• 제목/요약/키워드: Mechanistic study

검색결과 298건 처리시간 0.019초

A novel mechanism of Korean Red Ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

  • Min, Ji-Hyun;Cho, Hui-Jin;Yi, Young-Su
    • Journal of Ginseng Research
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    • 제46권5호
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    • pp.675-682
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    • 2022
  • Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

Bifidobacterium bifidum DS0908 and Bifidobacterium longum DS0950 Culture-Supernatants Ameliorate Obesity-Related Characteristics in Mice with High-Fat Diet-Induced Obesity

  • M. Shamim Rahman;Youri Lee;Doo-Sang Park;Yong-Sik Kim
    • Journal of Microbiology and Biotechnology
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    • 제33권1호
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    • pp.96-105
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    • 2023
  • Probiotic supplements have promising therapeutic effects on chronic diseases. In this study, we demonstrated the anti-obesity effects of two potential probiotics, Bifidobacterium bifidum DS0908 (DS0908) and Bifidobacterium longum DS0950 (DS0950). Treatment with DS0908 and DS0950 postbiotics significantly induced the expression of the brown adipocyte-specific markers UCP1, PPARγ, PGC1α, PRDM16 and beige adipocyte-specific markers CD137, FGF21, P2RX5, and COX2 in C3H10T1/2 mesenchymal stem cells (MSCs). In mice with high-fat diet (HFD)-induced obesity, both potential probiotics and postbiotics noticeably reduced body weight and epididymal fat accumulation without affecting food intake. DS0908 and DS0950 also improved insulin sensitivity and glucose use in mice with HFD-induced obesity. In addition, DS0908 and DS0950 improved the plasma lipid profile, proved by reduced triglyceride, low-density lipoprotein, and cholesterol levels. Furthermore, DS0908 and DS0950 improved mitochondrial respiratory function, confirmed by the high expression of oxidative phosphorylation proteins, during thermogenesis induction in the visceral and epididymal fat in mice with HFD-induced obesity. Notably, the physiological and metabolic changes were more significant after treatment with potential probiotic culture-supernatants than those with the bacterial pellet. Finally, gene knockdown and co-treatment with inhibitor-mediated mechanistic analyses showed that both DS0908 and DS0950 exerted anti-obesity-related effects via the PKA/p38 MAPK signaling activation in C3H10T1/2 MSCs. Our observations suggest that DS0908 and DS0950 could potentially alleviate obesity as dietary supplements.

Ensemble deep learning-based models to predict the resilient modulus of modified base materials subjected to wet-dry cycles

  • Mahzad Esmaeili-Falak;Reza Sarkhani Benemaran
    • Geomechanics and Engineering
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    • 제32권6호
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    • pp.583-600
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    • 2023
  • The resilient modulus (MR) of various pavement materials plays a significant role in the pavement design by a mechanistic-empirical method. The MR determination is done by experimental tests that need time and money, along with special experimental tools. The present paper suggested a novel hybridized extreme gradient boosting (XGB) structure for forecasting the MR of modified base materials subject to wet-dry cycles. The models were created by various combinations of input variables called deep learning. Input variables consist of the number of W-D cycles (WDC), the ratio of free lime to SAF (CSAFR), the ratio of maximum dry density to the optimum moisture content (DMR), confining pressure (σ3), and deviatoric stress (σd). Two XGB structures were produced for the estimation aims, where determinative variables were optimized by particle swarm optimization (PSO) and black widow optimization algorithm (BWOA). According to the results' description and outputs of Taylor diagram, M1 model with the combination of WDC, CSAFR, DMR, σ3, and σd is recognized as the most suitable model, with R2 and RMSE values of BWOA-XGB for model M1 equal to 0.9991 and 55.19 MPa, respectively. Interestingly, the lowest value of RMSE for literature was at 116.94 MPa, while this study could gain the extremely lower RMSE owned by BWOA-XGB model at 55.198 MPa. At last, the explanations indicate the BWO algorithm's capability in determining the optimal value of XGB determinative parameters in MR prediction procedure.

