• Title/Summary/Keyword: PD-1/PD-L1

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A Blockade of the Central MAPK Pathway Attenuates Referred Pain in Rats with Complete Freund's Adjuvant -Induced Inflammation of the Temporomandibular Joint

  • Won, Kyoung-A.;Lim, Nak-H.;Lee, Min-K.;Park, Min-K.;Yang, Gwi-Y.;Park, Yoon-Yub;Ahn, Dong-K.;Bae, Yong-C.
    • International Journal of Oral Biology
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    • v.35 no.3
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    • pp.83-89
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    • 2010
  • We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with $50\;{\mu}L$ of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors ($10\;{\mu}g$) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.

Influence of Serum VEGF Levels on Therapeutic Outcome and Diagnosis/Prognostic Value in Patients with Cervical Cancer

  • Du, Ke;Gong, Hong-Ying;Gong, Zhi-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8793-8796
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    • 2014
  • Objective: To explore the influence of serum vascular endothelial growth factor (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. Materials and Methods: A total of 37 patients diagnosed with cervical cancer by biopsy were selected and treated with concurrent chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted before treatment to assess VEGF levels, and its relationships with clinicopathological features and short-term therapeutic effects were analyzed. Results: The median VEGF level in 37 patients before treatment was 647.15 (393.35~1125.16) pg/mL. Serum VEGF levels in patients aged <50 years, in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with lymph node metastasis and tumor size >4 cm were significantly increased (P<0.05). The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size and serum VEGF level before treatment were independent risk factors affecting the therapeutic outcome, and the higher the level of serum VEGF, the worse the prognosis when tumor size>4 cm. Some 56.8% of patients manifested with myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with hepatic and renal injury during the treatment. Conclusions: Serum VEGF level may reflect the degree of malignancy of cervical cancer and predict therapeutic effect, which is of great importance to cancer diagnosis and prognosis.

Protective Effects of Gyungokgo on Oxidative Stress-Induced Apoptosis of H9c2 Cardiomyoblast Cells (산화적 손상으로 유발된 심근세포 고사에 대한 경옥고의 방어효과)

  • Shin Sun-Ho;Yang Kyung-Suk
    • The Journal of Korean Medicine
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    • v.25 no.3
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    • pp.149-159
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    • 2004
  • Backgrounds & Objectives : The water extract of Gyungokgo (GOG) has traditionally been used for treatment of general weakness and hemoptysis in oriental medicine. However, little is known about the mechanism by which the water extract of GOG rescues cells from these damages. This study was designed to investigate the protective mechanisms of GOG on H2O2­induced cell death in H9c2 cardiomyoblasts. Methods : In this study, we used H9c2 cells. Cells were treated with oxidative stress in the absence and presence of 1000㎍/ml GOG for 12hrs. Cells were treated with various concentrations of GOG for 12hrs. Cell viability was measured by MTT assay. Oxidative stress, which markedly decreased the viability of H9c2 cells, was characterized by apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. Results : GOG significantly reduced H₂O₂-induced cell death and apoptotic characteristics. The cotreatment of GOG and H₂O₂ in H9c2 cells also induced the phosphorylation of ERKs in a time-dependent manner. Moreover, PD098059, a MEK1 (upstream activator of ERK) inhibitor attenuated the protective effect of GOG on H₂O₂-induced cytotoxicity in H9c2 cardiomyoblast cells. Conclusions : These results suggest that MEK/ERK pathways play important roles in the protective effects of GOG in H9c2 cells. Taken together, they suggest that the protective effects of the water extracts of GOG against oxidative damages may be mediated by the regulation of HO-1, Fas/FasL and Bcl-XS proteins.

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Allometric Equations for Estimating the Standing Biomass of Basidiocarps (버섯 자실체의 현존량 추정을 위한 상대생장식)

  • Heo, Eun-Pork;You, Young-Han
    • The Korean Journal of Mycology
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    • v.37 no.1
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    • pp.55-59
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    • 2009
  • The mushroom takes in charge of decomposer in ecosystem and its production is important indicator for sounded ecosystem function. To determine standing crop of basidiocarps(fruit body of mushroom), a weight must be measured by harvesting mushroom individual in the field. But this method has profound affection on the basidiocarps population or its surrounding condition due to habitat destruction. Thus, in this study, without harvesting any mushroom in the field, we developed allometric equation using some morphological parameters to estimate standing crop biomass of basidiocarps. Lentinula edodes, Pleurotus ostreatus, Flammulina velutipes and Conocybe tenera were used for allometry. Morphological variables of the mushroom were pileus diameter, pileus area, stipe length and stipe thickness. Consequently, all the experimental mushrooms species showed significantly correlation in biomass estimation of basidiocarps from allometric equation (p<0.05). As a result of this research, the standing biomass of the basidiocarps could be indirectly estimated with proportional expression, allometric equation drived from morphological characters.

