• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.53-62
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• 2023

Objective: The aim of this study was to investigate the relationships of serum folate (vitamin B9), cobalamin (vitamin B12) levels and diet with semen parameters (semen standard parameters [SSP] and DNA fragmentation index [DFI]) in infertile men. Methods: Sperm samples were assessed for SSP and DFI (using the sperm chromatin dispersion test). Serum vitamin concentrations were measured with an immuno-electrochemiluminescence assay, and men completed a semi-quantitative food frequency questionnaire (FFQ). Results: Serum folate levels were positively correlated with sperm progressive motility and DFI. A comparison of SSP between two groups of patients according to serum folate concentration (B9 <4.840 ng/mL and B9 ≥4.840 ng/mL) showed significantly higher sperm concentration and sperm progressive motility in the latter group. However, there was no difference between these groups regarding DFI. Interestingly, serum folate levels were significantly higher in patients with a high DFI (using the cut-offs of 30% or 18%). FFQ data showed that the consumption of fruits and egg yolk correlated positively with sperm concentration and sperm motility, respectively. Conclusion: Serum folate levels showed significant associations with sperm concentration and sperm progressive motility. However, the positive association of serum folate with DFI raises the need for careful prescription of folate supplements.

• Journal of Nutrition and Health
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• v.31 no.6
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• pp.1006-1013
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• 1998

The present study was conducted to investigate the effect of different levels of ethanol ingestion on 131ate metabolism and plasma homocysteine concentration in Sprague-Dawley male rats receiving 0, 10, 30% of their caloric intake as ethanol for S weeks. Diets containing 10% ethanol had no effect on plasma and red blood cell(rbc) 131a1e. However, in rats fed a 30% ethanol diet, rbc folate increased and plasma 131ate decreased significantly, In the rats maintained first on a 30% ethanol diet for S weeks and then on a control diet for 2 weeks, the levels of plasma and rbc f31ate were normalized by withdrawal of ethanol. Urinary fo1ate excretion increased markedly in rats fed 10% and 30% ethanol diets and decreased to 51% of controls by withdrawal of ethanol. Plasma homocysteine concentration increased significantly in rats fed a 30% ethanol diet. The results suggest that chronic ingestion of ethanol increased urinary 131ate excretion markedly, which may decrease plasma 131ate and deplete liver folate.

• Journal of Nutrition and Health
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• v.33 no.3
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• pp.250-256
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• 2000

Hyperhomocysteinemia has been shown to be associated with increased risks for macrovascular angiopathy. The present study was conducted to document the relationship between plasma homocysteine levels and the presence of macrovascular angiopath in patients with Type II diabetes mellitus. Plasma total homocysteine was determined by a HPLC-fluorescence detection method in a total of 238 subjects, 127 diabetic patients and 111 control. Dietary information including folate intake was assessed by a 24-hour recall in a total 113 subjects, 70 diabetic patients and 43 control. Folate intake was significantly lower inn patients with diabetes mellitus than that in the control. The lowered folate intake in the diabetic patients was mainly due to reduced intakes of fruits and vegetables. The average plasma homocysteine level of patients with MA was 14.2$\mu$㏖/L, which was significantly higher than that of either the patients without MA(11.4$\mu$㏖/L) or the control(11.5$\mu$㏖/L). Twenty five percent of the diabetic patients were positively correlated with age (r=0.20), body weight (r=0.28), body mass index (r=0.28), body mass index (r=0.18), diastolic blood pressure (r=0.20), and total cholesterol (r=0.14). cigarette smokers had significantly higher levels of plasma homocysteine than the non-smokers. Further prospective studies are needed to investigate whether folate or other B vitamin supplementation could be beneficial for the prevention of hyperhomocysteinemia or macrovascular angiopathy in the diabetic patients.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.1
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• pp.3-10
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• 2018

The folate receptor (FR) is a promising cell membrane-associated target for nuclear imaging of various cancers (via imaging $FR-{\alpha}$) and potentially also inflammatory diseases (via imaging $FR-{\beta}$), through the use of folic acid-based radioconjugates. However, there have been several drawbacks of previously reported radioconjugates, such as a short half-life of the radiolabel ($^{68}Ga\;t_{1/2}$ 68 min), a complex and time-consuming multistep radiosynthesis, and a high renal uptake of radiolabeled folate derivatives. The goal of this study was to develop an imaging probe by directly labeling folate with radioactive iodine without using an extra prosthetic group. The radiolabeling of folate was optimized using various labeling conditions and the labeled tracers were isolated by high-performance liquid chromatography. The in vitro stability of labeled folate was checked in phosphate-buffered saline and serum. The tumor-targeting efficacy of the probe was also evaluated by biodistribution studies using a murine 4T1 tumor model.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5185-5188
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• 2016

Objective: Targeted-drug-delivery based lipid nanoparticles has emerged as a new and effective approach in cancer chemotherapy. Here, we investigated the ability of folate-modified nanostructured lipid carriers (NLCs) to enhance letrozol (LTZ) efficacy in MCF-7 breast cancer cells. Methods: New formulations were evaluated regarding to particle size and scanning electron microscope (SEM) features. Anti-proliferative effects of LTZ loaded nanoparticles were examined by MTT assay. To understand molecular mechanisms of apoptosis and cell cycle progression, flow cytometric assays were applied. Results: Optimum size of nanoparticles was obtained in mean average of $98{\pm}7nm$ with a poly dispersity index (PDI) of 0.165. The IC50 value was achieved for LTZ was $2.2{\pm}0.2{\mu}M$. Folate-NLC-LTZ increased the percentage of apoptotic cells from 24.6% to 42.2% compared LTZ alone (p<0.05). Furthermore, LTZ loaded folate targeted NLCs caused marked accumulation of cells in the subG1 phase. Conclusion: Taken together, our results concluded that folate targeted LTZ can be considered as potential delivery system which may overcome limitations of clinical application of LTZ and improve drug efficacy in tumor tissue.

