122,060 research outputs found
FABP1 in wonderland
No full textCannabinoid receptors hold a core position in the brain and control memory, cognition, movement, and pain sensitivity. sn-2 arachidonoylglycerol (2-AG) activates neuronal cannabinoid receptors as a full agonist. The brain may rely on circulating arachidonic acid to synthesize endogenous cannabinoids. This Editorial highlights a study by Martin and coworkers in the current issue of the Journal of Neurochemistry in which the authors describe, for the first time, that liver acts as a pool of arachidonic acid that under certain conditions feeds the brain to produce endocannabinoids. Therapeutics affecting liver FABP1 levels should take into account that FABP1 represents a fatty acid reservoirs for the brain. Read the highlighted article "FABP-1 gene ablation impacts brain endocannabinoid system in male mice" on doi: 10.1111/jnc.13664
Bellelli Vincenzo, Galetta Federica, Mitro Rocco, Area sacra del Manganello (Cerveteri, RM): Il pozzo sud, in Bollettino di Archeologia online, Anno XIII, n. 2, 2022, pp.61-95.
No full textThe sacred well investigated by the CNR-ISPC in the Etruscan sanctuary of Manganello at Cerveteri was uncovered in 2007, although its filling was investigated in 2019, after the area was secured. The authors present a preliminary report of the 2019 excavation and pay particular attention to the content of the well, which includes debris of the nearby buldings which composed the sanctuary and fragmentary ex votos
Lipid-activated nuclear receptors: from gene transcription to the control of cellular metabolism
No full textCellular homeostasis is maintained through a complicated network of signaling, transport and enzymatic events that take place in different compartments of the cell. The result of this composite network determines the cellular behavior in response to environmental challenges. Within this network, many cellular functions are regulated at the transcriptional level and consequently the comprehension of the molecular mechanisms of gene regulation is fundamental to fully understand how the cell reacts to environmental changes. Moreover, it offers an opportunity to find novel targets for the design of better strategies to improve healthy human nutrition and to treat metabolic diseases. In this framework, nuclear receptors have emerged as key regulators of many cellular functions in response to lipid action. In this review, we will discuss the new concepts on the biology of the recently "adopted" nuclear receptors sensing oxysterols (LXR), bile acids (FXR) and fatty acids (PPARs) and their function in the integrated regulation of lipid and glucose metabolism. We will also address the role played by other orphan nuclear receptors, such as FTF, SHP and HNF-4, acting in concert with these lipid-sensing nuclear receptors in the regulation of cellular metabolism
Inhibition of histone deacetylases for the treatment of hyperlipidemias and prevention of atherosclerosis and cardiovascular diseases
No full textThe present invention relates to the use of inhibitors of the histone deacetylases for the preparation of a medicament for the treatment of pathologies caused by increased levels of plasma cholesterol and plasma and hepatic triglycerides. Particularly, the invention relates to the use of said inhibitors for the preparation of a medicament for the treatment of diseases such as hyperlipidaemia, particularly, hypercholesterolaemia, hypertriglyceridaemia, atherosclerosis, cardiovascular and cerebrovascular pathologies, obesity, diabetes metabolic syndromes
Caractéristiques et pronostic de l'endocardite mitro-aortique
No full textL Endocardite infectieuse (EI) est une pathologie grave provoquant des dégâts valvulaires cardiaques responsables d une morbidité et d une mortalité importante. Dans environ 15% des cas elle touche de façon concomitante la valve aortique et la valve mitrale mais le profil et le pronostic de l EI mitro-aortique restent mal définis. L objectif de notre travail était de préciser les caractéristiques cliniques et paracliniques, et le pronostic des EI mitro-aortiques sur valve native en les comparant aux EI uni-valvulaires du cœur gauche. Méthode : Etude bicentrique portant sur 770 EI du cœur gauche sur valve native certaines selon les critères de la Duke University. Les patients ont été inclus entre janvier 1991 et aout 2011 dans les CHU d Amiens et Marseille. Résultats : Une EI mitro-aortique sur valve native est trouvée dans 16.6% des EI du cœur gauche sur valve native. La mortalité hospitalière de l EI mitro-aortique est de14.8%. Dans les EI du cœur gauche sur valve native, le sexe masculin (p=0.003), l apparition d un nouveau souffle (p<0.001), l insuffisance cardiaque (p=0.01), la survenue d une complication cérébro-vasculaire (p=0.008) et le streptocoque (p=0.04) ont été identifiés comme des facteurs indépendamment associés à la présence d une EI mitro-aortique. Dans l ensemble des EI du cœur gauche sur valve native, l EI mitro-aortique n est pas identifiée comme facteur prédictif de mortalité hospitalière. En revanche l EI mitro-aortique est identifiée comme facteur prédictif indépendant de mortalité à long terme (OR=1.46 ; IC : 1.1-1.94 ; p=0.01). Dans les EI mitro-aortiques sur valve native, nous n avons pas mis en évidence de facteur pronostique de mortalité hospitalière ; l index de Charlson (ou indice de comorbidité) a été identifié comme facteur pronostique indépendant de mortalité à long terme. Conclusion : Notre étude a permis d identifier 5 facteurs indépendamment associés à la présence d une EI mitro-aortique : le sexe masculin, l apparition d un nouveau souffle, l insuffisance cardiaque, la survenue de complications cérébrovasculaires, le streptocoque. Dans les conditions actuelles de prise en charge, l EI mitro-aortique est un facteur pronostique indépendant de mortalité à long terme de l EI du cœur gauche sur valve native. L EI mitro-aortique est donc associée à un risque de complications cérébrovasculaires et d insuffisance cardiaque plus élevé, et à une surmortalité à long terme.Infective endocarditis (IE) is a serious cardiac condition causing valvular