Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer's disease model induced with okadaic acid.

BACKGROUND: The presence of Transient Receptor Potential Vanilloid 1 (TRPV1) channels was detected in many regions of the human and rat brain, including the cortex and hippocampus. TRPV1 channels have functions such as the modulation of synaptic transmission and plasticity and the regulation of cognitive functions. Previous studies conducted with TRPV1 agonists and antagonists show that this channel is associated with the neurodegenerative process. In the present study, the purpose was to investigate the effects of capsaicin, which is a TRPV1 agonist, and capsazepine, a TRPV1 antagonist, in the Alzheimer's Disease (AD) model that was induced by intracerebroventricular (ICV) administration of okadaic acid (OKA). METHODS: The AD-like experimental model was created with bilateral ICV OKA injection. Intraperitoneal capsaicin and capsazepine injections were administered to the treatment groups for 13 days and histological and immunohistochemical examinations were performed from the cortex and hippocampal CA3 regions of the brain. The Morris Water Maze Test was used for spatial memory measurement. RESULTS: ICV OKA administration increased the levels of caspase-3, phosphorylated-tau-(ser396), Aß, TNF-α, and IL1-ß, from the cortex and hippocampal CA3 regions of the brain and decreased the phosphorylated-Glycogen synthase kinase-3 beta-(ser9) levels. In addition, the OKA administration corrupted the spatial memory. The TRPV1 agonist capsaicin reversed the pathological changes induced by ICV OKA administration, but not the TRPV1 antagonist capsazepine. CONCLUSIONS: It was found in the study that the administration of the TRPV1 agonist capsaicin reduced neurodegeneration, neuroinflammation, and deterioration in spatial memory in the AD model induced by OKA.

Evaluation of Coronary Flow Level with Mots-C in Patients with STEMI Undergoing Primary PCI. / Avaliação do Nível de Fluxo Coronário com MOTS-C em Pacientes com IAMCSST Submetidos à ICP Primária.

BACKGROUND: The protective effects of mitochondrial open reading frame of the 12S rRNA-c (MOTS-C) on cardiovascular diseases have been shown in numerous studies. However, there is little documentation of the relationship between MOTS-C and coronary blood flow in ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: We aimed to investigate the role of MOTS-C, which is known to have cytoprotective properties in the pathogenesis of the no-reflow phenomenon, by comparing the coronary flow rate and MOTS-C levels in patients with STEMI submitted to primary PCI. METHODS: 52 patients with STEMI and 42 patients without stenosis >50% in the coronary arteries were included in the study. The STEMI group was divided into two groups according to post-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade:(i) No-reflow: grade 0, 1, and 2 and (ii) grade 3(angiographic success). A p value of <0.05 was considered significant. RESULTS: MOTS-C levels were significantly lower in the STEMI group compared to the control group (91.9 ± 8.9 pg/mL vs. 171.8±12.5 pg/mL, p<0.001). In addition, the Receiver Operating Characteristics (ROC) curve analysis indicated that serum MOTS-C levels had a diagnostic value in predicting no-reflow (Area Under the ROC curve [AUC]:0.95, 95% CI:0.856-0.993, p<0.001). A MOTS-C ≥84.15 pg/mL measured at admission was shown to have 95.3% sensitivity and 88.9% specificity in predicting no-reflow. CONCLUSION: MOTS-C is a strong and independent predictor of no-reflow and in-hospital MACE in patients with STEMI. It was also noted that low MOTS-C levels may be an important prognostic marker of and may have a role in the pathogenesis of STEMI.

FUNDAMENTOS: Os efeitos protetores da fase de leitura aberta mitocondrial do 12S rRNA-c (MOTS-C) em doenças cardiovasculares foram demonstrados em vários estudos. Entretanto, há pouca documentação da relação entre MOTS-C e fluxo sanguíneo coronariano no infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). OBJETIVO: Nosso objetivo foi investigar o papel do MOTS-C, que é conhecido por ter propriedades citoprotetoras na patogênese do fenômeno de no-reflow, comparando a taxa de fluxo coronariano e os níveis de MOTS-C em pacientes com IAMCSST submetidos à ICP primária. MÉTODOS: 52 pacientes com IAMCSST e 42 pacientes sem estenose >50% nas artérias coronárias foram incluídos no estudo. O grupo IAMCSST foi dividido em dois grupos de acordo com o grau de fluxo TIMI (do inglês Thrombolysis In Myocardial Infarction) pós-ICP: (i) No-reflow: graus 0, 1 e 2 e (ii) grau 3 (sucesso angiográfico). Um valor de p <0,05 foi considerado significante. RESULTADOS: Os níveis de MOTS-C foram significativamente menores no grupo IAMCSST em comparação ao grupo controle (91,9 ± 8,9 pg/mL vs. 171,8±12,5 pg/mL, p<0,001). Além disso, a análise da curva Receiver Operating Characteristics (ROC) indicou que os níveis séricos de MOTS-C tinham um valor diagnóstico na previsão de no-reflow (Área sob a curva ROC [AUC]: 0,95, IC95%: 0,856-0,993, p < 0,001). Um valor de MOTS-C ≥84,15 pg/mL medido na hospitalização mostrou ter sensibilidade de 95,3% e especificidade de 88,9% na previsão de no-reflow. CONCLUSÃO: MOTS-C é um preditor forte e independente de no-reflow e eventos cardiovasculares adversos maiores (ECAM) intra-hospitalar em pacientes com IAMCSST. Também foi observado que baixos níveis de MOTS-C podem ser um importante marcador prognóstico e podem ter um papel na patogênese do IAMCSST.

