• 대한치과마취과학회지
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• 제14권2호
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• pp.101-106
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• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.3.1-3.14
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• 2018

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.392-400
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• 2002

We have previously found that the saponins but not other components in the ginseng reduce the secretion of catecholamines (CAs) from bovine adrenal chromaffin cells, a model of sympathetic nerves, evoked by acetylcholine (ACh) due to the blockade of $Na^+$ influx through nicotinic ACh receptor-operated cation channels, and it has been concluded that the inhibitory effect may be associated with the anti-stress action of ginseng. However, the saponins, which showed the great reduction of the CA secretion, were mainly the protopanaxiatriols. The protopanaxadiol and oleanolic acid saponins had a little or little such effect. Recent studies demonstrated that the oligosaccharides connected to the hydroxyl groups of the aglycones of the saponins are in turn hydrolyzed by gastric acid and enzymes in the intestinal bacteria when the ginseng is orally administrated. In this study, the effects of their major 6 kinds of metabolites on the secretion of CAs were investigated. All metabolites (M1, 2, 3 and 5 derived from the protopanaxadiols, and M4 and 11 from the protopanaxiatriols) reduced the ACh-evoked secretion from the cells. In the metabolites, the M4 inhibition was the most potent ($IC_{50}({\mu}M):M4(9)$ < M2 (18) < M3 (19) < M1l (22) < M5 (36) < MI (38)). Although M4 also reduced the CA secretion induced by high $K^+$, a stimulation activating voltage-sensitive $Ca^{2+}$ channels, the inhibitory effect was much less than that on the ACh-evoked secretion. M4 inhibited the ACh-induced $Na^+$ influx into the cells in a concentration-dependent manner similar to that of the inhibition of the ACh-evoked secretion. When the cells were washed by the incubation buffer after the preincubation of the cells with M4 and then incubated without M4 in the presence of ACh, the M4 inhibition was not completely abolished. On the other hand, its inhibition was maintained even by increasing the external ACh concentration. These results indicate that the saponins are metabolized to the more active substances in the digestive tract and the metabolites attenuate the secretion of CAs from bovine adrenal chromaffin cells stimulated by ACh due to the noncompetitive blockade of the ACh-induced $Na^+$ influx into the cells. These findings may further explain the anti-stress action of ginseng.

• Nutrition Research and Practice
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• 제15권6호
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• pp.798-806
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity. Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3'-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the anti-inflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/cholesterol diet (HFCD)-fed C57BL/6 mice. MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate pro-inflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue. RESULTS: Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements. CONCLUSIONS: PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.

• Journal of Periodontal and Implant Science
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• 제51권6호
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• pp.374-385
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• 2021

Purpose: The aim of this study was to evaluate the effects of locally delivered 1% alendronate (ALN) gel used as an adjunct to non-invasive periodontal therapy. Methods: Ligature-induced periodontitis was performed in 96 rats. The ligature was tied in the cervical area of the mandibular left first molar. The animals were randomly divided into 4 groups: 1) NT, no treatment; 2) SRP, scaling and root planning; 3) SRP/PLA, SRP followed by filling the periodontal pocket with placebo gel (PLA); and 4) SRP/ALN, SRP followed by filling the periodontal pockets with 1% ALN gel. Histomorphometric (percentage of bone in the furcation region [PBF]) and immunohistochemical (receptor activator of nuclear factor-κB ligand, osteoprotegerin, and tartrate-resistant acid phosphatase) analyses were performed. Data were statistically analyzed, with the threshold of statistical significance set at P≤0.05. Results: The SRP, SRP/PLA, and SRP/ALN groups presented a higher PBF than the NT group (P≤0.01) at 7, 15, and 30 days. The SRP/ALN group presented a higher PBF than the SRP/PLA group in all experimental periods, as well as a higher PBF than the SRP group at 15 and 30 days. No differences were observed in the immunohistochemical analyses (P>0.05 for all). Conclusions: Locally delivered 1% ALN gel used as an adjunct to SRP enhanced bone regeneration in the furcation region in a rat model of experimental periodontitis.

