• Hanyang Medical Reviews
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• v.33 no.1
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Korean Circulation Journal
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• v.54 no.6
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• pp.295-310
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• 2024

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has led to a global health crisis with substantial mortality and morbidity. To combat the COVID-19 pandemic, various vaccines have been developed, but unexpected serious adverse events including vaccine-induced thrombotic thrombocytopenia, carditis, and thromboembolic events have been reported and became a huddle for COVID-19 vaccination. Vaccine-related myocarditis (VRM) is a rare but significant adverse event associated primarily with mRNA vaccines. This review explores the incidence, risk factors, clinical presentation, pathogenesis, management strategies, and outcomes associated with VRM. The incidence of VRM is notably higher in male adolescents and young adults, especially after the second dose of mRNA vaccines. The pathogenesis appears to involve an immune-mediated process, but the precise mechanism remains mostly unknown so far. Most studies have suggested that VRM is mild and self-limiting, and responds well to conventional treatment. However, a recent nationwide study in Korea warns that severe cases, including fulminant myocarditis or death, are not uncommon in patients with COVID-19 VRM. The long-term cardiovascular consequences of VRM have not been well understood and warrant further investigation. This review also briefly addresses the critical balance between the substantial benefits of COVID-19 vaccination and the rare risks of VRM in the coming endemic era. It emphasizes the need for continued surveillance, research to understand the underlying mechanisms, and strategies to mitigate risk. Filling these knowledge gaps would be vital to refining vaccination recommendations and improving patient care in the evolving COVID-19 pandemic landscape.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.654-658
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• 2002

Purpose : Endocrine and immune systems are connected and interdependent. Adrenal glands play an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. These steroids have an antagonistic effect on the T cell progression into Th1 and Th2 cells and on the induction of correlated interleukins. Therefore we evaluated the role of adrenal androgen and cortisol as immune modulators in Kawasaki disease( KD) with changes of T cell immunity. Methods : From April to August in 2001, we examined serum DHEAS and 24 hour urine free cortisol(F) before administration of immunoglobulin and steroids by radioimmunoassay in 14 KD patients. It's clinical severity was determined by Harada score and coronary lesion. Results : The age of the patient group ranged from 4 months to 4 years; its average age was 2.3 years. Three patients(21.4%) were below 1 year, 2(14.3%) between 1 and 2 years, 5(35.7%) between 2 and 3 years, 4(28.6%) between 3 and 4 years of age. Male to female ratio was 1:1.3. DHEAS was significantly decreased in patients($11.1{\pm}6.0{\mu}g/dL$) more than controls($81.6{\pm}13.3{\mu}g/dL$)(P<0.05). Twenty-four hour urine free cortisol was significantly increased in patients($36.9{\pm}21.9{\mu}g/dL$) more than controls($13.6{\pm}5.5{\mu}g/dL$)(P<0.05). Ratio of DHEAS/F was decreased remarkably in patients($0.33{\pm}0.20$) more than controls($6.65{\pm}2.56$)(P=0.016). There was no difference between ratio of DHEAS/F and Harada score, but its ratio was very low in patients with coronary aneurysm. Conclusion : These data demonstrate that there are changes of DHEAS and cortisol in acute stage of KD and the dis-equilibrium between two steroids may be relevant in the T cell immune response induction of Kawasaki disease. These changes support the use of DHEAS/F ratio as one of the predictive factors of coronary arteries complication.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.1
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• pp.11-19
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• 2018

The gut microbiome has been studied extensively over the past decade with most scientific reports focused on the adverse role of the gut microbiome on gastrointestinal diseases. For example, the altered gut microbiome exacerbates the development of immune system-mediated damage in many diseases. The most studied pathologies include irritable bowel syndrome, inflammatory bowel diseases, and colitis-associated cancer. On the other hand, intestinal microflora is also beneficial and contributes to the intestinal physiology by the synthesis of vitamins, production of short chain fatty acids and bile acid metabolism, thereby maintaining gut homeostasis. Therefore, the balance between commensal and pathogenic bacteria populations influences mainly the maintenance of intestinal health. Changes in the intestinal microflora have been suspected to be the underlying causes of multiple diseases. Despite the immense amount of published data, the optimal gut microbiome composition is still controversial. This review briefly outlines the connection between the gut microbiome and critical gastrointestinal diseases focusing on three prominent intestinal disorders: irritable bowel syndrome, inflammatory bowel diseases, and colitis-associated cancer disorders. Finally, intervention strategies using natural products for the alleviation of these diseases and the maintenance of a health gut microbiome are suggested.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.1-17
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• 1999

Large bowel cancer shows the 4-5th frequency in cancers that occurs in Korea. The western medicine cures the Large bowel cancer by radiation, surgery and chemotherapy. While, Oriental medicine cures the Large bowel cancer by Herb-drugs, acupuncture, moxa and et al. With just one way of treating Large bowel cancer can't be effective remedy. Because each medicine has a strength and weakness, it is effective treatment when two medicine combines and supplement each other. We got the following result about a trend of oriental and western combination treatment for Large bowel cancer through studding records. 1. In Large bowel cancer, colon cancer is referred hematochezia(腸風下血), rectal cancer is refereed enterotoxin(腸毒), and anal cancer is accumulation of pathogens in yin(結陰). 2. The western medicine treats Large bowel cancer patient with surgery first. They need on assembly treatment such as chemical, radiation and immune treatment. In oriental medicine, they treats Large bowel cancer patients with differentiation of symptom and signs and treatment(辨證施治) for example, insufficiency of spleen and stomach(脾胃虛弱), collapse of the spleen-ql(脾氣下陷), stagnation of blood stasis and toxic agent(瘀毒內結), reinforcing both qi and blood(脾血下陷), stagnation of damp-phlegm(痰濕凝結) and cure for them by acupuncture and moxa too. 3. In combination with oriental and western medical treatment princple of Large bowel cancer by each stage is as follows. First stage is cured with radical surgery and herb-drugs without chemotherapy. The intermediate and terminal stage patients is used radiation before surgery, or after palliative surgery cour with chemotherapy, radiation and Herb-drugs. In terminal stage patients, unable for surgery, is used combination between chemotherapy, palliative radiation and Herb-drugs. 4. After radiation surgery, the terminal stage patients who have extensively lymph node metastasis or local contraindication is able to undergo combination of Herb-durgs and chemotherapy. 5. The cure-effect with oriental and western medicine combination treatment was better than that just with oriental or western medical treatment. 6. The merits of oriental and western medicine combination treatment lengthen one's life and diminish the bad effect of chemotherapy and complete radiation treatment, prevent from relapsing, maintain the balance in their environment of body and improve immunity.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.12
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• pp.1657-1667
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• 2010

Direct-fed microbials (DFM) are dietary supplements that inhibit gastrointestinal infection and provide optimally regulated microbial environments in the digestive tract. As the use of antibiotics in ruminant feeds has been banned, DFM have been emphasized as antimicrobial replacements. Microorganisms that are used in DFM for ruminants may be classified as lactic acid producing bacteria (LAB), lactic acid utilizing bacteria (LUB), or other microorganisms including species of Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, Bacillus and Propionibacterium, strains of Megasphaera elsdenii and Prevotella bryantii and yeast products containing Saccharomyces and Aspergillus. LAB may have beneficial effects in the intestinal tract and rumen. Both LAB and LUB potentially moderate rumen conditions and improve feed efficiency. Yeast DFM may reduce harmful oxygen, prevent excess lactate production, increase feed digestibility, and improve fermentation in the rumen. DFM may also compete with and inhibit the growth of pathogens, stimulate immune function, and modulate microbial balance in the gastrointestinal tract. LAB may regulate the incidence of diarrhea, and improve weight gain and feed efficiency. LUB improved weight gain in calves. DFM has been reported to improve dry matter intake, milk yield, fat corrected milk yield and milk fat content in mature animals. However, contradictory reports about the effects of DFM, dosages, feeding times and frequencies, strains of DFM, and effects on different animal conditions are available. Cultivation and preparation of ready-to-use strict anaerobes as DFM may be cost-prohibitive, and dosing methods, such as drenching, that are required for anaerobic DFM are unlikely to be acceptable as general on-farm practice. Aero-tolerant rumen microorganisms are limited to only few species, although the potential isolation and utilization of aero-tolerant ruminal strains as DFM has been reported. Spore forming bacteria are characterized by convenience of preparation and effectiveness of DFM delivery to target organs and therefore have been proposed as DFM strains. Recent studies have supported the positive effects of DFM on ruminant performance.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.100-116
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• 1996

