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To ensure high-quality bioresources and standardize biobanks, there is an urgent need to develop and disseminate educational training programs in accordance with ISO 20387, which was developed in 2018. The standardization of biobank education programs is also required to train biobank experts. The subdivision of categories and levels of education is necessary for jobs such as operations manager (bank president), quality manager, practitioner, and administrator. Essential training includes programs tailored for beginner, intermediate, and advanced practitioners, along with customized training for operations managers. We reviewed and studied ways to develop an appropriate range of education and training opportunities for standard biobanking education and the training of experts based on KS J ISO 20387. We propose more systematic and professional biobanking training programs in accordance with ISO 20387, in addition to the certification programs of the National Biobank and the Korean Laboratory Accreditation System. We suggest various training programs appropriate to a student's affiliation or work, such as university biobanking specialized education, short-term job training at unit biobanks, biobank research institute symposiums by the Korean Society of Pathologists, and education programs for biobankers and researchers. Through these various education programs, we expect that Korean biobanks will satisfy global standards, meet the needs of users and researchers, and contribute to the advancement of science.

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Seed dormancy is an important agronomic trait under the control of complex genetic and environmental interactions, which have not been yet comprehensively understood. From the field screening of rice mutant library generated by a Ds transposable element, we identified a pre-harvest sprouting (PHS) mutant dor1. This mutant has a single insertion of Ds element at the second exon of OsDOR1 (LOC_Os03g20770), which encodes a novel seed-specific glycine-rich protein. This gene successfully complemented the PHS phenotype of dor1 mutant and its ectopic expression enhanced seed dormancy. Here, we demonstrated that OsDOR1 protein binds to the GA receptor protein, OsGID1 in rice protoplasts, and interrupts with the formation OsGID1-OsSLR1 complex in yeast cells. Co-expression of OsDOR1 with OsGID1 in rice protoplasts attenuated the GA-dependent degradation of OsSLR1, the key repressor of GA signaling. We showed the endogenous OsSLR1 protein level in the dor1 mutant seeds is significantly lower than that of wild type. The dor1 mutant featured a hypersensitive GA-response of α-amylase gene expression during seed germination. Based on these findings, we suggest that OsDOR1 is a novel negative player of GA signaling operated in the maintenance of seed dormancy. Our findings provide a novel source of PHS resistance., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1 , which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3 , and ABA4 , was observed in OsRF1 -OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1 -OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Park, Kwon, Cho, Kim, Chung, Nam, Song, Kim and Yoon.)

The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The AP2/EREBP family transcription factors play important roles in a wide range of stress tolerance and hormone signaling. In this study, a heat-inducible rice ERF gene was isolated and functionally characterized. The OsERF115/AP2EREBP110 was categorized to Group-IIIc of the rice AP2/EREBP family and strongly induced by heat and drought treatment. The OsERF115/AP2EREBP110 protein targeted to nuclei and suppressed the ABA-induced transcriptional activation of Rab16A promoter in rice protoplasts. Overexpression of OsERF115/AP2EREBP110 enhanced thermotolerance of seeds and vegetative growth stage plants. The OsERF115/AP2EREBP110 overexpressing (OE) plants exhibited higher proline level and increased expression of a proline biosynthesis P5CS1 gene. Phenotyping of water use dynamics of the individual plant indicates that the OsERF115/AP2EREBP110 -OE plant exhibited better water saving traits under heat and drought combined stress. Our combined results suggest the potential use of OsERF115/AP2EREBP110 as a candidate gene for genetic engineering approaches to develop heat and drought stress-tolerant crops.

