Hyun-Jin Shim

Suppression of Toll‐Like Receptor 4 Dimerization by 1‐[5‐Methoxy‐2‐(2‐nitrovinyl)phenyl]pyrrolidine

Toll‐like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and triggers the activation of myeloid differention factor 88 (MyD88) and the Toll/interleukin‐1 receptor domain‐containing adapter, inducing interferon‐β (TRIF)‐dependent major downstream signaling pathways. To evaluate the therapeutic potential of 1‐[5‐methoxy‐2‐(2‐nitrovinyl)phenyl]pyrrolidine (MNP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. Here, we investigated whether MNP modulates the TLR4 signaling pathways and which anti‐inflammatory target in TLR4 signaling is regulated by MNP. MNP inhibited the activation of nuclear factor‐κB (NF‐κB) induced by LPS (TLR4 agonist), and it also inhibited the expression of cyclooxygenase‐2 and inducible nitric oxide synthase. MNP inhibited LPS‐induced NF‐κB activation by targeting TLR4 dimerization in addition to IKKβ. These results suggest that MNP can modulate the TLR4 signaling pathway at the receptor level to decrease inflammatory gene expression.

Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1

&NA; Toll‐like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll‐interleukin‐1 receptor domain‐containing adapter inducing interferon‐&bgr; (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF‐&kgr;B and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti‐inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of andrographolide in TLR signaling pathways. Andrographolide suppressed NF‐&kgr;B activation as well as COX‐2 expression induced by TLR3 or TLR4 agonists. Andrographolide also suppressed the activation of IRF3 and the expression of interferon inducible protein‐10 (IP‐10) induced by TLR3 or TLR4 agonists. Andrographolide attenuated ligand‐independent activation of IRF3 following overexpression of TRIF, TBK1, or IRF3. Furthermore, andrographolide inhibited TBK1 kinase activity in vitro. These results indicate that andrographolide modulates the TRIF‐dependent pathway of TLRs by targeting TBK1 and represents a potential new anti‐inflammatory candidate. HighlightsToll‐like receptors (TLR) play a significant role in the induction of innate immune responses.Andrographolide, the active component of Andrographis paniculata, exerts anti‐inflammatory effects.Andrographolide suppressed the activation of IRF3 and the expression of IP‐10 induced by TLR3 or TLR4 agonists.Andrographolide inhibited the kinase activity of TANK binding kinase 1 (TBK1).These results demonstrate that andrographolide inhibits the TRIF‐dependent signaling in the TLR3 and TLR4 by targeting TBK1.

Suppression of TLRs signaling pathways by 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine.

Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-κB and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the MyD88- or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

A case of vaginal delivery in β-thalassemia minor pregnant woman

The thalassemias are a group of autosomal recessive genetic disorders of hemoglobin synthesis. The thalassemias are classifi ed into two main varieties, αand β-, depending on which of the adult globin chain is produced in reduced amounts. The β-thalassemia is the homozygous and heterozygous state, and common in the Mediterranean region. Homozygous β-thalassemia is usually associated with severe anemia. β-Thalassemia minor, the heterozygous state, is characterized by hypochromia, microcytosis and an elevated of HgA2. No treatment is required for thalassemia minor, but it is important to exclude iron defi ciency anemia and postpartum genetic counseling. Recently, β-thalassemia minor keeps rising steadily in Korea due to the increase in international marriges. Recently we have experienced a vaginal delivery in a β-thalassemia minor Vietnam woman associated with mild anemia. We describe this case with a brief review of the literature.

A CASE OF LAPAROSCOPIC TREATMENT OF THE RETROPERITONEAL ECTOPIC PREGNANCY

자궁외임신은 전체 임신의 약 2%를 차지하며, 임신 초기 임신과 관련된 사망률의 대부분을 차지한다. 초기 진단은 주로 베타 사람 융모생식샘 자극호르몬 검사와 초음파로 이루어진다. 난관에 발생하는 빈도가 가장 많고, 그 다음 간질부, 자궁각, 난소, 자궁경부, 제왕절개부위, 그리고 복강에도 발생한다. 후복막에 발생하는 자궁외임신은 매우 드물어, 대개 3,372에서 7,931분만당 1예의 발생빈도를 보이며, 수술 전 진단은 매우 어려우며, 치료는 수술적 제거이다. 내원 3주 전 무월경 5주에 소파수술 후, 갑작스런 질 출혈로 내원한 26세 여성에서 자궁외임신으로 진단 후 메토트렉세이트 다회 요법을 시행 후 실패하여 복강경 통해 후복막에 착상된 자궁외임신으로 최종 진단하여 치료한 매우 드문 예를 경험하여 간단한 문헌 고찰과 함께 보고하는 바이다.

