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1
KESBEKE, FANJA, PETER J. M. HAASTERT, RENÉ J. W. DE WIT, and B. EWA SNAAR-JAGALSKA. "Chemotaxis to cyclic AMP and folic acid is mediated by different G proteins in Dictyostelium discoideum." Journal of Cell Science 96, no. 4 (August 1, 1990): 668–73. http://dx.doi.org/10.1242/jcs.96.4.668.
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Mutant Frigid A (fgdA) of Dictyostelium discoideum is defective in a functional Ga2 subunit of a G protein and is characterized by a complete blockade of the cyclic AMP-mediated sensory transduction steps, including cyclic AMP relay, chemotaxis and the cyclic GMP response. Folic acid-mediated transmembrane signal transduction was investigated in this mutant; the results show that: (1) cell surface folic acid receptors are present in fgdA mutants. (2) Folic acid induces intracellular responses, including activation of guanylate cyclase and chemotaxis. (3) The inhibitory effect of GTP on folic acid binding to membranes is present. (4) GTPγS binding and highaffinity GTPase are stimulated by folic acid. These data strongly suggest that folic acid receptors are coupled to guanylate cyclase and chemotaxis via a Ga protein that is different from Ga2. The results imply that surface receptors for cyclic AMP and folic acid are coupled to different G proteins.
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Selhub, J., S. Nakamura, and F. A. Carone. "Renal folate absorption and the kidney folate binding protein. II. Microinfusion studies." American Journal of Physiology-Renal Physiology 252, no. 4 (April 1, 1987): F757—F760. http://dx.doi.org/10.1152/ajprenal.1987.252.4.f757.
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Surface proximal convoluted tubules (PCT) in rats were microinfused in situ with [3H]folic acid to study the role of folate binding protein (FBP) in the kidney brush-border membrane for renal conservation and transport of folate [3H]folic acid absorption was linearly related to tubular length of PCT and occurred largely in this segment of the tubule. Unlabeled folate derivatives inhibited [3H]folic acid absorption, the extent of which was dependent on the type of unlabeled folate used and its concentration. At equivalent concentrations, inhibition was most effective with unlabeled folic acid, slightly lower than with 5-methyltetrahydrofolate and least effective with methotrexate. Comparisons between [3H]folic acid absorption before and after infusion of a saturating dose of unlabeled folic acid or repetitive injections of [3H]folic acid into the same tubular site revealed continuous and rapid regeneration of unsaturated folic acid uptake sites with an apparent half-life of 28.75 +/- 8.75 s. Determination of [3H] retained in the tubule at various periods after microinfusion of [3H]folic acid revealed slow cellular disappearance with an apparent half-life of 47.3 +/- 5.4 min. It is proposed that the brush-border FBP functions as a receptor of infused folic acid and that following the binding of the ligand the folic acid/FBP complex undergoes a rapid change that results in the internalization of folic acid and regeneration of unsaturated binding sites at the membrane surface. Internalized folic acid is slowly released into renal capillaries.
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Yao, Weijing, Qian Zha, Xu Cheng, Xin Wang, Jun Wang, and Rupei Tang. "Folic acid-conjugated soybean protein-based nanoparticles mediate efficient antitumor ability in vitro." Journal of Biomaterials Applications 31, no. 6 (November 23, 2016): 832–43. http://dx.doi.org/10.1177/0885328216679571.
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In this study, soy protein isolate was hydrolyzed by compound enzymes to give aqueous soy protein with low molecular weights. Folic acid modified and free soy protein nanoparticles were successfully prepared by a desolvation method as target-specific drug delivery, respectively. Ultraviolet spectrophotometry demonstrated that folic acid was successfully grafted onto soy protein. The shape and size of folic acid modified soy protein nanoparticles were detected by transmission electron microscopy, scanning electron microscope, and dynamic light scattering. In addition, a series of characteristics including kinetic stability, pH stability, and time stability were also performed. Doxorubicin was successfully loaded into folic acid modified soy protein nanoparticles, and the encapsulation and loading efficiencies were 96.7% and 23%, respectively. Doxorubicin-loaded folic acid modified soy protein nanoparticles exhibited faster drug release rate than soy protein nanoparticles in PBS solution (pH = 5). The tumor penetration and antitumor experiments were done using three-dimensional multicellular tumor spheroids as the in vitro model. The results proved that folic acid modified soy protein nanoparticles display higher penetration and accumulation than soy protein nanoparticles, therefore possessing efficient growth inhibitory ability against multicellular tumor spheroids.
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Wang, Zhenglin, Wei Xing, Yongli Song, Hongli Li, Yonggang Liu, Yong Wang, Chun Li, Yun Wang, Yan Wu, and Jing Han. "Folic Acid Has a Protective Effect on Retinal Vascular Endothelial Cells against High Glucose." Molecules 23, no. 9 (September 12, 2018): 2326. http://dx.doi.org/10.3390/molecules23092326.
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Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously affects the life quality of patients. Because of the damage caused by DR, there is an urgent need to develop effective drugs. Folic acid, a water-soluble vitamin, is one of the vitamin B complexes. Folic acid is widely found in the meat and vegetables. In the clinic, low folic acid levels in the body may have a certain correlation with DR. However, there is no relevant basic research proving a relationship between folic acid levels and DR. The purpose of this study was therefore to investigate whether folic acid has a protective effect on the retinal vascular endothelial cells against high glucose levels. Moreover, the molecular mechanism of action of folic acid was further explored. The results showed that folic acid significantly suppressed the cell viability, tube length, migrated cells and the percentage of BrdU+ cells compared with the high glucose group. Moreover, folic acid decreased the mRNA expression of TEAD1 and the protein expression of TEAD1 and YAP1. These findings indicate that folic acid can protect retinal vascular endothelial cells from high glucose-induced injury by regulating the proteins in the Hippo signaling pathway.
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Mikkelsen, Tina B., Merete Osler, and Sjurdur F. Olsen. "Validity of protein, retinol, folic acid and n–3 fatty acid intakes estimated from the food-frequency questionnaire used in the Danish National Birth Cohort." Public Health Nutrition 9, no. 6 (September 2006): 771–78. http://dx.doi.org/10.1079/phn2005883.
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AbstractObjectiveTo validate intakes of protein, folic acid, retinol and n–3 fatty acids estimated from a food-frequency questionnaire in week 25 of pregnancy (FFQ-25).DesignValidation was done against a 7-day weighed food diary (FD) and biomarkers of the nutrients in gestation week 32–38.Subjects and settingThe FFQ-25 to be validated was used in the Danish National Birth Cohort comprising 101 042 pregnant Danish women, of whom 88 participated in the present validation study.ResultsEstimated intakes of protein, retinol and folic acid did not differ significantly between the two dietary methods, but intake of n–3 fatty acids was one third larger when estimated from the FFQ-25. The intakes estimated from the two dietary methods were all significantly correlated, ranging from 0.20 for retinol intake to 0.57 for folic acid intake. Sensitivities of being correctly classified into low and high quintiles were between 0.22 and 0.77, and specificities were between 0.62 and 0.89. Urinary protein content did not correlate significantly with protein estimated from the FFQ (r = 0.17, P > 0.05), but did with intake estimated from the FD (r = 0.56, P < 0.0001). Erythrocyte folate correlated significantly with the estimated total intake from the FFQ (r = 0.55, P < 0.0001) and the FD (r = 0.52, P < 0.0001). No correlations with plasma retinol were found. Erythrocyte eicosapentaenoic acid (C20:5n-3) correlated significantly with n–3 fatty acids intake estimated from both the FFQ-25 (r = 0.37, P < 0.001) and the FD (r = 0.62, P < 0.0001).ConclusionThe FFQ-25 gives reasonable valid estimates of protein, retinol and folic acid intakes, but seems to overestimate intake of n–3 fatty acids.
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Ma, Lingling, Tiecheng Gao, Hao Cheng, Ning Li, Weining Huang, and Li Liang. "Encapsulation of Folic Acid and α-Tocopherol in Lysozyme Particles and Their Bioaccessibility in the Presence of DNA." Antioxidants 12, no. 3 (February 24, 2023): 564. http://dx.doi.org/10.3390/antiox12030564.
