• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.311-317
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• 2019

Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation ($IC_{50}$, ${\sim}1.42{\mu}M$). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-${\alpha}$ ($IC_{50}$, ${\sim}1.10{\mu}M$), and IL-6 ($IC_{50}$, ${\sim}1.24{\mu}M$). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, $PLC{\gamma}$, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.92-96
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• 2018

Chronic mucocutaneous candidiasis (CMC) is characterized by increased susceptibility to chronic and recurrent infections of the skin, mucous membranes, and nails by Candida species. It is a primary immunodeficiency disorder that is difficult to diagnose because of its heterogeneous clinical manifestations and genetic background. A 20-month-old boy who did not grow in height for 3 months was diagnosed as having hypothyroidism and he had hepatitis which was found at 5 years old. He presented with persistent oral thrush and vesicles on the body, the cause of which could not be identified from laboratory findings. No microorganism was detected in the throat culture; however, the oral thrush persisted. Immunological tests showed that immunoglobulin (Ig) subclass IgG and cluster of differentiation (CD)3, CD4, and CD8 levels were within normal limits. We prescribed oral levothyroxine and fluconazole mouth rinse. The patient was examined using diagnostic exome sequencing at the age of 6 years, and a c.1162A>G (p.K388E) STAT1 gene mutation was identified. A diagnosis of CMC based on the STAT1 gene mutation was, thus, made. At the age of 8 years, the boy developed a malar-like rash on his face. We conducted tests for detection of antinuclear antibodies and anti-dsDNA antibodies, which showed positive results; therefore, systemic lupus erythematosus (SLE) was also suspected. Whole exome sequencing is important to diagnose rare diseases in children. A STAT1 gene mutation should be suspected in patients with chronic fungal infections with a thyroid disease and/or SLE.

• Pediatric Infection and Vaccine
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• v.26 no.1
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• pp.71-79
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• 2019

Mycoplasma pneumoniae (MP) is the most common causative agent of community-acquired pneumonia in school-aged children. An 8-year-old boy who had been diagnosed with autism looked severely ill when he presented to our hospital due to dyspnea and lethargy. He had fever and cough 7 days prior to hospitalization. He had signs and symptoms of severe respiratory distress. The percutaneous oxygen saturation was 88% at high oxygen supply. Chest radiography showed diffusely increased opacity with moderate pleural effusion. He was intubated immediately and admitted to the intensive care unit. Under the clinical impression of mycoplasmal pneumonia, intravenous clarithromycin was started. Laboratory findings showed leukocytosis, hepatitis, decreased renal function, and presence of serum MP immunoglobulin (Ig) M (+) IgG (+) and sputum MP polymerase chain reaction (+). On hospital day 2, the patient developed multiple organ failure with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (ECMO) was performed with continuous renal replacement therapy (CRRT) and was weaned successfully. This is the first reported case of an ARDS due to MP infection complicated by multiple organ failure that was successfully treated with ECMO and CRRT in South Korea.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.827-837
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• 2019

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as $NF-{\kappa}B$ and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

• Fisheries and Aquatic Sciences
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• v.24 no.4
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• pp.153-162
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• 2021

In this study, a fish metabolic accelerator (a combination of butaphosphan and cyanocobalamin [BPC]) was injected into the muscle of the olive flounder, Paralichthys olivaceus, to investigate its effect on immunity and stress in fish maintained at low temperatures. A single dose of BPC was injected (100 mg/kg body weight) into the olive flounder, and its immunity and stress were observed after one and two weeks. Immunity tests revealed the presence of lysozyme (LZM), nitroblue tetrazolium (NBT), myeloperoxidase (MPO), anti-protease (AP), glutathione peroxidase (GPx), and total immunoglobulin (TIg). BPC injection was found to increase immunity activity compared to the control group. In particular, there was significantly high GPx activity. There was similarly high activity for MPO and GPx in the first week following the injection, followed by significant differences between the BPC-injected and control groups in the second week. There was a reduced low water-temperature stress response in the BPC-injected fish, as evidenced by the cortisol and glucose levels of the control and BPC groups. Lower levels were also observed in the BPC group than the control group during the second week. Cortisol levels were significantly lower in the BPC group than the control group. Histological examinations were conducted in the first and second weeks after the intramuscular injection of the recommended BPC dose to confirm the safety of BPC in aquaculture. There were no abnormalities observed in any tissue samples. This study confirms that the injection of BPC is safe even when used in a culture situation. BPC helps relieve stress and improves non-specific immune responses (innate immunity) in the olive flounder.

• Safety and Health at Work
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• v.12 no.1
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• pp.114-118
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• 2021

Background: Exposure to particulate matter (PM) emitted from vehicle exhaust might disrupt systemic function and elevate the risk of cardiovascular disease. In this study, we examined the changes of cardiometabolic biomarkers among vehicle inspectors exposed daily to PM0.25 and components. Methods: This cross-sectional study was conducted at two vehicle inspection centers, Pulogadung and Ujung Menteng, located in East Jakarta, Indonesia. The exposed respondents were 43 workers from vehicle inspection centers, and the unexposed group consisted of 22 staff officers working in the same locations. Vehicle exhaust particulate matter was measured for eight hours using a Leland Legacy personal pump attached to a Sioutas Cascade Impactor. The used filters were 25 and 37-mm quartz filters. The particulate matter concentration was analyzed using a gravimetric method, whereas trace elements were analyzed using energy dispersive X-ray fluorescence. An EEL Smoke Stain Reflectometer analyzed black carbon. Results: The personal exposure concentrations of PM0.25 were 10.4-fold higher than those in unexposed groups. Calcium and sulfur were the major components in the obtained dust, and their levels were 3.3- and 7.2-fold higher, respectively, in the exposed group. Based on an independent-samples t-test, high-density lipoprotein, triglyceride, HbA1c, total immunoglobulin E, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and nitric oxide levels were significantly different between the groups. Conclusions: In summary, it was suggested that PM0.25 exposure from vehicle exhaust might affect cardiometabolic biomarkers change.