An 82-year-old man with diabetes was admitted to the emergency department with a third-degree burn on his left leg. The deep swab specimen from his left leg was cultured on Sabouraud dextrose agar without cycloheximide and incubated at 25 °C for 5 days. On the basis of morphological characteristics and multigene phylogenetic analyses of the internal transcribed spacer region of ribosomal DNA and partial fragments of beta-tubulin and translation elongation factor 1-alpha, the causal agent of fungal skin infection was identified as Bisifusarium delphinoides , which was newly introduced by accommodating a Fusarium dimerum species complex. Thus, we describe here the first case of skin infection caused by B. delphinoides on a burn patient with diabetes mellitus based on morphological observation and molecular analysis., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Purpose: The present study investigated chest computed tomography (CT) patterns and lung histological features, as well as the consistency between radiological and histological features among patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA)., Materials and Methods: The medical records of 74 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with radiological lung parenchymal lesions were reviewed along with the histological results for 28 of them. Chest CT patterns were divided according 12 items mostly suggested by radiologists and histological features were divided according to necrotising granuloma, necrotising vasculitis, eosinophilic infiltration, and hemosiderin laden macrophages as defined by a pathologist., Results: The mean age was 57.1 years (22 men). The most common clinical manifestation other than lung manifestation was renal manifestation (62.2%), and the most common chest CT pattern was lung involvement of vasculitis (35.1%). In MPA patients, the major histological features were hemosiderin-laden macrophages in the alveolar space and vasculitis. In GPA patients, the major histological features were necrotizing vasculitis and necrotizing granuloma, while in EGPA patients, the major histological feature was only necrotising vasculitis. The consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%)., Conclusion: When lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for the proper classification of AAV, due to the discordance rate between radiological and histological findings in MPA and EGPA patients, but not GPA patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated-, systemic disease that is characterized by IgG4 plasma cell infiltration with fibrotic changes in various organs. The most affected organs are pancreas and salivary glands. Kidney can be rarely involved, and is usually represented as a renal mass and organomegaly. Usually, elevated levels of serum IgG4 more than 135 mg/dl with organ-specific features and biopsy results showing enriched infiltration of IgG4-positive plasma cells are needed to diagnose the disease. However, we experienced two unusual cases of IgG4-RD involving kidney. IgG4-related kidney disease (IgG4-RKD) was first reported as an extra pancreatic feature of autoimmune pancreatitis(AIP) in 2004. Herein, we describe two cases of such unique presentation of IgG4RKD and a literature review focusing on clinicopathologic features of IgG4RKD. Our cases are distinct in the fact that IgG4RD invades unusual organs such as perinephric capsule or scrotum. We reported the patient who showed extinct perirenal capsule invasion with multi-organ involvement including exocrine glands in comparison to previous IgG4RKD that often involved in renal parenchyma and renal pelvis lesions. And the other patient had scrotal invasion with multifocal renal parenchymes. Referring to the features observed in these two cases, we could propose that as every organ can be related to IgG4RD, we propose clinicians to confirm the disease using imaging, serologic, and pathologic studies. We also reviewed previous reports of IgG4-RKD and summarized diverse imaging findings and pathologic features.

Few reports have described epidermal cysts (ECs) arising from scar tissues, and the standard course of treatment has not been established. We aimed to report the findings of a Korean patient series with ECs arising from scar tissues, to describe patient management in the context of previous publications, and to present a simple algorithm for managing ECs arising from scar tissues.We managed 6 patients with ECs arising from scar tissues, and retrospectively reviewed their demographic and clinical data.The scars were located on the anterior chest wall (n = 3), shoulder (n = 1), forehead (n = 1), and ear lobule (n = 1). Two patients with anterior chest wall scars, 1 with a shoulder scar, and 1 with an ear lobule scar had keloid scars, whereas the other patients had hypertrophic scars. The scar sizes ranged from 2 × 1 cm to 9 × 7 cm. The EC sizes ranged from 0.2 × 0.2 cm to 2 × 1.5 cm. Three patients underwent total scar revisions with complete EC excisions, 2 underwent partial scar tissue excisions with complete EC excisions, and 1 had laser therapy for the scar and EC. No complications occurred, and all patients' final outcomes were satisfactory during the mean follow-up period of 14.8 months.We successfully managed the patients with ECs arising from scar tissues. We recommend that surgeons and patients first decide whether the ECs and scar tissue should be completely removed. Moreover, consideration should be given to the options chosen for the management of ECs. Finally, postoperative scar care is necessary to prevent hypertrophic and keloid scar recurrences.