Differential regulation of MyD88- and TRIF-dependent signaling pathways of Toll-like receptors by cardamonin

ABSTRACT Toll‐like receptors (TLRs) play a crucial role in the induction of innate immune response against bacterial and viral infections. TLRs induce downstream signaling via MyD88‐ and TRIF‐dependent pathways. Cardamonin is a naturally occurring chalcone from Alpinia species exhibiting anti‐inflammatory effects. However, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of cardamonin in TLR signaling pathways. Cardamonin inhibited NF‐&kgr;B activation as well as COX‐2 expression induced by TLR agonists. Cardamonin inhibited the activation of IRF3 and the expression of interferon‐inducible protein‐10 (IP‐10) induced by TLR3 or TLR4 agonists. Cardamonin also inhibited ligand‐independent NF‐&kgr;B activation overexpressed by MyD88, IKK&bgr;, or p65 and IRF3 activation overexpressed by TRIF, TBK1, or IRF3. However, cardamonin had no effect on TBK1 kinase activity in vitro. These results suggest that cardamonin modulates both the MyD88‐ and TRIF‐dependent pathways of TLRs and represents a potentially new anti‐inflammatory candidate. HighlightsToll‐like receptors (TLR) play a significant role in the induction of innate immune responses.Cardamonin is a naturally occurring chalcone from Alpinia species exhibiting anti‐inflammatory effects.Cardamonin suppressed the activation of IRF3 and the expression of IP‐10 induced by TLR3 or TLR4 agonists.These results demonstrate that cardamonin is a potential therapeutic candidate in the treatment of inflammatory diseases.

Anti-inflammatory Effects of Aster yomena Extracts by the Suppression of Inducible Nitric Oxide Synthase Expression

Ah-Yeon Kim, Hyeon-Myeong Shin, Ji-Soo Kim, Hyun-Jin Shim, Kung-Woo Nam, Kyung-A Hwang and Hyung-Sun Youn Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Chungnam, Asan 31538, Korea Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 31538, Korea Department of Life Science and Biotechnology, College of Natural Science, Soonchunhyang University, Asan 31538, Korea Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju 55365, Korea

Differential modulation of toll-like receptor agonists-induced iNOS expression by polyunsaturated and saturated fatty acids

ABSTRACT Toll-like receptors (TLRs) play critical roles in the induction of immune and inflammatory responses by recognizing invading microbial pathogens. One of the most important proteins for inflammatory responses is inducible nitric oxide synthase (iNOS). The dysregulated iNOS activation play important roles in the development of certain inflammatory diseases. The present study investigated the effects of arachidic acid (ACA), which is a saturated fatty acid (SFA), and eicosapentanoic acid (EPA), which is polyunsaturated fatty acid (PUFA), on inflammation by modulating NF-κB activation and iNOS expression induced by TLRs agonists in murine macrophages. EPA suppressed NF-κB activation and iNOS expression induced by a lipopolysaccharide, macrophage-activating lipopeptide 2-kDa, and polyriboinosinic polyribocytidylic acid, but ACA did not. These results suggested that EPA can modulate TLR signaling pathways and subsequent chronic inflammatory responses, but ACA did not mediate these effects. All the results suggest that EPA is a promising novel agent for the treatment of inflammatory diseases. GRAPHICAL ABSTRACT

A case of immature sacrococcygeal teratoma diagnosed by prenatal ultrasonography

천미골기형종은 생식세포 종양 중 매우 드문 아형이지만, 신생아에서는 가장 흔한 선천성 기형으로 한센결절의 다능성 간세포 또는 미성숙 생식세포에서 기원하며, 35,000-40,000 출산 중 1-2명의 태아에서 발생한다. 대부분의 천미골기형종은 양성종양이지만 약 20%에서 악성이며, 신생아에서 악성천미골기형종은 매우 드물다. 천미골기형종의 산전진단은 임신 제1삼분기 또는 제2삼분기 초기에도 초음파를 이용하여 이루어진다. 천미골기형종은 태아 사망률과 유병률의 중요한 원인이 되며, 빠르게 자라는 종양 내부의 동정맥 단락에 의한 태아의 고박출심부전과 이후의 태아수종, 양수과다증, 조산과 강한 관련이 있다. 저자들은 33세 여성에서 첫아이 임신 21주 5일에 태아수종과 양수과다증을 동반한 드문 천미골미성숙기형종을 산전초음파로 진단하였기에 간단한 문헌 고찰과 함께 보고하는 바이다.

A case of stillbirth due to extensive infarction in the basal layer of the placenta diagnosed by prenatal ultrasonography

A CASE OF STILLBIRTH DUE TO EXTENSIVE INFARCTION IN THE BASAL LAYER OF THE PLACENTA DIAGNOSED BY PRENATAL ULTRASONOGRAPHY Chi-Ok Ann, MD, Shi-Sun Kim, MD, Eun-Kyu Cho, MD, Hyun-Jin Shim, MD, Yun-Sook Kim, MD, Dong-Han Bae, MD, Seoung-Ha Yang, MD Departments of Obstetrics and Gynecology, Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea