• Title/Summary/Keyword: $PGD_2$

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Effect of Ullmus macrocarpa Hance Ethanol extract (Ulmus) on Improvement of allergic responses in RBL-2H3 mast Cells (RBL-2H3 비만세포에서 유백피 에탄올 추출물의 알레르기 반응 개선에 대한 효과)

  • Do, Hyun Ju;Oh, Tae Woo
    • Herbal Formula Science
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    • v.29 no.4
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    • pp.191-203
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    • 2021
  • Objectives : In this study, we investigate the anti-allergic effects of Ullmus macrocarpa Hance (Ulmus) on RBL-2H3 mast cell (basophilic leukemia cell line), which are mediated by FcεRIs. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in IgE-antigen-mediated RBL-2H3 cells. Cell toxicity was determined by MTT assay and the markers of degranulation such as beta-hexosaminidase, histamine, PGD2, TNF-α, IL-4, IL-6 production of inflammatory mediators and FcεRI-mediated protein expression by western blot. Results : Ulmus inhibited degranulation and production of allergic mediators (e.g., TNF-α, IL-4, and IL-6) in them. Ulmus reduced histamine levels, expression of FcεRI signaling-related genes such as Lyn, Syk, and Fyn, and extracellular signal-regulated kinase phosphorylation in mast cells. Also, Ulmus reduced PGD2 release and cyclooxygenase-2 expression, and cytosolic phospholipase A2 phosphorylation in FcεRI-mediated RBL-2H3 mast cells. Conclusions : These results indicate that Ulmus exhibits anti-allergic activity through inhibition of degranulation and inflammatory mediators and cytokine release. These findings suggest that Ulmus may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

Optimized Methods of Preimplantation Genetic Diagnosis for Trinucleotide Repeat Diseases of Huntington's Disease, Spinocerebellar Ataxia 3 and Fragile X Syndrome (삼핵산 반복서열 질환인 헌팅톤병, 척수소뇌성 운동실조증, X-염색체 취약 증후군의 착상전 유전진단 방법에 대한 연구)

  • Kim, Min-Jee;Lee, Hyoung-Song;Lim, Chun-Kyu;Cho, Jae-Won;Kim, Jin-Young;Koong, Mi-Kyoung;Son, In-Ok;Kang, Inn-Soo;Jun, Jin-Hyon
    • Clinical and Experimental Reproductive Medicine
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    • v.34 no.3
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    • pp.179-188
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    • 2007
  • Objectives: Many neurological diseases are known to be caused by expansion of trinucleotide repeats (TNRs). It is hard to diagnose the alteration of TNRs with single cell level for preimplantation genetic diagnosis (PGD). In this study, we describe methods optimized for PGD of TNRs related diseases such as Huntington's disease (HD), spinocerebellar ataxia 3 (SCA3) and fragile X syndrome (FXS). Methods: We performed the preclinical assays with heterozygous patient's lymphocytes by single cell PCR strategy. Fluorescent semi-nested PCR and fragment analysis using automatic genetic analyzer were applied for HD and SCA 3. Whole genome amplification with multiple displacement amplification (MDA) method and fluorescent PCR were carried out for FXS. Amplification and allele drop-out (ADO) rate were evaluated in each case. Results: The fluorescent semi-nested PCR of single lymphocyte showed 100.0% of amplification and 14.0% of ADO rate in HD, and 94.7% of amplification and 5.6% of ADO rate in SCA3, respectively. We could not detect the PCR product of CGG repeats in FXS using the fluorescent semi-nested PCR alone. After applying the MDA method in FXS, 84.2% of amplification and 31.3% of ADO rate were achieved. Conclusions: Fluorescent semi-nested PCR is a reliable method for PGD of HD and SCA3. The advanced MDA method overcomes the problem of amplification failure in CGG repeats of FXS case. Optimization of methods for single cell analysis could improve the sensitivity and reliability of PGD for complicated single gene disorders of TNRs.

