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1.  Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands 
Annals of Dermatology  2015;27(4):364-370.
Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin.
To evaluate the basic physiological role of PAR-2 in skin.
We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes.
Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker.
Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.
PMCID: PMC4530143  PMID: 26273149
Eccrine sweat glands; Epidermis; Keratinocytes; Terminal differentiation
2.  Meta-Analysis of Associations Between the Peroxisome Proliferator-Activated Receptor-γ Pro12Ala Polymorphism and Susceptibility to Nonalcoholic Fatty Liver Disease, Rheumatoid Arthritis, and Psoriatic Arthritis 
Introduction: The purpose of this study was to examine whether a Proline (Pro)-to-Alanine (Ala) exchange at codon 12 (Pro12Ala) polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARγ) is associated with susceptibility to nonalcoholic fatty liver disease (NAFLD), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). Methods: A meta-analysis was conducted on the association between the PPARγ Pro12Ala polymorphism and NAFLD, RA, and PsA. Results: Nine studies, including five on NAFLD, two on RA, and two on PsA, were available for the meta-analysis consisting of 8082 cases and 3790 controls. The meta-analysis revealed no association between the Ala allele of the PPARγ Pro12Ala polymorphism and NAFLD (odds ratios [OR]=0.936, 95% confidence interval [CI]=0.672–1.302, p=0.693). However, stratification by ethnicity indicated an association between the Ala allele and NAFLD in East Asians (OR=0.700, 95% CI=0.496–0.987, p=0.042), but not in Europeans (OR=1.128, 95% CI=0.863–1.475, p=0.378). Analysis using the dominant model showed the same Ala allele pattern in East Asians and Europeans (OR=0.688, 95% CI=0.484–0.978, p=0.037; OR=1.051, 95% CI=0.782–1.413, p=0.742), demonstrating a significant association between the Ala allele and NAFLD in East Asians. The meta-analysis revealed no association between the Ala allele and RA in East Asians (OR=0.467, 95% CI=0.188–1.161, p=0.101), and no association was found between the Ala allele and PsA in Europeans (OR=0.869, 95% CI=0.465–1.627, p=0.662). Conclusions: Our meta-analysis demonstrates that the PPARγ Pro12Ala polymorphism is associated with susceptibility to NAFLD in East Asians, but not in European populations.
PMCID: PMC4010165  PMID: 24697566
3.  Meta-Analysis of Genetic Association Studies 
Annals of Laboratory Medicine  2015;35(3):283-287.
The object of this review is to help readers to understand meta-analysis of genetic association study. Genetic association studies are a powerful approach to identify susceptibility genes for common diseases. However, the results of these studies are not consistently reproducible. In order to overcome the limitations of individual studies, larger sample sizes or meta-analysis is required. Meta-analysis is a statistical tool for combining results of different studies on the same topic, thus increasing statistical strength and precision. Meta-analysis of genetic association studies combines the results from independent studies, explores the sources of heterogeneity, and identifies subgroups associated with the factor of interest. Meta-analysis of genetic association studies is an effective tool for garnering a greater understanding of complex diseases and potentially provides new insights into gene-disease associations.
PMCID: PMC4390695  PMID: 25932435
Gene; Polymorphism; Association study; Meta-analysis
4.  Transplant physicians' perceptions of cord blood transplantation in Korea: a questionnaire survey 
Blood research  2014;49(4):228-233.
Although bone marrow (BM) or mobilized peripheral blood (PB) is frequently used as the source of hematopoietic stem cells, hematopoietic stem cell transplantation (HSCT) using cord blood (CB) is gradually gaining popularity in many countries. However, BM or PB is still preferred over CB in Korea. Therefore, we tried to assess the awareness of CB transplantation (CBT) among domestic HSCT physicians and develop strategies for boosting its utilization by administering questionnaires to some of these physicians.
A direct questionnaire survey was conducted using the "Audience Response System" among 301 members who attended the annual meeting of the Korean Society of Blood and Marrow Transplantation. The data were analyzed for only 67 board certified physicians who were directly involved in HSCT activities.
The poor outcomes resulting from insufficient experience in CBT was designated by the physicians as the main reason for the low domestic implementation of HSCT using CB. Other reasons identified in the survey were distrust in the quality and management of domestic CB and the high cost of obtaining CB.
