• Molecules and Cells
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• 제41권6호
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• pp.545-552
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• 2018

Spleen tyrosine kinase (SYK) is a cytosolic non-receptor protein tyrosine kinase. Because SYK mediates key receptor signaling pathways involving the B cell receptor and Fc receptors, SYK is an attractive target for autoimmune disease and cancer treatments. To date, representative oral SYK inhibitors, including fostamatinib (R406 or R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659, have been assessed in clinical trials. Here, we report the crystal structures of SYK in complex with two newly developed inhibitors possessing 4-aminopyrido[4,3-D]pyrimidine moieties (SKI-G-618 and SKI-O-85). One SYK inhibitor (SKI-G-618) exhibited moderate inhibitory activity against SYK, whereas the other inhibitor (SKI-O-85) exhibited a low inhibitory profile against SYK. Binding mode analysis indicates that a highly potent SYK inhibitor might be developed by modifying and optimizing the functional groups that interact with Leu377, Gly378, and Val385 in the G-loop and the nearby region in SYK. In agreement with our structural analysis, one of our SYK inhibitor (SKI-G-618) shows strong inhibitory activities on the ${\beta}$-hexosaminidase release and phosphorylation of SYK/Vav in RBL-2H3 cells. Taken together, our findings have important implications for the design of high affinity SYK inhibitors.

• 한방재활의학과학회지
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• 제18권2호
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• pp.1-15
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• 2008

Objectives : The aim of this study was to know the immunity response of Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) to rheumatoid arthritis in collagen-induced arthritis(CIA) mice. Methods : For this purpose, Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) was orally administerd to mice with arthritis induced by collagen II and then value of immunocyte in spleen, draining lymph node and paw joint and cytokine(IL-6, $TNF-{\alpha}$), rheumatoid factor (IgG and IgM) in serum were measured. Results : 1. The arthritis index was significantly decreased. 2. In total cell counts of spleen, DLN and paw joint, the cells in spleen decreased while there was a significant increase in DLN and significant decrease in paw joint. 3. In lymph nodes, CD3+, CD3+/CD69+, CD4+, CD8+ cells increased significantly. 4. In joints, CD3+ and CD11+b/Gr-1+ cells decreased significantly. 5. Serum IL-6 and $TNF-{\alpha}$ were decreased significantly. 6. Production of serum IgG and IgM decreased significantly. Conclusions : The results present that Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) controls abnormal activity of immune system, inhibitig collagen-induced arthritis(CIA).

• 동의생리병리학회지
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• 제33권5호
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• pp.275-281
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• 2019

Polysaccharides produced in microorganisms and plants are known to increase the immune response in the body. We proposed analysis of beta-glucan contents of phellinus linteus fruit body (FB) and mycelium (MC) cultured in cudrania tricuspidata. Also, we examined whether fruit body and mycelium can increase the immune response in cyclophosphamide-induced immunosuppression animal models. We injected cyclophosphamide (50 mg/kg) twice to produce immunosuppression mice. Then, FB (200 mg/kg) and MC (200 mg/kg) were oral administered for 14 days. In order to confirm the immune-enhancing effect of FB and MC, we analyzed spleen weight, the number of immune cells, cytokines, and immunoglobulins levels. Cyclophosphamide decreased the weight of spleen, the number of immune cells. However, FB and MC have significantly increased the weight of spleen, the number of white blood cell, lymphocyte and monocyte. In addition, they have significantly increased immune-related cytokines (IL-2 and IFN-${\gamma}$) and immunoglobulins (IgA, IgG, IgM) levels. As a results, phellinus linteus fruit body (FB) and mycelium (MC) cultured in cudrania tricuspidata can be used as effective natural materials for immune-enhancing.

• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.6-14
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• 2022

Brucella spp. are facultative intracellular pathogens that invade, survive and proliferate in numerous phagocytic and non-phagocytic cell types, thereby leading to human and animal brucellosis. Outer membrane proteins (Omps) are major immunogenic and protective antigens that are implicated in Brucella virulence. A strain deleted of the omp16 gene has not been obtained which suggests that the Omp16 protein is vital for Brucella survival. Nevertheless, we previously constructed an omp16 conditional deletion strain of Brucella, ∆Omp16. Here, the virulence and immune response elicted by this strain were assessed in a mouse model of infection. Splenomegaly was significantly reduced at two weeks post-infection in ∆Omp16-infected mice compared to infection with the parental strain. The bacterial load in the spleen also was significantly decreased at this post-infection time point in ∆Omp16-infected mice. Histopathological changes in the spleen were observed via hematoxylin-eosin staining and microscopic examination which showed that infection with the ∆Omp16 strain alleviated spleen histopathological alterations compared to mice infected with the parental strain. Moreover, the levels of humoral and cellular immunity were similar in both ∆Omp16-infected mice and parental strain-infected mice. The results overall show that the virulence of ∆Omp16 is attenuated markedly, but that the immune responses mediated by the deletion and parental strains in mice are indistinguishable. The data provide important insights that illuminate the pathogenic strategies adopted by Brucella.