Hydroxychavicol Inhibits In Vitro Osteoclastogenesis via the Suppression of NF-κB Signaling Pathway

  • Sirada Srihirun;Satarat Mathithiphark;Chareerut Phruksaniyom;Pitchanun Kongphanich;Wisutthaporn Inthanop;Thanaporn Sriwantana;Salunya Tancharoen;Nathawut Sibmooh;Pornpun Vivithanaporn
    • Biomolecules & Therapeutics
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    • 제32권2호
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    • pp.205-213
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    • 2024
  • Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

여성 리더의 성 역할과 신뢰가 조직 유효성에 미치는 영향: 교육교재 유통기업을 대상으로 (Women Leaders: Gender Roles, Trust, and Effects on Organizational Performance in Educational Material Distribution Enterprises)

  • 이남겸;황일영
    • 유통과학연구
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    • 제13권3호
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    • pp.93-100
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    • 2015
  • Purpose - Since the early 1990s, it has been observed that the number and substance of studies on female leadership have been increasing. One of the reasons for this development may be concerned with the increasing number of female labor market participants as well as the greater opportunities for them to take higher positions in various organizations. In addition to this, the transition from mechanistic organizational structures that emphasize authority, control, and efficiency toward organic ones that focus on environmental adaptability, equality, and trust has also encouraged research on female leadership. The research tendency is based on the assumption that male and female leaders tend to exhibit different leadership styles according to their gender differences. Recent research has cast doubt on this assumption, by showing that the sociological gender roles of men and women are independent such that some female leaders show authoritative and control-oriented leadership, which were once considered to be male leadership styles. Research design, data, and methodology - This research attempts to carry out an empirical study on the gender-related leadership styles of female leaders and to examine their effect on group performance in the K business organization. This study also focuses on leader attributes such as trust, and it aims to discover whether these attributes should be regarded as independent or as moderating variables between leadership styles and performance. For these purposes, this study generated four hypotheses based on a review of the literature and it tested them using a survey. Female workers in the sales departments of the K Company, all of whom are women, were asked to provide answers to the presented questionnaires. This study hypothesizes that the type of gender roles played by women leaders will affect the job satisfaction and organizational commitment among the members of the sales group, and that the level of trust that is garnered by women leaders will also affect the types of gender roles that they play as well as employee job satisfaction and organizational commitment. Results - The results of this study show that both androgynous and masculine leadership styles are superior to the feminine leadership style in terms of employee job satisfaction and organizational commitment. However, contrary to our expectations, this study fails to show the superiority of the androgynous leadership style over the masculine leadership style. Moreover, there are no significant differences between these two leadership styles with regard to group performance. Conclusions - This study shows that it is important that different attributes of leaders, such as how trusted they are, be treated as moderating variables between leadership and performance rather than as independent variables. Finally, as this is the first attempt to view the role of the gender in a new perspective, the managerial implications of this study for leadership research, as well as its limitations, are presented. Suggestions for future related research are also proposed.

아스팔트포장 잔존수명 예측 사례 연구 (A Case Study for the Estimation of Remaining Lives of Asphalt Pavements)

  • 이정훈;이현종;박희문;김인태
    • 한국도로학회논문집
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    • 제10권2호
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    • pp.1-13
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    • 2008
  • 본 연구에서는 다양한 아스팔트포장의 공용수명을 예측하기 위한 포장상태 평가의 사례를 제시하였다. ARAN(Automatic Road Analyzer)을 이용하여 균열 및 소성변형 감과 감전 포장의 표면파손 현황에 대한 조사를 실시하고 HPCI(Highway Pavement Condition Index)를 산정하였다. 포장 파손현황을 분석한 결과 가장 빈번한 형태의 파손은 Top-down 균열로 나타났다. FWD(Falling Weight Deflectometer)로부터 측정한 처짐데이터를 사용하여 포장의 탄성계수를 역산정하여 실내에서 구한 동탄성계수와 비교하였다. 그 결과를 역학적-경험적 방법과 AASHTO 93 설계법에 적용하여 포장의 지지력을 평가하였으며, 지지력은 설계수명 동안 충분한 것으로 평가되었다. 현재 포장의 주된 파손은 표층부의 Top-down 균열이므로 포장상태 평가로 계산된 HPCI와 기존 공용성 자료에 근거하여 포장의 잔존수명을 예측하였다. 포장상태 평가와 함께 포장의 조기파손 원인분석을 위해 대상구간의 코어 시편을 채취하여 공극률, 입도, 아스팔트 함량, 피로저항성 등의 물성을 측정하였다. 바인더를 태워 아스팔트 함량을 측정하는 방법은 현장시료의 경우 부정확한 것으로 나타났다. 실내시험결과 조기 균열이 발생한 가장 큰 이유는 다짐부족과 골재의 입도 부정확 등 시공시의 품질관리가 미흡한 것이 주된 원인으로 나타났다.

