• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.14 no.2
• /
• pp.168-173
• /
• 2014

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disorder caused by a mutation of the type III collagen (COL3A1). The manifestation of vEDS can be seen in skin, joints, blood vessels, and internal organs. The diagnosis of vEDS often is missed until the patient presents with a life-threatening complication such as spontaneous arterial rupture or bowel perforation. We report a 16-year-old male who had recurrent right thigh hematoma after simple exercise and minor trauma, respectively. He had a history of surgery due to spontaneous colon perforation at his age of 11 years. Gene test of COL3A1 revealed a novel mutation c.2931+dupT.

• Molecular & Cellular Toxicology
• /
• v.2 no.1
• /
• pp.21-28
• /
• 2006

Gadolinium chloride ($GdCl_{3}$) was known to block Kupffer cells and generally its toxicity study based on blocking these cells. Therefore, $GdCl_{3}$ frequently used to study toxic mechanisms of hepatotoxicants inducing injury through Kupffer cells. We also tried to investigate the effect of $GdCl_{3}\;on\;CCl_{4}$ toxicity, typical hepatotoxicants. Administration of $GdCl_{3}$ to mice significantly suppressed AST (asparatate amino transferase), ALT (alanine amino transferase) levels which were increased by $CCl_{4}$ treatment. However, $GdCl_{3}$ didn't inhibit the phagocytotic activity of Kupffer cells. Malondialdehyde (MDA) is a good indicator of the degree of lipid peroxidation. In this study, MDA increased by $GdCl_{3}$ administration not by $CCl_{4}$. To understand the toxicity of $GdCl_{3}$, we analyzed global gene expression profile of mice liver after acute $GdCl_{3}$ injection. Four hundred fifty two genes were differentially expressed with more than 2-fold in at least one time point among 3 hr, 6 hr, and 24 hr. Several genes involved in fibrogenesis regulation. Several types of pro-collagens (Col1a2, Col5a2, Col6a3, and Col13a1) and tissue inhibitor of metal-loproteinase1 (TIMP1) were up regulated during all the time points. Genes related to growth factors, chemokines, and oxidative stress, which were known to control fibrogenesis, were significantly changed. In addition, $GdCl_{3}$ induced abnormal regulation between lipid synthesis and degradation related genes. These data will provide the information about influence of $GdCl_{3}$ to hepatotoxicity.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.359-368
• /
• 2023

This study aims to explore the impact of Krill Oil (KO, Superba^TM Boost) on skin moisturization regulation. The research involved five groups: an intact control, a reference group (L-AA 100 mg/kg), and KO groups (400, 200, and 100 mg/kg), each comprising ten mice. Oral administration was conducted for 8 weeks (56 days), during which changes in body weight, hyaluronan, collagen type 1 (COL1), transforming growth factor-β1 (TGF-β1), ceramide, and water contents were analyzed in dorsal back skin tissue. Real-time PCR was employed to assess gene expression related to hyaluronic acid synthesis (HAS1, HAS2, HAS3), COL1 synthesis (COL1A1 and COL1A2), and TGF-β1. Results demonstrated that KO administration significantly increased hyaluronan content, hyaluronic acid synthesis (HAS1, HAS2, HAS3), COL1 content, COL1 synthesis (COL1A1 and COL1A2), TGF-β1 content, TGF-β1 mRNA expression, ceramide content, and water content in a concentration-dependent manner compared to the intact control. Importantly, no discernible disparities were noted between the KO and L-AA groups, even though they received equivalent oral dosages. This study accentuates the potential utility of exogenous KO in the regulation of skin moisture, thus positioning it as a promising avenue for the development of nutricosmetics. Future research endeavors should delve into the role of KO in safeguarding against both intrinsic and extrinsic aging-related skin manifestations, as well as its potential to ameliorate skin wrinkles, in conjunction with its moisturizing attributes.

