Basis Of Chronic Disease Research Articles

Bio-Guided Isolation of Compounds from Fraxinus excelsior Leaves with Anti-Inflammatory Activity.

Inflammation is the first physiological defence mechanism against external and internal stimuli. The prolonged or inappropriate response of the immune system may lead to the persistent inflammatory response that can potentially become a basis for chronic diseases e.g., asthma, type II diabetes or cancer. An important role in the alleviation of inflammatory processes, as an adjunct to traditional pharmacological therapy, is attributed to phytotherapy, especially to raw materials with a long tradition of use, e.g., ash leaves. Despite their long-term use in phytotherapy, the specific mechanisms of action have not been confirmed in a sufficient number of biological or clinical studies. The aim of the study is a detailed phytochemical analysis of infusion and its fractions, isolation of pure compounds from the leaves of Fraxinus excelsior and evaluation of their effect on the secretion of anti-inflammatory cytokines (TNF-α, IL-6) and IL-10 receptor expression in an in vitro model of monocyte/macrophage cells isolated from peripheral blood. Methods: Phytochemical analysis was carried out by the UHPLC-DAD-ESI-MS/MS method. Monocytes/macrophages were isolated from human peripheral blood using density gradient centrifugation on Pancoll. After 24 h incubation with tested fractions/subfractions and pure compounds, cells or their supernatants were studied, respectively, on IL-10 receptor expression by flow cytometry and IL-6, TNF-α, IL-1β secretion by the ELISA test. Results were presented with respect to Lipopolysaccharide (LPS) control and positive control with dexamethasone. Results: The infusion, 20% and 50% methanolic fractions and their subfractions, as well as their dominating compounds, e.g., ligstroside, formoside and oleoacteoside isolated from the leaves, show the ability to increase the IL-10 receptor expression on the surface of monocyte/macrophage cells, stimulated by LPS, and to decrease the secretion of pro-inflammatory cytokines, e.g., TNF-α, IL-6.

Pediatrik Akut Respiratuar Distres Sendromu Tanılı Hastalarda İnhale Nitrik Oksit Kullanımının Değerlendirilmesi

Objective: Nitric oxide therapy is not routinely used in the treatment of pediatric acute respiratory distress syndrome (PARDS), but it is recommended to be used as an adjunctive therapy in some selected cases. In our study, we aimed to discuss patients with PARDS who were treated with inhaled nitric oxide (iNO) therapy. Methods: The data of patients who were hospitalized in the pediatric intensive care unit with a diagnosis of PARDS and received iNO treatment between January 2016 and January 2018 were retrospectively analyzed. Age, gender, length of stay, mortality, number of days on mechanical ventilation, use of vasoactive drugs, mortality scores, lactate levels, OI (oxygenation index), PaO2/FiO2, methemoglobin levels, iNO administration time, echocardiographic findings and underlying primary diseases were recorded. Results: It was determined that 9 patients who were followed up with the diagnosis of PARDS were given iNO treatment. Except for one patient, they were diagnosed with pneumonia developing on the basis of chronic disease and PARDS secondary to septic shock. Five patients died while receiving iNO therapy. Seven patients were ventilated with iNO in addition to conventional mechanical ventilation methods. Two patients who died were ventilated with HFOV (high frequency oscillatory ventilation). In 3 of 9 patients, inhaled nitric oxide treatment was successful. Conclusion: Although inhaled nitric oxide treatment is a known treatment used in different diseases, the level of its effect in PARDS patients continues to be investigated. We think that this treatment can be beneficial when applied in selected patients and experienced centers.

Abstract 18405: Epidrug Treatment Rescues Proliferation and Differentiation in Human Cardiac Mesenchymal Cells of Type 2 Diabetic Patients: A Case of Epimetabolic Memory

Introduction: The origin of metabolic/epigenetic memory remains elusive. It, however, may be at the basis of chronic diseases and functional alteration associated to ageing and cardiovascular disease. HYPOTHESIS: Diabetes is known to alter cellular metabolism causing defects in tissue/organ regeneration. In this study we asked whether human cardiac stromal cells from diabetic and normoglycaemic voluntary donors revealed differences associated to their original metabolism and whether the alterations could be rescued by epigenetically active drugs. METHODS and RESULTS: D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of histone H3 lysine 9 and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5- related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-a general control of amino acid synthesis (GCN5a), determining a relative decreasein total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. CONCLUSIONS: This study investigated the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.

Fitness, nutrition and the molecular basis of chronic disease

The onset of chronic disease is often the prelude to the subsequent physiological and mental twilight in the aging population of modern society. While rates of obesity, specific types of cancer and cardiovascular disorders seem to be on the rise in this group, many new therapies have addressed diseases that have been largely untreatable in the past. Alzheimer’s disease has also recently come to the forefront of ongoing maladies most typically associated with an aging population. Ironically, though, many people seem to be living longer than expected. Recent biochemical, nutritional and genomic approaches have been able to elucidate some of the complex mechanisms, which lead to chronic diseases associated with an aging population such as Alzheimer’s, metabolic syndrome, tumor metastasis and cardiovascular disease. These diseases and their sequalae seem to be related in many respects, with the common culprit being the inflammatory environment created by the presence of excess fat – particularly within the vascular network. Although a substantial effort has been focused on the development of new-line therapeutics to address these issues, nutrition and overall fitness and their effects on stalling or potentially reversing the advent of these diseases has not been fully embraced in the research arena. This review discusses the role of the inflammatory environment in the development of chronic diseases in the aging population and also proposes a common pathology. The benefits that improvements and dedication in nutrition and fitness approaches may offer at the molecular level are also discussed.

Abstract CN04-02: Interrogating the heritable genome to achieve the goal of personalized cancer therapeutics.

Abstract CN04-02: Interrogating the heritable genome to achieve the goal of personalized cancer therapeutics.

Antioxidants in Foods: State of the Science Important to the Food Industry

Antioxidant foods and ingredients are an important component of the food industry. In the past, antioxidants were used primarily to control oxidation and retard spoilage, but today many are used because of putative health benefits. However, the traditional message that oxidative stress, which involves the production of reactive oxygen species (ROS), is the basis for chronic diseases and aging is being reexamined. Accumulating evidence suggests that ROS exert essential metabolic functions and that removal of too many ROS can upset cell signaling pathways and actually increase the risk of chronic disease. It is imperative that the food industry be aware of progress in this field to present the science relative to foods in a forthright and clear manner. This may mean reexamining the health implications of adding large amounts of antioxidants to foods.