• Title/Summary/Keyword: nuclear factor-activated T cell

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Effect of Water Extract of Cynanchi Wilfordii Radix in RANKL-induced Osteoclast Differentiation (백하수오(白何首烏) 물 추출물의 파골세포 분화에 미치는 영향)

  • Ahn, Yong-Hwan;Oh, Jae-Min;Lee, Myeung-Su;Jung, Jong-Hyuk;Chae, Soo-Uk;Moon, Seo-Young;Jeon, Byung-Hoon;Choi, Min-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.2
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    • pp.160-165
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    • 2012
  • Osteoporotic fracture became a serious social problem, which related with mortality and morbidity in old age population. Osteoclast which is responsible for bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Cynanchum wilfordii (Asclepiadaceae) roots have been used in Korean folk medicine for the treatment of diabetes mellitus and aging progression. Also, recent studies have shown that the extract and fractions of Cynanchi Wilfordii Radix have various pharmacological actions including scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the effect of extract of Cynanchi Wilfordii Radix in osteoclast differentiation had not been reported. Thus, we evaluated the effect of Cynanchi Wilfordii Radix on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Through our study, we found that Cynanchi Wilfordii Radix significantly inhibited osteoclast differentiation induced by RANKL. Cynanchi Wilfordii Radix suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Cynanchi Wilfordii Radix significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Cynanchi Wilfordii Radix inhibited the protein expression of c-fos and NFATc1. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

Physiological Activity of Coffee Beans and Roasted Black Beans (Rhynchosia nulubilis) Mixture Extracts for Coffee Alternative Beverage Development

  • Kim, Ae-Jung;Lee, Hankyu;Ko, Hyuk Wan;Ko, Seong Hee;Woo, Nariyah
    • The Korean Journal of Food And Nutrition
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    • v.29 no.2
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    • pp.178-185
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    • 2016
  • This study was designed to develop and to qualify a coffee alternative beverage using a mixture of coffee beans and roasted black beans (Rhynchosia nulubilis). Therefore, the total isoflavone content (TIC), total phenol content (TPC), antioxidant activity, anti-inflammatory activity, NFATc1 (Nuclear factor of activated T-cells c1) expression in RANKL (receptor activator of nuclear factor kappa-B ligand)-stimulated RAW264.7 cells and sensory evaluation were measured for 5 different Cb (coffee bean)-RoS (roasted seomoktae) mixture extracts (Cb100RoS0, Cb75RoS25, Cb50RoS50, Cb25RoS75, and Cb0RoS100). Cb0RoS100 had the highest TIC ($516.83{\pm}36.61mg/100g$) and TPC ($18.11{\pm}1.77mg$ TAE/100 g) along with the highest antioxidant activity as measured by DPPH radical scavenging activity ($73.55{\pm}8.11%$) and ABTS radical scavenging activity ($63.27{\pm}7.27%$). Also, Cb0RoS100 showed the highest anti-inflammatory activity as measured by NO production ($13.57{\pm}2.21{\mu}M$) and PGE2 production ($3.25{\pm}0.21ng/mL$). The more the RoS ratio was increased in the mixtures of Cb-RoS, the more the NFATc1 protein expression was decreased in RANKL-stimulated RAW264.7 cells. In case of sensory evaluation, Cb50RoS50 had the highest scores for flavor, delicate flavor and overall quality, which were similar to those in Cb alone (Cb100RoS0). We suggest that the use of RoS replacement instead of Cb in/as a coffee alternative beverage may help to reduce the risk of caffeine-related bone loss and/or bone disease by effectively blocking NFATc1 expression in RANKL-stimulated RAW264.7 cells compared with Cb alone.

