainly in the central nervous system (CNS). These receptors have gained increased attention as therapeutic target for several CNS related neurological diseases. In the current study, we aimed to identify novel H3R ligands using in silico virtual screening methods. To this end, a combination of ligand‐ and structure‐based approaches was utilized for screening of ZINC database on the homology model of human H3R. Structural similarity‐ and pharmacophore‐based approaches were employed to generate compound libraries. Various molecular modeling methodologies such as molecular docking and dynamics simulation along with different drug likeness filtering criteria were applied to select anti‐H3R ligands as promising candidate molecules based on different known parent lead compounds. In vitro binding assays of the selected molecules demonstrated three of them being active within the micromolar and submicromolar Ki range. The current integrated computational and experimental methods used in this work can provide new general insights for systematic hit identification for novel anti‐H3R agents from large compound libraries.

Introduction: The prevalence of nosocomial infections in patients hospitalized to three hospitals of Shahid Beheshti, Farshchian, and Be' saat in Hamadan was investigated for 2 years (2018 to 2020). Materials and Methods: The samples were cultured and characterized using morphological and diagnostic biochemical tests. The analysis of the frequency of the isolates and their antibiotic resistance were calculated using SPSS (version 22) at a significant level of P-value < 0.05. Results: Bacterial isolates were collected from the 1194 clinical specimens, of which 1394 were isolated from urine, 16 from CSF, and 588 from tracheal aspiration. Also, 654 (54.8%) isolates were obtained from females and 540 (45.2%) from males with the age range 15-73 years (P> 0.05). The results showed that 22.1% were gram-positive and 77.9% were gramnegative. In our study, the frequency of Klebsiella pneumoniae bacteria was higher than in some studies, and this indicates the genetic changes and resistance of this bacterium to many antibiotics. Conclusion: To prevent further spread of resistance, increase the effectiveness of antibiotics and prevent multidrug resistance, it is essential to establish a precise schedule for the use of antibiotics and assess the resistance pattern periodically in each region based on the antibiotic resistance pattern.

BackgroundMany types of tumors are organized in a hierarchy of heterogeneous cell populations with different molecular signature. Such heterogeneity may be associated with different responsiveness to microenvironment stimuli. In the present study, the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), as well-known mediators of inflammation, on cancerous behavior of three prostate tumor cells, LNCaP, PC3 and DU145, were investigated.MethodsExpression of TLR1-10, CD14 and MyD88 transcripts was investigated by RT-PCR. Protein expression of TLR2 and 4 was scrutinized by flow cytometry, immunofluorescent staining and Western blotting. Experiments were set up to assess the effects of LPS and LTA at different concentrations and times on cell proliferation, extracellular matrix invasion, adhesion and cytokine production.ResultsWe showed that prostate cancer cell lines differentially express TLR1-10, MyD88 and CD14 transcripts. DU145 failed to express TLR4 gene. Positively-identified TLR2 protein in all prostate cancer cells and TLR4 protein in PC3 and LNCaP by Western blotting was not accompanied by cell surface expression, as judged by flow cytometry. Immunofluorescent staining clearly demonstrated predominantly perinuclear localization of TLR2 and TLR4. LTA activation of all prostate cancer cells significantly increased cell proliferation. Regardless of lacking TLR4, DU145 cells proliferated in response to LPS treatment. While LPS caused increased invasiveness of LNCaP, invasive capacity of PC3 was significantly reduced after LPS or LTA stimulation. Stimulation of all prostate tumor cells with LTA was associated with increased cell adhesion and IL-8 production. IL-6 production, however, was differentially regulated by LPS stimulation in prostate tumor cells.ConclusionThe data shows that cancer cells originated from the same histologically origin exhibit heterogeneous response to the same TLR ligand. Therefore, a thorough and comprehensive judgment on how and to what extent a particular cancer is affected by TLR agonist could not be inferred by studying an individual cell line.