Gastric cancer shows the most high friquency in cancers that occurs in Korea. The western medicine treatment for gastric cancer has radiation and surgery, chemical treatment. While, oriental medicine cures the gastric cancer by herb-drugs, acupunture , moxa and srigma. With just one way of treating gastric cancer can't be effective remedy. Because each medicine has a strength and weakness. Thus, it is effective treatment when two medicine combins and supplement each other. We got the following result about a trend of oriental and westernal combination treatment for gastric cancer through studing records. 1. The western medicine treats gastric cancer patient with surgery first and right after surgery. They need on assembly treatent such as chemical and immune treatment. In oriental medicine, they treats gastric cancer patients with differentiation of symptone and signs and treatment(辨證施治)[for example:incoordination between liver and stomach(肝胃不和), insufficiency of spleen and stomach(脾胃虛弱), stagnation of blood stasis and toxic agent(瘀毒內阻), deficiency of yin by stomach heat(胃熱傷陰), reinforcing both qi and blood(氣血雙虧), stagnation of damp-phlegm(痰濕凝結)] and cure for them by acupuncture and stigma, too. 2. In combination with oriental and western medical treatment principle of gastric cancer by each stage is as follows. First stage and second stage gastric cancer is cured with radical surgery mainly. After operation, the herb of invigoration of the spleen(健脾), coordination of the stomach(和胃), and smoothing the liver and regurating the circulation of qi(疏肝理氣), is used for good gastroenteric condition. The second stage patients can be concidered using in combination with chimical treatment. The third stage gastric cancer is treated with radical surgery or with temporizing surgery. After those surgery, herb-drugs treatment is used jointly. The fourth stage patients who have no extensively metastasis or local contraindication can undergo temporizing and curcuit surgical operation. Herb-drugs and chemical treatments are used together for patients after operating. If he has operating contraindication, he would be treated with herb-drugs and chemical treatment. 3. In case of using in combination with oriental and western medical treatment as follows. As for herb-drugs with chemical treatment, reinforcing both qi and blood(補益氣血), invigorate the spleen and the stomach(健脾和胃), reinforcing liver and kidney(滋補脾腎), clear out the heat and relieve the toxic agent(淸熱解毒), can be used and with radiation treatment, clear out the heat and relieve the toxic agent(淸熱解毒), promoting the production body fluid and moisturizing the vicera(生津潤燥), reinforcing both qi and blood(補益氣血), invigorate the spleen and the stomach (健脾和胃), reinforcing liver and kidney(滋補肝腎) etc, can be used. 4. According to the research of oriental and western medical combination treatment are the 5-year-survival degree with oriental and western medicine combination treatment was for better than that just with oriental or western medical treatment. Especially, it has good effect on the third, fourth stage gastric cancer. That is, the middle and the end of stage gastric cancer. 5. The merits of oriental and western medicine combination treatment are lengthers one's life and diminish the bad effect of chemical treatment and radiation treatment be near completion, prevent from relapsing, maintain the balance in their eveirenment of body and improve immunity.

• Journal of Life Science
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• v.23 no.10
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• pp.1216-1222
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• 2013

NK cells are lymphoid immune cells that participate in innate immunity to protect against foreign pathogens and transforming cells. It is known that the activity of NK cells is regulated by a balance between activating and inhibitory signals rather than specific antigens. One important activating signal is mediated by the NKG2D receptor, which recognizes NKG2D ligands on cancer cells. Therefore, tumor cells that express sufficient amounts of NKG2D ligands could be eliminated by NKD2D+ cells, including NK cells. Oncogenes drive tumor cells to apoptosis resistant and uncontrolled proliferation by altered expression of many critical genes. Therefore, the expression of NKG2D ligands may be affected by oncogenes. This study focused on increasing the susceptibility of cancer cells to NK cells by regulating the expression of NKG2D ligands influenced by three oncogenes: k-ras, wnt, and c-myc. We demonstrated that inhibition of k-ras and c-myc increased the expression of NKG2D ligands and enhanced the susceptibility of cancer cells to NK cells. On the contrary, inhibition of the wnt pathway decreased MICA and ULBP1 transcripts. Although the decreased transcription of NKG2D ligands by inhibition of the wnt pathway, surface proteins of NKG2D ligands were not changed, and the susceptibility of HCT-116 cells was unaffected. The results demonstrate that the transcription of NKG2D ligands are regulated deferentially by the k-ras, c-myc, and wnt pathways and that the cytotoxicity of NK cells solely depends on the amount of surface NKG2D ligands.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.13-25
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• 1999

Background: Ineffective cell-mediated immune response in human tuberculosis is associated with a depressed Thl cytokine response and reduced production of IFN-$\gamma$. Most persons infected with Mycobacterium tuberculosis are healthy tuberculin reactors with protective immunity, but a minority with ineffective immunity develop extensive pulmonary tuberculosis. The cell-mediated immune response is an important aspect of host resistance to mycobacterial infection and is believed to be tightly regulated by a balance between Th1 cytokines including IFN-$\gamma$, IL-12, IL-18, regulated on activation, normal T cell expressed and secreted (RANTES) and Th2 counterparts such as IL-4, monocyte chemoattractant protein-l (MCP-l). Methods: Proliferation and mRNA expression of IFN-$\gamma$, RANTES and MCP-l by RT-PCR in peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with mycobacterial antigens were compared in pulmonary tuberculosis patients with cured and treatment failure and in tuberculin-positive and tuberculin-negative healthy subjects. Results: Defective proliferative responsiveness to aqueous TSP antigen was involved with treatment failure tuberculosis patients. Aqueous TSP antigen-induced IFN-$\gamma$ and RANTES mRNA expression was decreased in treatment failure tuberculosis patients compared with healthy tuberculin reactors and cured tuberculosis patients (23.1 % versus 90.0% for IFN-$\gamma$ and 46.2% versus 70.0% versus 46.2% for RANTES). The frequency of MCP-l mRNA expression to aqueous TSP antigen in treatment failure tuberculosis patients was greater than in healthy tuberculin reactors and cured tuberculosis patients (76.9% versus 40.0%). Conclusion: The increasing expression of MCP-1 mRNA in response to aqueous TSP antigen might be predicted to favor Th1 responses and restricted Th1 responses in treatment failure of pulmonary tuberculosis.