• Journal of Microbiology and Biotechnology
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• 제17권2호
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• pp.348-358
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• 2007

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

• Nutrition Research and Practice
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• 제12권2호
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• pp.110-117
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• 2018

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.

• 의료ㆍ복지 건축 : 한국의료복지건축학회 논문집
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• 제23권4호
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• pp.17-25
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• 2017

Purpose: Since hospitals have a big impact on the natural and social environment, hospitals' sustainability must be considered in various aspects including environmental, social, and economical aspects. So far, research on sustainable hospitals has mainly been conducted on indoor environment, but outdoor space of hospital is as important as well. The purpose of this research is to study the sustainability of hospital outdoor space and to make proposals for improving sustainable regional public hospitals. Methods: Through preceding research analysis and literature review, the concept of sustainable outdoor space of hospital was defined. Also, the evaluation contents of outdoor space were extracted from domestic and foreign green building certification criteria. With this analytic frame, we visited 4 regional public hospitals in Korea, interviewed the facility managers, and analyzed sustainability of hospital outdoor space. Results: Analysis of 4 regional public hospitals reveals that there is a lack of consideration for sustainability in all 4 categories; urban and network, natural environment, community, and user. In terms of community, sustainability has rarely been applied to all four hospitals. The site selection and terrain of the site were essential to sustainability. Implications: Establishing a master plan considering future expansion is critical. Also more attempt to show regional characteristics is needed. It is necessary to design a comprehensive outdoor space that considers sustainability and also healing environment. Level difference in the site can be used as a design element.

• 생약학회지
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• 제34권3호통권134호
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• pp.228-232
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• 2003

For effective management of atopic dermatitis, it is important to introduce a therapeutic agent although having the fewest side effects, has the greatest anti- inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM composed of several plant extracts. This study was designed to investigate anti-inflammatory and immunomodulatory effects of BSASM. As a first step, $NF-{\kappa}B$ luciferase reporter assay was performed to know the involvement of BSASM in the production of proinflammatory cytokines because $NF-{\kappa}B$ element has been known to play a major role in expression of cytokine genes such as interleukin-8 (IL-8) or tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. LPS (lipolysaccharide)-induced $NF-{\kappa}B$ activation was inhibited by BSASM. In addition, we found the fact that BSASM inhibits LPS-induced produced production of IL-8 and $TNF-{\alpha}$ proinflammatory cytokines, indicating BSASM has anti-inflammatory effect. In interleukin-2 (IL-2) luciferase reporter assay in Jurkat T cells, BSASM reduced PHA (Phytohemagglutinin)-induced IL-2 luciferase activity, suggesting the possibility that BSASM might also have an immunomodulatory function in T cell-mediated immune response. Based on these results, we suggest the possibility that BSASM can be introduced to improve symptom of immune-related skin diseases, namely, atopic dermatitis.

• 한국발생생물학회지:발생과생식
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• 제23권2호
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• pp.129-138
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• 2019

In many cases, obesity is associated with metabolic disorders. Recently, natural compounds that may be beneficial for improving obesity have received increasing attention. Bitter melon has received attention as a diabetes treatment. $NAD^+$-dependent deacetylase (Sirtuin 1, SIRT1) has emerged as a novel therapeutic target for metabolic diseases. In this study, ethanol extract of bitter melon (BME) suppressed adipocyte differentiation and significantly increased the expression of SIRT1 in fully differentiated 3T3-L1 cells. Moreover, it enhanced the activation of AMP-activated protein kinase (AMPK). In high-fat diet (HFD)-fed induced-obesity mice, BME suppressed HFD-induced increases in body weight and white adipose tissue (WAT) weight. BME also increased the expression of SIRT1 and suppressed peroxisome proliferator-activated receptor and sterol regulatory element binding protein 1 expressions of WAT from HFD-fed mice. These findings suggest that BME prevents obesity by activating the SIRT1 and AMPK pathway and that it may be a useful dietary supplement for preventing obesity.

• BMB Reports
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• 제54권8호
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• pp.419-424
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• 2021

Cold-induced norepinephrine activates β3-adrenergic receptors (β3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the β3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with β3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at -3.7 and -2.0 kb of the transcription start site. The CL316,243-induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in β3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity.

• Medical Lasers
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• 제9권2호
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• pp.142-149
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• 2020

Background and Objectives A picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element elicits therapeutic micro-injury zones in the skin. This study examined the patterns of tissue reactions after delivering multiple pulses of 1,064-nm, MLA-type, picosecond neodymium:yttrium-aluminum-garnet laser treatment. Materials and Methods Multiple pulses of picosecond laser treatment were delivered to ex vivo human or brown micropig skin and analyzed histopathologically. A high-speed cinematographic study was performed to visualize the multiple pulses of picosecond laser energy-induced skin reactions in in vivo human skin. Results In the ex vivo human skin, a picosecond laser treatment at a fluence of 0.3 J/cm² over 100 non-stacking passes generated multiple lesions of thermally-initiated laser-induced optical breakdown (TI-LIOB) in the epidermis and dermis. In the ex vivo micropig skin, stacking pulses of 20, 40, 60, 80, and 100 at a fluence of 0.3 J/cm² generated distinct round to oval zones of tissue coagulation in the mid to lower dermis. High-speed cinematography captured various patterns of twinkling, micro-spot reactions on the skin surface over 100 stacked pulses of a picosecond laser treatment. Conclusion Multiple pulses of 1,064-nm, MLA-type, picosecond laser treatment elicit marked TI-LIOB reactions in the epidermis and areas of round to oval thermal coagulation in the mid to deep dermis.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.285-297
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• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Journal of Veterinary Science
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• 제24권2호
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• pp.20.1-20.13
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• 2023

Background: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. Objectives: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. Methods: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. Results: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. Conclusions: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.

• 한국의사학회지
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• 제35권2호
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• pp.45-67
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• 2022

Currently, there are about 20,000 or so known ancient medical texts from the East Asian medical traditions. Although the most famous texts are widely known, many texts still exist only as original manuscripts. We are interested exploring these texts to uncover the potential benefits of their therapeutic knowledge. This study aims to develop a database program that automatically converts the treatment skills described in the text version into a more structured version. In the previous study, our team analyzed patterns in the way that treatment skills are described and then tried to design a database program algorithm that identified every meaningful keyword used to describe treatment skills and put that word in the right cell of a structured table. This study continues the development of this program. East Asian medical herbal treatment information is broken down into 4 elements: the first one is the name or title of treatment skills, and the second is the symptoms to which the treatment is applied, the third is ingredients used, the fourth is how information is processed and the indications taken. This study presents the algorithm's principles on how to analyze and structure the fourth element, the processing of information and taking of indications, which is described in a form of ancient natural language.