• The Korean Journal of Physiology and Pharmacology
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• 제23권2호
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

• 기호학연구
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• 제56호
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• pp.7-44
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• 2018

본 연구의 목적은 인지과학의 관점에 근거하여 한국어 맛 어휘, 특히 한국어 맛 형용사의 분류 체계를 제안하는데 있다. 이때 한국어 맛 형용사의 분류는 인지과학의 분과 학문들이 수용하는 '미각'과 '향미'와 '맛'의 정의에 근거하여 이루어진다. 국내에서는 맛 어휘와 관련하여 많은 연구가 이루어져 왔다. 그래서 맛 어휘의 분류와 관련된 연구 결과물들이 꾸준히 발표되었으나, 연구자에 따라 크고 작은 차이를 보인다. 이는 연구자들이 맛 어휘를 범주화하는데 있어 객관적이고 보편적인 기준보다는 주관적이고 직관적인 기준을 적용했기 때문이다. 우리가 일상생활에서 흔히 말하는 '맛'은 미각 수용기 세포가 지각하는 감각 이상의 것을 포괄한다. 게다가 우리 인간이 지각하는 맛의 80~90%는 냄새에 좌우되어, 맛의 지각에 있어 후각의 중요성이 강조된다. 한편 음식의 식감과 색상과 온도, 음식을 먹는 주변 환경, 음식을 먹는 사람의 개인적 사회문화적 기호척도 등이 맛 지각에 큰 영향을 미친다. 먹는 것과 맛을 보는 것은 우리의 일상생활에서 중요한 부분을 차지한다. 그래서 맛 지각에 대한 언어학적 접근은 결코 간과할 수 없는 연구 영역이다. 본 연구자는 인지과학의 관점에 따른 맛 어휘의 분류가 맛 지각의 인지 메커니즘을 이해하는데 도움을 줄 수 있다는 가정에서 출발한다. 본 연구는 우리 인간의 심상어휘집에 '존재할 혹은 존재할지 모르는' 맛 어휘 낱말밭의 모습을 기하학적 모델로 형상화하고자 하는 후속 연구의 사전 작업임을 이 자리를 빌려 밝혀둔다.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.367-379
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• 2019

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

• 한국산업보건학회지
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• 제31권2호
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• pp.173-183
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• 2021

Objectives: This study evaluated the skin permeability of lawsone in henna hair dyes to understand the exposure characteristics of henna hair dyes in the human body. It examined the protective effects of protectants by applying protectants A, B, and C to test skin. Methods: Skin absorption tests were conducted using Franz diffusion cells according to OECD test guideline 428. After applying one kind of natural henna hair dye and chemical henna hair dye, respectively, to a standardized pig skin model, samples of receptor fluid were collected at 1h, 3h, 6h, and 24h. The skin permeation of lawsone was determined using HPLC. After the skin absorption experiment, the skin to which hair dye was applied was analyzed to determine the residual amount of lawsone in the skin. Results: The cumulative permeation of both natural and chemical henna hair dyes increased over time, and the natural henna hair dye had a flux value (t=3.194, p<.05) high both in the K_p value (t=3.207, p<.05) and the residual amount (t=22.701, p<.001). For skin treated with a protectant, the cumulative permeation of natural henna hair dye 24h control and the cumulative permeation of protectant A, B, and C increased over time. Flux and K_p values were in the order control > protectant A > protectant C > protectant B. The residual amount (F=4.469, p<.05) was in the order of protectant C > protectant A > protectant B > control. At 3h, the dye application time of natural henna hair dye, the lawsone flux value (F=4.454, p<.05) and K_p value (F=4.455, p<.05) were higher in the control group than in the protectant groups. The 24h cumulative permeation of the chemical henna hair dye increased with time in both the control and the protectant groups, and the flux and K_p values were in the order of protectant A > protectant C > protectant B > control. The residual amount (F=7.901, p<.01) was in the order of protectant B > protectant A> protectant C > control. Conclusions: Within the normal dyeing time for henna hair dye (three hours for natural henna hair dyes and 30 minutes for chemical henna hair dyes) lawsone skin penetration was not observed even when no protective agent was applied. After that time, however, evidence of skin penetration and retention of lawsone and the protective effect of protective agents were observed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권4호
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• pp.377-383
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• 2021

Purpose: We investigated the association of effector memory (EM) CD8⁺ T cell and CD4⁺ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8⁺ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4⁺ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rα^low CD8⁺ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα^lowCX3CR1⁺ CD8⁺ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα^lowCX3CR1⁺ and IL-7Rα^highCX3CR1^- CD8⁺ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4⁺ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8⁺ T cells might be related to the morbidity of obesity.