Search results for "muta"
showing 10 items of 6895 documents
Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice
2020
Early brain insult, interfering with its maturation, may result in psychotic-like disturbances in adult life. Redox dysfunctions and neuroinflammation contribute to long-term psychiatric consequences due to neurodevelopmental abnormalities. Here, we investigated the effects of early pharmacological modulation of the redox and inflammatory states, through celastrol, and indomethacin administration, on reactive oxygen species (ROS) amount, levels of malondialdehyde (MDA) and antioxidant enzymes (superoxide dismutase 1, SOD1, glutathione, GSH, and catalase, CAT), as well as of pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-α, interleukin-6, IL-6, and interleukin-1 beta, IL-1β), i…
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
2017
Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major…
DLG4-related synaptopathy: a new rare brain disorder
2021
Contains fulltext : 245031.pdf (Publisher’s version ) (Closed access) PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyp…
14-3-3 Proteins regulate K2P5.1 surface expression on T lymphocytes
2016
K2P5.1 channels (also called TASK-2 or KCNK5) have already been shown to be relevant in the pathophysiology of autoimmune disease since they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P5.1 channels in vitro provokes enhanced T-cell effector functions. However, the molecular mechanisms regulating intracellular K2P5.1 channel trafficking are unknown so far. Thus, the aim of the study is to elucidate the trafficking of K2P5.1 channels on T lymphocytes. Using mass spectrometry analysis, we have identified 14-3-3 proteins as novel binding partners of K2P5.1 channels. We show that a non-classical 14-3-3 co…
FMF is not always "fever": from clinical presentation to "treat to target".
2020
AbstractFamilial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease.Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier.Attacks consist of …
Biostimulation proved to be the most efficient method in the comparison of in situ soil remediation treatments after a simulated oil spill accident
2016
The use of in situ techniques in soil remediation is still rare in Finland and most other European countries due to the uncertainty of the effectiveness of the techniques especially in cold regions and also due to their potential side effects on the environment. In this study, we compared the biostimulation, chemical oxidation, and natural attenuation treatments in natural conditions and pilot scale during a 16-month experiment. A real fuel spill accident was used as a model for experiment setup and soil contamination. We found that biostimulation significantly decreased the contaminant leachate into the water, including also the non-aqueous phase liquid (NAPL). The total NAPL leachate was …
Pesticide residues in honey bees, pollen and beeswax: Assessing beehive exposure
2018
In order to study the distribution of pesticide residues in beekeeping matrices, samples of live in-hive worker honey bees (Apis mellifera), fresh stored pollen and beeswax were collected during 2016–2017 from 45 apiaries located in different landscape contexts in Spain. A total of 133 samples were screened for 63 pesticides or their degradation products to estimate the pesticide exposure to honey bee health through the calculation of the hazard quotient (HQ). The influence of the surrounding environment on the content of pesticides in pollen was assessed by comparing the concentrations of pesticide residues found in apiaries from intensive farming landscapes to those found in apiaries loca…
Biological and anticancer properties of Inonotus obliquus extracts
2018
Abstract Inonotus obliquus (IO) has traditionally been used in folk medicine in the treatment of gastrointestinal cancer, cardiovascular disease and diabetes. The aim of our study was to evaluate the biological and metabolic properties of IO extracts. Free radical scavenging properties, inhibition of the activity of xanthine oxidase (XOi), induction of reactive oxygen species (ROS) production, cell viability and expression of superoxide dismutase (SOD1), catalase (CAT) and KI67 mRNA in the human colorectal adenocarcinoma (Caco-2) and normal human skin fibroblast (BJ) cell lines were measured. It was found that 80% ethanol extract of IO exhibited the highest properties inhibiting the activit…
Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.
2016
BACKGROUND Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. OBJECTIVE To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. METHODS We tested a targeted re-sequencing approach, using a 45…
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
2020
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading …