• Nutrition Research and Practice
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• 제2권4호
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• pp.195-199
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• 2008

Alcoholism has been associated with folate deficiency in humans and laboratory animals. Previous study showed that ethanol feeding reduces the dehydrogenase and hydrolase activity of 10-formyltetrahydrofolate dehydrogenase (FDH) in rat liver. Hepatic ethanol metabolism generates acetaldehyde and acetate. The mechanisms by which ethanol and its metabolites produce toxicity within the liver cells are unknown. We purified FDH from rat liver and investigated the effect of ethanol, acetaldehyde and acetate on the enzyme in vitro. Hepatic FDH activity was not reduced by ethanol or acetate directly. However, acetaldehyde was observed to reduce the dehydrogenase activity of FDH in a dose- and time-dependent manner with an apparent $IC_{50}$ of 4 mM, while the hydrolase activity of FDH was not affected by acetaldehyde in vitro. These results suggest that the inhibition of hepatic FDH dehydrogenase activity induced by acetadehyde may play a role in ethanol toxicity.

• 대한한의학회지
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• 제38권1호
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• pp.72-80
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• 2017

Objectives: The purpose of this study is to evaluate the urinary organic acid comprehensive profile for chemotherapy induced peripheral neuropathy (CIPN). Methods: Participants are 66 patients with CIPN who had symptom (Visual analog scale ${\geq}30mm$, Eastern Cooperative Oncology Group ${\leq}2$). Participants were tested with organic acid comprehensive profile markers. Results: Positive Correlation was observed in the neurotransmitter metabolism markers, N-methyl-D-aspartate (NMDA) modulators markers, detoxification markers, energy production markers, amino acid metabolism markers, and intestinal dysbiosis markers. Especially, all the neurotransmitter metabolism markers were showed positive rate of 44%. In addition, neuro-endo-immune was associated with energy metabolism (mitochondrial dysfunction) in CIPN of cancer patient. especially detoxification, intestinal bacterial hyperplasia, vitamin deficiency (folate, complex B group, vitamin C). Conclusions: Significant urinary organic acid comprehensive profile results were obtained in cancer patients who induced peripheral neuropathy by chemotherapy.

• Journal of Pharmaceutical Investigation
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• 제31권3호
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• pp.161-165
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• 2001

Acebutolol (ABT) is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism in the gastrointestine and liver. The purpose of this study was to report the pharmacokinetic changes of ABT and its metabolite, diacetolol (DAT) after oral administration of acebutolol to control rabbits and rabbits with mild and severe folate-induced renal failure (FIRRs). Both of the area under the plasma concentration-time curve $(AUC^0_{\infty})$ of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the $AUC^0_{\infty}$ of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of $AUC^0_{\infty}$ of ABT and DAT. The elimination half-life of ABT and DAT was significantly prolonged in mild (p<0.05) and severe (p<0.01) FIRRs, but the half-life of DAT was more influenced than that of ABT in severe FIRRs. The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal disorder on the base of the serum creatinine concentration.

• 한국식생활문화학회지
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• 제35권5호
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• pp.493-502
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• 2020

The objective of this study was to investigate the effects of dietary vitamin B intake on biomarkers related to lipid metabolism, inflammation and blood glucose control, that are important in the development of type 2 diabetes and its complications. Seventy-six adults (42 males, 34 females) were recruited from a group of diabetes patients who had visited the medical center for treatment. Data on anthropometric characteristics and dietary intake of thiamine, riboflavin, niacin, vitamin B₆ and folate were collected using 24-hour diet recall and the CAN Pro 4.0 program. Also, data on clinical indices such as serum lipids, blood pressure, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and homeostasis model assessment 2-insulin resistance (HOMA2-IR) were collected and analyzed for correlation with dietary vitamin B intake. Results from the dietary intake survey showed that riboflavin and folate intake (in males) and folate intake (in females) were below the Dietary Reference Intake for Koreans. Statistical analysis revealed a negative correlation between hs-CRP and dietary intake of B vitamins. Riboflavin intake was inversely associated with systolic blood pressure after adjustments for age, BMI, smoking, alcohol consumption, exercise, ingestion of diabetes mellitus medication and energy intake (p<0.05). Our results suggest that dietary vitamin B may influence inflammation and consequently may help in better management of type 2 diabetes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8093-8100
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• 2016

