Search results for "Integument"

Analysis of nucleophosmin–anaplastic lymphoma kinase (NPM‐ALK)‐reactive CD8+ T cell responses in children with NPM‐ALK+ anaplastic large cell lymphoma

2016

Summary Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8+ T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8+ T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM–ALK were used as antigen-presenting cells for T cell …

The torso integration hypothesis revisited in Homo sapiens: Contributions to the understanding of hominin body shape evolution.

2018

Objectives: Lower thoracic widths and curvatures track upper pelvic widths and iliac blades curvatures in hominins and other primates (torso integration hypothesis). However, recent studies suggest that sexual dimorphism could challenge this assumption in Homo sapiens. We test the torso integration hypothesis in two modern human populations, both considering and excluding the effect of sexual dimorphism. We further assess covariation patterns between different thoracic and pelvic levels, and we explore the allometric effects on torso shape variation. Material and Methods: A sex-balanced sample of 50 anatomically connected torsos (25 Mediterraneans, 25 Sub-Saharan Africans) was segmented fro…

Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and De…

2016

Objective.Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-β (TGF-β). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-β might modulate this molecule.Methods.After ethical approval, mesenchymal stem cells (MSC) and fibroblasts …

Raman Spectroscopic Measurements of Dermal Carotenoids in Breast Cancer Operated Patients Provide Evidence for the Positive Impact of a Dietary Regim…

2015

Dermal carotenoids are a feasible marker of the body antioxidative network and may reveal a moderate to severe imbalance of the redox status, thereby providing indication of individual oxidative stress. In this work noninvasive Resonance Raman Spectroscopy (RRS) measurements of skin carotenoids (skin carotenoid score (SCS)) were used to provide indications of individual oxidative stress, each year for five years, in 71 breast cancer (BC) patients at high risk of recurrence. Patients’ SCS has been correlated with parameters relevant to BC risk, waist circumference (WC), and body mass index (BMI), in the aim of monitoring the effect of a dietary regimen intended to positively affect BC risk f…

5-HT1A Receptor Function Makes Wound Healing a Happier Process

2018

Skin wound healing is a multistage phenomenon that is regulated by cell–cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis reve…

Controlled Transdermal Release of Antioxidant Ferulate by a Porous Sc(III) MOF

2020

Summary The Sc(III) MOF-type MFM-300(Sc) is demonstrated in this study to be stable under physiological conditions (PBS), biocompatible (to human skin cells), and an efficient drug carrier for the long-term controlled release (through human skin) of antioxidant ferulate. MFM-300(Sc) also preserves the antioxidant pharmacological effects of ferulate while enhancing the bio-preservation of dermal skin fibroblasts, during the delivery process. These discoveries pave the way toward the extended use of Sc(III)-based MOFs as drug delivery systems (DDSs).

Long Pentraxin 3-Mediated Fibroblast Growth Factor Trapping Impairs Fibrosarcoma Growth

2018

Fibrosarcomas are soft tissue mesenchymal tumors originating from transformed fibroblasts. Fibroblast growth factor-2 (FGF2) and its tyrosine-kinase receptors (FGFRs) play pivotal roles in fibrosarcoma onset and progression, FGF2 being actively produced by fibroblasts in all stages along their malignant transformation to the fibrosarcoma stage. The soluble pattern recognition receptor long pentraxin-3 (PTX3) is an extrinsic oncosuppressor whose expression is reduced in different tumor types, including soft tissue sarcomas, via hypermethylation of its gene promoter. PTX3 interacts with FGF2 and other FGF family members, thus acting as a multi-FGF antagonist able to inhibit FGF-dependent neov…

Constitutive psgl-1 correlates with cd30 and tcr pathways and represents a potential target for immunotherapy in anaplastic large t-cell lymphoma

2021

Simple Summary P-selectin glycoprotein ligand-1 (PSGL-1), coded by the SELPLG gene, is the major ligand of selectins and plays a pivotal role in tethering, rolling and extravasation of immune cells. PSGL-1 involvement in core molecular programs, such as SYK, PLCγ2, PI3Kγ or MAPK pathways, suggests additional functions beyond the modulation of cell trafficking. Recently, several studies identified a novel mechanism responsible for PSGL-1-mediated immune suppression in the tumor microenvironment and proved a novel concept of PSGL-1 as a critical checkpoint molecule for tumor immunotherapy. The immunotherapeutic approach has gained an ever-growing interest in the treatment of several hematolog…

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem ce…

2016

AbstractHutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process an…

2019

The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8+T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8+T cells. One key molecule is IFN-γ that is synthesized by CD8+T cells under the control of NFATc1 and NFATc2. CD8+T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. …