RESUMEN
BACKGROUND: Nrf2 constitutes a therapeutic reference point for renal fibrosis and chronic kidney diseases. Nrf2-related signaling pathways are recognized to temper endothelial-to-mesenchymal transition (EMT) in fibrotic tissue. Nevertheless, the mechanism by which Nrf2 mitigates renal interstitial fibrosis is imprecise. METHODS: The relationship between Nrf2 and renal interstitial fibrosis was investigated using the unilateral ureteral obstruction (UUO) model of Nrf2-/- mice. The mice were separated into four groups, based on the treatment and intervention: Nrf2-/-â¯+â¯UUO, Nrf2-/-â¯+â¯Sham, WTâ¯+â¯UUO and WTâ¯+â¯Sham. Histological examination of renal tissue following the hematoxylin-eosin and Masson staining was carried out, as well as immunohistochemical staining. Additionally, to confirm the in vivo discoveries, in vitro experiments with HK-2 cells were also performed. RESULTS: The Nrf2-/-â¯+â¯UUO group showed more severe renal interstitial fibrosis compared to the WTâ¯+â¯UUO, Nrf2-/-â¯+â¯Sham and WTâ¯+â¯Sham groups. Furthermore, the manifestations of α-SMA and Fibronectin significantly increased, and the manifestation of E-cadherin considerably decreased in kidney tissues from the group of Nrf2-/-â¯+â¯UUO, compared to the WTâ¯+â¯UUO group. The Nrf2 protein level significantly decreased in HK-2 cells, in reaction to the TGF-ß1 concentration. In addition, the overexpression of Nrf2 presented contradictory results. What is more, the PI3K/Akt signaling pathway was discovered to be activated in the proteins extracted from cultured cells, and treated with Nrf2 siRNA and kidney tissues from the Nrf2-/-â¯+â¯UUO group. CONCLUSIONS: The results we obtained demonstrate that Nrf2 signaling pathway may perhaps offset the development of EMT, prompted by TGF-ß1 and renal interstitial fibrosis. Likewise, the anti-fibrotic effect of Nrf2 was imparted by the inactivation of PI3K/Akt signaling. From our discoveries, we deliver new insight related to the prevention and treatment of kidney fibrosis.
Asunto(s)
Transición Epitelial-Mesenquimal , Fibrosis/prevención & control , Enfermedades Renales/prevención & control , Factor 2 Relacionado con NF-E2/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Obstrucción Ureteral/prevención & control , Animales , Cadherinas/genética , Cadherinas/metabolismo , Modelos Animales de Enfermedad , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrosis/etiología , Fibrosis/metabolismo , Fibrosis/patología , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/etiología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
BACKGROUND: Urinary tract infection (UTI) is one of most common pediatric infections. The aim of this study was to investigate the etiology and antimicrobial resistance patterns in children hospitalized at Children's Hospital of Nanjing Medical University. METHODS: We conducted a retrospective, descriptive study of all UTI from 1 January 2013 to 30 November 2016 in children discharged from Nanjing Children's Hospital. The isolated pathogens and their resistance patterns were examined using midstream urine culture. RESULTS: A total of 2,316 children with UTI were included in the study. The occurrence rates of isolated pathogens were as follows: Enterococcus spp., 35.15%; Escherichia coli, 22.32%; Staphylococcus aureus spp., 7.73%; Streptococcus spp., 7.51%; and Klebsiella spp., 6.95%. Uropathogens had a low susceptibility to linezolid (3.47%), vancomycin (0.92%), imipenem (5.74%), and amikacin (3.17%), but they had a high susceptibility to erythromycin (90.52%), penicillin G (74.01%), cefotaxime (71.41%), cefazolin (73.41%), cefuroxime (72.52%), and aztreonam (70.11%). CONCLUSIONS: There is high antibiotic resistance in hospitalized children with UTI. Susceptibility testing should be carried out on all clinical isolates, and the empirical antibiotic treatment should be altered accordingly.