RESUMO
During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Músculo Esquelético , Fatores de Transcrição , Animais , Camundongos , Regulação da Expressão Gênica , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
This case study systematically assessed diverse approaches to sinus augmentation in the presence of sinus pathology. Three patients were carefully selected and categorized as pseudocyst (PsC) (type 1), mucous retention cyst (MRC) smaller than 20 mm (type 2), and MRC larger than 20 mm in size (type 3). All patients underwent sinus augmentation procedures, with each case utilizing a unique surgical approach. Spontaneous drainage was performed for the patient with PsC (type 1), followed by uncomplicated sinus augmentation. For the patient with an MRC smaller than 20 mm (type 2), aspiration of the cyst contents preceded sinus augmentation. Conversely, the patient with a larger MRC (type 3) underwent cyst enucleation followed by sinus augmentation after complete recovery of the sinus membrane. No complications were noted in any of the cases, and follow-up revealed stable implant installation at the site of sinus augmentation. Within the constraints of this study, the choice of surgical procedure, whether involving spontaneous drainage, aspiration, or enucleation, should be guided by an anticipated pathologic diagnosis and the size of the sinus cyst. This informed approach empowers clinicians to make well-informed decisions for the best possible outcomes and sustained results. Overall, this study offers valuable insights for clinicians seeking to optimize sinus augmentation procedures in the presence of sinus pathology.
Assuntos
Cistos , Levantamento do Assoalho do Seio Maxilar , Humanos , Masculino , Pessoa de Meia-Idade , Cistos/cirurgia , Implantação Dentária Endóssea/métodos , Drenagem/métodos , Seio Maxilar/cirurgia , Mucocele/cirurgia , Doenças dos Seios Paranasais/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , IdosoRESUMO
OBJECTIVE: To examine the clinical and radiographic features in men and women in the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, a large well-defined cross-sectional study of patients with AS, in order to understand the influence of gender in determining the severity of ankylosing spondylitis. METHODS: Extensive clinical assessments and spine radiographs were performed in 302 men and 100 women with AS of > or = 20 years duration. Radiographs were scored using the Bath Ankylosing Spondylitis Radiographic Index Spine (BASRI-spine) score (range 2-12). Functional impairment was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S). RESULTS: Radiographic severity was worse among men. The unadjusted median BASRI-spine score for men was 10, compared with 6.5 for women (p<0.001). Functional disability, as measured by the BASFI and HAQ-S, was not different between men and women. However, after adjusting for radiographic spinal damage, women were found to report worse functioning than men at any given level of radiographic damage. Women had a slightly earlier age of disease onset; however, disease duration was identical in both groups. Women more frequently reported family histories of AS in first-degree relatives and were more likely to be treated with intra-articular steroids, sulphasalazine and prednisone. CONCLUSIONS: Among patients with longstanding AS, men have more severe radiographic changes; findings of treatment differences suggest that women may have more peripheral arthritis. At any given level of radiographic damage, self-reported functional limitations were worse for women.
Assuntos
Fatores Sexuais , Espondilite Anquilosante/diagnóstico por imagem , Idade de Início , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Índice de Gravidade de Doença , Coluna Vertebral/diagnóstico por imagem , Espondilite Anquilosante/fisiopatologia , Inquéritos e QuestionáriosRESUMO
Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.