• Title/Summary/Keyword: FOS

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The estrogen-related receptor γ modulator, GSK5182, inhibits osteoclast differentiation and accelerates osteoclast apoptosis

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Lee, Dong-Kyo;Jin, Xian;Che, Xiangguo;Choi, Je-Yong
    • BMB Reports
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    • v.54 no.5
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    • pp.266-271
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    • 2021
  • Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

Determination of Resistance Factors of Load and Resistance Factor Design for Drilled Shaft Based on Load Test (LRFD 설계를 위한 현장타설말뚝의 주면지지력 저항계수 산정)

  • Kim, Seok-Jung;Kwon, Oh-Sung;Jung, Sung-Jun;Han, Jin-Tae;Kim, Myoung-Mo
    • Journal of the Korean Geotechnical Society
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    • v.26 no.7
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    • pp.17-24
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    • 2010
  • Load Resistance Factor Design method is used increasingly in geotechnical design world widely and resistance factors for drilled shafts are suggested by AASHTO. However, these resistance factors are determined for intact rock conditions; by comparison, most of bedrocks in Korea have weathered condition, so that applying the AASHTO resistance factors is not reasonable. Thus, this study suggests the proper resistance factors for design of drilled shaft in Korea. The 22 cases of pile load test data from 8 sites were chosen and reliability-based approach is used to analyze the data. Reliability analysis was performed by First Order Second Moment Method (FOSM) applying 4 bearing capacity equations. As a result, when the Factor of Safety (FOS) was selected as 3.0, the target reliability indexes (${\beta}_c$) were evaluated as 2.01~2.30. Resistance factors and load factors are determined from optimization based on above results. The resistance factors ranged between 0.48 and 0.56 and load factors for dead load and live load are evaluated as approximately 1.25 and 1.75 respectively. However, when the target reliabilities are considered as 3.0, the resistance factors are evaluated as approximately 50% of the results when the target reliability index was 2.0.

Effect of Wind Load on Pile Foundation Stability in Solar Power Facilities on Slopes (풍하중이 경사지 태양광 발전시설의 기초 안정성에 미치는 영향 분석)

  • Woo, Jong-Won;Yu, Jeong-Yeon;Song, Ki-Il
    • Journal of the Korean Geotechnical Society
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    • v.39 no.12
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    • pp.47-60
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    • 2023
  • At present, in South Korea, there is a growing concern regarding solar power facilities installed on slopes because they are prone to damage caused by natural disasters, such as heavy rainfall and typhoons. Each year, these solar power facilities experience soil erosion due to heavy rainfall and foundation damage or detachment caused by strong wind loads. Despite these challenges, the interaction between the ground and structures is not adequately considered. Current analyses primarily focus on the structural stability under external loads; the overall facility site's stability-excluding the solar structures-in relation to its surrounding slopes is neglected. Therefore, in this study, we use finite-difference method analysis to simulate the behavior of the foundation and piles to assess changes in lateral displacement and bending stress in piles, as well as the safety factor of sloped terrains, in response to various influencing factors, such as pile diameter, spacing between piles, pile-embedding depth, wind loads, and dry and wet conditions. The analysis results indicate that pile spacing and wind loads significantly influence lateral displacement and bending stress in piles, whereas pile-embedding depth strongly influences the safety factor of sloped terrains. Moreover, we found that under certain conditions, the design criteria in domestic standards may not be met.

OLIGONOL PREVENTED THE RELAPSE OF DEXTRAN SULFATE SODIUM-ULCERATIVE COLITIS THROUGH ENHANCING NRF2-MEDIATED ANTIOXIDATIVE DEFENSE MECHANISM

  • K.-J. KIM;J.-M. PARK;J.-S. LEE;Y.S. KIM;N. KANGWAN;Y.-M. HAN;E.A. KANG;J.M. AN;Y.K. PARK;K.-B. HAHM
    • The Korean Journal of Physiology and Pharmacology
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    • v.69 no.3
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    • pp.359-371
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    • 2018
  • Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

The Effects of Acupuncture on Alleviating Pain and Depression and Modulating Brain Neural Activity (침 치료의 통증 및 우울증 개선 효과와 뇌신경 반응성 조절 기전 연구)

