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Immunomodulatory Effects of phellinus linteus Extracts on Liver Damage Induced by Carbon Tetrachloride in Rats. (상황버섯 추출물이 사염화탄소로 간 손상이 유발된 흰쥐에서의 면역조절 효과)

  • An, Chi-Sun;Choi, Se-Young;Jin, Hai-Lan;Jeon, Yun-Hui;Hur, Sun-Jin;Kim, Ick-Hee;Park, Geum-Duck;Jeoung, Young-Jun;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.3
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    • pp.217-222
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    • 2009
  • The purpose of this study evaluated the immunoregulatory effect of phellinus linteus ethanol (PLE) extracts on liver damage on carbon tetrachloride ($CCl_4$) induced in rats. Four-week old Male Sprague-Dawley rats were divided into the three experimental groups randomly; Control group, $CCl_4$ group, $CCl_4$ + PLE group. We found that effect of PLE on $IFN-\gamma$, STAT1 and pSTAT1 was decrease in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. IL-4, STAT6 and pSTAT6 decreased significantly lower in $CCl_4$ + PLE than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group with $CCl_4$ + PLE group. In our data indicate that IgA levels in MLN lymphocytes were low, while IgE was high in $CCl_4$ + PLE group compared with $CCl_4$ group. Therefore, the results of this study show that PLE can be proposed to protect the liver against $CCl_4$-induced immunoregulatory activity in rats.

Zika Virus Proteins NS2A and NS4A Are Major Antagonists that Reduce IFN-β Promoter Activity Induced by the MDA5/RIG-I Signaling Pathway

  • Ngan, Nguyen Thi Thuy;Kim, Seong-Jun;Lee, Jeong Yoon;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.10
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    • pp.1665-1674
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    • 2019
  • Zika virus (ZIKV) is a mosquito-transmitted, emerging Flavivirus that causes Guillain-$Barr{\acute{e}}$ syndrome and microcephaly in adults and fetuses, respectively. Since ZIKV was first isolated in 1947, severe outbreaks have occurred at various places worldwide, including Yap Island in 2007, French Polynesia in 2013, and Brazil in 2015. Although incidences of ZIKV infection and dissemination have drastically increased, the mechanisms underlying the pathogenesis of ZIKV have not been sufficiently studied. In addition, despite extensive research, the exact roles of individual ZIKV genes in the viral evasion of the host innate immune responses remain elusive. Besides, it is still possible that more than one ZIKV-encoded protein may negatively affect type I interferon (IFN) induction. Hence, in this study, we aimed to determine the modulations of the IFN promoter activity, induced by the MDA5/RIG-I signaling pathway, by over-expressing individual ZIKV genes. Our results show that two nonstructural proteins, NS2A and NS4A, significantly down-regulated the promoter activity of IFN-${\beta}$ by inhibiting multiple signaling molecules involved in the activation of IFN-${\beta}$. Interestingly, while NS2A suppressed both full-length and constitutively active RIG-I, NS4A had inhibitory activity only on full-length RIG-I. In addition, while NS2A inhibited all forms of IRF3 (full-length, regulatory domain-deficient, and constitutively active), NS4A could not inhibit constitutively active IRF3-5D. Taken together, our results showed that NS2A and NS4A play major roles as antagonists of MDA5/RIG-I-mediated IFN-${\beta}$ induction and more importantly, these two viral proteins seem to inhibit induction of the type I IFN responses in differential mechanisms. We believe this study expands our understanding regarding the mechanisms via which ZIKV controls the innate immune responses in cells and may pave the way to development of ZIKV-specific therapeutics.

Ginsenoside fractions regulate the action of monocytes and their differentiation into dendritic cells

  • Lee, Yeo Jin;Son, Young Min;Gu, Min Jeong;Song, Ki-Duk;Park, Sung-Moo;Song, Hyo Jin;Kang, Jae Sung;Woo, Jong Soo;Jung, Jee Hyung;Yang, Deok-Chun;Han, Seung Hyun;Yun, Cheol-Heui
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.29-37
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    • 2015
  • Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

Antioxidant Constituents from Melothria heterophylla; Regulation of Matrix Metalloproteinase-1 Expression in Ultraviolet A-irradiated Human Dermal Fibroblasts (백렴으로부터 항산화 물질의 분리와 자외선이 조사된 사람 섬유아세포의 Matrix Metalloproteinase-1 발현에 미치는 영향)

