ABSTRACT
Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.
Subject(s)
Mitochondria , Mitophagy , Neurons , Receptors, G-Protein-Coupled , Animals , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Neurons/metabolism , Mitochondria/metabolism , Mice , Humans , Oxidative Phosphorylation , Microtubule-Associated Proteins/metabolism , Microtubule-Associated Proteins/genetics , Reactive Oxygen Species/metabolism , Mice, Knockout , NeurogenesisABSTRACT
This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.
Subject(s)
Drugs, Chinese Herbal , Influenza, Human , Pharyngitis , Humans , Influenza, Human/drug therapy , Drugs, Chinese Herbal/adverse effects , Capsules , Cough/drug therapy , Cough/chemically induced , Rhinorrhea , Multicenter Studies as TopicABSTRACT
<p><b>OBJECTIVE</b>Long term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment.</p><p><b>METHODS</b>Twelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved.</p><p><b>RESULTS</b>The growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (P<0.05), and then to 6.9∓0.4cm/year one year later.</p><p><b>CONCLUSIONS</b>The long-term glucocorticoid treatment can decrease the hGH secretion, and thus leads to short stature and agenesis. However, the rhGH replacement can safely and effectively improve growth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.</p>