• The Journal of Korean Medicine
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• v.29 no.1
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• pp.179-191
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• 2008

Background and Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus,and has increased in Korea. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently skin barrier dysfunction and hyperresponsive Th2 cells in the acute phase have been reported as important mechanisms. Cheonggi-san(CGS) is used in oriental clinics for treatingacute skin lesions of eczema or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic effects of its internaluse on atopic dermatitis-like skin lesions, induced in NC/Nga mice by the mite antigen D. pteronyssinus and disrupting skin barrier. Materials and Methods : The NC/Nga mice were classified into three groups: control group, atopic dermatitis elicitated group(AD), and CGS treated group (CT). Atopic dermatitis-like skin lesions were induced on the back of female NC/Nga mice, 12 weeks of age, by tape stripping, 5% SDS applied to disrupt skin barrier and painting 3 times a week with D. pteronyssinus crude extract solution for 3 weeks. CT was treated with CGS orally after atopic dermatitis was elicitated. We observed changes of skin damage, mast cells, substance P, angiogenesis, skin barrier, Th2 cell differentiation, nuclear factor-${\kappa}B(NF-{\kappa}B)$ p65 activation and COX-2 in NC/Nga mice with atopic dermatitis-like skin lesions. Results : The skin damages as eczema were seenin AD, but mitigated in CT. The degranulated mast cells in dermal papillae increased in AD, but decreased in CT. The substance P positive reacted cells in CT remarkably decreased. The angiogenesis increased in AD, but decreased in CT. The decrease of lipid deposition and ceramide in AD was seen, but anincrease of lipid deposition and ceramide in CT was seen. The distribution of IL-4 positive reacted cells in dermal papillae increased in AD, but decreased in CT. The distribution of NF-${\kappa}B$ p65 positive reacted cells & COX-2 positive reacted cells in CT decreased. Conclusion : The results may suggest that the CGS per os decreases the dysfunction of the skin barrier, inhibits Th2 cell differentiation and inhibits NF-${\kappa}B$ p65 activation in NC/Nga mice with atopic dermatitis-like skin lesions.

• Journal of Life Science
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• v.24 no.5
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• pp.588-593
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• 2014

Tumor angiogenesis is important in tumorigenesis and therapeutic interventions in cancer. To know inhibitor and effector of tumor angiogenesis in cancer, the specific gene of tumor and angiogenesis may develop the mechanisms of cancer suppression and therapy. Recently, we described the role of RalA-binding protein 1 (RLIP76) in tumor angiogenesis. Tumor vascular volumes were diminished, and vessels were fewer in number, shorter, and narrower in RLIP76 knockout mice than in wild-type mice. Moreover, angiogenesis in basement membrane matrix plugs was blunted in the knockout mice in the absence of tumor cells, with endothelial cells isolated from the lungs of these animals exhibiting defects in migration, proliferation, and cord formation in vitro. RLIP76 is expressed in most human tissues and is overexpressed in many tumor types. In addition, the protein regulates tumorigenesis and angiogenesis in vivo and in vitro. As the export of chemotherapy agents is a prominent cellular function of RLIP76, it is a major factor in mechanisms of drug resistance. Moreover, RLIP76 acts as a selective effector of the small GTPase, R-Ras, and regulates R-Ras signaling, leading to cell spreading and migration. Furthermore, in skin carcinogenesis, RLIP76 knockout mice are resistant, with tumors that form showing diminished angiogenesis. Thus, RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.

• Environmental Mutagens and Carcinogens
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• v.25 no.1
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• pp.40-46
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic compound and tumor promoter. In our experiment, we investigated the effects of TCDD on gene expression in mouse skin carcinogenesis. We used cDNA microarray to detect the differential gene expression in tumors induced in hairless mouse skin by MNNG plus TCDD protocol. We found that erb-2, c-ets2 and p27$^{kip1}$ were significantly up-regulated, but TNFR2, AKT-l, integrin $\beta$l, maspin, IGF-l, c-raf-l, Rb were significantly down-regulated, in tumor region, respectively. We also found that the expression of 53 genes involved in cen cycle, signal transduction, apoptosis, adhesion molecule, angiogenesis, and invasion, were changed two fold more, in tumor surrounding region. These data suggest that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis in mouse skin carcinogenesis.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.477-490
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• 2014

Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen species and other components of plasma. The outcome of first clinical trials regarding wound healing is pointed out.

• Journal of Environmental Science International
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• v.17 no.7
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• pp.809-816
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• 2008

The oriental ore minerals, which mainly consisted of talc, actinolite, sericite, and halloysite were developed, and then used to examine the healing effect on the skin wound in rats. Full-thickness square wounds were formed on the backs of rats after the hairs on the dorsal surface were shaved. The ore minerals were applied to examine the healing effect from day 0 to 15 after wounding. Notable wound healings in terms of congestion around the wound, wound contraction and epithelialization were found in ore mineral-treated groups. Moreover, microscopic results revealed the formation of epithelial layer, hair follicles and progressive angiogenesis in ore mineral-treated groups, while complete epithelial layer could not be found in the control. These results suggest that ore minerals from Korean indigenous ores may have wound healing effect on the skin injury in rats.

• Archives of Plastic Surgery
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• v.42 no.1
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• pp.11-19
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• 2015

Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.130-144
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• 2007

UV-irradiated skin shows acutely erythema, edema, pigmantation (sunbum) and chronically coarse wrinkling, roughness, dryness, laxity (photoaging). Jawoongo(紫雲膏, JW) is clinically useful external application and effective bum, sunburn, wound and symptom of dryness(燥症) in skin disease. In this experiment, we examined if JW could cure the UVB-mediated acute skin damages, inhibit UVB-mediated oxidative stress and inflammation of skin, and block the photoaging. In vivo test, we found that JW could effectively cure the UVB-mediated acute skin damages(erythema, edema, angiogenesis, hyperplasia, infiltration of lymphocytes) and inhibit expression of HSP70, CYP1A1 and p53. We also found that JW could repair destruction of collagen fiber and inhibit activation of MMP-9, and inhibit expression of $NF-{\kappa}B$ p65, iNOS, hyperplasia of keratynocyte. In vitro test, we found that JW could inhibit expression of IKK, iNOS mRNA, and production of NO. These findings shows that JW could cure the UVB-mediated acute skin damages, inhibit UVB-mediated oxidative stress and inflammation of skin, and block photoaging.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.227-244
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• 2011

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of miRNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

• The Journal of Korean Physical Therapy
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• v.15 no.3
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• pp.16-44
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• 2003

Skeletal muscle regeneration is a vital process for various muscle myopathies and muscular adaptation to physiological overload. Angiogenesis is the key event in the process of muscle regeneration, and vascular endothelial growth factor(VEGF) plays an important role in it. The purpose of this study was to evaluate the effect of GaAlAs(830nm) laser and immunoreactivity of VEGF on angiogenesis after muscle contusion injury. Muscle contusion injury was induced in the triceps surae muscle by dropping a metal bead(31.4g). GaAlAs laser irradiation(power 20 mW, frequency 2000 Hz, treatment time 15 min) was applied directly to the skin of injured muscle daily for seven days. The experimental group I was irradiated immediately by laser after injury, whereas the experimental group II was irradiated after 1 day of injury. The control group was non-irradiated. The results of this study were as follows. 1. In morphological observation, there were no significant changes in experimental and control groups for 7 days. At 3 days, however, the splited muscle fibers were observed in experimental groups, and the muscle atrophy and granular tissue viewed at 7 days in control group. 2. The VEGF was expressed in muscle fiber that located in the interspace between gastrocnemius and soleus muscles. As the time coursed, the immunoreactivity of VEGF also seemed to be strong in the individual muscle fibers. 3. The experimental group I & II showed higher immunoreactivity of VEGF than control group(p<0.05). Then, the experimental group I showed higher than group II especially(p<0.05). These data suggest GaAlAs semiconduct diode laser irradiation(830nm) enhanced angiogenesis in the skeletal muscle induced contusion injury, and immediate laser irradiation after injury promoted the angiogenesis greatly than after 1 day of injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.887-893
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• 2011

The purpose of this study was to investigate the wound healing effects of Danggwieumja (DG), which is commonly used for skin inflammation, skin wound, skin pruritus, and chronic hives etc. The 1.5 cm ${\times}$ 1.5 cm full-thickness skin wound was induced to two groups, DG (n=16) and Saline (n=16) group. The DG extract and Saline were orally administrated daily for 15 days after skin wound induction. Then, the body weight of rats and the congestion indices were daily measured for 15 days after skin wound induction. The wound contractions and epithelizations were also measured. The wound contractions were daily measured for 15 days after wound induction and wound epithelizations were measured for 8 days from day 7 after wound induction. For evaluating angiogenesis, the immunoreactivities of vWF and VEGF protein were measured immunohistochemistrically on day 15. In results, although the percentage increases in mean body weight of rats in the DG and Saline groups hve no significant differences, DG extract decreased the time of wound healing and congestion around wound, and improved wound contraction and epithelization. The contraction percentage of DG group was significantly increased on day 5 (P<0.05) and day 7 (P<0.01) than that of Saline group. DG group showed significant increase of wound epithelization on day 7 (P<0.05) as compared to Saline group. Moreover, DG extract reduced the inflammation of skin dermis and promoted the growth of vascular vessels of dermis by accelerating vascular endothelial growth factor (VEGF) protein. These results suggest that DG has the beneficial effects on skin incision wound and can be the suitable wound healing agent for various surgical wounds.