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

  • Li, Xian;Lu, Yue;Jin, Ye;Son, Jong-Keun;Lee, Seung Ho;Chang, Hyeun Wook
    • Biomolecules & Therapeutics
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    • v.22 no.1
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    • pp.27-34
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    • 2014
  • Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$) and 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular $Ca^{2+}$ influx via phospholipase $C{\gamma}1$ ($PLC{\gamma}1$) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum $LTC_4$, $PGD_2$, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

  • Jeong, Kyu-Tae;Lee, Eujin;Park, Na-Young;Kim, Sun-Gun;Park, Hyo-Hyun;Lee, Jiean;Lee, Youn Ju;Lee, Eunkyung
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.421-427
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    • 2015
  • Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

  • Lu, Yue;Li, Xian;Park, Young Na;Kwon, Okyun;Piao, Donggen;Chang, Young-Chae;Kim, Cheorl-Ho;Lee, Eunkyung;Son, Jong Keun;Chang, Hyeun Wook
    • Biomolecules & Therapeutics
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    • v.22 no.3
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    • pp.193-199
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    • 2014
  • The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

Studies on blood types in Thoroughbred horses (더러브렛 말의 혈액형에 관한 연구)

  • Cho, Gil-jae;Kim, Bong-hwan
    • Korean Journal of Veterinary Research
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    • v.40 no.4
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    • pp.683-689
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    • 2000
  • The present study was carried out to investigate the blood markers of Thoroughbred horses (TB) The blood red cell types and blood protein types (biochemical polymorphisms) were tested from 1,125 Thoroughbred horses by serological and electrophoretic procedures, and their phenotypes, gene frequencies, heterozygosity, polymorphic information content values and exclusion probability were estimated. The blood group and biochemical polymorphism phenotypes observed with high frequency were Aaf(91.7%), Ca(94.7%), K-(94.5%), Ua(75.9%), P-(50.6%), Qabc(82.6%), ALB-BB(67.7%), GC-FF(92.7%), AIB-KK(99.6%), ES-II(77.9%), TF-DF1(23.6%), PI-LL(23.2%), HB-B2B2(73.6%), PGD-FS(45.4%) and genotypes Dcgm/dk(16.9%), Dbcm/cgm(13.6%), Dbcm/dk(11.9%), Dcegmn/cegmn(10.0%), Dcgm/cgm(8.7%) in TB. Alleles observed with high frequency were Aaf(0.796), Ca(0.769), Ddk(0.266), Dcgm(0.261), Dbcm(0.211), K-(0.972), P-(0.710), Qabc(0.565), Q-(0.368), Ua(0.509), $HB^{B2}$(0.858), $PGD^F$(0.634), $ALB^B$(0.825), $GC^F$(0.927), $AIB^K$(0.998), $ES^I$(0.881), $TF^{F1}$(0.346), $TF^D$(0.319), $TF^{F2}$(0.184), $PI^L$(0.479), $PI^N$(0.214), $PI^U$(0.116) in TB. The heterozygosity, polymorphic information content (PIC) and exclusion probability (PE) were calculated. The mean heterozygosity and PIC value were 0.3899 and 0.3375, respectively. The highest heterozygosity and PIC were estimated 0.7834 and 0.7492 in blood group D locus, respectively. The cumulated PE obtained by blood groups and biochemical polymorphisms was 0.9813.

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Analysis of Redcell and Blood Protein Typing in Mongolian Horse (몽고말의 적혈구항원형 및 혈액단백질형 분석)

  • Cho, G.J.;Cho, B.W.
    • Journal of Animal Science and Technology
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    • v.46 no.6
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    • pp.887-896
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    • 2004
  • The present study was carried out to investigate the blood markers of Mongolian horses. The blood redcell types and blood protein types(biochemical polymorphisrns) were tested from 19 Mongolian horses by serological and electrophoretic procedure, and their phenotypes and gene frequencies were estimated. The blood group and biochemical polymorphism phenotypes observed with high frequency were $A^{af}$(42.1%), $C^a$(89.5%), $K^-$(84.2%), $U^a$(63.2%), $P^a$(42.1%) $P^-$42.1%), $Q^c$(31.6%) $Q^-$(31.6%), $AL^{AB}$((52.6%), AI$B^K$(89.5%), $ES^1$(63.2%), $GC^F$(78.9%), $HB^BI$1(68.4%), PG$D^F$(84.2%), $TF^{FIR}$(21.1%), $TF^{F2R}$(21.1%)(21.1%), and genotypes $D^{cgm/dghm}$(15.8%), $D^{dghm/dghm}$(15.8%), $D^{ad/dghm}$(10.5%), $D^{ade/dghm}$(10.5%), in Mongolian horses, respectively. Alleles observed with high frequency were $A^a$(0.4211), $C^a$(0.8947), $K^-$(0.8421), $U^a$(0.6316), $P^a$(0.4474), $Q^c$(0.4474), $D^{dghm}$(0.4211), $AL^B$(0.6579), $AIB^K$(0.9211), $ES^I$(0.7895), $GC^F$(0.8947), $HB^{BI}$(0.7895), $PGD^F$(0.8421) and $TF^R$(0.3421) in Mongolian horses. These results present basic information for estimating the genetic relationships between the Korean native horse, and developing a system for parentage verification and individuals identification in Mongolian horse.

