• IMMUNE NETWORK
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• v.22 no.6
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• pp.49.1-49.15
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• 2022

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H₂O₂-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H₂O₂-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.

• Herbal Formula Science
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• v.31 no.4
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• pp.315-325
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• 2023

Objectives : Recently, research has been actively conducted on the efficacy of complexes based on oriental medicine prescriptions for improving immune activity and allergies. In this study, In this study, we aimed to examine the effect of Angelica gigas Nakai and Corni fructus extract (AC), medicinal herbs, among candidate drugs derived through preliminary experiments with various components of oriental medicine prescriptions for allergies, on allergies in RBL-2H3 cells. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in anti-DNP-IgE activated DNP-HSA in RBL-2H3 cells. Cell toxicity was determined by WST-1 assay and the markers of degranulation such as beta-hexosaminidase, histamine, TNF-α and IL-6 production of inflammatory mediators and FcεRI-mediated expression. Results : The results showed that treatment with AC extract (20, 40 and 80㎍/㎖) noncytotoxic levels and significantly inhibited the release of β-hexosaminidase, histamine and the production of TNF-α and IL-6 in RBL-2H3 by the antigen stimulation. Conclusions : These results indicate that AC extract exhibits anti-allergic activity through inhibition of degranulation and inhibition of inflammatory mediators and cytokine release. These findings suggest that AC extract may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• Parasites, Hosts and Diseases
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• v.30 no.1
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• pp.43-48
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• 1992

Paragonimus westermani is a common fluke in Uorea. The present study aimed to observe the cell mediated immune response in experimental paragonimiasis of mice. The mouse (BALB/c) was orally inoculated with 40 metacercariae of P. westermani from Cambaroides similis. During the infection (1, 2, 4, 6 weeks) of mouse, blastogenic response of splenic Iymphocytes to P. westermani adult antigen, metacercaria antigen, and PHA were observed. Sera from infected and noninfected mice added to normal mouse splenic Lymphocytes with or without PHA. The blastogenic response of splenic Lymphocytes to PHA was reduced after 1 week of infection. However after 6 weeks of infection, the response was restored to the control level. The blastogenic response of splenic Iymphocytes to P. westermani adult or metacercaria antigen increased significantly on 1 week after infection, and maintained up to 6 weeks after infection. The response of non-infected mice was suppressed by addition of the infected mouse serum. The present results suggested that cellular immunity was involved in P. westermani infected mice and that P. westermani anti.serum inhibited proliferation of T Iymphocytes.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.486-494
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• 2017

Objective: An experiment was conducted to determine the nutrient intake, digestibility, microbial protein synthesis, haemato-biochemical attributes, immune response and growth performance of Gaddi kids fed with oat fodder based basal diet supplemented with either tea seed or tea seed saponin (TSS) extract. Methods: Eighteen male kids, $7.03{\pm}0.16$ months of age and $19.72{\pm}0.64kg$ body weight, were distributed into three groups, $T_0$ (control), $T_1$, and $T_2$, consisting of 6 animals each in a completely randomized design. The kids were fed a basal diet consisting of concentrate mixture and oat fodder (50:50). Animals in group III ($T_2$) were supplemented with TSS at 0.4% of dry matter intake (DMI), and group II ($T_1$) were supplemented with tea seed at 2.6% of DMI to provide equivalent dose of TSS as in $T_2$. Two metabolism trials were conducted, 1st after 21 days and 2nd after 90 days of feeding to evaluate the short term and long term effects of supplementation. Results: The tea seed ($T_1$) or TSS ($T_2$) supplementation did not affect DMI as well as the digestibility of dry matter, organic matter, crude protein, neutral detergent fibre, and acid detergent fibre. Nutritive value of diet and plane of nutrition were also comparable for both the periods. However, the average daily gain and feed conversion ratio (FCR) were improved (p<0.05) for $T_1$ and $T_2$ as compared to $T_0$. The microbial protein supply was also higher (p<0.05) for $T_1$ and $T_2$ for both the periods. There was no effect of supplementation on most blood parameters. However, the triglyceride and low density lipoprotein cholesterol levels decreased (p<0.05) and high density lipoprotein-cholesterol level increased (p<0.05) in $T_2$ as compared with $T_0$ and $T_1$. Supplementation also did not affect the cell mediated and humoral immune response in goats. Conclusion: Tea seed at 2.6% of DMI and TSS at 0.4% DMI can be fed to Gaddi goats to improve growth rate, FCR and microbial protein synthesis.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.8
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• pp.1366-1372
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• 2018

