• 제목/요약/키워드: expression dynamics

검색결과 176건 처리시간 0.022초

Fuzzy neural network controller of interconnected method for civil structures

  • Chen, Z.Y.;Meng, Yahui;Wang, Ruei-yuan;Chen, Timothy
    • Advances in concrete construction
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    • 제13권5호
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    • pp.385-394
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    • 2022
  • Recently, an increasing number of cutting-edged studies have shown that designing a smart active control for real-time implementation requires piles of hard-work criteria in the design process, including performance controllers to reduce the tracking errors and tolerance to external interference and measure system disturbed perturbations. This article proposes an effective artificial-intelligence method using these rigorous criteria, which can be translated into general control plants for the management of civil engineering installations. To facilitate the calculation, an efficient solution process based on linear matrix (LMI) inequality has been introduced to verify the relevance of the proposed method, and extensive simulators have been carried out for the numerical constructive model in the seismic stimulation of the active rigidity. Additionally, a fuzzy model of the neural network based system (NN) is developed using an interconnected method for LDI (linear differential) representation determined for arbitrary dynamics. This expression is constructed with a nonlinear sector which converts the nonlinear model into a multiple linear deformation of the linear model and a new state sufficient to guarantee the asymptomatic stability of the Lyapunov function of the linear matrix inequality. In the control design, we incorporated H Infinity optimized development algorithm and performance analysis stability. Finally, there is a numerical practical example with simulations to show the results. The implication results in the RMS response with as well as without tuned mass damper (TMD) of the benchmark building under the external excitation, the El-Centro Earthquake, in which it also showed the simulation using evolved bat algorithmic LMI fuzzy controllers in term of RMS in acceleration and displacement of the building.

Single-cell RNA sequencing reveals the heterogeneity of adipose tissue-derived mesenchymal stem cells under chondrogenic induction

  • Jeewan Chun;Ji-Hoi Moon;Kyu Hwan Kwack;Eun-Young Jang;Saebyeol Lee;Hak Kyun Kim;Jae-Hyung Lee
    • BMB Reports
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    • 제57권5호
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    • pp.232-237
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    • 2024
  • This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation.

중국 해양관련 법령의 발전과 입법체계에서의 지위 및 해석 (Development of Chinese Maritime Related Laws and Status and Interpretation in Legislation System)

  • 양희철;이문숙;박성욱;강량
    • Ocean and Polar Research
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    • 제30권4호
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    • pp.427-444
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    • 2008
  • The most important bases of maritime laws in China are laws enacted by Constitution, a legislative institution of National People's Congress and Legislation of NPC Standing Committee. However, in reality, the institution, which become the basis of Chinese marine policy and leads overall maritime affairs, is a State Council of the Chinese central government and many objects of our researches on Chinese marine policy and laws are composed centering on this administration law. Therefore, in understanding Chinese maritime laws, it becomes an important prerequisite to understand relevant laws (statutes), administration law, statutes of local province, mutual authority relationships of these legislative institutions, and interpretation authority regarding laws (statutes). In May 2003, Chinese State Council ratified and declared ${\ll}$Guideline of the national maritime economic development plan${\gg}$ and this is the first macroinstructive document enacted by the Chinese government for promoting maritime economy in integration development. This plan guideline shows very well a new policy and deployment direction of maritime policy in China. China is already striving to lead its maintenance stage of domestic legislation into a new stage under the UN maritime laws agreement system and this is an expression of intention to take national policy regarding the ocean as a new milestone for the national economy through concurrent developments in various fields such as national territory, economy, science technology, national defense, and maritime biology. In this point, Chinese maritime policy and maritime legislation provide lots of indexes of lessons in many parts. In particular, regarding Korea, which has to solve many issues with China in Yellow Sea, East China Sea, and Balhae, we have to realize that we can maximize national interest only with a systematic approach to research on changes of domestic policies and maritime legislation within China. In addition, in understanding Chinese maritime related laws, we have to realize it is an important task to not only understand legislative subjects for mutual creation of order within the entire frame of law orders of China but also to predict and react to direction of policy of Chinese domestic legislation through dynamics of these subjects.

지구성 훈련에 반응한 골격근의 미토콘드리아 항상성 조절 (Regulation of Mitochondrial Homeostasis in Response to Endurance Exercise Training in Skeletal Muscle)

  • 주정선
    • 생명과학회지
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    • 제27권3호
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    • pp.361-369
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    • 2017
  • 미토콘드리아의 항상성은 미토콘드리아 생합성과 마이토파지(자가포식에 의한 미토콘드리아 분해)로 불리는 2가지 주요 과정들에 의해 정교하게 조절되고 있다. 지구성 운동 훈련에 반응하여 골격근에서 미토콘드리아 생합성에 관한 기전들은 잘 정립되어 있는 반면 지구성 운동 훈련 후 골격근의 마이토파지 조절 기전과 마이토파지와 미토콘드리아 생합성의 협응을 조절하는 기전은 아직 명확히 밝혀져 있지 않다. 최근 연구들에 의하면 지구성 운동 훈련은 골격근에서 미토콘드리아 생합성, 미토콘드리아 역동성, 미토콘드리아 분해와 관련된 유전인자들의 발현을 증가시킨다고 하였다. 하지만 골격근에서 자가포식이 억제되었을 경우, 지구성 운동 훈련에 의한 미토콘드리아 생합성과 관련된 지표들인 Cox IV와 citrate synthase의 증가는 상쇄되었다. 따라서 자가포식과 마이토파지는 골격근의 미토콘드리아 생합성에 중요한 역할을 하며 정반대되는 이 두 과정(이화 또는 동화작용)의 협응 과정이 지구성 운동 훈련에 반응하여 대사적 기능과 지구력 운동 수행능력을 향상시키는 것과 같은 골격근의 적응에 중요한 듯하다. 지구성 운동은 미토콘드리아의 일정한 숫자를 유지시키기 위해 미토콘드리아 생합성, 미토콘드리아의 융합과 분열, 자가포식/마이토 파지들의 각각의 과정들을 조절하는 것으로 여겨진다. 지구성 운동 훈련은 골격근에서 마이토파지를 활성화시켜 미토콘드리아 양과 질을 조절하여 늙고 건강하지 않은 미토콘드리아를 젊고 건강한 미토콘드리아로 교체시킬 수 있다. 이 총론에서 미토콘드리아 생합성과 마이토파지의 분자학적 기전과 서로 상반되는 이 두 과정간의 협응이 골격근의 지구성 훈련에 대한 세포적 적응에 관련한다는 내용이 논의될 것이다.

Functional Defects of Hb Kempsey (${\beta}99Asp{\rightarrow}Asn$) Can be Compensated by Insertion of a New Intersubunit Hydrogen Bond at the ${\alpha}_1{\beta}_2$ Subunit Interface