A Study of Influence of Filgrastim on PET/CT In Diffuse Large B cell Lymphoma (미만성 거대 B 세포 림프종 환자에서 Filgrastim 사용이 PET/CT 영상에 미치는 영향에 대한 고찰)

  • NamKoong, Hyuk;Park, Hoon-Hee;Ban, Yung-Gak;Kang, Sin-Chang;Kim, Sang-Kyoo;Lim, Han-Sang;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.3
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    • pp.17-23
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    • 2009
  • Purpose: It has been known that PET/CT is very valuable in follow-up study of diffuse large B cell lymphoma (DLBCL). Generally, in DLBCL, radiotherapy and chemotherapy has been progressed, because the lesion hasn‘t been limited to one site. And, it has lead to the decrease of leukocyte like neutropenia, due to myelosuppression of chemotherapy. So, in that case, administration of Filgrastim (Granulocyte colony-stimulating factor; G-CSF) is universal. However, in short time after administration, PET/CT has limitation to offer accurate images, through the uptake of $^{18}F$-FDG is increased in the region that is activated bone marrow by hematopoietic growth. Therefore, the aim of this study is that PET/CT in a certain period of time after administration of Filgrastim is able to show normal degree of $^{18}F$-FDG uptake. Materials and Methods: 10 patients under follow-up study of diffuse large B cell lymphoma were examined in this study from January, 2007 to January, 2009 (Male: 4 persons; Female: 6 persons; The mean age: 53.8 years old; The mean weight: 57.3 Kg). Using PET/CT (Discovery STe; GE Healthcare, Milwaukee, WI, USA), whole body images were acquired in 1 hour after $^{18}F$-FDG injection. For image analysis, each ROI ($120\;mm^2$) was drawn on $C^6$ (the sixth C-spine), $L_4$ (the forth L-spine), liver, spleen, and lung, then SUV (Standard Uptake Value)s were measured. We compared with each uptake between in 1-day and 5~7 days after administration of Filgrastim at same patient, so confirmed significance about these by SPSS version 12. Results: In case of $C_6$, $L_4$, spleen, every SUV of 1 day later was remarkably higher than that of 5~7 days later, but liver and lung were similar. Also, the images acquired after 5~7 days distinct remarkably and show normal degree of $^{18}F$-FDG uptake, because uptake of bone was almost disappeared. Conclusions: In this study, each SUV was prominent difference as a period of time after Filgrastim’s administration. And Filgrastim makes concentrate uptake of $^{18}F$-FDG in bone, but, after 5~7 days, bone‘s uptake was greatly decreased. Therefore, we are able to infer a certain period of time that shows normal degree of uptake, by numerical value proven. Also, we consider that this study contribute to advanced study about the other agent like Pegfilgrastim, Lenograstim besides Filgrastim, afterwards.

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Transcriptional regulation of chicken leukocyte cell-derived chemotaxin 2 in response to toll-like receptor 3 stimulation

  • Lee, Seokhyun;Lee, Ra Ham;Kim, Sung-Jo;Lee, Hak-Kyo;Na, Chong-Sam;Song, Ki-Duk
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.12
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    • pp.1942-1949
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    • 2019
  • Objective: Leukocyte cell-derived chemotaxin 2 (LECT2) is associated with several physiological processes including inflammation, tumorigenesis, and natural killer T cell generation. Chicken LECT2 (chLECT2) gene was originally identified as one of the differentially expressed genes in chicken kidney tissue, where the chickens were fed with different calcium doses. In this study, the molecular characteristics and gene expression of chLECT2 were analyzed under the stimulation of toll-like receptor 3 (TLR3) ligand to understand the involvement of chLECT2 expression in chicken metabolic disorders. Methods: Amino acid sequence of LECT2 proteins from various species including fowl, fish, and mammal were retrieved from the Ensembl database and subjected to Insilco analyses. In addition, the time- and dose-dependent expression of chLECT2 was examined in DF-1 cells which were stimulated with polyinosinic:polycytidylic acid (poly [I:C]), a TLR3 ligand. Further, to explore the transcription factors required for the transcription of chLECT2, DF-1 cells were treated with poly (I:C) in the presence or absence of the nuclear factor ${\kappa}B$ ($NF{\kappa}B$) and activated protein 1 (AP-1) inhibitors. Results: The amino acid sequence prediction of chLECT2 protein revealed that along with duck LECT2 (duLECT2), it has unique signal peptide different from other vertebrate orthologs, and only chLECT2 and duLECT2 have an additional 157 and 161 amino acids on their carboxyl terminus, respectively. Phylogenetic analysis suggested that chLECT2 is evolved from a common ancestor along with the actinopterygii hence, more closely related than to the mammals. Our quantitative polymerase chain reaction results showed that, the expression of chLECT2 was up-regulated significantly in DF-1 cells under the stimulation of poly (I:C) (p<0.05). However, in the presence of $NF{\kappa}B$ or AP-1 inhibitors, the expression of chLECT2 is suppressed suggesting that both $NF{\kappa}B$ and AP-1 transcription factors are required for the induction of chLECT2 expression. Conclusion: The present results suggest that chLECT2 gene might be a target gene of TLR3 signaling. For the future, the expression pattern or molecular mechanism of chLECT2 under stimulation of other innate immune receptors shall be studied. The protein function of chLECT2 will be more clearly understood if further investigation about the mechanism of LECT2 in TLR pathways is conducted.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.59-69
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    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Temporal expression profiling of long noncoding RNA and mRNA in the peripheral blood during porcine development

