1,721,047 research outputs found
Effects of TNF-related apoptosis-inducing ligand on an animal model of type 2 diabetes
Full text linkBackground and aim of the study: Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) has recently been shown to ameliorate the natural history of diabetes mellitus (DM). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to a high fat diet (HFD).
Methods: To test this hypothesis, 27 male mice C57bl6 aged 8 weeks were randomly allocated to standard diet, HFD, or HFD + TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, glucose tolerance test (GTT) and insulin tolerance tests (ITT) were performed. Pro-inflammatory cytokines together with adipose tissue gene expression and apoptosis were measured.
Results: TRAIL treatment reduced significantly the increased adiposity associated with a HFD. In addition, it reduced significantly hyperglycaemia and hyperisulinemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by HFD and ameliorated skeletal muscle free fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis.
Conclusions: This data shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and type 2 DM
Hypertension and diabetes: emphasis on the renin-angiotensin system in atherosclerosis
No full textCardiovascular diseases (CVDs) are the major causes of morbidity and mortality in persons wit diabetes, and many factors, including hypertension, contribute to this high prevalence of macrovascular complications. (...) Finally, the recent identification of new components of the RAS should provide fertile territory to not only examine new targets linked to the RAS but potentially to design more rational treatments for the prevention of CVD in patients with diabetes and hypertension
State of art and recent developments of anti-cancer strategies based on TRAIL
No full textMulticellular organisms require apoptosis whereby the human body eliminates unnecessary and/or damaged cells. Apoptosis, or programmed cell death, can indeed be considered as a constitutive anti-cancer mechanism that seems to be defective in more than 50% of cancers. Molecular insights on the biology of the apoptotic process have led to the development of new anti-cancer strategies aiming at recovering and stimulating this process. Preclinical and clinical studies of our and other groups have demonstrated that targeting the extrinsic apoptotic pathway by various death receptors agonists is a safe and effective anti-cancer strategy, which thus may become a new cornerstone of cancer therapy. Here, we review the most recent acquisitions and patents on TRAIL or TRAIL mimetics, as well as the combination therapies that could be used with them
Cross-sex hormone therapy for gender dysphoria
No full textGender identity is the sense one has of being male or female. Gender dysphoria (GD) refers to the distress caused by the incongruence between gender identity and biological sex in gender-nonconforming individuals. Cross-sex hormone therapy (CHT) aims at easing GD, improving well-being, and quality of life of gender-nonconforming individuals. This can be achieved by inducing and maintaining the desired-sex characteristics in accordance with the specific aspirations and expectations of each individual. Nevertheless, CHT can be associated with potentially serious long-term complications
Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease
Full text linkCardiovascular diseases (CVD) remain the major cause of death and premature disability in Western societies. Assessing the risk of CVD is an important aspect in clinical decision-making. Among the growing number of molecules that are studied for their potential utility as CVD biomarkers, a lot of attention has been focused on osteoprotegerin (OPG) and its ligands, which are receptor activator of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand. Based on the existing literature and on our experience in this field, here we review what the possible roles of OPG and TRAIL in CVD are and their potential utility as CVD biomarkers
Minimally-invasive treatments for benign thyroid nodules: recommendations for information to patients and referring physicians by the Italian Minimally-Invasive Treatments of the Thyroid group
Full text linkPurpose: In this paper, the members of the Italian Working Group on Minimally-Invasive Treatments of the Thyroid (MITT group) aim to summarize the most relevant information that could be of help to referring physicians and that should be provided to patients when considering the use of MITT for the treatment of benign thyroid nodules. Methods: An interdisciplinary board of physicians with specific expertise in the management of thyroid nodules was appointed by the Italian MITT Group. A systematic literature search was performed, and an evidence-based approach was used, including also the knowledge and the practical experience of the panelists to develop the paper. Results: The paper provides a list of questions that are frequently asked by patients to operators performing MITT, each with a brief and detailed answer and more relevant literature references to be consulted. Conclusions: This paper summarizes the most relevant information to be provided to patients and general practitioners/referring physicians about the use of MITT for the treatment of benign thyroid nodules
Potential role of TRAIL in the management of autoimmune diabetes mellitus
No full textType 1 diabetes mellitus (T1DM) is an autoimmune disease, due to the immune-mediated destruction of pancreatic β-cells, whose incidence has been steadily increasing during the last decades. Insulin replacement therapy can treat T1DM, which, however, is still associated with substantial morbidity and mortality. For this reason, great effort is being put into developing strategies that could eventually prevent and/or cure this disease. These strategies are mainly focused on blocking the immune system from attacking β-cells together with functional islet restoration either by regeneration or transplantation. Recent experimental evidences suggest that TNFrelated apoptosis-inducing ligand (TRAIL), which is an immune system modulator protein, could represent an interesting candidate for the cure for T1DM and/or its complications. Here we review the evidences on the potential role of TRAIL in the management of T1DM
Prevention of accelerated atherosclerosis by AT1 receptor blockade in experimental renal failure.
No full textThe mechanisms of uraemia-induced atherosclerosis have not been fully delineated. The aims of this study were (i) to investigate the extent and the phenotype of atherosclerosis, including the activation of local renin-angiotensin system (RAS), in a mouse model of mild uraemia and (ii) to determine the effects of angiotensin II type1 (AT1) receptor blockade on the uraemic atherosclerosis, clarifying the mechanisms of its action.Mild uraemia was induced by 5/6 nephrectomy in 8-week-old apo E-deficient mice (apoE-KO). After nephrectomy, the animals received either treatment with candesartan or no treatment for 12-weeks. Sham-operated apoE-KO mice were used as controls.Uraemia led to a two-fold increase in aortic plaque area. This was associated with a significant upregulation of aortic angiotensin-converting enzyme (ACE), AT1 receptor, connective tissue growth factor (CTGF), monocyte chemoattractant protein (MCP)-1 and vascular cell adhesion molecule (VCAM)-1. Candesartan significantly reduced aortic atherosclerosis, prevented the upregulation of the uraemia-induced genes and led to changes predicting greater stability of the plaques, without influencing blood pressure or serum lipids.This study indicates that uraemia leads to an acceleration of aortic atherosclerosis. The upregulation of aortic RAS and the reduced atherosclerosis following AT1 receptor blocker treatment highlights the pivotal role of the local RAS in the development and acceleration of atherosclerosis in uraemia
Linking diabetes and atherosclerosis
No full textCardiovascular diseases are the major causes of morbidity and mortality in people with diabetes. (...) In this review we focus on the major causes and mechanisms of atherosclerotic disease in patients with diabetes and highlight emerging targets for therapeutic interventions
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