• Title/Summary/Keyword: Jak2

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Transcriptional Properties of the BMP, $TGF-\beta$, RTK, Wnt, Hh, Notch, and JAK/STAT Signaling Molecules in Mouse Embryonic Stem Cells

  • Rho Jeung-Yon;Bae Gab-Yong;Chae Jung-Il;Yu Kweon;Koo Deog-Bon;Lee Kyung-Kwang;Han Yong-Mahn
    • Reproductive and Developmental Biology
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    • v.30 no.2
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    • pp.143-156
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    • 2006
  • Major characteristics of embryonic stem cells (ESCs) are sustaining of sternness and pluripotency by self-renewal. In this report, transcriptional profiles of the molecules in the developmentally important signaling pathways including Wnt, BMP4, $TGF-\beta$, RTK, Hh, Notch, and JAK/STAT signaling pathways were investigated to understand the self-renewal of mouse ESCs (mESCs), J1 line, and compared with the NIH3T3 cell line and mouse embryonic fibroblast (MEF) cells as controls. In the Wnt signaling pathway, the expression of Wnt3 was seen widely in mESCs, suggesting that the ligand may be an important regulator for self-renewal in mESCs. In the Hh signaling pathway, the expression of Gli and N-myc were observed extensively in mESCs, whereas the expression levels of in a Shh was low, suggesting that intracellular molecules may be essential for the self-renewal of mESCs. IGF-I, IGF-II, IGF-IR and IGF-IIR of RTK signaling showed a lower expression in mESCs, these molecules related to embryo development may be restrained in mESCs. The expression levels of the Delta and HESS in Notch signaling were enriched in mESCs. The expression of the molecules related to BMP and JAK-STAT signaling pathways were similar or at a slightly lower level in mESCs compared to those in MEF and NIH3T3 cells. It is suggested that the observed differences in gene expression profiles among the signaling pathways may contribute to the self-renewal and differentiation of mESCs in a signaling-specific manner.

Bottom-up Approach: the Effects of Performing Arts Fostering Program, Chang-jak-san-shil (상향식접근(bottom-up approach)이론을 이용한 창작산실육성지원사업의 효과연구)

  • Kim, InSul;Shin, Hyesun;Lee, Heungjae
    • Review of Culture and Economy
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    • v.19 no.2
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    • pp.97-120
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    • 2016
  • This study aims to identify how performing artists in Korea, who are the target beneficiaries of the Arts Council Korea's Performing Arts Fostering Program, Chang-jak-san-shil(CJSS), would perceive and assess the current state of CJSS and its effects. To do so, this paper has adopted a bottom-up approach as a theoretical lens for policy evaluative analysis. This research engages with qualitative research design by conducting a series of in-depth interviews and FGIs with 28 participants in total. The interview participants consist of CJSS grantees(n=21) and peer-review panels(n=7) based on the intension to enhance objectivity and reliability of the study. Results of the data analysis suggest that the grant program still carries pressing needs to achieve a success as follows: providing post-program support, enhancing transparency of the panel appointment process and the peer review process, reflecting different nature of each arts discipline, and having more open communications with arts professionals. Based on these findings, this paper will provide and discuss about policy implications which can contribute to the performing arts domain at large.

Role of IFNLR1 gene in PRRSV infection of PAM cells

  • Qin, Ming;Chen, Wei;Li, Zhixin;Wang, Lixue;Ma, Lixia;Geng, Jinhong;Zhang, Yu;Zhao, Jing;Zeng, Yongqing
    • Journal of Veterinary Science
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    • v.22 no.3
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    • pp.39.18-39.18
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    • 2021
  • Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

Nucleopolyhedrovirus Induces Suppressor of Cytokine Signaling in the Beet Armyworm, Spodoptera exigua

  • Noh Mi-Young;Jo Yong-Hun;Kim Seon-Am;Lee Yong-Seok;Bang In-Seok;Kim Seon-Gon;Park Jong-Dae;Chun Jae-Sun;Seo Sook-Jae;Han Man-Deuk;Kim Ik-Soo;Han Yeon-Soo
    • International Journal of Industrial Entomology and Biomaterials
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    • v.12 no.2
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    • pp.63-67
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    • 2006
  • Suppressor of cytokine signaling (SOCS) is known to playa key role as a negative feedback regulator in JAK/STAT signaling cascade in innate immunity. Our laboratory has recently been interested in elucidating the interactions between Spodoptera exigua (Se) and SeNPV. This context leads us to clone and characterize SeSOCS that may have important functions in response to SeNPV infection. Using the RT-PCR and TA cloning approach, we found a partial fragment (416 bp) of SeSOCS. Blast search and multiple alignment data showed that it has a homology to various insects such as Anopheles gambiae (78%), Aedes aegypti (75%), Drosophila melanogastar (77%), Mus musculus (69%), and Homo sapiens (69%). Temporal induction patterns of SeSOCS were analysed after being immune-challenged with either NPV or laminarin. It showed that the level of SeSOCS mRNA was strongly induced in a biphasic manner in response to SeNPV and laminarin, respectively. It seems that SOCS, a negative regulator of JAK/STAT signaling system is also present in S. exigua and may playa role in innate immunity albeit its precise role should be further elucidated at the molecular and cellular level in the early phase of SeNPV infection in larvae.

