RESUMO
OBJECTIVE: Previous studies suggested that hypoxia-inducible factor-1α (HIF-1α) plays an important role in the progression of inflammation and remodeling of chronic rhinosinusitis with nasal polyposis. However, the molecule mechanisms of HIF-1α activation and regulation of cytokine expressions, such as interleukin (IL) 25 and IL-17RB, in nasal polyposis are not clear. METHOD: The IL-25 and IL-17RB levels in human nasal epithelial cells after stimulation by lipopolysaccharide (LPS) were detected by enzyme-linked immunosorbent assay method, and the proteins of HIF-1α and p-Akt were detected by Western blot method. Moreover, we evaluated the cytokine levels in the nasal mucosa of a murine model of nasal polyposis. RESULTS: The levels of IL-25 and IL-17RB showed dose- and time-dependent release in response to LPS stimulation. The proteins of HIF-1α and p-Akt were both increased significantly after LPS stimulation. After inhibition of PI3K/Akt pathway by PI3K inhibitor LY294002, the levels of IL-25 and IL-17RB and HIF-1α were decreased by LPS stimulation. CONCLUSIONS: Inhibition of PI3K or HIF-1α pathway could significantly reduce growth factor production and decrease nasal inflammation. The HIF-1α pathway could be a novel therapeutic approach for reducing nasal airway inflammation and remodeling in nasal polyposis.
Assuntos
Remodelação das Vias Aéreas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pólipos Nasais/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/metabolismo , Humanos , Inflamação , Interleucina-17/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Mucosa Nasal/citologia , Pólipos Nasais/induzido quimicamenteRESUMO
BACKGROUND: Risedronate is widely used in the therapy of osteoporosis and other metabolic bone diseases. This meta-analysis was aimed to assess whether administration risedronate could increase the bone mineral density (BMD) in patients undergoing primary total hip arthroplasty (THA). METHODS: Electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese Wanfang database were searched for all relevant studies. Inclusion criterion was that patients prepared for THA and use risedronate as intervention group and placebo as control group. BMD change in Gruen zone 1 and 7 were primary outcomes. Meta-analysis was performed using Stata 12.0 software. RESULTS: Six RCTs were finally included in this meta-analysis. Compared with control group, risedronate has a beneficial role in increasing BMD in Gruzen 1, 2 6, and 7 at 3 months (Pâ<â.05). Oral risedronate has a beneficial role in preservation of BMD in all of the Gruen zones at 6 and 12 months (Pâ<â.05). Moreover, oral risedronate could significantly increase the Harris hip scores and bone alkaline phosphatase than control group (Pâ<â.05). CONCLUSION: Oral risedronate has an effect on the preservation of periprosthetic BMD in proximal regions (Gruen zone 1, 2, 3, and 7) at 3 months and all of the regions at 6 and 12 months after THA.
