Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

A Case of Gastric Granular Cell Tumor: Review of Literature and Features of Endoscopic Ultrasonography

Granular cell tumor was originally described as granular cell myoblastoma by Abrikossoff. The incidence of GCT in the gastrointestinal tract is low, and most granular cell tumors occur in the esophagus and large bowel. Gastric granular cell tumors are rare and difficult to distinguish from carcinoid tumors by gross endoscopic findings and endoscopic ultrasonography findings. We report a case of gastric granular cell tumor, treated by endoscopic submucosal dissection, and review the endoscopic ultrasonography findings of recently reported gastric granular cell tumors.

A Case of Fungating Type Natural Killer Like T Cell Lymphoma of the Ascending Colon / 대한소화기학회지

Primary colorectal lymphoma is a very rare disease entity that accounts for less than 0.2-0.65% of all colon cancers. It is as an extranodal lymphoma of the colon that mainly arises from B cells and primary colorectal lymphoma that arises from T cells is very rare both in Western countries and in Korea. Colonic lymphoma can be classified endoscopically into 5 categories as follows: fungating, ulcerative, infiltrative, ulcerofungating, and ulceroinfiltrative type. The endoscopic features of primary colorectal lymphoma differ according to their cellular origin; about half of B cell lymphomas are fungating type whereas most of T cell lymphomas are of ulcerative or ulceroinfiltrative type. Mass forming primary T cell lymphoma of the colon is extremely rare. Herein, we present a case of primary natural killer like T cell lymphoma of the colon presenting as fungating type with review of literature.

Effect of Soil Ameliorators on Ectomycorrhizal Fungal Communities that Colonize Seedlings of Pinus densiflora in Abandoned Coal Mine Spoils

In this study, the effect of soil ameliorators on ectomycorrhizal (ECM) fungal communities in coal mine spoils was investigated. Organic fertilizers and slaked lime were applied as soil ameliorators in 3 abandoned coal mine spoils. One year after the initial treatment, roots of Pinus densiflora seedlings were collected and the number of ECM species, colonization rate, and species diversity were assessed. The results showed that the soil ameliorators significantly increased ECM colonization on the roots of P. densiflora. The results suggest that soil ameliorators can have a positive effect on ECM fungi in terms of growth of host plants and show the potential use of soil ameliorator treatment for revegetation with ECM-colonized pine seedlings in the coal mine spoils.

Secretion of adenylate kinase 1 is required for extracellular ATP synthesis in C2C12 myotubes

Extracellular ATP (exATP) has been known to be a critical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly increased with the high level of adenylate kinase 1 (AK1) and ATP synthase beta during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase beta in C2C12 myotubes, suggesting that AK1 is required for exATP synthesis in myotubes. However, membrane-bound AK1beta was not involved in exATP synthesis because its expression level was decreased during myogenesis in spite of its localization in the lipid rafts that contain various kinds of receptors and mediate cell signal transduction, cell migration, and differentiation. Interestingly, cytoplasmic AK1 was secreted from C2C12 myotubes but not from C2C12 myoblasts. Taken together all these data, we can conclude that AK1 secretion is required for the exATP generation in myotubes.

STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination

Hypoxia-inducible factor 1alpha (HIF-1alpha) is rapidly degraded by the ubiquitin-proteasome pathway under normoxic conditions. Ubiquitination of HIF-1alpha is mediated by interaction with von Hippel-Lindau tumor suppressor protein (pVHL). In our previous report, we found that hypoxia-induced active signal transducer and activator of transcription3 (STAT3) accelerated the accumulation of HIF-1alpha protein and prolonged its half-life in solid tumor cells. However, its specific mechanisms are not fully understood. Thus, we examined the role of STAT3 in the mechanism of pVHL-mediated HIF-1alpha stability. We found that STAT3 interacts with C-terminal domain of HIF-1alpha and stabilizes HIF-1alpha by inhibition of pVHL binding to HIF-1alpha. The binding between HIF-1alpha and pVHL, negative regulator of HIF-1alpha stability, was interfered dose-dependently by overexpressed constitutive active STAT3. Moreover, we found that the enhanced HIF-1alpha protein levels by active STAT3 are due to decrease of poly-ubiquitination of HIF-1alpha protein via inhibition of interaction between pVHL and HIF-1alpha. Taken together, our results suggest that STAT3 decreases the pVHL-mediated ubiquitination of HIF-1alpha through competition with pVHL for binding to HIF-1alpha, and then stabilizes HIF-1alpha protein levels.

LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression

Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.

In Vitro Induction of Carcinoembryonic Antigen (CEA) Specific Cytotoxic T Lymphocytes Using Dendritic Cells Pulsed with CEA Peptide

