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This study aimed to evaluate the potential of mesenchymal stem cell-derived exosomes loaded with curcumin (Curc-Exos) as an effective therapeutic strategy for rheumatoid arthritis through modulation of proliferation and inflammatory response in HIG-82 synovial cells. For this purpose, Exos were isolated and characterized with BCA protein assay, DLS, FE-SEM, and TEM. The Curc was embedded by mixing it with Exos in a 1:4 ratio. It was found that the Curc stability has improved after loading on Exos compared to the free Curc. Besides, the in vitro studies using LPS-stimulated HIG-82 synovial cells indicated the efficiency of Curc-Exos in enhancing cytotoxicity and apoptosis compared to the free Curc treatment. It was also revealed that Curc-Exos significantly could reduce the expression levels of anti-apoptotic proteins IAP1 and IAP2 and inflammatory mediators including IL-6, TNF-α, MMP1, and PGE2. This preliminary study confirmed the suitability of Curc-Exos in counteracting the proliferation and inflammatory response of rheumatoid arthritis synovial fibroblasts in vitro.
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Artrite Reumatoide , Curcumina , Exossomos , Células-Tronco Mesenquimais , Sinoviócitos , Humanos , Exossomos/metabolismo , Sinoviócitos/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Artrite Reumatoide/terapia , Artrite Reumatoide/metabolismo , Proliferação de Células , Células-Tronco Mesenquimais/metabolismo , Fibroblastos/metabolismoRESUMO
Background: Childhood hand function is considered to be one of the strongest predictors of the ability to participate in daily activities as children with cerebral palsy (CP) reach adulthood. The manual ability classification system (MACS) is currently the most widely used for grading hand function in children with CP. However, the MACS method is subjective and may be affected by the raters' experience. Hand knob is an important control center for hand movement. Therefor this study aimed to develop and validate an objective model for hand function estimation in children with CP and visualize it as a nomogram. Methods: A total of 70 Children (2-12 years old) with CP underwent magnetic resonance imaging (MRI) scanning, MACS assessment. According to MACS, children with CP were divided into mild impairment group (grade I-III) and severe impairment group (grade IV-V). Hand function prediction models based on (I) hand knob score, (II) clinical features, and (III) the combination of clinical features and hand knob score were developed and validated separately. The models were subjected to stepwise regression according to the maximum likelihood method, and the Akaike information criterion was used to select the best model. Model discrimination was assessed using receiver operating characteristic (ROC) and calibration curves. The nomogram was finally built according to the best model. Results: The area under the curve (AUC) of the hand knob score model in the training set was 0.752, the clinical features model was 0.819, and the hand knob score and clinical features combined model was 0.880. The AUC of the hand knob score model in the validation set was 0.765, the clinical features model was 0.782, and the combined model was 0.894. The best model was the hand knob score-clinical features combined model, and the nomogram finally incorporated two assessment items: the hand knob score and white matter injury. The estimated probability of hand function injury degree of the combined model displayed good agreement with the actual occurrence probability. Conclusions: The hand knob score-clinical features combined model can be used to preliminarily assess the degree of hand impairment in children with CP, with good calibration.
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This study proposed an investigation-based multiple-criteria coordinated model to evaluate the sustainable development of urban public transport (PT) infrastructure, based on economic, social and environmental data from 2009 to 2019. The main problem with the traditional approach for assessing urban PT development is that economic and social benefits are considered individually, but also attention to environmental factors and coordination among the three issues are nearly overlooked. This leads to the likelihood of inaccuracies in the handling/assessment of sustainable development or an imbalance among the attributes in different cities. An investigation-based coordinated model was introduced in which a survey of 35 sub-criteria was conducted to derive the criteria necessary for coupling/coordination. A case study involving 13 cities in Jiangsu Province, China, illustrated the problems in coordinating PT systems and verified the efficacy of the proposed approach. With employing the entropy method, this study validated coordination of the PT infrastructure development of various cities in a balanced manner and used panel regression formulas to analyse the theoretical gap and empirical bottlenecks existing among economic, social and environmental benefits. With the findings of the study, the data-based investigation from 13 cities enabled the city planners/managers (including ones from other cities with similar urban levels) to give the individual priority between the ternary benefits, advance technology, allow big data-based informatisation and implement near-future autonomous PT vehicles.
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Desenvolvimento Econômico , Desenvolvimento Sustentável , China , Cidades , EmpregoRESUMO
OBJECTIVE: To observe effects of manganese on function and pathology of liver in rats. METHODS: 36 male SD rats were randomly divited into 3 groups, each group contained 12 rats. Solutions contained MnCl2 of 5.0 g/L and 0.5 g/L were respectively administrated to the high dose and low dose Mn-exposed groups consecutively by oral drinking for 60 days, while distilled water was given to the contal group. Fluorospectrophotometry was carried out to exame the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), as well as the protein level in liver plasmas. HE staining for the liver sections was applied to exam the pathological changes of liver in rats. RESULTS: (1) In fluorospe-ctrophotometry, activities of ALT, AST, ALP in high and low dose Mn-exposed groups were significantly higher than those in control group in liver plasmas. In high dose Mn-exposed groups, ALT, AST, ALP was respectively (60.79 +/- 9.88), (49.77 +/- 8.36) and (49.43 +/- 8.88) U/ml, P < 0.01, in low dose Mn-exposed groups, ALT,AST,ALP was respectively (47.35 +/- 8.11), (37.31 +/- 6.77) and (32.34 +/- 4.53) U/ml (P < 0.05). Significant relationships between effects and dose were obvious in the above changes. No changes in PRO levels was found among 3 groups. (2) Pathologically in high dose and low dose Mn-exposed groups the hepatic lobules were injured in different levels. Mainly the arrangements of some hepatic cords became loose or disordered and liver cells were somewhat different in shape and apparent volume. Some hepatic cells appeared lipopexic and numerous granulocytic immersion occurred around the central vein. CONCLUSION: manganese exposure resulted in the poisonous effects on liver in rats.