Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells

Kim, J.H.,Choi, Y.J.,Lee, B.H.,Song, M.Y.,Ban, C.Y.,Kim, J.,Park, J.,Kim, S.E.,Kim, T.G.,Park, S.H.,Kim, H.P.,Sung, Y.C.,Kim, S.C.,Shin, E.C. Mosby 2016 The journal of allergy and clinical immunology Vol.137 No.5

<P>Background: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. Objective: We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. Methods: PD-1 expression on IL-17A-producing gamma delta T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. Results: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)V gamma 1(-) gamma delta T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)V gamma 1(-) gamma delta T-cell population, V gamma 4(-) gamma delta T cells with V gamma 6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)V gamma 4(-)(V gamma 6(+)) gamma delta Tcells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Conclusion: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.</P>

Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non-diabetic individuals

Shin, H. D.,Park, K. S.,Park, B. L.,Cheong, H. S.,Cho, Y. M.,Lee, H. K.,Lee, J.-Y.,Lee, J.-K.,Kim, H. T.,Han, B. G.,Kim, J. W.,Koh, I.,Kim, Y. J.,Oh, B.,Kimm, K.,Park, C. Blackwell Science Ltd 2006 Diabetic medicine Vol.23 No.1

<P>Abstract</P><P>Aims </P><P>Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (<I>CD14</I>) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.</P><P>Methods </P><P>We have sequenced the gene, including all exons, exon/intron boundaries, and the −1.5 kb of the 5′ flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.</P><P>Results </P><P>Eight polymorphisms, including four non-synonymous forms, were identified in <I>CD14</I>. No polymorphisms were found in association with T2DM. However, one common promoter SNP (<I>−260T>C</I>) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 ± 0.81 vs. 1.46 ± 0.80 mmol/l; <I>P</I> = 0.0007) and BMI (23.96 ± 3.00 vs. 23.28 ± 3.22 kg/m<SUP>2</SUP>; <I>P</I> = 0.04) as compared with subjects carrying T/T genotypes.</P><P>Conclusion </P><P>Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.</P>

임신 및 각종 갑상선질환에서 갑상선 기능 판정에 관한 연구 : 혈청유리 T4의 진단적 의의에 관한 고찰 The diagnostic value of free thyroxine by RIA

이종철,유명희,윤휘중,신영태,정순일,조보연,이문호,이명철 대한핵의학회 1981 핵의학 분자영상 Vol.15 No.1

To evaluate the diagnostic accuracy of the measurement of free thyroxine(FT4) by radioimmunoassay, we measured free T4 and T4, T3, T3RU, TSH and TBG serum levels by radioimmunoassay in 18 healthy persons and 52 patients with various thyroid diseases and 11 normal pregnant women. The results are as follows. 1) In 19 cases of overt hyperthyroidism, T3, free T4 and FTI, T4/TBG ratio reflect hyperfunction in all cases. T4 is increased in 94%(18/19) and TBG and TSH are decreased in 79%(15/19). 2) In 8 patients with overt hypothyroidism, TSH is increased in all cases and free T4 and FTI is decreased in all cases. T4 is decreased in 87.5%(7/8), T3 is decreased in 75%(6/8) and T4/TBG ratio is decreased in 62.5%(5/8). 3) In 5 patients who are clinically in euthyroid state after treatment of hyperthyroidism, T4 free T4, FTI and TSH are in the normal range in all cases and T3 is normal in 60%(3/5) and slightly increased in 40%(2/5). 4) In 10 patients who showed clinically borderline hypothyroidism after treatment of hyperthyroidism, TSH is increased in all cases and free T4 and FTI are decreased in all cases, but T4 and T3, T4/TBG ratio are in the normal limit in all cases. So after treatment of hyperthyroidism, TSH, free T4 or FTI are recommended as optimal function test. 5) In normal pregnancy, free T4, FTI and T4/TBG ratio reflect normal function, but the other parameters unreliable due to the influence of increased TBG. Also TBG and TSH level in pregnancy is increased significantly compared with normal healthy control group. 6) The coefficients of correlation between T4 and FTI were 0.862(p〈0.001) and 0.685(p〈0.001) between free T4 and T4/TBG ratio. In most patients, diagnostic value of free T4 was comparable and even superior to FTI, so free T4 measurement can be used routinely with thyrotropin assay in the diagnosis of hypothyrodism or with T3 for the diagnosis of hyperthyroidism.