Increasing the use of donated CB would foremost require increasing the inventory of donated CB containing a sufficient cell number for CBT and securing structured quality control of the CB banks. In addition, it would be necessary to minimize CB supply costs and continue to provide academic data, including CBT guidelines, so that clinicians could perform CBT with more confidence.
PMCID: PMC4278003  PMID: 25548755
Cord blood; Utilization; Questionnaire
5.  Effects of GC7101, a Novel Prokinetic Agent on Gastric Motor Function: Ex Vivo Study 
GC7101, an extract of Lonicera Flos, is a novel developing drug for reflux esophagitis and functional dyspepsia. However, the drug’s exact pharmacological mechanism of action remains unclear. This study assessed the effects of GC7101 on gastrointestinal (GI) motor function.
We used male guinea pigs to evaluate the effects of GC7101 on GI motility. The contraction of antral circular muscle in the presence of different doses of GC7101 was measured in a tissue bath. The prokinetic effects of GC7101 were tested using the charcoal transit assay from the pylorus to the most distal point of migration of charcoal mixture. To clarify the mechanism of action of GC7101, atropine, dopamine and the selective 5-hydroxytryptamine 4 receptor antagonist, GR113808 were used.
The maximal amplitude of circular muscle contraction was induced by 5 mg mL−1 GC7101. The area under the curve of contraction was significantly increased at 5 mg mL−1 GC7101. Addition of 10−6 M atropine, 10−8 M dopamine or 10−7 M GR 113808 to GC7101 5 mg mL−1 decreased the amplitude and area under curve compared to GC7101 5 mg mL−1 alone. GC7101 accelerated GI transit in a dose dependent manner except 100 mg kg−1. Delayed GI transit caused by atropine, dopamine and GR 113808 was restored by GC7101 50 mg kg−1.
GC7101, an extract of Lonicera Flos, exerts a gastric prokinetic effect in guinea pig through cholinergic, antidopaminergic and serotonergic mechanisms. Therefore, GC7101 might be a novel drug for the treatment of functional dyspepsia.
PMCID: PMC4204422  PMID: 25273117
Functional dyspepsia; Gastrointestinal motility; Lonicera Flos; Prokinetic
6.  Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials 
The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA).
A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches.
Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies.
Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
PMCID: PMC4164730  PMID: 25228842
Tofacitinib; Efficacy; Safety; Arthritis, rheumatoid
7.  Clinical utilization of cord blood over human health: experience of stem cell transplantation and cell therapy using cord blood in Korea 
Korean Journal of Pediatrics  2014;57(3):110-116.
Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
PMCID: PMC4000756  PMID: 24778692
Cord blood; Transplantation; Cell therapy
8.  Clinical characteristics of hemophagocytic lymphohistiocytosis following Kawasaki disease: differentiation from recurrent Kawasaki disease 
Blood research  2013;48(4):254-257.
Our aim was to investigate the clinical pattern of hemophagocytic lymphohistiocytosis following Kawasaki disease (HLH-KD), to enable differentiation of HLH from recurrent or refractory KD and facilitate early diagnosis.
We performed a nationwide retrospective survey and reviewed the clinical characteristics of patients with HLH-KD, including the interval between KD and HLH, clinical and laboratory findings, treatment responses, and outcomes, and compared them with historical data for both diseases.
Twelve patients with HLH-KD, including 5 previously reported cases, were recruited. The median age was 6.5 years (range, 9 months-14.7 years). Eight patients were male and 4 were female. The median interval between the first episode of KD and the second visit with recurrent fever was 12 days (3-22 days). Of the 12 children, 2 were initially treated with intravenous IgG (IVIG) for recurrent KD when they presented at the hospital with recurrent fever. Eventually, 10 children received chemotherapy under an HLH protocol and 2 received supportive treatment. Two patients died of combined infections during chemotherapy, 1 was lost to follow up, and 9 remain alive. The overall survival rate at 4 years was 81.1% with a median follow up of 45.1 months.
A diagnosis of HLH-KD should be considered when symptoms similar to recurrent KD develop within 1 month of the first episode of KD. Our findings will help physicians differentiate between HLH and the recurrent form of KD.
