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OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies worldwide and it is considered the fourth most common cause of cancer death. This study aimed to find critical genes/pathways in GC pathogenesis to be used as biomarkers or therapeutic targets. METHODS: Differentially expressed genes were explored between human gastric cancerous and noncancerous tissues, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses were done. Hub genes were identified based on the protein-protein interaction network constructed in the STRING database with Cytoscape software. The hub genes were selected for further investigation using GEPIA2 and DrugBank databases. RESULTS: Ten overexpressed hub genes in GC were identified in the current study, including FN1, TP53, IL-6, CXCL5, ELN, ADAMTS2, WISP1, MMP2, CTGF, and THBS1. The study demonstrated the PI3K-Akt pathway's central involvement in GC, with pronounced alterations in essential components. Survival analysis revealed significant correlations between CTGF, FN1, IL-6, THBS1, and WISP1 overexpression and reduced overall survival times in GC patients. CONCLUSION: A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required.

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OBJECTIVES: Drug resistance among gram-negative bacteria is a worldwide challenge. Due to the importance of drug-resistant Klebsiella pneumoniae and Escherichia coli strains in hospital-acquired infections, we aimed to determine the phenotypic and genotypic characteristics of ESBL-, AmpC-, and carbapenemase-producing isolates obtained from hospitalized patients in Tehran and Ilam (Iran). MATERIALS AND METHODS: In total, 90 K. pneumoniae isolates and 65 E. coli isolates were collected from various infections. Phenotypic identification of bacterial isolates was performed using standard methods. Phenotypic screening of ESBL, AmpC, and carbapenemase enzymes was carried out. Detection of ESBL, AmpC, and carbapenemase genes was also performed by the PCR method. RESULTS: Phenotypic detection tests showed that 36 (40%) K. pneumoniae and 23 (35.4%) E. coli isolates were ESBL producers. Moreover, 18 (20%) and 6 (9.2%) K. pneumoniae and E. coli isolates were AmpC producers, respectively. Modified Hodge test results indicated that 39 (43.3%) K. pneumoniae and 18 (27.7%) E. coli isolates produced carbapenemase. Molecular tests showed that 40% of K. pneumoniae and 36.9% of E. coli isolates were ESBL positive. AmpC was detected in 24.4 and 13.8% of K. pneumoniae and E. coli isolates. Carbapenemase was detected in 34 (37.8%) K. pneumoniae and 13 (20%) E. coli isolates. -Conclusion: In this study, 3 K. pneumoniae isolates simultaneously carried ESBL, AmpC, and carbapenemase genes. Up-to-date strategies such as combination therapy or utilization of new antimicrobial agents might help to combat such drug-resistant organisms.

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BACKGROUND AND OBJECTIVE: Today, resistance to multiple classes of antibiotics, and notably to the ß-lactam and aminoglycosides in A. baumannii is becoming a great problem and it necessitates to make a new approach to combat with multidrug-resistant (MDR), extensive drug-resistance (XDR) or Pandrug-resistant (PDR) isolates. In this case, a new strategy and ways should be designed and introduced against such infections. Therefore the aim of the present study was the evaluation of antibacterial activity of nanoconjugate gentamicin and amikacin with gold against clinical isolates of A. baumannii that were collected from burn wound infection. There are some patents of gold nanoparticles that are conjugated with antibiotics (WO2017161296A1, US20090181101A1). METHODS: Eighteen A. baumannii were collected from burn wound infections. For confirmation and detection of aminoglycoside-resistant genes, PCR was carried out. Gold nanoparticles and nanoconjugates were prepared according to the protocol. For the evaluation of the nanoconjugate, Dynamic light cattering, Transmission electron microscopy and FTIR Analysis were carried out. Then, the antibacterial activity of nanoconjugates was conducted by using micro broth dilution method. RESULT: Prevalence of aminoglycoside-resistant genes was aacC1, aphA6, aadA1, aadB genes 55.5%, 22.2%, 38.8% and 22.2% respectively. Synthesis of bare nanoconjugates resulted in nanoparticle in a size of 10 nm. Amikacin bound to Gnps showed excellent antibacterial activity (94.5%) and just one isolate showed intermediate resistance. Also, gentamicin bound to Gnps had a good antimicrobial effect (50%) in contrast to gentamicin alone. CONCLUSION: Our study showed that a combination of amikacin and gentamicin with Gnps has a significant antibacterial efficiency against clinical isolates of A. baumannii. Gnps can be used as extraordinary molecular carriers for targeting, and delivery of the antibiotic molecules to the specific infection.

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BACKGROUND: Mycobacterium tuberculosis as an intracellular pathogen causes Tuberculosis (TB). Due to the long time required for treatment, hepatotoxicity of drugs and also emergence of Multidrug-Resistant (MDR) and Extremely Drug Resistant (XDR) strains, TB is currently a major public health problem. Some medicinal plants possess remarkable activity against Mycobacterium. Among them, Lamiaceae family are of pharmaceutical interest because of their potential antimicrobial properties. The aim of the study was to evaluate the in vitro activities of Satureja rechingeri, Satureja khuzestanica and Zataria multiflora against MDR M. tuberculosis and two Non-Tuberculous Mycobacteria (NTM). METHODS: The essential oils were prepared by the standard method. The confirmed strains were obtained from the microbial collection of Tehran University of Medical Sciences. Minimum Inhibitory Concentrations (MICs) of essential oils of plants against mycobacterial strains were determined using standard broth microdilution method. RESULTS: MDR M. tuberculosis was completely inhibited by Z. multiflora at 78µg/ml concentration. S. rechingeri and S. khuzestanica also showed same anti-mycobacterial activity against MDR M. tuberculosis with MICs of 156 µg/ml. The MICs of the essential oils against M. tuberculosis H37Rv, M. kansasii and M. fortuitum were in the range from 39 to 156 µg/ml. CONCLUSION: The studied medicinal plants showed notable effects against mycobacterial strains. Our results indicated that utilization of Lamiaceae family can be helpful for treatment of mycobacterial infections.

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BACKGROUND: Rising rates of antimicrobial resistance among Enterobacteriaceae limit the use of reliably active forms of available drugs. The aim of this study was to investigate the prevalence of fosfomycin (US6794490B2) resistance gene among ESBL producing isolates in Iran. METHOD: We tested 355 isolates of Enterobacteriacea collected from various clinical samples including urine, wounds, blood and other sources during June 2016 to July 2017. Antibiotic sensitivity and Extended Spectrum Beta Lactamase (ESBL) production were tested using agar dilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. ESBL genes (blaTEM, bla SHV,bla CTX-M), plasmid-encoded fosfomycin resistance genes (fosA, fosB, fosA3 and fosC2) and chromosomal mutations (murA, glpT, uhpT) were detected by Polymerase Chain Reaction (PCR). RESULTS: In this study, 151 of the 355 isolates were ESBL-positive. blaCTX-M (77%) was the most common gene followed by blaSHV (70%) and blaTEM (58%), either alone or in combination. Eighty nine percent (132/151) of the ESBL-positive isolates were MDR. Antimicrobial susceptibility rates were higher for fosfomycin (92.8%) and imipenem (35.5%) among ESBL-positive isolates. None of the ESBL- positive isolates harbored any mutations or plasmid-mediated fosfomycin resistance determinants. CONCLUSION: In conclusion, fosfomycin showed good antimicrobial activity against multidrug resistance ESBL- positive Enterobacteriaceae.

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