RESUMO
Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.
Assuntos
Estenose das Carótidas , Disfunção Cognitiva , Demência Vascular , Animais , Camundongos , Demência Vascular/tratamento farmacológico , Doenças Neuroinflamatórias , NF-kappa B , Disfunção Cognitiva/tratamento farmacológico , Neurogênese , Modelos Animais de DoençasRESUMO
(1) Background: Exercise is effective in promoting and maintaining bone mass. The aim of this study was to detect the exercise-induced metabolic changes in bone tissue of zebrafish. (2) Methods: Thirty-eight zebrafish (Danio rerio, six months old) were analyzed. The exercise group (n = 19) received 8 weeks of counter-current swimming training. The control group (n = 19) was not subjected to exercise. Mineralization was quantified, and alkaline phosphatase (Alp) and anti-tartrate acid phosphatase (Trap) activities were estimated (n = 12). The metabolomics (n = 12) and transcriptomics (n = 14) data of bone tissue were used for the integration analyses. (3) Results: The results showed that the exercise training improved the bone mineralization of zebrafish, e.g., the exercise group (5.74 × 104 ± 7.63 × 103) had a higher mean optical density than the control group (5.26 × 104 ± 8.56 × 103, p = 0.046) for the caudal vertebrae. The amount of mineralized matrix in scales of the exercised zebrafish was also higher (0.156 ± 0.012 vs. 0.102 ± 0.003, p = 0.005). Both histological staining and biochemical analysis revealed increased Alp activity (0.81 ± 0.26 vs. 0.76 ± 0.01, p = 0.002) and decreased Trap activity (1.34 ± 0.01 vs. 1.36 ± 0.01, p = 0.005) in the exercise group. A total of 103 different metabolites (DMs, VIP ≥ 1, fold change (FC) ≥ 1.20 or ≤0.83, p < 0.050) were identified. Alanine, aspartate and glutamate metabolism, ß-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis were the significantly enriched metabolic pathways (p < 0.050). A total of 35 genes (q ≤ 0.050 (BH), |Log2FC| ≥ 0.5) were coenriched with the 103 DMs in the four identified pathways. Protein-protein interaction network analysis of the 35 genes showed that entpd3, entpd1, and cmpk2 were the core genes. (4) Conclusions: The results of this study suggest that alanine, aspartate and glutamate metabolism, ß-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis contributed to exercise-induced improvements in bone mass.
Assuntos
Transcriptoma , Peixe-Zebra , Animais , Ácido Aspártico , Metabolômica , Alanina , beta-Alanina , Pirimidinas , GlutamatosRESUMO
(1) Background: Optimal bone mass accumulation during adolescence is crucial for maximising peak bone mass during adulthood. Dietary antioxidant vitamins may contribute to bone mass accumulation. This 2.5-year-long longitudinal study aimed to evaluate the relationships between dietary vitamin A, C, and E intakes and the annual changes in bone parameters among Chinese adolescents. (2) Method: Subjects aged 10-18 years (n = 1418) were recruited from a secondary school in Jiangmen, China. Dietary vitamin A, C, and E intakes were assessed using 24 h dietary records over 3 consecutive days. The Sahara Clinical Bone Sonometer was used to measure the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). Their annual changes were then calculated (i.e., BUA%/year, SOS%/year). The associations were detected after adjusting for the baseline bone phenotype; age; sex; weight; height; pubertal stage; physical activity; and dietary intakes of vitamin D, calcium and energy. (3) Results: A curvilinear relationship was found between the dietary intake of vitamin C and BUA%/year (p = 0.026); further analyses in the subgroups revealed that this relationship was observed in male adolescents (p = 0.012). A positive association was observed only in boys with a dietary vitamin C intake of ≥159.01 mg/day (ß = 0.395, p = 0.036). Moreover, a linear positive association was shown between the dietary intake of vitamin E and BUA%/year in female adolescents (ß = 0.082, p = 0.033). (4) Conclusion: Our findings indicated that dietary vitamin C intake has a threshold effect on bone mass gain in male adolescents and that dietary vitamin E intake could be a positive predictor of bone mass gain in female adolescents.
