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1.
Biochem Biophys Res Commun ; 723: 150186, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830298

RESUMO

The aim of this study was to investigate the anti-cancer effects of resveratrol (RES) against gastric cancer (GC) and explore the potential mechanisms. We first measured the anti-cancer effects of RES on GC cell lines (i.e. AGS and HGC-27). Then protein-protein interaction (PPI) network was constructed, followed by GO and KEGG analysis to screen the possible targets. Molecular docking analysis was given to visualize the pharmacological effects of RES on GC cell lines. For the in vivo experiments, xenograft tumor model was established, and Western blot analysis was performed to determine the expression of protein screened by network pharmacology. Our results showed that RES could promote the apoptosis of GC cells. Five hub targets were identified by network pharmacology, including AKT1, TP53, JUN, ESR1 and MAPK14. GO and KEGG analyses revealed the PI3K/Akt/P53 signaling pathway was the most related signaling pathway. Molecular docking analysis indicated that RES could form 3 hydrogen bonds with AKT1 and 3 hydrogen bonds with TP53. The inhibitory effects of RES on the proliferation and promoting effects of RES on the apoptosis of AGS and HGC-27 cells were significantly reversed when blocking the PI3K-Akt signaling pathway using the LY294002. In vivo results showed that RES induced significant decrease of tumor volume and tumor weight without changing the body weight, or inducing significant cytotoxicities. Western blot analysis proved that RES could induce down-regulation of p-Akt and up-regulation of P53 in vivo. In conclusion, RES showed anti-cancer effects in GC by regulating the PI3K/Akt/P53 signaling pathway.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Resveratrol , Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Animais , Humanos , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/farmacologia , Transdução de Sinais , Estilbenos/farmacologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Arq Neuropsiquiatr ; 80(7): 663-670, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36254437

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon and serious subtype of stroke, which leads to the loss of the patient's ability to produce and live for many years. OBJECTIVE: To investigate the clinical effect of nimodipine in the treatment of SAH. METHODS: Electronic databases including China National Knowledge Infrastructure (CNKI), VIP, SinoMed, China Master's Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed and Embase were searched from 2010 and 2021. All randomized controlled trials evaluating the efficacy of nimodipine in the treatment of SAH were included in our meta-analysis. The patients were divided into control group and treatment group. Meta-analysis was performed with Stata16.0 software. RESULTS: A total of 10 studies were included. Compared with the control group, the treatment group had higher effective rate (OR = 3.21, 95% CI: 2.25, 4.58; p < 0.001), and lower incidence of adverse reactions (OR = 0.35, 95% CI: 0.19, 0.67; p = 0.001). Before treatment, no significant differences were identified in middle cerebral artery blood flow velocity and Glasgow coma scale (GCS) score between the two groups. However, after treatment, the middle cerebral artery blood flow velocity (SMD = -1.36, 95% CI: -2.28, -0.49; p = 0.002) and GCS score (SMD = 1.24, 95% CI: 0.58, 1.89; p < 0.001) in the treatment group were significantly better than those in the control group. CONCLUSIONS: Nimodipine is effective in the treatment of SAH, lowering incidence of adverse reactions and therefore improving the prognosis of patients.


ANTECEDENTES: Hemorragia subaracnóidea (SAH) é um subtipo raro e grave de acidente vascular cerebral (AVC), o que leva à perda da capacidade do paciente de produzir e viver por muitos anos. OBJETIVO: Investigar o efeito clínico da nimodipina no tratamento da SAH. MéTODOS: As bases de dados eletrônicas, incluindo a China National Knowledge Infrastructure (CNKI), VIP, SinoMed, Masters Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed e Embase foram pesquisadas no período de 2010 a 2021. Todos os ensaios controlados aleatorizados que avaliam a eficácia da nimodipina no tratamento da SAH foram incluídos na nossa meta-análise. Os pacientes foram divididos em grupo controle e grupo de tratamento. Meta-análise foi realizada com o software Stata 16.0. RESULTADOS: Foram incluídos um total de dez estudos. Em comparação com o grupo controle, o grupo de tratamento tinha uma taxa mais elevada (OR = 3,21, 95% CI: 2,25, 4,58; p < 0,001), e menor incidência de reações adversas (OR = 0,35, 95% CI: 0,19, 0,67; p = 0,001). Antes do tratamento, não foram identificadas diferenças significativas na velocidade média do fluxo sanguíneo da artéria cerebral e na pontuação de Glasgow coma scale (GCS) entre os dois grupos. No entanto, após o tratamento, a velocidade média do fluxo sanguíneo da artéria cerebral (SMD = −1,36, 95% CI: −2,28, 0,49; p = 0,002) e a pontuação do GCS (SMD = 1,24, 95% CI: 0,58, 1,89; p < 0,001) no grupo de tratamento foram significativamente melhores do que os do grupo controle. CONCLUSõES: A nimodipina é eficaz no tratamento da SAH, diminuindo a incidência de reações adversas e, consequentemente, melhorando o prognóstico dos doentes.