Population Genetic Structure of Potentilla discolor Bunge, Rosaceae in Korea (한국내 솜양지꽃의 집단 유전 구조)

  • Huh, Man-Kyu
    • Journal of Life Science
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    • v.16 no.6
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    • pp.898-903
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    • 2006
  • The genetic diversity and population structure of fifteen Potentilla discolor Bunge populations in Korea were determined using genetic variations at 19 allozyme loci. Fourteen of the 19 loci (73.7%) showed detectable polymorphism. Genetic diversity at the species level and at the population level was high ($H_{ES}\;=\;0.215$, $H_{EP}\;=\;0.196$, respectively), whereas the extent of the population divergence was relatively low $(G_{ST}\;=\;0.069)$. Total genetic diversity values $(H_T)$ varied between 0.0 and 0.656, giving an average overall polymorphic loci of 0.292. The interlocus variation of genetic diversity within populations $(H_S)$ was high (0.274). On a per locus basis, the proportion of total genetic variation due to differences among populations $(G_{ST})$ ranged from 0.010 for Pgm-2 to 0.261 for Pgd-2 with a mean of 0.069, indicating that about 6.9% of the total allozyme variation was among populations. Wide geographic ranges, perennial herbaceous nature and the persistence of multiple generations are associated with the high level of genetic variation in P. discolor. The estimate of gene flow based on $G_{ST}$ was high among Korean populations of P. discolor (Nm = 3.36).

Outcomes of preimplantation genetic diagnosis using either zona drilling with acidified Tyrode's solution or partial zona dissection

  • Kim, Hyun Jung;Kim, Chung Hyon;Lee, Soo Min;Choe, Seung Ah;Lee, Joong Yeup;Jee, Byung Chul;Hwang, Doyeong;Kim, Ki Chul
    • Clinical and Experimental Reproductive Medicine
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    • v.39 no.3
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    • pp.118-124
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    • 2012
  • Objective: To review the outcomes of preimplantation genetic diagnosis (PGD) using zona drilling with acid Tyrode's solution (chemical zona pellucida drilling, chemical ZD) and those of partial zona dissection (PZD). Methods: Clinical outcomes of seventy-one couples undergoing 85 PGD cycles from January 2005 to December 2010 were included. Blastocyst formation and the hatching rate, clinical pregnancy rate, ongoing pregnancy rate, implantation rate, and fetal gender ratio of the PZD and chemical ZD groups were compared. Results: Application of PZD resulted in a significantly higher rate of clinical pregnancy (40.7% vs. 15.4%, p=0.022), ongoing pregnancy (35.6% vs. 11.5%, p=0.023), and implantation (18.1% vs. 5.7%, p=0.007) compared with chemical ZD. Among non-transferred embryos, the rate of blastocyst formation on day 5 (49.1% vs. 39.5%, p=0.016) and hatching on day 6 (47.2% vs. 26.5%, p<0.001) were also significantly higher in the PZD group. Conclusion: The mechanical zona dissection (ZD) method showed better outcomes than chemical ZD in terms of the blastocyst development and pregnancy rate. In this study, the fact that chemical ZD was conducted in different period from mechanical method should be considered in interpreting the result.

Screening of Arachidonic Acid Cascade Related Enzymes Inhibitors from Korean Indigenous Plants (2) (한국 자생식물로부터 아라키돈산 대사계 효소 저해제 검색 (2))

  • 정혜진;문태철;이은경;손건호;김현표;강삼식;배기환;안인파;권동렬
    • YAKHAK HOEJI
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    • v.47 no.2
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    • pp.69-77
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    • 2003
  • Arachidonic acid (AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2$ (PLA$_2$) enzymes and is sequentially converted to cyclooxygenases (COXs) and lipoxygenases (LOXs) then to various bioactive PGs, and LTs. In order to find the specific inhibitors of AA metabolism especially PLA$_2$, COX-2, 5-LO and lyso PAF acetyltransferase, 120 Korean residential plants extracts were evaluated for their inhibitory activity on PGD$_2$, LTC$_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of ten indigenous plant such as Salix gracilistyla, Sedum kamtschaticum, Cirsium chanroenicum, Hypericum ascyron, Astilbe chinensis, Agrimonia pilosa, Aristolochia manshuriensis, Vodia daniellii, Pyrola japonica, Styrax obassia were found to inhibit production of inflammatory mediators in vitro assay system.