Objective: To determine the functional relevance of diffusion tensor imaging (DTI) metrics and conventional MRI (signal intensity change in T2, compression ratio) by measuring the correlation of these parameters with clinical outcome measured by the modified Japanese Orthopedic Association (mJOA) score., Materials and Methods: A total of 20 cervical myelopathy (CM) patients participated in this prospective cohort study. The severities of CM were assessed using the mJOA score. Conventional MRIs (T2-weighted images) measuring the signal changes of spinal cords and the degree of compression at the lesion level and DTI metrics [fractional anisotropy (FA), apparent diffusion coefficient (ADC)] at each lesion and below each lesion (C7/T1) level were acquired using a 3-T Achieva MRI. These parameters were correlated with the mJOA scores to determine the functional relevance., Results: Ninety percent of CM patients showed signal changes and 30 % of patients noted a more than 40% canal compression ratio in conventional MRIs at the lesion level; however, these findings were not correlated with the mJOA score (p < 0.05). In contrast, FA values on DTI showed high sensitivity to CM (100%), which was well correlated with the mJOA score (p = 0.034, r = 0.475) below the lesion level (C7/T1)., Conclusions: This study showed a meaningful symptomatic correlation between mJOA scores and FA values below the lesion levels in CM patients. It could give us more understanding of the pathological changes in spinal cords matched with various clinical findings in CM patients than the results from conventional MRI.

Autogenous microfat grafting is widely used to augment depressed deformities or for other cosmetic purposes. Since the microfat survival rate is unpredictable due to absorption and calcification, previously cryopreserved fat is widely used for secondary procedures. Sphingosylphosphorylcholine (SPC) is a lysophospholipid, which has a role in several cellular responses, and is known to stimulate DNA synthesis and proliferation. Since endothelial progenitor cells (EPCs) are known to enhance the survival rate of transplanted fat tissue, the present study assessed the effects of SPC on EPCs, in order to verify its positive effects on proliferation. Cryopreserved human fat tissues mixed with various concentrations of SPC were grafted into the nude mouse model. After grafting, the viability of each SPC mixed group was determined and compared with that of the non‑SPC group. SPC exhibited a positive effect on EPC proliferation and angiogenic potential over 3 days when used at specific concentrations. The fat grafts of the 3 µM SPC‑treated group weighed significantly more and the volume was markedly increased, as compared with the control group. A reverse transcription‑quantitative polymerase chain reaction was conducted on the total RNA extracted from SPC‑treated fat tissues, which detected increased mRNA expression levels of matrix metallopeptidase‑9 and tumor necrosis factor‑α compared with in the control group. These results indicate that specific concentrations of SPC may exert favorable effects on grafted cryopreserved human fat tissue, which may be due to the increased mRNA expression levels of genes associated with angiogenesis.

Human mesenchymal stem cells (MSCs) are a promising tool for therapeutic applications in cell-based therapy and regenerative medicine, and MSCs from the human palatine tonsils have recently been used as a new tissue source. However, the understanding of the proliferation and differentiation capacity of tonsil-derived MSCs (T-MSCs) is limited. In this study, we compared the proliferative potential of T-MSCs with those of bone marrow MSCs (BM-MSCs) and adipose tissue-derived MSCs (A-MSCs). Additionally, we investigated the underlying mechanism of T-MSC function. We showed that T-MSCs proliferated faster than A-MSCs and BM-MSCs in methylthiazolyl diphenyl-tetrazolium (MTT) assays, cell count assays, and cell cycle distribution analyses. DNA microarray and real-time PCR analyses revealed that the expression of fibroblast growth factor-5 (FGF5) was significantly elevated in T-MSCs compared with those in A-MSCs and BM-MSCs. Cell growth curves showed a difference in cell growth between untreated cells and siFGF5-treated T-MSCs. The administration of recombinant human FGF5 (rhFGF5) to the cells transfected with siFGF5 led to a significant increase in the proliferation rates. The administration of rhFGF5 to T-MSCs led to an increase in the levels of phosphorylated ERK1/2. However, treatment with siFGF5 resulted in an overall decrease in the level of phosphorylated ERK1/2. The osteogenic differentiation of T-MSCs was reduced following siFGF5 transfection, and it recovered to near-normal levels when rhFGF5 was added. These findings indicate that T-MSCs show significantly higher proliferative potential compared with those of BM-MSCs and A-MSCs. FGF5 facilitates cell proliferation through ERK1/2 activation, and it influences the osteogenic differentiation of T-MSCs.