In vitro shoot initiation of Artocarpus heterophyllus Lam. (Jak Fruit) Effect of the explant type and the season of explant collection

  • Kahk, Kasturiarachchi;Wtpsk, Senarath;Lee, Kui-Jae
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2003.10b
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    • pp.2-3
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    • 2003
  • A method for rapid propagation of mature Jack fruit was developed. Four types of explants (mature embryos, apical meristems of young seedlings, apices from mature plants and nodal segments) were used. It has been found 88% of young apical meristems produced shoots in Campbell and Durzan (CD) medium compared to 60% in Murashige and Skoog (MS) medium. Only 1/3 of them produced multiple shoots. Shoot initiation from nodal segments was very rare. Mature apices produced callus. Although removal of the sheathing cover around mature buds enhanced the shoot initiation but success rate was low in growth regulator free medium. Embryos respond to the CD medium but not to the MS medium. Embryos from seeds soaked in water for 24 hours produced shoots after 8 weeks of incubation and the success rate was 70% while embryos from dry seeds only produced roots. There was no significant effect of cold storage (refrigeration) for 7 days on shoot initiation from mature embryos (65%) but the ability for shoot induction declines with storage time (55% after 21 days of cold storage). Mature axillary buds were established in Modified Campbell and Durzan (CD) medium supplemented with 0.5mg/1 and IBA. There was a significant difference in the growth performance of shoots according to the period of the year in which explants were collected. Highest (60%) was observed in November-January period. It was only 30% when the explants were collected in February-April or May-July and decreased to 20% in August-October. The shoots produced in November-January showed a higher vigor than those produced in other months. Since Jak fruit show seasonal changes in fruit bearing and shedding of leaves, it can be suggested that the difference in growth performances of tissues cultured in artificial culture media would have been affected by endogenous rhythms.

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Prunus Yedoensis Inhibits the Inflammatory Chemokines, MDC and TARC, by Regulating the STAT1-Signaling Pathway in IFN-γ-stimulated HaCaT Human Keratinocytes

  • Kang, Gyeoung-Jin;Lee, Hye-Ja;Yoon, Weon-Jong;Yang, Eun-Jin;Park, Sun-Son;Kang, Hee-Kyoung;Park, Myung-Hwan;Yoo, Eun-Sook
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.394-402
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    • 2008
  • Atopic dermatitis (AD) is an inflammatory skin disease commonly characterized by infiltration of inflammatory cells into skin lesions. Keratinocytes produce many chemokines that are involved in the pathogenesis of skin disorders. In particular, macrophage-derived chemokine (MDC/CCL22) and thymus and activationregulated chemokine (TARC/CCL17) are Th2-type cytokines. Serum MDC and TARC levels are increased in AD patients. In this study, we investigated the anti-inflammatory effect and mechanism of action of the active fraction from Prunus yedoensis bark. We evaluated their inhibitory effects on the AD-like inflammatory markers (MDC and TARC) and JAK-STAT pathway (STAT1) in HaCaT keratinocytes. The EtOAc fraction of the crude extract (80% EtOH) and the E5 sub-fraction potently inhibited the induction of MDC and TARC mRNA and protein at 50 ${\mu}g$/mL in HaCaT cells. In addition, the E5 sub-fraction inhibited the phosphorylation of STAT1 protein associated with IFN-$\gamma$ signaling transduction in a dose-dependent manner. Thus, P. yedoensis may have antiatopic activity by suppressing the inflammatory chemokines (MDC and TARC).

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

  • Kyung-Jun, Boo;Edson Luck, Gonzales;Chilly Gay, Remonde;Jae Young, Seong;Se Jin, Jeon;Yeong-Min, Park;Byung-Joo, Ham;Chan Young, Shin
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.161-167
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    • 2023
  • Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

An Aspect of Medical Life and Yakro in Joseon in the 19th Century Based on the Records of Sin Dae-woo's Family, Seo Yugu, and Lee Kyugyung (19세기 조선 의약 풍경과 '약로(藥露)' - 신대우 가계 기록물과 서유구, 이규경의 저술을 중심으로)

