• Journal of Interdisciplinary Genomics
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• v.2 no.2
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• pp.20-25
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• 2020

Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) is a multisystem lysosomal storage disease that is inherited in an autosomal recessive manner. It consists of four subtypes (MPS IIIA, B, C, and D), each characterized by the deficiency of different enzymes that catalyze the metabolism of the glycosaminoglycan heparan sulfate at the lysosomal level. The typical clinical manifestation of MPS III includes progressive central nervous system (CNS) degeneration with accompanying systemic manifestations. Disease onset is typically before the age of ten years and death usually occurs in the second or third decade due to neurological regression or respiratory tract infections. However, there is currently no treatment for CNS symptoms in patients with MPS III. Invasive and non-invasive techniques that allow drugs to pass through the blood brain barrier and reach the CNS are being tested and have proven effective. In addition, the application of genistein treatment as a substrate reduction therapy is in progress.

• Journal of mucopolysaccharidosis and rare diseases
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• v.3 no.1
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• pp.1-8
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• 2017

Mucopolysaccharidosis (MPS) type III, or Sanfilippo syndrome is a rare autosomal recessive lysosomal storage disorder. It is caused by a deficiency of one of four enzymes involved in the degradation of the glycosaminoglycan (GAG) heparan sulfate. The resultant cellular accumulation of heparan sulfate causes various clinical manifestations. MPS III is divided into four subtypes depending on the deficient enzyme: MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID. All the subtypes show similar clinical features and are characterized by progressive degeneration of the central nervous system (CNS). Main purpose of the treatment for MPS III is to prevent neurologic deterioration. However, conventional enzyme replacement therapy has a limitation due to inability to cross the blood-brain barrier. Several experimental treatment options for MPS III are being developed.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1299-1303
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• 2005

Human articular chondrocytes (HAC) were cultivated as a monolayer in a serum-free medium for primary culture (SFM-P). An optimized SFM-P provides $95\%$ proliferation rate of that obtainable from primary and secondary chondrocyte cultures grown in a control medium with serum. The gradual decrease in the amounts of synthesized glycosaminoglycan and type II collagen was improved by coating the culture dishes with type IV collagen and fibronectin. A significant improvement in the expression of type II collagen and aggrecan mRNA could be achieved. In addition, the monolayer cultures showed better synthesis of the extracellular matrices than alginate-bead cultures in SFM-P.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.2
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• pp.37-41
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• 2018

Mucopolysaccharidosis III (MPS III, Sanfilippo syndrome) is a rare autosomal recessive disease caused by a deficiency of one of four enzymes involved in the degradation of glycosaminoglycan (GAG). The resultant cellular accumulation of GAG causes various clinical manifestations. MPS III is divided into four subtypes depending on the deficient enzyme. All the subtypes show similar clinical features and are characterized by progressive degeneration of the central nervous system. A number of genetic and biochemical diagnostic methods have been developed. However, there is no effective therapy available for any form of MPS III, with treatment currently limited to clinical management of neurological symptoms. Main purpose of the treatment for MPS III is to prevent neurologic deterioration. Because conventional intravenous enzyme replacement therapy (ERT) has a limitation due to inability to cross the blood-brain barrier, several innovative therapeutic approaches for MPS III are being developed. This review covers the currently developing new therapeutic options for MPS III including high dose ERT, substrate reduction therapy, intrathecal or intraventricular ERT, fusion protein delivery using bioengineering technology, and gene therapy.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.98.2-99
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• 2003

Introduction: We previously reported that a new glycosaminoglycan, acharan sulfate (AS) from the African giant snail Achatina fulica showed anticoagulation activity in vitro, but it was much less than that of heparin. In the present study, the anticoagulant activity of AS was investigated in vivo. Methods: AS and heparin were administered to rats in various concentrations and anticoagulant activities were measured. Both were also compared in thrombin-induced Results: Intravenous administration of acharan sulfate prolonged the coltting time (APTT) in mice and rats in a dose-dependent manner. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.229.2-230
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• 2003

Extracellular matrix(ECM) is composed of the ground materials(proteoglycan) and nano size diameter fibrous proteins(ex. collagens) that together form a composite-like structure. In this study, fibrous scaffold with biomimetic architecture based on collagen nanofibers interpenetrated in PLGA/chitosan microfibrous matrix. Chitosan was selected for its structure similarity to glycosaminoglycan and neutralizing capacity for PLGA acidic metabolite. Collagen nanofiber were prepared by electrospinning. (omitted)

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.634-641
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• 2016

The objective of this research was to investigate the in vivo effects of treatment with mulberry extract complex (MEC) on cartilage degeneration and pain severity in an experimental model of rat degenerative arthritis. Monosodium iodoacetate ($2mg/50{\mu}L$) was injected into right knee joints of rats, followed by administration of MEC for 8 weeks at 400 mg/kg or 800 mg/kg of body weight. The experimental data show that treatment with MEC inhibited degradation of glycosaminoglycan and collagen in cartilage. On the other hand, concentrations of cartilage oligomeric matrix protein, C-terminal telopeptide-2, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 in serum decreased in comparison with the control. The MEC at all dose levels could inhibit formation of xylene-induced ear edema. In this study, MEC demonstrated significant anti-arthritis activity, which is required for improvement of degenerative arthritis. Based on these results, MEC may be employed for the development of new health foods to ease symptoms of degenerative arthritis.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.8-27
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• 2000

