• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.538-545
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• 2017

Objective: The goal of this study was to investigate the effects of cupric citrate (CuCit) on growth performance, antioxidant indices, serum lipid metabolites, serum immune indices, and tissue residues of copper (Cu), zinc, and iron in weaned pigs. Methods: A total of 180 weaned pigs ($Duroc{\times}Landrace{\times}Large$ White) with an average body weight of $8.98{\pm}1.21kg$ were randomly assigned to a corn-soybean meal control ration, or 4 similar rations with 30, 60, 120, or 240 mg/kg Cu as CuCit. All diets contained 10 mg/kg Cu as cupric sulfate from the vitamin-mineral premix. The experiment was divided into two phases: 0 to 14 d (phase 1) and 15 to 28 d (phase 2). Results: Average daily gain (ADG; linearly, p<0.01) and average daily feed intake (ADFI; linearly and quadratically, p<0.05) were affected by an increase in CuCit during phase 2. Overall period, ADG (p<0.05) and ADFI (p<0.01) were linearly increased with increasing dietary levels of CuCit. Serum malondialdehyde concentrations (p<0.05) and glutathione peroxidase activity (p<0.01) linearly decreased and increased respectively with an increase in CuCit. Serum levels of Cu-Zn superoxide dismutase were linearly affected with an increase in CuCit (p<0.01). Hepatic malondialdehyde levels decreased with an increase in CuCit (linearly and quadratically, p<0.01). Serum total cholesterol concentrations were quadratically affected (p<0.05) and decreased in pigs fed Cu as CuCit at 60 and 120 mg/kg and increased in pigs fed 240 mg/kg Cu as CuCit. Serum high-density lipoprotein concentrations were linearly affected with an increase in CuCit (p<0.01). Serum $IL-1{\beta}$ levels were quadratically affected (p<0.05) by dietary treatment. Compared with other treatments, 240 mg/kg Cu from CuCit quadratically increased hepatic (p<0.01) and renal (p<0.05) Cu concentrations, and quadratically decreased hepatic and renal iron concentrations (p<0.05). Conclusion: Cu administered in the form of CuCit at a dosage range of 30 to 60 mg/kg, effectively enhanced the growth performance and antioxidant status of weaned pigs.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.149-154
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• 2017

To increase the efficiency of esterase production by Bacillus, high cell-density culture of recombinant Escherichia coli through fed batch fermentation was tested. Cells were cultured to $OD_{600}$ of 76 (35.8 g/l DCW) with dissolved oxygen level controlled to least above 30% air saturation by supplying pure oxygen. Cells were cultured to an $OD_{600}$ of 90 (42.4 g/l DCW) with glucose feeding controlled to at least 1 g/l. However, the cells reached stationary phase at the late stage of culture, despite glucose being supplied. Cells were cultured to an $OD_{600}$ of 185 (87.3 g/l DCW) by supplying additional medium with fortified yeast extract. To increase the productivity of the recombinant protein, cell growth and esterase productivity based on induction time were evaluated. Late exponential phase induction for esterase production in fed batch fermentation resulted in maximum optical density $OD_{600}$ of 190 (89 g/l DCW) and maximum esterase activity of 1745 U/l, corresponding to a 5.8-fold enhancement in esterase production, compared to the early exponential phase induction. In this study, we established fermentation methods for achieving maximum production of Bacillus-derived esterase by optimizing IPTG induction time in high-cell density culture by supplying pure oxygen and a nitrogen source.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.2
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• pp.267-272
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• 2017

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.354-360
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• 2020

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

• Journal of Periodontal and Implant Science
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• v.32 no.4
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• pp.733-744
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• 2002

The fibroblasts are the principal cells in the periodontal ligament of peridontium. As the periodontal ligament fibroblasts (PDLF) show similar phenotype with osteoblasts, the PDLF are thought to play an important role in alveolar bone remodeling. Cell-to-cell contacted signaling is crucial for osteoclast formation. Recently it has been reported that PDLJ enhance the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The aims of this study were to $clarify\;^{1)}$ the mechanism of PDLF-induced osteoclastogenesis $and\;^{2)}$ whether we can use preosteoclast cell line instead of primary hematopoietic preosteoclast cells for studying the mechanism of PDLF-induced osteoclastogenesis. Osteoclastic differentiation of mouse macrophage cell line RAW264.7 was compared with that of mouse bone marrow-derived M-CSF dependent cell (MDBM), a well-known hematopoietic preosteoclast model, by examining, 1) osteoclast-specific gene expression such as calcitonin receptor, M-CSF receptor (c-fms), cathepsin K, receptoractivator nuclear factor kappa B (RANK) ,2) generation of TRAP(+) multinucleated cells (MNCs), and 3) generation of resorption pit on the $OAAS^{TM}$ plate. RAW264.7 cultured in the medium containing of soluble osteoclast differentiation Factor (sODF) showed similar phenotype with MDBM-derived osteoclasts, those are mRNA expression pattern of osteoclast-specific genes, TRAP(+) MNCs generation, and bone resorbing abivity. Formation of resorption pits by osteoclastic MNCs differentiated from sODF-treated RAW264.7, was completely blocked by the addition of osteoprotegerin (OPG), a soluble decoy receptor for ODF, to the sODF-containing culture me야um. The effects of PDLF on differentiation of RAW264.7 into　the TRAP(+) multinucleated osteoclast-like cells were examined using coculture system. PDLF were fxed with paraformaldehyde, followed by coculture with RAW264.7, which induced formation of TRAP(+) MNCs in the absence of additional treatment of sODF. When compared with untreated and fixed PDLF (fPDLF), IL-1 ${\beta}$-treated, or lipopolysaccha-ride-treated and then fixed PDLF showed two-folld increase in the supporting activity of osteoclastogenesis from RAW264.7 coculture system. There were no TRAP(+) MNCs formation in coculture system of RAW264.7 with PDLF of no fixation. These findigs suggested that we can replace the primary hematopoietic preosteoclasts for RAW264. 7 cell line for studying the mechanism of PDLF-induced osteoclastogenesis, and we hypothesize that PDLF control osteoclastogenesis through ODF expression which might be enhanced by inflammatory signals.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.409-416
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• 2017

1,2,3,4,6-Penta-O-galloyl-${\beta}$-D-glucose (PGG) is a gallotannin isolated from Galla Rhois. In a previous study, PGG was shown to suppress the allergic response by attenuating immunoglobulin E production both in vitro and in vivo. However, the effect of PGG on bacteria-induced inflammation at physiological concentration remains unclear. Therefore, the aim of this study was to investigate the effect of PGG on lipopolysaccharide (LPS)-stimulated macrophages. PGG inhibited release of nitric oxide (NO) and prostaglandin $E_2$ by alleviating protein expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Furthermore, PGG suppressed the release of interleukin-6 and tumor necrosis factor-${\alpha}$ induced by LPS. Further study indicated that PGG blocked translocation of the p65 subunit of nuclear factor-${\kappa}B$ from the cytosol into the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of PGG. Collectively, these data suggest that PGG might be useful for the treatment of inflammatory disease.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.149-164
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• 2007

Objectives : Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease in the gastrointestinal tract. The sources and pathologic mechanisms of IBD are still unknown. Moreover conventional therapies for IBD are not always effective, and they often have serious side effects. The purpose of this study is to examine the effect of Moxi-tar herbal acupuncture in IBD affected mice. Methods : Mice were treated with 5 % 2, 4, 6 - trinitrobenzenesulfonic acid (TNBS) on day 1 and day 7. To assume the preemptive effect and therapeutic effect, herbal acupuncture was practiced with Moxi-tar at BL25 (Daejangsu) on day 0, day 3, and day 6. The end of day in treatment with Moxi-tar herbal acupuncture, the mortality and the inflammatory factors of the colon were measured by the various methods. Results TNBS induced high mortality but herbal acupuncture with Moxi-tar at BL25 sup-pressed the mortality caused by TNBS. TNBS induced infiltration of immune cells in all layers of the colon and increased myeloperoxygenase (MPO) activity, while the treatment with Moxi-tar herbal acupuncture at BL25 suppressed the infiltration of immune cells and the increase of MPO activity caused by TNBS to normal levels, Herbal acupuncture with Moxi-tar regulated $NF-{\kappa}B$ activity, which is an important factor for the pathogenesis of chronic colitis, and reduced the expressions of $TNF-{\alpha}$, $IL-1{\beta}$, and ICAM-1 in the colons of TNBS treated mice. Furthermore herbal acupuncture suppressed macro- and micro- colonic damages caused by TNBS. Conclusions : This study demonstrates that herbal acupuncture with Moxi-tar at BL25 isa potential preemptive and/or therapeutic method targeting the chronic IBD.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.211-219
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• 2021

