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showing 10 items of 7305 documents
The Gut Metagenome Changes in Parallel to Waist Circumference, Brain Iron Deposition, and Cognitive Function.
2017
Context Microbiota perturbations seem to exert modulatory effects on emotional behavior, stress-, and pain-modulation systems in adult animals; however, limited information is available in humans. Objective To study potential relationships among the gut metagenome, brain microstructure, and cognitive performance in middle-aged, apparently healthy, obese and nonobese subjects after weight changes. Design This is a longitudinal study over a 2-year period. Setting A tertiary public hospital. Patients or other participants Thirty-five (18 obese) apparently healthy subjects. Intervention(s) Diet counseling was provided to all subjects. Obese subjects were followed every 6 months. Main outcome me…
Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus
2017
Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8) and GDM (n=8) pregnancies. S-Nitrosylation was measured using the biotin-switch …
β(3)‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?
2019
β(3)‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β(3)‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β(3)‐adrenoceptor agonist, are considerably lower than the EC(50) for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β(3)‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression o…
Birth Mode-Related Differences in Gut Microbiota Colonization and Immune System Development.
2018
<b><i>Background:</i></b> The process of early gut colonization is extremely variable among individuals and is influenced by numerous factors. Among these, the mode of birth will strongly shape the early microbial exposure and immune environment of the neonate. <b><i>Summary:</i></b> Here, I review how the concomitant processes of microbiota and immune system development are altered by C-section delivery and the effects of such alterations on long-term health. <b><i>Key messages:</i></b> C-section delivery impinges on microbiota and immune system development through various means: (i) if labor is lacking, intrauterine i…
DNA demethylation caused By 5-Aza-2'-Deoxycytidine induces mitotic alterations and aneuploidy
2016
Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduc…
Mild Parkinsonian Signs in a Hospital-based Cohort of Mild Cognitive Impairment Types: A Cross-sectional Study
2018
Background:Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results.Objective:To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes.Methods:A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated…
Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
2017
Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire…
Human Achilles tendon glycation and function in diabetes
2016
Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly ( n = 22) and well ( n = 22) controlled diabetic patients, including healthy age-matched (45–70 yr) controls ( n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effe…
Two simple criteria to estimate an objective's performance when imaging in non design tissue clearing solutions
2019
Tissue clearing techniques are undergoing a renaissance motivated by the need to image fluorescent neurons, and other cells, deep in the sample without physical sectioning. Optical transparency is achieved by equilibrating tissues with high refractive index (RI) solutions. When the microscope objective is not perfectly matched to the RI of the cleared sample, aberrations are introduced. We present two simple-to-calculate numerical criteria predicting: (i) the degradation in image quality (brightness and resolution) from optimal conditions of any clearing solution/objective combination; (ii) which objective, among several available, achieves the highest resolution in a given medium. We deriv…
Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants:a Prospective Lynch Syndrome Database r…
2021
Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%,…