In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells

Byun, J.S.,Sohn, J.M.,Leem, D.G.,Park, B.,Nam, J.H.,Shin, D.H.,Shin, J.S.,Kim, H.J.,Lee, K.T.,Lee, J.Y. Pergamon Press 2016 Bioorganic & medicinal chemistry letters Vol.26 No.3

As a result of our continuous research, new 3,4-dihydroquinazoline derivative containing ureido group, KCP10043F was synthesized and evaluated for T-type Ca<SUP>2+</SUP> channel (Ca<SUB>v</SUB>3.1) blockade, cytotoxicity, and cell cycle arrest against human non-small cell lung (A549) cells. KCP10043F showed both weaker T-type Ca<SUP>2+</SUP> channel blocking activity and less cytotoxicity against A549 cells than parent compound KYS05090S [4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N',N'-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline 2 hydrochloride], but it exhibited more potent G<SUB>1</SUB>-phase arrest than KYS05090S in A549 cells. This was found to be accompanied by the downregulations of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D2, cyclin D3, and cyclin E at the protein levels. However, p27<SUP>KIP1</SUP> as a CDK inhibitor was gradually upregulated at the protein levels and increased recruitment to CDK2, CDK4 and CDK6 after KCP10043F treatment. Based on the strong G<SUB>1</SUB>-phase cell cycle arrest of KCP10043F in A549 cells, the combination of KCP10043F with etoposide (or cisplatin) resulted in a synergistic cell death (combination index=0.2-0.8) via the induction of apoptosis compared with either agent alone. Taken together with these overall results and the favorable in vitro ADME (absorption, distribution, metabolism, and excretion) profiles of KCP10043F, therefore, it could be used as a potential agent for the combination therapy on human lung cancer.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

Conjugated Linoleic Acid ( CLA ) 급여가 난황의 콜레스테롤과 CLA 함량에 미치는 효과

박구부(G . B . Park),이정일(J . I . Lee),박태선(T . S . Park),김진형(J . H . Kim),신택순(T . S . Shin),강석중(S . J . Kang),하영래(Y . L . Ha),주선태(S . T . Joo) 한국축산학회 1999 한국축산학회지 Vol.41 No.1

The effects of dietary conjugated linoleic acid (CLA) on the concentration of cholesterol and CLA in egg yolk were investigated. CLA was synthesized according to the method of Alkali isomerization using safflower oil. A total of 250 hens (200 days age) were fed a control diet (a commercial laying hen feed) or CLA-supplemented diets (T1 ; 1% CLA and 4% safflower oil, T2; 2.5% CLA and 2.5% safflower oil, T3; 5% CLA, and T4; 5% safflower oil) for 6 weeks. Eggs were collected for analysis of CLA, cholesterol and fatty acid levels in the yolk. CLA concentration in egg yolk was increased by level of dietary CLA or dwation of feed. The yolk CLA concentration of T3 rapidly increased for 2 weeks, and maintained there after. On the other hand, the concentration of T4 was not significantly different from that of control during the feeding period. These results implied that CLA could not be synthesized by hen and it was necessary to supplement the diet with CLA for CLA accumulation in egg yolk. The level of CLA in egg yolk depended on the amount of CLA supplemented, and over-supplementation of CLA was not necessary. As the yolk CLA increased, the levels of cholesterol, linoleic acid and arachidonic acid decreased but that of palmitic acid increased. It was suggested that a lowcholesterol egg might be produced with over 1% CLA-supplemented diet. The concentration of CLA in egg yolk was unchanged during 28 days storage at 4℃. However, the level of cholesterol decreased during the storage.

RF 마그네트론 스퍼터링법에 의한 a-축 배향 $YBa_2Cu_3O_{7-\delta}$박막의 제조

이재준,김영환,신진,이경희,최상삼,한택상,Lee, J.J.,Kim, Y.H.,Shin, J.,Lee, K.H.,Choi, S.S.,Hahn, T.S. 한국재료학회 1994 한국재료학회지 Vol.4 No.4

a-측으로 배향된 $YBa_2Cu_3O_{7-\delta}$ 고온 초전도 박막을 $LaAIO_{3}$(100)단결정 기판에 이중 타게트 off-axis rf마그네트론 스퍼터링법으로 증착하였다. 박막은 기판온도(Ts)$590^{\circ}C$와 $680^{\circ}C$사이에서 단일공정으로 증착하는 one-step방법과, $590^{\circ}C$의 저온에서 a-축으로 배향된 YBCO박막(두께-30nm)을 면저 만들어 틀로 작용시킨 후 그 틀위에 나머지 부분을 기판온도를 승온하면서 증착하는 방법인 two-step방법 등 두 가지 방법을 사용하여 증착시켰다. one-step방법에서는 $T_s$가 증가함에 따라 감소하였으며, ($00 \ell$)피크는 증가하였다. Two-step방법으로 증착한 박막은 증착속도가 감소함에 따라 (h00)피크가 우세하게 나타났다. 박막의 미세구조는 a-축, c- 축 배향성이 혼재하여 핀홀과 같은 결함들이 생성되었다. 모든 경우 $T_s$가 감소함에 따라 a-축 배향성은 우세하였으나 전기적 특성은 저하되었고, 긴 전이온도 폭을 가졌다. A-axis oriened YBCO thin flims were grown on $LaAIO_{3}$ single crystal substrate by off-axis rf magnetron sputtering method. We used two kinds of process to get a-axis oriented fi1ms;one-step process and two-step process. In one-step process, films are grown in single step in which substrate temperature( $T_s$) is in the range of $590^{\circ}C$ to $680^{\circ}C$. On the other hand, in two step process a-axis oriented thin film templates i f about 30nm thickness is deposited at low temperature first, and subsequently films are grown at elevated temperature to the final thickness of about 100nm. In the case of one step process($T_s$ ~)$600^{\circ}C$), prefered a-axis orientation is dominant and Cu-rich phases segregate at the surface. Segregations decrease and ($00 \ell$) peaks increase upon increasing $T_s$. The films prepared by two step method appeared to have strong(h00) peaks as the deposition rate increased. Microstructure shows pin holes resulted from mixed phases of a-axis and c-axis oriented films. In both cases of one step and two step process, as TS decreases, prepared films show stronger a-axis orientation. However electrical properties of the films are depressed with lower $T_c$ and wider $\Delta T$ as $T_s$ decreases.

