Unraveling the swine genome: implications for human health.

Schook, Lawrence B,Collares, Tiago V,Darfour-Oduro, Kwame A,De, Arun Kumar,Rund, Laurie A,Schachtschneider, Kyle M,Seixas, Fabiana K Annual Reviews 2015 Annual review of animal biosciences Vol.3 No.-

<P>The pig was first used in biomedical research in ancient Greece and over the past few decades has quickly grown into an important biomedical research tool. Pigs have genetic and physiological traits similar to humans, which make them one of the most useful and versatile animal models. Owing to these similarities, data generated from porcine models are more likely to lead to viable human treatments than those from murine work. In addition, the similarity in size and physiology to humans allows pigs to be used for many experimental approaches not feasible in mice. Research areas that employ pigs range from neonatal development to translational models for cancer therapy. Increasing numbers of porcine models are being developed since the release of the swine genome sequence, and the development of additional porcine genomic and epigenetic resources will further their use in biomedical research.</P>

Molecular Docking-assisted Protein Chip Screening of Inhibitors for Bcl-2 Family Protein-protein Interaction to Discover Anticancer Agents by Fragment-based Approach

Myoung-Schook Yoou,조성준,최영진 한국바이오칩학회 2019 BioChip Journal Vol.13 No.3

For fragment-based cancer drug discovery, we introduced a molecular docking simulation combined with a protein chip assay. Protein chip technology was used to find fragment-hits that had inhibitory activity against Bcl-2 protein from 131 pre-selected fragment chemicals. Molecular docking simulation was performed for the 12 identified fragment-hits to establish the binding mode of these compounds in the Bcl-2 site. Using the molecular docking-assisted protein chip screening system, we derived a virtual compound structure with an important scaffold feature for interaction with the Bcl-2 protein. We then tested the anticancer activity of 26 compounds that were similar to the scaffold structure. The anticancer activity was confirmed by MTT-assay in A549 lung cancer cells. Finally, three chemicals showed dose-dependent inhibitory activity against cancer cell proliferation. We suggest that the present molecular docking-assisted protein chip assay can be used as a platform technology in the fragment-based drug development process to discover inhibitory agents of protein-protein interactions.

Ameliorative effect of atractylenolide III in the mast cell proliferation induced by TSLP

Yoou, Myoung-schook,Nam, Sun-Young,Jin, Mu Hyun,Lee, So Young,Kim, Mi-Sun,Roh, Seok Seon,Choi, In Hwa,Woo, Nariyah,Lim, SeokWon,Kim, Dong Hyun,Jang, Jae-Bum,Kim, Hyung-Min,Jeong, Hyun-Ja Pergamon 2017 Food and Chemical Toxicology Vol. No.

<P><B>Abstract</B></P> <P>Atractylenolide III (ATL-III) is an active compound of <I>Atractylodes lancea</I>, which has been widely used for the treatment of cancer. Cancer is closely connected with inflammation, and many anti-inflammatory agents are also used to treat cancer. We investigated the influence of ATL-III on thymic stromal lymphopoietin (TSLP)-induced inflammatory reactions. Pretreatment with ATL-III suppressed murine double minute 2 levels and promoted p53 levels in TSLP-treated human mast cell, HMC-1 cells. Mast cell proliferation increased by TSLP or IL-3 stimulation was significantly decreased by ATL-III pretreatment. Interleukin (IL)-13 and phosphorylated signal transducer and activator of transcription 3, 5, and 6 levels in TSLP-treated HMC-1 cells were also decreased by ATL-III pretreatment. In addition, ATL-III decreased the TSLP-induced production of proinflammatory cytokines (IL-6, IL-1β, tumor necrosis factor-α, and IL-8). ATL-III decreased the levels of Bcl2 and procaspase-3 and increased caspase-3 activation and cleaved PARP levels. Furthermore, ATL-III decreased TSLP-induced mast cell proliferation and the production of inflammatory cytokine by LAD2 cells. Taken together, these findings suggest that ATL-III plays a useful role as an anti-inflammatory agent and should be viewed as a potential anti-cancer agent.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Atractylenolide III attenuates the level of MDM2 and proliferation of mast cells. </LI> <LI> Atractylenolide III attenuates the levels of phosphorylated STAT6. </LI> <LI> Atractylenolide III attenuates the IL-13 production. </LI> <LI> Atractylenolide III induces the activation of caspase-3. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Mac-1-mediated Uptake and Killing of Bordetella bronchiseptica by Porcine Alveolar Macrophages