  • Keun Hyang Eom;Seul-Ki Won;Ji-Hye Song;Ji-Yeun Park
    • Korean Journal of Acupuncture
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    • v.41 no.3
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    • pp.79-89
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    • 2024
  • Objectives : We aimed to identify the effects of acupuncture treatment on alleviating pain and depression and modulating brain neural activity in the neuropathic pain and depression comorbidity mouse model (PDCM). Methods : We performed partial sciatic nerve ligation on the right hind paw of mice to induce neuropathic pain and injected reserpine (2 mg/kg, intraperitoneal) for 10 days from the day of the surgery to induce pain and depression. Acupuncture treatment was performed for 10 days at the following locations: 1) ST36 and SP6 (Joksamni and Sameumgyo; JS), 2) KI1 and HT7 (Yongcheon and Sinmun; YS), 3) LR1, PC9, KI10, and PC3 (Pericardium tonification; PT), or 4) LR1, HT9, KI10, and HT3 (Heart tonification; HT). Pain-like behavior was measured using the von Frey test and depressive-like behavior was assessed using the open field test. Then, the c-Fos expression was analyzed in the brain regions of neocortex, striatum, hypothalamus, hippocampus, midbrain, and medulla to examine brain neural activity. Results : In PDCM, pain-like behavior was alleviated by acupuncture treatment on the JS, YS, PT, and HT, and depressive-like behavior was improved by acupuncture treatment on the JS and YS. JS and YS were derived as an optimized acupoint combination for improving neuropathic pain and depression comorbidity. Brain neural activities in the neocortex (infralimbic cortex) and hypothalamus (paraventricular hypothalamic nucleus; PVN) were commonly altered by both JS and YS acupuncture treatments. In addition, neural activities in the neocortex (prelimbic cortex; PrL) and midbrain (substantia nigra, lateral part of the dorsal raphe nucleus) were altered exclusively by JS acupuncture treatment, while changes in the area 2 of the anterior cingulate cortex and the cornu ammonis 3 of the hippocampus were specific to YS acupuncture treatment. Brain neural activity in the PrL and PVN regions was significantly correlated with changes in pain behavior. Conclusions : Both JS and YS acupuncture treatments alleviated pain and depressive-like behaviors, which were associated with modulation of neural activities in the neocortex, hypothalamus, hippocampus, and midbrain.

1-β-D-Arabinofuranosyl-cytosine Induces Chromosomal Breaks in vitro (In vitro에서 1-β-D-arabinofuranosyl-cytosine의 염색체 파열 유도)

  • Jeon, In-sang
    • Clinical and Experimental Pediatrics
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    • v.46 no.12
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    • pp.1186-1193
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    • 2003
  • Purpose : Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-${\beta}$-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. Methods : T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. Results : Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. Conclusion : S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.

Cell study on the Magnesium ion implanted surface with PSII (PSII를 이용한 마그네슘 이온 주입 임플란트에 대한 MC3T3-E1 골모양 세포 반응 연구)

  • Shin, Hyeong-Joo;Kim, Dae-Gon;Park, Chan-Jin;Cho, Lee-Ra;Lee, Hee-Su;Cha, Min-Sang
    • Journal of Dental Rehabilitation and Applied Science
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    • v.25 no.4
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    • pp.361-374
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    • 2009
  • For successful osteogenesis around the implants, interaction between implant surface and surrounding tissue is important. Biomechanical bonding and biochemical bonding are considered to influence the response of adherent cells. But the focus has shifted surface chemistry. The purpose of this study is to evaluate the MC3T3-E1 osteoblast like cell responses of magnesium (Mg) ion implanted titanium surface produced using a plasma source ion implantation method. Commercially pure titanium disc was used as substrates. The discs were prepared to produce four different surface, A: Machine turned surface, B: Mg implanted surface, C: sandblasted surface, D: sandblasted and Mg implanted surface. MC3T3 El osteoblastic like cells were cultured on the disc specimens. Cell adhesion, proliferation, differentiation, and synthesis of extracellular matrix were evaluated. The cell adhesion morphology was evaluated by SEM. RT PCR assay was used for assessment of cell adhesion, proliferation and differentiation. ALP activity was measured for cell differentiation. The results of this study were as follows: 1. SEM showed that cell on Mg ion groups was more proliferative than that of non Mg ion groups. On the machine turned surface, cell showed some degree of contact guidance in aligning with the machining grooves. 2. In RT PCR analysis, osteonectin and c-fos mRNA were more expressed on sandblasted and Mg ion implanted group. 3. ALP activity was not significantly different among all groups. Within the limitations of this study, the following conclusions were drawn: It might indicate Mg ion implanted titanium surface induce better bone response than non Mg ion groups.

