Translational research : the journal of laboratory and clinical medicine
-
Randomized Controlled Trial Observational Study
Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery.
This work aimed to explore the link between angiopoietin-like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross-sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. ⋯ In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow-up.
-
The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. ⋯ While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiological mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review, we highlight current knowledge regarding the pathophysiological consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiological and molecular mechanisms that may contribute to these adverse outcomes.
-
Estrogen receptor alpha (ERα) also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1) is a ligand-activated transcription factor. It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. ⋯ Comparative analysis of ER_Apt1 to ER alpha monoclonal antibody was also performed to analyze the expression of ER alpha in various malignant cancer cell line. Cytochemical and immunohistochemistry assay indicates its potential use as a diagnostic agent against ERα positive carcinomas. The nucleotide aptamer sequences described in the present study can be used for the detection, treatment, prophylaxis and diagnosis of ERα-related disorder.
-
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs antioxidant, innate immune and cytoprotective responses and its deregulation is prominent in chronic inflammatory conditions. To examine the hypothesis that Nrf2 might be implicated in systemic sclerosis (SSc), we investigated its expression, activity, and mechanism of action in SSc patient samples and mouse models of fibrosis and evaluated the effects of a novel pharmacologic Nrf2 agonist. We found that both expression and activity of Nrf2 were significantly reduced in SSc patient skin biopsies and showed negative correlation with inflammatory gene expression. ⋯ In wild-type mice, treatment with a novel pharmacologic Nrf2 agonist 2-trifluoromethyl-2'-methoxychalcone prevented dermal fibrosis induced by TGF-β. These findings are the first to identify Nrf2 as a cell-intrinsic antifibrotic factor with key roles in maintaining extracellular matrix homeostasis and a pathogenic role in SSc. Pharmacologic reactivation of Nrf2, therefore, represents a novel therapeutic strategy toward effective treatment of fibrosis in SSc.
-
The links between systemic insulin resistance (IR), brain-specific IR, and Alzheimer's disease (AD) have been an extremely productive area of current research. This review will cover the fundamentals and pathways leading to IR, its connection to AD via cellular mechanisms, the most prominent methods and models used to examine it, an introduction to the role of extracellular vesicles (EVs) as a source of biomarkers for IR and AD, and an overview of modern clinical studies on the subject. ⋯ Ultimately, examining the relation between IR and AD can be seen as a means of advancing the understanding of both disease states, with IR being a promising target for therapeutic strategies in AD treatment. In conclusion, we highlight the therapeutic potential of targeting brain IR in AD and the main strategies to pursue this goal.