Objective: A disintegrin and metallopeptidase with thrombospondin motifs type 8 (ADAMTS8) is crucial for diverse physiological processes, such as inflammation, tissue morphogenesis, and tumorigenesis. The chicken ADAMTS8 (chADAMTS8) gene was differentially expressed in the kidney following exposure to different calcium concentrations, suggesting a pathological role of this protein in metabolic diseases. We aimed to examine the molecular characteristics of chADAMTS8 and analyze the gene-expression differences in response to toll-like receptor 3 (TLR3) stimulation. Methods: The ADAMTS8 mRNA and amino acid sequences of various species (chicken, duck, cow, mouse, rat, human, chimpanzee, pig, and horse) were retrieved from the Ensembl database and subjected to bioinformatics analyses. Reverse-transcription polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR) experiments were performed with various chicken tissues and the chicken fibroblast DF-1 cell line, which was stimulated with polyinosinic-polycytidylic acid (poly[I:C]; a TLR3 ligand). Results: The chADAMTS8 gene was predicted to contain three thrombospondin type 1 (TSP1) domains, whose amino acid sequences shared homology among the different species, whereas sequences outside the TSP1 domains (especially the amino-terminal region) were very dif­ferent. Phylogenetic analysis revealed that chADAMTS8 is evolutionarily clustered in the same clade with that of the duck. chADAMTS8 mRNA was broadly expressed in chicken tissues, and the expression was significantly up-regulated in the DF-1 cells in response to poly(I:C) stimulation (p<0.05). These results showed that chADAMTS8 may be a target gene for TLR3 signaling. Conclusion: In this report, the genetic information of chADAMTS8 gene, its expression in chicken tissues, and chicken DF-1 cells under the stimulation of TLR3 were shown. The result suggests that chADAMTS8 expression may be induced by viral infection and correlated with TLR3-mediated signaling pathway. Further study of the function of chADAMTS8 during TLR3-dependent inflammation (which represents RNA viral infection) is needed and it will also be important to examine the molecular mechanisms during different regulation, depending on innate immune receptor activation.

• Journal of Sasang Constitutional Medicine
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• v.1 no.1
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• pp.87-112
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• 1989

In order to investigate experimentally the effects of Sung-yangikgibujat'ang (SIT) and Kwangyebujalijungt'ang (KBT) on Yang-insufficient syndrome (陽虛證) induced by Hydrocortisone acetate (H.A.) in experimental animals (Mice and Rat), the author experimented various activities. Delayed type hypersensitivity (DTH), Rosette forming cells (RFC), hemagglutinin (HA) titers, Hemolysin (HL) titers, Body weight, Whole blood viscosity, Plasma Viscosity, Hematocrit, RBC, Albumin, Total protein, Triglyceride, cholesterol and Glucose were measured. The results summerized as follows; 1. In DTH and RFC all the experimental groups were increased significantly in comparison to the H.A.-treated group. 2. In HA titers SIT_treated group were increased significantly and KBT-treated group showed increasing tendancy, but showed no significance. 3. In HL titers all the experimental groups showed increasing tendancy, but showed no significance. 4. In body weight all the experimental groups showed increasing tendancy, but showed no significance. 5. In whole blood viscosity all the experimental groups were decreased significantly in comparison to the H.A.-treated group. 5. In whole blood viscosity all the experimental groups were decreased significantly in comparison to the H.A.-treated group. 6. In plasma viscosity KBT-treated group were decreased significantly and SIT-treated group showed decreasing tendancy, but showed no significance. 7. In Hematocrit SIT-treated group were decreased significantly and KBT-treated group showed decreasing tendancy, but showed no significance. 8. In RBC, albumin and cholesterol all the experimental groups were decreased significantly in comparison to the H.A.-treated group. 9. In total protein and triglyceride KBT-treated group were decreased significantly and SIT-treated group showed decreasing tendancy, but showed no significance. 10. In Glucose SIT-treated group were decreased significantly and KBT-treated group showed decreasing tendancy, but showed no significance. From above findings, it has been demonstrated that Sungyangikgibujat'ang and Kwangyebujalijungt'ang seem to produce the effectiveness on the recovery from depression of the cell-mediated immune response, blood circulation and energy metabolic rate, induced by Hydrocortisone acetate, and in the humoral immune response Sungyangikgibujat'ang have the effectiveness on the recovery, and in cellular component of blood Sungyangikgibujat'ang was more effective than Kwangyebujalijungt' ang, and in plasma of blood Kwangyebujalijungt'ang was more effective than Sungyangikgibujat'ang. Therefore it is suggested that Sungyangikgibujat'ang and Kwangyebujalijungt'ang have the effectiveness on the recovery from Yang-insufficient syndrome more or less.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.5
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• pp.690-699
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• 2017

