• Nutrition Research and Practice
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• v.18 no.1
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• pp.19-32
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr^tm1Her/J (Ldlr^-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)₂D₃ for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)₂D₃ treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)₂D₃ treatment. The 1,25(OH)₂D₃ treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

• Journal of Life Science
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• v.20 no.8
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• pp.1221-1229
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• 2010

Nerium indicum, an India-Pakistan-originated shrub belonging to the oleander family, is reported to possess many pharmacological activities including cardiac muscle stimulation, and anti-diabetes, anti-angiogenesis, anti-cancer and neuro-protective activities. However, the anti-inflammatory properties of N. indicum were unclear. In this study, we investigated the effects of ethanol extract of the N. indicum leaf and stem (ENIL and ENIS) on the expression of anti-inflammatory mediators in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate-13-acetate (PMA), pre-treatment with ENIS significantly inhibited the expression of both cyclooxygenase-2 (COX-2) mRNA and protein, which are associated with inhibition of the release of prostaglandin $E_2\;(PGE_2)$, whereas the inhibitory effects appeared weakly in ENIL. Moreover, ENIS significantly attenuated PMA-induced IkappaB ($I{\kappa}B$) degradation and suppressed elevated nuclear factor kappa B (NF-${\kappa}B$) nuclear translocation. Taken together, these findings provide important new insights that N. indicum exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-kB signaling pathway.

• Journal of Life Science
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• v.28 no.12
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• pp.1448-1454
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• 2018

Insects have been investigated as a novel source of food and biomaterial in several recent studies. However, their osteoblastogenic cell activity has not been sufficiently researched and so, to investigate the potential of this natural material for promoting osteoblastogenesis, we studied the activity of Locusta migratoria ethanol extract (LME) on MG-63 pre-osteoblast cells. The cytotoxicity and proliferation effects of LME on MG-63 cells were measured by MTS assay, and there was no cytotoxicity up to $1,000{\mu}g/ml$. With LME treatment of 500 and $1,000{\mu}g/ml$ for 48 hr, cell proliferation increased to 105% and 116% versus control, respectively. The osteoblastogenic activity of the LME was measured through alkaline phosphatase (ALP) staining at three and five days. As a result, both 500 and $1,000{\mu}g/ml$ LME concentrations were seen to increase ALP activity by more than three times compared with control at three and five days. In addition, the expression level of the osteogenic markers ALP and RUNX2 was markedly increased after LME treatment. These results demonstrate that Locusta migratoria ethanol extract promotes osteoblastogenesis as evidenced by the increased osteogenic markers and suggest that LME may be a potential agent for bone formation and osteoporosis prevention.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.5
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• pp.761-767
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• 2007

This study was conducted to determine the effects of exogenous zinc-metallothionein (Zn-MT) on anti-oxidative function and pork quality. After feeding a corn-soybean meal-based diet for two weeks, 48 pigs ($Duroc{\times}Landrace{\times}Chinese\;Black Pig$) were assigned randomly to four groups. Pigs in Group 1 were maintained under non-stress conditions, whereas pigs in Groups 2, 3 and 4 were aggressively handled for 25 min to produce stress. Pigs in Groups 1, 2, 3, and 4 received intramuscular administration of saline (control group; CON), 0 (negative control group; NCON), 0.8 (low dose group; LOW), and 1.6 (high dose group; HIGH) mg rabbit liver Zn-MT per kg body weight, respectively. Pigs were slaughtered at 3 and 6 h post-injection. Zn-MT treatment increased (p<0.05) the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) while decreasing the concentration of malondialdehyde (MDA) in liver. These responses were greater (p<0.05) at 6 h than at 3 h post Zn-MT injection. Zn-MT treatment increased (p<0.05) hepatic SOD mRNA levels in a time and dose-dependent manner and decreased (p<0.05) serum glutamate-pyruvate transaminase and lactate dehydrogenase activities (indicators of tissue integrity). Zn-MT administration decreased (p<0.05) lactate concentration and increased (p<0.05) pH and water-holding capacity in the longissimus thorasis meat. Collectively, our results indicate that intramuscular administration of Zn-MT to pre-slaughter stressed pigs improved tissue anti-oxidative ability and meat quality.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Korean Journal of Plant Resources
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• v.31 no.5
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• pp.466-477
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• 2018

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

• Journal of Ginseng Research
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• v.31 no.4
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• pp.181-190
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• 2007

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

• Journal of Life Science
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• v.31 no.11
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• pp.987-994
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• 2021

Our previous studies have reported that antimicrobial peptides (AMPs) derived from the larvae of white-spotted flower chafer (Protaetia brevitarsis seulensis) exert anti-inflammatory and neuroprotective activities. This study explored the anti-inflammatory effects of protaetiamycine 9 (CVLKKAYFLTNLKLRG-NH₂), a novel AMP, derived from P. b. seulensis against lipopolysaccharide (LPS)-mediated inflammatory response in RAW264.7 macrophage cells. Protaetiamycine 9 (25, 50, 75, and 100 ㎍/ml) did not cause cytotoxic effects against RAW264.7 cells. The RAW264.7 cells were pre-treated with various concentrations of protaetiamycine 9 (25-100 ㎍/ml) for 1 hr and then exposed to LPS (100 ng/ml) for 24 hr. Protaetiamycine 9 treatments decreased the LPS-induced secretion of inflammatory mediators, such as nitric oxide (NO), in a dose-dependent manner. Protaetiamycine 9 (25-100 ㎍/ml) effectively downregulated the LPS-induced increase in mRNA and the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. Protaetiamycine 9 also suppressed the production and gene expression of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, compared to the presence of LPS alone. Furthermore, protaetiamycine 9 inhibited the degradation of inhibitory kappa B alpha (IκB-α) and the phosphorylation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In conclusion, these results suggest that protaetiamycine 9 exhibits LPS-mediated inflammatory responses by blocking IκB-α degradation and MAPK phosphorylation.