Background/aims: Although tonsil-mesenchymal stem cells (T-MSCs) have been studied as a new autologous or homologous source of MSCs, research on specific markers of MSCs and localization for purified T-MSC isolation has not yet been reported. This study investigates the expression of W5C5 (SUSD2) in tonsil stromal cells and the colony-forming ability and differentiation potential of W5C5+ cells to determine the usefulness of W5C5+ MSCs as a marker that can be used for the purification of T-MSCs. In addition, the location of W5C5+ cells expressed in the tonsil tissues is examined., Methods: T-MSCs were isolated from the tonsillar tissues of 12 patients undergoing tonsillectomy. The colony-forming ability, surface markers, proliferation potential, and differentiation capacities of purified W5C5+ MSCs, W5C5- MSCs, and unselected T-MSCs were evaluated. The location of the W5C5+ cells in the tonsillar tissues was also investigated by immunohistochemistry., Results: W5C5 was expressed in 2.5±0.4% of fresh human tonsil stromal cells. W5C5+ cells formed many colonies, but W5C5- cells did not form any colonies. The colony-forming number of W5C5+ cells (74.4 ± 9.8) was significantly higher than that of unselected tonsil stromal cells (23.6 ± 3.7). However, the differences in proliferation potential, surface marker expression, and differentiation potential between W5C5+ T-MSCs and unselected T-MSCs were not significant. W5C5+ cells were identified in the perivascular area around the blood vessels., Conclusion: W5C5+ T-MSCs possessed typical MSC properties with high colony-forming efficiency, and niches of W5C5+ T-MSCs were located in the perivascular area of tonsil tissues. These findings suggest that W5C5 is a useful single marker for the isolation of purified T-MSCs., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Vitamin D receptor (VDR) has been suggested to play a role in the pathogenesis of type 1 diabetes mellitus (T1DM). There has been no case-control study examining the association between VDR polymorphisms and T1DM among Korean subjects with a low incidence of T1DM., Methods: Eighty-one T1DM patients and 113 unrelated healthy controls with no history of DM or other autoimmune diseases were investigated at either Pusan National University Children's Hospital or Korea University Anam Hospital between March 2009 and September 2013. Polymerase chain reaction-restriction fragment length polymorphism was utilized to genotype single nucleotide substitutions at TaqI, BsmI, and ApaI alleles., Results: All frequencies in T1DM and control subjects were in Hardy-Weinberg equilibrium, although ApaI in controls and TaqI in T1DM showed relatively weak equilibrium. TaqI and BsmI differences were significant (P = 0.045 and P = 0.012, respectively) after applying Bonferroni correction. The TT genotype carrier frequency among controls was higher than among the T1DM patients (P = 0.015; OR, 2.98; 95%CI: 1.19-7.42). T allele frequency was higher among controls than T1DM patients (P = 0.019; OR, 2.78; 95%CI: 1.15-6.72). The frequency of bb genotype carriers among controls was higher than among T1DM patients (P = 0.004; OR, 4.13; 95%CI: 1.4-12.10). The frequency of the b allele among controls was higher than that among T1DM patients (P = 0.016; OR, 3.20; 95%CI: 1.19-8.60)., Conclusions: T and b TaqI and BsmI alleles are protective against T1DM in Korean subjects., (© 2015 Japan Pediatric Society.)

Background: The use of cryopreserved adipose tissue for soft tissue augmentation is common, but unpredictability of fat graft viability remains a limitation. Adipose-derived stem cell (ADSC) and stromal vascular fraction (SVF) have been introduced to enhance viability and improve the survival of transplanted fat tissue., Objective: To investigate whether supplementation with ADSC or SVF improved the survival of cryopreserved fat grafts., Methods: The cryopreserved fat grafts were treated with ADSC, SVF, or normal saline in 30 six-week-old male nude mice to test whether ADSC and SVF could improve the survival of the transplanted fat tissue. The authors examined the weight, volume, and histological features of each group (n = 10) at 8 weeks after transplantation to evaluate the survival of the fat tissue., Results: There was no difference between the control and SVF groups with respect to weight, volume, and histological findings. However, the ADSC group showed a significant increase in weight and volume compared with the control and SVF groups. Histological examination showed that the ADSC supplementation improved the quality of the transplanted fat grafts., Conclusion: Taken together, these results suggest a potential clinical utility of ADSC but no advantage of SVF in facilitating cryopreserved fat transfer.