  • Yeh, Byung-Il;Choi, Jong-Whan;Sohn, Joon-Hyung;Lee, Hyean-Woo;Han, Dong-Pyou;Jung, Seun-Ho;Kim, Hyun-Won
    • BMB Reports
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    • 제31권6호
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    • pp.590-594
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    • 1998
  • X-ray crystallographic studies of the deoxy form of human adult hemoglobin (Hb A) have shown that ${\beta}99Asp$ is hydrogen bonded to both ${\alpha}42Tyr$ and ${\alpha}97Asn$ in the ${\alpha}_1{\beta}_2$ subunit interface, suggesting that the essential role of ${\beta}99Asp$ is to stabilize the deoxy-Hb by creating the intersubunit hydrogen bond. In particular, for Hb Kempsey (${\beta}99Asp{\rightarrow}Asn$), molecular dynamics simulation indicated that a new hydrogen bond involving ${\beta}99Asn$ can be induced by replacing ${\alpha}42Tyr$ with a strong hydrogen-bond acceptor such as Asp. Designed mutant recombinant (r) Hb (${\beta}99Asp{\rightarrow}Asn$, ${\alpha}42Tyr{\rightarrow}Asp$) have been produced in the Escherichia coli expression system and have shown that functional defects of Hb Kempsey could be compensated by the ${\alpha}42Tyr{\rightarrow}Asp$ substitution. However, as the ${\alpha}42 Tyr{\rightarrow}Asp$ mutation has never been reported before, it is still possible that the functional properties of r Hb (${\beta}99Asp{\rightarrow}Asn$, ${\alpha}42Tyr{\rightarrow}Asp$) may be due to the mutation itself. Thus, it is required to produce r Hb (${\alpha}42Tyr{\rightarrow}Asp$) and r Hb Kempsey (${\beta}99Asp{\rightarrow}AsnX$( as controls, and to compare their properties with those of r Hb (${\beta}99Asp{\rightarrow}Asn$, ${\alpha}42Tyr{\rightarrow}Asp$). r Hb (${\alpha}42Tyr{\rightarrow}Asp$) could not be purified because it is an unstable hemoglobin which forms Heinz bodies. r Hb Kempsey (${\beta}99Asp{\rightarrow}Asn$) exhibits very high oxygen affinity and greatly reduced cooperativity. Thus, r Hb (${\beta}99Asp{\rightarrow}Asn$) and r Hb (${\alpha}42Tyr{\rightarrow}Asp)$ compensate each other.

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2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells

  • Mustafa, Ebtihal H;Mahmoud, Huda T;Al-Hudhud, Mariam Y;Abdalla, Maher Y;Ahmad, Iman M;Yasin, Salem R;Elkarmi, Ali Z;Tahtamouni, Lubna H
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3213-3222
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    • 2015
  • Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

최근 중의학에서 시스템생물학의 발전 현황 - 한의학에 미치는 영향 및 시사점을 중심으로 - (Current Status of Systems Biology in Traditional Chinese medicine - in regards to influences to Korean Medicine)

  • 이승은;이선동
    • 대한예방한의학회지
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    • 제21권2호
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    • pp.1-13
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    • 2017
  • Objectives : This paper serves to explore current trends of systems biology in Traditional Chinese Medicine (TCM) and examine how it may influence the Traditional Korean medicine. Methods : Literature review method was collectively used to classify Introduction to systems biology, diagnosis and syndrome classification of systems biology in TCM perspective, physiotherapy including acupuncture, herbs and formula functions, TCM systems biology, and directions of academic development. Results : The term 'Systems biology' is coined as a combination of systems science and biology. It is a field of study that tries to understand living organism by establishing a theory based on an ideal model that analyzes and predicts the desired output with understanding of interrelationships and dynamics between variables. Systems biology has an integrated and multi-dimensional nature that observes the interaction among the elements constructing the network. The current state of systems biology in TCM is categorized into 4 parts: diagnosis and syndrome, physical therapy, herbs and formulas and academic development of TCM systems biology and its technology. Diagnosis and syndrome field is focusing on developing TCM into personalized medicine by clarifying Kidney yin deficiency patterns and metabolic differences among five patterns of diabetes and analyzing plasma metabolism and biomarkers of coronary heart disease patients. In the field of physical therapy such as acupuncture and moxibustion, researchers discovered the effect of stimulating acupoint ST40 on gene expression and the effects of acupuncture on treating functional dyspepsia and acute ischemic stroke. Herbs and formulas were analyzed with TCM network pharmacology. The therapeutic mechanisms of Si Wu Tang and its series formulas are explained by identifying potential active substances, targets and mechanism of action, including metabolic pathways of amino acid and fatty acid. For the academic development of TCM systems biology and its technology, it is necessary to integrate massive database, integrate pharmacokinetics and pharmacodynamics, as well as systems biology. It is also essential to establish a platform to maximize herbal treatment through accumulation of research data and diseases-specific, or drug-specific network combined with clinical experiences, and identify functions and roles of molecules in herbs and conduct animal-based studies within TCM frame. So far, few literature reviews exist for systems biology in traditional Korean medicine and they merely re-examine known efficacies of simple substances, herbs and formulas. For the future, it is necessary to identify specific mechanisms of working agents and targets to maximize the effects of traditional medicine modalities. Conclusions : Systems biology is widely accepted and studied in TCM and already advanced into a field known as 'TCM systems biology', which calls for the study of incorporating TCM and systems biology. It is time for traditional Korean medicine to acknowledge the importance of systems biology and present scientific basis of traditional medicine and establish the principles of diagnosis, prevention and treatment of diseases. By doing so, traditional Korean medicine would be innovated and further developed into a personalized medicine.