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연성포장설계의 소성변형과 피로파괴 예측모델에 대한 신뢰성 연구 (A Study of Reliability of Predictive Models for Permanent Deformation and Fatigue Failure Related to Flexible Pavement Design)

  • 김도완;한범수;김연주;문성호
    • 한국도로학회논문집
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    • 제16권6호
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    • pp.105-113
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    • 2014
  • PURPOSES: The objective of this paper is to select the confidential intervals by utilizing the second moment reliability index(Hasofer and Lind; 1974) related to the number of load applications to failure which explains the fatigue failure and rut depth that it indicates the permanent deformation. By using Finite Element Method (FEM) Program, we can easily confirm the rut depth and number of load repetitions without Pavement Design Procedures for generally designing pavement depths. METHODS : In this study, the predictive models for the rut depth and the number of load repetitions to fatigue failure were used for determining the second moment reliability index (${\beta}$). From the case study results using KICTPAVE, the results of the rut depth and the number of load repetitions to fatigue failure were deducted by calculating the empirical predictive equations. Also, the confidential intervals for rut depth and number of load repetitions were selected from the results of the predictive models. To determine the second moment reliability index, the spreadsheet method using Excel's Solver was used. RESULTS : From the case studies about pavement conditions, the results of stress, displacement and strain were different with depth conditions of layers and layer properties. In the clay soil conditions, the values of strain and stresses in the directly loaded sections are relatively greater than other conditions. It indicates that the second moment reliability index is small and confidential intervals for rut depth and the number of load applications are narrow when we apply the clay soil conditions comparing to the applications of other soil conditions. CONCLUSIONS : According to the results of the second moment reliability index and the confidential intervals, the minimum and maximum values of reliability index indicate approximately 1.79 at Case 9 and 2.19 at Case 22. The broadest widths of confidential intervals for rut depth and the number of load repetitions are respectively occurred in Case 9 and Case 7.

Effect of Dietary Chlorella Complex on Anticancer Activity in Mice

  • Jung Jae-Hak;Jin Kyong-Suk;Kim Yong-Ho;Lee Yong-Woo
    • 대한의생명과학회지
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    • 제11권2호
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    • pp.185-192
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    • 2005
  • Dietary chlarella has known as one of the best candidates for development of multifunctional probiotic foods owing to an excellent nutritional value such as high amount of proteins and various, valuable fatty acids. So many efforts were devoted to studying the chlorella as therapeutic agents or foods fighting against many diseases in the aged people such as cardiovascular diseases and cancers. In this study, we investigated sizes and weights of tumors derived from mice injected subcutaneously with tumorigenic cells to see if antitumor activity would be found in mice dieted with the chlarella complex. After BALB/c mice were dieted with $5\%$ organic cultured chlorella complex diet throughout for 19weeks, the fibrosarcoma was induced by subcutaneous injection of tumorigenic cells at the 3 weeks before sacrifice. The average weight of tumors in the diet group were significantly reduced to $60\%\;(P=0.012)$ of the one in control group, indicating that diet with the chlarella complex may have anticancer activity in mice. When the mice were dieted with $5\%$ organic cultured chlorella complex for 4 weeks before injecting the tumorigenic cells in order to see tumor-preventive effect of the diet, the potential preventive activity of the diet against cancer was implicated by the observation that the tumors were greatly reduced in the diet group to $37\%$ (P=0.l44) of the control group. Especially, when the $5\%$ diet were applied to mice after injecting with the tumorigenic cells, the tumors derived from the $5\%$ diet group were also decreased to $95\%$ (P=0.002) of those in the control group, suggesting that the diet with the organic cultured chlorella complex may also have therapeutic effect against tumor formation. As results, it was shown that the chlorella complex tested in this study had preventive and therapeutic effects on fighting against tumorigenesis. Therefore, the identification and further mechanistic study of the components which may be associated with antitumor activity from diet of the chlorella complex in the future will contribute to the development of anticancer probiotic foods, alternative therapeutic treatment against cancer, and a new anticancer drug.

