Search results for "folate"
showing 10 items of 110 documents
Folate-mediated targeting of polymeric conjugates of gemcitabine.
2005
The synthesis of two new macromolecular prodrugs for active tumor targeting was set up. Gemcitabine (2'-deoxy-2',2'-difluorocytidine) was conjugated to alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) through succinyl or diglycolyl hydrolysable spacers. The targeting agent folic acid was attached to the macromolecular backbone through the aminocaproic spacer. The two conjugates [PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide and PHEA-(5'-diglycolyl-gemcitabine)-1'-carboxypentyl-folamide], were purified and extensively characterised by spectroscopic (UV, IR and NMR) and chromatographic analyses to determine the correct chemical structure, the purity degree and the reaction yi…
Gene-diet interaction in plasma lipid response to plant sterols and stanols: A review of clinical trials
2021
Abstract Plant sterols and stanols (PS) are well known for their cholesterol-lowering effect by reducing intestinal absorption of cholesterol. However, genetic factors modulate the low-density lipoprotein cholesterol (LDL-C) response to PS therapy. This review examines clinical trials evaluating the impact of the main genes associated with response of plasma lipid concentrations to PS intake: APOE, CYP7A1, ABCG5/G8, NPC1L1, CETP, APOA4/A5, SCARBI, HMGCR, PPARα, LIPC, MTHFR and LPA. Evidence indicates that carriers of mutant allele of the CYP7A1 c. −204 A > C variant experience a greater plasma cholesterol reduction after PS intake, although there is discrepancy for the rest of genetic varia…
Folate-targeted supramolecular vesicular aggregates based on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs.
2010
Supramolecular vesicular aggregates (SVAs) have the advantage of combining the safe and biocompatible properties of colloidal vesicular carriers based on phospholipids with those of polymeric materials, i.e. polyaspartyl-hydrazide (PAHy) copolymers. To provide SVAs with a certain tumour selectivity, folate moieties were chemically conjugated to PAHy copolymers. Physicochemical properties (mean sizes, polydispersity index and zeta potential) of folate-targeted SVAs (FT-SVAs) loaded with gemcitabine were evaluated. The antiproliferative and anticancer activity of gemcitabine-loaded FT-SVAs was evaluated against two cancer cell lines, i.e. MCF-7 cells which over-express the folate receptor and…
MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized con…
2018
Aims To study how MTHFR 677C→T genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations. Methods 2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 μg of 5-methyl-THF, 3 mg of vitamin B6 and 20 μg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR …
Buerger`s Disease and Hyperhomocysteinemia: Is there a Relationship?
2009
Thromboangiitis obliterans, also known as Buerger's disease, is a cause of juvenile lower limb ischaemia. Buerger's disease is idiopathic and one of diagnostic criteria is the absence of atherosclerotic risk factors other than smok- ing. A possible involvement of thrombophilia has been investigated and the role of hyperhomocysteinemia is still matter of discussion. We describe 9 patients with Buerger's disease followed-up for the past 3 years. We found a significant in- crease in circulating homocysteine levels (mean: 31.6 in patients vs 8.2 μmol/L in control subjects). We also analyzed the C677T mutation of MTHFR; 5/9 Buerger's patients were heterozygotes and 4/9 homozygotes for the mutati…
Association between dietary folate intake and serum insulin-like growth factor-1 levels in healthy old women
2013
Abstract Objective High serum levels of insulin-like growth factor-1 (IGF-1) seem to coincide with higher rates of some types of cancer and the risk of all-cause mortality in old people. Eating vegetables seems to reduce IGF-1 levels because they are rich in micronutrients such as vitamins. This study investigates the possible association between vitamin intake and IGF-1 levels in a representative group of healthy elderly women with Mediterranean dietary habits. Design This cross-sectional study included 124 healthy women with a mean age of 71.3 ± 4.2 years and a mean body mass index (BMI) of 27.37 ± 3.48 kg/m 2 attending a mild fitness program twice a week at public gyms in Padova. The mai…
Exploring Chemical Reactivity in Enzyme Catalyzed Processes Using QM/MM Methods: An Application to Dihydrofolate Reductase
2015
Enzymes are the catalysts used by living organisms to accelerate chemical processes under physiological conditions. In this chapter, we illustrate the current view about the origin of their extraordinary rate enhancement based on molecular simulations and, in particular, on methods based on the combination of Quantum Mechanics and Molecular Mechanics potentials which provide a solution to treat the chemical reactivity of these large and complex molecular systems. Computational studies on Dihydrofolate Reductase have been selected as a conductor wire to present the evolution and difficulties to model chemical reactivity in enzymes. The results discussed here show that experimental observatio…
The Correlation Between Abnormal Uterine Artery Flow in the First Trimester and Genetic Thrombophilic Alteration: A Prospective Case-Controlled Pilot…
2020
Introduction. Evaluation of the first trimester uterine artery flow can predict the development of obstetrical complications. A genotype, making women prone to microthrombi. constitutes the main known susceptibility factor for anomalous development of placenta. Our aim was to study whether polymorphisms of 10 genes leading to blood clotting abnormalities are related to abnormal uterine artery blood flow in the first trimester, and may predict placenta-related diseases. Material and methods. In primary analyses we included 19 singleton pregnancies with abnormal blood flow in the uterine arteries during the first trimester of gestation, and 24 matched control with normal flow patterns. All pa…
Photogenotoxicity of folic acid.
2013
Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). FA is photoreactive and has been shown to generate DNA modifications when irradiated with UVA (360 nm) in the presence of DNA under cell-free conditions. To investigate the relevance of this reaction for cells and tissues, we irradiated three different cell lines (KB nasopharyngeal carcinoma cells, HaCaT keratinocytes, and a melanoma cell line) in the presence of FA and quantified cytotoxicity and DNA damage generation. The results indicate that FA is phototoxic and photogenotoxic by two different mechanisms. First, ext…
(18) F-labeled folic acid derivatives for imaging of the folate receptor via positron emission tomography.
2013
The folate receptor (FR) is already known as a proven target in diagnostics and therapy of cancer. Furthermore, the FR is involved in inflammatory and autoimmune diseases. The major advantage as a valuable target is its strongly limited expression in healthy tissues. Over the past two decades, several folic acid-based radiopharmaceuticals addressing the FR have been developed, and some of them show great potential for applications in clinical routine. However, most of these radiofolates were developed for single photon emission computed tomography imaging, and only a few can be used for positron emission tomography (PET) imaging. The development of suitable (18) F-labeled derivatives for PE…