RESUMO
OBJECTIVE: Glucocorticoids (GCs)-induced osteoblast apoptosis has been identified as an important cause of GCs related osteonecrosis of the femoral head (ONFH). Glycogen synthase kinase 3ß (GSK3ß) has been proved to mediate dexamethasone (Dex)-induced osteoblast apoptosis. This study aimed to investigate the underlying mechanism of GSK3ß in Dex-induced osteoblast apoptosis. METHODS: Osteoblast cells were transfected with lentivirus expressing GSK3ß-shRNA, and a DNA microarray was performed to analyze gene expression after Dex treatment with or without GSK3ß-shRNA. Some differentially expressed genes were further validated by quantitative real-time-PCR (qRT-PCR). RESULTS: 460 genes were up-regulated (at least 2-fold) with Dex treatment but down-regulated (at least 2-fold) with GSK3ß-shRNA treatment. In addition, 315 genes were down-regulated (at least 2-fold) with Dex treatment but up-regulated (at least 2-fold) with GSK3ß-shRNA treatment. Among these genes, the apoptosis-related genes Hoxb8, Kif18a, Dock8, Dlk1, Tnfsf14, Casq2, Bcl2l14 and mechanosensation-related gene Piezo2 were selected for further qRT-PCR analysis. 7 of 8 genes (Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2, Bcl2l14) showed the same tendency between gene chip results and qRT-PCR results. The microarray data also showed that apoptotic pathway, MAPK pathway, TGFß pathway and Wnt pathway might be related to the mechanism of GSK3ß in Dex-induced osteoblast apoptosis. CONCLUSION: Our findings indicate that GSK3ß-shRNA treatment can alter various genes expression levels and change diverse signaling pathways involved in Dex-induced osteoblast apoptosis. Furthermore, Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2 and Bcl2l14 genes may play an important role in the GSK3ß-mediated osteoblast apoptosis process.
Assuntos
Apoptose/efeitos dos fármacos , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Osteoblastos/efeitos dos fármacos , Animais , Apoptose/genética , Proteínas de Ligação ao Cálcio , Calsequestrina/genética , Calsequestrina/metabolismo , Linhagem Celular , Perfilação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Mecanotransdução Celular , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Osteoblastos/citologia , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismoRESUMO
The aim of this study was to summarize the administration model of a COVID-19 designated hospital transformed from a community hospital to improve the emergency capacity of community hospitals and the efficiency of diagnosis and treatment of medical staff in the COVID-19 pandemic. This study analyzed the surrounding environment, ward layout, area management, treatment process, medical staff, and patient management of the designated community hospital. From February 5, 2020, to February 18, 2020, the designated community hospital has received 198 COVID-19 mild and general patients (including 41 in the hospital at the beginning of the period). Among them, 39 were transferred to module hospitals, 131 were discharged, and 28 were in the hospital at the end of the period, and none of them became severe. There were 41 medical staff, and none of them had COVID-19 infection. We have achieved excellent results in the prevention and control stratagems implemented in this new community-designated hospital that specializes in treating patients with COVID-19. Its diagnosis and treatment model has completed the treatment of COVID-19 patients successfully. After adjustment, this community hospital can shoulder the critical task of being a designated hospital for COVID-19, which includes admission, isolation, and therapy of suspected and mild COVID-19 patients, reducing the medical burden of superior hospitals. Our experience provides concepts for community hospitals to temporarily undertake medical responsibilities to reduce the spread of COVID-19 during the pandemic.
Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Hospitais Comunitários , SARS-CoV-2 , Pandemias , HospitalizaçãoRESUMO
BACKGROUND: Circular RNAs (circRNAs) have pivotal roles in the progression of many diseases, including osteoarthritis (OA). The detained function and regulatory mechanism of circ_0136474 in OA are still largely unknown. METHODS: The chondrocytes (CHON-001 cells) were exposed to interleukin-1 beta (IL-1ß) to mimic the injury in OA. The expression levels of circ_0136474, microRNA-140-3p (miR-140-3p), methyl-CpG-binding protein 2 (MECP2) mRNA were measured by qRT-PCR. Cell proliferation was assessed using CCK-8 assay. Flow cytometry was employed for measuring cell apoptosis. All protein levels were evaluated via western blot analysis. ELISA was used for detecting the concentrations of the inflammatory cytokines. Dual-luciferase reporter analysis and RNA Immunoprecipitation analysis were conducted for confirming the association between miR-140-3p and circ_0136474 or MECP2. RESULTS: Circ_0136474 was upregulated in IL-1ß-induced CHON-001 cells and OA cartilage tissues. Circ_0136474 deficiency alleviated IL-1ß-stimulated CHON-001 cell damage via enhancing cell proliferation and reducing extracellular matrix (ECM) degradation, apoptosis, and inflammation. Circ_0136474 was a sponge of miR-140-3p, and miR-140-3p inhibition reversed the roles of circ_0136474 knockdown in IL-1ß-treated CHON-001 cells. Moreover, miR-140-3p directly targeted MECP2, and upregulation of miR-140-3p attenuated L-1ß-triggered CHON-001 cell injury via targeting MECP2. Additionally, circ_0136474 regulated MECP2 level via sponging miR-140-3p. CONCLUSION: Circ_0136474 knockdown alleviated IL-1ß-triggered CHON-001 cell damage through modulation of miR-140-3p/MECP2 axis, indicating a new target for treatment of OA.
Assuntos
MicroRNAs , Osteoartrite , Humanos , Apoptose/genética , Condrócitos , Inflamação , Proteína 2 de Ligação a Metil-CpG/genética , MicroRNAs/genética , Osteoartrite/genética , RNA Circular/genéticaRESUMO
CONTEXT: The associations of circulating insulin-like growth factor-1 (IGF-1) levels with bone mineral density and fracture risk are inconclusive in observational studies. OBJECTIVE: We conducted a mendelian randomization study to assess the associations of serum IGF-1 levels with estimated bone mineral density (eBMD) and fracture. METHODS: Genetic instruments for IGF-1 were selected at the genome-wide significance level (Pâ <â 5â ×â 10-8) from a genome-wide association study including 358â 072 individuals of European ancestry. Summary-level data for eBMD (426â 824 individuals) and fracture (53â 184 fracture cases and 373â 611 noncases) were obtained from the UK Biobank study. Univariable and multivariable mendelian randomization analyses methods were used to estimate the associations of IGF-1 with eBMD and fracture. The main outcome measure included the change of eBMD and odds ratio of fracture per genetically predicted 1-SD increase of serum IGF-1 levels. RESULTS: For 1-SD increase in IGF-1, the change of eBMD levels was 0.04 g/cm2 (95% CI, 0.01-0.07; Pâ =â .011) and the odds ratio of fracture was 0.94 (95% CI, 0.91-0.98; Pâ =â .003). The associations persisted with similar magnitude after adjustment for height. The association was consistent for fracture but not for eBMD after excluding genetic instruments that might directly influence these outcomes. The association between IGF-1 and fracture was somewhat attenuated after adjustment for eBMD (odds ratio 0.96; 95% CI, 0.92-0.99; Pâ =â .012). CONCLUSION: The present study supports a role for IGF-1 in preventing fracture, possibly and partly mediated by greater bone mineral density.
Assuntos
Densidade Óssea , Fraturas Ósseas/sangue , Fraturas Ósseas/genética , Fator de Crescimento Insulin-Like I/genética , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Análise da Randomização MendelianaRESUMO
BACKGROUND: Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS. METHODS AND FINDINGS: A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83). CONCLUSION: Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.