• 한국균학회소식:학술대회논문집
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• 2014.10a
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• pp.15-15
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• 2014

Fusarium graminearum (teleomorph Gibberella zeae) is an important plant pathogen that causes head blight of major cereal crops such as wheat, barley, and rice, as well as causing ear and stalk rot on maize worldwide. Plant diseases caused by this fungus lead to severe yield losses and accumulation of harmful mycotoxins in infected cereals [1]. Fungi utilize spore production as a mean to rapidly avoid unfavorable environmental conditions and to amplify their population. Spores are produced sexually and asexually and their production is precisely controlled. Upstream developmental activators consist of fluffy genes have been known to orchestrate early induction of condiogenesis in a model filamentous fungus Aspergillus nidulans. To understand the molecular mechanisms underlying conidiogenesis in F. graminearum, we characterized functions of the F. graminearum fluffy gene homologs [2]. We found that FlbD is conserved regulatory function for conidiogenesis in both A. nidulans and F. graminearum among five fluffy gene homologs. flbD deletion abolished conidia and perithecia production, suggesting that FlbD have global roles in hyphal differentiation processes in F. graminearum. We further identified and functionally characterized the ortholog of AbaA, which is involved in differentiation from vegetative hyphae to conidia and known to be absent in F. graminearum [3]. Deletion of abaA did not affect vegetative growth, sexual development, or virulence, but conidium production was completely abolished and thin hyphae grew from abnormally shaped phialides in abaA deletion mutants. Overexpression of abaA resulted in pleiotropic defects such as impaired sexual and asexual development, retarded conidium germination, and reduced trichothecene production. AbaA localized to the nuclei of phialides and terminal cells of mature conidia. Successful interspecies complementation using A. nidulans AbaA and the conserved AbaA-WetA pathway demonstrated that the molecular mechanisms responsible for AbaA activity are conserved in F. graminearum as they are in A. nidulans. F. graminearum ortholog of Aspergillus nidulans wetA has been shown to be involved in conidiogenesis and conidium maturation [4]. Deletion of F. graminearum wetA did not alter mycelial growth, sexual development, or virulence, but the wetA deletion mutants produced longer conidia with fewer septa, and the conidia were sensitive to acute stresses, such as oxidative stress and heat stress. Furthermore, the survival rate of aged conidia from the F. graminearum wetA deletion mutants was reduced. The wetA deletion resulted in vigorous generation of single-celled conidia through autophagy-dependent microcycle conidiation, indicating that WetA functions to maintain conidia dormancy by suppressing microcycle conidiation in F. graminearum. In A. nidulans, FlbB physically interacts with FlbD and FlbE, and the resulting FlbB/FlbE and FlbB/FlbD complexes induce the expression of flbD and brlA, respectively. BrlA is an activator of the AbaA-WetA pathway. AbaA and WetA are required for phialide formation and conidia maturation, respectively [5]. In F. graminearum, the AbaA-WetA pathway is similar to that of A. nidulans, except a brlA ortholog does not exist. Amongst the fluffy genes, only fgflbD has a conserved role for regulation of the AbaA-WetA pathway.

• Journal of Haehwa Medicine
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• v.13 no.2
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• pp.277-287
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• 2004

