Hong, Sung-Wook;O, Eunju;Lee, Jun Young;Yi, Jaeu;Cho, Kyungjin;Kim, Juhee;Kim, Daeun;Surh, Charles D.;Kim, Kwang Soon
BMB Reports
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v.52
no.4
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pp.283-288
/
2019
$Foxp3^+$ regulatory $CD4^+$ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.
The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.
Two experiments were conducted to standardize in ovo injection of amino acids (AA) and to evaluate the effect of in ovo injection of limiting AA(s) on pre and post hatch growth performance, immune response and development of digestive organs. Combinations of essential and non-essential amino acids (Lys+Arg, Lys+Met+Cys, Thr+Gly+Ser, Ile+Leu+Val and Gly+Pro) were injected into 50 eggs in each treatment group at 14 d of embryonic age. Standardization of injection site, needle length and embryonic age revealed that when AA were injected in to the broad end of the egg with a 11 mm needle and at the narrow end with a 24 mm needle both at the 7$^{th}$ and 14$^{th}$ d of incubation there was poor hatchability. However, better hatchability was recorded when the AA were injected in the narrow end of the egg with a 11 mm needle and in the broad end with a 24 mm needle on the 14$^{th}$ d of incubation. The chick to egg weight ratio was higher (p<0.018) when AA were injected on the 14$^{th}$ d of incubation. When a combination of amino acids were injected a 63.6 or 63.2 g difference in body weight of bird at 21 d was recorded between uninjected control and Ile+Leu+Val or Gly+Pro group, respectively. Higher feed intake (p<0.047) was recorded in the AA injected groups and feed conversion ratio (FCR) was numerically better in Gly+Pro, Lys+Met+Cys AA injected groups than in the uninjected control. Significantly higher immune response to cell mediated (p<0.033) and humoral (p<0.002) immunity was observed in in ovo amino acid injected birds, especially in Lys+Met+Cys, Thr+Gly+Ser or Ile+leu+Val groups. The digestive organ weights at 21 d did not differ between specific AA injected groups and the uninjected control. In ovo injected amino acids may act as immunomodulators and their role in gastrointestinal development needs further research.
Kim, Ju Hwan;Shin, Chang Yell;Jang, Sun Woo;Kim, Dong-Seok;Lee, Wonae;Kim, Hyung-Gun;Kim, Hak Rim
The Korean Journal of Physiology and Pharmacology
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v.25
no.5
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pp.439-448
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2021
DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4+ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ+ Th1 cells, IL-4+ Th2 cells, IL-9+ Th9 cells, IL-17+ Th17 cells, and Foxp3+ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.
Im, Young Bin;Park, Woo Bin;Jung, Myunghwan;Kim, Suk;Yoo, Han Sang
Journal of Microbiology and Biotechnology
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v.26
no.6
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pp.1132-1139
/
2016
Brucellosis is a zoonotic disease caused by Brucella, a genus of gram-negative bacteria. Cytokines have key roles in the activation of innate and acquired immunities. Despite several research attempts to reveal the immune responses, the mechanism of Brucella infection remains unclear. Therefore, immune responses were analyzed in mice immunized with nine recombinant proteins. Cytokine production profiles were analyzed in the RAW 264.7 cells and naive splenocytes after stimulation with three recombinant proteins, metal-dependent hydrolase (r0628), bacterioferritin (rBfr), and thiamine transporter substrate-binding protein (rTbpA). Immune responses were analyzed by ELISA and ELISpot assay after immunization with proteins in mice. The production levels of NO, TNF-α, and IL-6 were time-dependently increased after having been stimulated with proteins in the RAW 264.7 cells. In naive splenocytes, the production of IFN-γ and IL-2 was increased after stimulation with the proteins. It was concluded that two recombinant proteins, r0628 and rTbpA, showed strong immunogenicity that was induced with Th1-related cytokines IFN-γ, IL-2, and TNF-α more than Th2-related cytokines IL-6, IL-4, and IL-5 in vitro. Conversely, a humoral immune response was activated by increasing the number of antigen-secreting cells specifically. Furthermore, these could be candidate diagnosis antigens for better understanding of brucellosis.
The purpose of this study is to analyze the factors affecting innovation activities related to the introduction of the 4th Industrial Revolution technology for Korean firms faced to the severe global trade and competition environments. This paper conducted an empirical analysis using the 'The Survey of Business Activities' distributed by the Statistics Korea in 2019. According to the results of the analysis, it was found that the firm size, labor cost, R&D, and intellectual property rights had a significant influence on the firms' adoption of the 4th industrial revolution technology. It was also found that the dummy variables such as strategic alliance between companies, review of entry into a new business, transfer of main business operations, and holding of subsidiaries had statistically significant effects on innovation activities. In addition, this paper showed that the firm characteristics had impacts on innovation activities of firms by the 4th industrial revolution technology type. In order for Korean firms to adapt to the challenges by the 4th Industrial Revolution, it is important to provide policy support and an environment in line with the characteristics of the firms.
Journal of Physiology & Pathology in Korean Medicine
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v.23
no.5
/
pp.1080-1086
/
2009
This study was designed to investigate the effects of Gastrodiae Elata Pharmacopuncure at GB20 on motor control and cognitive dysfunction recovery after mild traumatic brain injury in rats. Rats were divided into three groups; (1) no treatment after traumatic brain injury(experiment I), (2) Treatment with NPA after traumatic brain injury(experiment II), (3) Treatment with GEP after traumatic brain injury(experiment III). In our study, we carried out behavioral test(Rotarod, Morris water maze) and immunohistochemistry study of the change BDNF in the hippocampus(pre, $7^{th}$, $14^{th}$ day). In Rotarod test(motor control function) was significantly increased in the experimental group III as compared with experimental group I, II on $7^{th}$(p<0.01) and $14^{th}$ day(p<0.001). In Morris water maze test(cognitive function) was significantly decreased in the experimental group III as compared with experimental group I, II on $14^{th}$ day(p<0.001). In immunohistochemistric response of BDNF in the hippocampus, the experimental group III was more immune response than the other groups on $14^{th}$ day. These results imply that Gastrodiae Elata Pharmacopuncure at GB20 can play a role in facilitating recovery of motor control and cognitive function after mild traumatic brain injury in rats.
Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.
The effect of the hydroxyapatite coatings on Titanium implants has been the subject of recent investigations. So far, the use of HA coating remains substantially controversial.This study was aimed to evaluate histologically the bone healing patterns around titanium plasm sprayed(TPS) amd HA-coated implant after implantation into the femur neck of ten adult dogs. After implantation, animals were sacrificed at the intervals of 2,4,6,8 and 12 weeks.The fluorescent dyes were injected on the postoperative 4th and 12th week into the animals supposed to be killed at the 12th week. The morphology and direction of new bone formation was similar in both TPS and HA-coated implants.There was a tendency toward more bone formation in the cortical bone area than in the cancellous bone area. Histologically,in the interface of the HA-coated implants, bone response and bone maturation was faster, compared to the TPS implants in the 2nd and 4th week. By fluorescent microscopy, new bone formation was active in the 4th week around both implants and was directed from the periosteum overlying cortical bone to the cancellous bone. These results suggest that the bone formation and maturation is faster during the early healing stage in the interface of the HA-coated implant and where the cortical bone quality is poor, HA coated implant is superior to the TPS implant in the early phase of new bone formation.
This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 1011 CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.
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