PURPOSE: Dendritic cells (DCs) are the most potent antigen- presenting cells for initiating the T cell immune response in vivo. Recent studies have shown that active immunotherapy with tumor antigen pulsed DC tumor antigen specific cytotoxic T lymphocyte (CTL) response. The aim of this study was to establish clinically compatible procedures for generating human DCs and to determine if the CEA peptide- pulsed DCs can activate the CEA specific CTL responses in vitro. METHODS: DCs were generated from the peripheral blood monocytes (PBMCs) of HLA A2+ healthy donors using GM-CSF and IL-4. Phenotypic analysis was performed using flow cytometry with FITC- or PE-conjugated Abs against CD1a, CD14, CD80, HLA-DR, CD83 and CD86. The immature DCs were pulsed with a CEA peptide (HLA A2 epitope, [YLSGANLNL]) and the tumor lysates isolated from HLA A2+ CEA positive cell line, NCI-H498, and were incubated with the autologous PBMCs in order to generate an antigen specific CTLs in vitro. After three rounds of stimulation, the presence of a CEA-specific CTL response was determined using a CEA positive cell line as the specific targets with the standard 51Cr release assay, the ELISPOT assay, and the flow cytometry using CEA peptide-MHC tetramer. RESULTS: The DCs obtained after 6 days of culture expressed high levels of CD1a, HLA-DR, and CD80, which corresponded to the immature DC phenotype. The 51Cr- release assay showed that DCs pulsed with the CEA peptide or the lysates of the CEA-positive NCI-H498 cell line could stimulate the CEA-specific CTL responses. The CTL response to DCs pulsed with the CEA peptide was also generated using the DCs pulsed with the CEA peptide. In the ELISPOT assay, the number of CEA peptide-specific, INF-gamma-secreting spots were increased in the CTLs generated by DCs pulsed with the CEA pepide and the tumor lysates. In the peptide-MHC tetramer assay, the CD8+ T cells with the receptors specific to CEA-peptide were increased by stimulation with the DCs pulsed with the CEA peptide and the tumor lysates. CONCLUSION: These findings show that the CEA peptide pulsed DCs can generate CEA specific CTL responses and antigen bearing DCs can be used as the target cells for a cytotoxicity assay. This study provides the foundations for DC-based cancer immunotherapy for CEA expressing solid tumors.

Biological Effects of Fibronectin Type III 10 domain on Human Osteoblast-like cells / 대한치주과학회지

No abstract available.

Absent Bow-Tie Sign in Knee MRI

PURPOSE: 'Absent bow-tie sign'is interpreted as positive when a bow-tie-shaped body segment is seen on only one or no slice of 4- or 5-mm thick sagittal images, and is a well known as a useful sign in diagnosing bucket-handle meniscal tears. In practice, however, we have found that this sign was also positive in certain cases other than bucket-handle tears. We have assumed that if the normal range of meniscal body width, as determined among Westerners, is transferred to the Korean population without verification and modification this might lead to misdiagnosis. The purpose of this study, therefore, is to examine the reliability of the 'absent bow-tie sign'. MATERIALS AND METHODS: Among 454 cases in which knee MRI had been performed, we retrospectively evaluated 862 menisci, the total remaining after cases of discoid meniscus or those involving previous meniscectomy had been excluded. Among the 862 menisci, 614 were normal, 97 showed degeneration, 43 showed buck-et-handle tearing, and 108 showed tears other than bucket-handle tear. In all cases, proton-denwity and T2-weighted images were obtained in both sagittal and coronal planes, with 3mm section thickness and 1mm gap. We recorded the number of sagittal images in which the body segment of each meniscus had a bow-tie appear-ance, and measured the width of each meniscal body, as seen on midcoronal images. RESULTS: In all cases but one of bucket-handle tears (97.7%), the bow-tie sign was absent, as it was in 73.2% ofnon-bucket-handle tears, 35.0% of degenerated menisci and 27.5% of normal menisci. Among the non-tear group, 56.4% of menisci in the female group and 27.1% in the male group had bodies less than 9mm wide. CONCLUSION: In the diagnosis of bucket-handle tears, the 'absent bow-tie sign'is a very sensitive indicator. It is nonspecific, however, and merely suggests some significant deficiency in the meniscus body or small menis-ci,so can be positive in other cases. Thus the interpreter should be aware of the characteristics of this sign especially when used to interpret MRI of the knee of a female Korean patient.

Papillary Tumors of the Breast: US Findings of the Benign and Malignant Lesions

PURPOSE: To determine which sonographic findings usefully differentiate between benign and malignant papillary tumors. MATERIALS AND METHODS: We retrospectively rev i ewed the ultrasonographic findings of 42 surgically proven cases of papillary breast lesions [11 malignant lesions (7 inva s i ve papillary carcinomas, 4 intraductal papillary carcinomas) and 31 benign intraductal pa-pillomas]. All 42 cases were classified sonographically as cystic or ductal, or solid type, and the shape, wall change, margin, internal echo-pattern, posterior echo change and other associated findings for the two types were then analysed. RESULTS: Among the 25 cases (5 malignant and 20 benign) of cystic or ductal type, tubular shaped lesions were more frequently benign (60%). In all 20 benign lesions the wall of cystic portion was well-defined, smooth and thin. The solid portion of the cystic type showed an illdefined irregular margin in four malignant lesions (80%) and a smooth margin in 19 which were benign (95%). The internal echo-pattern was heterogeneous mixed-echo in three cases of malignancy, and homogeneously hypoechoic in 19 benign lesions (95%). Posterior enhancement was seen in two malignant lesions (40%), while in 19 benign lesions (95%), there was no posterior echo change. There were 17 solid type lesions (6 malignant cases, 11 benign cases), and most of these, whether benign or malignant, were smooth, oval or lobulated, hypoechoic masses. Posterior enhancement, howeve r, was more frequently observed in malignant lesions (three cases, 50%) than in those which were benign (one case, 9%). CONCLUSION: In cystic or ductal type lesions, an ill-defined irregular thick cystic wall, an illdefined irregular margin, a heterogeneous mixed internal echo-pattern and posterior enhancement of the solid portion suggested malignancy. In solid type lesions, posterior enhancement was more frequently found in malignant than in benign lesions.