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Protein particles have been reported as the potential carriers for the co-encapsulation of bioactive components. In this study, lysozyme, a basic protein, was used to simultaneously encapsulate folic acid and α-tocopherol at pH 4.0. The encapsulation efficiency and loading capacity of folic acid or α-tocopherol increased with its respective concentration. Folic acid had no influence on the encapsulation of α-tocopherol. However, the encapsulation of folic acid was improved by α-tocopherol below 40 μg/mL but reduced by α-tocopherol at higher concentrations. The encapsulation by lysozyme shielded folic acid, α-tocopherol, or both partially from the attack of 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation. No masking effect of lysozyme encapsulation on α-tocopherol was found in DPPH antioxidant activity assay. Furthermore, the DNA coating was used to improve the dispersion of lysozyme with folic acid and α-tocopherol. The lysozyme/DNA particles with folic acid and α-tocopherol showed a homogenous size distribution of 180–220 nm with ζ-potential values between −33 and −36 mV. The release and bioaccessibility of folic acid in lysozyme/DNA with α-tocopherol were similar to that of folic acid alone, while the release of α-tocopherol was delayed and its bioaccessibility was improved by encapsulation in lysozyme/DNA with folic acid. The data gathered here would provide guidance for the use of lysozyme-based co-encapsulating carriers in the development of functional foods.
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Xu, Yajun, Yunan Tang, and Yong Li. "Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice." British Journal of Nutrition 99, no. 3 (March 2008): 455–61. http://dx.doi.org/10.1017/s0007114507812074.
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Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration and the protective effect of folic acid using proteomic techniques. Alcohol (5·0 g/kg) was given intragastrically from gestational day (GD) 6 to15, with or without 60·0 mg folic acid/kg given intragastrically during GD1–16 to pregnant Balb/c mice. The control group received distilled water only. Results of litter evaluation on GD18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol. Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in energy production, signal pathways and protein translation, which are all important for central nervous system development.
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Zhang, Zhanpeng. "Progress of Folic Acid-Folate Receptor as Drug Carriers in Targeted Drug Delivery System." SHS Web of Conferences 144 (2022): 01002. http://dx.doi.org/10.1051/shsconf/202214401002.
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Targeted drug delivery system is an effective method for the diagnosis and treatment of cancer, it has received much attention because of its low side effects and therapeutic efficacy. Folic acid receptor is highly expressed on the surface of most cancer cells, but is low or not expressed on the surface of normal cells, and the ligand folate has a high affinity. Folic acid receptor is attached to drug carriers and can be targeted to cancer cells. This paper introduces folic acid and folate receptors, briefly describes the mechanism of action of folic acid receptor-mediated targeted drug delivery, discusses the progress on four types of folic acid-folate receptor-mediated cancer treatment: folate acid-conjugated magnetic nanoparticles, drug binding of small-molecule folic acid, folic acid receptor-bound protein, and folic acid-conjugated polysialic acid. It also analyzes the favorable points and future development trends of each treatment mechanism.
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Turek, J. J., C. P. Leamon, and P. S. Low. "Endocytosis of folate-protein conjugates: ultrastructural localization in KB cells." Journal of Cell Science 106, no. 1 (September 1, 1993): 423–30. http://dx.doi.org/10.1242/jcs.106.1.423.
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It has been demonstrated that proteins covalently conjugated to folic acid may be taken up by cells via endocytosis after binding to a folate binding protein (FBP) in the cell membrane. The proteins taken up in this manner remain catalytically active and they may modify physiological processes occurring in the cytosol. Confocal fluorescence microscopy of KB cells incubated with FITC-bovine serum albumin-folic acid conjugates showed that after uptake, the conjugates resided in large vesicular structures. The purpose of the present study was to determine the subcellular localization of protein-folic acid conjugates in KB cells using folic acid-bovine serum albumin-colloidal gold (F-BSA-CG) as a tracer. F-BSA-CG conjugates were taken up via uncoated pits or caveolae, and resided primarily in multivesicular bodies (MVBs) and other tubular endosomes at early time points (15-60 min). At later time points (6 hours), conjugates were still contained in MVBs but some were also found in secondary lysosomes or free in the cytoplasm. Coincubation of KB cells with transferrin-colloidal gold (TF-CG) and F-BSA-CG resulted in colocalization of TF-CG and F-BSA-CG within endosomal elements at times later than 15 minutes, indicating that the caveolae-mediated F-BSA-CG endocytic pathway converged with a pathway utilized by clathrin-coated pits.
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Huang, Xiaoli, Shu Gao, Wei Xia, Shaoying Hou, and Kun Wu. "Folic acid facilitates in vitro maturation of mouse and Xenopus laevis oocytes." British Journal of Nutrition 109, no. 8 (August 30, 2012): 1389–95. http://dx.doi.org/10.1017/s0007114512003248.
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The water-soluble B vitamins, folate and folic acid, play an important role in reproductive health, but little is known about the effects of folic acid on infertility. The present study tested the hypothesis that folic acid affects oocyte maturation, a possible cause of female infertility. We have studied the in vitro maturation of mouse and Xenopus oocytes. Hypoxanthine (Hx) was used as an inhibitor of mouse oocyte maturation to mimic in vivo conditions by maintaining high levels of cyclic-AMP. The frequency of first polar body (PB1) formation and germinal vesicle breakdown (GVBD) in mouse oocytes was decreased by Hx. This effect was counteracted by folic acid added to the medium. PB1 extrusion and GVBD percentages rose to 27·7 and 40·0 % from 12·8 and 19·9 %, respectively, by exposure to 500 μm-folic acid. Folic acid also restored the spindle configuration, which had been elongated by Hx, as well as normalising the distribution of cortical granules (CG). In folic acid-treated Xenopus eggs, extracellular signal-regulated kinase 1 was phosphorylated, cyclin B2 and Mos were up-regulated and the frequency of GVBD was accelerated. Taken together, the findings suggest that folic acid facilitates oocyte maturation by altering the expression and phosphorylation of proteins involved in M-phase-promoting factor and mitogen-activated protein kinase pathways, as well as causing changes in spindle configuration and CG migration.
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Lam, Tsz Yan, Sai Wang Seto, Alice Lai Shan Au, Christina Chui Wa Poon, Rachel Wai Sum Li, Ho Yeung Lam, Wing Sze Lau, et al. "Folic Acid Supplementation Modifies β-Adrenoceptor–Mediated In Vitro Lipolysis of Obese/Diabetic (+db/+db) Mice." Experimental Biology and Medicine 234, no. 9 (September 2009): 1047–55. http://dx.doi.org/10.3181/0902-rm-44.
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The effects of folic acid (5.7 and 71 μg/kg, 4 weeks) consumption on the β-adrenoceptors (β-ARs)–elicited lipolysis in vitro of the abdominal adipocytes of lean/control (+ m/+ db) and obese/diabetic (+ db/+ db) mice (female) were investigated. β-AR agonists (salbutamol, a β2-AR agonist; BRL 37344 and CGP 12177, β3-AR agonists; adrenaline, a β-AR agonist)–mediated lipolysis, β2-, and β3-ARs protein expression of the adipose tissues after folic acid consumption were evaluated. Our results demonstrate that a smaller magnitude of the basal (spontaneous) and the β-AR agonists–triggered lipolysis was observed in + db/+ db mice, and folic acid supplementation (71 μg/kg) resulted in an improvement of both the baseline and the β-ARs–mediated lipolysis. In controls, a lower β2-and β3-ARs protein expression of the adipose tissues was detected in + db/+ db mice, compared to + m/+ db mice. In both strains fed with folic acid (71 μg/kg), a reduction of β2-AR protein expression was observed compared to the respective controls. In + db/+ db mice, folic acid (5.7 and 71 μg/kg) consumption caused a dose-dependent increase of β3-AR protein expression compared to controls. We demonstrate that lipolysis elicited by β-AR (β2- and β3-ARs) agonists was blunted in + db/+ db mice. Folic acid consumption has significant modulatory effects on β-ARs protein expression and lipolysis.
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Maryati, Yati, and Agustine Susilowati. "Changes in folate characteristics and its identification in broccoli (Brassica oleracea Italica) extract fermented by Lactic Acid Bacteria Mixed Culture (LAB)." MATEC Web of Conferences 154 (2018): 04001. http://dx.doi.org/10.1051/matecconf/201815404001.
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Broccoli (Brassica oleracea Italica) was fermented by cultures of lactic acid bacteria (LAB) as a potential source of natural folic acid. This study aimed to evalte characteristic changes and to identify folate compounds from broccoli extract, fermented by mixed LAB cultures (L. bulgaricus, S. thermophulus, L.acidophilus, Bd. bifidum). The formulation of broccoli extract was fermented with variation of LAB starter culture with concentrations of 10 and 20%(v/v), and the change of characteristic of folic acid compound during fermentation (0 to 48 hours) with an interval of 8 hours was evaluated. The results showed that the fermentation of broccoli extract with different concentration of LAB culture had an effect on the concentration of folic acid produced, as well as the change of concentration of folic acid during the fermentation time interval. The optimum condition was obtained based on the highest folic acid concentration of 6.74%, at culture concentration of 20% during 24 hour fermentation with the value of folic acid concentration of 72.11 μg/mL, pH value of 4.29, total sugars of 34.61%, total acids of 0, 97%, dissolved protein of 14.64 mg/mL and total LAB of log 13.02 + 0.05 cfu / ml.
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Jiao, Baihai, Changlong An, Hao Du, Melanie Tran, Penghua Wang, Dong Zhou, and Yanlin Wang. "STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy." Cells 10, no. 11 (November 6, 2021): 3057. http://dx.doi.org/10.3390/cells10113057.
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Renal fibrosis is a pathologic feature of chronic kidney disease, which can lead to end-stage kidney disease. Myeloid fibroblasts play a central role in the pathogenesis of renal fibrosis. However, the molecular mechanisms pertaining to myeloid fibroblast activation remain to be elucidated. In the present study, we examine the role of signal transducer and activator of transcription 6 (STAT6) in myeloid fibroblast activation, macrophage polarization, and renal fibrosis development in a mouse model of folic acid nephropathy. STAT6 is activated in the kidney with folic acid nephropathy. Compared with folic-acid-treated wild-type mice, STAT6 knockout mice had markedly reduced myeloid fibroblasts and myofibroblasts in the kidney with folic acid nephropathy. Furthermore, STAT6 knockout mice exhibited significantly less CD206 and PDGFR-β dual-positive fibroblast accumulation and M2 macrophage polarization in the kidney with folic acid nephropathy. Consistent with these findings, STAT6 knockout mice produced less extracellular matrix protein, exhibited less severe interstitial fibrosis, and preserved kidney function in folic acid nephropathy. Taken together, these results have shown that STAT6 plays a critical role in myeloid fibroblasts activation, M2 macrophage polarization, extracellular matrix protein production, and renal fibrosis development in folic acid nephropathy. Therefore, targeting STAT6 may provide a novel therapeutic strategy for fibrotic kidney disease.
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Wang, Ding, Merlin D. Lindemann, and Mark J. Estienne. "Effect of Folic Acid Supplementation and Dietary Protein Level on Growth Performance, Serum Chemistry and Immune Response in Weanling Piglets Fed Differing Concentrations of Aflatoxin." Toxins 12, no. 10 (October 9, 2020): 651. http://dx.doi.org/10.3390/toxins12100651.
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Effects of folic acid and protein levels on growth and serum chemistry in pigs fed aflatoxin were determined in two experiments. Increasing aflatoxin (250 to 800 ppb) decreased (P < 0.05) weight gain and feed intake for both of the 35-day trials. In Experiment 1, increasing aflatoxin (0, 250, 500 ppb), increased linearly (P < 0.05) aspartate aminotransferase (AST), alkaline phosphatase (ALKP) and ɣ-glutamyl transferase (GGT). Folic acid (0, 2.0, 5.0, 12.5 ppm) increased linearly (P < 0.05) serum K, Ca, P, Mg, and AST with the largest effect observed at 12.5 ppm. Folic acid decreased (P < 0.05) blood urea nitrogen (BUN): creatinine and Na:K. In Experiment 2, aflatoxin (800 ppb) increased (P < 0.05) glucose and GGT, and decreased (P < 0.05) Na:K and albumin:globulin. Increasing protein from 15 to 18% elevated BUN: creatinine (P < 0.05), albumin: globulin (P < 0.05), albumin (P < 0.05) and ALKP (P < 0.05). Folic acid (2 ppm) elevated (P < 0.05) BUN, and interacted with both aflatoxin (P < 0.10) and protein (P < 0.05) on BUN. Adding folic acid to aflatoxin contaminated diets improved some measures of clinical chemistry in Experiment 1 but not traditional growth performance measures. The higher protein level reduced the effects of aflatoxicosis on growth.
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Aspiyanto, Aspiyanto, Agustine Susilowati, Puspa Dewi Lotulung, Hakiki Melanie, and Yati Maryati. "Potency of Stirred Microfiltration Cell in Separation of Fermented Beans as Protein Isolate for Natural Source of Folic Acid." Indonesian Journal of Chemistry 19, no. 1 (January 29, 2019): 9. http://dx.doi.org/10.22146/ijc.25164.
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Protein isolate from soy bean (Glycine soja L.) tempeh, mung bean (Phaseolus radiatus L.) tempeh and kidney bean (Phaseolus vulgaris L.) tempeh are natural source of folic acid with main role in brain smartness. 0.15 µm microfiltration (MF) membrane fitted in dead-end stirred microfiltration cell (SMFC) was able to separate protein isolate from three (3) kinds of tempeh at stirrer rotation speed 400 rpm, room temperature and pressure 40 psia for 30 minutes. The result of experimental work showed that SMFC had potential use in separation of protein isolate affected by kinds of bean and membrane performance on isolate composition in retentate and permeate. SMFC was able to retain better protein isolate in retentate than that passing across permeate. Retentate of protein isolate from soy bean tempeh, mung bean tempeh and kidney bean tempeh had subsequently compositions of folic acid 362.07, 254.07 and 506.07 µg/mL, total solids 5.56, 4.08 and 1.82 %, N-Amino 4.34, 3.36 and 0.56 mg/mL, and dissolved protein 0.79, 0.34 and 0.72 mg/mL. In this process condition, SMFC was able to increase folic acid in protein isolate retentate of soy tempeh of 0.59 times, mung bean tempeh of 1.1 times and kydney bean tempeh of 1.42 times before purification process in retentate. Based on both SMFC performance and efficiency, all the best purification optimization were obtained kidney beans tempeh. Identification of monomer of kidney bean tempeh protein isolate gave monomers of folic acid, glutamic acid and folic acid fractionation with molecular weight of 443.5797, 148.1643 and 221.2132 Da. and relative intensity of 1.28, 50.11 and 7.05 %, respectively.
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Bourassa, P., P. Chanphai, and H. A. Tajmir-Riahi. "Folic acid delivery by serum proteins: loading efficacy and protein morphology." Journal of Biomolecular Structure and Dynamics 35, no. 16 (November 25, 2016): 3499–506. http://dx.doi.org/10.1080/07391102.2016.1259589.
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Ratajczak, Alicja Ewa, Aleksandra Szymczak-Tomczak, Anna Maria Rychter, Agnieszka Zawada, Agnieszka Dobrowolska, and Iwona Krela-Kaźmierczak. "Does Folic Acid Protect Patients with Inflammatory Bowel Disease from Complications?" Nutrients 13, no. 11 (November 12, 2021): 4036. http://dx.doi.org/10.3390/nu13114036.
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Folic acid, referred to as vitamin B9, is a water-soluble substance, which participates in the synthesis of nucleic acids, amino acids, and proteins. Similarly to B12 and B6, vitamin B9 is involved in the metabolism of homocysteine, which is associated with the MTHFR gene. The human body is not able to synthesize folic acid; thus, it must be supplemented with diet. The most common consequence of folic acid deficiency is anemia; however, some studies have also demonstrated the correlation between low bone mineral density, hyperhomocysteinemia, and folic acid deficiency. Patients with inflammatory bowel disease (IBD) frequently suffer from malabsorption and avoid certain products, such as fresh fruits and vegetables, which constitute the main sources of vitamin B9. Additionally, the use of sulfasalazine by patients may result in folic acid deficiency. Therefore, IBD patients present a higher risk of folic acid deficiency and require particular supervision with regard to anemia and osteoporosis prevention, which are common consequences of IBD.
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Susilowati, Agustine, Puspa Dewi Lotulung, Yati Maryati, and Aspiyanto. "Modification process in nixtamalization of folic acid-rich dent corn (Zea mays identata) and its identification as smart food fortificant." MATEC Web of Conferences 154 (2018): 01017. http://dx.doi.org/10.1051/matecconf/201815401017.