  • Gu, Yiren;Zhou, Rui;Jin, Long;Tao, Xuan;Zhong, Zhijun;Yang, Xuemei;Liang, Yan;Yang, Yuekui;Wang, Yan;Chen, Xiaohui;Gong, Jianjun;He, Zhiping;Li, Mingzhou;Lv, Xuebin
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.5
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    • pp.836-847
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    • 2020
  • Objective: We investigated the temporal expression profiles of long noncoding RNA (lncRNA) and mRNA in the peripheral blood of pigs during development and identified the lncRNAs that are related to the blood-based immune system. Methods: Peripheral blood samples were obtained from the pigs at 0, 7, 28, and 180 days and 2 years of age. RNA sequencing was performed to survey the lncRNA and mRNA transcriptomes in the samples. Short time-series expression miner (STEM) was used to show temporal expression patterns in the mRNAs and lncRNAs. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed to assess the genes' biological relevance. To predict the functions of the identified lncRNAs, we extracted mRNAs that were nearby loci and highly correlated with the lncRNAs. Results: In total of 5,946 lncRNA and 12,354 mRNA transcripts were identified among the samples. STEM showed that most lncRNAs and mRNAs had similar temporal expression patterns during development, indicating the expressional correlation and functional relatedness between them. The five stages were divided into two classes: the suckling period and the late developmental stage. Most genes were expressed at low level during the suckling period, but at higher level during the late stages. Expression of several T-cell-related genes increased continuously during the suckling period, indicating that these genes are crucial for establishing the adaptive immune system in piglets at this stage. Notably, lncRNA TCONS-00086451 may promote blood-based immune system development by upregulating nuclear factor of activated T-cells cytoplasmic 2 expression. Conclusion: This study provides a catalog of porcine peripheral blood-related lncRNAs and mRNAs and reveals the characteristics and temporal expression profiles of these lncRNAs and mRNAs during peripheral blood development from the newborn to adult stages in pigs.

Glatiramer acetate inhibits the activation of NFκB in the CNS of experimental autoimmune encephalomyelitis (Glatiramer acetate 투여에 의한 자가면역성 뇌척수염 마우스의 중추신경계에서의 NFκB 활성 억제)

  • Hwang, Insun;Ha, Danbee;Kim, Dae Seung;Joo, Haejin;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.51 no.3
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    • pp.217-225
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    • 2011
  • Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B ($NF{\kappa}B$) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, $NF{\kappa}B$ activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of $NF{\kappa}B$ activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of $NF{\kappa}B$ and phospho-$I{\kappa}B$ proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of $NF{\kappa}B$ and phospho-$I{\kappa}B$ significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of $NF{\kappa}B$ and phophorylation of $I{\kappa}B$ in the CNS. Subsequently, the inhibition of $NF{\kappa}B$ activation and $I{\kappa}B$ phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.