RESUMO
We hypothesized that the respiratory exercises have uniform effects on ventilation in healthy subjects but the effects varied in patients with chronic obstructive pulmonary disease (COPD). In this study, a total of 30 healthy volunteers and 9 patients with COPD were included. Data were recorded continuously during (1) diaphragmatic breathing; (2) pursed lip breathing with full inhalation; (3) pursed lip combining diaphragmatic breathing. The sequence of the three breathing exercises was randomized using machine generated random permutation. Spatial and temporal ventilation distributions were evaluated with electrical impedance tomography. Results showed that, tidal volume was significantly larger during various breathing exercises compared to quiet tidal breathing, in both healthy and COPD (p < 0.01). However, for other EIT-based parameters, statistical significances were only observed in healthy volunteers, not in patients. Diaphragmatic breathing alone might not be able to decrease functional residual capacity in COPD and the effect varied largely from patient to patient (6:3, decrease vs. increase). Ventilation distribution moved toward ventral regions in healthy during breathing exercises (p < 0.0001). Although this trend was observed in the COPD, the differences were not significant. Ventilation became more homogeneous when diaphragmatic breathing technique was implemented (p < 0.0001). Again, the improvements were not significant in COPD. Regional ventilation delay was relatively high in COPD and comparable in various breathing periods. In conclusions, the impact of pursed lip and diaphragmatic breathing varied in different patients with COPD. Breathing exercise may need to be individualized to maximize the training efficacy with help of EIT.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Pulmão , Respiração , Exercícios Respiratórios , Testes de Função Respiratória/métodosRESUMO
Unloading-induced bone loss is a threat to human health and can eventually result in osteoporotic fractures. Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation-unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions, and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS)6-liposome delivery to the bone-formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of lncRNA OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.
Assuntos
Proteínas Homeobox A10/metabolismo , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Animais , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Elevação dos Membros Posteriores/métodos , Proteínas Homeobox A10/genética , Camundongos , Osteoblastos/metabolismo , Osteogênese/fisiologiaRESUMO
Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.
Assuntos
Apoptose , Diferenciação Celular , Osteoblastos/metabolismo , Osteogênese , Osteoporose/prevenção & controle , RNA Longo não Codificante/metabolismo , Células 3T3 , Animais , Modelos Animais de Doenças , Marcação de Genes , Elevação dos Membros Posteriores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/patologia , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima , Simulação de Ausência de Peso , Proteínas Elk-1 do Domínio ets/genética , Proteínas Elk-1 do Domínio ets/metabolismoRESUMO
A growing body of evidence has revealed that microRNAs (miRNAs) play crucial roles in regulating osteoblasts and bone metabolism. However, the effects of miRNAs in osteoblast mechanotransduction remain to be defined. In this study, we investigated the regulatory effect of miR-33-5p in osteoblasts and tested its anti-osteopenia effect when delivered by an osteoblast-targeting delivery system in vivo. First, we demonstrated that miR-33-5p could promote the activity and mineralization of osteoblasts without influencing their proliferation in vitro. Then our data showed that supplementing miR-33-5p in osteoblasts by a targeted delivery system partially recovered the osteopenia induced by mechanical unloading at the biochemical, microstructural, and biomechanical levels. In summary, our findings demonstrate that miR-33-5p is a key factor in the occurrence and development of the osteopenia induced by mechanical unloading. In addition, targeted delivery of the mimics of miR-33-5p is a promising new strategy for the treatment of pathological osteopenia.
Assuntos
Doenças Ósseas Metabólicas/patologia , Doenças Ósseas Metabólicas/fisiopatologia , Técnicas de Transferência de Genes , Elevação dos Membros Posteriores , MicroRNAs/administração & dosagem , Osteoblastos/metabolismo , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Calcificação Fisiológica , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Masculino , Camundongos Endogâmicos C57BL , Osteogênese , Substâncias Protetoras/metabolismoRESUMO
[Purpose] The aim of our study was to explore the changes in the blood of servicemen in sub-health conditions during a 21-day balneotherapy program. [Subjects and Methods] For this study, 129 servicemen in sub-health condition were recruited. The subjects were randomly divided into either the balneotherapy group (70) or the control group (59). Subjects in the balneotherapy group received whole-body immersion bath therapy in thermomineral water (30â min daily) for 21 days. Their blood samples were examined 1 day before and after balneotherapy. The parameters studied included mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC), lactic acid (LAC), alanine aminotransferase (ALT), glucose (GLU), and triglycerides (TG) levels. [Results] After 21 days of balneotherapy, MCH levels and MCHC increased significantly and WBC counts increased significantly. LAC levels decreased significantly. ALT, GLU, and TG levels decreased signiï¬cantly. In the control group, there were no statistical differences before and after tap water baths following the same procedure. [Conclusion] A 21-day balneotherapy program signiï¬cantly improved blood cell counts and blood biochemical indexes and reduced ponogen levels in servicemen in sub-health condition.