  • Cho, Young-Ho;Kim, Jin-Hui;Sim, Gwan-Sub;Lee, Bum-Chun;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.4 s.54
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    • pp.323-327
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    • 2005
  • Although many studies have been performed to elucidate the molecular consequence of ultraviolet irradiation on an aging, little is known about the effect of natural products. Matrix metalloproteinases (MMPs) we known to play an important role in (a) photoaging. Hete we investigated the effect of $1,2,4,6-tetra-O-galloyl-{\beta}-{_D}-gluco- pyranose (1)$ and 3,4,5-trihydroxybenzoic acid (2) on the expression of MMP-1 in UVA-irradiated human skin fibroblasts (products), (on the) activity of MMP-1, and (on the) scavenging activities of free radicals. Compounds 1 and 2 were isolated from Melothria heterophylla (Cucurbitaceae). These compounds were found to scavenge free radicals and reactive oxygen species (ROS) and were measured to have the $SC_{50}$ values of $3.9{\mu}M\;and\;13.3{\mu}M$ against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $4.3{\mu}M\;and\; 4.0{\mu}M$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Compounds 1 and 2 showed a dose-dependent inhibitory effect on the e):pression and activity of MMP-1 in the UVA-irradiated human skin fibroblasts. Therefore, we concluded that compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level. Also, these compounds were determined to have a potent antioxidant activity. From these results, we suggest that these compounds nay be used as (a) new anti-aging agents for the photo-damaged skin.

Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells

  • Xu, Qian;Liu, Zhihua;Guo, Ling;Liu, Rui;Li, Rulei;Chu, Xiang;Yang, Jiajia;Luo, Jia;Chen, Faming;Deng, Manjing
    • Molecules and Cells
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    • v.42 no.11
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    • pp.763-772
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    • 2019
  • Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of $HIF-1{\alpha}$, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of $HIF-1{\alpha}$, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride ($CoCl_2$, $100{\mu}mol/L$), an agonist of $HIF-1{\alpha}$, and suppressed by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, $10{\mu}mol/L$), an antagonist of $HIF-1{\alpha}$. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF ($hVEGF_{165}$) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via $HIF-1{\alpha}$-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs.

Intraoperative fluid therapy for video-assisted ovariohysterectomy in dogs

  • Oliveira, Marilia Teresa de;Feranti, Joao Pedro Scussel;Coradini, Gabriela Pesamosca;Chaves, Rafael Oliveira;Correa, Luis Felipe Dutra;Linhares, Marcella Teixeira;Thiesen, Roberto;Silva, Marco Augusto Machado;Brun, Mauricio Veloso
    • Journal of Veterinary Science
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    • v.22 no.3
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    • pp.44.1-44.15
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    • 2021
  • Background: Intraoperative fluids are still poorly studied in veterinary medicine. In humans the dosage is associated with significant differences in postoperative outcomes. Objectives: The aim of this study is to verify the influence of three different fluid therapy rates in dogs undergoing video-assisted ovariohysterectomy. Methods: Twenty-four female dogs were distributed into three groups: G5, G10, and G20. Each group was given 5, 10, and 20 mL·kg-1·h-1 of Lactate Ringer, respectively. This study evaluated the following parameters: central venous pressure, arterial blood pressure, heart rate, respiratory rate, temperature, acid-base balance, and serum lactate levels. Additionally, this study evaluated the following urinary variables: urea, creatinine, protein to creatinine ratio, urine output, and urine specific gravity. The dogs were evaluated up to 26 h after the procedure. Results: All animals presented respiratory acidosis during the intraoperative period. The G5 group evidenced intraoperative oliguria (0.80 ± 0.38 mL·kg-1·h-1), differing from the G20 group (2.17 ± 0.52 mL·kg-1·h-1) (p = 0.001). Serum lactate was different between groups during extubation (p = 0.036), with higher values being recorded in the G5 group (2.19 ± 1.65 mmol/L). Animals from the G20 group presented more severe hypothermia at the end of the procedure (35.93 ± 0.61℃) (p = 0.032). Only the members of the G20 group presented mean potassium values below the reference for the species. Anion gap values were lower in the G20 group when compared to the G5 and G10 groups (p = 0.017). Conclusions: The use of lactated Ringer's solution at the rate of 10 mL·kg-1·h-1 seems to be beneficial in the elective laparoscopic procedures over the 5 or 20 mL·kg-1·h-1 rates of infusion.

Novel reassortant 2.3.4.4B H5N6 highly pathogenic avian influenza viruses circulating among wild, domestic birds in Xinjiang, Northwest China

  • Zhang, Qian;Mei, Xindi;Zhang, Cheng;Li, Juan;Chang, Nana;Aji, Dilihuma;Shi, Weifeng;Bi, Yuhai;Ma, Zhenghai
    • Journal of Veterinary Science
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    • v.22 no.4
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    • pp.43.1-43.10
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    • 2021
  • Background: The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. Objectives: This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. Methods: AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. Results: Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016-2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. Conclusions: These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.

