• Molecules and Cells
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• v.43 no.5
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• pp.459-468
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• 2020

Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

• Journal of Agricultural Extension & Community Development
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• v.9 no.1
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• pp.1-10
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• 2002

The objectives of this study were to explore to upbringing system for the future farmers of the 4-H Clubs, future farmers organization and the Center for 4-H in the USA to suggest some implications to 4-H programs in Korea. To train future leaders in agricultural and agri-business areas leaders in the United States felt the need to create various organizations such as 4-H Club, Future Farmers of America (FFA), Young Farmer Association (YFA), and cooperate each other. The members in future farmer's groups benefit from opportunities and involvement of farming and agri-related activities and contribute to improve their communities. One of them, the 4-H Club remains strong in the country covering young people as members and adult as volunteer leaders. Youth in 4-H learn by doing, and members find opportunities for leadership. 4-H members contribute to their family, community, and country in meaningful ways to make a difference. The Center for 4-H has provided a range of challenging opportunities around the arts, sciences, environment, technology, business, animals, foods, and health while always stressing leadership and citizenship for 4-H members. The Center has been supporting research, teaching, and outreach in community based non-formal youth development education. The Center is particularly interested in youth development opportunities including foster resiliency, promote safe and healthy behaviors, and support youth in communities in various ways.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.21-28
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• 2008

Background: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. Methods: Balb/c $(H-2^d)$ mice were fed with dendritic cell line, DC2.4 $(H-2^d)$ every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. Results: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-${\gamma}$, IL-5, and TNF-${\alpha}$. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. Conclusion: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.

• BMB Reports
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• v.47 no.7
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• pp.399-404
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• 2014

B7-H4 is a member of B7 family of co-inhibitory molecules and B7-H4 protein is found to be overexpressed in many human cancers and which is usually associated with poor survival. In this study, we developed a therapeutic vaccine made from a fusion protein composed of a tetanus toxoid (TT) T-helper cell epitope and human B7-H4IgV domain (TT-rhB7-H4IgV). We investigated the anti-tumor effect of the TT-rhB7-H4IgV vaccine in BALB/c mice and SP2/0 myeloma growth was significantly suppressed in mice. The TT-rhB7-H4IgV vaccine induced high-titer specific antibodies in mice. Further, the antibodies induced by TT-rhB7-H4IgV vaccine were capable of depleting SP2/0 cells through complement-dependent cytotoxicity (CDC) in vitro. On the other hand, the poor cellular immune response was irrelevant to the therapeutic efficacy. These results indicate that the recombinant TT-rhB7-H4IgV vaccine might be a useful candidate of immunotherapy for the treatment of some tumors associated with abnormal expression of B7-H4.

• BMB Reports
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• v.49 no.10
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• pp.560-565
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• 2016

Granzyme A (GzmA) was first identified as a cytotoxic T lymphocyte protease protein with limited tissue expression. A number of cellular proteins are known to be cleaved by GzmA, and its function is to induce apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates during apoptotic cell death. Here, we demonstrated that histone H4 was cleaved by GzmA during staurosporine-induced cell death; however, in the presence of caspase inhibitors, staurosporine-treated Raji cells underwent necroptosis instead of apoptosis. Furthermore, histone H4 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. These results suggest that histone H4 is a novel substrate for GzmA in staurosporine-induced cells.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.184-191
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• 2003

New pyranone derivative, 2-((3E)-4(2H, 3H, -benzo[3, 4-d] 1, 3-dioxolan-5-yl)-2-oxo-but-3-enyloxy)-5-hydroxy-4H-pyran-4-one (Seletinoid $G^{TM}$), was designed as a novel retinoid on the assumption that the pyranone ring may mimic the carboxylic acid moiety in retinoid structure. The enolic hydroxy of pyranone at five position was easily deprotonated to form an enolate. The role of enolate was similar to that of carboxylic acid. To evaluate the value of Seletinoid G as an anti-aging ingredient, various tests were performed for example inhibitory effect for MMP-l expression, anti-oxidative activity, procollagen synthesis in hairless mouse and primary skin irritation. The result of this study suggested that our new synthetic retinoid could be used as a safe material for anti-aging cosmetics.

• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.128-136
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• 2012

We report the solid-phase library construction of 222 number of a novel N-[alkyl sulfonamido-spiro(2H-1-benzopyran-2,4-piperidine)-6-yl] substituted amide 1A and amine 1B derivatives. The polymer-bound N-[alkylsulfonamido-spiro(2H-1-benzopyran-2,4-piperidine)-6-yl] substituted amide 9 and amine 10 derivatives were obtained by first diversity generation with various acid chlorides and alkyl halides. Further reactions on the resins 9 and 10 with substituted sulfonyl chlorides produced the desired N-[alkylsulfonamido-spiro(2H-1-benzopyran-2,4-piperidine)-6-yl] substituted amide 1A and amine 1B analogues.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.216-222
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• 2018

The efficacy of standard therapeutic strategies for Helicobacter pylori (H. pylori) infection is decreasing over time due to the emergence of drug-resistant strains. As an alternative, the present study investigated the capacity of Lactobacilllus paracasei (L. paracasei) HP7, isolated from kimchi, to inhibit H. pylori growth. The effects of L. paracasei HP7 on H. pylori adhesion and H. pylori-induced inflammation were examined in AGS human gastric adenocarcinoma epithelial cells and a mouse model of H. pylori SS1 infection. L. paracasei HP7 reduced H. pylori adhesion to AGS cells and suppressed the inflammatory response in infected cells by downregulating interleukin-8. H. pylori colonization in the stomach of C57BL/6 mice was demonstrated by rapid urease test, and results showed significant decrease in mice post-treated with L. paracasei HP7. Additionally, L. paracasei HP7 decreased gastric inflammation and epithelial lesions in the stomach of H. pylori-infected mice. These results demonstrate that L. paracasei HP7 treatment can inhibit H. pylori growth and is thus a promising treatment for patients with gastric symptoms such as gastritis that are caused by H. pylori infection.

• Proceedings of the KIEE Conference
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• 2003.07c
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• pp.1592-1594
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• 2003

This paper presents the deposition and characterization of microcrystalline silicon(${\mu}c$-Si:H) films by HWCVD(Hot-wire Chemical Vapor Deposition) method at low substrate($300^{\circ}C$). The filament temperature, pressure and $SiH_4$ concentration were determined to be a critical parameter for the deposition of poly-Si films. Series A was deposited under the conditions of $1380^{\circ}C$(Tf), 100 mTorr and $2{\sim}10%\{SC:SiH_4/(SiH_4+H_2)\}$ for 60 min. Series B was deposited under the conditions of $1400{\sim}1450^{\circ}(T_f)$, 30 mTorr and $2{\sim}12%$(SC) for 60 min. The physical characteristics were measured by Raman and FTIR spectroscopy, dark and photoconductivity measurements under AM1.5 illumination.

• Journal of Powder Materials
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• v.18 no.3
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• pp.244-249
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• 2011

Spherical nanosized cobalt powder with an average size of 150-400 nm was successfully prepared at room temperature from cobalt sulfate heptahydrate ($CoSO_4{\cdot}7H_2O$). Wet chemical reduction method was adopted to synthesize nano cobalt powder and hypophosphorous acid ($H_3PO_2$) was used as reduction agent. Both the HCP and the FCC Co phase were developed while $CoSO_4{\cdot}7H_2O$ concentration ranged from 0.7 M to 1.1 M. Secondary phase such as $Co(OH)_2$ and $CO_3O_4$ were also observed. Peaks for the crystalline Co phase having HCP and FCC structure crystallized as increasing the concentration of $H_3PO_2$, indicating that the amount of reduction agent was enough to reduce $Co(OH)_2$. Consequently, a homogeneous Co phase could be developed without second phase when the $H_3PO_2/CoSO_4{\cdot}7H_2O$ ratio exceeded 7.