Search results for "Retinoid"

CYP27A1, CYP24A1, and RXR-α Polymorphisms, Vitamin D, and Multiple Sclerosis: a Pilot Study.

2018

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Hypovitaminosis D seems to contribute to MS susceptibility as both an environmental and a genetic risk factor. The aim of our study was to investigate the association of SNPs in CYP27A1, CYP24A1, and RXR- α genes, vitamin D status, and MS risk. We performed a nested case-control study on patients with multiple sclerosis and healthy controls. Serum 25(OH)D3 levels and genotyping of CYP27A1, CYP24A1, and RXR-α -SNPs were investigated both in MS patients and in healthy controls. Serum 25(OH)D3 levels were measured by a high-performance liquid chromatograp…

2019

These days, the important role of retinoids in adult brain functionality and homeostasis is well accepted and has been proven by genomic as well as non-genomic mechanisms. In the healthy brain, numerous biological processes, e.g., cell proliferation, neurogenesis, dendritic spine formation as well as modulation of the immune system, have been attributed to retinoid signaling. This, together with the finding that retinoid metabolism is impaired in Alzheimer's disease (AD), led to preclinical and early clinical testing of natural and synthetic retinoids as innovative pharmaceuticals with multifactorial properties. Acitretin, an aromatic retinoid, was found to exert an anti-amyloidogenic effec…

Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer’s Disease

2016

Amyloid-b (Ab) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPAR dimeric receptor. As we have previously demonstrated, estrogenic compounds, such as genistein, have antioxidant activity, which can be evidenced by increased expression of manganese superoxide dismutase (MnSOD). Furthermore, genistein is a non-toxic, well-tested, and inexpensive drug that activates PPARg receptor. We isolated and cultured cortical astrocytes from dissected cerebral cortices of neonatal mice (C57BL/6 J). Preincubation with genistein (5 mM) for 24 hours, prior to the addit…

Clearing Amyloid-β Through PPARγ/ApoE Activation by Genistein is an Experimental Treatment of Alzheimer's Disease

2016

Amyloid-β (Aβ) clearance from brain, which is decreased in Alzheimer’s disease, is facilitated by apolipoprotein E. Apo E is up-regulated by activation of the retinoid X receptor moiety of the RXR/PPARγ dimeric receptor. Genistein, a non-toxic, well tested and inexpensive drug has a multifaceted protective effect: antioxidant (because it stimulates the expression of antioxidant genes), anit-inflammatory and stimulator of activates the PPARγ receptor, which results in increased expression of ApoE. Treatment of an Alzheimer’s mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit m…

Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis.

2015

Background & Aims The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. Methods The expression of liver VDR was investigated in apolipoprotein E knockout ( apoE −/− ) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE −/− mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR t…

N-retinylidene-N-retinylethanolamine adduct induces expression of chronic inflammation cytokines in retinal pigment epithelium cells

2021

Blindness due to photoreceptor degeneration is observed in both genetic and acquired eye disorders. Long blue light exposure can contribute to increase levels of oxidative compounds within the retinal pigment epithelium (RPE), enhancing risk of retinal damage. In retina, reactive oxygen species contribute to the activation of inflammatory cascade. If chronic, this inflammatory response can result in photoreceptor death. Therefore, we investigated the effects of the endogenous adduct N-retinylidene-N-retinylethanolamine (A2E) on RPE cells, in order to identify the most dysregulated cytokines and their related inflammatory pathways. RPE cells were exposed to A2E and blue light for 3h and 6h. …

Role of Vitamin A in Mammary Gland Development and Lactation

2019

Vitamin A (all-trans-retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. …

9-cis-Retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene

1997

The role of retinoic acids (RA) on liver fatty acid- binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-ci's-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10 -6 M 9-CK-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-c/s-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome prol…

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycl…

2009

Background The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy-with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Re…

Absorption of Drugs after Oral Administration

2007

After oral administration, drugs must be absorbed through the gastrointestinal tract to achieve the systemic circulation and exert their pharmacological effects. The successful formulation of an optimized oral drug delivery system requires a detailed consideration and a good understanding of the intestinal absorption process, its possibilities and limitations. This article gives an overview and update on the concepts, possibilities, and limitations of drug absorption after oral administration. Keywords: oral administration; drug absorption; oral drug delivery system; gastrointestinal tract; intestinal absorption