• Journal of Genetic Medicine
• /
• v.19 no.2
• /
• pp.63-75
• /
• 2022

Purpose: Osteoporosis is a common calcium and metabolic skeletal disease which is characterized by decreased bone mass, microarchitectural deterioration of bone tissue and impaired bone strength, thereby leading to enhanced risk of bone fragility. In this study, we aimed to identify novel genes for susceptibility to osteoporosis and/or bone density. Materials and Methods: To identify differentially expressed genes (DEGs) between control and osteoporosis-induced cells, annealing control primer-based differential display reverse-transcription polymerase chain reaction (RT-PCR) was carried out in pre-osteoblast MC3T3-E1 cells. Expression levels of the identified DEGs were evaluated by quantitative RT-PCR. Association studies for the quantitative bone density analysis and osteoporosis case-control analysis of single nucleotide polymorphism (SNPs) were performed in Korean women (3,570 subjects) from the Korean Association REsource (KARE) study cohort. Results: Comparison analysis of expression levels of the identified DEGs by quantitative RT-PCR found seven genes, Anxa6, Col5a1, Col6a2, Eno1, Myof, Nfib, and Scara5, that showed significantly different expression between the dexamethason-treated and untreated MC3T3-E1 cells and between the ovariectomized osteoporosis-induced mice and sham mice. Association studies revealed that there was a significant association between the SNPs in the five genes, ANXA6, COL5A1, ENO1, MYOF, and SCARA5, and bone density and/or osteoporosis. Conclusion: Using a whole-genome comparative expression analysis, gene expression evaluation analysis, and association analysis, we found five genes that were significantly associated with bone density and/or osteoporosis. Notably, the association P-values of the SNPs in the ANXA6 and COL5A1 genes were below the Bonferroni-corrected significance level.

• Imaging Science in Dentistry
• /
• v.35 no.4
• /
• pp.191-198
• /
• 2005

Purpose: To characterize the effects of 2-deoxy-D-glucose (2DG) and quercetin (QCT) on cytokine secretion of IL-6, $TGF-\beta$ and gene expression of Col I in irradiated MC3T3-E1 cells Materials and Methods: The MC3T3-El cells were cultured in an a-MEM supplemented with 5mM 2DG or 10mM QCT and then the cells were incubated 12h before irradiation with 2, 4, 6, and 8Gy X-ray using a linear accelerator delivered at a dose rate of 1.5Gy/min. Level of IL-6 and $TGF-\beta$ was determined by ELISA. Also expression of Col I was examined by RT-PCR. Results: In accordance with the radiation dose, the amount of $TGF-\beta$ was not different in RA + QCT, but it showed a peak value in control and RA + 2DG at 4Gy on the 3rd day. However, all groups showed a decreasing tendency dose-dependently in RA+QCT on the 7th day (p<0.01). In accordance with the radiation dose, the amount of IL-6 increased dose-dependently in all groups on the 3rd day. On the 7th and 21st day, all groups showed peak values at 4Gy. RA+QCT showed a slightly increased amount of IL-6 at 2Gy, but it showed a slightly decreased amount at 4, 6, and 8Gy. In accordance with the period of culture after irradiation, the expression of Col I increased dose-dependently in RA+QCT. Conclusion: The result showed that QCT acted as radiosensitizer in the secretion of $TGF-\beta$ and gene expression of Col I during differentiation in irradiated MC3T3-E1 cells at the cellular level.

• Genomics & Informatics
• /
• v.12 no.4
• /
• pp.247-253
• /
• 2014

Osteosarcoma is the most common primary bone tumor, generally affecting young people. While the etiology of osteosarcoma has been largely unknown, recent studies have suggested that cyclooxygenase-2 (COX-2) plays a critical role in the proliferation, migration, and invasion of osteosarcoma cells. To understand the mechanism of action of COX-2 in the pathogenesis of osteosarcoma, we compared gene expression patterns between three stable COX-2-overexpressing cell lines and three control cell lines derived from U2OS human osteosarcoma cells. The data showed that 56 genes were upregulated, whereas 20 genes were downregulated, in COX-2-overexpressed cell lines, with an average fold-change > 1.5. Among the upregulated genes, COL1A1, COL5A2, FBN1, HOXD10, RUNX2, and TRAPPC2 are involved in bone and skeletal system development, while DDR2, RAC2, RUNX2, and TSPAN31 are involved in the positive regulation of cell proliferation. Among the downregulated genes, HIST1H1D, HIST1H2AI, HIST1H3H, and HIST1H4C are involved in nucleosome assembly and DNA packaging. These results may provide useful information to elucidate the molecular mechanism of the COX-2-mediated malignant phenotype in osteosarcoma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.35 no.4
• /
• pp.63-74
• /
• 2022

