• BMB Reports
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• v.55 no.7
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• pp.348-353
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• 2022

Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer.

• Development and Reproduction
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• v.27 no.3
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• pp.137-147
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• 2023

Pharyngeal pouches are an important epithelial structure controlling facial skeletal development in vertebrates. A series of pouches arise sequentially in the pharyngeal endoderm through collective cell migration followed by rearrangement of pouch-forming cells. While crucial transcription factors and signaling molecules have been identified in pouch formation, a role for Neuropilins (Nrps) in pouch development has not yet been analyzed in any vertebrates. Nrps are cell surface receptors essential for angiogenesis and axon guidance. In all vertebrates, the two Nrp family members, Nrp1 and Nrp2, are conserved in the genome, with two paralogs for Nrp1 (Nrp1a and Nrp1b) and Nrp2 (Nrp2a and Nrp2b) being identified in zebrafish. Here, I report a potential requirement of Nrp signaling in pouch development in zebrafish. nrp1a and nrp2b were expressed in the developing pouches, with sema3d, a ligand for Nrps, being expressed in the pouches. Knocking down Nrps signaling in the pharyngeal endoderm led to severe defects in pouches and facial cartilages. In addition, blocking Mitogen-activated protein kinase (MAPK) activities, a downstream effector of Nrp signaling, in the pharyngeal endoderm caused similar defects in pouches and facial skeleton to those by knocking down Nrps signaling. My results suggest that Nrp signaling acts for pouch formation through MAPK.

• Nutrition Research and Practice
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• v.3 no.3
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• pp.208-211
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• 2009

This study investigated the effect of vitamin $B_6$ deficiency on antioxidant enzyme activities and lipid profile in rats with exercise-induced oxidative stress. Forty eight rats were fed either a vitamin $B_6$ deficient diet (B6-) or a control diet (control) for 4 weeks and then subdivided into 3 groups: pre-exercise (PreE); post-exercise (PostE); recess after exercise (recessE). Compared to those of control group, plasma catalase and hepatic cytosol superoxide dismutase (SOD, EC 1.15.1.1) activities of B6- group were lower regardless of exercise. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) of B6 - group was lower in PreE and there was no difference between PostE and recessE. The level of malondialdehyde (MDA) of B6- was significantly higher in PreE and PostE. High-density lipoprotein-cholesterol (HDL-C) level of B6- group was lower regardless of exercise. Atherosclerotic index of $B_6$- group was higher in PreE and there was no difference between PostE and recessE. It is suggested that a reduction in antioxidative status caused by vitamin $B_6$ deficiency may be aggravated under exercise-induced oxidative stress.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.122-127
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• 2009

Folate is generally considered as a safe water-soluble vitamin for supplementation. However, we do not have enough information to confirm the potential effects and safety of folate supplementation and the interaction with vitamin $B_{12}$ deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin $B_{12}$ deficiency. On this basis, the present study was conducted to examine the effects of high-dose folic acid (FA) supplementation on biomarkers involved in the methionine cycle in vitamin $B_{12}$-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or $100{\mu}g$ (daily dietary requirement) vitamin $B_{12}/kg$ diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin $B_{12}$-deficiency resulted in increased plasma homocysteine (p<0.01), which was normalized by dietary supplementation of high-dose FA (p<0.01). However, FA supplementation and vitamin $B_{12}$ deficiency did not alter hepatic and brain S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations and hepatic DNA methylation. These results indicated that supplementation of high-dose FA improved homocysteinemia in vitamin $B_{12}$-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.

• Nutrition Research and Practice
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• v.8 no.3
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• pp.233-240
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• 2014

Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the $NF{\kappa}B$ pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of $NF{\kappa}B$. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.