The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells

  • Fan, Hui-Jie;Tan, Zhang-Bin;Wu, Yu-Ting;Feng, Xiao-Reng;Bi, Yi-Ming;Xie, Ling-Peng;Zhang, Wen-Tong;Ming, Zhi;Liu, Bin;Zhou, Ying-Chun
    • Journal of Ginseng Research
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    • 제44권2호
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    • pp.258-266
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    • 2020
  • Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

동적인 개념을 적용한 알츠하이머 질병 네트워크의 특성 분석 (Characterization of the Alzheimer's disease-related network based on the dynamic network approach)

  • 김만선;김정래
    • 한국지능시스템학회논문지
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    • 제25권6호
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    • pp.529-535
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    • 2015
  • 지금까지 생체 네트워크 분석 연구는 정적(static)인 개념으로만 다루어졌다. 그러나 실제 생명현상이 발생하는 세포 내에서는 세포의 상태 및 외부 환경에 따라 일부 단백질과 그 상호작용만이 선택적으로 활성화된다. 따라서 생체 네트워크의 구조가 시간의 흐름에 따라 변화하는 동적(dynamic)인 개념이 적용되어야 하며, 이런 개념은 질병의 진행 추이를 분석하는데 효율적이다. 본 논문에서는 동적인 네트워크 방법을 알츠하이머 질병에 적용하여 질병이 진행되는 단계에 따라 변화하는 단백질 상호작용 네트워크의 구조적, 기능적 특징에 대하여 분석하고자 한다. 우선, 유전자 발현데이터를 기반으로 각 질병의 진행 상태에 따른 부분 네트워크(정상, 초기, 중기, 말기)를 구축하였다. 이를 기반으로, 네트워크의 구조적 특성 분석을 수행하였다. 또한 기능적 특성 분석을 위해 유전자 군집(module)을 탐색하고, 군집별 유전자 기능(Gene Ontology) 분석을 수행했다. 그 결과, 네트워크의 특성들은 각 질병의 단계와 잘 대응되며, 동적 네트워크 분석법이 중요한 생물학적 이벤트를 설명하는데 이용될 수 있음을 보였다. 결론적으로 제안된 연구 방법을 통하여 그동안 알려지지 않았던 질병유발에 관련된 주요 네트워크 변화를 관측할 수 있고, 질병에 관여하는 복잡한 분자 수준의 발생 기작과 진행 과정을 이해하는데 중요한 정보를 획득할 수 있다.

Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway

  • Xu, Hong-Lin;Chen, Guang-Hong;Wu, Yu-Ting;Xie, Ling-Peng;Tan, Zhang-Bin;Liu, Bin;Fan, Hui-Jie;Chen, Hong-Mei;Huang, Gui-Qiong;Liu, Min;Zhou, Ying-Chun
    • Journal of Ginseng Research
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    • 제46권1호
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    • pp.156-166
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    • 2022
  • Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.