• Biomolecules & Therapeutics
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• 제27권3호
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• pp.318-326
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• 2019

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 ($S1P_2$) has not been fully investigated. Therefore, in this study, the roles of $S1P_2$ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the $7^{th}$ day after bleomycin administration, $S1P_2$ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the $28^{th}$ day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from $S1P_2$ deficient mice showed less inflammation and fibrosis. Increase in TGF-${\beta}1$-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a $S1P_2$ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of $S1P_2$ were elucidated using a bleomycin-induced fibrosis model. Notably, $S1P_2$ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that $S1P_2$ could be a promising therapeutic target for the treatment of pulmonary fibrosis.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.80-90
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• 2017

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, $S1P_{1-5}$. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn's disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications.

• The Plant Pathology Journal
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• 제38권4호
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• pp.383-394
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• 2022

In Japan, the P1 protein (S-type) encoded by leek yellow stripe virus (LYSV) isolates detected in Honshu and southward is shorter than the P1 (N-type) of LYSV isolates from garlic grown in Hokkaido due to a large deletion in the N-terminal half. In garlic fields in Hokkaido, two types of LYSV isolate with N- and S-type P1s are sometimes found in mixed infections. In this study, we confirmed that N- and S-type P1 sequences were present in the same plant and that they belong to different evolutionary phylogenetic groups. To investigate how LYSV with S-type P1 (LYSV-S) could have invaded LYSV with N-type P1 (LYSV-N)-infected garlic, we examined wild Allium spp. plants in Hokkaido and found that LYSV was almost undetectable. On the other hand, in Honshu, LYSV-S was detected at a high frequency in Allium spp. other than garlic, suggesting that the LYSV-S can infect a wider host range of Allium spp. compared to LYSV-N. Because P1 proteins of potyviruses have been reported to promote RNA silencing suppressor (RSS) activity of HC-Pro proteins, we analyzed whether the same was true for P1 of LYSV. In onion, contrary to expectation, the P1 protein itself had RSS activity. Moreover, the RSS activity of S-type P1 was considerably stronger than that of N-type P1, suggesting that LYSV P1 may be able to enhance its RSS activity when the deletion is in the N-terminal half and that acquiring S-type P1 may have enabled LYSV to expand its host range.

• 대한수학회보
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• 제57권2호
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• pp.429-441
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• 2020

Let M(X, Y) denote the space of multipliers from X to Y, where X and Y are analytic function spaces. As we known, for Dirichlet-type spaces 𝓓_α^p, M(𝓓_p-1^p, 𝓓_q-1^q) = {0}, if p ≠ q, 0 < p, q < ∞. If 0 < p, q < ∞, p ≠ q, 0 < s < 1 such that p + s, q + s > 1, then M(𝓓_p-2+s^p, 𝓓_q-2+s^q) = {0}. However, X ∩ 𝓓_p-1^p ⊆ X ∩ 𝓓_q-1^q and X ∩ 𝓓_p-2+s^p ⊆ X ∩ 𝓓_q-2+s^p whenever X is a subspace of the Bloch space 𝓑 and 0 < p ≤ q < ∞. This says that the set of multipliers M(X ∩ 𝓓 _p-2+s^p, X∩𝓓_q-2+s^q) is nontrivial. In this paper, we study the multipliers M(X ∩ 𝓓_p-2+s^p, X ∩ 𝓓_q-2+s^q) for distinct classical subspaces X of the Bloch space 𝓑, where X = 𝓑, BMOA or 𝓗^∞.

• 대한예방한의학회지
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• 제10권1호
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• pp.141-153
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• 2006

In order to study the changes in hematology and serum chemistry of rats injected with glycerol, Sprague-Dawley albino rats weighing 240 to 260 gm were injected intramuscularly with a 50% solution of glycerol(8ml/kg). We measured the values of hematology and serum chemistry, and compared the measured values of S1 group(passed for 1day after injection of glycerol), S2 group(passed for 2days after injection of glycerol), S3 group(passed for 3days after injection of glycerol), S4 group(passed for 3days after injection of glycerol) and S5 group(passed for 4days after injection of glycerol) with those of Normal group(non-treated group). The results are summarized as follows : 1. In body temperature, S1, S2, S4 groups showed significantly higher compared with Normal group, especially S2 group was higher than S1 group(p<0.05). But S5 group was lower than Normal group(p<0.05). 2. In RBC, S1 group was lower than Normal group(p<0.05). And in Hct, S1, S2, S3 groups were lower than Normal group(p<0.05), in Hb, S1 and S3 groups were lower than Normal group(p<0.05). 3. In WBC, S1, S2 groups were higher than Normal group(p<0.05). and in WBC differential count, S2, S3, S5 groups were higher than N, S1, S4 groups in monocyte(p<0.05). 4. In GOT, S1 group was higher than Normal group(p<0.05), and S2, S3, S4, S5 groups were lower than S1 group(p<0.05). In GPT, S1 group was higher than Normal group(p<0.05), and S2, S3 groups were lower than S1 group(p<0.05), S4, S5 groups were lower than N, S1, S2, S3 groups(p<0.05). 5. In total cholesterol and creatinine, S4 group was higher than Normal group(p<0.05). According to the above experimental results, we could find the anemia, inflamation, damage of renal function for 4 days by intramuscularly injection with a 50% solution of glycerol(8ml/kg) in rat.

