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Sulforaphane (SFN) is considered an antioxidant agent, but the biological effects on hypoxia-treated osteoblasts remain unclear. Therefore, the aims of this study were to investigate the effects of SFN on the activity and mineralization of osteoblasts in hypoxia. Osteoblasts were treated with hypoxia with or without SFN, and apoptosis was assayed with caspase 3 Activity Assay Kit and flow cytometer. The levels of reactive oxygen species (ROS) were measured with DCFH-DA. The levels of glutathione (GSH) and glutathione disulphide were determined by the o-phthalaldehyde fluorimetric assay. Mineralization of Osteoblasts was detected by Alizarin red staining and alkaline phosphatase (ALP) staining, and the relative proteins levels were examined by Western blotting. Our results showed that SFN reduced the hypoxia-mediated apoptosis and ROS levels in osteoblasts. The utilization of SFN improved the inhibitory effect of osteoblast mineralization by hypoxia. Additionally, the effect of alleviating hypoxia by SFN will be an increase in osteoblast activity. These findings clarify the effects of SFN on hypoxia-treated osteogenesis and will help identify novel therapeutic strategies for the protection of skeletal health.
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Calcificação Fisiológica/efeitos dos fármacos , Isotiocianatos/farmacologia , Osteoblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Osteoblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , SulfóxidosRESUMO
Lifestyles are associated with all-cause mortality, yet limited research has explored the association in the elderly population with multimorbidity. We aim to investigate the impact of adopting a healthy lifestyle on reducing the risk of all-cause mortality in older individuals with or without multimorbidity in both China and UK. This prospective study included 29,451 and 173,503 older adults aged 60 and over from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and UK Biobank. Lifestyles and multimorbidity were categorized into three groups, respectively. Cox proportional hazards regression was used to estimate the Hazard Ratios (HRs), 95% confidence intervals (95% CIs), and dose-response for all-cause mortality in relation to lifestyles and multimorbidity, as well as the combination of both factors. During a mean follow-up period of 4.7 years in CLHLS and 12.14 years in UK Biobank, we observed 21,540 and 20,720 deaths, respectively. For participants with two or more conditions, compared to those with an unhealthy lifestyle, adopting a healthy lifestyle was associated with a 27%-41% and 22%-42% reduction in mortality risk in the CLHLS and UK Biobank, respectively; Similarly, for individuals without multimorbidity, this reduction ranged from 18% to 41%. Among participants with multimorbidity, individuals with an unhealthy lifestyle had a higher mortality risk compared to those maintaining a healthy lifestyle, with HRs of 1.15 (95% CI: 1.00, 1.32) and 1.27 (95% CI: 1.16, 1.39) for two conditions, and 1.24 (95% CI: 1.06, 1.45) and 1.73 (95% CI: 1.56, 1.91) for three or more conditions in CLHLS and UK Biobank, respectively. Adherence to a healthy lifestyle can yield comparable mortality benefits for older individuals, regardless of their multimorbidity status. Furthermore, maintaining a healthy lifestyle can alleviate the mortality risks linked to a higher number of diseases.
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BACKGROUND: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. METHODS: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. RESULTS: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. CONCLUSIONS: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.