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A modification on nixtamalization process of dent corn (Zea mays identata) was conducted in order to recover natural folic acid-rich corn. Nixtamalization process on varieties of white dent corn and yellow dent corn subsequently were performed by steeping solution of Ca(OH)2 at concentrations of 0, 10, 20 and 30 % (w/w corn dissolved protein) for 18 hours, and boiling at 90 °C for 15, 30, 45 and 60 minutes. Result of research showed that concentration of Ca(OH)2 solution becoming more and more high and long boiling time increased both folic acid and reducing sugar, dropped total solids and total sugar, and fluctuated dissolved protein for both types of corn. Nixtamalization optimalization of white dent corn and yellow dent corn were achieved at combination of Ca(OH)2 20 % (w/w corn dissolved protein) for 60 minutes of boiling and Ca(OH)2 30 % for 30 minutes of boiling and gave folic acid of 466.81 and 506.74 μg/mL, respectively. In this condition, it is occurred an increase of folic acid 192.3 % (1.9 folds) and 139.89 % (1.4 folds) when compared to initial material of corn. Identification on folic acid monomer and glutamic acid monomer of both nixtamalized dent corn and yellow dent corn at optimum operation condition displayed domination of folic acid monomer with molecular weight (MW) 442.56 Dalton (Da.) with relative intensity 25.51 %, and 441.73 Da. with relative intensity 100 %, while glutamic acid monomer of nixtamalized yellow dent corn and nixtamalized white dent corn were dominated by monomer with MWs of 148.27 Da. and 148.32 Da., and relative intensity 3.73 and 1.8 %.
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Kuo, Ko-Lin, Chin-Wei Chiang, Yi-Ming Arthur Chen, Chih-Chin Yu, and Tzong-Shyuan Lee. "Folic Acid Ameliorates Renal Injury in Experimental Obstructive Nephropathy: Role of Glycine N-Methyltransferase." International Journal of Molecular Sciences 24, no. 7 (April 6, 2023): 6859. http://dx.doi.org/10.3390/ijms24076859.
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Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and GNMT knockout (GNMT−/−) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast, GNMT−/− mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in GNMT−/− mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target.
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Blakeborough, Peter, and Dallyn N. Salter. "Folate transport in enterocytes and brush-border-membrane vesicles isolated from the small intestine of the neonatal goat." British Journal of Nutrition 59, no. 3 (May 1988): 485–95. http://dx.doi.org/10.1079/bjn19880058.
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1. The uptake of 5-methyltetrahydrofolate (MTHF) and folic acid (pteroylmonoglutamate) by enterocytes and brush-border-membrane vesicles prepared from the small intestine of the 6-d-old male goat was determined using a rapid-filtration assay.2. Both MTHF and folic acid were taken up by membrane vesicles at 25° and enterocytes at 37° by a pH-dependent mechanism with maximum uptake when the pH of the incubation medium was 5·0.3. Experiments in which the osmotic pressure of the medium was raised in successive increments with the non-absorbable sugar cellobiose indicated that transport rather than membrane binding was the main component of uptake.4. Experiments at pH 5·0 showed that uptake of MTHF and folic acid was saturable and that the characteristics of folate transport were similar in both tissue preparations: (a) transport rates of both MTHF and folic acid were constant during the first 1-2 min for a given folate concentration, then declined to reach a steady-state in 10-30 min; (b) initial velocities of transport of MTHF and folic acid increased in proportion to their concentrations up to 7-10 μM, but the rate of increase slowed thereafter until saturation was reached at 20-25 μM (Km for brushborder-membrane vesicles 40·8 and 62·9 μM, Km for enterocytes 50·9 and 55·2 μM for MTHF and folic acid respectively). Values of Vmax for membrane vesicles (pmol/mg protein per min) were 46·5 MTHF or 40·3 folic acid; enterocytes Vmax (pmol/107 cells per min) 15·9 MTHF or 30·6 folic acid; (c) uptake of MTHF and folic acid by brush-border-membrane vesicles and enterocytes measured under steady-state conditions approached saturation at 50 μM for each analogue (Km for membrane vesicles 58·1 and 55·2 μM, Km for enterocytes 43·1 and 49·4 μM for MTHF and folic acid respectively; Vmax for membrane vesicles 49·7 and 77·8 pmol/mg protein, for enterocytes 52·8 and 54·7 pmol/107 cells for MTHF and folic acid respectively).5. It was concluded that transport of MTHF and folic acid was by a similar pH-dependent mechanism both in brush-border-membrane vesicles and in intact enterocytes. At pH 5·0, transport involved a saturable carrier-mediated process located in the brush-border membrane.
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Wang, Hexian, Qiang Fan, Longlong Zhang, Danli Shi, Haibo Wang, Shoulian Wang, and Bangjian Bian. "Folate-targeted PTEN/AKT/P53 signaling pathway promotes apoptosis in breast cancer cells." Pteridines 31, no. 1 (October 17, 2020): 158–64. http://dx.doi.org/10.1515/pteridines-2020-0020.
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AbstractObjective Folate deficiency is closely related to the occurrence of human tumors and plays an important role in cell growth, differentiation, repair, and host defense. We studied the effects of folic acid on the apoptosis of breast cancer cells (MDA-MB-231) and on the activity of the PTEN/AKT/P53 signaling pathway in breast cancer cells.Methods Breast cancer cells (MDA-MB-231) were treated with folate alone or in combination with a PTEN specific inhibitor, SF1670. Cell viability was detected by a MTT assay, and the expression levels of apoptosis-related proteins and PTEN/AKT/P53 signaling pathway were detected via Western blot analysis. Rate of apoptosis was measured via cytometry.Results Folic acid inhibited the cell viability of MDAMB-231 cells and the expressions of Bcl-2 and p-AKT proteins and upregulate the expression of Bax, PTEN, and P53 proteins, thereby inducing apoptosis in these cells. SF1670 treatment inhibited the expressions of Bcl-2 and p-AKT protein and upregulate Bax, PTEN, and P53 protein expression.Conclusion Folic acid has cytotoxic effects on MDAMB-231 cells and can induce apoptosis by targeting the PTEN/AKT/P53 signaling pathway.
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He, Lijie, Qian Wang, Daniel Mandler, Musen Li, Rabah Boukherroub, and Sabine Szunerits. "Detection of folic acid protein in human serum using reduced graphene oxide electrodes modified by folic-acid." Biosensors and Bioelectronics 75 (January 2016): 389–95. http://dx.doi.org/10.1016/j.bios.2015.08.060.
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Huot, Pedro S. P., Anna Ly, Ignatius M. Y. Szeto, Sandra A. Reza-López, Daniel Cho, Young-In Kim, and G. Harvey Anderson. "Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner." Applied Physiology, Nutrition, and Metabolism 41, no. 4 (April 2016): 411–20. http://dx.doi.org/10.1139/apnm-2015-0503.
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Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring’s metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring’s diet with that of the maternal diet. Female Sprague–Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.
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Kobue-Lekalake, Rosemary, Oduetse Daniel Gopadile, Gulelat Desse Haki, Eyassu Seifu, Moenyane Molapisi, Bonno Sekwati-Monang, John Gwamba, Kethabile Sonno, Boitumelo Mokobi, and Geremew Bultosa. "Effects of Bambara groundnut and butternut blend on proximate, mineral, beta-carotene and folic acid contents of sorghum flour." AIMS Agriculture and Food 7, no. 4 (2022): 805–18. http://dx.doi.org/10.3934/agrfood.2022049.
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<abstract> <p>The refined sorghum flour (SF) used is limited in fiber and micronutrients because of bran removal during milling, and protein digestibility is poor due to kafrin crosslinking. In this research, the effects of Bambara groundnut (BG) (15%, 25%, 35%) and butternut (BU) powder (23%) blending on SF were investigated, using 100% SF as a control. The proximate, mineral, beta-carotene and folic acid compositions of the flour mix were determined. As the BG levels increased, the protein, fat, fiber, and ash contents increased significantly (p < 0.05), ranging between 8.62–14.19%, 2.36–3.38%, 1.37–3.04% and 0.87–2.19%, respectively. The iron, zinc, calcium and phosphorus contents in mg/100 g were 3.43–5.08, 2.96–3.74, 80.00–106.67 and 150.63–594.53, respectively. The beta-carotene (mg/100 g) and folic acid (μg/100 g) contents were < 0.01–0.63 and 0.75–1.42, respectively. The mineral, beta-carotene and folic acid contents of the flour mix varied significantly (p < 0.05) from the control. The pro-vitamin A beta-carotene content was improved in the blend flours with the addition of BU powder, whereas, in the control sample, it was not detected (<0.01 mg/100 g). With the 35% BG blend, increases of 37% protein, 45% crude fiber, 48% iron, 26% zinc, 133% calcium and 154% folic acid contents from the control were observed. The study showed food-to-food fortification of SF with BG flour and BU powder has the potential to combat malnutrition, and the public health challenges associated with deficiencies in bioactive fibers, proteins and micronutrients (pro-vitamin A carotenoids, folic acid and minerals).</p> </abstract>
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Pellis, Linette, Yvonne Dommels, Dini Venema, Ab van Polanen, Esther Lips, Hakan Baykus, Frans Kok, Ellen Kampman, and Jaap Keijer. "High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells." British Journal of Nutrition 99, no. 4 (September 10, 2007): 703–8. http://dx.doi.org/10.1017/s0007114507824147.
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Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12and other micronutrients involved in the folate–methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.
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Venter, F. S., H. Cloete, J. V. Seier, M. J. Faber, and J. E. Fincham. "Folic acid and vitamin B12 status of vervet monkeys used for nutritional research." Laboratory Animals 27, no. 1 (January 1, 1993): 59–64. http://dx.doi.org/10.1258/002367793781082386.
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Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys ( Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12·8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90·7, 132·3 and 152·8 ng/ml, respectively. A megadose of 25·6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml.
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Burdge, Graham C., Karen A. Lillycrop, Alan A. Jackson, Peter D. Gluckman, and Mark A. Hanson. "The nature of the growth pattern and of the metabolic response to fasting in the rat are dependent upon the dietary protein and folic acid intakes of their pregnant dams and post-weaning fat consumption." British Journal of Nutrition 99, no. 3 (March 2008): 540–49. http://dx.doi.org/10.1017/s0007114507815819.
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The nutritional cues which induce different phenotypes from a single genotype in developing offspring are poorly understood. How well prenatal nutrient availability before birth predicts that after birth may also determine the offspring's response to later metabolic challenge. We investigated the effect of feeding pregnant rats diets containing protein at 180 g/kg (Control) or 90 g/kg (protein-restricted, PR) and either 1 or 5 mg folic acid/kg on growth and metabolic response to fasting in their offspring, and also the effect of diets with different fat contents (40 g/kg (Fat4) or 100 g/kg (Fat10)) after weaning. Offspring of dams fed the PR diet with 5 mg/kg folic acid were significantly lighter than other offspring. The PR offspring fed the Fat4diet had lower plasma TAG than the Control offspring, but this relationship was reversed when offspring were fed Fat10. Increasing the folic acid content of the Control or PR maternal diets induced opposing effects on plasma TAG, NEFA, β-hydroxybutyrate and glucose concentrations in offspring fed Fat4. The effect was accentuated in offspring fed the Fat10diet such that these metabolites were increased in the Control offspring, but reduced in the PR offspring. These data show for the first time that maternal dietary folic acid intake alters offspring phenotype depending upon dietary protein intake, and that this effect is modified by fat intake after weaning. Prevention by increased folic acid intake of an altered metabolic phenotype by maternal protein-restriction may be at the expense of somatic growth.
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Shikh, E. V., A. A. Makhova, N. N. Eremenko, G. V. Ramenskaya, and O. B. Dorogun. "Rational combinations in pharmacotherapy for iron deficiency." Voprosy ginekologii, akušerstva i perinatologii 22, no. 3 (2023): 108–16. http://dx.doi.org/10.20953/1726-1678-2023-3-108-116.
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Iron deficiency remains one of the most common deficiencies worldwide. An inadequate and unbalanced diet may cause a lack of other nutrients necessary for hematopoiesis, which increases the risk of iron deficiency and makes it difficult to treat. Various pharmacotherapeutic approaches are being studied and applied, including combination medications, which in addition to iron consist of folic acid, copper/manganese gluconate, ascorbic acid, multivitamins, serine, and cyanocobalamin. Folate is a component that affects both the efficacy and safety of pharmacotherapy for iron deficiency. Preclinical animal studies comparing the dynamics of hematological indices confirmed a more rapid achievement of target values with the simultaneous use of iron and folic acid. Clinical studies in a group of pregnant women with iron-deficiency anemia (IDA) demonstrated that folic acid in combination with iron was more effective than iron as monotherapy. The combination of iron and folic acid is also rational in terms of increasing safety: folic acid prevents iron accumulation in the liver and the associated development of fibrosis. Ironinduced liver injury is related to oxidative stress catalyzed by iron overload. Folic acid regulates the transcription of genes involved in oxidative stress in the liver and the activity of 5'-AMP-activated protein kinase. Key words: iron deficiency, folic acid, hematopoiesis, rational pharmacotherapy
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KOSAKA, Chiya, and Catherine J. PEARS. "Chemoattractants induce tyrosine phosphorylation of ERK2 in Dictyostelium discoideum by diverse signalling pathways." Biochemical Journal 324, no. 1 (May 15, 1997): 347–52. http://dx.doi.org/10.1042/bj3240347.
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Two homologues of mitogen-activated protein kinases have been identified in Dictyostelium discoideum (ERK1 and EKR2). We here demonstrate transient tyrosine phosphorylation of ERK2 in response to the chemoattractants cAMP and folic acid that correlates with activity. To investigate the signalling pathways, we studied the response in strains with altered cAMP-dependent protein kinase (PKA) status. The degree of cAMP-induced ERK2 tyrosine phosphorylation was increased in cells overexpressing PKA activity but no such increase was observed in the response to folic acid. Our observations suggest that cAMP-induced ERK2 tyrosine phosphorylation is positively modulated by a PKA-regulated step which is not involved in the response to folic acid, suggesting the presence of diverse signalling pathways leading to ERK2 activation.
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Clark, Daniel F., Rachael Schmelz, Nicole Rogers, Nuri E. Smith, and Kimberly R. Shorter. "Acute high folic acid treatment in SH-SY5Y cells with and without MTHFR function leads to gene expression changes in epigenetic modifying enzymes, changes in epigenetic marks, and changes in dendritic spine densities." PLOS ONE 16, no. 1 (January 7, 2021): e0245005. http://dx.doi.org/10.1371/journal.pone.0245005.
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Epigenetics are known to be involved in various disorders, including neurobiological disorders like autism. Dietary factors such as folic acid can affect epigenetic marks using methylenetetrahydrofolate reductase (MTHFR) to metabolize folic acid to a one-carbon methyl group. As MTHFR mutations are frequent, it is curious as to whether excess folic acid, with or without functioning MTHFR, could affect gene expression, epigenetics, and neuromorphology. Here, we investigated gene expression and activity of epigenetic modifying enzymes, genome-wide DNA methylation, histone 3 modifications, and dendritic spine densities in SH-SY5Y cells with or without a knockdown of MTHFR and with or without an excess of folic acid. We found alterations to gene expression of epigenetic modifying enzymes, including those associated with disorders like autism. Grouping the epigenetic modifying enzymes by function indicated that gene expression was widely affected for genes that code for enzymes affecting DNA methylation, histone acetylation, histone methylation, histone phosphorylation, and histone ubiquitination when excess folic acid treatment occurred with or without the knockdown of MTHFR. MTHFR was significantly reduced upon excess folic acid treatment whether MTHFR was knocked-down or not. Further, methyl-CpG binding protein 2 expression was significantly decreased with excess folic acid treatment with and without proper MTHFR expression. Global DNA methylation decreased due to the knockdown alone while global hydroxymethylated DNA increased due to the knockdown alone. TET2 expression significantly increased with the MTHFR knockdown alone. Excess folic acid alone induced a decrease in TET3 expression. Excess folic acid induced an increase in dendritic spines without the MTHFR knockdown, but folic acid induced a decrease in dendritic spines when MTHFR was knocked-down. The knockdown alone also increased the dendritic spines significantly. Histone 3 acetylation at lysine 18 was significantly increased when excess folic acid was applied to cells with the MTHFR knockdown, as was histone 3 phosphorylation at serine 10. Broadly, our results indicate that excess folic acid, even with functioning MTHFR, could have detrimental effects on cells.
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Susilowati, Agustine, Aspiyanto, Yati Maryati, Hakiki Melanie, and Puspa Dewi N. Lotulung. "Fermentation time difference of nixtamalized horse dent corn (Zea mays var. indenata) by Bifidobacterium bifidum and Bifidobacterium brevis as source of natural folic acid." IOP Conference Series: Earth and Environmental Science 911, no. 1 (November 1, 2021): 012065. http://dx.doi.org/10.1088/1755-1315/911/1/012065.