Components of extracellular matrix and the matrix-degrading enzymes are some of the key regulators of tumor metastasis and angiogenesis. Hyaluronic acid (HA), a matrix glycosaminoglycan, is known to promote tumor adhesion and migration, and its small fragments are angiogenic. Until now, we have compared levels of hyaluronidase, an enzyme that degrade HA, in normal adult prostate, benign prostate hyperplasia and prostate cancer tissues and in conditioned media from epithelial explant cultures, using a substrate (HA)-gel assay and ELISA-like assay (Kim et al., unpublished results). The present review described an overall characterization of hyaluronidases and its application to human diseases. The hyaluronidases are a family of enzymes that have, until recently, deed thorough explication. The substrate for these enzymes, hyaluronan, is becoming increasingly important, recognized now as a major participant in basic processes such as cell motility, wound healing, embryogenesis, and implicated in cancer progression. And in those lower life forms that torment human beings, hyaluronidase is associated with mechanisms of entry and spread, e.g. as a virulence factor for bacteria, for tissue dissection in gas gangrene, as a means of treponema spread in syphilis, and for penetration of skin and gut by nematode parasites. Hyaluronidase also comprises a component of the venom of a wide variety of organisms, including bees, wasps, hornets, spiders, scorpions, sh, snakes and lizards. Of particular interest is the homology between some of these venom hyaluronidases and the enzyme found in the plasma membrane of mammalian spermatozoa, attesting to the ancient nature of the conserved sequence, a 36% identity in a 300 amino acid stretch of the enzyme protein. Clearly, hyaluronidase is of biological interest, being involved in the pathophysiology of so many important' human disorders. Greater effort should be made in studying this family of enzymes that have, until recently, been overlooked. Also, oriental medical application of the hyaluronidase will be discussed with respect to inhibition and suppression of inflammation and malignacy.

• Herbal Formula Science
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• v.16 no.2
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• pp.115-131
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• 2008

실험목적 : 빈소산은 11가지 생약으로 구성된 복합 한약 처방으로 관절염을 포함한 다양한 염증성 질환의 치료제로 사용되어 왔으나, 관절염에 대한 직접적인 효력평가는 찾아 보기 힘들다. 따라서 본 실험에서는 빈소산 추출물이 Freund's complete adjuvant (FCA)로 유발된 rat 류마티스성 관절염에 미치는 치료 효과를 dexamethasone (15mg/kg, 복강 투여) 의 효과와 비교 평가하였다. 실험방법 : 류마티스성 관절염은 FCA (10mg in 1ml paraffin oil 0.1ml/rats)를 좌측 후지에 피내 투여하여 유발하였다. 실험동물은 Wistar 랫트를 사용하였고, FCA 투여 14일 후 유사한 무릎관절 둘레를 나타내는 류마티스성 관절염 유발 rat와 정상 rat 및 실험군을 그룹당 9마리씩 나누었다. 실험동물은 100 또는 200mg/kg의 빈소산 추출물을 FCA 투여 14일 후부터 14일간 경구 투여하였으며, dexamethasone은 15mg/kg 농도로 복강 투여한 다음, 희생하여, 체중, 연골내 collagen 함량 및 chondroitin sulphate, heparin sulphate 및 hyaluronic acid와 같은 뼈내 glycosaminoglycan 함량의 변화를 각각 관찰하였다. 실험결과는 항염 효과가 이미 입증되어 있는 dexamethasone 15mg/kg 복강 투여군과 비교하였다. 결과 : FCA 투여는 현저한 체중, 연골내 collagen 함량 및 chondroitin sulphate, heparin sulphate 및 hyaluronic acid와 같은 뼈내 glycosaminoglycan 함량의 감소와 함께 유발 관절 둘레 및 조직내 prostaglandin $E_2$의 증가와 같은 전형적인 류마티스성 염증을 초래하였으나, 이러한 류마티스성 관절염 소견은 dexamethasone 및 모든 용량의 빈소산 추출물 투여에 의해 현저히 억제되었으며, 특히 빈소산 투여군에서는 투여 용량 의존적인 감소가 인정되었다. 결론 : 이상에서 빈소산 추출물은 투여 용량 의존적인 prostaglandin $E_2$ 억제를 매개하여 FCA 유발 류마티스성 관절염에 대한 치료 효과를 나타내는 것으로 관찰되었다. 따라서 새로운 관절염에 대한 치료제로서 개발 가능성이 있을 것으로 판단된다. 한편 빈소산 추출물은 주로 prostaglandin $E_2$ 억제작용에 의해 항염 효과를 나타내는 것으로 관찰되었으나, 금후 다른 작용기전에 대한 연구와 빈소산의 구성성분 중 유효 성분 규명을 위한 실험이 수행되어야 할 것으로 판단된다.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.44-48
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• 2015

Mucopolysaccharidosis (MPS) IIIA is a lysosomal storage disorder caused by abnormalities of the enzyme Heparan N-sulfatase that is required for degradation of heparan sulfate. The patient in this study was a 5 year-old boy who presented with macrocephaly and developmental delay. Urinary excretion of glycosaminoglycan was increased (26 g/moL creatinine, reference range: <7 g/moL creatinine) and a distinct band of heparan sulfate was shown in electrophoresis. Heparan N-sulfatase activity was significantly decreased in skin fibroblasts (0.2 pmoL/min/mg protein, reference range: 9-64 pmoL/min/mg protein). PCR and direct sequencing analysis of the SGSH gene showed compound heterozygous mutations: c.1040C>T (p.S347F) and c.703G>A (p.D235N). This is the first report for a Korean patient with MPS IIIA who was confirmed by biochemical investigation and molecular genetic analyses.