Objectives: Human mesenchymal stem cells (MSCs) are efficacious in various cellular therapeutic applications and have been isolated from several tissues. Recent studies have reported that human tonsil tissue contains a new source of progenitor cells, potentially applicable for cell-based therapies. Information about the effects of donor age, long-term passage and cryopreservation are essential for clinical applications and cell-based therapies. Therefore, the authors investigated how the morphology, cell-surface markers, proliferation potential and differentiation capacity of tonsil-derived MSCs (T-MSCs) were affected by donor age, long-term passage, and cryopreservation., Materials and Methods: T-MSCs were isolated from tonsillar tissue of 20 patients undergoing tonsillectomy. Authors evaluated the effects of donor-age, long-term passage, and cryopreservation on the morphology, surface markers, proliferation potential and differentiation capacities of T-MSCs., Results: T-MSCs exhibited a fibroblast-like, spindle-shaped appearance. There were no significant morphological differences according to donor age, long-term passage or cryopreservation. T-MSCs isolated from donors of various ages were positive for markers CD90, CD44, and CD73, but negative for CD45, CD31, and HLA-DR. There were no significant differences in the expression of positive and negative surface markers as a function of donor age, long-term passage and cryopreservation. T-MSCs from different donor age groups showed similar proliferation potentials after passage 2. After long-term passage and cryopreservation, there were no significant morphological differences. Cryopreservation did not affect the proliferation potential of T-MSCs, but there was a significant decrease in the proliferation potential in long-term passage T-MSCs (passage 15). The effect of donor age, long-term passage and cryopreservation on the in vitro adipogenic, osteogenic, and chondrogenic differentiation potential of T-MSCs was not significant., Conclusion: The effect of donor age, long-term passage culture, and cryopreservation on T-MSC properties are negligible, except for the proliferation capacity of long-term cultured T-MSCs. Therefore, T-MSCs are considered to be promising MSCs that can be used as future alternative sources for autologous or allogenic MSCs.

Aim: To evaluate the benefit of aerobic exercise on colonic transit time (CTT) for psychiatric inpatients in a closed ward., Methods: Sixty consecutive adult inpatients of the Somang Hospital Psychiatry Unit (Eumsung-gun, South Korea), without CTT-related diseases or drug therapies, were recruited for study from March to June of 2012. Upon enrollment, the patients were randomly assigned to partake in a 12-wk instructor-led group aerobic exercise program (exercise group; n = 30) or to maintain their ordinary daily activities (control group; n = 30). The exercise program was structured as 10 min warm-up (stretching), 40 min exercise, and 10 min cool-down (stretching) for three days each week. The exercise sessions consisted of walking only in week one and aerobics from weeks two to 12, with increasing intensity (50% heart rate reserve (HRR) for weeks one to four, 60% HRR for weeks five to eight, and 70% HRR for weeks nine to 12). CTT was measured before (baseline) and after (week 12) the exercise program, in duplicate (on days four and seven), using abdominal radiography and the multiple radio-opaque marker technique. Changes in the exercising patients' CTT and weight-, cardiovascular- and fitness-related parameters were statistically assessed., Results: The study dropout rate was 30.0%, with 23 patients in the exercise group and 19 patients in the control group completing the study. At week 12, the exercise group showed decreases in body weight (mean ± SE) baseline: 69.4 ± 2.8 vs study-end: 67.6 ± 2.7; P < 0.635) and body mass index (BMI) (25.2 ± 1.1 vs 24.9 ± 0.8; P < 0.810), but the extent of change was not significantly different from that experienced by the control group (body weight: 68.8 ± 4.0 vs 68.8 ± 3.9; BMI: 24.3 ± 1.1 vs 24.4 ± 1.2). However, the exercise group showed significant improvements in leg muscle strength (baseline: 41.7 ± 4.3 vs study-end: 64.1 ± 5.0; P < 0.001), cardio-respiratory endurance (120.5 ± 4.5 vs 105.4 ± 2.8; P < 0.004), and leg muscle elasticity and power output (21.5 ± 2.6 vs 30.6 ± 2.8; P < 0.001). The exercise group showed an exercise-induced reduction in total CTT (baseline: 54.2 ± 8.0 vs 30.3 ± 6.1), which was significantly different from that experienced by the control group over the 12-wk period (48.6 ± 9.3 vs 48.3 ± 12.3; P = 0.027); however, the exercise-induced decreases in CTT involving the three colonic segments examined (right, left and recto-sigmoid) showed no significant differences from the control group., Conclusion: A 12-wk aerobic exercise program can benefit psychiatric inpatients by increasing intestinal motility, possibly decreasing risk of metabolic- and cardiovascular-related disease.

Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A were identified as the causes of KS in 55.8-80.0% of patients. To elucidate further the molecular characteristics of Korean patients with KS, we screened a cohort of patients with clinically defined KS for mutations in KMT2D and KDM6A. Whole-exome sequencing and direct sequencing for validation were performed in 12 patients with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11 (91.7%) patients. No recurrent mutation was observed, and 10 out of the 11 mutations found were novel. KMT2D mutations were detected in 10 patients, including four small deletions or insertions and four nonsense and two missense mutations. One girl had a novel splice-site mutation in KDM6A. Each patient had a unique individual mutation. This is the first report of mutational analysis via exome sequencing in Korean patients with KS. Because the mutation-detection rate was high in this study, rigorous mutation analysis of KMT2D and KDM6A may be an important tool for the early diagnosis and genetic counseling of Korean patients with KS.

The Prototheca species is achlorophyllic algae and rarely causes human infection. Human protothecosis presents clinically as a cutaneous infection, olecranon bursitis, and disseminated systemic disease. We report a case of human cutaneous protothecosis involving the left wrist. A 68-year-old man presented with an ill-defined erythematous lesion with crust at the dorsal aspect of his left wrist. A punch biopsy was performed to reveal the histologic features of granulomatous inflammation with necrosis at the upper dermis, containing Prototheca organisms, of which, the characteristic features were highlighted by special staining. Through a molecular study, the Prototheca zopfii species was identified.

Objective: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma., Methods: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012., Results: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity., Conclusions: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.

Background/aims: Narrow band imaging (NBI) is an optical endoscopic technique for predicting polyp histology during colonoscopy. However, it has not been elucidated the impact of polyp characteristics on the diagnostic capabilities of NBI. We aimed to evaluate which polyp characteristics can influence the diagnostic accuracy of NBI for discriminating neoplastic from non-neoplastic colorectal polyps., Methodology: A total of 232 colorectal polyps from 134 patients undergoing screening or surveillance colonoscopy were retrospectively analyzed. White light imaging (WLI) and NBI images of polyps were assessed by two experienced endoscopists and two trainees and then compared with histopathology., Results: When classified according to polyp morphology, NBI as well as WLI had a significantly lower sensitivity and diagnostic accuracy for non-polypoid lesions than for polypoid lesions in both experienced and trainee groups. In contrast, the specificity of NBI and WLI for non-polypoid lesions was higher than that for polpyoid lesions. As for polyp size, the diagnostic accuracy of NBI for polyps ≤5mm was significantly lower than for polyps of 6 to 9mm or ≤10mm in the experienced group., Conclusions: NBI had a significantly lower diagnostic accuracy for predicting polyp histology in non-polypoid or diminutive colorectal lesions.