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.640-648
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• 2005

목 적 : 가와사끼병은 여러 가지 면역학적 이상을 보이는 혈관염으로 혈관 내피세포의 면역학적 기전과 관련하여 세포부착 분자가 관여하는 것으로 알려져 있다. 본 연구는 가와사끼병에서 세포부착분자 sICAM-1과 sVCAM-1을 급성 발열기와 아급성기로 나누어 비교 분석하였고 이들의 심장병변과 관련된 임상적 의의를 찾고자 하였다. 방 법 : 2002년 1월부터 2004년 6월까지 중앙대학교 의료원 소아과에 전형적인 가와사끼병으로 입원한 32명을 대상으로 감마글로불린 투여 전 급성 발열기와 발병 2주의 아급성기의 Troponin T와 I, 심장 초음파 검사 소견, sICAM-1, sVCAM-1을 비교, 분석하였고, 가와사끼병이 아닌 급성 발열성 질환으로 입원한 16명을 대조군으로 하였다. 결 과 : sICAM-1 및 sVCAM-1은 급성 발열기 가와사끼병에서 대조군에 비하여 의미있게 증가하고(P=0.019, P=0.049) 특히 sICAM-1은 급성발열기에 비하여 아급성기때 의미있게 감소하였다(P=0.0015). 급성 발열기, 아급성기 모두에서 sICAM-1과 sVCAM-1은 상호간에 양의 상관관계를 나타내었다(P=0.0067, P=0.015). sICAM-1, sVCAM-1 모두 정맥용 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 관상동맥 병변의 정도를 의미있게 반영하지는 못하였으나, sVCAM-1의 경우 급성 발열기 및 아급성기 모두 심염군에서 통계적으로 의미있게 증가하였다(P=0.025, P=0.014). 또한 급성 발열기 sVCAM-1과 Troponin T는 양의 상관관계를 나타내었다(r=0.63, P=0.00063). 결 론 : sICAM-1과 sVCAM-1은 가와사끼병의 병인에 중요한 역할을 하나 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 가장 중요한 합병증인 관상동맥병변을 직접적으로는 반영하지는 못한다. 그러나 sVCAM-1의 경우 심염에 있어 중요한 역할을 하는 것으로 여겨진다. 이에 대해서는 다양한 세포부착분자에 대하여 가와사끼병에서의 면역학적인 기전에 대한 추가 연구가 있어야 할 것으로 생각한다.

• 한국축산식품학회지
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• 제27권2호
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• pp.235-243
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• 2007

