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BACKGROUND: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. OBJECTIVE: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. METHODS: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. RESULTS: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). CONCLUSIONS: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

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ABSTRACT Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

RESUMO Antecedentes: No momento, a etiologia e a patogênese da doença de Moyamoya (DMM) não são completamente claras. Os pacientes geralmente são diagnosticados após eventos cerebrovasculares. Sendo assim, é de grande importância clínica explorar os fatores preditivos de DMM. Objetivo: Este estudo teve como objetivo investigar o nível sérico de CoQ10B, a quantidade de células progenitoras endoteliais (CPE) e a função mitocondrial de CPE em pacientes com DMM. Métodos: Quarenta e um pacientes com DMM e 20 controles saudáveis foram recrutados neste estudo. Aqueles com DMM foram divididos em dois grupos: tipo isquêmico (n=23) e tipo hemorrágico (n=18). Amostras de sangue foram coletadas da veia antecubital e analisadas por CoQ10B Ensaio de Imunoadsorção Enzimática (ELISA) e citometria de fluxo. As medidas da função mitocondrial de CPE incluem taxa de consumo de oxigênio (TCO), potencial de membrana mitocondrial, concentração de Ca2+, atividade de adenosina trifosfatases (ATPase) e nível de espécies reativas de oxigênio (ROS). Resultados: O nível sérico de CoQ10B em pacientes com DMM foi significativamente menor do que em controles saudáveis (p<0,001). O número relativo de CPE em pacientes com MMD foi significativamente maior do que em controles saudáveis (p<0,001). Além disso, a TCO, o potencial de membrana mitocondrial e a atividade ATPase diminuíram e os níveis de Ca2+e ROS aumentaram em pacientes com MMD (p<0,001). Conclusões: Nossos resultados mostraram obviamente diminuição do nível sérico de CoQ10B e aumento do número de CPE em pacientes com DMM em comparação com pacientes saudáveis, e a função mitocondrial de CPE em pacientes com DMM estava anormal.

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Inflammatory processes play a pivotal role in the development and progression of depression. Since Follistatin-like protein 1 (FSTL1) has been identified as a novel inflammatory protein, a variety of studies suggest that targeting FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. In the study, we aimed to investigate the causal relationship between FSTL1 signaling and the development of depression. To explore the effect and mechanism of FSTL1 on chronic stress-induced depression, the chronic unpredictable mild stress (CUMS) paradigm was used. Animals subjected to CUMS for 4 weeks exhibited depressive-like symptoms, including decreased sucrose preference and obvious behavioral despair, concomitantly with increased FSTL1 level in the hippocampus. In contrast, mice with FSTL1 knockdown abolished CUMS induced depression-like and anxiety-like behaviors. Moreover, FSTL1 knockdown reversed CUMS induced synaptic plasticity deficits in the PP-DG pathway of the hippocampus and increased the expression of synaptic associated proteins in the hippocampus of CUMS exposed mice. Microglia activation induced by CUMS paradigm could be significantly inhibited by FSTL1 knockdown. Furthermore, Western blot revealed that FSTL1 knockdown considerably decreased the expression of indicated molecules TLR4/MyD88/NF-κB signaling pathway in CUMS exposed mice. In conclusion, our data implies that FSTL1 may modulate the microglial activation through TLR4/MyD88/NF-κB signaling, which affects depression-like behaviors and synaptic function deficits induced by CUMS in mice. These results suggested that the role of FSTL1 in mediating microglia-related mechanisms in depression may shed light on developing new therapeutic strategies to treat this prevalent disease.

