Orexin B protects dopaminergic neurons from 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity associated with reduced extracellular signal-regulated kinase phosphorylation.

BACKGROUND: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is a major pathological hallmark of Parkinson's disease (PD). Orexin B (OXB) has been reported to promote the growth of DA neurons. However, the roles of OXB in the degeneration of DA neurons still remained not fully clear. METHODS: An in vivo PD model was constructed by administrating 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Pole test was performed to investigate the motor function of mice and the number of DA neurons was detected by immunofluorescence (IF). A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+). OXB was added to the culture medium 2 h after MPP + treatment. Microscopic analysis was carried out to investigate the function of OXB in the cell model of PD 24 h after MPP + challenge. RNA-Seq analysis of the PD cell model was performed to explore the possible mechanisms. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK). RESULTS: OXB significantly decreased the DA neurons death caused by MPTP, alleviated MPP+-induced neurotoxicity in SH-SY5Y cells, and robustly enhanced the weight and motor ability of PD mice. Besides, RNA-Seq analysis demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the pathology of PD. Furthermore, MPP + led to increased levels of phosphorylation of ERK (p-ERK), OXB treatment significantly decreased the levels of p-ERK in MPP+-treated SH-SY5Y cells. CONCLUSIONS: This study demonstrated that OXB exerts a neuroprotective role associated with reduced ERK phosphorylation in the PD model. This suggests that OXB may have therapeutic potential for treatment of PD.

Nasal nitric oxide testing for allergic rhinitis patients: Systematic review and meta-analysis.

BACKGROUND: Nasal nitric oxide (nNO) levels in allergic rhinitis (AR), healthy people or nonallergic rhinitis (NAR) have shown contradicting results in previous studies. By meta-analysis, we reviewed studies that measured nNO in AR patients to assess nNO's ability to discriminate AR from healthy people or NAR. METHODS: We systematically searched PubMed, Cochrane, Embase, Ovid, Web of Science, Wanfang Data, CNKI until December 15, 2020. Differences were expressed as standardized mean differences (SMD) with 95% confidence interval (CI), by random-effects method. RESULTS: A total of 10 original studies with 561 AR patients, 327 healthy controls, 123 NAR patients were included in the narrative synthesis and 9 studies in the meta-analysis. nNO in AR was significantly increased compared with healthy controls (SMD: 0.989; 95% CI: 0.402, 1.576; p = .001) or NAR (SMD: 0.680; 95% CI: 0.101, 1.259; p = 0.021). However, subgroup analysis based on measuring process and patient characteristics showed that no significant differences were detected in nNO between AR patients with nasal polyps or sinusitis or marked ostial obstruction and healthy controls. CONCLUSIONS: nNO is a potential indicator for recognizing AR. Nasal polyps, sinusitis and marked ostial obstruction should be considered before nNO is applied to detect AR.