Effect of Moutan Cortex Radicis on gene expression profile of differentiated PC12 rat cells oxidative-stressed with hydrogen peroxide (모단피의 PC12 cell 산화억제 효과 및 neuronal 유전자 발현 profile 분석에 대한 연구)

  • Kim Hyun Hee;Rho Sam Woong;Na Youn Gin;Bae Hyun Su;Shin Min Kyu;Kim Chung Suk;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.529-541
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    • 2003
  • Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

Mechanisms for Anti-wrinkle Activities from Fractions of Black Chokeberries (블랙초크베리 분획물로부터의 주름억제 효과에 대한 작용기전)

  • Choi, Eun-Young;Kim, Eun-Hee;Lee, Jae-Bong;Do, Eun-Ju;Kim, Sang-Jin;Kim, Se-Hyeon;Park, Jeong-Yeol;Lee, Jin-Tae
    • Journal of Life Science
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    • v.26 no.1
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    • pp.34-41
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    • 2016
  • Black chokeberries (scientific name Aronia melanocarpa) have been reported to have major effects due to anti-oxidant, anti-inflammatory, and anti-cancer capabilities. In this study, we investigated the anti- wrinkle effects of A. melanocarpa, including collagenase inhibition effects and their molecular biological mechanisms, such as oxidative stress-induced matrix metalloproteinase (MMP), mitogen-activated protein (MAP) kinase, and activator protein (AP)-1 expression and/or phosphorylation. In collagenase inhibition activity, the ethyl acetate fraction of black chokeberry (AE) was 77.2% at a concentration of 500 μg/ml, which was a significant result compared to that of Epigallocatechin gallate (positive control, 83.9% in 500 μg/ml). In the reactive oxygen species (ROS) assay, the AE produced 78% of ROS in 10 μg/ml and 70% of ROS in 75 μg/ml, which was a much lower percentage than the ROS production of H2O2-induced CCRF S-180II cells. In the MTT assay, cell viability was increased dose-dependently with AE in H2O2-induced cells. In protein expression by western blot assay, the AE suppressed the expression and phosphorylation of MMPs (MMP-1, -3, -9), MAPK (ERK, JNK, and p38), and AP-1 (c-Fos and c-Jun), and expressed the pro-collagen type I in H2O2-induced cells. These results suggest that black chokeberries have anti-wrinkle and collagen-production effects, and they may be used in applications for material development in the functional food and cosmetic industries.

Forward Osmotic Pressure-Free (△𝜋≤0) Reverse Osmosis and Osmotic Pressure Approximation of Concentrated NaCl Solutions (정삼투-무삼투압차(△𝜋≤0) 법 역삼투 해수 담수화 및 고농도 NaCl 용액의 삼투압 근사식)

  • Chang, Ho Nam;Choi, Kyung-Rok;Jung, Kwonsu;Park, Gwon Woo;Kim, Yeu-Chun;Suh, Charles;Kim, Nakjong;Kim, Do Hyun;Kim, Beom Su;Kim, Han Min;Chang, Yoon-Seok;Kim, Nam Uk;Kim, In Ho;Kim, Kunwoo;Lee, Habit;Qiang, Fei
    • Membrane Journal
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    • v.32 no.4
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    • pp.235-252
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    • 2022
  • Forward osmotic pressure-free reverse osmosis (Δ𝜋=0 RO) was invented in 2013. The first patent (US 9,950,297 B2) was registered on April 18, 2018. The "Osmotic Pressure of Concentrated Solutions" in JACS (1908) by G.N. Lewis of MIT was used for the estimation. The Chang's RO system differs from conventional RO (C-RO) in that two-chamber system of osmotic pressure equalizer and a low-pressure RO system while C-RO is based on a single chamber. Chang claimed that all aqueous solutions, including salt water, regardless of its osmotic pressure can be separated into water and salt. The second patent (US 10.953.367B2, March 23, 2021) showed that a low-pressure reverse osmosis is possible for 3.0% input at Δ𝜋 of 10 to 12 bar. Singularity ZERO reverse osmosis from his third patent (Korea patent 10-22322755, US-PCT/KR202003595) for a 3.0% NaCl input, 50% more water recovery, use of 1/3 RO membrane area, and 1/5th of theoretical energy. These numbers come from Chang's laboratory experiments and theoretical analysis. Relative residence time (RRT) of feed and OE chambers makes Δ𝜋 to zero or negative by recycling enriched feed flow. The construction cost by S-ZERO was estimated to be around 50~60% of the current RO system.