lesions responsible for severe complications and mortality. The frequency of left-sided bivalvular lesions among IE is about 15%, however its characteristics and prognosis have rarely been studied. The objective was to specify the characteristics and the prognosis of left-sided bivalvular IE compared with left-sided univalvular IE. Methods: In two referral centers, 770 consecutive patients with definite left-sided IE were included between January 1991 and august 2011. Results: 16.6% of left-sided IE were bivalvular. In-hospital death rate was 14.8%. In multivariate analysis, the following variables were independent and significant predictors of left-sided bivalvular IE: male gender (p=0.003), new murmur (p<0.001), heart failure (p=0.01), cerebrovascular complications (p=0.008) and streptococci (p=0.04). Among left-sided IE, bivalvular ones were not identified as a predictor of in-hospital death. However they were identified as an independent predictor of late mortality (OR=1.46 ; CI : 1.1-1.94 ; p=0.01). About left-sided bivalvular IE, multivariate analysis did not reveal any predictor for in-hospital death. Nevertheless Charlson comorbidity index was identified as an independent predictor of late mortality. Conclusion: 5 independent and significant predictors of left-sided bivalvular IE were identified: male gender, new murmur, heart failure, cerebrovascular complications and streptococci. Under the current caring, left-sided bivalvular IE was identified as an independent predictor of late mortality among left-sided IE. In conclusion, left-sided bivalvular IE is associated with a higher hazard of cerebrovascular complications, heart failure, and late mortality.AMIENS-BU Santé (800212102) / SudocSudocFranceF
Fluorescence Resonance Energy Transfer Techniques to Study Ligand-Mediated Interactions of PPARs with Coregulators
No full textThe capacity to induce the association of peroxisome proliferator-activated receptors (PPARs) with different transcriptional coregulators is determined by the peculiar 3D-structure that the receptors adopt when bound with a specific ligand. The fluorescence resonance energy transfer assay is a technique widely used to evaluate coregulator recruitment to nuclear receptors induced by ligands. With this assay it is possible to quantitatively determine the interaction and the affinity of coregulators with PPARs when these receptors are complexed with ligands. Here, we describe the use of this technique to assess the preferential interaction and the affinity of PPARγ with coregulators as a function of the chemical structure of the bound ligan
Mitochondria, lysosomes, and dysfunction: their meaning in neurodegeneration
No full textIn the last decades, lysosomes and mitochondria were considered distinct and physically separated organelles involved in different cellular functions. While lysosomes were thought to exclusively be the rubbish dump of the cell involved in the degradation of proteins and other cell compartments, mitochondria were considered solely involved in the oxidation of energy substrate to get ATP, together with other minor duties. Nowadays, our view of these organelles is profoundly changed since studies demonstrated that mitochondria and lysosome are mutually functional, maintaining proper cell homeostasis. Furthermore, the onset of neurodegenerative diseases (i.e., Parkinson's disease, Alzheimer's disease, lysosomal storage disorders, and amyotrophic lateral sclerosis) is tightly linked to mutations in mitochondrial and lysosomal regulators. In this context, mitochondrial dysfunction leads to lysosomal impairment and buildup of autophagy by-products, whereas lysosomal imperfections trigger functional and morphological mitochondrial defects. Here, we provide an updated overview covering recent findings about mitochondria and lysosomal interaction in physiology and pathophysiology, focusing the attention on the molecular mechanism that control their interdependence
Non-insulin anti-diabetic drugs : an update on pharmacological interactions
No full textNowadays, the goal in the management of type 2 diabetes mellitus (T2DM) remains personalized control of glucose. Since less than 50% of patients with T2DM achieve glycemic treatment goal and most of them take medications for comorbidities associated to T2DM, drug interactions, namely pharmacokinetic and pharmacodynamic interactions, may enhance or reduce the effect of compounds involved in hyperglycemia. Hence, clinicians should be aware of the severe complications in T2DM patients in case of a concomitant use of these medications. It is within this context that this review aims to evaluate the effect of a second drug on the pharmacokinetic of these compounds which may lead, along with several pharmacodynamic interactions, to severe clinical complications, i.e., hypoglycemia. Available drugs already approved in Europe, USA and Japan have been included
T0901317 is a potent PXR ligand: Implications for the biology ascribed to LXR
No full textAbstractThe liver X receptors (LXRα and β) are nuclear receptors that coordinate carbohydrate and lipid metabolism. Insight into the physiologic roles of the LXRs has been greatly facilitated by the discovery of potent synthetic agonists. Here we show that one of these compounds, T0901317, is also a high-affinity ligand for the xenobiotic receptor pregnane X receptor (PXR). T0901317 binds and activates PXR with the same nanomolar potency with which it stimulates LXR activity. T0901317 induces expression not only of LXR target genes, but also of PXR target genes in cells and animals, including the scavenger receptor CD36, a property not shared by more specific LXR ligands, such as GW3965. Activation of PXR targets may explain why T0901317 induces dramatic liver steatosis, while GW3965 has a milder effect. These results suggest that many of the biological activities heretofore associated with LXR activation may be mediated by PXR, not LXR. Since T0901317 has been widely used in animals to study LXR function, the in vivo effects of this compound ascribed to LXR activation should be re-examined
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