본 연구는 조사료인 호맥 사일리지를 배합사료와 혼합급여 시 비육돈의 성장, 혈액성상 및 도체특성에 미치는 영향을 알아보기 위해 시험을 실시하였다. 3원 교잡종($Landrace{\times}Yorkshire{\times}Duroc$) 비육돈 18두를 공시하였으며 시험개시시 평균체중은 $74.22{\pm}0.71kg$이었고 28일간 개체별 사양시험을 실시하였다. 시험설계는 호맥 사일리지 첨가에 따라 1) Con(basal diet), 2) S1(basal diet+1.66% rye silage), 3) S2(basal diet+3.32% rye silage)로 3처리로 하여 처리당 6반복, 반복당 1마리씩 $1.8{\times}1.8m$ 크기의 돈방에 개별 수용하였다. 생산성에서 $4{\sim}7$주 동안 일당사료 섭취량에서는 CON구가 S1구와 S2구와 비교하여 유의적으로 높게 나타났다(p<0.05). 전체 사양시험기간 동안($0{\sim}7$주) 일당사료섭취량에서는 CON구와 S2구가 S1구와 비교하여 유의적으로 높게 나타났다(p<0.05). 혈중 스트레스 관련 호르몬인 코티졸 함량의 변화는 대조구와 비교하여 호맥 사일리지를 급여한 S1구와 S2구에서 유의적으로 감소하였다(p<0.05). 육색에서 명도를 나타내는 $L^*$값은 S2구가 CON구와 비교하여 유의적으로 높게 나타났고(p<0.05) 황색도를 나타내는 $b^*$값은 S1구와 S2구가 CON구와 비교하여 높게 나타났다(p<0.05). 도체 등지방 두께는 CON구가 S1구와 S2구와 비교하여 유의적으로 높게 증가하였다(p<0.05). 살코기 내 지방산 조성에서는 포화지방산 중 palmitic acid와 stearic acid의 함량은 CON구가 S1구와 S2구와 비교하여 유의적으로 높은 함량을 나타내었다(p<0.05). 불포화 지방산에서는 eicosenoic acid와 linolenic acid의 함량이 S2구가 CON구와 S1구와 비교하여 유의적으로 높았다(p<0.05). 총 포화지방산 함량은 CON구가 다른 처리구와 비교하여 가장 높았으며(p<0.05) 포화지방산과 불포화지방산 비율에서는 S1구와 S2구가 CON구와 비교하여 유의적으로 높은 결과를 보였다(p<0.05). 지방 내 지방산 조성에서는 불포화지방산 중 linolenic acid의 함량은 S2구가 S1구와 CON구와 비교하여 유의적으로 높았다(p<0.05). 건물 소화율에서는 S1구와 S2구가 CON구와 비교하여 유의적으로 높게 나타났고(p<0.05) 질소 소화율에서는 S1구가 처리구중에서 가장 높은 결과를 보였다(p<0.05). 분변 내 휘발성 지방산 발생량에서는 분을 1일간 발효 후 측정한 결과 S1구와 S2구가 CON구와 비교하여 유의적으로 높게 나타났다(p<0.05). 결론적으로, 비육돈 사료 내 3.32%의 호맥 사일리지의 혼합급여는 혈액 내 코티졸 함량, 도체육의 명도와 황색도, 지방산 조성 및 영양소 소화율에 영향을 미치는 것으로 사료되나 이에 대한 보다 많은 연구가 필요할 것으로 판단된다.

• 대한수학회지
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• 제43권4호
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• pp.783-801
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• 2006

Let A be the mod p Steenrod algebra for p an arbitrary odd prime and S the sphere spectrum localized at p. In this paper, some useful propositions about the May spectral sequence are first given, and then, two new nontrivial homotopy elements ${\alpha}_1{\jmath}{\xi}_n\;(p{\geq}5,n\;{\geq}\;3)\;and\;{\gamma}_s{\alpha}_1{\jmath}{\xi}_n\;(p\;{\geq}\;7,\;n\;{\geq}\;4)$ are detected in the stable homotopy groups of spheres, where ${\xi}_n\;{\in}\;{\pi}_{p^nq+pq-2}M$ is obtained in [2]. The new ones are of degree 2(p - 1)($p^n+p+1$) - 4 and 2(p - 1)($p^n+sp^2$ + sp + (s - 1)) - 7 and are represented up to nonzero scalar by $b_0h_0h_n,\;b_0h_0h_n\tilde{\gamma}_s\;{\neq}\;0\;{\in}\;Ext^{*,*}_A^(Z_p,\;Z_p)$ in the Adams spectral sequence respectively, where $3\;{\leq}\;s\;<\;p-2$.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.373-383
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• 2021

Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.

• Journal of applied mathematics & informatics
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• 제22권1_2호
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• pp.361-372
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• 2006

In this paper, we consider the multi-point boundary value problems for one-dimensional p-Laplacian at resonance: $({\phi}_p(x'(t)))'=f(t,x(t),x'(t))$, subject to the boundary value conditions: ${\phi}_p(x'(0))={\sum}^{n-2}_{i=1}{\alpha}_i{\phi}_p(x'({\epsilon}i)),\;{\phi}_p(x'(1))={\sum}^{m-2}_{i=1}{\beta}_j{\phi}_p(x'({\eta}_j))$ where ${\phi}_p(s)=/s/^{p-2}s,p>1,\;{\alpha}_i(1,{\le}i{\le}n-2){\in}R,{\beta}_j(1{\le}j{\le}m-2){\in}R,0<{\epsilon}_1<{\epsilon}_2<...<{\epsilon}_{n-2}1,\;0<{\eta}1<{\eta}2<...<{\eta}_{m-2}<1$, By applying the extension of Mawhin's continuation theorem, we prove the existence of at least one solution. Our result is new.