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Demência , Multimorbidade , Humanos , Estudos Prospectivos , Fatores de Risco , Estilo de Vida , Estilo de Vida Saudável , Demência/epidemiologia , Demência/etiologiaRESUMO
The inflammation/immune response pathway is considered a key contributor to the development of Langerhans cell histiocytosis (LCH) bone metastasis. However, the dynamic changes in the immune microenvironment of LCH bone metastasis and critical regulators are still unclear. Expression profiling by arrays of GSE16395, GSE35340, and GSE122476 was applied to detect the immune microenvironment changes in the development of LCH bone metastasis. The single-cell high-throughput sequencing of GSE133704, involved in LCH bone lesions, was analyzed. The online database Metascape and gene set variation analysis (GSVA) algorithms were used to detect the gene function of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network of hub regulators was constructed by the STRING database. In these results, key immune cells, such as Tem cells, NK T cells, CD8(+) T cells, and Th1 cells, were identified in LCH bone metastasis. These genes, which include LAG3, TSPAN5, LPAR5, VEGFA, CXCL16, CD74, and MARCKS, may significantly correlate with the cellular infiltration of B cells, aDCs, pDCs, cytotoxic cells, T cells, CD8+ T cells, T helper cells, and Tcm cells. In conclusion, our study constructed an atlas of the immune microenvironment of LCH bone metastasis. Genes including LAG3, TSPAN5, LPAR5, VEGFA, CXCL16, CD74, and MARCKS may be involved in the development of LCH bone metastasis. The hub gene-immune cell interactive map may be a potential prognostic biomarker for the progression of LCH bone metastasis and synergetic targets for immunotherapy in LCH patients.
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Neoplasias Ósseas , Histiocitose de Células de Langerhans , Humanos , Linfócitos T CD8-Positivos/metabolismo , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/diagnóstico , Biomarcadores/metabolismo , Mapas de Interação de Proteínas/genética , Fatores Imunológicos , Neoplasias Ósseas/genética , Microambiente Tumoral/genéticaRESUMO
Diseases caused by bacterial infection have resulted in serious harm to human health. It is crucial to develop a multifunctional antibiotic-independent antibacterial platform for combating drug-resistant bacteria. Herein, titanium diboride (TiB2) nanosheets integrated with quaternized chitosan (QCS) and indocyanine green (ICG) were successfully prepared as a synergetic photothermal/photodynamic antibacterial nanoplatform (TiB2-QCS-ICG). The TiB2-QCS-ICG nanocomposites exhibit effective photothermal conversion efficiency (24.92%) and excellent singlet oxygen (1O2) production capacity simultaneously under 808 nm near-infrared irradiation. QCS improved TiB2 stability and dispersion, while also enhancing adhesion to bacteria and further accelerating the destruction of bacteria by heat and 1O2. In vitro experiments indicated that TiB2-QCS-ICG had excellent antibacterial properties with an inhibition rate of 99.99% against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), respectively. More importantly, in vivo studies revealed that the nanoplatform can effectively inhibit bacterial infection and accelerate wound healing. The effective wound healing rate in the TiB2-QCS-ICG treatment group was 99.6% which was much higher than control groups. Taken together, the as-developed TiB2-QCS-ICG nanocomposite provides more possibilities to develop metal borides for antibacterial infection applications.
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Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Escherichia coli , Verde de Indocianina/farmacologia , Compostos de Boro/farmacologia , Nanocompostos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: This study aimed to explore whether dietary flaxseed oil has effects on acute anterior cruciate ligament (ACL) rupture prognosis after surgical reconstruction. METHODS: Patients with primary acute ACL rupture diagnosed by magnetic resonance imaging and clinical examination were recruited at Quanzhou First Hospital Affiliated to Fujian Medical University and randomized to either the placebo group or the flaxseed oil group by computer-generated random numbers. Patients in the placebo group took six corn oil capsules daily, while patients in the flaxseed oil group took six flaxseed oil capsules daily. The outcomes were evaluated by specific scales. RESULTS: Compared to the placebo group, the flaxseed oil group showed significantly higher International Knee Documentation Committee (IKDC) score (P = 0.007) and total Knee Injury and Osteoarthritis Outcome Score (KOOS) (P = 0.0003) after two-year administration. Patients treated with flaxseed oil exhibited a significantly higher rate of return to sporting level before injury (P = 0.04) and a lower rate of occurrence of giving way (P = 0.04) than those in the placebo group. Patients with flaxseed oil showed significantly less severe adverse events on index knee (P = 0.047). CONCLUSION: The administration of dietary flaxseed oil enhanced the prognosis of acute ACL rupture.