PMCID: PMC3894383  PMID: 24466549
Hemophagocytic lymphohistiocytosis; Kawasaki disease; Recurrent
9.  Meta-analysis of randomized controlled trials of bosentan for treatment of pulmonary arterial hypertension 
We assessed the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH).
We surveyed randomized controlled trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. Results are presented as odds ratios (ORs) or weighted mean differences (WMDs).
Meta-analysis of seven RCTs including a total of 410 patients and 296 controls revealed that the 6-minute work distance was significantly higher in the bosentan group than in the placebo group (WMD, 46.19; 95% confidence interval [CI], 21.20 to 71.19; p = 2.9 × 10-5). Compared with the placebo, bosentan significantly reduced the mean pulmonary arterial pressure in patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 × 10-6). The bosentan therapy group worsened less clinically than the placebo group (OR, 0.252; 95% CI, 0.140 to 0.454; p = 4.6 × 10-7). The incidence of serious adverse events did not differ between the bosentan and placebo groups (OR, 0.948; 95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver function test (LFT) were significantly higher in the bosentan group than in the placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045).
This meta-analysis shows that bosentan can treat PAH effectively. However, bosentan increased the incidence of abnormal LFT results compared with the placebo.
PMCID: PMC3846996  PMID: 24307846
Bosentan; Efficacy; Safety; Hypertension, pulmonary
11.  Effect of Human Parathyroid Hormone on Hematopoietic Progenitor Cells in NOD/SCID Mice Co-Transplanted with Human Cord Blood Mononuclear Cells and Mesenchymal Stem Cells 
Yonsei Medical Journal  2012;54(1):238-245.
We evaluated the effect of human parathyroid hormone (hPTH) on the engraftment and/or in vivo expansion of hematopoietic stem cells in an umbilical cord blood (UCB)-xenotransplantation model. In addition, we assessed its effect on the expression of cell adhesion molecules.
Materials and Methods
Female NOD/SCID mice received sublethal total body irradiation with a single dose of 250 cGy. Eighteen to 24 hours after irradiation, 1×107 human UCB-derived mononuclear cells (MNCs) and 5×106 human UCB-derived mesenchymal stem cells (MSCs) were infused via the tail vein. Mice were randomly divided into three groups: Group 1 mice received MNCs only, Group 2 received MNCs only and were then treated with hPTH, Group 3 mice received MNCs and MSCs, and were treated with hPTH.
Engraftment was achieved in all the mice. Bone marrow cellularity was approximately 20% in Group 1, but 70-80% in the hPTH treated groups. Transplantation of MNCs together with MSCs had no additional effect on bone marrow cellularity. However, the proportion of human CD13 and CD33 myeloid progenitor cells was higher in Group 3, while the proportion of human CD34 did not differ significantly between the three groups. The proportion of CXCR4 cells in Group 3 was larger than in Groups 1 and 2 but without statistical significance.
We have demonstrated a positive effect of hPTH on stem cell proliferation and a possible synergistic effect of MSCs and hPTH on the proportion of human hematopoietic progenitor cells, in a xenotransplantation model. Clinical trials of the use of hPTH after stem cell transplantation should be considered.
PMCID: PMC3521258  PMID: 23225826
Umbilical cord blood; parathyroid hormone; bone marrow niches
12.  Thromboembolic events identified during diagnosis of germ cell tumors in 2 children 
The Korean Journal of Hematology  2012;47(3):233-236.
We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.
PMCID: PMC3464343  PMID: 23071481
Thromboembolism; Germ cell tumor; Chemotherapy
13.  Enactment of a Law for Governmental Support of the Use of Cord Blood, and Ethical Issues 
In Korea, cord blood banking projects have been developed since 1996, and the 1st successful cord blood transplant was performed in 1998. Recently, “Cord Blood Management and Research Act” was legislated in 2010, and has been come into effect on July 1st, 2011. This review focuses the backgrounds, aims, and legislation process as well as principal articles in this act.
PMCID: PMC3840985  PMID: 24298360
Cord blood; Act
14.  Roles of protein arginine methylation in DNA damage signaling pathways 
Cell Cycle  2011;10(9):1343-1344.
