RESUMO
Traumatic brain injury (TBI) causes a high rate of mortality and disability worldwide, and there exists almost none effective drugs to protect against TBI. Neurotoxicity occurring after TBI can be derived from microglia and astrocytes, and causes neuronal death and synapse loss. Bexarotene has been demonstrated to protect neurons in CNS diseases. In the present study, we aimed to investigate the potential role of bexarotene in protecting against neurotoxicity after TBI, as well as the underlying mechanism. The controlled cortical impact (CCI) model was established on adult C57BL/6 mice, followed by intraperitoneal administration of bexarotene for 14 consecutive days. We found that bexarotene improved sensorimotor function and cognitive recovery in CCI mice. In addition, bexarotene decreased neuronal death and synapse loss, as well as inhibited apoptotic cascade. Moreover, bexarotene treatment reduced M1 microglia polarization, microglia-derived pro-inflammatory cytokines, and the number of A1 astrocytes after CCI. These effects of bexarotene were partially abolished by T0070907, an antagonist of peroxisome proliferator-activated receptor gamma (PPARγ). Additionally, bexarotene enhanced nuclear translocation and transcriptional activity of PPARγ. These findings show that bexarotene inhibits neurotoxicity in mice after TBI, at least in part through a PPARγ-dependent mechanism.
Assuntos
Bexaroteno/uso terapêutico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , PPAR gama/metabolismo , Animais , Benzamidas/toxicidade , Bexaroteno/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , PPAR gama/agonistas , PPAR gama/antagonistas & inibidores , Piridinas/toxicidadeRESUMO
Alzheimer's disease (AD) is the world's leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.
RESUMO
ABSTRACT: Minute clear cell renal cell carcinoma (MccRCC) has a diameter of <1.5âcm and can be diagnosed using multi-slice spiral CT (MSCT). Recently, the role of the neutrophil-lymphocyte ratio (NLR) in the development of MccRCC has attracted attention. This study aimed to further explore the relationship between the NLR and MccRCC.This was a prospective study of 100 patients who were diagnosed with MccRCC using MSCT at Urumqi Friendship Hospital, China. The study investigated a series of pretreatment factors, including NLR and patients' general clinical data. Statistical methods employed included Pearson's chi-square test, Spearman-rho correlation test, Cox regression analysis, and receiver operator characteristic curve analysis.Based on Pearson's χ2, Spearman-rho test, and univariate/multivariate Cox regression analysis, the overall survival of patients with MccRCC was shown to be significantly related to NLR (Pâ<â.001). NLR (hazard ratio = 50.676, 95%CI, 17.543-146.390, Pâ<â.001) is a significant independent risk-factor for MccRCC. A receiver operator characteristic curve was plotted to examine specificity and sensitivity between NLR and MccRCC (area under curve = 0.958, Pâ<â.001).The level of the NLR plays a crucial role in the survival of patients with MccRCC, as diagnosed with MSCT. The higher the NLR, the worse the prognosis for patients with MccRCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Linfócitos/imunologia , Neutrófilos/imunologia , Tomografia Computadorizada Espiral/métodos , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To detect cerebral autoregulation (CA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) by near-infrared spectroscopy and to assess its association with delayed cerebral ischemia (DCI). METHODS: From January to August 2017, 81 patients (average age 53.25 ± 10.27 years) were studied. Near-infrared spectroscopy was used to monitor CA, and associated factors were evaluated. Monitoring of CA was carried out at 5 time points (preoperative day 1 and postoperative days 1, 2, 3, and 7). Patients were sorted into 2 groups according to whether DCI occurred (DCI group and non-DCI group). The relationship between CA and DCI in patients with aSAH was analyzed. RESULTS: Among 81 patients, CA trended toward being impaired in patients with aSAH with a poorer grade. DCI occurred in 39 of 51 (48.15%) patients with impaired CA. DCI occurred in 6 of 30 (7.4%) patients with intact CA. CONCLUSIONS: Impaired CA monitored by near-infrared spectroscopy was shown in patients with aSAH before and after surgical intervention. Older age, smoking, hypertension, and especially impaired CA are independent risk factors for patients with DCI.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Homeostase/fisiologia , Monitorização Fisiológica/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Adulto , Idoso , Isquemia Encefálica/epidemiologia , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/tendências , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/tendências , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Hemorragia Subaracnóidea/epidemiologia , Fatores de TempoRESUMO
This study reports the syntheses of Fe(3)O(4)@SiO(2)-Gn-PAMAM-Pd(0) composites and their applications as magnetically recoverable catalysts for the hydrogenation of allyl alcohol. The controlled growth of polyamidoamine (PAMAM) dendrimers with different generations on Fe(3)O(4)@SiO(2) surfaces was monitored by FT-IR spectra. Subsequently, Pd nanoparticles with diameters of about 2.5 nm were stabilized homogeneously on the surface of Fe(3)O(4)@SiO(2)-Gn-PAMAM (n = 1-4), investigated by thermogravimetry (TG) and transmission electron microscopy (TEM) measurements. The Fe(3)O(4)@SiO(2)-Gn-PAMAM-Pd(0) have high catalytic activity for the hydrogenation of allyl alcohol and the rate of the reaction can be controlled by changing the generation of PAMAM. In particular, the composites made of superparamagnetic Fe(3)O(4) nanocrystals with diameters of about 10 nm are very suitable as catalyst supports for catalyst separation under a relatively low external magnetic field and catalyst re-dispersion after removing the external magnetic field.