ABSTRACT
BACKGROUND: Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infection in human. This study aimed to investigate the relationship between the presence of genes involved in biofilm formation in K. pneumoniae isolated from patients and the presence of antibiotic resistance genes. METHODS: Biochemical tests were used for the identification of K. pneumonia isolated from urine samples referred to hospitals in Tehran, Iran, from Sep 2018 to Jan 2020. The antibiotic resistance pattern was performed and biofilm formation was assessed phenotypically. Finally, ß-lactamase genes and adhesion genes were detected by the PCR method. RESULTS: We collected 457 K. pneumoniae isolates from hospitals in Tehran, Iran. 110 isolates were resistant to imipenem. Fifty isolates were positive for metallo-ß-lactamases that thirty-nine isolates (35.45%) has blaKPC gene, 18 isolates (16.36%) had blaVIM-1 gene and 9 isolates (8.18%) had blaIMP-1 gene detected by PCR. Sixty isolates (54.54%) had strong biofilm, 35 isolates (31.81%) had moderate biofilm and 15 isolates (13.63%) had weak biofilm. The presence of adhesion genes in K. pneumoniae isolates significantly correlated with resistance genes (P<0.001). CONCLUSION: It is clear antibacterial resistance has been significant association with biofilm formation in K. pneumoniae isolates. Therefore, understanding resistance pattern and mechanisms leading to biofilm formation can facilitate efficient treatment of infections caused by K. pneumoniae.
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of cholinergic neurons. Amyloid beta is a misfolded protein that represents one of the key pathological hallmarks of AD. Numerous studies have shown that Aß1-42 induces oxidative damage, neuroinflammation, and apoptosis, leading to cognitive decline in AD. Recently, fibroblast growth factor 21 (FGF21) has been suggested to be a potential regulator of oxidative stress in mammalian cells. FGF21 has been shown to improve insulin sensitivity, reduce hyperglycemia, increase adipose tissue glucose uptake and lipolysis, and decrease body fat and weight loss by enhancing energy expenditure. In this study, we investigated the effect of FGF21 Aß1-42 toxicity in SH-SY5Y neuroblastoma cells. Our data shows that FGF21 significantly decreased Aß1-42-induced toxic effects and repressed oxidative stress and apoptosis in cells exposed to Aß1-42 peptide. Our investigation also confirmed that FGF21 pretreatment favorably affects HSP90/TLR4/NF-κB signaling pathway. Therefore, FGF21 represents a viable therapeutic strategy to abrogate Aß1-42-induced cellular inflammation and apoptotic death in the SH-SY5Y neuroblastoma cells.
Subject(s)
Amyloid beta-Peptides/toxicity , Cell Death/drug effects , Fibroblast Growth Factors/pharmacology , Peptide Fragments/toxicity , Animals , Caspase 3/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , HSP90 Heat-Shock Proteins/metabolism , Humans , Klotho Proteins , Membrane Proteins/genetics , Membrane Proteins/metabolism , NF-kappa B/metabolism , Neuroblastoma/pathology , RNA, Ribosomal, 18S/metabolism , Reactive Oxygen Species/metabolism , Receptors, Fibroblast Growth Factor/genetics , Receptors, Fibroblast Growth Factor/metabolism , Time Factors , Toll-Like Receptor 4/metabolismABSTRACT
Recent studies have shown that neuroinflammation plays an important role in Alzheimer's disease (AD). Microglial cells are responsible for the phagocytosis of Amyloid-ß (Aß). However, it has been demonstrated that in AD patients the efficiency of phagocytosis decreases due to proinflammatory cytokines, such as Interleukin-1ß (IL-1ß), which is produced through the activation of NLRP3 inflammasome. In this study, we aimed at deciphering the mechanism underlying the NLRP3 activation. The results showed that Aß induces an increase in the level of reactive oxygen species (ROS). According to this study, ROS produced from both mitochondria and NADPH oxidase was responsible for NLRP3 activation. In addition, it was observed that this high level of ROS activated the transient receptor potential melastatin 2 (TRPM2) channel, which causes an increase in the level of intracellular calcium. The results demonstrated that in the absence of intracellular calcium, caspase-1 cannot be activated and therefore the level of IL-1ß decreases. Altogether, our findings supported the role of TRPM2 channel in ROS-induced NLRP3 activation in microglial cells through the exposure to Aß.