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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by the destruction of cartilage and bone. The present study aims to investigate the role of HtrA serine peptidase 2 (HtrA2) in the collagen-induced arthritis. The expressions of HtrA2 were determined in the database BioGPS and bone marrow-derived macrophages (BMDMs). The populations of myeloid and lymphoid cells were determined in wild type and HtrA2 knockout (HtrA2MKO) mice using flow cytometry. In addition, the expressions of pro-inflammatory cytokines (Il6, Tnf, and Il1ß) were determined in the activated BMDMs from wild type (WT) and HtrA2MKO mice. STRING database was used to predict the interactive proteins of HtrA2 and Co-Immunoprecipitation was used to confirm these interactions. A collagen-induced arthritis model was established to investigate the effects of HtrA2 on the arthritis symptoms. It was found that HtrA2 reduction was associated with the activation of myeloid cells. Interestingly, HtrA2 deficiency did not affect the development of myeloid and lymphoid cells. Further studies demonstrated that HtrA2 deficiency suppressed the production of pro-inflammatory cytokines in BMDMs induced by lipopolysaccharide or CpG. Co-Immunoprecipitation results demonstrated that HtrA2 enhanced the stability of TNF receptor-associated factor 2 (TRAF2). HtrA2 participated in the activation of the inflammatory response in a collagen-induced arthritis model. In summary, HtrA2 modulates inflammatory responses in BMDMs by controlling TRAF2 stability in a collagen-induced arthritis mouse model.
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Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Colágeno/farmacologia , Serina Peptidase 2 de Requerimento de Alta Temperatura A/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/metabolismo , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismoRESUMO
Large and non-volatile electric field control of magnetization is promising to develop memory devices with reduced energy consumption. Herein, we report the electric field control of magnetization with a non-volatile memory effect in an intermediate band Nd0.5Sr0.5MnO3 film grown on a (011)-cut 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) single crystal. Applying an electric field across the ferroelectric PMN-PT increases the magnetization of the Nd0.5Sr0.5MnO3 film along both in-plane [100] and [011[combining macron]] directions. Moreover, the magnetization does not recover to its original state after withdrawal of the electric field at temperatures below 70 K, demonstrating a non-volatile memory effect. Detailed investigation showed that (011)-PMN-PT exhibits an anisotropic in-plane strain due to an electric field-induced rhombohedral to orthorhombic phase transition. This electric field-induced anisotropic strain can dynamically transfer to Nd0.5Sr0.5MnO3 film and modulate the magnetization of the Nd0.5Sr0.5MnO3 film through adjusting its phase balance between ferromagnetic (FM) and charge-orbital ordered antiferromagnetic (COO AFM) phases. The non-volatile memory effect can be ascribed to the competition of thermal energy and energy barriers between the FM and COO AFM phases at low temperatures. This work broadens the knowledge of electric field control of magnetism in the intermediate band-manganite ferromagnetic/ferroelectric multiferroic heterostructures, and may also pave a way for the control of antiferromagnetism and to design antiferromagnet-based memories.
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We propose an effective method to boost the accuracy of multi-person pose estimation in images. Initially, the three-layer fractal network was constructed to regress multi-person joints location heatmap that can help to enhance an image region with receptive field and capture more joints local-contextual feature information, thereby producing keypoints heatmap intermediate prediction to optimize human body joints regression results. Subsequently, the hierarchical bi-directional inference algorithm was proposed to calculate the degree of relatedness (call it Kinship) for adjacent joints, and it combines the Kinship between adjacent joints with the spatial constraints, which we refer to as joints kinship pattern matching mechanism, to determine the best matched joints pair. We iterate the above-mentioned joints matching process layer by layer until all joints are assigned to a corresponding individual. Comprehensive experiments demonstrate that the proposed approach outperforms the state-of-the-art schemes and achieves about 1% and 0.6% increase in mAP on MPII multi-person subset and MSCOCO 2016 keypoints challenge.