육계사료와 식용유 정제 폐백토(Spent Bleaching Clay) 급여가 육계의 생산성에 미치는 영향

전해열,손장호,이길왕,김선구,강한석,신택순,조병욱,Jeon H. Y.,Son J. H.,Lee K. W.,Kim S. K.,Kang H. S.,Shin T. S.,Cho B. W. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.4

본 연구는 Spent Bleaching Clay(SBC)를 육계사료의 에너지 공급원으로 활용 가능성을 구명하기 위하여 실시하였다. 부화 직후의 120수의 병아리(한협 3호)를4처리 3반복, 반복당 10수(암수 각각 5수씩)를 Control(T1) 사료에 SBC를 $2.0\%(T2),\;4.0\%(T3)$ 및 $6.0\%(T4)$ 첨가한 4처리로 배치하였다. 시험사료 급여전 1주일은 시판사료를 급여하였다. 4주간의 시험 기간동안 증체중 및 사료 섭취량은 T3 및 T4 처리구에서 증가하는 경향이 인정되었다. 사료효율은 T3구에서 개선되는 경향이 인정되었다. 가슴살 및 다리살에서 치방산 조성을 사료의 처리에 따른 효과는 인정되지 않았다. 육계 초기 및 후기 사료 급여시 모두, 사료중의 건물, 조단백질 및 조지방 이용율은 T4 처리구가 다른 처리구에 비해서 유의하게 감소하였으며(p<0.05), 대사에너지가도 T4 처리구가 다른 3구에 비해서 유의하게 저하하였다(p<0.05). 사료중의 조회분의 이용율은 사료의 처리에 따른 차이는 인정되지 않았다. 결론적으로 본 시험의 결과 육계사료에 $2\~4\%$의 SBC첨가는 육계의 성장 및 사료효율 개선의 가능성이 있음이 사료된다. This study was conducted to evaluate the feasibility of spent bleaching clay(SBC) as an energy resource for meat type chicks. A total of one hundred twenty 1-d old broiler chicks(Han-hyop, No. 3) were divided into four groups and each group was assigned to one of the following diets: 0(T1), 2.0(T2), 4.0(T3) and $6.0\%$ SBC(T4). Each treatment had 3 replications of 10 birds. Before feeding experimental diets, they were fed a commercial diet for a week Body weight gain and feed intake tended to increase in T3 and T4, respectively. Feed efficiency(feed intake/ gain) tended to decrease in T3 compared to other groups. Fatty acid composition of breast and thigh meat was not significantly affected by feeding SBC. Utilization of dry matter, energy, crude protein and crude fat was lower in T4 than in the other groups during both starter and finisher periods(p<0.05). Crude ash utilization was not significantly affected by feeding dietary SBC. These results indicate that broiler diets may be supplemented with 2 to $4\%$ SBC without adverse effect on growth.

한국 밀식사과원의 정지전정에 따른 수체생장과 생산성 및 경영효율 비교

정혜웅,김경훈,송태영,홍성일,한호균,김귀권,신종협,여덕환,김병철,박준권,Jung, H.W.,Kim, K.H.,Song, T.Y.,Hong, S.I.,Han, H.K.,Kim, K.K.,Shin, J.H.,Yeo, D.H.,Kim, B.C.,Park, J.K. 국립한국농수산대학교 교육개발센터 2017 현장농업연구지 = Journal of practical agricultural resear Vol.19 No.1

The present study conducted a comparison on tree growth and productivity of high-density apple orchards by several orchard management systems: making scaffolds by heading-back and thinning out pruning (T-1), maintaining scaffolds upward and bearing shoots downward (T-2), managing branches slightly upward without heading-back (T-3), keeping leaders downward and shoots pending (T-4), maintaining leaders high and branches horizontal with severe pinching (T-5), making leaders with lower branches vigorous and upper shoots pending (T-6), and controlling very high planting density with bending branches (T-7). In conclusion, the orchards of (T-5) and (T-6) management systems showed a superior performance in controlling tree growth, productivity, and quality of fruits. Also, superior management efficiency was obtained in the orchards of (T-5) and (T-6).

AA2219-T87 알루미늄 합금 마찰교반용접부의 용접속도 변경에 따른 기계적 특성 변화

신민철(M.C. Shin),유준태(J.T. Yoo),이상훈(S.H. Lee),윤종훈(J.H. Yoon),박충희(C.H. Park),정연희(Y.H. Jeong) 대한용접·접합학회 2023 대한용접학회 특별강연 및 학술발표대회 개요집 Vol.2023 No.10