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Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury in Rats: Involved in Inhibition of NF-κB and Inflammation Response

  • Wang, Lijun;Liu, Haiyan;Zhang, Ligong;Wang, Gongming;Zhang, Mengyuan;Yu, Yonghui
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.383-389
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    • 2017
  • Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

Gene Expression Profile in Carpal Tunnel Syndrome Patients

  • Kim, Hye-Won;Kim, Ki-Nam;Seo, Sang-Hui;Lee, Seung-Ho;Sohn, Sung-Hwa;Kim, Yu-Ri;HaLee, Young-Mie;Shim, Jae-Sun;Ahn, Duck-Sun;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.266-272
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    • 2006
  • Carpal tunnel syndrome (CTS) is one of the most common disorders by under pressure of the median nerve at the wrist in these days. However, pathological mechanism of CTS is unknown. We carried out this study to identify the changes of gene expression and to evaluate possible mechanism in CTS. 120 CTS patients and 30 control patients were included in this study. Patients with a history of diabetes, hypertension, thyroid diseases, and arthritis were excluded. CTS patients were divided to three experimental groups-Mild, Moderate, and Severe group-according to elecrodiagnosis. Radioactive cDNA microarrays (Nylon membrane including 1,152 genes) were used to examine the difference of gene expression profile in CTS. We identified up-regulated genes by more than 2.0 value of z-ratio, and down-regulated genes by less than-2.0 value of z-ratio. 20 genes such as the ITGAL, ITGAM, PECAM1, VIL2, TGFBR2, RAB7, RNF5 and NFKB1 were up-regulated, and 28 genes such as PRG5, CASP8, CDH1, IGFBP5, CBX3, HREV107, PIN, and WINT2 were down-regulated. These genes were related with TGF beta signaling pathway, NF-Kb signaling pathway, antiapoptotic pathway and T cell receptor signaling pathway. However, there were no differences in gene expression profiles according to severities of symptoms. We suggest that CTS could be related with proinflammatory mechanism and antiapoptotic mechanism.

Rosmarinic Acid Down-Regulates the LPS-Induced Production of Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1α (MIP-1α) via the MAPK Pathway in Bone-Marrow Derived Dendritic Cells

  • Kim, Hyung Keun;Lee, Jae Joon;Lee, Jun Sik;Park, Yeong-Min;Yoon, Taek Rim
    • Molecules and Cells
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    • v.26 no.6
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    • pp.583-589
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    • 2008
  • In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-$1{\alpha}$ ($MIP-1{\alpha}$) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and $MIP-1{\alpha}$ induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of $NF-{\kappa}B$. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.

Twist2 Regulates CD7 Expression and Galectin-1-Induced Apoptosis in Mature T-Cells

  • Koh, Han Seok;Lee, Changjin;Lee, Kwang Soo;Park, Eun Jung;Seong, Rho H.;Hong, Seokmann;Jeon, Sung Ho
    • Molecules and Cells
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    • v.28 no.6
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    • pp.553-558
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    • 2009
  • In the periphery, a galectin-1 receptor, CD7, plays crucial roles in galectin-1-mediated apoptosis of activated T-cells as well as progression of T-lymphoma. Previously, we demonstrated that $NF-{\kappa}B$ downregulated CD7 gene expression through the p38 MAPK pathway in developing immature thymocytes. However, its regulatory pathway is not well understood in functional mature T-cells. Here, we show that CD7 expression was downregulated by Twist2 in Jurkat cells, a human acute T-cell lymphoma cell line, and in EL4 cells, a mature murine T-cell lymphoma cell line. Furthermore, ectopic expression of Twist2 in Jurkat cells reduced galectin-1-induced apoptosis. While full-length Twist2 decreased CD7 promoter activity, a C-terminal deletion form of Twist2 reversed its inhibition, suggesting an important role of the C-terminus in CD7 regulation. In addition, CD7 expression was enhanced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate, which indicates that Twist2 might be one of candidate factors involved in histone deacetylation. Based on these results, we conclude that upregulation of Twist2 increases the resistance to galectin-1-mediated-apoptosis, which may have significant implications for the progression of some T-cells into tumors such as Sezary cells.