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Abstract Bifidobacterium sp. as microbes has potential role in fermentation of nixtamalized horse dent corn (Zea mays var. indentata) to degrade complex components into folic acid-rich corn biomass. Fermentation process on both nixtamalized yellow corn and white corn by Bifidobacterium brevis and Bifidobacterium bifidum as substrat of A, B, C and D were conducted at concentration of corn folic acid inoculum 40% (w/w) and 37 °C for 0, 8, 16, and 24 hours, respectively. Based on dissolved protein yielded, the experiment result showed that the best result of optimization in fermentation of both nixtamalized yellow corn (biomass B) and white corn (biomass D) was achieved by using inoculum of B. bifidum for 16 hours with composition of folic acid of 213.58 and 297.72 μg/mL, total solids of 21.14 and 21.07%, dissolved protein of 0.42 and 0.39 mg/mL, reducing sugars of 34.2 and 37.8 mg/mL, total sugars of 104.7 and 98.6 mg/mL, total acids of 0.37 and 0.44%, N-amino of 0.28 and 0.26 mg/g, and pH 4.82 and 4.49, respectively. In this condition, biomass of B. and biomass of D indicated domination of folic acid monomer with molecular weight (MW) 442.29 and 442.59 Dalton (Da.) at relative intensity 100%, particles size of 1115.1 nm and 1075.7 nm, and particle index of 0.827 and 0.849, respectively. Meanwhile, volatile compounds were dominated by 2,3-butanediol of 4.46 and 10.65%, palmitic acid of 7.63 and 8.26%, octadecenoic acid of 6.31 and 9.5%, lactic acid of 2.37% and 0.53%, respectively.
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Said, H. M., T. Y. Ma, A. Ortiz, A. Tapia, and C. K. Valerio. "Intracellular regulation of intestinal folate uptake: studies with cultured IEC-6 epithelial cells." American Journal of Physiology-Cell Physiology 272, no. 2 (February 1, 1997): C729—C736. http://dx.doi.org/10.1152/ajpcell.1997.272.2.c729.
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Although the mechanism of folate uptake in the small intestine has been well characterized, very little is known about the intracellular regulation of the uptake process. Using mature confluent monolayers of the intestinal epithelial cell line IEC-6 as an in vitro intestinal epithelial cell model, we have found the uptake of folic acid to be similar to that of the native small intestine in that it is 1 ) temperature, energy, and pH dependent, 2) Na+ independent, 3) inhibited by structural analogs and anion transport inhibitors, and 4) saturable as a function of substrate concentration [apparent Michaelis constant (Km) = 0.45 +/- 0.06 microM; maximal velocity (Vmax) = 3.08 +/- 0.14 pmol x mg protein(-1) x 5 min(-1)]. Furthermore, IEC-6 cells were found by Northern blot analysis to lack the expression of the membrane folate-binding protein. Pretreatment of IEC-6 monolayers with specific protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin A25 caused a significant inhibition in folic acid uptake. On the other hand, their negative controls, genistin and tyrphostin A1, respectively, had no effect. The inhibitory effect of genistein was mediated through inhibition in the Vmax of the folate uptake process with no change in the apparent Km. Pretreatment of IEC-6 monolayers with compounds that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) level (e.g., dibutyryl cAMP) also resulted in a significant (though modest) inhibition in folic acid uptake; however, specific inhibitors of protein kinase A did not affect the uptake process. Specific modulators of protein kinase C and Ca2+/calmodulin-mediated pathways did not significantly affect folic acid uptake. These results demonstrate the suitability of IEC-6 monolayers as an intestinal epithelial model to study folate transport and demonstrate for the first time that uptake of folic acid is regulated by a PTK- and a cAMP-mediated pathway.
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Attias, Z., H. Werner, and N. Vaisman. "Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner." Endocrine-Related Cancer 13, no. 2 (June 2006): 571–81. http://dx.doi.org/10.1677/erc.1.01156.
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The insulin-like growth factor-I receptor (IGF-IR) has an important role in colorectal cancer development and progression. IGF-IR displays a potent anti-apoptotic activity and is overexpressed in primary tumors and colon cancer-derived cell lines. Folic acid, a member of the vitamin B family, is a chemopreventive agent whose deficiency has been linked to an enhanced colon cancer risk. The present study was aimed at testing the hypothesis that part of the modulatory effect of folic acid on malignant transformation may be attributed to its ability to regulate IGF-IR gene expression. Regulation of IGF-IR gene expression by folic acid was assessed using western blots, RT-PCR, transient transfections and chromatin immunoprecipitation assays. Activation of the IGF-IR signaling pathway was evaluated by measuring phosphorylation of ERK, and apoptosis was assayed using poly (ADP-ribose) polymerase cleavage and annexin V-FITC staining. Results obtained showed that folic acid induced a dose-dependent decrease in IGF-IR protein and mRNA levels in the HCT116 +/+ colon cancer cell line. This effect was associated with a significant reduction in IGF-IR promoter activity. Similar effects were elicited by the folic acid metabolites dihydrofolic acid and tetrahydrofolic acid. In addition, folic acid abrogated the IGF-I-stimulated phosphorylation of the downstream signaling molecule ERK1/2 and exhibited a pro-apoptotic activity. Moreover, folic acid induced a significant decrease in Sp1 binding to the IGF-IR promoter region. Finally, folic acid had no effect in wild-type p53-depleted HCT116 −/− and Caco-2 cells. In conclusion, the mechanism of action of folic acid involves regulation of IGF-IR gene expression. The ability of folic acid to downregulate the IGF-I signal transduction pathway may allow the micronutrient to function as a chemopreventive agent. Folic acid deficiency, on the other hand, may lead to increased IGF-IR gene expression, with ensuing pathological activation by endocrine and/or autocrine/paracrine IGF-I.
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McNeil, Christopher J., Susan M. Hay, Garry J. Rucklidge, Martin Reid, Gary Duncan, Christopher A. Maloney, and William D. Rees. "Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets." British Journal of Nutrition 99, no. 2 (February 2008): 262–71. http://dx.doi.org/10.1017/s0007114507798999.
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The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.
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Cianciulli, Antonia, Rosaria Salvatore, Chiara Porro, Teresa Trotta, and Maria Antonietta Panaro. "Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways." Mediators of Inflammation 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/5240127.
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We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-αand IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.
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Ahmed, Omyma G., Ghaydaa A. Shehata, Rasha M. Ali, Rania Makboul, Eman S. H. Abd Allah, and Nessren M. Abd el-Rady. "Folic acid ameliorates neonatal isolation-induced autistic like behaviors in rats: epigenetic modifications of BDNF and GFAP promotors." Applied Physiology, Nutrition, and Metabolism 46, no. 8 (August 2021): 964–75. http://dx.doi.org/10.1139/apnm-2020-0923.
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The current study investigated the role of epigenetic dysregulation of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) genes and oxidative stress as possible mechanisms of autistic-like behaviors in neonatal isolation model in rats and the impact of folic acid administration on these parameters. Forty Wistar albino pups were used as follows: control, folic acid administered, isolated, and isolated folic acid treated groups. Isolated pups were separated from their mothers for 90 min daily from postnatal day (PND) 1 to 11. Pups (isolated or control) received either the vehicle or folic acid (4 mg/kg/day) orally from PND 1 to 29. Behavioral tests were done from PND 30 to 35. Oxidative stress markers and antioxidant defense in the frontal cortex homogenate were determined. DNA methylation of BDNF and GFAP genes was determined by qPCR. Histopathological examination was carried out. Neonatal isolation produced autistic-like behaviors that were associated with BDNF and GFAP hypomethylation, increased oxidative stress, increased inflammatory cell infiltration, and structural changes in the frontal cortex. Folic acid administration concurrently with isolation reduced neonatal isolation-induced autistic-like behaviors, decreased oxidative stress, regained BDNF and GFAP gene methylation, and ameliorated structural changes in the frontal cortices of isolated folic acid treated rats. Novelty: Neonatal isolation induces “autistic-like” behavior and these behaviors are reversed by folic acid supplementation. Neonatal isolation induces DNA hypomethylation of BDNF and GFAP, increased oxidative stress markers, and neuroinflammation. All of these changes were reversed by daily folic acid supplementation.
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Matte, J. J., C. Farmer, C. L. Girard, and J. P. Laforest. "Dietary folic acid, uterine function and early embryonic development in sows." Canadian Journal of Animal Science 76, no. 3 (September 1, 1996): 427–33. http://dx.doi.org/10.4141/cjas96-062.
