Search results for " Gl"
showing 10 items of 7230 documents
The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbβ3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen
2020
The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbβ3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Fu…
Differential role of interleukin-1β in neuroinflammation-induced impairment of spatial and nonspatial memory in hyperammonemic rats.
2019
Activated microglia and increased brain IL-1β play a main role in cognitive impairment in much pathology. We studied the role of IL-1β in neuroinflammation-induced impairment of the following different types of learning and memory: novel object recognition (NOR), novel object location (NOL), spatial learning, reference memory (RM), and working memory (WM). All these processes are impaired in hyperammonemic rats. We assessed which of these types of learning and memory are restored by blocking the IL-1 receptor in vivo in hyperammonemic rats and the possible mechanisms involved. Blocking the IL-1 receptor reversed microglial activation in the hippocampus, perirhinal cortex, and prefrontal cor…
New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics
2017
Item does not contain fulltext Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic ne…
Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma
2021
A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…
Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome
2018
Objective To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sjogren's syndrome (SS) and in patients with primary SS and primary SS-associated lymphoma. Methods Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS-associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and p…
Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations
2020
Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESU…
Estimating Global Burden of Disease due to congenital anomaly: an analysis of European data
2017
ObjectiveTo validate the estimates of Global Burden of Disease (GBD) due to congenital anomaly for Europe by comparing infant mortality data collected by EUROCAT registries with the WHO Mortality Database, and by assessing the significance of stillbirths and terminations of pregnancy for fetal anomaly (TOPFA) in the interpretation of infant mortality statistics.Design, setting and outcome measuresEUROCAT is a network of congenital anomaly registries collecting data on live births, fetal deaths from 20 weeks’ gestation and TOPFA. Data from 29 registries in 19 countries were analysed for 2005–2009, and infant mortality (deaths of live births at age <1 year) compared with the WHO Mortality …
Trends in Food Habits and Their Relation to Socioeconomic Status among Nordic Adolescents 2001/2002-2009/2010
2016
BACKGROUND: In the Nordic countries, substantial policy and intervention efforts have been made to increase adolescents' consumption of fruit and vegetables and to reduce their intake of sweets and soft drinks. Some initiatives have been formulated in a Nordic collaboration and implemented at national level. In recent years, social inequalities in food habits have been attracted particular governmental interest and several initiatives addressing the socioeconomic gradient in food habits have been highlighted. However, few internationally published studies have evaluated how trends in adolescents' food habits develop in the context of Nordic nutrition policy, or have compared differences bet…
Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics
2017
Background: Non-Celiac Wheat Sensitivity (NCWS) has recently been included among the gluten-related disorders. As no biomarkers of this disease exist, its frequency has been estimated based on self-reported symptoms, but to date no data are available about self-reported NCWS in teenagers. Aim: To explore the prevalence of self-reported NCWS in a group of high school students and to study their demographic and clinical characteristics. Methods: The study was performed between April 2015 and January 2016 in two high schools of a coastal town in the south of Sicily (Italy). A total of 555 students (mean age 17 years, 191 male, 364 female) completed a modified validated questionnaire for self-r…
The pituitary gland prevents shock-associated death by controlling multiple inflammatory mediators
2018
Abstract Bacterial infections cause a major burden of disease worldwide. Sepsis and septic shock are life-threatening complications of infections. The hypothalamic-pituitary-adrenal (HPA) axis initiates the release of endogenous glucocorticoids that modulate the host stress response and acute inflammation during septic shock. It is an ongoing controversial debate, if therapeutic manipulations of the HPA axis could benefit the clinical situation in the context of shock. Here, we have studied Long Evans rats with hypophysectomy followed by endotoxic shock. The shock-associated lethality was substantially higher in hypophysectomized rats as compared to control mice after cranial sham surgery (…