Search results for "Aryl"
showing 10 items of 810 documents
Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.
2017
Background 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptiona…
The Relation between Eating Habits and Abdominal Fat, Anthropometry, PON1 and IL-6 Levels in Patients with Multiple Sclerosis
2020
Background: Multiple sclerosis (MS) is a chronic neurodegenerative disease of an inflammatory, demyelinating and autoimmune nature. Diets with a high caloric density could be especially relevant in terms of the pathogenesis related to an increase in adipose tissue that is metabolically active and releases mediators, which can induce systemic inflammation and an increased oxidation state. The aim of this study was to analyse the eating habits related to calorie intake and their impact on abdominal obesity associated with anthropometric variables, the activity of the oxidation marker paraoxonase 1 (PON1), and interleukin 6 (IL-6) levelsin MS patients. Methods: An analytical and quantitative o…
Reported muscle symptoms during statin treatment amongst Italian dyslipidaemic patients in the real‐life setting: the PROSISA Study
2021
Aim: Statin-associated muscle symptoms (SAMS) are a major determinant of poor treatment adherence and/or discontinuation, but a definitive diagnosis of SAMS is challenging. The PROSISA study was an observational retrospective study aimed to assess the prevalence of reported SAMS in a cohort of dyslipidaemic patients. Methods: Demographic/anamnestic data, biochemical values and occurrence of SAMS were collected by 23 Italian Lipid Clinics. Adjusted logistic regression was performed to estimate odds ratio (OR) and 95% confidence intervals for association between probability of reporting SAMS and several factors. Results: Analyses were carried out on 16 717 statin-treated patients (mean ± SD, …
Bioactive triterpenes of protium heptaphyllum gum resin extract display cholesterol-lowering potential
2021
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and…
Identification of the Privileged Position in the Imidazo[1,2-a]pyridine Ring of Phosphonocarboxylates for Development of Rab Geranylgeranyl Transfera…
2017
Members of the Rab GTPase family are master regulators of vesicle trafficking. When disregulated, they are associated with a number of pathological states. The inhibition of RGGT, an enzyme responsible for post-translational geranylgeranylation of Rab GTPases represents one way to control the activity of these proteins. Because the number of molecules modulating RGGT is limited, we combined molecular modeling with biological assays to ascertain how modifications of phosphonocarboxylates, the first reported RGGT inhibitors, rationally improve understanding of their structure-activity relationship. We have identified the privileged position in the core scaffold of the imidazo[1,2-a]pyridine r…
The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling
2018
Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in various plastic compounds, such as polyvinyl chloride (PVC), and products including baby toys, packaging films and sheets, medical tubing, and blood storage bags. Epidemiological data suggest that phthalates increase the risk of the nervous system disorders; however, the impact of DEHP on the brain cells and the mechanisms of its action have not been clarified. The aim of the present study was to investigate the effects of DEHP on production of reactive oxygen species (ROS) and aryl hydrocarbon receptor (AhR), as well as Cyp1a1 and Cyp1b1 mRNA and protein expression in primary mouse cortical neurons and glial cells in the in vit…
Elastin-derived peptide VGVAPG affects the proliferation of mouse cortical astrocytes with the involvement of aryl hydrocarbon receptor (Ahr), peroxi…
2019
Abstract During aging and ischemic and hemorrhagic stroke, elastin molecules are degraded and elastin-derived peptides are released into the brain microenvironment. Val-Gly-Val-Ala-Pro-Gly (VGVAPG) is a repeating hexapeptide in the elastin molecule. It is well documented that the peptide sequence binds with high affinity to elastin-binding protein (EBP) located on the cell surface, thereby transducing a molecular signal into the cell. The aim of our study was to investigate whether EBP, aryl hydrocarbon receptor (Ahr), and peroxisome proliferator-activated receptor gamma (Pparγ) are involved in VGVAPG-stimulated proliferation. Primary astrocytes were maintained in DMEM/F12 medium without ph…
Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses
2015
Rhodamine 123 (R123) transport substrate sensitizes P-glycoprotein (P-gp) to inhibition by compound 2c (cis-cis) N,N-bis(cyclohexanolamine)aryl ester isomer in a concentration-dependent manner in human MDR1-gene transfected mouse T-lymphoma L5178 cells as shown previously. By contrast, epirubicin (EPI) concentration changes left unaltered 2c IC50 values of EPI efflux. To clarify this discrepancy, defined molecular docking (DMD) analyses of 12 N,N-bis(cyclohexanolamine)aryl esters, the highly flexible aryl ester analog 4, and several P-gp substrate/non-substrate inhibitors were performed on human P-gp drug- or nucleotide-binding domains (DBD or NBD). DMD measurements yielded lowest binding e…
Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (…
2016
Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood–brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM–100 µM) and time-dependent (3–…
Statins in liver disease: not only prevention of cardiovascular events
2018
Statins are lipid-lowering agents and one of the most pre-scribed drugs worldwide. Their main mechanism of action –inhibition of the mevalonate pathway through an effect on hydroxy-methylglutaryl CoA reductase, thus affecting the synthesis of cholesterol in the liver – makes this class of drugs pivotal in primary and secondary prevention of cardio-vascular risk, as extensively demonstrated in large prospective, randomized controlled trials. Along the years, we learned that the lower the better, and LDL-cholesterol targets have been progressively reduced to values ≤70 mg/dL for secondary prevention or in the presence of diabetes.