RESUMEN
Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.
Asunto(s)
Anticarcinógenos/farmacología , Extractos Vegetales/farmacología , Neoplasias Gástricas/prevención & control , Vitis , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavonoides/análisis , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Intercelular/genética , Interleucina-8/análisis , Interleucina-8/genética , Fenoles/análisis , Polifenoles , ARN Mensajero/análisis , Neoplasias Gástricas/patología , Factor de Necrosis Tumoral alfa/farmacología , Vitis/químicaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by significant clinical heterogeneity with early diagnosis being a major challenge, complicated by the absence of formal diagnostic criteria. Instead, classification criteria have been developed to enable the homogenous inclusion of patients in clinical trials, with the most commonly used those of the American College of Rheumatology (ACR 1997) and the Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC 2012). These criteria are widely used in clinical practice as diagnostic tools, although they fail to diagnose up to 20% of patients with SLE or may delay diagnosis. These restrictions have led to the recent (2018) introduction of new classification criteria jointly by the European League Against Rheumatism (EULAR) and ACR. AIMS OF THE STUDY: We will compare the sensitivity and specificity of the earlier and new classification criteria after a systematic analysis (retrospective study) of a group of SLE patients. In addition, we will examine which set of criteria permits the earliest classification of the disease in a prospective cohort of patients with undifferentiated connective tissue disease (UCTD). The prognostic impact (permanent organ damage) of the classification of SLE patients with the three sets of criteria will also be examined. METHODS: Data from the existing Cretan lupus registry will be used to retrospectively include consecutively registered patients aged ≥15 years diagnosed with SLE during 01/2005-12/2016 by an expert physician and followed-up for at least 6 months. All sets of criteria (ACR 1997, SLICC 2012, EULAR/ACR 2018) will be tested at the time of physician-based diagnosis and also at last follow-up. A prospective study arm will include cases with a diagnosis of UCTD and will be followed-up in the outpatient clinic for 3-5 years. ANTICIPATED BENEFITS: This is the first study to include the application of the new criteria (EULAR/ACR 2018) to a group of SLE patients. Determining their diagnostic value in comparison to existing criteria or diagnosis by a specialist will provide important information both for the value of their application at the level of clinical studies and for their use in clinical practice as diagnostic criteria.
RESUMEN
Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPHË scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.
Asunto(s)
Antioxidantes/farmacología , Vitis/química , Antiinflamatorios/farmacología , Proliferación Celular/efectos de los fármacos , Quimioprevención , Neoplasias del Colon/patología , Ciclooxigenasa 2/metabolismo , Países en Desarrollo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Frutas/química , Glutatión/metabolismo , Grecia , Células HT29 , Humanos , Interleucina-8/metabolismo , Polifenoles/farmacología , Factor de Transcripción ReIA/metabolismoRESUMEN
Currants and sultanas (Vitis vinifera L., Family Vitaceae) are dried vine products produced in Greece and used widely in the Mediterranean diet. We investigated the polar methanol extracts from the raisins for the antiradical activity, polyphenol content, cytotoxicity in peripheral blood mononuclear cells, total glutathione (GSH) levels, oxidized glutathione (GSSG) levels, and inhibition of low-density lipoprotein (LDL) oxidation. Extracts exhibited 1,1-diphenyl-2-picrylhydrazyl scavenging activity and inhibited tert-butylhydroperoxide (tBHP)-induced cytotoxicity, GSH decrease, and LDL oxidation. Fluorescence microscopy revealed the characteristic apoptotic patterns with tBHP and inhibition with the extracts. Elevated levels of total GSH and unaltered levels of GSSG with extract treatment demonstrated the induction of gamma-glutamylcysteine synthetase. The antioxidant activity was correlated to the polyphenolic content. Greek currants and sultanas are suggested as antioxidant components of the Mediterranean basin.
Asunto(s)
Antioxidantes/farmacología , Extractos Vegetales/farmacología , Vitis/química , Antioxidantes/análisis , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Flavonoides/análisis , Flavonoides/farmacología , Depuradores de Radicales Libres/metabolismo , Disulfuro de Glutatión/metabolismo , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Fenoles/análisis , Fenoles/farmacología , Extractos Vegetales/análisis , PolifenolesRESUMEN
In recent years, natural dietary agents have drawn a great deal of attention owing to their demonstrated ability to suppress cancer. We aimed to investigate the in-vitro gastric cancer preventive activity of a methanol extract obtained from table olives of Greek origin. Tested were AGS cell proliferation, induction of apoptosis and inhibition of inflammation. AGS stomach cancer cells were cultured at a density of 10 cells/ml. Methanol extract of olive was added to cultures at concentrations of 2.0, 1.6, 1.0, and 0.4 microg phenols/ml. Effect on cellular viability was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and percentages of early and late apoptotic cells were assayed by annexin V-FITC staining on a FACS scan. Interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM)-1 mRNA and protein production were measured by applying reverse transcriptase-PCR and enzyme-linked immunosorbent assay. Olive extract significantly suppressed cell proliferation at 2.0, 1.6, and 1.0 microg phenols/ml. Flow cytometric analysis of Annexin-V labeled cells indicated that 2.0 microg phenols/ml significantly induced apoptosis. Similarly, at 2.0, 1.6, and 1.0 microg phenols/ml a significant decrease of ICAM-1 and IL-8 protein levels was observed. ICAM-1, as well as IL-8, mRNA expression were decreased in the presence of 2.0 microg phenols/ml. Results indicate that the methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death and suppressing inflammation in AGS cells.
Asunto(s)
Adenocarcinoma/prevención & control , Apoptosis/efectos de los fármacos , Flavonoides/uso terapéutico , Olea/química , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Neoplasias Gástricas/prevención & control , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Flavonoides/aislamiento & purificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Polifenoles , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Human zinc deficiency is thought to be prevalent worldwide, particularly in populations with diets low in zinc and animal protein and high in inhibitors of zinc absorption, such as phytic acid. Confirmation of zinc deficiency is, however, difficult in the absence of a reliable and sensitive marker of zinc status. Under controlled conditions, T-lymphocyte metallothionein-2A (MT-2A) mRNA levels change in relation to zinc status and the objective of the present study was to investigate whether these transcript levels could be related to dietary zinc intake, plasma zinc or other biochemical parameters influenced by, or influencing, zinc metabolism in human subjects likely to be zinc deficient. Rural Koreans (n 110, age 50-80 years) with a range of zinc and phytic acid dietary intake were recruited for the study and blood samples were analysed for plasma zinc, HDL, LDL, alpha-tocopherol and thiobarbituric acid reactive substances, mononuclear cell (MNC) MT-2A mRNA, serum protein and albumin, and blood haematocrit, Hb and glucose. Multiple correlation and principal component analysis showed a significant negative correlation between plasma zinc and MNC MT-2A mRNA levels. Female subjects had higher MT-2A transcript levels than males and MT-2A mRNA levels tended to increase with age. There was no significant association between dietary zinc intake or any index of zinc intake relating to dietary inhibitors of zinc absorption. It is concluded that MNC MT-2A mRNA levels cannot be used to predict poor zinc nutrition.