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

• Journal of Preventive Medicine and Public Health
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• 제45권6호
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• pp.387-393
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• 2012

Objectives: Even though several epidemiological studies have observed positive associations between blood lead levels and homocysteine, no study has examined whether this association differs by the levels of micronutrients, such as folate, vitamin B6, and vitamin B12, which are involved in the metabolism of homocysteine. In this study, we examined the interactions between micronutrients and blood lead on homocysteine levels. Methods: This study was performed with 4089 adults aged ${\geq}20$ years old in the US general population using the National Health and Nutrition Examination Survey 2003-2004. Results: There were significant or marginally significant interactions between micronutrients and blood lead levels on mean homocysteine levels. Positive associations between blood lead and homocysteine were clearly observed among subjects with low levels of folate or low vitamin B6 (p-trend <0.01, respectively). However, in the case of vitamin B12, there was a stronger positive association between blood lead and homocysteine among subjects with high levels of vitamin B12, compared to those with low levels of vitamin B12. In fact, the levels of homocysteine were already high among subjects low in vitamin B12, irrespective of blood lead levels. When we used hyperhomocysteinemia (homocysteine>15 ${\mu}mol/L$) as the outcome, there were similar patterns of interaction, though p-values for each interaction failed to reach statistical significance. Conclusions: In the current study, the association between blood lead and homocysteine differed based on the levels of folate, vitamin B6, or vitamin B12 present in the blood. It may be important to keep sufficient levels of these micronutrients to prevent the possible harmful effects of lead exposure on homocysteine levels.

• Journal of Nutrition and Health
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• 제38권7호
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• pp.495-502
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• 2005

This study was performed to investigate effects of dietary folic acid supplementation on plasma homocysteine levels, thiobarbituric acid reactive substance s (TBARS) level s and liver SAM/SAH ratio in hyperhomocysteinaemia-induced pregnant rats. Forty-two female Sprague-Dawley rats were divided three groups (C: control diet, HFD: $0.3\%$ homocystine and 0 mg folic acid diet, HFS: $0.3\%$ homocystine and 8 mg/kg folic acid diet) according to homocystine and folic acid levels in the diet. They were fed experimental diets for 5 weeks prior to the mating and also during the entire period of pregnancy till gestational day 20. Dietary folic acid supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet, with a concomitant increase in plasma and liver folate levels. Liver TBARS levels in homocysteine-folic acid-deficient group (HFD) were higher than those in control group. Dietary folic acid supplementation increased hepatic SAM/SAM ratio in homocysteine-folic acid- sopplemetantion group (HFS) when compared to the HFD (p < 0.05). These data suggest that folate depletion and elevated plasma homocysteine may promote oxidative stress in rat livers and influence the remethylation cycle of the homocysteine metabolism detrimentally. In conclusion, dietary folic acid supplementation was found to be effective for lowering plasma homocysteine levels, relieving oxidative stress, and improving the methylation status in the body.

• 한국식품영양과학회지
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• 제34권8호
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• pp.1175-1181
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• 2005