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퍼포먼스.이벤트의 결합체로서 건축환경연구 (A Study on the Architectural Environment as a Combination of Performance and Event)

  • 김주미
    • 디자인학연구
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    • 제14권
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    • pp.121-138
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    • 1996
  • 전환기적 시대상황의 인식과 뉴 패러다임에 기초하여 미래 건축환경의 변화를 예측하고 그에 대응할 수 있는 건축언어와 새로운 디자인 전략을 제안하는데 본 연구의 목적이 있었으며, 그 연구내용과 결과는 다음과 같다. 첫째, 현대 예술 속에서 공간, 인간의 신체, 그리고 움직임을 재해석하고 그 예술적 의도를 환경디자인과 결합시켜 퍼포먼스·이벤트건축의 가능성을 고찰하였다. 둘째, 건축환경은 물질들만의 집합보다는 공간, 움직임, 우연적 상황 그리고 이벤트들의 결합체로서 보았다. 또한 퍼포먼스장소로서의 환경을 이해함과 동시에 디자인 행위자체를 퍼포먼스 과정으로 제시하였다. 셋째, 인간은 환경과의 상호작용을 통해 항상 반응하며 스스로의 조절을 통해 적응하는 유기체적 시스템이다. 건축 또한 현시대의 불확정적인 인식체계와 빠르게 변화하는 사회구조, 테크놀러지의 발전과 함께 인간의 행위, 활동이 결합되어 끊임없이 변화하는 역동적 시스템으로 설명되었다. 넷째, 본 연구자는 종래 모더니즘 디자인에서의 형태와 기능의 인과론적, 기계론적 조형태도에서 벗어나 상대론 적, 유기론 적 관점을 취하과자 하였다. 특히 탈 물질적인 환경의 개념을 강조하였으며 형태와 기능의 상호 텍스트 성, 그리고 시간의 흐름 속에서 상호변화 가능성을 지원할 수 있는 탈 프로그램 방법을 제안하였다. 결과적으로 퍼포먼스·이벤트건축의 전략은 인간의 자율적 기능의 회복과 예술로서의 환경을 어느 정도 가능하게 할 수 있는 개념이라고 보았으며, 시스템적 세계관으로의 전환을 강조하였다.

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초등 예비교사가 인식적 행위주체로서 고안한 생명과학 관련 지식 구성 활동의 인식적 목표 및 특성 탐색 (Exploring the Epistemic Goals and Features of Biology-Related Knowledge Construction Activities Shaped by Pre-Service Elementary Teachers as Epistemic Agents)

  • 하희수
    • 한국과학교육학회지
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    • 제41권1호
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    • pp.47-57
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    • 2021
  • 본 연구에서는 학습자의 인식적 행위주체성을 촉진하기 위하여 인식적 목표를 명시화하는 지식 구성 활동을 설계하여 초등 예비교사를 위한 생물학 강좌에 도입하였고, 이 활동에 참여한 예비교사들이 어떠한 유형의 인식적 목표를 어떻게 고안하였으며, 이 목표를 중심으로 정교한 수준의 인식적 특성을 지닌 지식 구성 활동이 형성되도록 촉진하거나 이를 제한한 요인을 탐색했다. 이를 위해 활동에 참여한 예비교사들의 실행 및 산출물을 녹음 및 수집했으며, 녹음 자료는 전사하여 본 연구의 분석 자료로 활용하였다. 분석 결과, 예비교사들이 고안한 인식적 목표의 유형은 '자연 현상에 대한 의미 형성하기', '실용적 선택안 제시하기', '문제 현상의 기작에 기반한 해결책 제시하기'로 도출되었다. 각 인식적 목표 유형은 예비교사들이 탐구하기로 선정한 자연 현상에 대한 지식을 바탕으로 어떠한 결론을 얻고자 하는가에 따라 서로 다르게 고안되었다. 예비교사가 인식적 목표를 명시화하는 활동 구조는 이들이 근거 기반의 지식 주장 정당화가 수반되는 지식 구성 활동을 고안하도록 촉진할 수 있는 것으로 분석되었다. 예비교사가 고안한 지식은 지식의 본성 측면에서 주로 현상에 관한 기술에 그쳤으며, 현상의 기작에 관한 설명 구성은 자연 현상이 일어나는 기작에 대한 의미를 형성하고자 하거나 현상의 기작에 대한 이해를 바탕으로 문제해결을 위한 해결책을 제시하고자 계획할 때 나타났다. 그러나 예비교사들이 활용 가능한 시간적·물리적 자원의 한계에 따라 기작에 대한 설명 산출 과정에서 정교한 수준의 인식적 특성을 지닌 지식 구성 활동이 제한될 수 있는 것으로 분석되었다. 본 연구는 학습자의 인식적 행위주체성을 촉진하는 교수학습 전략의 고안 및 인식적 행위주체성을 중심으로 한 예비교사 교육에 대한 논의에 기여할 수 있을 것으로 기대한다.