Use Of FA Research Articles

Association between the Use of Folic Acid Supplements during Pregnancy and Children's Cognitive Function at 7-9 Years of Age in the INMA Cohort Study.

This study investigated the association between maternal low (<400 μg/day) or high (≥1000 μg/day) folic acid supplements (FAs) use during pregnancy and the attentional function and working memory in boys and girls at age 7–9. A longitudinal analysis based on 1609 mother–child pairs from the Spanish Infancia y Medio Ambiente Project was carried out. Multivariable regression analyses revealed that, compared to the recommended FAs use, a low FAs use during the second period of pregnancy was associated with a lower alertness in all children (β = 18.70 ms; 95% CI: 7.51; 29.89) and in girls (β = 30.01 ms; 95% CI: 12.96; 47.01), and with a lower N-back Task performance in boys (d’ number 2-back (β = −0.25; 95% CI: −0.49; 0.01)). A high FAs use throughout the two periods of pregnancy was associated with a better N-back Task performance only in girls (d’ number 2-back (β = 0.28; 95% CI: 0.01; 0.56) and d’ number 3-back (β = 0.32; 95% CI: 0.08; 0.56)). The maternal use of FAs beyond the periconceptional period may affect children’s attentional function and working memory at age 7–9 differently for boys and girls.

The Use of Lower or Higher Than Recommended Doses of Folic Acid Supplements during Pregnancy Is Associated with Child Attentional Dysfunction at 4-5 Years of Age in the INMA Project.

We assessed the association between the use of lower- and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4–5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400–999 (recommended dose), and ≥1000 μg/day. Child attentional function was assessed by Conners’ Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 μg/day was associated with higher risk of omission errors—IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 μg/day and ≥1000 μg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 μg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 μg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4–5, particularly in boys.

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

Cancer cells must adapt their metabolism in order to meet the energy requirements for cell proliferation, survival in nutrient-deprived environments, and dissemination. In particular, FA metabolism is emerging as a critical process for tumors. FA metabolism can be modulated through intrinsic changes in gene expression or signaling between tumor cells and also in response to signals from the surrounding microenvironment. Among these signals, extracellular vesicles (EVs) could play an important role in FA metabolism remodeling. In this review, we will present the role of EVs in tumor progression and especially in metabolic reprogramming. Particular attention will be granted to adipocytes. These cells, which are specialized in storing and releasing FAs, are able to shift tumor metabolism toward the use of FAs and, subsequently, increase tumor aggressiveness. Recent work demonstrates the involvement of EVs in this metabolic symbiosis.

Insulator surface modification of field-effect transistor using isolated poly(3-hexylthiophene) nanofiber

The surface modification of insulators and electrodes of field-effect transistor (FET) devices using a poly(3-hexylthiophene) (P3HT) nanofiber was investigated. The mobility of the P3HT nanofiber using an insulator surface modified by perfluorodecyltrimethoxysilane (FAS) was much larger than that modified by other reagents, i.e. octadecyltrimethylsilane (OTS) and 3-aminopropyltrimethoxysilane (APS). In addition, the threshold increased with the use of FAS and was in a normally-on state. In particular, an FET of isolated nanofibers upon insulator surface modification by FAS showed a high mobility of 6.8×10−1cm2V−1s−1.

The Involvement of Epithelial Fas in a Human Model of Graft Versus Host Disease

Graft-versus-host disease (GVHD) is an important complication occurring after hematopoietic stem-cell transplantation (HSCT). Animal model studies have shown the involvement of the Fas (APO-1/CD95)/Fas-Ligand pathway in GVHD pathogenesis, but its association with cutaneous GVHD in human remains to be established. In the present study, Fas involvement in skin damage was assessed using a human skin explant model of GVHD. Fas and FasL expression were measured by immunohistochemistry and blockade of Fas pathway was investigated using an antagonistic anti-human Fas monoclonal antibody. In addition, levels of soluble Fas (sFas) were determined in the serum of patients receiving allogeneic HSCT with and without GVHD. The results showed that Fas up-regulation in the epithelium of human skin explants correlated with graft-versus-host reaction (GVHR) in the skin explant model (P<0.001). Decreased GVHR grades were observed by using a Fas blocking monoclonal antibody. Levels of sFas were increased post-HSCT (P<0.001) but rather than being associated with the severity of GVHD, sFas levels differed with the conditioning treatments the patients received before the HSCT. Higher GVHR grades were associated with increased Fas expression in the epithelium of the skin explants. In addition, by blocking Fas-mediated apoptosis, the GVHR grades were decreased. Our study thus shows the involvement of Fas in cutaneous GVHD damage, and supports the potential use of Fas as a therapeutic target.

