• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• Journal of Genetic Medicine
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• v.13 no.1
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• pp.41-45
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• 2016

Marfan syndrome (MFS) is an inherited connective tissue disorder with a mutation in the fibrillin-1 (FBN1) gene. Fibrillin is a major building block of microfibrils, which constitute the structural component of the connective tissues. A 10-year-old girl visited our hospital with the chief complaint of precocious puberty. According to her medical history, she had a pulmonary wedge resection for a pneumothorax at 9 years of age. There was no family history of MFS. Mid parental height was 161.5 cm. The patient's height was 162 cm (>97th percentile), and her weight was 40 kg (75th-90th percentile). At the time of initial presentation, her bone age was approximately 11 years. From the ophthalmologic examination, there were no abnormal findings except myopia. There was no wrist sign. At the age of 14 years, she revisited the hospital with the chief complaint of scoliosis. Her height and weight were 170 cm and 50 kg, respectively, and she had arachnodactyly and wrist sign. We performed an echocardiograph and a test for the FBN1 gene mutation with direct sequencing of 65 coding exons, suspecting MFS. There were no cardiac abnormalities including mitral valve prolapse. A cytosine residue deletion in exon 7 (c.660delC) was detected. This is a novel mutation causing a frameshift in protein synthesis and predicted to create a premature stop codon. We report the case of a patient with MFS with a novel FBN1 gene missense mutation and a history of pneumothorax at a young age without cardiac abnormalities during her teenage years.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.350.1-350
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• 1998

No Abstract, See Full Text

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.286.1-286
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• 1999

No Abstract, See Full Text

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.171-178
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• 2021

In this study, exosomal-like nano-vesicles derived from probiotics were isolated and various physiological activities were evaluated on the skin. This study show that Lactococcus lactis subsp. lactis (LL) are incubated, and then isolated LL derived exosomal nanovesicles (LVs) at the range of 70 ~ 200 nm by high-pressure homogenizer and ultrafiltration. The vesicle numbers were an average of 1.81 × 10¹¹ particles/mL. This study finds out the bacterial nanovesicles' beneficial effect on the skin. Fibrillin (FBN1) gene expression increased by 23% in fibroblast cells. Fibronectin (FN1) and filaggrin (FLG) gene expression increased by 65% and 400% in keratinocytes. We could see that cornified envelope (CE) formation ability was increased by 30% compared to the control group. Furthermore, collagen type I alpha 1 (COL1A1) protein expression increased by 83% compared to the UV-irradiated control group. These results suggest that LVs could help skin barrier improvement and used as an ingredient for cosmetics or pharmaceuticals.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.143-148
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• 2014

Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.139-145
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• 2021

Plant-derived exosome-like nanovesicles (PELNs) are known to include various biological activities and possess high biocompatibility. Because PELNs can influence immune responses, cell differentiation, and proliferation regulation, they can be applied in multiple industries. However, the studies on the skin physiological of exosome-like nanovesicles derived from plant callus are insignificant compared to nanovesicles derived from mammalian cells. In this study, callus was induced from apple fruit (Malus domestica), and exosome-like nanovesicles (ACELNs) were isolated for improving skin barrier and anti-aging. The yield of ACELNs was 6.42 × 10⁹ particles/mL, and the particle size was ranged from 100 to 200 nm. HDF cells and HaCaT cells were concentration-dependent, increased in cell, and decreased in cytotoxicity. The cornified envelope formation was significantly increased compared to the control group. The COL1A1 expression and the FBN1 expression in HDF cells were increased. In addition, the ACELNs promoted collagen biosynthesis in UVA-irradiated HDF cells. These results might be considered as potential materials that could improve skin barrier and prevent skin aging.

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

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.43-46
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• 2020

The Shprintzen-Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI. SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.

• Journal of Animal Science and Technology
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• v.60 no.5
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• pp.13.1-13.7
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• 2018

Background: The objective of this study was to underline that litter size as a key trait of sows needs new parameters to be evaluated and to target an individual optimum. Large individual variation in litter size affects both production and piglet's survival and health negatively. Therefore, two new traits were suggested and analyzed. Two data sets on 5509 purebred German Landrace sows and 3926 Large White and crossing sows including at least two parental generations and at least five parities were subjected to variance components analysis. Results: The new traits for evaluating litter size were derived from the individual numbers of total born piglets (TBP) per parity: In most cases, sows reach their maximum litter size in their fourth parity. Therefore, data from at least five parities were included. The first observable maximum and minimum of TBP, and the individual variation expressed by the range were targeted. Maximum of TBP being an observable trait in pig breeding and management yielded clearly higher heritability estimates ($h^2{\sim}0.3$) than those estimates predominantly reported so far. Maximum TBP gets closer to the genetic capacity for litter size than other litter traits. Minimum of TBP is positively correlated with the range of TBP ($r_p=0.48$, $r_g$ > 0.6). The correlation between maximum of TBP and its individually reached frequency was negative in both data sets ($r_p=-0.28$ and - 0.22, respectively). Estimated heritability coefficients for the range of TBP comprised a span of $h^2=0.06$ to 0.10. Conclusion: An optimum both for maximum and range of total born piglets in selecting sows is a way contributing to homogenous litters in order to improving the animal-related conditions both for piglets' welfare and economic management in pig.