• 대한한방내과학회지
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• 제38권4호
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• pp.468-478
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• 2017

Objectives: This study investigated the effects of Douchi Hataedock on Th2-skewed conditions to control allergic rhinitis. Methods: NC/Nga mice were divided into three groups: 10 mice were assigned to the control group (CTRL; no treatment), 10 mice to allergic rhinitis-induced (ARE) without treatment group, and 10 mice to the allergic rhinitis-induced (FGT) after Douchi Hataedock treatment group. The 3-week-old mice of the FGT group were given one 10 mg/kg dose of Douchi Hataedock extract and resensitized to allergic antigens at weeks four, five, and six. Allergic rhinitis was induced primarily in mice nasal cavities for five days after one week of final sensitization. The second induction used the same method one week after the first induction was completed. After one week, the nasal mucosal tissues of each group were observed. Immunohistochemical staining for IL-4, STAT6, CD40, $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, p-IkB, and iNOS in the nasal mucosa was also performed. Results: The FGT group had less respiratory epithelial damage and less mucin secretion in goblet cells than the ARE group and showed a 62% decrease in IL-4, 85% decrease in STAT6, 71% decrease in CD40, 69% decrease in $Fc{\varepsilon}RI$, 43% decrease in substance P, 49% decrease in MMP-9, 43% decrease in NF-kB p65, 38% decrease in p-IkB, and 73% decrease in iNOS compared to the ARE group. Conclusions: Douchi Hataedock lessens inflammation in epithelial and goblet cells and reduces inflammatory mediator secretion in a mouse allergic rhinitis model.

• IMMUNE NETWORK
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• 제8권3호
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• pp.90-97
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• 2008

Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

• 대한한방소아과학회지
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• 제32권2호
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• pp.1-10
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• 2018

Objectives This study investigated the effects of Hataedock treatment with Douchi on induction of allergic rhinitis in obese induced NC/Nga mice. Methods NC/Nga mice were divided into control group (Ctrl), allergic rhinitis induced obese mice group (ARE), and allergic rhinitis induced obese mice group with Douchi Hataedock treatment (FGT). The 3-week-old mice of the FGT group were given one 10 mg/kg dose of Douchi Hataedock extract and sensitized with allergic antigens at weeks 4, 5, and 6. After 1 week of final sensitization, allergic rhinitis was induced primarily in mice nasal cavities for five days. After one week of the completion with the first induction, the second induction was introduced by the same method. After 1 week, few samples of the nasal mucosal tissues of each group were prepared. The factor of Th2 differentiation and inflammation control such that IL-4, STAT6, CD40, $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, p-IkB, iNOS and COX-2 were observed by immunohistochemistry. Also, the difference in nasal mucosal injury was observed by histochemical method (PAS staining). Results The FGT group showed that reduced IL-4 production, STAT6 expression and CD40 expression by regulating excessive Th2 differentiation. Also, production of substance P and MMP-9 and activity of $Fc{\varepsilon}RI$ in mast cells were decreased. Inhibition of $NF-{\kappa}B$ p65 activity was induced by inhibition of p-IkB, and the production of inflammatory enzymes iNOS and COX-2 were decreased. In addition, the damage of intramural respiratory epithelium was low and excessive mucin secretion in goblet cells was low. Conclusions This study confirmed the possibility of controlling the allergic rhinitis in obese children who are expected to have an overactive inflammation.

• Toxicological Research
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• 제20권4호
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• pp.307-313
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• 2004

The present study was undertaken to investigate the effects of mistletoe (Viscum album var. coloratum) growing on Carpinus laxiflora BL. on proliferation and differentiation of HL-60 acute promyelocytic leukemia cells. Aqueous extract and its $(NH_2)_2SO_4$ saturated fractions of the mistletoe exhibited potent anti-proliferation activity against HL-60 cells. Moreover, when HL-60 cells were treated with 0~30% and 30～70% $(NH_2)_2SO_4$ saturated fractions of the mistletoe, HL-60 expressed CD 66b or CD 14 cell surface antigens and showed activity to reduce nitroblue tetrazolium, indicating that mistletoe induces the differentiation of HL-60 into granulocytes or monocytes. To understand how mistletoe induces the differentiation, we investigated the expression of molecules for modulating the proliferation and differentiation of leukemia cells, such as c-Myc and myeloblastin. The 0~30% $(NH_2)_2SO_4$ saturated fraction of the mistletoe reduced the mRNA levels of c-Myc and myeloblastin in a time-dependent manner. The results indicate that the mistletoe induces the differentiation of HL-60 cells via the decrease of c-Myc and myeloblastin expressions. Thus, it is suggested that mistletoe has a therapeutic potential for the treatment of acute promyelocytic leukemia.