Jong-keukLee,LawrenceB.Schook,MarkS.Rutherford 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.1

The role of Mac-1 as a receptor for Bordetellabronchiseptica infection of alveolar macrophages (AM) was examined using 6 strains (2 ATCC and 4pathogenic field isolates) to assess B. bronchisepticabinding, uptake and replication in primary porcineAM .All B.bronchiseptica strains were rapidly killedby porcine serum in a dose- and time-dependentmanner. However, heat-inactivated porcine serum(HIS) did not demonstrate any bacterial-killing act-ivity, suggesting that complement may have a directkilling activity. All field isolates were more resistantto direct complement-mediated B. bronchisepticakilling.The uptake of B.bronchiseptica into AM wasinhibited approximately 50% by antiMac-1 monoclonalantibodies in the medium.However,B.bronchisepticaphagocytosed in the presence of serum or HIS wasnot altered by anti-Mac-1 antibodies although morebacteria were internalized by addition of serum orHIS. These data suggest that Mac-1 is a target fordirect uptake of B. bronchiseptica via opsonin-independent binding.The phagocytosed B.bronchise-ptica, either via direct or serum-mediated binding,were efficiently killed by AM within 10 hr pos-tinfection. This demonstrates that Mac-1-mediated B.bronchiseptica uptake is a bacterial killing pathwaynot leading to productive infections in AM .

Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets

Ji, P.,Schachtschneider, K.M.,Schook, L.B.,Walker, F.R.,Johnson, R.W. Academic Press 2016 Brain, behavior, and immunity Vol.54 No.-

Although poorly understood, early-life infection is predicted to affect brain microglial cells, making them hypersensitive to subsequent stimuli. To investigate this, we assessed gene expression in hippocampal tissue obtained from a previously published study reporting increased microglial cell activity and reduced hippocampal-dependent learning in neonatal piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus that induces interstitial pneumonia. Infection altered expression of 455 genes, of which 334 were up-regulated and 121 were down-regulated. Functional annotation revealed that immune function genes were enriched among the up-regulated differentially expressed genes (DEGs), whereas calcium binding and synaptic vesicle genes were enriched among the down-regulated DEGs. Twenty-six genes encoding part of the microglia sensory apparatus (i.e., the sensome) were up-regulated (e.g., IL1R1, TLR2, and TLR4), whereas 15 genes associated with the synaptosome and synaptic receptors (e.g., NPTX2, GABRA2, and SLC5A7) were down-regulated. As the sensome may foretell microglia reactivity, we next inoculated piglets with culture medium or PRRSV at PD 7 and assessed hippocampal microglia morphology and function at PD 28 when signs of infection were waning. Consistent with amplification of the sensome, microglia from PRRSV piglets had enhanced responsiveness to chemoattractants, increased phagocytic activity, and secreted more TNFα in response to lipopolysaccharide and Poly I:C. Immunohistochemical staining indicated PRRSV infection increased microglia soma length and length-to-width ratio. Bipolar rod-like microglia not evident in hippocampus of control piglets, were present in infected piglets. Collectively, this study suggests early-life infection alters the microglia sensome as well as microglial cell morphology and function.

Therapeutic potential of traditional Korean music, Daegeum Sanjo in atopic dermatitis-like murine model

Ko, Kyung Ja,Yoou, Myoung-schook,Han, Na-Ra Cellmed Orthocellular Medicine and Pharmaceutical 2019 셀메드 (CellMed) Vol.9 No.1

Atopic dermatitis (AD) is an allergic and inflammatory skin. Recently, the limitations and side effects of drug therapy, and possibility of alternative therapies, such as music therapy are emerging in the treatment of AD. Thus, the present study determined whether traditional Korean music, Daegeum Sanjo, regulates AD symptoms by comparing the rhythm, Jinyangjo-jangdan and Jungmori-jangdan in an AD-like murine model. Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo reduced the duration of scratching behavior increased by DNFB challenge. Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo attenuated clinical symptoms. However, Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo did not inhibit IgE, histamine, interleukin (IL)-4, IL-6, or thymic stromal lymphopoietin levels in serum or AD-like skin lesions. In conclusion, the present study suggests that it is possible for Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo to ameliorate AD symptoms. However, further study is needed to clarify significant mechanisms of Jinyangjo-jangdan and Jungmori-jangdan of Daegeum Sanjo therapy for AD symptoms.