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The present study was designed to determine the role of folic acid on uterine environment and embryonic development during early gestation in the pig. Thirty-two, third parity, crossbred sows received a diet supplemented with 0 or 15 mg kg−1 of folic acid. The treatments started 2 wk before expected estrus and lasted until slaughter on either day 12 or 15 after mating. One uterine horn was used to collect conceptuses and uterine "flushings" for hormonal and metabolite determinations; conceptuses from the other horn were enzymatically dispersed and placed in cell culture with and without dehydroepiandrosterone (DHEA). The decrease in serum folates was attenuated (P ≤ 0.06) and the total and saturated folate binding capacities in early gestation were increased (P < 0.01) in sows receiving additional dietary folic acid. The volume of uterine flushings recovered was greater (P ≤ 0.02) on day 15 than on day 12, as was its content of protein (P ≤ 0.06). In sows receiving the dietary supplement of folic acid, total uterine prostaglandin (PG)E2 was three times higher on day 12 and two times higher on day 15 (P < 0.04) than for sows fed the experimental diet without supplement; although numerically substantial (60% higher), the effect was not significant for PGF2α (P ≥ 0.16). Conceptus homogenates contained more folic acid (P ≤ 0.02) and DNA (P ≤ 0.0001) on day 15 than on day 12. Their total protein content, in sows slaughtered on day 12 of gestation, tended (P ≤ 0.07) to be higher in supplemented than in unsupplemented animals. The synthesis of estradiol-17β by the conceptus cells, used as an index of embryonic maturity, tended (P ≤ 0.07) to be lower for treated than untreated sows, especially in conceptus cell culture without DHEA. Therefore, the improvement in embryonic survival attributed to dietary supplements of folic acid might be linked to changes on the secretion of uterine prostaglandins and possibly on embryonic development. Key words: Folic acid, uterus, embryo, sow
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Noriega, Guillermo O., Adela A. Juknat, and Alcira M. del C. Batlle. "Non-Essential Activation of Rat Liver Porphobilinogen-Deaminase by Folic Acid." Zeitschrift für Naturforschung C 47, no. 5-6 (June 1, 1992): 416–19. http://dx.doi.org/10.1515/znc-1992-0616.
Full textAbstract:
This report demonstrates the ability of folic acid to activate rat liver porphobilinogen-deaminase (PBG -D). Lineweaver-Burk analysis revealed an increase in Vmax (38%) without affecting the Km. In the concentration range assayed, secondary replots of 1/Δslope and 1/Δintersect versus 1/[folic acid] yielded straight lines, indicating the binding of a single molecule of activator to the enzyme PBG-D , with a KA = 1.66 mᴍ. Results presented here show that folic acid acts as a non-essential activator (α = 1; β = 1.6). The activating effect of folic acid has been observed employing the 35-70% ammonium sulphate precipitated fraction, desalted by dialysis or gel filtration, whereas no action was detected when other partially purified PBG -D preparations were utilized as the enzyme source, suggesting either the presence of sites saturated for the activator, or the existence of a different structural protein conformation, or both.
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Letendre, Marie, Jean F. Bernier, Christiane L. Girard, and J. Jacques Matte. "Effects of intramuscular injections of folic acid on folates status and growth performance of weanling pigs." Canadian Journal of Animal Science 71, no. 4 (December 1, 1991): 1223–31. http://dx.doi.org/10.4141/cjas91-144.
Full textAbstract:
In the first of two trials, 24 piglets (2 wk old) were used to measure the dose–response curve of serum folates after intramuscular injections of folic acid (0, 10, 20 or 30 mg). Administration of 10 mg of folic acid was sufficient (P < 0.01) to prevent the decrease of serum folates observed 1 wk after weaning. In the second trial, 72 piglets (2 wk old) were used to study the effect of repeated intramuscular injections of folic acid (0 or 2.5 mg kg−1 of body weight) on hematological status, liver development, and concentrations of serum and hepatic folates, as well as on growth performance up to 10 wk of age. Serum and liver folates were increased (P < 0.01) by repeated injections of folic acid. However, no treatment effects (P > 0.10) were observed on total content of DNA, RNA and protein in the liver. Hemoglobin, hematocrit, total body weight gain, gain: feed ratio and total feed intake were also not influenced (P > 0.10) by the injections of folic acid. Therefore, although a decrease in serum folates is observed during the weaning period, it does not seem to have detrimental effects on the growth performance of weanling piglets. Key words: Folic acid, folates, growth performance, piglets, weaning
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Au-Yeung, Kathy K. W., Johnny C. W. Yip, Yaw L. Siow, and Karmin O. "Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophagesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum." Canadian Journal of Physiology and Pharmacology 84, no. 1 (January 2006): 141–47. http://dx.doi.org/10.1139/y05-136.
Full textAbstract:
Folic acid supplementation is a promising approach for patients with cardiovascular diseases associated with hyperhomocysteinemia. We have demonstrated that homocysteine (Hcy) activates nuclear factor-κB (NF-κB), a transcription factor that plays an important role in inflammatory responses. The aim of the present study was to investigate the effect of folic acid on Hcy-induced NF-κB activation in macrophages. Hcy treatment (100 μmol/L) resulted in NF-κB activation and increased monocyte chemoattractant protein-1 (MCP-1) expression in THP-1 derived macrophages. Hcy-induced NF-κB activation was associated with a significant increase in the intracellular superoxide anion levels. There was a significant increase in phosphorylation and membrane translocation of NADPH oxidase p47phox subunit in Hcy-treated cells. Addition of folic acid (200 ng/mL) to the culture medium abolished NADPH oxidase-dependent superoxide anion generation in macrophages by preventing phosphorylation of p47phox subunit. Consequently, Hcy-induced NF-κB activation and MCP-1 expression was inhibited. Such an inhibitory effect of folic acid was independent of its Hcy-lowering ability. Taken together, these results suggest that folic acid treatment can effectively inhibit Hcy-induced oxidative stress and inflammatory responses in macrophages. This may represent one of the mechanisms by which folic acid supplementation exerts a protective effect in cardiovascular disorders.
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Samblas, Mirian, J. Alfredo Martínez, and Fermín Milagro. "Folic Acid Improves the Inflammatory Response in LPS-Activated THP-1 Macrophages." Mediators of Inflammation 2018 (July 4, 2018): 1–8. http://dx.doi.org/10.1155/2018/1312626.
Full textAbstract:
DNA methylation has been suggested as a regulatory mechanism behind some inflammatory processes. The physiological actions of methyl donors, such as folic acid, choline, and vitamin B12 on inflammation-related disease have been associated with the synthesis of the universal methyl donor S-adenosyl methionine (SAM). The aim of this study was to evaluate the effects of folic acid, choline, vitamin B12, and a combination of all on preventing the lipopolysaccharide- (LPS-) induced inflammatory response in human THP-1 monocyte/macrophage cells. Folic acid and the mixture of methyl donors reduced interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) expression as well as protein secretion by these cells. Folic acid and choline decreased C-C motif chemokine ligand 2 (CCL2) mRNA levels. In addition to this, the methyl donor mixture reduced Cluster of differentiation 40 (CD40) expression, but increased serpin family E member 1 (SERPINE1) expression. All methyl donors increased methylation levels in CpGs located in IL1B, SERPINE1, and interleukin 18 (IL18) genes. However, TNF methylation was not modified. After treatment with folic acid and the methyl donor mixture, ChIP analysis showed no change in the binding affinity of nuclear factor-κB (NF-κB) to IL1B and TNF promoter regions after the treatment with folic acid and the methyl donor mixture. The findings of this study suggest that folic acid might contribute to the control of chronic inflammation in inflammatory-related disease.
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Cao, Rui, Jun Xie, and Li Zhang. "Abnormal methylation caused by folic acid deficiency in neural tube defects." Open Life Sciences 17, no. 1 (January 1, 2022): 1679–88. http://dx.doi.org/10.1515/biol-2022-0504.
Full textAbstract:
Abstract Neural tube closure disorders, including anencephaly, spina bifida, and encephalocele, cause neural tube defects (NTDs). This congenital disability remained not only a major contributor to the prevalence of stillbirths and neonatal deaths but also a significant cause of lifelong physical disability in surviving infants. NTDs are complex diseases caused by multiple etiologies, levels, and mechanisms. Currently, the pathogenesis of NTDs is considered to be associated with both genetic and environmental factors. Here, we aimed to review the research progress on the etiology and mechanism of NTDs induced by methylation modification caused by folic acid deficiency. Folic acid supplementation in the diet is reported to be beneficial in preventing NTDs. Methylation modification is one of the most important epigenetic modifications crucial for brain neurodevelopment. Disturbances in folic acid metabolism and decreased S-adenosylmethionine levels lead to reduced methyl donors and methylation modification disorders. In this review, we summarized the relationship between NTDs, folic acid metabolism, and related methylation of DNA, imprinted genes, cytoskeletal protein, histone, RNA, and non-coding RNA, so as to clarify the role of folic acid and methylation in NTDs and to better understand the various pathogenesis mechanisms of NTDs and the effective prevention.
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Calvet, J. P., and L. J. Chadwick. "Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse." Journal of the American Society of Nephrology 5, no. 6 (December 1994): 1324–32. http://dx.doi.org/10.1681/asn.v561324.
Full textAbstract:
Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.