• Molecules and Cells
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• 제44권11호
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• pp.795-804
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• 2021

Memory T (T_M) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how T_M cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, T_M cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin⁺ cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of T_M cells. The numbers of CD127^hiCD62L^hi T_M cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127^loKLRG1^hi T_M cells were adoptively transferred into anti-N-cadherin-treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, without functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127^hiCD62L^hi T_M cells and homing of CD127^loKLRG1^hi T_M cells to lymphoid organs.

• 대한수의학회지
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• 제22권2호
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• pp.221-232
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• 1982

This paper dealt with the pathological and clinical findings on the experimentally induced rodenticide (fluoroacetate, zinc phosphide, thallium sulfate, coumarin) and NaCN poisoning of ruminants (Holstein cattle and/or Korean native goat) for the purpose of the diagnosis in the accidental rodenticide poisoning of cattle. The results observed are summarized as follows: Fluoroacetate poisoning (cattle and goat): in the clinical signs, there were depression, convulsion, dyspnea, groan, grinding of the teeth, vomiting, opisthotonus and post-mortem tympany. In the macroscopical findings, the blood was more or less poor coagulative and dark red, bloody fluid with foam in the trachea, hyperemia and hemorrhage of tracheal mucosa and lung, cloudy swelling and hyperemia of kidney, epicardial hemorrhage(cattle), and hyperemia of abomasum, intestine and brain were observed. In the microscopical findings, there were pulmonary edema and hemorrhage, necrosis of convoluted tubular epithelium and interstitial hemorrhage of kidney, focal coagulative necrosis of myocardium, hemorrhage of pancreas and spleen, dilatation of Virchow-Robin space and hyperemia of brain, and necrosis with desquamation of mucosal epithelia of abomasum and upper small intestine. In the histological lesions of the liver, lobular peripheral hyperemia, centrilobular necrosis and cytoplasmic inclusion bodies of the hetatic cells were observed. The cytoplasmic inclusion body of the hepatic cells was not seen in the affected goat, but hydropic degeneration of the hepatic cells was marked. Zinc phosphide poisoning (cattle and goat): clinically, the affected animals died in recumbent position after ataxia, dyspnea and convulsion. In the macroscopical findings, hyperemia and hemorrhage of lung, cloudy swelling and hyperemia of liver and kidney, hemorrhage of spleen (cattle), and catarrh of abomasum and small intestine were observed. In the microscopical findings, necrosis of the convoluted tubular epithelium and hyperemia of kidney, hemorrhage of spleen, hyperemia of lung, hyperemia or hemorrhage of heart, cloudy. swelling and fatty changes of hepatic cells, dilatation of hepatic central vein, hyperemia of brain, and catarrh of abomasal and small intestinal mucosae were observed. Thallium sulfate poisoning (cattle): in the macroscopical findings dark red color of blood, hyperemia and hemorrhage of lung, bloody fluid with foam in the tracheal mucosa, petechiae of tracheal mucosa, cloudy swelling and hemorrhage of liver, necrotic lesions and hemorrhage of renal cortex and epicardial hemorrhage were observed. In the microscopical findings, severe hemorrhages of the lung, cloudy swelling and necrosis of hepatic cells, hyperemia and hemorrhage of liver, focal coagulative necrosis of mycordium, necrosis of the convoluted tubular epithelium and hyperemia of kidney, hyperemia and hemorrhage of spleen and dilatation of Virchow-Robin apace in brain were observed. Coumarin poisoning (goat): the poisoned animals died in the state of groan and depression. In the macroscopical findings, poor coagulation of blood, hemorrhage of lung, cloudy swelling and severe hemorrhages of liver, cloudy swelling and hemorrhage of kidney, abomasal hemorrhage, catarrh of small intestine, and hyperemia and hemorrhage of the other organs were observed, In the microscopical findings, hyperemia and hemorrhage of lung and kidney, cloudy swelling of the convoluted tubular epithelium of kidney, severe hepatic hyperemia, cloudy swelling and hydropic degeneration of heptatic cell, and hyperemia and hemorrhage of brain and spleen were observed. NaCN poisoning (cattle and goat): clinically, there were convulsion, severe dyspnea, paresis of hind limb, depression and then rigor of four limbs. In the macroscopical findings, bright red color of blood, hyperemia and bright and red tinge of lung cloudy swelling of kidney and liver, and hyperemia of abomasum were observed. In the microscopical findings, cloudy swelling and hydropic degeneration of hepatic cell, hyperemia and edema of lung, necrosis and degeneration of the convoluted tubular epithelium and hemorrhage in kidney, dilatation of Virchow-Robin space of brain and hemorrhage of spleen were observed.