• Nutrition Research and Practice
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• v.4 no.4
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• pp.303-310
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• 2010

Consumption of vegetables and fruits is associated with a reduced risk of stroke, but it is unclear whether their protective effects are due to antioxidant vitamins or folate and metabolically related B vitamins. The purpose of the study was to test the hypothesis that intake of fruits and vegetables, which are major sources of antioxidant and vitamin B complex vitamins, reduces the risk of stroke. Cases consisted of patients diagnosed with first event of stroke (n = 69). Controls (n = 69) were age-, sex-, and body mass index-matched to cases. Multivariable-adjusted regression analysis showed that subjects who ate four to six servings of vegetable per day had a 32% reduction in the risk of stroke, and those with more than six servings per day had a reduction of 69% after adjusting for age, sex, BMI, and family history of stroke. Intakes of total fat, plant fat, calcium, potassium, vitamin $B_1$, vitamin $B_2$, vitamin $B_6$, niacin, and folate were significantly and negatively associated with the risk of stroke. Although the trend was not significant, stroke risk was reduced in the second quartile (1.21-2.66 servings per week) of fish intake. However, intake of fruits (average daily intake of 1.0 serving) and antioxidant vitamins such as carotene, vitamin C, and vitamin E was not associated with the risk of stroke. In conclusion, our observational study suggests that intake of fat and vegetables, rich sources of vitamin B complex, calcium, and potassium may protect against stroke.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.453-462
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• 2020

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dose-dependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides- and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immune-enhancing agent acting via AMPK-NF-κB signaling pathway.

• Nutrition Research and Practice
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• v.8 no.6
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• pp.688-694
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• 2014

BACKGROUND/OBJECTIVES: Recent research regarding vitamin $B_6$ status including biochemical index is limited. Thus, this study estimated intakes and major food sources of vitamin $B_6$; determined plasma pyridoxal 5'-phosphate (PLP); and assessed vitamin $B_6$ status of Korean adults. MATERIALS/METHODS: Three consecutive 24-h diet recalls and fasting blood samples were collected from healthy 20- to 64-year-old adults (n = 254) living in the Seoul metropolitan area, cities of Kwangju and Gumi, Korea. Vitamin $B_6$ intake and plasma PLP were analyzed by gender and by vitamin $B_6$ supplementation. Pearson's correlation coefficient was used to determine associations of vitamin $B_6$ intake and plasma PLP. RESULTS: The mean dietary and total (dietary plus supplemental) vitamin $B_6$ intake was $1.94{\pm}0.64$ and $2.41{\pm}1.45mg/day$, respectively. Median (50th percentile) dietary intake of men and women was 2.062 and 1.706 mg/day. Foods from plant sources provided 70.61% of dietary vitamin $B_6$ intake. Only 6.3% of subjects consumed total vitamin $B_6$ less than Estimated Average Requirements. Plasma PLP concentration of all subjects was $40.03{\pm}23.71nmol/L$. The concentration of users of vitamin $B_6$ supplements was significantly higher than that of nonusers (P < 0.001). Approximately 16% of Korean adults had PLP levels < 20 nmol/L, indicating a biochemical deficiency of vitamin $B_6$, while 19.7% had marginal vitamin $B_6$ status. Plasma PLP concentration showed positive correlation with total vitamin $B_6$ intake (r = 0.40984, P < 0.0001). CONCLUSIONS: In this study, vitamin $B_6$ intake of Korean adults was generally adequate. However, one-third of subjects had vitamin $B_6$ deficiency or marginal status. Therefore, in some adults in Korea, consumption of vitamin $B_6$-rich food sources should be encouraged.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.597-615
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• 2023

Healthy aging can be defined as an extended lifespan and health span. Nutrition has been regarded as an important factor in healthy aging, because nutrients, bioactive food components, and diets have demonstrated beneficial effects on aging hallmarks such as oxidative stress, mitochondrial function, apoptosis and autophagy, genomic stability, and immune function. Nutrition also plays a role in epigenetic regulation of gene expression, and DNA methylation is the most extensively investigated epigenetic phenomenon in aging. Interestingly, age-associated DNA methylation can be modulated by one-carbon metabolism or inhibition of DNA methyltransferases. One-carbon metabolism ultimately controls the balance between the universal methyl donor S-adenosylmethionine and the methyltransferase inhibitor S-adenosylhomocysteine. Water-soluble B-vitamins such as folate, vitamin B6, and vitamin B12 serve as coenzymes for multiple steps in one-carbon metabolism, whereas methionine, choline, betaine, and serine act as methyl donors. Thus, these one-carbon nutrients can modify age-associated DNA methylation and subsequently alter the age-associated physiologic and pathologic processes. We cannot elude aging per se but we may at least change age-associated DNA methylation, which could mitigate age-associated diseases and disorders.

• Nutrition Research and Practice
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• v.17 no.1
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.