• 대한이식학회지
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• 제32권4호
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• pp.108-112
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• 2018

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.

• Journal of Microbiology and Biotechnology
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• 제29권3호
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• pp.489-499
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• 2019

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCNs to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic $CD8^+$ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and $CD8^+$ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권5호
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• pp.387-395
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• 2022

Purpose: Toxins produced by Clostridioides difficile infection (CDI) can cause enteritis and diarrhea. Although the number of pediatric CDI cases is increasing, the clinical management of pediatric CDI, including patient characteristics and prognosis, remains unclear. This study aimed to elucidate the background and clinical course of patients with CDI and evaluate the reliability of diagnostic tests in a tertiary pediatric hospital in Japan. Methods: We retrospectively analyzed the clinical data of children diagnosed with CDI between 2011 and 2021 at the Saitama Children's Medical Center in Saitama, Japan. Results: During the study period, 1,252 C. difficile antigen/toxin tests were performed, and 37 patients were diagnosed with CDI. The main underlying diseases among the patients were hematological and malignant disorders and gastrointestinal diseases, including inflammatory bowel disease (IBD) (59.4%). Two patients (5.4%) had an unremarkable medical history. Among the 37 patients, 27 (73.0%) were immunocompromised, 25 (67.6%) had a history of antibiotic use within the past two months, and 6 (16.2%) were negative on the initial test but were positive on the second test. Finally, 28 patients (75.7%) required primary antibiotic therapy only, and two patients with IBD required additional antibiotic therapy as secondary treatment. Conclusion: The number of pediatric patients with CDI is increasing. Both a comprehensive interview, including underlying diseases and history of antibiotic use, and an understanding of the features of clinical examinations should be emphasized to appropriately diagnose and treat CDI.

• Korean Circulation Journal
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• 제53권6호
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• pp.351-366
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• 2023

Along with the development of immunosuppressive drugs, major advances on xenotransplantation were achieved by understanding the immunobiology of xenograft rejection. Most importantly, three predominant carbohydrate antigens on porcine endothelial cells were key elements provoking hyperacute rejection: α1,3-galactose, SDa blood group antigen, and N-glycolylneuraminic acid. Preformed antibodies binding to the porcine major xenoantigen causes complement activation and endothelial cell activation, leading to xenograft injury and intravascular thrombosis. Recent advances in genetic engineering enabled knock-outs of these major xenoantigens, thus producing xenografts with less hyperacute rejection rates. Another milestone in the history of xenotransplantation was the development of co-stimulation blockaded strategy. Unlike allotransplantation, xenotransplantation requires blockade of CD40-CD40L pathway to prevent T-cell dependent B-cell activation and antibody production. In 2010s, advanced genetic engineering of xenograft by inducing the expression of multiple human transgenes became available. So-called 'multi-gene' xenografts expressing human transgenes such as thrombomodulin and endothelial protein C receptor were introduced, which resulted in the reduction of thrombotic events and improvement of xenograft survival. Still, there are many limitations to clinical translation of cardiac xenotransplantation. Along with technical challenges, zoonotic infection and physiological discordances are major obstacles. Social barriers including healthcare costs also need to be addressed. Although there are several remaining obstacles to overcome, xenotransplantation would surely become the novel option for millions of patients with end-stage heart failure who have limited options to traditional therapeutics.

• IMMUNE NETWORK
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• 제16권1호
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• pp.61-74
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• 2016

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24⁺ cDC1 cells compared to in pDCs and CD172α⁺ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s).

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2006년도 춘계학술대회
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• pp.3-12
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• 2006

1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.