Electrical properties of multilayer actuator and linear ultrasonic motor using low temperature PZW-PMN-PZT ceramics (저온소결 PZW-PMN-PZT 세라믹을 이용한 적층액츄에이터 및 선형초음파 모터의 전긱적 특성)

  • Lee, Il-Ha;Yoo, Ju-Hyun;Hong, Jae-Il;Jeong, Yeong-Ho;Yoon, Hyun-Sang
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2008.11a
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    • pp.206-206
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    • 2008
  • 압전소자를 이용한 초음파 모터는 전자기적 원리로 동작하는 기존의 모터에 비해 구조가 간단하고 소형, 경량화가 가능하며 저속에서 큰 토크가 가능하고 ${\mu}m$단위 까지 정밀제어가 가능하다는 장점 등으로 인해 그 응용분야가 점차 확대되고 있다. 초음파 모터의 원리는 수평과 수직방향에서 변위가 타원형 운동을 형성하는 것이다. 따라서 선택한 타원운동의 방식에 의해서 모터의 형상이 달라진다. 초음파 모터는 액츄에이터를 사용하여 만들기 때문에 액츄에이터의 특성은 모터의 타원변위나 토크에 영향을 미친다. 단판형 액츄에이터에 비하여 적층 액츄에이터는 입력 임피던스를 낮추어 낮은 구동전압에서 구동이 가능하며 큰 변위와 토크를 발생하기 때문에 진동자의 수명 향상과 구동전압을 낮추기에 적합하다. 적층 액츄에이터는 변위량이나 응력 등을 개선하기 위해서 전기기계 결합계수(kp) 및 압전 d상수가 큰 재료가 요구되며, 고전압에서 장시간 구동 시 마찰에 의한 열손실을 감소시키기 위해 높은 기계적 품질계수(Qm)를 가져야한다. 적층 시 내부전극으로 사용하는 Pd, Pt가 함유된 전극은 가격이 비싸 제조비용을 상승시킨다. 상대적으로 값싼 Ag전극을 사용하면 비용절감을 할 수 있지만 융점이 낮아서 저온소결이 불가피하다. 따라서, 특성이 우수한 적층 액츄에이터를 제조하기 위해서 저손실, 저온소결 할 수 있는 액츄에이터 재료가 필요한 실정이다. L1-B4 혈 선혈 초음파 모터는 L1모드와 B4모드의 공진 주파수가 일치하여야 큰 변위를 얻을 수 있는데 이전의 논문에서 Atila를 이용한 시뮬레이션 결과를 분석한 봐 있다. 적층 액츄에이터의 층수를 5,7,9,11,13,15층으로 하여 L1-B4모드에서의 공진주파수를 비교한 결과 13 층일 때 두 모드가 비슷한 공진주파수를 보였고, 티원변위궤적도 다른 층수에 비해 크게 나타났다. 본 연구에서는 시뮬레이션 결과 가장 좋은 특성을 보인 13층 액츄에이터로 선형 초음파 모터를 제작하였다. 또한, 액츄에이터는 압전 및 유전특성이 우수한 저온소결 PZW-PMN-PZT세라믹을 이용하여 제작하였고, 내부전극으로 Ag전극을 사용하였다. 제작된 13 층 선형초음파모터를 가지고 프리로드 및 전압에 따른 속도를 조사하였고, 시뮬레이션 결과와 비교해 보았다.

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Free Radical Scavening and Inflammatory from the Rice Varieties Contained High C3G pigment (C3G색소 고함유 벼품종의 자유라디칼 소거작용 및 항염효과)

  • Park, Sun-Zik;Ryu, Su-Noh
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.51 no.spc1
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    • pp.107-112
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    • 2006
  • Free Radical Scavening and inflammatory of the methanol extracts, which were prepared from 6 difffrent bran of rice, were evaluated to investigate bioactive substances. Among them, the extract of C3GHibyeo and Heugjinjubyeo showed strong DPPH scavening activities (73.25% and 50.38% at 0.4 mg/ml, respectively). The extract of C3GHibyeo and Heugjinjubyeo showed strong thrombin inhibition activities (258.76% and 243.52% inhibition at 5 mg/ml, respectively). The result of antibacterial activity by Zone assay showed that C3GHi rice extract $(250{\mu}g\;and\;500{\mu}g)$ inhibited attachment of Helicobactor pylori on the ATCC48504 and COO1 cell line. But no effect on the SEO cell line. Cytotoxicity of blackish purple rice extract on the H. pylori doesn't showed. These result support a functional superiority of rice-base livelihood, and suggest that the development of healthy food using functional ingredients of rice is possible.

