14 research outputs found
Red blood cell transfusion in surgery:an observational study of the trends in the USA from 2011 to 2016
Detecting genomic indel variants with exact breakpoints in single- and paired-end sequencing data using SplazerS
Cytomegalovirus Viral Load Kinetics in Patients with HIV/AIDS Admitted to a Medical Intensive Care Unit: A Case for Pre-Emptive Therapy
Effect of the different types of land-use on the distribution of soil organic carbon in north Nile Delta, Egypt
Comprehensive transcriptome analysis using synthetic long-read sequencing reveals molecular co-association of distant splicing events
Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes
An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro
Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis
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Mendelian and sporadic FTD: disease risk and avenues from genetics to disease pathways through in silico modelling.
Frontotemporal dementia (FTD) is regarded as the second most common form of young-onset dementia after Alzheimer's disease (AD).FTD is a complex neurodegenerative condition characterised by heterogeneous clinical, pathological and genetic features. No efficient measures for early diagnosis and therapy are available.Familial (Mendelian) forms of disease have been studied over the past 20 years. Conversely, the genetics of sporadic forms of FTD (up to 70% of all cases) is understudied and still poorly understood. All this taken together suggests that more powerful and in-depth studies to tackle missing heritability and define the genetic architecture of sporadic FTD, with particular focus on the different subtypes (i.e. clinical and pathological diagnoses), are warranted.In parallel, it will be critical to translate the genetic findings into functional understanding of disease, i.e. moving from the identification of risk genes to the definition of risk pathways. It will be necessary to implement a paradigm shift - from reductionist to holistic approaches - to better interpret genetics and assist functional studies aimed at modelling and validating such risk pathways.In this chapter, we focus on the heterogeneous features of FTD touching upon its complex genetic landscape and discuss how novel approaches (e.g. computationally driven systems biology) promise to revolutionise the translation of genetic information into functional understanding of disease pathogenesis