RESUMO
The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.
Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Canadá , Biomarcadores , Progressão da Doença , NeuroimagemRESUMO
[This corrects the article DOI: 10.1155/2016/1845638.].
RESUMO
Cervical cancer accounts for the second most frequent cancer and also third leading cause of cancer mortality (15%) among women worldwide. The major problems of chemotherapeutic treatment in cervical cancer are non-specific cytotoxicity and drug resistance. Plant-derived products, known as natural therapies, have been used for thousands of years in cancer treatment with a very low number of side effects. Allium atroviolaceum is a species in the genus Allium and Liliaceae family, which could prove to have beneficial effects on cancer treatment, although there is a lack of corresponding attention. The methanolic extract from the A.atroviolaceum flower displayed marked anticancer activity on HeLa human cervix carcinoma cells with much lower cytotoxic effects on normal cells (3T3). The A.atroviolaceum extract induced apoptosis, confirmed by cell cycle arrest at the sub-G0 (apoptosis) phase, characteristic morphological changes, evident DNA fragmentation, observed by fluorescent microscope, and early and late apoptosis detection by Annexin V. Furthermore, down-regulation of Bcl-2 and activation of caspase-9 and -3 strongly indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. Moreover, combination of A.atroviolaceum extract with doxorubicin revealed a significant reduction of IC50 and led to a synergistic effect. In summary, A.atroviolaceum displayed a significant anti-tumour effect through apoptosis induction in HeLa cells, suggesting that the A.atroviolaceum flower might have therapeutic potential against cervix carcinoma.
Assuntos
Allium/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Regulação para Baixo/efeitos dos fármacos , Flores/química , Extratos Vegetais/farmacologia , Proteína X Associada a bcl-2/metabolismo , Anexina A5/metabolismo , Antineoplásicos/farmacologia , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM) and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT2 Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.