• Journal of Nutrition and Health
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• v.32 no.4
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• pp.376-383
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• 1999

The effects of $\beta$-carotene substitutionl for vitamin A and the chronic consumption of ethanol of ethanol on hepatic folate metabolism were studied it rats. The substitution of $\beta$-carotene for vitamin A depressed hepatic 10-formyl-tetreahydrofolate dehydrogenase(10-formyl-tetrahydrofolate : NADP oxidoreductase, E.C. 1.5. 1.6)activity to 65% of controls(p<0.001) and enhanced hepatic 5, 10-methy-lenetetrahydrofolate reductase(E. C. 6.3.3.2)activity by 56% with respect to control levels(p<0.001). Hepatic activity of 10-formyltertrahydrofolate dehydrogenase was depressed to about half that of control levels by ethanol administration to rats(36% ethanol diet, p<0.001). The activity of 5, 10-methyleneterahydrofolate reductase was not changed by ethanol consumption. The increased activity of 5, 10-methyleneterahydrofolate reductase and the decreased activity of 10-formyltetrahydrofolate dehydrogenase appeared to decrease the level of nonmethyl folate conezyme and the rate of one-carbon metabolism. Plasma homocysteine concentrations were significantly higher in rats fed ethanol(p<0.01) o $\beta$-carotene(p<0.001) than in controls, which suggests that increased activity of 5, 10-methylenetetrahydrofolate reductase can depress homocysteine metabolism. We concluded that dietary substitution of $\beta$-carotene for vitamin A or chronic administration of ethanol resulted in changes in the activity of hepatic folate-dependent enzymes, which could affect the distribution of folate derivatives, plasma homocysteine levels and one-carbon metabolism.

• Korean Journal of Clinical Pharmacy
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• v.8 no.1
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• pp.23-28
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• 1998

The pharmacokinetics of atenolol (25 mg/kg, i.v.) in the folate-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folate (50, 100, and 200 mg/kg). At folate dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and AUC of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The elimination rate constant $(K_{el})$ and total body clearance $(CL_t)$ of atenolol decreased significantly, and half-life ($t_{1/2}$) and mean residence time (MRT) of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The serum creatinine concentration $(S_{cr})$ correlated well (p<0.05) with half-life $(t_{1/2})$ and elimination rate constant $(K_{el})$ of atenolol, as well as BUN with AUC and total body clearance $(CL_t)$ of atenolol.

• Journal of Nutrition and Health
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• v.35 no.10
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• pp.1045-1052
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• 2002

Hyperhomocysteinemia, resulted from an interaction between the mutation of MTHFR gene and B vitamin deficiency, is suggested as a possible cause for complications and adverse outcomes of pregnancy. The purpose of the present study was to investigate the relationship between the intakes of B vitamins and serum homocysteine concentrations with the C677T mutation in the MTHFR genotypes in 135 normal pregnant women of 24-28 weeks of gestation. Dietary intake of B vitamins did not differ among the three genotypes, but the negative correlation between dietary folate intake and the serum homocysteine level was the strongest in the T/T type (r ＝ -0.249) than in other genotypes (C/T: r＝ -0.040, C/C:r＝ 0.126, p＜0.05). Among the subject with the T/T type, the pregnant women who consumed folate less than 50% of the RDA had higher serum homocysteine levels than those who consumed folate greater than 125% of the RDA (10.4$\pm$5.9 vs 7.0$\pm$1.5 $\mu$mol/L, p＜0.05). Serum homocysteine levels were higher in the women with micronutrient supplements than those with no supplements in the T/T type, but such relation was not present in the C/C or the C/T type. In conclusion, serum homocysteine concentrations were influenced by the interrelationship between the MTHFR polymorphisms and dietary folate intake or micronutrient supplementation.

• Korean Journal of Food Science and Technology
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• v.51 no.5
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• pp.425-431
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• 2019

Selected leafy vegetables, widely used for Korean Namul dishes, were heat-treated in different ways and their folate retention was investigated. The Lactobacillus casei method was applied for folate estimation and validated to ensure reliability of analytical data. The folate content in Namul highly varied, from 29.7 to $293.4{\mu}g/100g$, depending on the heating methods and the types of vegetables. Most of the Namul variants showed increased folate content on heat treatment. Frying yielded higher folate retention than the other cooking methods (blanching, steaming, baking, and panfrying), and pig weed showed the highest folate retention (3.3 times, $293.4{\mu}g/100g$). L. casei assay for folate estimation showed 95.7% recovery and relative standard deviations less than 2% for both reproducibility and repeatability, indicating good accuracy and precision. Quality of the folate assay was assured by monitoring a quality control chart and a proficiency test (z-score= -0.1) during the entire of study.

• Journal of Nutrition and Health
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• v.42 no.5
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• pp.423-433
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• 2009

Folate and vitamin $B_{12}$ are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin $B_{12}$ deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folatesufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin $B_{12}$-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 ${\pm}$ 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 ${\pm}$ 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 ${\pm}$ 9.6 nmol/L) compared with rats fed FD and FDH (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin $B_{12}$ deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin $B_{12}$ deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.