Objective: This study aimed to examine the effect of sodium butyrate (SB) on growth performance, immune status, organs weights, and microarchitecture of lymphoid organs and small intestine. Methods: A total of 120, 1-d-old broiler chicks were distributed into the following four treatment groups: corn-soy based basal diet (BD) without supplement (control), or the same BD supplemented with 0.1 g/kg zinc bacitracin (ZnB), 0.5 g/kg SB (SB-0.5), or 1.0 g/kg SB (SB-1), respectively. Six birds/group were killed on d-21 and d-35, and samples were collected. Results: Cell-mediated immune response at 48 h post-Phytohemagglutinin-P injection, and antibody titer against Newcastle disease vaccine and sheep red blood cells on d-35 was noted higher (p<0.05) in SB-1 compared to ZnB and control. Lower (p<0.05) feed conversion ratio (FCR) was attained by the supplemented groups. Thymus and spleen weighed more (p<0.05) in SB-1, and bursa registered more (p<0.05) weight in both SB groups compared to control. On d-21, areas of thymus medulla and spleen germinal centers were noted higher (p<0.05) in SB-1 group. The villus height and villus surface area increased (p<0.05) in duodenum and jejunum in both SB groups on d-21, and in SB-1 on d-35, respectively compared to ZnB and control. On d-21, number of goblet cells containing mucins of acidic nature increased (p<0.05) in all the segments of small intestines in SB-1 group compared to control, and on d-35 in ileum compared to other groups. Conclusion: In conclusion, SB improved growth performance and immunity as well as modulated morphology of lymphoid organs and gut mucosa in broiler chickens.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.284-287
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• 2018

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutation of one of two genes, TSC1 (encoding hamartin, 9q34) and TSC2 (encoding tuberin, 16p13). It invades the central nervous system and various parts of the body, causing various symptoms. Crohn's disease (CD) is a chronic immune-mediated disease that has not been clearly elucidated. It is thought to be caused by an excessive immune response of the body to bacteria that normally exist in the digestive tract with genetic factors. No cases have been reported in which both of the above-mentioned diseases occurred simultaneously. We report a case of CD in a patient with TSC. A 12-year-old boy was brought to our hospital because of abdominal pain. Skin lesions were observed in the TSC. Fundus examination revealed a hamartoma in the right retina. Brain magnetic resonance imaging revealed a subendothelial giant cell astrocytoma (SEGA). On the basis of these findings, he was diagnosed as having TSC. Blood test results showed increased levels of inflammatory markers. On abdominal ultrasonography, his colon walls were observed to be thickened with increased vascularity of the proximal ascending colon, ileocecal valve, and terminal ileum. Colonoscopy revealed discontinuous ulcerations and inflammations of the ileum, IC valve, and cecum, similar to those found in CD. Everolimus was administered orally for the SEGA but was discontinued frequently owing to the exacerbation of CD. The possibility of CD should be kept in mind in patients with TSC considering to undergo treatment for SEGA.