• Environmental Analysis Health and Toxicology
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• 제3권1_2호
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• pp.21-31
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• 1988

The effect of capsaicin on the toxicity of ethanol in mice were studied. Capsaicin was administered i.p. every other day for 4 weeks and 5% ethanol was provided ad libitum by tap water for 4 weeks. The administration of capsaicin 3.0 mg/kg showed the increase of body weight gain, ratio of liver wt./body wt., s-GPT. s-triglyceride and s-cholesterol, and showed the decrease of BUN as compared to control group. Capsaicin administered 3.0 mg/kg showed severe moth eaten appearance. eosinophilic necrosis and cholangitis in mouse liver The administration of 5% ethanol showed the decrease of body weight gain, ratios of liver, kidney and spleen wt./body wt., s-tryglyceride and s-cholestrol. Ethanol administered 5% solution showed little fatty change, moth eaten appearance, Kupffer cell proliferation, spotty necrosis and nuclear regeneration. The administration of capsaicin and ethanol together decreased the influence of ethanol on body weight gain, ratios of liver, kidney and spleen wt./body wt., s-triglyceride and s-cholesterol, and showed the less severe moth eaten appearance, eosinophilic necrosis and cholangitis. It might be concluded that the administration of capsaicin and ethanol together decreased the toxicity caused by capsaicin or ethanol respectively.

• 한국어병학회지
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• 제32권2호
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• pp.81-89
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• 2019

As an epidemiological survey, mortality of marbled rockfish, Sebastiscus tertius observed from a fish farm in Gyeongnam province of South Korea. The major macroscopic sign of the diseased fish was severe multifocal dermal ulceration. Histological observation revealed inflammation, necrosis and colonization of bacteria in various tissues (gill, liver, spleen and kidney). Bacteria was isolated from spleen and kidney in moribund and mortality fish. Seven bacterial isolates from the diseased fish were identified as Aeromonas salmonicida subsp. salmonicida using API 20E and 20NE, API 50CH API ZYM system. Under light microscopy, infected marbled rockfish showed the lifting of the lamella epidermal layer, edematous changes and hypertrophy of epithelial cell in the gill filament. The atrophy of the mucosal fold, erythema in the intestine, and the necrosis of hematopoietic tissue and renal tubule cells with karyolysis were observed in the kidney. In this study was demonstrated the histological reaction of red marbled rockfish infected by Aeromonas salmonicida. Furthermore, this is the first account of extensive dermatitis in Sebastiscus tertius due to atypical A. salmonicida infection, which has high potential in aquaculture among native fish species.

• 한국식품위생안전성학회지
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• 제15권4호
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• pp.282-286
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• 2000

한천올리고당을 식품으로 활용하기 위한 전제 조건인 안전성 실험결과, 한천올리고당 LD$_{50}$ 은 1359mg/kg으로 GRAS(Generally Recognized As Safe)등급에 해당하는 무해첨가물에 해당되었다. 또한 5% 한천올리고당의 항돌연변이 효과는 TA 98균주에 88.3%, TA 100균주에 54%의 저해효과를 나타내어 강력한 항돌연변원성 물질임을 알 수 있었다. 한천올리고당의 면역활성을 평가하기 위하여 비장세포에 한천올리고당을 200${\mu}\ell$/$m\ell$ 첨가하여 배양한 결과, 대조군과 비교시 배양 20일 이후에도 비장세포수가 감소하지 않아 한천올리고당의 면역증진 효과를 알 수 있었다.

• 한국식품위생안전성학회지
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• 제5권3호
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• pp.111-120
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• 1990

정상 마우스와 Cyclophosphamide(CY)로 처리된 마우스에 Royal Jell(RJ)를 투여하여 면역계에 미치는 영향을 실험한 결과 다음과 같은 결론을 얻었다. 1. 정상 마우스에 RJ를 투여하였을 때는 대조군에 비하여 마우스의 체중, 비장, 흉선 , WBC 수 , DNFB에 대한 접촉성 과민 반응으로 측정된 세포성 면역반응 및 면양 적혈구에 대한 응집가와 용혈가로 측정된 체액성 면역 반응이 투여일에 따라 증가 또는 감소되었고, RBC수와 간 중량은 영향을 받지 않았다. 2. 증가 작용을 보여준 투여일에 RJ를 병용 투여함으로써, CY 처리로 인한 마우스의 생존율, 비장의 중량 , WBC수 및 세포성 면역 반응의 감소가 약간 억제되었으나, CY를 감소된 흉선의 중량 및 체액성 면역반응에는 영향을 나타내지 않았다.