녹즙분말과 콜레스테롤 첨가식이로 8주간 사육한 흰쥐의 혈중 지질, 호모시스테인 및 엽산수준에 미치는 효과를 관찰한 결과는 다음과 같다. 흰쥐의 혈중 총 콜레스테롤 농도는 녹즙이나 콜레스테롤 보충에 의해 유의한 영향을 받지 않았으나 중성지질 농도는 녹즙군에서 낮았다(p<0.001). HDL-콜레스테롤과 LDL-콜레스테롤의 경우, 식이 콜레스테롤의 영향을 받아, HDL-콜레스테롤은 콜레스테롤군보다 무콜레스테롤군에서 높았으며 (p<0.001), LDL-콜레스테롤은 콜레스테롤군에서 높았다(p<0.05). HDL-콜레스테롤 수준은 녹즙군에서 높았으며 (p<0.05), LDL-콜레스테롤 농도는 콜레스테롤과 케일의 상호효과가 나타나 무콜레스테롤군에서 만 녹즙에 의한 감소효과를 보였다 HDL/LDL비율은 콜레스테롤 보충군에서 낮았으며 (p<0.05), 녹즙보충군에서 높았으나 통계적으로 유의한 결과를 나타내지 못하였다. 혈청 엽산, 비타민 $B_{12}$ 및 혈장 호모시스테인 농도는 녹즙분말이나 콜레스테롤 보충에 의해 영향을 받지 않았다. 혈중 엽산과 비타민 $B_{12}$ 농도사이에는 유의한 양의 상관성 (r=0.5632, p<0.001)이 관찰되었으나, 혈중 호모시스테인 농도는 혈중 엽산, 비타민 $B_{12}$ 및 콜레스테롤 농도 사이에는 모두 유의한 상관성이 관찰되지 않았다. 본 연구결과를 종합하여 보면, 엽산이 충분히 공급되는 경우, 녹즙보충시 나타나게 되는 심혈관계질환 예방효과는, HDL 농도의 증가 및 중성지방 농도의 감소에 의한 것이며, 녹즙내 엽산보충에 의한 호모시스테인 농도 변화와는 관련이 적은 것으로 사료된다.

• 한국임상약학회지
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• 제1권1호
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• pp.1-7
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• 1991

Folates are involved in a variety of important biosynthesis by way of donating one carbon unit. Since folate metabolism was well understood a number of antifol have been developed. Among these antifols, aminopterin was first used in the treatment of childhood leukemia. However due to its toxicity and purity problems. it was immediately replaced by another antifols. methotrexate (MTX). MTX is shown to be active against various malignancies including leukemia breast cancer, osteogenic sarcoma, and head and neck cancer. Clinically, MTX therapy is divided into 3 categories. depeding on the dose administered; low-dose is defined as doses < $80\;mg/m^2$ intermediate-dose as doses $\geqq\;80\;mg/m^2$ and < $1000\;mg/m^2$ and high-dose as doses $\geqq\;1000\;mg/m^2$. Leucovorin should be administered to minimize MTX toxicities when MTX doses are greater than $80-100\;mg/m^2$. The clinical pharmacokinetics (ADME) of MTX is discussed in this text.

• Journal of Microbiology and Biotechnology
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• 제18권8호
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• pp.1368-1376
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• 2008

In our previous study, the expression of active H-ferritins in Saccharomyces cerevisiae was found to reduce cell growth and reactive oxygen species (ROS) generation upon exposure to oxidative stress; such expression enhanced that of high-affinity iron transport genes (FET3 and FTR1). The results suggested that the recombinant cells expressing H-ferritins induced cytosolic iron depletion. The present study analyzes metabolic changes under these circumstances via proteomic methods. The YGH2 yeast strain expressing A-ferritin, the YGH2-KG (E62K and H65G) mutant strain, and the YGT control strain were used. Comparative proteomic analysis showed that the synthesis of 34 proteins was at least stimulated in YGH2, whereas the other 37 proteins were repressed. Among these, the 31 major protein spots were analyzed via nano-LC/MS/MS. The increased proteins included major heat-shock proteins and proteins related to endoplasmic reticulum-associated degradation (ERAD). On the other hand, the proteins involved with folate metabolism, purine and methionine biosynthesis, and translation were reduced. In addition, we analyzed the insoluble protein fractions and identified the fragments of Idh1p and Pgk1p, as well as several ribosomal assembly-related proteins. This suggests that intracellular iron depletion induces imperfect translation of proteins. Although the proteins identified above result from changes in iron metabolism (i.e., iron deficiency), definitive evidence for iron-related proteins remains insufficient. Nevertheless, this study is the first to present a molecular model for iron deficiency, and the results may provide valuable information on the regulatory network of iron metabolism.