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1.
Am J Transl Res ; 11(3): 1541-1554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30972181

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disease with limited treatments and no cure. Neurotropin (NTP) is an analgesic drug widely prescribed for neuropathic pain. Increasing evidence suggests that NTP may also protect against neurodegeneration, but NTP's treatment potential against memory impairments of AD remains to be explored. APP/PS1 mice, which model AD, were given NTP for three months then cognitively tested with the Morris water maze. Their Aß burden, microglial and astrocytic activation, and BDNF levels were compared to untreated controls using immunofluorescent staining. Expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and NF-κB pathway related proteins (p65 and IκB-α) were examined by ELISA or Western blots in vivo and in vitro in the microglia cell line. Lastly, BV-2 cells were pre-treated with the selective BDNF inhibitor ANA-12 and with NTP to examine mechanistic pathways. Taken together, NTP treatment reduced cognitive impairment, Aß deposits, and glial activation in cortex and hippocampus APP/PS1 mice. IL-1ß, IL-6 and TNF-α also decreased after NTP treatment in vivo and in vitro, and BDNF levels rose. Also, NTP reduced p65 and IκB-α activation and the effect of NTP on pro-inflammatory cytokines and NF-κB pathway related proteins was abolished by BDNF inhibitor. Our results indicate that NTP reduces neuroinflammation and improves the cognitive deficits in APP/PS1 mice possibly via BDNF/NF-κB pathway. NTP may be a new promising drug candidate for patients with AD.

2.
Radiother Oncol ; 133: 167-175, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935575

RESUMO

PURPOSE: Radiotherapy (RT) is the most effective treatment for nasopharyngeal carcinoma (NPC) but may cause stenosis of the carotid arteries. This meta-analysis evaluates the prevalence of carotid stenosis after radiation therapy. MATERIALS AND METHODS: Online search for studies reporting carotid stenosis in patients with NPC who received radiation therapy (RT) compared to NPC patients who did not receive RT and compared to healthy controls. RESULTS: Twelve studies were included for a total analysis of 1928 patients (837 received RT and 1091 were controls). RT patients showed a statistically significant higher incidence of overall stenosis (pooled risk ratio = 4.17 [2.44, 7.10], p < 0.00001) and an even greater incidence of significant stenosis (50% or more) (pooled risk ratio = 8.72 [3.53, 21.55], p < 0.00001). Analyzing by individual blood vessels showed that the RT patients had significantly higher incidence of stenosis in common carotid artery (CCA), external carotid artery (ECA), carotid bulb, CCA and internal carotid artery (ICA), and CCA/ICA/carotid bulb. CONCLUSIONS: NPC patients who receive RT have increased risk of developing carotid stenosis, and should be screened after treatment.


Assuntos
Artérias Carótidas/patologia , Artérias Carótidas/efeitos da radiação , Estenose das Carótidas/epidemiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/epidemiologia , Idoso , Estenose das Carótidas/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Estudos Observacionais como Assunto , Prevalência , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Radioterapia/estatística & dados numéricos
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