Assuntos
Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Escala de Coma de Glasgow , Humanos , Nimodipina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Hemorragia Subaracnóidea/tratamento farmacológico , Resultado do Tratamento
3.
Arq. neuropsiquiatr ; 80(7): 663-670, July 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403520

RESUMO

Abstract Background Subarachnoid hemorrhage (SAH) is an uncommon and serious subtype of stroke, which leads to the loss of the patient's ability to produce and live for many years. Objective To investigate the clinical effect of nimodipine in the treatment of SAH. Methods Electronic databases including China National Knowledge Infrastructure (CNKI), VIP, SinoMed, China Master's Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed and Embase were searched from 2010 and 2021. All randomized controlled trials evaluating the efficacy of nimodipine in the treatment of SAH were included in our meta-analysis. The patients were divided into control group and treatment group. Meta-analysis was performed with Stata16.0 software. Results A total of 10 studies were included. Compared with the control group, the treatment group had higher effective rate (OR = 3.21, 95% CI: 2.25, 4.58; p < 0.001), and lower incidence of adverse reactions (OR = 0.35, 95% CI: 0.19, 0.67; p = 0.001). Before treatment, no significant differences were identified in middle cerebral artery blood flow velocity and Glasgow coma scale (GCS) score between the two groups. However, after treatment, the middle cerebral artery blood flow velocity (SMD = — 1.36, 95% CI: —2.28, —0.49; p = 0.002) and GCS score (SMD = 1.24, 95% CI: 0.58, 1.89; p < 0.001) in the treatment group were significantly better than those in the control group. Conclusions Nimodipine is effective in the treatment of SAH, lowering incidence of adverse reactions and therefore improving the prognosis of patients.


Resumo Antecedentes Hemorragia subaracnóidea (SAH) é um subtipo raro e grave de acidente vascular cerebral (AVC), o que leva à perda da capacidade do paciente de produzir e viver por muitos anos. Objetivo Investigar o efeito clínico da nimodipina no tratamento da SAH. Métodos As bases de dados eletrônicas, incluindo a China National Knowledge Infrastructure (CNKI), VIP, SinoMed, Masters Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed e Embase foram pesquisadas no período de 2010 a 2021. Todos os ensaios controlados aleatorizados que avaliam a eficácia da nimodipina no tratamento da SAH foram incluídos na nossa meta-análise. Os pacientes foram divididos em grupo controle e grupo de tratamento. Meta-análise foi realizada com o software Stata 16.0. Resultados Foram incluídos um total de dez estudos. Em comparação com o grupo controle, o grupo de tratamento tinha uma taxa mais elevada (OR = 3,21, 95% CI: 2,25, 4,58; p < 0,001), e menor incidência de reações adversas (OR = 0,35, 95% CI: 0,19, 0,67; p = 0,001). Antes do tratamento, não foram identificadas diferenças significativas na velocidade média do fluxo sanguíneo da artéria cerebral e na pontuação de Glasgow coma scale (GCS) entre os dois grupos. No entanto, após o tratamento, a velocidade média do fluxo sanguíneo da artéria cerebral (SMD = −1,36, 95% CI: −2,28, 0,49; p = 0,002) e a pontuação do GCS (SMD = 1,24, 95% CI: 0,58, 1,89; p < 0,001) no grupo de tratamento foram significativamente melhores do que os do grupo controle. Conclusões A nimodipina é eficaz no tratamento da SAH, diminuindo a incidência de reações adversas e, consequentemente, melhorando o prognóstico dos doentes.

4.
J Cell Biochem ; 120(10): 17151-17158, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31134677

RESUMO

AIMS: In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR-224-3p in cerebral I/R injury. METHODS: Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 were measured to evaluate the function of miR-224-3p. RESULTS: Overexpression of miR-224-3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase-3 was significantly reduced. We further provided the possible mechanism that miR-224-3p may protect cells from cerebral I/R injury by targeting FAK family-interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR-224-3p. CONCLUSIONS: We evaluated the function and mechanism of miR-224-3p in ischemic brain injury. miR-224-3p may serve as a potential target for new therapeutic intervention.


Assuntos
Apoptose/genética , Proteínas Relacionadas à Autofagia/genética , MicroRNAs/genética , Neurônios/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Caspase 3/genética , Caspase 3/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Vetores Genéticos , Glucose/deficiência , Glucose/farmacologia , Camundongos , MicroRNAs/agonistas , MicroRNAs/metabolismo , Modelos Biológicos , Mimetismo Molecular , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Oxigênio/farmacologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Transfecção
5.
Neurosciences (Riyadh) ; 22(1): 56-61, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28064332

RESUMO

Infarction of the symmetrical middle cerebellar peduncles is often induced by ischemic cerebrovascular disease. Adams described the anterior inferior cerebellar artery (AICA) syndrome as early as 1943, but clinical and imaging studies following this failed to shed more light regarding the condition until the advent of magnetic resonance imaging that comprehension regarding AICA improved significantly. Infarction of the middle cerebellar peduncles (MCP) is uncommon and the endovascular treatment of this condition is even more rare. We studied 4 patients with simultaneous bilateral cerebellar infarction of whom 2 received intracranial vascular therapy and demonstrated improvement in symptoms. Our findings suggest that patients with vertebral basilar artery stenosis with potential bilateral cerebellar infarction may benefit from endovascular treatment.


Assuntos
Infarto Cerebral/cirurgia , Procedimentos Endovasculares/métodos , Pedúnculo Cerebelar Médio/cirurgia , Angiografia Cerebral , Infarto Cerebral/diagnóstico , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pedúnculo Cerebelar Médio/irrigação sanguínea , Inibidores da Agregação Plaquetária/uso terapêutico , Stents
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