Search results for "HRI"
showing 10 items of 2945 documents
The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM
2018
The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk fact…
Sclerostin and antisclerostin antibody serum levels predict the presence of axial spondyloarthritis in patients with inflammatory bowel disease
2018
Objective.The early diagnosis of inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA/IBD) in patients affected by IBD represents a major topic in clinical practice; in particular, to date there are no available serum biomarkers revealing the presence of joint inflammation in these patients. Sclerostin (SOST), an antagonist of the Wnt/β-catenin pathway, and antisclerostin-immunoglobulin G (anti-SOST–IgG) have been recently studied in patients with ankylosing spondylitis (AS) as a putative marker of disease activity.Methods.SOST and anti-SOST-IgG serum levels were assayed in 125 patients with IBD, 85 with axial or peripheral SpA, and in control groups (patients with AS and rheu…
12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature
2020
Abstract Background Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of…
Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort
2016
Background: Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies. Objectives: We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother–child pairs. Methods: We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (A…
Inflammasome activation in Ankylosing Spondylitis is associated to gut dysbiosis
2021
Objective: We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis. Methods: An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn’s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA–B27–transgenic rats. The NLRP3 inhibitor MCC950 was admini…
Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts
2016
Item does not contain fulltext Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Deltaep), strong inhibition of bone formation was observed, different from classical inflammatory bone loss where osteoclast activation leads to bone deg…
Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8
2018
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the s…
Dietary Magnesium and Incident Frailty in Older People at Risk for Knee Osteoarthritis: An Eight-Year Longitudinal Study.
2017
Inadequate magnesium (Mg) intake is associated with lower physical performance, but the relationship with frailty in older people is unclear. Therefore, we aimed to investigate whether higher dietary Mg intake is associated with a lower risk of frailty in a large cohort of North American individuals. Details regarding Mg intake were recorded through a food-frequency questionnaire (FFQ) and categorized as greater than/equal to Recommended Dietary Allowance (RDA) vs. lower. Frailty was defined using the Study of Osteoporotic Fractures index. Multivariable Coxâs regression analyses, calculating hazard ratios (HRs) with 95% confidence intervals (CIs), were undertaken by sex. In total, 4421 in…
Adherence to the Mediterranean diet is associated with better quality of life: data from the Osteoarthritis Initiative
2016
BACKGROUND The Mediterranean diet has positively influenced various medical conditions, but only a paucity of studies has considered the relation between the Mediterranean diet and quality of life (QOL) among people living in North America. OBJECTIVE We investigated whether a higher adherence to the Mediterranean diet (aMED) was associated with better QOL and decreased pain, stiffness, disability, and depression in a large cohort of North Americans from the Osteoarthritis Initiative. DESIGN aMED was evaluated through a validated Mediterranean diet score categorized into quintiles. Outcomes of interest were QOL [assessed with the 12-Item Short-Form Health Outcome Survey (SF-12)]; disability,…
Clinical Characteristics of Patients Carrying the Q703K Variant of the NLRP3 Gene: A 10-year Multicentric National Study
2016
Objective.The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C>A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS).Methods.Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the…