PMCID: PMC3117038  PMID: 21445011
BRCA1; p300; CARM1; DNA damage; protein methylation; p21; Gadd45; cell cycle; apoptosis; cancer
15.  Triple disruption of the superior shoulder suspensory complex 
The superior shoulder suspensory complex (SSSC) is an extremely important structure composed of a ring of bone and soft tissues at the superior aspect of the shoulder. Double disruption leads to instability of the construct and usually requires operative treatment. Triple disruption of the SSSC is extremely rare and is encountered in high-energy trauma cases often in association with other injuries. The authors experienced a case of triple disruption involving the acromion, coracoid process, and acromioclavicular separation. This type of SSSC disruption is unlikely to have been caused by a single impact and is rather caused by multiple impacts during one traumatic event.
PMCID: PMC3391788  PMID: 22787337
Superior shoulder suspensory complex; SSSC; triple disruption
16.  Early-onset Childhood Sarcoidosis with Incidental Multiple Enchondromatosis 
The triad of rash, arthritis, and uveitis seems to be characteristic for early-onset childhood sarcoidosis. We describe an interesting case of early-onset childhood sarcoidosis coexisting enchondromatosis, which clinically masquerade as Langerhans cell histiocytosis. A 33 months old girl presented with skin rash, subcutaneous nodules with polyarthritis, and revealed the involvement of lymph nodes as well as spleen during work-up. She also presented with multiple osteolytic lesions which pathologically proven enchondromatosis. Oral prednisone was prescribed at 2 mg/kg/day for 2 months until when subcutaneous nodules and joint swellings almost disappeared, and then slowly tapered over a period of 5 months. We report an unusual case of early-onset childhood sarcoidosis presented with osteolytic bone lesions which were irrelevant to sarcoidosis.
PMCID: PMC3247783  PMID: 22219622
Sarcoidosis; Polyarthritis; Enchondromatosis; Nodule; Childhood
17.  A Multi-Classifier Based Guideline Sentence Classification System 
Healthcare Informatics Research  2011;17(4):224-231.
An efficient clinical process guideline (CPG) modeling service was designed that uses an enhanced intelligent search protocol. The need for a search system arises from the requirement for CPG models to be able to adapt to dynamic patient contexts, allowing them to be updated based on new evidence that arises from medical guidelines and papers.
A sentence category classifier combined with the AdaBoost.M1 algorithm was used to evaluate the contribution of the CPG to the quality of the search mechanism. Three annotators each tagged 340 sentences hand-chosen from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) clinical guideline. The three annotators then carried out cross-validations of the tagged corpus. A transformation function is also used that extracts a predefined set of structural feature vectors determined by analyzing the sentential instance in terms of the underlying syntactic structures and phrase-level co-occurrences that lie beneath the surface of the lexical generation event.
The additional sub-filtering using a combination of multi-classifiers was found to be more effective than a single conventional Term Frequency-Inverse Document Frequency (TF-IDF)-based search system in pinpointing the page containing or adjacent to the guideline information.
We found that transformation has the advantage of exploiting the structural and underlying features which go unseen by the bag-of-words (BOW) model. We also realized that integrating a sentential classifier with a TF-IDF-based search engine enhances the search process by maximizing the probability of the automatically presented relevant information required in the context generated by the guideline authoring environment.
PMCID: PMC3259557  PMID: 22259724
Knowledge Bases; Data Mining; Natural Language Processing
18.  Efficacy and Safety of Monthly 150 mg Oral Ibandronate in Women with Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials 
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10-8) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10-8). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
PMCID: PMC3192207  PMID: 22016595
Ibandronic acid; Efficacy; Safety; Osteoporosis; Review
19.  API5 confers tumoral immune escape through FGF2-dependent cell survival pathway 
Cancer research  2014;74(13):3556-3566.
Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to immunotherapies to which they are otherwise resistant. In this study, we show that the anti-apoptotic gene API5 acts as an immune escape gene in tumors by rendering them resistant to apoptosis triggered by tumor antigen-specific T cells. Its RNAi-mediated silencing in tumor cells expressing high levels of API5 restored antigen-specific immune sensitivity. Conversely, introducing API5 into API5low cells conferred immune resistance. Mechanistic investigations revealed that API5 mediated resistance by upregulating FGF2 signaling through a FGFR1/PKCδ/ERK effector pathway that triggered degradation of the pro-apoptotic molecule BIM. Blockade of FGF2, PKCδ or ERK phenocopied the effect of API5 silencing in tumor cells expressing high levels of API5, to either murine or human antigen-specific T cells. Our results identify a novel mechanism of immune escape that can be inhibited to potentiate the efficacy of targeted active immunotherapies.