The Effects of Yeouigeumhwang-san on Anti-Inflammation and Anti- Propionibacterium acnes (여의금황산(如意金黃散)이 여드름 유발균과 염증에 미치는 영향)

  • Yoo, Jin-Gon;Seo, Hyeong-Sik
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.2 s.33
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    • pp.77-88
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    • 2007
  • Objectives : This experimental study was performed to investigate the effects of Yeouigeumhwang-san(YUGHS) on anti-inflammation and anti-Propionibacterium acnes. Methods : The cytotoxicity of YUGHS about viability of Raw 264.7 cell was tested by using a colorimetric tetrazolium assay(MTT assay). To investigate the anti-inflammatory effets of YUGHS on LPS-induced macrophage Raw 264.7 cell, we used ELISA kit and Western blots. Inhibitory effects of YUGHS on Propionibactrium acnes were investigated by using paper disk diffusion method. Results : 1. YUGHS has no cytotoxicity under 50 ${\mu}g/ml$ concentration but over 50 ${\mu}g/ml$ has a little cytotoxicity in Raw 264.7 cell. 2. Concentration of 100 ${\mu}g/ml$ YUGHS inhibited the production of NO in the Raw 264.7 cell stimulated with LPS. 3. All concentrations of YUGHS did not inhibit the production of $TNF-{\alpha}$ in the Raw 264.7 cell stimulated with LPS. 4. All concentrations of YUGHS significantly inhibited the production of $PGE_2$ in the Raw 264.7 cell stimulated with LPS. 5. YUGHS did not inhibit the expression of COX-2 but concentration of 50 ${\mu}g/ml$ YUGHS inhibited iNOS expression in the Raw 264.7 cell stimulated with LPS. 6. YUGHS has the effect of blocking $NF-{\kappa}B$ into nucleus in LPS-induced macrophage Raw 264.7 cell 7. YUGHS did not have the inhibitory effect of Propionibactrium acnes. Conclusions : These results indicate that Yeouigeumhwang-san has anti-inflammatory effets. If further study is performed, the use of Yeouigeumhwang-san will be valuable and benificial in the therapy of acnes.

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Zu Ethos und Pathos in Hitlers Reden (히틀러 연설에서의 에토스와 파토스에 관하여)

  • Kim Tschong-Young
    • Koreanishche Zeitschrift fur Deutsche Sprachwissenschaft
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    • v.10
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    • pp.231-249
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    • 2004
  • In dieser Albeit wird der Versuch unternommen, die Charakteristik der Rhetorik von Hitler zu analysieren. Im Abschnitt fwei wird die allgemeine Charakteristik der Hillers Reden beschrieben. Die Reden von Hitler sind Elemente eines verzweigten, flexiblen und inhaltlich nor schwer bestimmten Komplexes von Manipulations-und Machttechniken, die trotz seiner Tendenz zur Zentralisierung nur schwer als System zu fassen sind. Dies macht die Schwierigkeit jeder analytischen Erfassung aus. Seine Rede vermag im Bezug auf Logik und Argumentation wenig zu $\"{u}berzeugen$, aber or wirkte. In diesel Analyse wird die Rede von Hitler folgende Systematisierung $m\"{o}glich$: 1) Am Anfang weist Hitler auf die allgemeine Not hin. 2) Danach diffamiert or seine Gesner und provoziert starke Emotionen bei seinen $Zuh\"{o}rern$. 3) Zum $Schlu{\ss}$ $l\"{o}st$ Hitler bei den Deutschen eine starke Kampfbereitschaft aus und entwickelt vor semen $Zuh\"{o}rern$ seine Vision eines $bl\"{u}henden$, starken Deutschlands. 4) $Abschlie{\ss}end$ erkifirt Hitier seine $pers\"{o}nlichen$ ethischen Vorstellungen und seine sich daraus ergebenden Handlungen. Er liegt $gro{\ss}en$Wert darauf, die Ethik seine Handlungen zu $begr\"{u}nden$. Danach wird die Selbstdarstellung von Hitler beschrieben. $F\"{u}nf$ Realisierungsformen sind $daf\"{u}r$ relevant: a) $pers\"{o}nliche$ $Erz\"{a}hlungen$, b) Diffamierungen, c) sittlich wertvolle Ermahnungen, d) Taten und e) Ziele. Im Abschnitt drei wird die Rhetorik von Hitler gemacht. Hier handeit es sich um Ethos und Pathos. Hitler versuchte, die durch die Aktivierung zwischen ihm und Publikum vorhanden, $unbewu{\ss}ten$ psychischen Potentiate, die durch den Akt der Rede aktiviert werden, zu realisieren. Er hat jeder Sammlung nur gesagt, was sie $h\"{o}ren$ wollte, den wahren Sachverhalt nur auf $h\"{o}chst$ vordergryndige Weise.

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Genomic Organization and Isoform-Dependent Expression Patterns of Wap65 genes in Various Tissues during Immune Challenges in the Mud Loach Misgurnus mizolepis