An ectopic hamartomatous thymoma is an extremely rare benign tumor of the lower neck that is the most common in middle-aged males. Pathologically, the tumor is characterized by a mixture of spindle cells, epithelial cells, mature adipose tissue, and lymphocytes. The histogenesis of this tumor is controversial. Recently, an origin from a remnant of the cervical sinus of His was proposed. Malignant lesions such as synovial sarcomas or malignant peripheral nerve sheath tumors can have similar clinical features and radiologic images. Thus, recognition of this tumor is important because it follows a benign clinical course and conservative surgical excision is the treatment of choice. Here, we report the case of a 34-year-old man with an ectopic hamartomatous thymoma in the left supraclavicular region and a review of the literature on this tumor., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Thioredoxin (TRX) is a ubiquitous redox protein that is involved in numerous biological functions, including the first unique step in DNA synthesis. TRX provides control over a number of transcription factors affecting cell proliferation and death through a mechanism referred to as redox regulation. In mammals, there are at least 3 members of the TRX family: TRX1, TRX2, and sperm TRX. To investigate the role of TRX1 and TRX2 in human adipose tissue-derived mesenchymal stem cells (hADSC), we modulated TRX1 and TRX2 expressions in hADSC using a lentiviral gene transfer system and small interfering RNA technique. Reverse transcription-polymerase chain reaction analysis confirmed the changes in expression of TRX1 and TRX2 in lentivirus-transduced or small interfering RNA-transfected cells. Although overexpression of TRX1 and TRX2 did not affect the differentiation of hADSC into adipogenic and osteogenic lineages, it increased the proliferation of hADSC compared with control lentivirus-transduced cells, decreased reactive oxygen species production, and inhibited oxidant-induced cell death. Downregulation of TRX1 and TRX2 inhibited cell proliferation. The treatment of U0126 blocked TRX-induced increase in cell proliferation. Overexpression of TRX1 and TRX2 increased ERK1/2 phosphorylation, nuclear factor-kappaB activation, and β-catenin/Tcf promoter activities and inhibited lucine zipper tumor suppressor 2 expression. On the contrary, downregulation of TRX1 and TRX2 expression induced inhibition of ERK1/2 phosphorylation, nuclear factor-kappaB activation, and β-catenin/Tcf promoter activities and increased lucine zipper tumor suppressor 2 expression. Activation of Wnt signal increased ERK1/2 activities in hADSC. These results indicated that TRX1 and TRX2 regulate the proliferation and survival of hADSC; these processes are mediated by the activation of ERK1/2.

β-catenin is a component of the adhesion complex linking cadherin and actin cytoskeleton, as well as a major mediator of the Wnt pathway, which is a critical signal cascade regulating embryonic development, cell polarity, carcinogenesis, and stem cell function. NF-κB functions as a key regulator of immune responses and apoptosis, and mutations in NF-κB signaling can lead to immune diseases and cancers. We previously showed that NF-κB-mediated modulation of β-catenin/Tcf signaling is mediated by leucine zipper tumor suppressor 2 (Lzts2) and that lzts2 expression is differentially regulated in various cancer cells. Its functional significances, however, are poorly understood. We showed that NF-κB-induced modulation of β-catenin/Tcf pathway is regulated by lzts2 expression in mesenchymal stem cells (MSCs) and several cancer cells, and that NF-κB-induced lzts2 expression is differentially regulated among cancer cell types. Here, using a promoter-reporter assay and EMSA, we demonstrate that NF-κB regulates lzts2 transcription by directly binding to the lzts2 promoter, and that NF-κB-induced lzts2 transcription differs by cell types. Modulation of lzts2 expression by lentiviral techniques affected proliferation and tumorigenicity of several cancer cell lines such as breast, colon, prostate cancer, and glioma, but did not affect cisplatin sensitivity or cell migration. Our data indicate that lzts2 expression is transcriptionally regulated by NF-κB activities, and the modulation of lzts2 expression affects cell proliferation and tumor growth through the Wnt/β-catenin pathway in various cancer cell lines.

Tumor necrosis factor-alpha (TNF-alpha) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF-alpha inhibits the mineralization of osteoblasts, the effect of TNF-alpha on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF-alpha on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF-kappaB activation on TNF-alpha activity. TNF-alpha treatment dose-dependently increased osteogenic differentiation over the first 3 days of treatment. TNF-alpha activated ERK and increased NF-kappaB promoter activity. PDTC, an NF-kappaB inhibitor, blocked the osteogenic differentiation induced by TNF-alpha and TLR-ligands, but U102, an ERK inhibitor, did not. Overexpression of miR-146a induced the inhibition of IRAK1 expression and inhibited basal and TNF-alpha- and TLR ligand-induced osteogenic differentiation. TNF-alpha and TLR ligands increased the expression of transcriptional coactivator with PDZ-binding motif (TAZ), which was inhibited by the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter. TNF-alpha also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF-alpha enhances osteogenic differentiation of hADSC via the activation of NF-kappaB and a subsequent increase of TAZ expression., (J. Cell. Physiol. 223: 168-177, 2010. (c) 2009 Wiley-Liss, Inc.)

