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Cell Metab ; 33(10): 1957-1973.e6, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34614408


Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis.

Células-Tronco Mesenquimais , Adipogenia , Envelhecimento , Animais , Medula Óssea , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese , Ratos
Front Neurol ; 12: 794856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069424


Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population. Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic-clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies. Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I 2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = -6.02; 95% CI -6.50 to -5.54; I 2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = -4.56, 95% CI -6.02 to -3.10; I 2 = 82.6%) and lower frequency of tonic-clonic seizures (WMD = -3.32; 95% CI -4.75 to -1.89; I 2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups. Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Brain Behav ; 10(1): e01461, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31793238


INTRODUCTION: To evaluate effectiveness of human urinary kallindinogenase (HUK) in patients with acute ischemic stroke (AIS) according to Chinese ischemic stroke subclassification (CISS) and analyzed risk factors of clinical efficacy. METHODS: In this retrospective study, 134 patients received conventional therapy were enrolled to control group, and 132 patients received HUK treatment were enrolled to HUK group. National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the clinical efficacy. Multivariate analysis of risk factors was performed by using logistic regression. RESULTS: After treatment, NIHSS score of HUK group was significant lower than that of control group (p = .009). Effectiveness rate was 71.2% in HUK group, and 53.7% in control group, respectively (p = .003). The NIHSS of patients with large artery atherosclerosis (LAA) subtype in HUK group was significantly lower than that in control group (p = .005). The absence of HUK (OR = 2.75), homocysteine (OR = 0.15), and CS subtype (OR = 0.18) were risk factors for HUK clinical efficacy. CONCLUSIONS: Human urinary kallindinogenase is an effective therapeutic approach for treatment of patients with AIS, especially in patients with LAA subtype. The absence of HUK, elevated homocysteine, and cardiogenic stroke subtype were risk factor for clinical efficacy of HUK.

AVC Isquêmico/tratamento farmacológico , Calicreínas/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento