Search results for "Wester"
showing 10 items of 1157 documents
TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles
2019
Background Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signaling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Here, we evaluate if ethanol and the TLR4 response change the release and inflammatory content of astrocyte-derived EVs, and whether these vesicles are capable of communicating with neurons by spreading neuroinflammation. Methods Cortical neurons and astrocytes in culture were used. EVs were isolated from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated …
Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity.
2017
Abstract Pyrrolo[3′,2′:6,7]cyclohepta[1,2-b]pyridines were synthesized as a new class of tricyclic system in which the pyridine ring is annelated to a cycloheptapyrrole scaffold, with the aim of obtaining new photosensitizing agents with improved antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached, which allowed the isolation of derivatives of the title ring system with a good substitution pattern on the pyrrole moiety. Photobiological studies revealed that the majority of the new compounds showed a potent cytotoxic effect upon photoactivation with light of the proper wavelength, especially when decorated with a 2-ethoxycabonyl group an…
The IgGFc-binding protein FCGBP is secreted with all GDPH sequences cleaved but maintained by interfragment disulfide bonds
2021
Mucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus. It is comprised of repeated von Willebrand D (vWD) domain assemblies, most of which have a GDPH amino acid sequence that can be autocatalytically cleaved, as previously observed in the mucins MUC2 and mucin-5AC. However, the functions of FCGBP in the mucus are not understood. We show that all vWD domains of FCGBP with a GDPH sequence are cleaved and …
Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins.
2017
Abstract Context Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Objective To determine whether reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to determine whether proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in determining low LDL levels in this conditio…
Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.
2017
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNF alpha and IL-6), mitochondrial and total reactive oxygen species (ROS) produc…
The genomic history of Southern Europe
2018
Farming was first introduced to southeastern Europe in the mid-7th millennium BCE - brought by migrants from Anatolia who settled in the region before spreading throughout Europe. However, the dynamics of the interaction between the first farmers and the indigenous hunter-gatherers remain poorly understood because of the near absence of ancient DNA from the region. We report new genome-wide ancient DNA data from 204 individuals-65 Paleolithic and Mesolithic, 93 Neolithic, and 46 Copper, Bronze and Iron Age-who lived in southeastern Europe and surrounding regions between about 12,000 and 500 BCE. We document that the hunter-gatherer populations of southeastern Europe, the Baltic, and the Nor…
Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease
2018
SUMMARY Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. T…
Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers
2015
// Giorgio Mauri 1 , Elena Jachetti 1 , Barbara Comuzzi 1 , Matteo Dugo 2 , Ivano Arioli 1 , Silvia Miotti 1 , Sabina Sangaletti 1 , Emma Di Carlo 3, 4 , Claudio Tripodo 5 , Mario P. Colombo 1 1 Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 20133, Milano, Italy 2 Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 20133, Milano, Italy 3 Department of Medicine and Science of Aging, Section of Anatomic Pathology and Molecular Medicine, “G. d’Annunzio” University, 66100, Chieti, Italy 4 Ce.S.I. Aging Research Center, “G…
Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage.
2015
Abstract Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Amyloid-s-peptide (As) forms senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks of AD neuropathology. Evidence support the involvement of immune system in AD progression and current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune components in the neurodegenerative process. Pathologically, immune system components have been detected in the brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates …
Brief Report: Functional Interaction of Endoplasmic Reticulum Aminopeptidase 2 and HLA-B27 Activates the Unfolded Protein Response.
2017
Objective: The basic mechanisms underlying the pathogenesis of ankylosing spondylitis (AS) remain unresolved. We previously reported an association of the single-nucleotide polymorphism (SNP) rs2549782 in the endoplasmic reticulum aminopeptidase 2 gene (ERAP2) with AS. It is known that patients homozygous for the G allele (GG) of another ERAP2 SNP, rs2248374, lack expression of ERAP2 (ERAP2 null). The present study utilized this information to study the impact of ERAP2 deficiency on HLAâB27 expression in patients with AS, specifically focusing on the functional interaction of ERAP2 and HLAâB27 in peripheral blood mononuclear cells (PBMCs) from patients with AS and assessing the effects …