Expression Analysis of Chicken Interleukin-34(IL-34) for Various Pathogenic Stimulations (주요 병원균 자극에 의한 닭의 Interleukin-34 발현 분석 비교)

  • Hong, Yeong Ho
    • Korean Journal of Poultry Science
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    • v.48 no.3
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    • pp.111-122
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    • 2021
  • Recently, interleukin 34 (IL-34) was identified as the second functional ligand for macrophage colony-stimulating factor receptor (M-CSFR). IL-34 functions similarly to M-CSF through its binding to the M-CSFR. There is still insufficient information on IL-34 in chickens, which has until now been reported only through predicted sequences and not through experimental research. Thus, to confirm its expression and to determine its potent biological activity, several chicken lines and cell lines were used. Cloning of recombinant chicken IL-34 and M-CSF genes was performed to investigate their modulatory effects on proinflammatory cytokine expression in vitro. The expression levels of IL-34, M-CSF, and M-CSFR genes were upregulated in broiler chickens with leg dysfunction (cause unknown). However, IL-34 was downregulated in most pathogen-stimulated tissues. M-CSFR expression was enhanced by recombinant IL-34 and M-CSF proteins in vitro. IFN-γ expression was enhanced by recombinant IL-34, but not by M-CSF. However, IL-12 expression was not regulated in any of the treated cells, and IL-1β was decreased in all tissues. These results indicate that IL-34 and M-CSF have roles in both the classical and alternative macrophage activation pathways. Collectively, our findings demonstrate the expression of IL-34 in chickens for pathogenic trials, both in vitro and in vivo. Our results suggest that the IL-34 protein plays a role in both pro- and anti-inflammatory functions in macrophages. Therefore, further research is needed to determine the cytokines or chemokines that can be induced by IL-34 and to further elucidate the functions of IL-34 in the inflammatory pathway.

A Study on the Methodology of Early Diagnosis of Dementia Based on AI (Artificial Intelligence) (인공지능(AI) 기반 치매 조기진단 방법론에 관한 연구)

  • Oh, Sung Hoon;Jeon, Young Jun;Kwon, Young Woo;Jeong, Seok Chan
    • The Journal of Bigdata
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    • v.6 no.1
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    • pp.37-49
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    • 2021
  • The number of dementia patients in Korea is estimated to be over 800,000, and the severity of dementia is becoming a social problem. However, no treatment or drug has yet been developed to cure dementia worldwide. The number of dementia patients is expected to increase further due to the rapid aging of the population. Currently, early detection of dementia and delaying the course of dementia symptoms is the best alternative. This study presented a methodology for early diagnosis of dementia by measuring and analyzing amyloid plaques. This vital protein can most clearly and early diagnose dementia in the retina through AI-based image analysis. We performed binary classification and multi-classification learning based on CNN on retina data. We also developed a deep learning algorithm that can diagnose dementia early based on pre-processed retinal data. Accuracy and recall of the deep learning model were verified, and as a result of the verification, and derived results that satisfy both recall and accuracy. In the future, we plan to continue the study based on clinical data of actual dementia patients, and the results of this study are expected to solve the dementia problem.

Kimchi cabbage (Brassica rapa L.) by-products treated with calcium oxide and alkaline hydrogen peroxide as feed ingredient for Holstein steers

  • Son, A-Rang;Kim, Seon-Ho;Valencia, Raniel A.;Jeong, Chang-Dae;Islam, Mahfuzul;Yang, Chul-Ju;Lee, Sang-Suk
    • Journal of Animal Science and Technology
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    • v.63 no.4
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    • pp.841-853
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    • 2021
  • This study aimed to investigate the effects of Kimchi cabbage by-products either treated or untreated with calcium oxide (CaO) and alkaline hydrogen peroxide (AHP) as substitutional ingredient of total mixed ration (TMR) on in vitro fermentation, in situ disappearance and growth performance of Holstein steers. Cannulated Holstein (600 ± 47 kg) was used for both the in vitro and in situ experiments. The treatments used were TMR only (CON), TMR + 30% Kimchi cabbage by-products fresh matter (FM) basis (TC), TMR + 30% Kimchi cabbage by-products FM basis + 5% CaO FM basis (TCC), and TMR + 30% Kimchi cabbage by-products FM basis + 5% CaO FM basis + 3.22% AHP FM basis (TCCA). For in vivo experiment, thirty-four Holstein steers (273 ± 45 kg) were subjected to a 150-day feeding trial, divided into two groups: CON and TC. In the in vitro experiment, pH of TCCA was greatest (p < 0.05) among other treatments at all incubation times. Ammonia nitrogen and volatile fatty acid concentrations were not significantly different for each treatment. However, butyrate was greater (p < 0.05) in TCC and CON than in both TC and TCCA. During in situ experiment, the dry matter (DM) disappearance was greatest (p < 0.05) in TCCA among other treatments. Also, disappearance of neutral detergent fiber (NDF) and acid detergent fiber (ADF) were observed greatest (p > 0.05) in TCCA treatment. In the in vivo experiment, average daily gain (ADG) did not differ between CON and TC. In blood profile analysis, alanine aminotransferase, aspartate aminotransferase, glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total protein concentration were not significantly different between treatments. But, creatinine concentration was greater (p < 0.05) in TC than in CON. Overall results suggest that Kimchi cabbage by-products either treated or untreated with CaO and AHP can be used as substitutional ingredient in TMR for Holstein steers.