Trichoblastoma is occasionally observed in association with a pre-existing nevus sebaceous in the Korean literature. However, there has been no report on the pigmented type. Herein, we report the first Korean case of a pigmented trichoblastoma arising from the nevus sebaceous on the forehead. A 28-year-old male presented with a dark nodular lesion within a yellowish plaque on the forehead. The surrounding yellowish plaque on the forehead had existed since birth. The central, dark-pigmented nodule began to appear three years ago and enlarged gradually. Histopathologic findings of central pigmented lesion showed heavy melanin deposits within and around the tumor nests. Complete excision was made as treatment.

Vitiligo is a common skin disease, but its pathogenesis has not been fully determined, though an autoimmune etiology is considered likely. Kawasaki disease (KD) is an acute multisystem vasculitis of childhood associated with coronary arteriopathy, and is diagnosed based on clinical criteria. Furthermore, vitiligo has been associated with several other diseases, but no report has been issued about the relationship between vitiligo and Kawasaki's disease. The author's report the case of an 8-year-old male child that presented with depigmented lesions, which developed from the desquamative skin lesions of Kawasaki's disease.

The proangiogenic action of human adipose tissue-derived mesenchymal stem cells (hASCs) transplantation has been shown to be mediated by secretory factors. In this study, we determined if human granulocyte chemotactic protein-2(GCP2) or monocyte chemoattractant protein-1(MCP1) is involved in the proangiogenic action of hASCs transplantation in the hindlimb ischemia model. hASCs secrete GCP2 and MCP1, which leads to increased tubule formation. The downregulation of GCP2 or MCP1 decreased MCP1 and GCP2 secretion, respectively, whereas the external addition of GCP2 or MCP1 increased MCP1 and GCP2, respectively. Additionally, the treatment of GCP2 and MCP1 increased VEGF secretion, while the downregulation of GCP2 and MCP1 showed the opposite effect on VEGF secretion. Downregulation of GCP2 and MCP1 expression also inhibited hASCs-induced proangiogenic action, while the overexpression of GCP2 increased it. Finally, the downregulation of MCP1 or VEGF inhibited the GCP2 overexpression-induced increase in blood flow recovery. Taken together, these data indicate that the proangiogenic action of hASCs transplantation is mediated by the interaction between GCP2, MCP1 and VEGF, which are secreted from the transplanted cells., (2009 S. Karger AG, Basel.)

beta-Catenin/Tcf and NF-kappaB pathways play an important role in biological functions. We determined the underlying mechanisms of differential interaction between two pathways in various human cancer cell lines. NF-kappaB positively regulated beta-catenin/Tcf pathways in human glioblastoma, whereas it has an opposite effect on beta-catenin/Tcf pathways in colon, liver, and breast cancer cells. Expression of lucine zipper tumor suppressor 2 (lzts2) was positively regulated by NF-kappaB activity in colon, liver, and breast cancer cells, whereas negatively regulated in glioma cells. Downregulation of lzts2 increased the beta-catenin/Tcf promoter activity and inhibited NF-kappaB-induced modulation of the nuclear translocation of beta-catenin. These data indicate that the differential crosstalk between beta-catenin/Tcf and NF-kappaB pathway in various cancer cells is resulted from the differences in the regulation of NF-kappaB-induced lzts2 expression.

Purpose: To clarify the role of vascular endothelial growth factor (VEGF) expression as an independent prognostic factor in Stage IB cervical cancer., Methods and Materials: A total of 117 patients with Stage IB cervical cancer who had undergone radical hysterectomy and pelvic lymph node dissection with complete histopathologic examination were included. Eighty-eight (75.2%) patients received postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry., Results: Of 117 patients, 35 (29.9%) showed high-intensity VEGF expression and 69 (59%) had a high score for area of VEGF expression. Strong correlations were found between high VEGF intensity and both deep stromal invasion (p = 0.01) and positive pelvic lymph nodes (p = 0.03). The area of VEGF expression was significantly associated with tumor size (p = 0.02). In a multivariate analysis, high VEGF intensity (p = 0.009) and tumor size (p = 0.01) were significant prognostic factors for overall survival and disease-free survival (p = 0.001 and p = 0.003, respectively). However, the area of VEGF expression was not a prognostic factor for overall survival or disease-free survival., Conclusion: Our findings on the correlation between VEGF expression and prognosis were conflicting. Functional and quantitative tools to assess tumor angiogenesis in addition to the expression of VEGF need to be developed and would be helpful to support the finding that tumor angiogenesis correlates significantly with prognosis in early-stage cervical cancer.