Avaliação do Nível de Fluxo Coronário com MOTS-C em Pacientes com IAMCSST Submetidos à ICP Primária / Evaluation of Coronary Flow Level with Mots-C in Patients with STEMI Undergoing Primary PCI

Resumo Fundamentos Os efeitos protetores da fase de leitura aberta mitocondrial do 12S rRNA-c (MOTS-C) em doenças cardiovasculares foram demonstrados em vários estudos. Entretanto, há pouca documentação da relação entre MOTS-C e fluxo sanguíneo coronariano no infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo Nosso objetivo foi investigar o papel do MOTS-C, que é conhecido por ter propriedades citoprotetoras na patogênese do fenômeno de no-reflow, comparando a taxa de fluxo coronariano e os níveis de MOTS-C em pacientes com IAMCSST submetidos à ICP primária. Métodos 52 pacientes com IAMCSST e 42 pacientes sem estenose >50% nas artérias coronárias foram incluídos no estudo. O grupo IAMCSST foi dividido em dois grupos de acordo com o grau de fluxo TIMI (do inglês Thrombolysis In Myocardial Infarction) pós-ICP: (i) No-reflow: graus 0, 1 e 2 e (ii) grau 3 (sucesso angiográfico). Um valor de p <0,05 foi considerado significante. Resultados Os níveis de MOTS-C foram significativamente menores no grupo IAMCSST em comparação ao grupo controle (91,9 ± 8,9 pg/mL vs. 171,8±12,5 pg/mL, p<0,001). Além disso, a análise da curva Receiver Operating Characteristics (ROC) indicou que os níveis séricos de MOTS-C tinham um valor diagnóstico na previsão de no-reflow (Área sob a curva ROC [AUC]: 0,95, IC95%: 0,856-0,993, p < 0,001). Um valor de MOTS-C ≥84,15 pg/mL medido na hospitalização mostrou ter sensibilidade de 95,3% e especificidade de 88,9% na previsão de no-reflow. Conclusão MOTS-C é um preditor forte e independente de no-reflow e eventos cardiovasculares adversos maiores (ECAM) intra-hospitalar em pacientes com IAMCSST. Também foi observado que baixos níveis de MOTS-C podem ser um importante marcador prognóstico e podem ter um papel na patogênese do IAMCSST.

Abstract Background The protective effects of mitochondrial open reading frame of the 12S rRNA-c (MOTS-C) on cardiovascular diseases have been shown in numerous studies. However, there is little documentation of the relationship between MOTS-C and coronary blood flow in ST-segment elevation myocardial infarction (STEMI). Objective We aimed to investigate the role of MOTS-C, which is known to have cytoprotective properties in the pathogenesis of the no-reflow phenomenon, by comparing the coronary flow rate and MOTS-C levels in patients with STEMI submitted to primary PCI. Methods 52 patients with STEMI and 42 patients without stenosis >50% in the coronary arteries were included in the study. The STEMI group was divided into two groups according to post-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade:(i) No-reflow: grade 0, 1, and 2 and (ii) grade 3(angiographic success). A p value of <0.05 was considered significant. Results MOTS-C levels were significantly lower in the STEMI group compared to the control group (91.9 ± 8.9 pg/mL vs. 171.8±12.5 pg/mL, p<0.001). In addition, the Receiver Operating Characteristics (ROC) curve analysis indicated that serum MOTS-C levels had a diagnostic value in predicting no-reflow (Area Under the ROC curve [AUC]:0.95, 95% CI:0.856-0.993, p<0.001). A MOTS-C ≥84.15 pg/mL measured at admission was shown to have 95.3% sensitivity and 88.9% specificity in predicting no-reflow. Conclusion MOTS-C is a strong and independent predictor of no-reflow and in-hospital MACE in patients with STEMI. It was also noted that low MOTS-C levels may be an important prognostic marker of and may have a role in the pathogenesis of STEMI.

Synthesis and anticancer properties of novel hydrazone derivatives incorporating pyridine and isatin moieties.

Nine novel hydrazone derivatives (4a-i) incorporating pyridine and isatin moieties were synthesized through one-pot, four-component heterocyclic condensation reactions. The structures of all new compounds (2a-e, 3a, 3c-e, and 4a-e) were identified by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and Fourier-transform infrared spectroscopic techniques and elemental analysis. Cell viability assays for the tested hydrazone derivatives were performed and the log IC50 values of the compounds were calculated after a 24-h treatment. All hydrazide derivatives tested showed a promising antitumor activity against A-2780 cells as compared with the standard drug docetaxel with a log IC50 value of 0.2200 µM (p < .05). Seven of the examined compounds (4b-e, 4g-i) showed high cytotoxic activity against A-2780 cells as compared with the standard drug docetaxel. Whereas the log IC50 of docetaxel was 0.2200 µM for A-2780 cells at 24 h, the IC50 values of these compounds were -0.4987, -0.4044, -0.8138, -0.3868, -0.6954, -0.4751, and 0.1809 µM, respectively. Three of the compounds, 4b, 4d, and 4i, showed high cytotoxic activity against MCF-7 cells as compared with docetaxel (p < .05). Whereas the log IC50 of docetaxel was 0.2400 µM for MCF-7 cells at 24 h, the log IC50 values of compounds 4b, 4d, and 4i were -0.1293, -0.1700, and 0.2459 µM, respectively.