PMCID: PMC4394897  PMID: 24769442
20.  Bi-phasic expression of Heterochromatin Protein 1 (HP1) during breast cancer progression: Potential roles of HP1 and chromatin structure in tumorigenesis 
Journal of nature and science  2015;1(7):e127-.
Epigenetics in cancer prognosis and therapy is gaining recognition in recent years. Breast cancer is a genetic disease harboring numerous genetic mutations, including tumor suppressor BRCA1 and BRCA2 mutations. However, the functions of BRCA1 in cancer cells are also altered by non-genetic mechanisms, including DNA methylation and chromatin structure. Therefore, identification of epigenetic markers for breast cancer is very important for early diagnosis and effective therapy. This review focuses on recent findings on the roles of Heterochromatin protein 1 (HP1) in BRCA1 functions and breast cancer progression. We previously showed that BRCA1 function and breast cancer progression are frequently associated with HP1 expression level and potentially with chromatin structure. Herein, we suggest that bi-phasic expression of HP1 during breast cancer progression indicates dual roles of HP1 in tumorigenesis. Exploiting differential HP1 expression in tumors could lead to effective cancer therapy. Re-setting the chromatin structure may be a critical step for high-efficiency cancer therapy for many breast cancer patients.
PMCID: PMC4465567  PMID: 26082944
Epigenetics; HP1; breast cancer; BRCA1; PARP inhibitor; biomarker
21.  Downregulation of NFAT2 promotes melanogenesis in B16 melanoma cells 
Anatomy & Cell Biology  2010;43(4):303-309.
Nuclear factor of activated T-cells (NFAT) proteins are, calcium-regulated transcription factors, key regulator of stimulation-dependent gene activation. In our microarray analysis for the genes expressed in human black and white hairs, NFAT2 was significantly upregulated in the white hair, compared to the black hair. The aim of this study was to investigate functional role of NFAT2 in melanogenesis. Western blot analysis was performed to investigate the expression of NFAT2 protein in B16 melanoma cells. Our data showed that NFAT2 expression was increased in the hypopigmented B16 cells, while tyrosinase and MITF expression was decreased. To investigate the potential role of NFAT2, the recombinant adenovirus expressing microRNA specific for NFAT2 was transduced into the cultured B16 melanoma cells. Consistently, inhibition of NFAT2 enhanced tyrosinase activity and melanin content. Moreover, cyclosporine A, which is known as a calcineurin inhibitor blocking NFAT activation, enhanced tyrosinase activity and melanin content. These data suggest that NFAT2 may play an important role in regulation of melanogenesis in melanocyte.
PMCID: PMC3026182  PMID: 21267404
Melanogenesis; Melanocyte; B16 melanoma cells; NFAT2; Cyclosprorin A
22.  Virilizing Adrenocortical Oncocytoma in a Child: A Case Report 
Journal of Korean Medical Science  2010;25(7):1077-1079.
Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.
PMCID: PMC2890887  PMID: 20592902
Adrenal Cortex Neoplasms; Adenoma, Oxyphilic; Virilism; Child
23.  Implication of Cord Blood for Cell-Based Therapy in Refractory Childhood Diseases 
Since cord blood (CB) contains hematopoietic stem cells as well as a mixture of multipotent stem cells, CB has the ability to give rise to hematopoietic, epithelial, endothelial and neural tissues. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. This review focuses clinical and pre-clinical application of CB cell-based therapy for inherited metabolic diseases as well as tissue regenerations in neonatal hypoxic-ischemic encephalopathy, cerebral palsy, and juvenile diabetes.
PMCID: PMC4022686  PMID: 24855537
Cord blood; Stem cells; Regenerative medicine
24.  Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes 
Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.
PMCID: PMC4503095  PMID: 26191223
Keratinocytes; poly (I:C); Paeonia lactiflora Pallas extract; NF-κB; inflammasome

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