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Inhibitory Effect of Biotransformed-Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand

  • Park, Bobae;Yu, Sun Nyoung;Kim, Sang-Hun;Lee, Junwon;Choi, Sung Jong;Chang, Jeong Hyun;Yang, Eun Ju;Kim, Kwang-Youn;Ahn, Soon-Cheol
    • Journal of Microbiology and Biotechnology
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    • v.32 no.8
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    • pp.1017-1025
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    • 2022
  • Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

Genetic diversity and selection of Tibetan sheep breeds revealed by whole-genome resequencing

  • Dehong Tian;Buying Han;Xue Li;Dehui Liu;Baicheng Zhou;Chunchuan Zhao;Nan Zhang;Lei Wang;Quanbang Pei;Kai Zhao
    • Animal Bioscience
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    • v.36 no.7
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    • pp.991-1002
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    • 2023
  • Objective: This study aimed to elucidate the underlying gene regions responsible for productive, phenotypic or adaptive traits in different ecological types of Tibetan sheep and the discovery of important genes encoding valuable traits. Methods: We used whole-genome resequencing to explore the genetic relationships, phylogenetic tree, and population genetic structure analysis. In addition, we identified 28 representative Tibetan sheep single-nucleotide polymorphisms (SNPs) and genomic selective sweep regions with different traits in Tibetan sheep by fixation index (Fst) and the nucleotide diversity (θπ) ratio. Results: The genetic relationships analysis showed that each breed partitioned into its own clades and had close genetic relationships. We also identified many potential breed-specific selective sweep regions, including genes associated with hypoxic adaptability (MTOR, TRHDE, PDK1, PTPN9, TMTC2, SOX9, EPAS1, PDGFD, SOCS3, TGFBR3), coat color (MITF, MC1R, ERCC2, TCF25, ITCH, TYR, RALY, KIT), wool traits (COL4A2, ERC2, NOTCH2, ROCK1, FGF5, SOX9), and horn phenotypes (RXFP2). In particular, a horn-related gene, RXFP2, showed the four most significantly associated SNP loci (g. 29481646 A>G, g. 29469024 T>C, g. 29462010 C>T, g. 29461968 C>T) and haplotypes. Conclusion: This finding demonstrates the potential for genetic markers in future molecular breeding programs to improve selection for horn phenotypes. The results will facilitate the understanding of the genetic basis of production and adaptive unique traits in Chinese indigenous Tibetan sheep taxa and offer a reference for the molecular breeding of Tibetan sheep.

Clinicopathological Characteristics of Superficially Spreading Early Gastric Cancer (표층 확장형 조기위암의 임상병리학적 특성)

  • Kwon, Sung-Joon;Kim, Hyoung-Ju
    • Journal of Gastric Cancer
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    • v.5 no.4 s.20
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    • pp.288-294
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    • 2005
  • Purpose: Superficially spreading (SS) early gastric cancer (EGC) is characterized by wide horizontal extension without deep vertical invasion. It is a relatively rare form of EGC, and it's clinicopathological (C-P) characteristics are not evident. This study aimed to clarify their C-P characteristics. Materials and Methods: We defined SS EGC as invading less than the submucosal layer that measured more than 60 mm in diameter or wider than $5{\times}5cm \;(25cm^2)$ in width. The C-P characteristics and prognosis were compared between 69 patients with SS EGC and 319 patients with the common type EGC (EGC except SS type). Results: For SS EGC lymph node metastases, Lauren's diffuse type, lymphatic invasion were significantly higher than in common type EGC. In patients with SS EGC, all of the metastatic lymph nodes were anatomically distributed within the paragastric region, with fewer along the left gastric artery and common hepatic artery. In 6 cases of SS EGC with resection marqins less than 10 mm, there was no death during the follow-up period (4 to 13 years after operation) if margins were not involved. Age (>58 yrs), tumor site (upper 1/3), lymph node metastasis, submucosal invasion were statistically significant poor prognostic factor in univariate survival analysis. In multivariate survival analysis, age and lymph node metastasis were independent prognostic factors. However, tumor diameter or width was not a significant prognostic factor. Conclusion: Although SS EGC has histologically distinct properties, gastrectomy with free surgical margins and appropriate lymph node dissection $(D1+{\beta})$ could be a suitable treatment.

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Optimum Population in Korea : An Economic Perspective (한국의 적정인구: 경제학적 관점)

  • Koo, Sung-Yeal
    • Korea journal of population studies
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    • v.28 no.2
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    • pp.1-32
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    • 2005
  • The optimum population of a society or country can be defined as 'the population growth path that maximizes the welfare level of the society over the whole generations of both the present and the future, under the paths allowed by its endowments of production factors such as technology, capital and labor'. Thus, the optimum size or growth rate of population depends on: (i) the social welfare function, (ii) the production function, and (iii)demographic economic interrelationship which defines how the national income is disposed into consumption(birth and education of children included) and savings on the one hand and how the demographic and economic change induced thereby, in turn, affect production capacities on the other. The optimum population growth path can, then, be derived in the process of dynamic optimization of (i) under the constraints of (ii) and (iii), which will give us the optimum population growth rate defined as a function of parameters thereof. This paper estimates the optimum population growth rate of Korea by: specifying (i), (ii), and (iii) based on the recent development of economic theories, solving the dynamic optimization problem and inserting empirical estimates in Korea as the parametric values. The result shows that the optimum path of population growth in Korea is around TFR=1.81, which is affected most sensitively, in terms of the size of the partial elasticity around the optimum path, by the cost of children, share of capital income, consumption rate, time preference, population elasticity of utility function, etc. According to a survey implemented as a follow up study, there are quite a significant variations in the perceived cost of children, time preference rate, population elasticity of utility across different socio-economic classes in Korea, which implied that, compared to their counterparts, older generation and more highly educated classes prefer higher growth path for the population of Korea.