• Journal of Veterinary Clinics
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• v.38 no.3
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• pp.120-126
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• 2021

Intradermal skin test (IDST) is generally considered a useful tool in identifying causal allergens in canine atopic dermatitis. Currently, multiple allergen simultaneous test (MAST), an in vitro testing method for allergen-specific immunoglobulin E, is being used as an alternative method. However, there are no reports comparing the IDST and MAST results in the same dogs. This study compared the results of both tests to evaluate the agreement and correlation between them. The sensitivity, specificity, and accuracy of the MAST were 76.2%, 64%, and 66.7%, respectively. Moderate positive predicted value (PPV, 50-75%) or high sensitivity (80-100%) were identified for indoor allergens, such as cat epithelia, house dust, and house dust mites. In contrast, high negative predicted value (NPV, 93.3-100%) and specificity (60-100%) were observed for environmental allergens and fungi. Although the agreement between IDST and MAST for all allergens was fair (κ = 0.301), that for each allergen was poor (κ < 0.01), except for birch (κ = 0.158). Spearman's rank correlation analysis revealed a low correlation between the MAST and IDST results (ρ = 0.308, p = 0.001). As compared to the IDST results, the MAST results did not identify the causative allergens sufficiently. IDST may not be performed for environmental allergens and fungi with high NPV and specificity if the MAST result is negative, but it may have to be performed for indoor allergens with moderate PPV and high sensitivity when the MAST result is positive.

• Pediatric Infection and Vaccine
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• v.27 no.3
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• pp.184-189
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• 2020

Lyme disease is a common vector-borne disease caused by Borrelia burgdorferi. Erythema migrans represents the most common manifestation during the early phase of this disease; however, systemic manifestations involving the nervous system, joints, or heart are known to occur. We report a case of Lyme disease accompanied by cardiac complications in a 13-year-old Korean male adolescent. The patient developed annular erythematous lesions on his lower extremities after a field trip during his visit to Connecticut, USA, for a boarding school camp, and his skin lesions were consistent with erythema migrans. Indirect immunofluorescence assay and Western blot analysis for Lyme immunoglobulin M showed positive results. Electrocardiography revealed a first-degree atrioventricular block, and he was diagnosed with Lyme carditis and received a 4-week course of oral doxycycline. Follow-up electrocardiography performed a week later revealed normal findings, and the patient showed an uneventful recovery. Lyme carditis often presents as an asymptomatic heart block that can progress to an advanced heart block; however, this condition is reversible with appropriate antibiotic treatment.

• Journal of the Korean Applied Science and Technology
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• v.39 no.1
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• pp.18-26
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• 2022

The present study aimed to evaluate the effect of Eucommia ulmoides extracts on rheumatoid arthritis biomarker in a CIA-induced DBA/1 mice. For evaluation, Eucommia ulmoides extracts was administered orally at dose of 100 mg/kg/day for 4 weeks after production of an animal model of rheumatoid arthritis and we confirmed the treatments' effects based on serum biomarker, radiological, structural parameter analysis. Compared to the negative control group, the Eucommia ulmoides extracts treatments significantly reduced the serum level of inflammation and immunoglobulin markers (i.e., TNF-α, IgG, and hs-CRP), and significantly decreased the monocyte count of white blood cells. Furthermore, the Eucommia ulmoides extracts treatments effectively preserved the joint destruction, and little the joint deformation. Moreover, compared to the negative control group, the Eucommia ulmoides extracts treatments increased the bone volume, and significantly decreased bone inflammation. The results indicate that the Eucommia ulmoides extracts improved rhrumatoid arthritis symptoms. Thus, the Eucommia ulmoides extracts may be a novel therapeutic option for the management of rheumatoid arthritis.

• Pediatric Infection and Vaccine
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• v.29 no.1
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• pp.54-60
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• 2022

Salmonella meningitis is rare yet poses causes significant neurological morbidity in children. Infants, especially those under 3 months of age, and those with immunocompromised states, such as malignancy, malaria, and human immunodeficiency virus infection, are at increased risk for developing Salmonella meningitis. Herein, we describe a case of Salmonella meningitis in a previous healthy 8-year-old girl who presented with high fever, vomiting, and altered mental status. Group D Salmonella species were isolated in cerebrospinal fluid culture, and no abnormal findings were noted in brain magnetic resonance imaging. Immunoglobulin levels and lymphocyte subset counts were within the normal ranges, and no genetic mutation responsible for primary immunodeficiency disease was detected by next-generation sequencing. The patient's condition improved rapidly with third-generation cephalosporin, and no complications or sequalae developed. Nontyphoidal Salmonella can cause meningitis in immunocompetent children and can be successfully treated with early administration of antibiotics.