  • JEON Jong-wook
    • The Journal of Korean Medical History
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    • v.35 no.1
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    • pp.135-147
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    • 2022
  • Sin Dae-woo was a scholar representing the Ganghwa School in the late Joseon Dynasty. He was Jeong Je-du's grandson-in-law and also in charge of organizing Jeong Je-du's collection of writings. His three sons had a particularly close relationship with their father, so even when they published a collection of writings after his father's death, the names of the three were combined and marked as Jin-jak-shin. The records they left include Seokcheon Il-seung, who described the history of the family along with the collection of writings, Seongdo Il-rok, a diary of the time of Seongcheon Busa, and many letters exchanged over time. These records draw attention as they contain records of medical life, such as eye diseases that the family suffered, infectious diseases that caused many casualties, and Yakro (distilled herbal essence) that showed records of being used for treatment at the time. In this paper: 1) We examine the medicines, prescriptions, acupuncture, and medication used to treat eye diseases. 2) We carefully examine the epidemic, the responses of the parties to it, and the attitudes of those who stood at the boundary between death and life. 3) We look for clues to the use of Western-origin drugs called Yakro. Intellectuals of the time looked deeper into Lee Kyugyung's book and Seo Yu-gu's book on how they were reflected in Joseon's medical life. In conclusion, in the 18th and 9th centuries, we see that the influential families of the Ganghwa school freely brought in famous acupuncturists, used prescriptions that were included in medical books or not, and used Yakro from western origin that were not traditional methods of Joseon. Thus, we reveal that doctors of the Joseon had the capacity to pursue their medical life more actively and had open-minded exchanges than our existing perceptions.

The Gene Expression Profile of LPS-stimulated Microglial Cells

  • Sohn, Sung-Hwa;Ko, Eun-Jung;Kim, Sung-Hoon;Kim, Yang-Seok;Shin, Min-Kyu;Hong, Moo-Chang;Bae, Hyun-Su
    • Molecular & Cellular Toxicology
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    • v.5 no.2
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    • pp.147-152
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    • 2009
  • This study was conducted to evaluate the inflammatory mechanisms of LPS-stimulated BV-2 microglial cells. The inflammation mechanism was evaluated in BV-2 cells with or without LPS treated using the Affymetrix microarray analysis system. The microarray analysis revealed that B cell receptor signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, MAPK signaling pathway, Neuro-active ligand-receptor interaction, TLR signaling path-way, and T cell receptor signaling pathway-related genes were up-regulated in LPS stimulated BV-2 cells. Selected genes were validated using real time RTPCR. These results can help an effective therapeutic approach to alleviating the progression of neuro-in-flammatory diseases.

Brief low [Mg2+]o-induced Ca2+ spikes inhibit subsequent prolonged exposure-induced excitotoxicity in cultured rat hippocampal neurons

  • Kim, Hee Jung;Yang, Ji Seon;Yoon, Shin Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.101-109
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    • 2016
  • Reducing $[Mg^{2+}]_o$ to 0.1 mM can evoke repetitive $[Ca^{2+}]_i$ spikes and seizure activity, which induces neuronal cell death in a process called excitotoxicity. We examined the issue of whether cultured rat hippocampal neurons preconditioned by a brief exposure to 0.1 mM $[Mg^{2+}]_o$ are rendered resistant to excitotoxicity induced by a subsequent prolonged exposure and whether $Ca^{2+}$ spikes are involved in this process. Preconditioning by an exposure to 0.1 mM $[Mg^{2+}]_o$ for 5 min inhibited significantly subsequent 24 h exposure-induced cell death 24 h later (tolerance). Such tolerance was prevented by both the NMDA receptor antagonist D-AP5 and the L-type $Ca^{2+}$ channel antagonist nimodipine, which blocked 0.1 mM $[Mg^{2+}]_o$-induced $[Ca^{2+}]_i$ spikes. The AMPA receptor antagonist NBQX significantly inhibited both the tolerance and the $[Ca^{2+}]_i$ spikes. The intracellular $Ca^{2+}$ chelator BAPTA-AM significantly prevented the tolerance. The nonspecific PKC inhibitor staurosporin inhibited the tolerance without affecting the $[Ca^{2+}]_i$ spikes. While $G{\ddot{o}}6976$, a specific inhibitor of $PKC{\alpha}$ had no effect on the tolerance, both the $PKC{\varepsilon}$ translocation inhibitor and the $PKC{\zeta}$ pseudosubstrate inhibitor significantly inhibited the tolerance without affecting the $[Ca^{2+}]_i$ spikes. Furthermore, JAK-2 inhibitor AG490, MAPK kinase inhibitor PD98059, and CaMKII inhibitor KN-62 inhibited the tolerance, but PI-3 kinase inhibitor LY294,002 did not. The protein synthesis inhibitor cycloheximide significantly inhibited the tolerance. Collectively, these results suggest that low $[Mg^{2+}]_o$ preconditioning induced excitotoxic tolerance was directly or indirectly mediated through the $[Ca^{2+}]_i$ spike-induced activation of $PKC{\varepsilon}$ and $PKC{\xi}$, JAK-2, MAPK kinase, CaMKII and the de novo synthesis of proteins.