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.17-26
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• 2018

Objective : In this study, we investigated the effect of SAL5(mixing extracts of Schisandra chinensis Baillon, Artemisia capillaris Thunb., and Aloe vera Linne) on chronic ethanol-induced fatty liver model. Methods : Sprague-Dawley male rats were fed Liber-DeCarli (normal), ethanol liquid diet (control), SAL5 (200 mg/kg). We administrated the SAL5 on chronic ethanol-induced fatty liver model for 5 weeks. We measured alkaline phosphtase (ALP), alanine transminase (ALT), aspartate transminase (AST) and ${\gamma}-glutamyl$ transpeptase (${\gamma}-GTP$) in serum and triglyceride (TG), superoxide dismutase (SOD), catalase, glutathione (GSH) and malondialdehyde (MDA) level in liver. Liver histopathology was examined by Hematoxylin-eosin and Oil red O staining of the fixed liver tissues. Real-time PCR was performed to measure the mRNA expression of inflammatory cytokines and MMP-2, MMP-9. Results : SAL5 administration resulted in significantly decreased liver marker enzymes activities of alanine transminase (ALT), ${\gamma}-glutamyl$ transpeptase (${\gamma}-GTP$) in serum and triglyceride (TG) activities in liver. The control group decreased the activities of superoxide dismutase (SOD), catalase (CAT) with the reduced level of glutathione (GSH) in liver. On the other hand, SAL5 group increased the activities of SOD, CAT and the level of GSH. SAL5 delayed the development of an alcoholic fatty liver by reversing fat accumulation in the liver, as evidenced in histological observations. The gene expression of mRNA were significantly decreased at the $IL-1{\beta}$, $TNF-{\alpha}$, NOS-II and MMP-2 by SAL5. Conclusions : These results indicate that SAL5 might have protective effect chronic ethanol-induced fatty liver models.

• Journal of Nutrition and Health
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• v.57 no.4
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• pp.403-417
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• 2024

Purpose: This study investigated the anti-inflammatory effects of Evodiae Fructus (EF) on hydrochloric acid (HCl)/ethanol-induced gastritis, focusing on its impact on oxidative stress by analyzing inflammatory cytokines and inflammation-related factors. The total polyphenol and flavonoid contents were determined through in vitro experiments, while the radical scavenging activity was confirmed using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. Methods: In vivo experiments were conducted on rats divided into 5 groups (n = 7/in each group): normal group (Normal), 150 mM HCl/60% ethanol-induced gastritis group (Control), 150 mM HCl/60% ethanol-induced gastritis group administered 10 mg/kg sucralfate (SC), 150 mM HCl/60% ethanol-induced gastritis group administered EF at the doses of 100 mg/kg or 200 mg/kg (EF100 or EF200). The mice were pretreated with the extract (EF) or drug (SC), and after 1 hour, 150 mM HCl/60% ethanol (v/v) mixture was administered orally. Reactive oxygen species (ROS) levels, peroxynitrite (ONOO^-), and pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1 beta were assessed in serum. Additionally, western blotting of the gastric tissues confirmed the expression of inflammation-related proteins. Results: EF alleviated the gastric mucosal damage caused by 150 mM HCl/60% ethanol. The assessment of oxidative stress in the serum showed that EF significantly reduced ROS and ONOO^- levels and significantly decreased the levels of pro-inflammatory cytokines. Western blot analysis revealed that EF reduced ROS-generating nicotinamide adenine dinucleotide phosphate oxidase subunits, including gp91^phox, p22^phox, and p47^phox. Additionally, EF mitigated the inflammation by inhibiting the mitogen-activated protein kinase signaling pathway. Conclusion: These results indicate that EF is a potential herbal medicine candidate for the treatment of oxidative stress-induced gastritis.