Search results for "Acellular"

Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix.

2019

Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that are present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy as polyP. However, the function and metabolism of this long-neglected polymer are scarcely known, especially in higher eukaryotes. In recent years, interest in polyP experienced a renaissance, beginning with the discovery of polyP as phosphate source in bone mineralization. Later, two discoveries placed polyP into the focus of regenerative medicine applications. First, polyP shows morphogenetic activity, i.e., induc…

Adhesion Molecules in Kidney Diseases

2010

TCTN3 Mutations Cause Mohr-Majewski Syndrome

2012

Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of 13 OFDS subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary sequencing, we identified truncating TCTN3 mutations as the cause of an extreme form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly syndromes) led us to identify four additional truncating TCTN3 mutations in un…

CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in he…

2016

Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-r…

Relationship between apoptosis and survival molecules in human cumulus cells as markers of oocyte competence

2017

SummaryTo select from a single patient the best oocytes able to reach the blastocyst stage, we searched for valuable markers for oocytes competence. We evaluated the DNA fragmentation index (DFI) and the level of some survival molecules, such as AKT, pAKT and pERK1/2, in individual cumulus cell–oocyte complexes (COC). The study included normo-responder women. The average age of the patients was 34.3. DFI in cumulus cells was evaluated using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labelling (TUNEL) assayin situ. AKT, pAKT and pERK1/2 were measured by immunological assay and densitometric analysis of fluorescent signals using NIS-Elements BR 3.10 image software. Statisti…

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

2020

Background: Eryptosis is a physiological, apoptosis-like death of injured erythrocytes crucial to prevent premature haemolysis and the pathological sequalae generated by cell-free haemoglobin. When dysregulated, the process is associated to several inflammatory-based pathologies. 4-Hydroxy-trans-2-nonenal (HNE) is an endogenous signalling molecule at physiological levels and, at higher concentrations, is involved in the pathogenesis of several inflammatory-based diseases. This work evaluated whether HNE could induce eryptosis in human erythrocytes. Methods: Measurements of phosphatidylserine, cell volume, intracellular oxidants, Ca++, glutathione, ICAM-1, and ceramide were assessed by flow …

Histone deacetylase inhibition by suberoylanilide hydroxamic acid: a therapeutic approach to treat human uterine leiomyoma.

2022

Objective To evaluate the effect of inhibition of histone deacetylases (HDACs) by suberoylanilide hydroxamic acid (SAHA) treatment of human uterine leiomyoma primary (HULP) cells in vitro on cell proliferation, cell cycle, extracellular matrix (ECM) formation, and transforming growth factor β3 (TGF-β3) signaling. Design Prospective study comparing uterine leiomyoma (UL) vs. adjacent myometrium (MM) tissue and cells with or without SAHA treatment. Setting Hospital and university laboratories. Patient(s) Women with UL without any hormone treatment. Intervention(s) Myomectomy or hysterectomy surgery in women for leiomyoma disease. Main Outcome Measure(s) HDAC activity was assessed by enzyme-li…

Effects of muscular exercise on erythrocyte adenosine triphosphate concentration in patients with insulin-dependent diabetes mellitus.

1987

Type I diabetes mellitus represents a metabolic disorder in which intracellular glycolytic pathway is inhibited by insulin deficiency, with the subsequent decreased availability of energetic substrates such as ATP. Some aspects of the energetic metabolism in response to an intensive demand (muscular exercise) were investigated, in a group of 10 ketotic diabetic patients, by measuring erythrocyte adenosine triphosphate (ATP) and blood glucose, free fatty acids (FFA) and lactate levels. In the diabetic subjects, in comparison with normal subjects, the decreased levels of erythrocyte ATP at rest did not increase after exercise, while the increased levels of FFA at rest did not diminish after e…

Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a novel mechanism underlying vasospastic angina.

2012

Abstract A 37-year old male patient presented with frequent angina attacks (up to 40/day) largely resistant to classical vasodilator therapy. The patient showed severe coronary and peripheral endothelial dysfunction, increased platelet aggregation and increased platelet-derived superoxide production. The endothelial nitric oxide synthase (eNOS)-inhibitor N G -nitro- l -arginine methyl ester (L-NAME) reduced superoxide formation in platelets identifying “uncoupled” eNOS as a superoxide source. Oral l -arginine normalized coronary and peripheral endothelial dysfunction and reduced platelet aggregation and eNOS-derived superoxide production. Plasma concentrations of the endogenous NOS inhibito…

Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients.

2017

Summary T helper 9 (Th9) cells and interleukin (IL)-9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL-9 and Th9 cells in patients with systemic sclerosis (SSc) have not yet been studied adequately. IL-9, IL-9R, transcription factor PU.1 (PU.1), IL-4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)-β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL-9 was also analysed by confocal microscopy analysis. Peripheral IL-9-producing cells were also studied by flow cytometry. The functional relevance of IL-9 increased expression in SSc …