  • Kim, Yi Kyung;Cho, Young Sun;Lee, Sang Yoon;Nam, Yoon Kwon
    • Fisheries and Aquatic Sciences
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    • v.17 no.4
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    • pp.471-478
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    • 2014
  • Genomic organization, including the structural characteristics of 5'-flanking regions of two 65-kDa protein (WAP65) isoform genes associated with warm temperature acclimation, were characterized and their transcriptional responses to immune challenges were examined in the intestine, kidney and spleen of the mud loach (Misgurnus mizolepis; Cypriniformes). Both mud loach Wap65 isoform genes displayed a 10-exon structure that is common to most teleostean Wap65 genes. The two mud loach Wap65 isoforms were predicted to possess various stress- and immune-related transcription factor binding sites in their regulatory regions; however, the predicted motif profiles differed between the two isoforms, and the inflammation-related transcription factor binding motifs, such as NF-${\kappa}B$ and CREBP sites, were more highlighted in the Wap65-2 isoform than the Wap65-1 isoform. The results of qRT-PCR indicated that experimental immune challenges using Edwardsiella tarda, lipopolysaccharide or polyI:C induced the Wap65-2 isoform more than Wap65-1 isoform, although modulation patterns in response to these challenges were tissue- and stimulant-dependent. This study confirms that functional diversification between the two mud loach Wap65 isoforms (i.e., closer involvement of Wap65-2 in the acute phase of inflammation and innate immunity) occurs at the mRNA level in multiple tissues, and suggests that such differential modulation patterns between the two isoforms are related to the different transcription factor binding profiles in their regulatory regions.

Analysis of MAPK Signaling Pathway Genes in the Intestinal Mucosal Layer of Necrotic Eenteritis-Afflicted Two Inbred Chicken Lines

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Korean Journal of Poultry Science
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    • v.44 no.3
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    • pp.199-209
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    • 2017
  • Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

Complete Sequences of HIV-1 in a Korean Long-term Nonprogressor with HIV-1 Infection (장기간 진행하지 않는 인면역결핍바이러스(Human Immunodeficiency Virus, HIV)-1 감염자로부터 분리한 HIV-1의 전체 염기서열 결정)

  • Cho, Young-Keol;Lee, Hee-Jung;Desrosiers, Ronald C.
    • The Journal of Korean Society of Virology
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    • v.29 no.2
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    • pp.107-118
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    • 1999
  • To characterize the molecular nature of human immunodeficiency virus (HIV)-1, we determined the full-length HIV-1 sequences from cultured peripheral blood mononuclear cells (PBMC) of a Korean long-term nonprogressor (LTNP). Without antiretroviral therapy, the individual has maintained CD4+ T counts over $500/{\mu}l$ from 1989 to 1999. Plasma viral RNA copy was 992 U/ml in 1998. Culture supernatant showed positive from culture days 9. A series of 9 overlapping PCR products were amplified from cultured PBMC and cloned About 9.2 kb from R of 5' LTR to R of 3' LTR was determined by automated sequencing. The G-to-A hypermutations were shown throughout the entire region. As a result of G to A hypermutations, premature stop codon was found in integrase coding region. Though there was no recombination between subtypes over all genomes, TATA box in both LTRs was TAAAA which is detected in subtype E instead of TATAA in subtype B. And, there were nucleotide GC insertion between $NF-{\kappa}B$ I and Sp1 III, and duplication of $TCF-1{\alpha}$ in LTR. We could not find any deletion of amino acid in Nef, Gag, Pol and Env gene. This study is the first report on molecular nature of full genomes of HIV-1 isolated in Korea.

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A Study on the Oxidative Stabilities and Organoleptic Properties of Korean Red Pepper Seed Oil upon Species and Dried Methods (품종 및 건조방법에 따른 고추씨기름의 산화안정성과 기호성에 관한 연구)

  • 김복자;안명수
    • Korean journal of food and cookery science
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    • v.14 no.4
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    • pp.380-387
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    • 1998
  • The stability of red pepper seed oils during storage at 20${\pm}$3$^{\circ}C$, 40${\pm}$3$^{\circ}C$ and heating at 140${\pm}$3$^{\circ}C$ or 180${\pm}$3$^{\circ}C$ were measured to evaluate red pepper seed oil as a cooking oil. Two species of red pepper seeds (native, improved) were dried by either sunlight or heating to prepare the oil samples of NS (native, sunlight-dried), IS (improved, sunlight-dried), NF (native, heated), and IF (improved, heated). During storage at 20${\pm}$3$^{\circ}C$ or 40${\pm}$ 3$^{\circ}C$, acid values (AV) of all red pepper seed oils were higher than that of soy bean oil (SBO), however, peroxide values (POV) were similar to SBO. Antioxidative stability of NS was better than SBO but IF was not. By the heat treatments at 140${\pm}$3$^{\circ}C$ or 180${\pm}$3$^{\circ}C$, NS was identified to have better antioxidative stability than SBO and IF was the lowest. In sensory evaluation of each deep-fat fried potato-chip at 180${\pm}$5$^{\circ}C$, potato-chips fried in NS were better than that of SBO for color, taste, and flavor. NS-fried potato-chips got the highest score in overall acceptance (p<0.05), however, those of IF showed little acceptance. When blended oils (SBO: NOS, 0, 25, 50, 75%) were used, 50% blended oil was the best for taste, color, flavor, cripness, and total acceptance.

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