Objectives : Skin aging is generally characterized by wrinkles, sagging, loss of elasticity roughness, pigmentation and dryness. This changes is caused by reducing the elements constituting the extracellular matrix contributing to the physiological properties of the skin, such as collagen fiber, elastic fiber, and hyaluronic acid. Adequate skin hydration is important to maintain normal skin function and reduce skin aging. The present study is objective to observe skin moisturizing effects of Unripe apple(UA, Immature fruit of Malus pumila Mill) in vivo and its underlying molecular mechanisms. Methods : ICR mice were orally administerd UA(100, 200 and 400mg/kg/day) for 8 weeks, and skin water contents and the expression of transforming growth factor (TGF)-𝛽1, ceramide, hyaluronan and collagen type I(COL1) were measured in dorsal back skin of the mice. Gene expression of hyaluronan synthase(HAS1, HAS2, HAS3), collagen synthase(COL1A1, COL1A2) and TGF-𝛽1 were also determined by realtime RT-PCR. Results : Skin water contents and the expression of TGF-𝛽1, ceramide, COL1 and hyaluronan were significantly increased in UA group(100, 200 and 400mg/kg/day) compared to vehicle control. The mRNA expression of HAS isoform(HAS1, HAS2, HAS3), COL1A1, COL1A2, and TGF-𝛽1 were also significantly increased by UA. Conclusions : UA has skin moisturizing effects and enhancement activities in skin function related components(COL1, hyaluronan, ceramide and TGF-𝛽1). These results suggested that UA can be a developing candidate for developing alternative skin protective agent or functional food ingredient.

• Molecular & Cellular Toxicology
• /
• v.3 no.2
• /
• pp.137-144
• /
• 2007

The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.

• Journal of Korean Medicine Rehabilitation
• /
• v.30 no.2
• /
• pp.47-66
• /
• 2020

Objectives The purpose of this study is to evaluate the bone healing effect of Dohongsamul-tang (Taohongsiwu-tang; DH) on femur fractured mice. Methods Mice were randomly divided into 4 groups (naive, control, positive control and DH). All groups except naive group were subjected to bone fracture on both hind limb femurs. Naive group received no treatment at all. Control group was fed with normal saline, and positive control group was orally medicated with tramadol. DH-treated group was orally medicated with DH. We analysed the levels of BMP2, COX2, Col2a1, Sox9, Runx2, and Osterix genes on 3, 7 and 14 days after fracture. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, total cholesterol, and triglyceride levels were measured for safety assessment. Results In morphological, histological analysis, callus formation process of DH-treated group was faster than the control group. BMP2, Sox9 gene expression were significantly increased at 7 days after fracture compared to the control group. COX2, Col2a1 gene expression were significantly increased at 14 days after fracture compared to the control group. Total cholesterol was significantly increased by DH at 3 days. Triglyceride was significantly decreased by DH at 3, 7 days after fracture compared to the control group. Conclusions Dohongsamul-tang promoted bone healing process after fracture by stimulating the bone regeneration factors. And DH shows no hepatotoxicity, nephrotoxicity and serum lipid abnormality. In conclusion, it seems that DH helps to promote fracture regeneration after bone fracture by regulating gene expressions related to bone repair.

• Journal of Sericultural and Entomological Science
• /
• v.50 no.1
• /
• pp.15-19
• /
• 2012

A number of researcher have studied biomaterials for cartilage regeneration and are now proceeding. Silk protein was attempted for use as biomedical materials by many researchers because it is natural polymer with biocompatibility and excellent mechanical strength. In this study, we want to know a possibility of silk protein on the cartilage regeneration. We isolated chondrocytes from nasal cartilage and confirmed optimal culture condition of the cells. To observe the effects of silk fibroin on chondrogenesis, we added silk fibroin solutions to the culture medium of chondrocyte and detected gene expression levels related chondrogenesis such as col2, col10. The chondrocytes showed optimal growth when they were cultured in DMEM medium supplemented with 10% FBS 100 ${\cdot}{\ddot{I}}$M ascorbic acid. The levels of col2 gene expression were increased in non-autoclaved silk fibroin, but decreased in autoclaved one. Also the gene expression levels of col10 were increased in silk fibroin, particulary at 3D culture. Based on the results of this study, we had seen the possibility of silk fibroin for cartilage regeneration. In future studies, we should know more clearly the relationship between cartilage regeneration and the silk protein.