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Sereen, Khadira, Vijayalakshmi K, Priya Nagappan, and Shinu Balima. "EFFECT OF SESAMOL IN ASSOCIATION WITH FOLIC ACID ON 6-OHDA INDUCED PARKINSONIAN ANIMALS- BIOCHEMICAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL EVIDENCE." Asian Journal of Pharmaceutical and Clinical Research 10, no. 4 (April 1, 2017): 46. http://dx.doi.org/10.22159/ajpcr.2017.v10i4.12961.
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Objective: Parkinson’s disease (PD) is the world’s second neurodegenerative disorder. Degeneration of dopaminergic neurons is the hallmark of the disease. Here is a novel approach to treat PD with a phenolic compound Sesamol (SA) and in combination with Folic acid (FA).Methods: The study was designed with five groups of animals and 6 rats in each group. The rats was infused with 6-hydroxydopamine (10μg/2μl in 0.1% ascorbic acid saline) once for the development of PD, Group 1(control), Group 2(Lesion), Group 3(Lesion+ SA), Group 4(Lesion + SA+ FA) and Group 5(Lesion+ L-dopa). The biochemical parameter like glucose, triglycerides, protein, folic acid, TBARS and antioxidant profile in serum were estimated. The neurotransmitters level in striatum was estimated and histopathology of striatum and mid-brain tissues was carried out.Results: The results showed that 6-hydroxydopamine induced lesion has a significant alteration in the level of glucose, triglycerides, protein and folic acid where as TBARS level was elevated and the activities of antioxidants and neurotransmitters level were reduced. This was significantly restored on SA+FA treatment. The lesion group shows an abnormal architecture of striatum and mid-brain, whereas on SA+FA treatment there was minimal abnormality.Conclusion: Thus our study demonstrates that Sesamol has neuroprotective effect against 6-hydroxy dopamine insult and showed a synergic effect when combined with Folic acid.Keywords: Parkinson’s disease, Sesamol, Folic acid, 6-Hydroxy dopamine, Neurotransmitter, Antioxidant
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Merzel, Rachel L., Carolina Frey, Junjie Chen, Rachel Garn, Mallory van Dongen, Casey A. Dougherty, Ananda Kumar Kandaluru, Philip S. Low, E. Neil G. Marsh, and Mark M. Banaszak Holl. "Conjugation Dependent Interaction of Folic Acid with Folate Binding Protein." Bioconjugate Chemistry 28, no. 9 (August 9, 2017): 2350–60. http://dx.doi.org/10.1021/acs.bioconjchem.7b00373.
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Said, H. M., and R. Redha. "A carrier-mediated transport for folate in basolateral membrane vesicles of rat small intestine." Biochemical Journal 247, no. 1 (October 1, 1987): 141–46. http://dx.doi.org/10.1042/bj2470141.
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The mechanism of exit of folate from the enterocyte, i.e. transport across the basolateral membrane, is not known. In this study we examined, using basolateral membrane vesicles, the transport of folic acid across the basolateral membrane of rat intestine. Uptake of folic acid by these vesicles represents transport of the substrate into the intravesicular compartment and not binding to the membrane surface. The rate of folic acid transport was linear for the first 1 min of incubation but decreased thereafter, reaching equilibrium after 5 min of incubation. The transport of folic acid was: (1) saturable as a function of concentration with an apparent Km of 0.6 +/- 0.17 microM and Vmax. of 1.01 +/- 0.11 pmol/30 s per mg of protein; (2) inhibited in a competitive manner by the structural analogues 5-methyltetrahydrofolate and methotrexate (Ki = 2 and 1.4 microM, respectively); (4) electroneutral; (5) Na+-independent; (6) sensitive to the effect of the anion exchange inhibitor 4,4′-di-isothiocyanatostilbene-2,2′-disulphonic acid (DIDS). These data indicate the existence of a carrier-mediated transport system for folic acid in rat intestinal basolateral membrane and demonstrate that the transport process is electroneutral, Na+-independent and sensitive to the effect of anion exchange inhibition.
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Girard, C. L., and J. J. Matte. "Impact of B-vitamin supply on major metabolic pathways of lactating dairy cows." Canadian Journal of Animal Science 86, no. 2 (June 1, 2006): 213–20. http://dx.doi.org/10.4141/a05-058.
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Knowledge of the major nutrient requirements of dairy cows has increased substantially during the past decades. Little is known, however, about the importance of the roles played by B vitamins. Since most of those vitamins act as essential cofactors in energy, protein and lipid metabolism, it is likely that as milk yield increases, the demand for these cofactors also increases. The supply of B vitamins from dietary sources and synthesis by the ruminal microflora is generally sufficient to avoid deficiency symptoms, but could be insufficient for optimizing metabolic efficiency, production, composition and the nutritional quality of milk in high-producing dairy cows. Results from recent experiments show how the supply of three B vitamins — folic acid, biotin and vitamin B12 — affects major metabolic pathways. Supplementary biotin has frequently been reported to increase milk yield but has a limited effect on milk composition. Folic acid supplements have been found to increase milk and milk protein yields in multiparous cows without affecting dry matter intake when vitamin B12 supply was adequate. An insufficient vitamin B12 supply blocked those effects but they can be restored through vitamin B12 supplementation. Supplemental vitamin B12 and biotin increased milk and milk protein yields without changing dry matter intake. Vitamin B12 utilization by tissues increased in cows fed supplementary folic acid simultaneously; plasma glucose also increased in these cows but plasma biotin decreased. From these findings, it appears that, in high-producing dairy cows, especially in early lactation, the strong competition for nutrients that occurs between gluconeogenesis, methylneogenesis and protein synthesis increases the amount of folic acid, vitamin B12 and biotin required to maintain metabolic efficiency, especially when the nutrient supply is limited. These observations emphasize the need to review the paradigm according to which B-vitamin supply by ruminal microflora cannot be limiting in dairy cow. Key words: Dairy cow, B vitamins, folic acid, vitamin B12, biotin, lactation, metabolism
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Chen, Jiaxi, Tongtian Zhuang, Jianru Chen, Yangzi Tian, Xiuli Yi, Qingrong Ni, Weigang Zhang, et al. "Homocysteine induces melanocytes apoptosis via PERK–eIF2α–CHOP pathway in vitiligo." Clinical Science 134, no. 10 (May 2020): 1127–41. http://dx.doi.org/10.1042/cs20200218.
Full textAbstract:
Abstract Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)–eukaryotic translation initiation factor 2α (eIF2α)–C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.
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Mahruba, Syeda Nusrat, Shelina Begum, Shorifa Shahjadi, Sharmin Afroz, Umme Raihan Siddiqi, and Jobaida Parvin. "Serum vitamin B12 and folic acid status in Autism spectrum disorder children." Journal of Bangladesh Society of Physiologist 14, no. 2 (January 1, 2020): 43–47. http://dx.doi.org/10.3329/jbsp.v14i2.44783.
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Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. The etiology of ASD involves gene-environmental interaction. Vitamin B12 and folic acid have important roles as methyl donor in many biosynthetic pathways, protein synthesis and formation of myelin sheath throughout the central nervous system. Therefore, deficiency of vitamin B12 and folic acid may act as environmental risk factor for ASD.
Objective: To evaluate serum vitamin B12 and folic acid levels in ASD children.
Methods: This cross-sectional study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, from 2018 to 2019. Total 100 children 3-10 years of age were enrolled for this study.Among them fifty (50) diagnosed children with ASD were included in the study group. Fifty (50) healthy children constituted the control group. ASD children were selected from the Parent’s Forum for autistic children. No children were included receiving any vitamin supplementation or had acute illness. For this study, serum level of vitamin B12 and folic acid were measured by automated analyzer.For statistical analysis unpaired “t” test and chi square test were done.
Result: The mean values of vitamin B12 and folic acid were significantly lower in ASD children than those of control group (p value <0.05). In addition 4% ASD children had vitamin B12 deficiency.
Conclusion: Low serum vitamin B12 and folic acid was associated with ASD.
J Bangladesh Soc Physiol. 2019, December; 14(2): 43-47
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Harper, A. F., M. D. Lindemann, and E. T. Kornegay. "Fetal survival and conceptus development after 42 days of gestation in gilts and sows in response to folic acid supplementation." Canadian Journal of Animal Science 76, no. 1 (March 1, 1996): 157–60. http://dx.doi.org/10.4141/cjas96-023.
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The effects of feeding 2 ppm supplemental folic acid (FA) on fetal survival and development were assessed in sows (n = 32). Number of live fetuses and fetal survival at day 45 ± 3 of gestation was not influenced by FA. Fetal pig weight, length, protein and RNA content were increased (P < 0.05) with FA treatment, suggesting enhanced development of embryo/fetal tissues with maternal FA supplementation. Key words: Folic acid, gilt, sow, fetal pigs