I have come to next conclusions in consequence of documentary study about medical books of many generations regarding venesection therapy. 1. Venesection therapy is much used for five sensory organ disease. Besides that internal disease, pain paralysis disease of muscle and joints, sugical disease, disease of woman and children, fever sunstroke CVA emergency case follow that in the order of frequency of use. 2. It is used for swollen tongue, eye pain, pharyngitis, swelling and pain in the throat, bleeding from the eye ear nose mouth or subcutaneous tissue, tonsillitis, aphthae and so on in the five sensory organ disease. Focus, sosang, jinjin yuye, taiyang, baihui are used for five sensory organ disease in the order of frequency of use. 3. It is used for malaria, headache, precordial pain, head-wind, abdominal colic, diseases characterized by acute diarrhea and vomiting, and so on in the Internal disease. Superficial venules and lymph vessesls, taiyang, quze are used for Internal disease in the order of frequency of use. 4. It is used for low back pain, hypochondriac pain, numbness, knee pain, tinea pedis, red swelling pain of hand and arm, flaccidity-syndrome, and so on in the pain paralysis disease of muscle and joints. Weizhong, superficial venules and lymph vessesls, Ashi point, zhigou are used for pain paralysis disease of muscle and joints in the order of frequency of use. 5. It is used for furuncle, tinea capitis, and so on in the sugical disease. Focus, weizhong are used for sugical disease in the order of frequency of use. 6. It is used for inflammatory disease with redness of skin, and so on in the disease of woman and children. Focus, weizhong, yanglingquan, yaoshu, sanyinjiao are used for disease of woman and children in the order of frequency of use. 7. It is used for fever, CVA, sunstroke, cadaverous coma, common cold, and so on in the fever sunstroke CVA emergency case. Sosang, weizhong, chize are used for fever sunstroke CVA emergency case in the order of frequency of use. 8. The urinary bladder channel of foot-taiyang is most used. Next there are the du channel, the stomach channel of foot-yangming, the lung channel of hand-taiyin, the gall baldder channel of foot-shaoyang, the triple-warmer channel of hand-shaoyang, the large intestine channel of hand-yangming, the spleen channel of foot-taiyin, the kidney channel of foot-shaoyin the pericardium channel of hand-jueyin the liver channel of foot-jueyin, the ren channel, the heart channel of hand-shaoyin, the small intestine channel of hand-taiyang in the order of frequency in use. 9. Superficial venules and lymph vessesls, focus, five shu points, extra-point, back point are used in the venesection therapy, those are characteristic of locating an acupuncture point.

• Advances in Traditional Medicine
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• v.9 no.2
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• pp.115-127
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• 2009

Samsoeum (SSE) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the SSE is still not fully understood. The aim of the present study is to elucidate whether and how SSE modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that SSE significantly decreased compound 48/80-induced systemic anaphylaxis, ear-swelling response, histamine release from preparation of rat peritoneal mast cells and anti-dinitropheny IgE-induced passive cutaneous reaction. Also, SSE inhibited the expression of inflammatory cytokine and cyclooxygenase-2 in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of SSE is through suppression of nuclear factor-${\kappa}B$ activation and $I{\kappa}B-{\alpha}$ phosphorylation/degradation in HMC-1. These results provided new insight into the pharmacological actions of SSE as a potential molecule for therapy of inflammatory allergic diseases.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.437-442
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• 2020

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.35 no.2
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• pp.95-104
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• 2022

Objectives : This study is to report a case of otitis media with effusion accompanied by atopic dermatitis improved by Korean medicine monotherapy. Methods : A 31-year-old woman patient visited our clinic for aural fullness, hearing loss, and tinnitus of the left ear on August 14th, 2021. She also had abdominal pain, diarrhea, and general weakness because of side effects of antibiotics. Besides, she had nasal congestion, rhinorrhea, and dry skin. Through otoscopy, her tympanum was fully filled with yellow effusion. She only took Korean medicine therapy including acupuncture and herbal medicine weekly. The treatment continued for about 4 months(total 14 visits) until December 4th, 2021. Otoscopy, numerical rating scale(NRS), scoring atopic dermatitis(SCORAD) index were used to assess the symptoms. Results : On August 30, 2021, her intestinal symptoms improved. The left tympanum was recovered to normal condition as the treatment continued. The effusion disappeared on October 16th, 2021. On November 6th, 2021, peritympanic blood congestion also almost alleviated. Subjective symptoms including aural fullness, hearing loss, and tinnitus disappeared on October 16, 2021. Nasal symptoms and dry skin also improved. The SCORAD index dropped from 15 to 4. Conclusions : These results suggests that otitis media with effusion can be sufficiently managed by Korean medicine therapy. Further, active application of Korean medicine therapy to common otolaryngological diseases is necessary.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.4
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• pp.292-297
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• 2022

Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.