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OBJECTIVE: To assess physical activity in children following acute venous thromboembolism (VTE), examine predictors of reduced physical activity and its relationship to post-thrombotic syndrome. STUDY DESIGN: Using a case-control study design, we enrolled 44 children with acute VTE, and compared physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire and health-related quality of life at 3 and 6 months after diagnosis relative to 44 age- and sex-matched controls. We assessed post-thrombotic syndrome scores using the Manco-Johnson Instrument to measure symptoms and signs attributed to sequelae of DVT in cases. RESULTS: The physical activity of VTE cases was decreased at 3 months after diagnosis (36.6 ± 29.0 vs 56.8 ± 25.0; P = .002), but the differences disappeared at 6 months (57.5 ± 39.0 vs 56.8 ± 25.0; P = .60) relative to controls. At 3 and 6 months after diagnosis, overall, 70% and 50% of VTE cases were below their pre-VTE physical activity levels; providers did not address physical activity in the majority. In multivariable analysis, physical activity of cases was lower by 32 points for completely veno-occlusive thrombosis at diagnosis, 11 points for a diagnosis of pulmonary embolism relative to DVT, and increased by 0.72 points for every unit increase in health-related quality of life score. Physical activity at 3 months after diagnosis did not predict the short-term risk of post-thrombotic syndrome. CONCLUSIONS: VTE limits physical activity in children in the first 3 months after the acute event, but the differences were nonexistent at 6 months. Only 50 percent of VTE survivors resume their pre-VTE physical activity levels within 6 months after diagnosis.

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The micellization of binary mixtures of water-soluble block copolymers E(m)B(n)E(m) and E(m)S(n)E(m) in dilute solution was investigated by light-scattering methods. We use the notation E, B, and S to denote chain units derived, respectively, from ethylene oxide, butylene oxide, and styrene oxide and the subscripts to denote number-average chain lengths in chain units. Two distinct distributions of micelles were formed in solutions of a 50:50 wt % mixture of copolymers E64B20E64 and E137S18E137, which had hydrophobic blocks of similar length but very different hydrophobicity. One distribution of micelles was formed in solutions of a mixture (50:50 wt %) of copolymers E135B20E135 and E82S9E82, which had hydrophobic blocks of different length but similar hydrophobicity. In this case, the properties of the micelles formed in solutions of the mixture were very similar to those of micelles of E82S9E82 alone. This result extended to concentrated solutions, because the hard-gel boundary for the mixture proved to be very similar to that of solutions of E82S9E82 alone.

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Micellar solutions of EmPnEm copolymers may be mobile at ambient temperature and form hard gels on warming to body temperature, whereas micellar solutions of EmSnEm copolymers do not show this effect (E denotes oxyethylene, P oxypropylene and S oxyphenylethylene, and subscripts m and n denote chain lengths). The aim of this study was to combine the desirable gelation characteristics of solutions of the EmPnEm copolymers with the greater solubilising capacities of solutions of the EmSnEm copolymers. Accordingly, the gelation characteristics in aqueous solution of binary mixtures of the triblock copolymer E62P39E62 (Pluronic F87) with E137S18E137, E82S9E82 or E76S5E76 were investigated by rheological techniques. We have shown that 50/50 wt.% mixtures of E62P39E62 with either E137S18E137 or E82S9E82 at a total copolymer concentration of approximately 30 wt.% are fluids of low viscosity at temperature below 22-25 degrees C and gels of high elastic modulus at body temperature.The mixed systems have potential as vehicles for the controlled delivery of solubilised drug from gels formed in situ following subcutaneous injection of a low viscosity aqueous solution.

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Triblock copolymer S5E45S5 was synthesized by oxyanionic polymerization of styrene oxide initiated by a preformed difunctional polyethylene glycol. Here E denotes OCH2CH2, S denotes OCH2CH(C6H5), and the subscripts denote number-average block lengths in repeat units. Previous work on the closely related copolymer S4E45S4 indicated that micelles would form in aqueous solutions of copolymer S5E45S5, and that they would undergo transient intermicellar bridging. Dynamic light scattering was used to confirm this. Rheometry and small-angle X-ray scattering were used to explore gel boundaries, structures, and properties. At moderate copolymer concentrations (14 and 20 wt %) measurements of the dynamic shear moduli indicated the formation of low-modulus soft gels attributed to spherical micelles forming transient networks. A region of low storage modulus at c approximately 30 wt % preceded a change to hard gel. A 40 wt % hard gel was disordered, while at higher concentrations (49 and 60 wt %) the micelles packed into hexagonal structures with high values of the storage modulus (G' approximately 10 kPa at 25 degrees C and 1 Hz).