Assuntos
Antioxidantes , Calcâneo , Animais , Ácido Ascórbico , Densidade Óssea , Calcâneo/diagnóstico por imagem , Cálcio , Ingestão de Alimentos , Feminino , Estudos Longitudinais , Masculino , Ultrassonografia , Vitamina A , Vitamina D , Vitamina E , VitaminasRESUMO
BACKGROUND: Bone mineral acquisition during adolescence is crucial for maximizing peak bone mass. Fat mass (FM) and bone mass are closely related. This study investigated the association of FM distribution with bone mass in Chinese male adolescents. METHOD: A total of 693 male adolescents aged 10-18 years were recruited from a secondary school in Jiangmen, China. Their bone mass and body composition were measured by quantitative ultrasound and bioelectrical impedance analysis, respectively. The associations of the measures of fat distribution with bone parameters, i.e., broadband ultrasound attenuation, speed of sound (SOS), and stiffness index (SI), were analyzed using multiple linear regression. Age, height, body mass index, stage of puberty, physical activity, sedentary behavior, dietary energy intake, and dietary calcium and vitamin D intake were adjusted in the model. Further subgroup analyses of prepubertal and pubertal participants were conducted. RESULTS: The measures of fat distribution showed negative associations with SOS and SI in total subjects (p < 0.010). In prepubertal boys, the measures of fat distribution were only associated with SOS (ß = -0.377 to -0.393, p < 0.050). In pubertal boys, the measures of fat distribution had associations with all bone parameters (ß = -0.205 to -0.584, p < 0.050). The strongest association was between trunk FM and SOS (ß = -0.584, p < 0.001). CONCLUSION: This study supported that the measures of fat distribution were negatively associated with bone parameters in Chinese male adolescents. Trunk FM had the strongest association with bone parameter. These associations appear to be stronger in pubertal boys than in prepubertal boys.
Assuntos
Composição Corporal/fisiologia , Distribuição da Gordura Corporal/estatística & dados numéricos , Índice de Massa Corporal , Densidade Óssea , Puberdade/fisiologia , Adolescente , Cálcio da Dieta/análise , Criança , China , Dieta/estatística & dados numéricos , Impedância Elétrica , Ingestão de Energia , Exercício Físico , Humanos , Masculino , Comportamento Sedentário , Ultrassonografia , Vitamina D/análiseRESUMO
BACKGROUND: Bone mass acquisition during growth is a major determinant of the risk of developing osteoporosis later in life. Body composition is an anthropometric determinant of bone mineral density (BMD) and significantly influences its development during childhood and adolescence. OBJECTIVE: This study aimed to systematically examine the association between body composition and bone mineral density in children and adolescents. METHODS: Observational studies addressing this association were identified from PubMed (MEDLINE), Embase, Scopus and the Cochrane Library (up to January 2021). The study populations consisted of healthy children and adolescents. The DerSimonian and Laird method was used to compute pooled estimates of effect size and the respective 95% confidence intervals for upper limbs, femoral neck (FN), lumbar spine (LS) and total body, respectively. Subgroup analyses were further performed based on age, sex and ethnicity. RESULTS: Thirty-one published studies were eligible for inclusion in this systematic review and meta-analysis, including three longitudinal studies. The combined population from all the studies amounted to 21,393 (11,205 males and 10,188 females). The pooled estimates of the correlation coefficients for lean mass (LM) and BMD ranged from 0.53 to 0.74 (p < 0.050), and the pooled regression coefficients ranged from 0.23 to 0.79 for FN, LS and total body (p < 0.050). For fat mass (FM), the pooled correlation coefficients ranged from 0.10 to 0.50 (p < 0.050) and the pooled regression coefficient was only significant for FN BMD with a weak strength (pooled ß = 0.07, p < 0.050). The pooled regression coefficients for body fat percentage (BF%) were between -0.54 and -0.04 (p < 0.050). The subgroup analysis revealed a stronger association in Asians than in Caucasians for LM and in males compared to females for BF% (p < 0.050). CONCLUSIONS: This systematic review and meta-analysis supports a positive association between LM and BMD. BF% appears to have a deleterious effect on bone acquisition in children and adolescents.