Activated natural killer T cells induce liver injury by Fas and tumor necrosis factor-α during alcohol consumption

Background & aims : Chronic alcohol abuse induces liver injury and increases the severity of viral hepatitis, but the precise mechanisms responsible are not well understood. In particular, little is known about the role of natural killer T cells in alcohol-induced liver injury. Natural killer T cells are mediators of important regulator and effector functions making use of Fas and tumor necrosis factor (TNF)-α in apoptosis induction. This report analyzes the role of natural killer T cells, Fas, and TNF-α in a model of chronic alcohol consumption. Methods : Mice fed alcohol by intragastric tube were assayed for serum alanine aminotransferase values, liver histology, and liver mononuclear cells before and after activation of natural killer T cells by ligand α-galactosylceramide. Results : In alcohol-consuming animals, liver natural killer T cells increase, and further activation by α-galactosylceramide causes lethal liver injury. This is explained by alcohol-induced hepatocyte sensitization to cell-mediated lysis, which develops concomitant to increased cytolytic activity of natural killer T cells. Natural killer T cell-mediated apoptosis proceeds by the Fas pathway, and Fas is essential for alcohol-associated liver injury. TNF-α plays an additional role as a defect in TNF receptor-1 inhibits alcohol-associated liver injury. Alcohol-fed natural killer T cell-deficient Jα281 −/− mice express a delay in alcohol-induced liver injury. Conclusions : Alcohol consumption induces an increase of natural killer T cells in the liver and a high sensitivity of hepatocytes to cell-mediated lysis. Stimulation of natural killer T cells during alcohol consumption induces serious liver injury by a mechanism that involves concomitant signals by Fas and tumor necrosis factor receptor-1 on alcohol-stressed hepatocytes.

Spontaneous tolerance: experience with the rat liver transplant model

Soluble major histocompatibility complex (MHC) class I antigens released from hepatocytes and the passenger leukocyte population of the liver allograft have both been considered as important contributors for spontaneous liver tolerance upon allogeneic transplantation into fully MHC-mismatched hosts. This study was conducted to delineate the role of “passenger leukocytes” (PL) as well as local intra-graft defence mechanisms of long-term accepted liver allografts in more detail. Orthotopic liver transplantation was performed in male inbred rats as follows ( n = 4–6): (i) Lewis (LEW; RT1. l) → LEW; (ii) DA (RT1. av1) → DA; (iii) DA → LEW; (iv) LEW → DA; (v) LEW (10-Gy whole body irridiation [WBI], d-7) → DA; (vi) LEW (10-Gy WBI, d-7) → LEW; (vii) LEW (10-Gy WBI, d-7) → LEW (parked for 36 hours) → DA; and (viii) LEW (10-Gy WBI, d-7) → DA (parked for 36 hours) → DA. The model specifically investigated the role of PLs as potential contributors to liver tolerance as WBI destroys this nonresident liver population. Characterization of Fas/FasL expression and the frequency of apoptotic cell death was performed by immunohistochemistry and TUNEL staining. Reverse transcriptase—polymerase chain reaction, by the use of Fas and FasL-specific cDNA probes, was performed on isolated hepatocytes of tolerized and rejected livers at various time points after transplantation. Animal survival in the various experimental groups was calculated using Kaplan-Meier survival statistics and related log-rank statistics as follows: (i) < 100 days; (ii) ≥ 100 days; (iii) > 100 days; (iv) 11.3 ± 1.0 day; (v) 9.0 ± 0.5 days; (vi) > 100 days; (vii) 5/6 > 100 days; and (viii) 8.0 ± 1.5 days. Immunohistochemistry revealed high numbers of proliferating cells in tolerized liver allografts. Apoptotic cell death of hepatocytes could be detected in both rejecting and to a lower extent in tolerized animals. Conversely, only tolerized but not rejected liver allografts revealed upregulation of FasL-expression on hepatic parenchymal cells from day 3 onwards. Irridiated LEW livers, in turn, loose their ability to survive in allogeneic DA hosts (group v) whereas they survive in syngeneic hosts (group vi), indicating that irridiation itself does not destroy the liver parenchyma. Reconstitution of irridiated LEW livers with syngeneic (group vii) but not with allogeneic (group viii) PLs restored tolerance induction. The underlying mechanisms of immune-privilege observed with liver allografts appear to share characteristics of clonal exhaustion suggesting that alloreactive lymphocytes are depleted by AICD via the FasL/Fas signal transduction pathway. The high frequency of apoptotic lymphocytes found in the portal tract of tolerized (but not rejected) LEW grafts supposes that functional FasL expression on graft hepatocytes mediates specific elimination of graft-directed effector lymphocytes. This mechanism constitutes peripheral deletion as one of the possible tolerogenic mechanisms involved. Chimerical liver grafts consisting of donor (LEW) parenchyma and host (DA) passenger leukocytes loose their tolerogenic capacity. In contrast, syngeneic reconstitution with LEW-PLs, restores liver graft acceptance upon transplantation into allogeneic DA hosts. This phenomenon is not relying on the induction of micro- or macrochimeric hosts, as no LEW PLs were found in spleen, thymus or the blood compartment from long-term surviving DA rats. Thus, non-resident liver cells contribute significantly to liver graft acceptance. Subsequently, liver tolerance appears to be mainly induced in the graft itself.