Anti-inflammatory effects of isoacteoside from <i>Abeliophyllum distichum</i>

Nam, Sun-Young,Kim, Hee-Yun,Yoou, Myoung-Schook,Kim, A. Hyun,Park, Byoung Jun,Jeong, Hyun-Ja,Kim, Hyung-Min Taylor & Francis 2015 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY Vol.37 No.3

<P>Isoacteoside, a dihydroxypheynylethyl glycoside, is a major bioactive component of <I>Abeliophyllum distichum</I> (White Forsythia) which is a deciduous shrub native to the south and central areas of Korea. The present study is designed to evaluate the anti-inflammatory activities and underlying mechanisms of isoacteoside in human mast cell line, HMC-1 cells. We isolated isoacteoside from <I>A. distichum</I>. The anti-inflammatory effect of isoacteoside was investigated in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) secretion and mRNA expression by ELISA and RT-PCR, respectively. In addition, mechanism related to anti-inflammatory was investigated by Western blotting. Isoacteoside significantly suppressed the production and mRNA expression of proinflammatory cytokines including IL-1β, IL-6, IL-8 and TNF-α in PMACI-stimulated HMC-1 cells without cytotoxicity. It was found that anti-inflammatory effects of isoacteoside are mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways. Taken together, the present findings provide new insights that isoacteoside may be a promising anti-inflammatory agent for inflammatory disorders.</P>

Effect of massage therapy by VOSKIN 125+ painkiller® on inflammatory skin lesions

Han, Na‐,Ra,Moon, Phil‐,Dong,Yoou, Myoung‐,schook,Chang, Tae‐,soun,Kim, Hyung‐,Min,Jeong, Hyun‐,Ja John Wiley Sons, Inc. 2018 Dermatologic therapy Vol.31 No.5

Nomenclature for factors of the SLA system, update 2008

Ho, C.-S.,Lunney, J. K.,Ando, A.,Rogel-Gaillard, C.,Lee, J.-H.,Schook, L. B.,Smith, D. M. Blackwell Publishing Ltd 2009 Tissue antigens Vol.73 No.4

<P>Abstract</P><P>This report summarizes the new swine leukocyte antigen (SLA) allele sequences and haplotypes designated by the SLA Nomenclature Committee of the International Society for Animal Genetics. There have been 74 new SLA alleles, comprising 18 SLA-1 alleles, 11 SLA-2 alleles, six SLA-3 alleles, two SLA-6 alleles, one SLA-DRA allele, 20 SLA-DRB1 alleles, three SLA-DQA alleles and 13 SLA-DQB1 alleles. Twelve new SLA class I and four new class II haplotypes have also been designated. This is the first official update since the 2005 reports on the nomenclature for factors of the SLA class I and II systems. This report also summarizes recent updates to the Immunopolymorphism Database–Major Histocompatibility Complex (IPD-MHC) website (http://www.ebi.ac.uk/ipd/mhc/sla/). All information has now been integrated to the SLA section of the IPD-MHC database, which serves as the repository for maintaining a list of all recognized <I>SLA</I> genes and their allelic sequences.</P>

Protective effect of porcine placenta in a menopausal ovariectomized mouse

Han, Na-Ra,Park, Chan-Lee,Kim, Na-Rae,Kim, Hee-Yun,Yoou, Myoung-Schook,Nam, Sun-Young,Moon, Phil-Dong,Jeong, Hyun-Ja,Kim, Hyung-Min BioScientifica 2015 Reproduction Vol.150 No.3

<P>Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis.</P><P><B>Free Korean abstract</B>: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.</P>