Regulation of tumor-associated macrophage (TAM) differentiation by NDRG2 expression in breast cancer cells

  • Lee, Soyeon;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • BMB Reports
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    • v.55 no.2
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    • pp.81-86
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    • 2022
  • Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

Anti-inflammatory Effects of UDCA on Splenocytes Exposed to PMA/Ionomycin

  • Park, So-Young;Woo, Jong-Shick;Jung, Yu-Jin;Won, Tae-Joon;Hih, Yun-Ju;Lee, Chan-Woo;Kim, Hyo-Shin;Joo, Seong-Soo;Lee, Do-Ik;Hwang, Kwang-Woo
    • Biomolecules & Therapeutics
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    • v.16 no.2
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    • pp.126-131
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    • 2008
  • Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

The Analysis of MMPI and Clinical Study for Somatization Disorder and Depressive Disorder Patients (우울증성 장애 및 신체형 장애 환자에 대한 MMPI분석과 임상고찰)

  • Choe, Byeong-Man;Jung, In-Chul;Lee, Sang-Ryong;Park, Ji-Un
    • Journal of Oriental Neuropsychiatry
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    • v.13 no.2
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    • pp.41-56
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    • 2002
  • The Analysis of MMPI and Clinical Study was carried out the 28 patients with somatoform disorder and depressive disorder who were treated in Daejeon University Oriental Hospital from 19 June 2001 to 17 April 2002. The results were summarized as follows. 1. The ratio of female was higher, especially in the depressive disorder, the ratio of female was higher and in the age distribution, the 40 aged were higher frequence. 2. In the somatoform disorder, symptoms appeared to be busy in physical symptoms, and they were in descending order the digestive organs system, head and face portion and musculoskeletal system symptoms, in the depressive disorder, appeared to be busy in psychosomatic system symptoms and in the prescription drugs, soyosan(逍遙散), punsimkiyyin(分心氣飮) were used to be busy. 3. In the scales of L, F, K, somatoform disorder showed ${\wedge}$ typed graph, and depressive disorder showed ${\vee}$ typed graph. 4. In the somatoform disorder, scales of Hs, Hy, D, Pa were higher, and in the depressive disorder, scales of Hy, Hs, Pd, D were higher. 5. In the scales of Hs, D, Hy, somatoform disorder showed ${\vee}$ typed graph, and depressive disorder showed/typed graph. 6. the average of T-scores and the ratio over 65 score and 70 score showed common distribution.

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Purification and Characterisation of a Burkholderia pseudomallei Protease Expressed in Recombinant E. coli

  • Ling, Jessmi M.L.;Nathan, Sheila;Hin, Lee Kok;Mohamed, Rahmah
    • BMB Reports
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    • v.34 no.6
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    • pp.509-516
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    • 2001
  • A genomic DNA fragment that contains the gene, which codes for a novel extracellular serine protease in Burkholderia pseudomallei, was cloned by using pQE40 as a vector. It was maintained in Escherichia coli JM109. The expression of the gene(s) resulted in the production of a 52 kDa protease. The recombinant protease was purified from the culture filtrate via ammonium sulfate fractionation, gel filtration, and anion-exchange chromatography. The purified protease had an optimum pH and temperature of pH 8.9 and $38^{\circ}C$, respectively. The protease activity was inhibited by EGTA, EDTA, and PMSF, but not 1,10-phenanthroline. The first 11 amino acid residues from the N-terminus of the purified protease were identified as LAPNDPYYYGY. PNDPYY was found to show homology to the Bacillus cereus microbial serine protease and B. subtilis PD498 serine protease. These results indicate that the protease that was purified in this study is an extracellular calcium-dependent serine protease. The purified protease was able to digest the human serum 19A, IgG, albumin, and transferrin, as well as bovine muscle actin and myosin. Furthermore, it was able to promote or cause dermonecrosis in experimental rabbits. These results propose the possible role of a novel B. pseudomallei extracellular calcium-dependent serine protease in the virulence of the pathogen.

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