Publications by authors named "Jae Sung Ryu"

36 Publications

Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.

Int J Pharm 2021 Sep 19;606:120904. Epub 2021 Jul 19.

Department of Electronic Materials and Devices Engineering, Soonchunhyang University, Asan 31538, Republic of Korea; Department of Chemical Engineering, Soonchunhyang University, Asan 31538, Republic of Korea. Electronic address:

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120904DOI Listing
September 2021

Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases.

Int J Mol Sci 2020 Nov 7;21(21). Epub 2020 Nov 7.

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea.

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.
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http://dx.doi.org/10.3390/ijms21218366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664655PMC
November 2020

Long-Term Expansion of Functional Human Pluripotent Stem Cell-Derived Hepatic Organoids.

Int J Stem Cells 2020 Jul;13(2):279-286

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.

A human cell-based liver model capable of long-term expansion and mature hepatic function is a fundamental requirement for pre-clinical drug development. We previously established self-renewing and functionally mature human pluripotent stem cell-derived liver organoids as an alternate to primary human hepatocytes. In this study, we tested long-term prolonged culture of organoids to increase their maturity. Organoid growing at the edge of Matrigel started to deteriorate two weeks after culturing, and the expression levels of the functional mature hepatocyte marker were decreased at four weeks of culture. Replating the organoids weekly at a 1:2 ratio in fresh Matrigel, resulted in healthier morphology with a thicker layer compared to organoids maintained on the same Matrigel and significantly increased expression until three weeks, although, it decreased sharply at four weeks. The levels of the fetal hepatocyte marker were considerably increased in long-term cultures of organoids. Therefore, we performed serial passaging of organoids, whereby they were mechanically split weekly at a 1:3∼1:5 ratio in fresh Matrigel. The organoids expanded so far over passage 55, or 1 year, without growth retardation and maintained a normal karyotype after long-term cryopreservation. Differentiation potentials were maintained or increased after long-term passaging, while expression considerably decreased after passaging. Therefore, these data demonstrate that organoids can be exponentially expanded by serial passaging, while maintaining long-term functional maturation potential. Thus, hepatic organoids can be a practical and renewable cell source for human cell-based and personalized 3D liver models.
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http://dx.doi.org/10.15283/ijsc20060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378903PMC
July 2020

Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors.

Int J Mol Sci 2020 Mar 13;21(6). Epub 2020 Mar 13.

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea.

Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.
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http://dx.doi.org/10.3390/ijms21061967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139639PMC
March 2020

Targeting CYP4A attenuates hepatic steatosis in a novel multicellular organotypic liver model.

J Biol Eng 2019 8;13:69. Epub 2019 Aug 8.

1Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141 Republic of Korea.

Background: Non-alcoholic fatty liver disease (NAFLD) begins as simple hepatic steatosis, but further progress to chronic liver diseases results in severe liver damage and hepatic failure. However, therapeutic options are scarce due to the lack of reliable human in vitro liver models for understanding disease progression mechanisms and developing therapies.

Results: We describe here a novel method for generating 3D hepatic spheroids using HepaRG cells, vascular endothelial cells, and mesenchymal stem cells cultured on a thick layer of soft matrix in a narrow conical tube; this method improved self-organization efficiency and functional competence. We further developed a 3D hepatic steatosis model with excess glucose and palmitate, accurately recapitulating steatosis phenotypes such as neutral lipid accumulation, enhanced expression of lipogenesis and gluconeogenesis markers, increased intracellular triglyceride content, and reduced glucose uptake. The expression and activity of cytochrome P450 4A (CYP4A), a hepatic glucose and lipid homeostasis enzyme, that is highly expressed in liver tissues from NAFLD patients, was induced in our in vitro steatosis model, and inhibiting CYP4A with the selective inhibitor HET0016 or a specific siRNA ameliorated steatosis-related pathology through reduced ER stress and improved insulin signaling.

Conclusions: We provide here a novel 3D human cell-based hepatic model that can be easily generated and reliably simulate hepatic steatosis pathology. We have experimentally validated its potential for target validation and drug evaluation by focusing on CYP4A, which may serve as a translational platform for drug development.
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http://dx.doi.org/10.1186/s13036-019-0198-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686528PMC
August 2019

Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids.

J Hepatol 2019 11 9;71(5):970-985. Epub 2019 Jul 9.

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea; Department of Functional Genomics, Korea University of Science & Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea. Electronic address:

Background & Aims: The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids have not been developed.

Methods: We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. The organoids were applied to screening platforms for the prediction of toxicity and the evaluation of drugs that target hepatic steatosis through real-time monitoring of cellular bioenergetics and high-content analyses.

Results: Our organoids were morphologically indistinguishable from adult liver tissue-derived epithelial organoids and exhibited self-renewal. With further maturation, their molecular features approximated those of liver tissue, although these features were lacking in 2D differentiated hepatocytes. Our organoids preserved mature liver properties, including serum protein production, drug metabolism and detoxifying functions, active mitochondrial bioenergetics, and regenerative and inflammatory responses. The organoids exhibited significant toxic responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis.

Conclusions: Our organoids exhibit self-renewal (expandable and further able to differentiate) while maintaining their mature hepatic characteristics over long-term culture. These organoids may provide a versatile and valuable platform for physiologically and pathologically relevant hepatic models in the context of personalized medicine.

Lay Summary: A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.
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http://dx.doi.org/10.1016/j.jhep.2019.06.030DOI Listing
November 2019

A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming.

Exp Mol Med 2018 12 6;50(12):1-15. Epub 2018 Dec 6.

Department of Functional Genomics, Korea University of Science & Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon, 34113, Republic of Korea.

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.
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http://dx.doi.org/10.1038/s12276-018-0185-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283868PMC
December 2018

Multigenerational effects of maternal cigarette smoke exposure during pregnancy on sperm counts of F1 and F2 male offspring.

Reprod Toxicol 2018 06 22;78:169-177. Epub 2018 Apr 22.

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Republic of Korea; Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Republic of Korea; Research Institute of Medical Science, Konkuk University, Seoul, Republic of Korea. Electronic address:

Animal models and human studies showed that in utero cigarette smoke exposure decreases sperm counts of offspring. This study used a mouse model to investigate the effects of maternal exposure to cigarette smoke on reproductive systems in F1 and F2 male offspring. Female ICR mice were exposed either to clean air or to cigarette smoke during pregnancy at the post-implantation stage. Epididymal sperm counts were decreased in a cigarette smoke dose-dependent manner in F1 (by 40-60%) and F2 males (by 23-40%) at postnatal day 56. In F1, the seminiferous epithelium heights were lower in the cigarette smoke-exposed groups than in the control group, and these effects were sustained in F2 males. Results suggest that maternal cigarette smoke exposure during pregnancy can have a multigenerational adverse effect on sperm counts in male offspring, which is mediated through in utero exposure of fetal germ cells to cigarette smoke.
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http://dx.doi.org/10.1016/j.reprotox.2018.04.011DOI Listing
June 2018

Roles of gangliosides in the differentiation of mouse pluripotent stem cells to neural stem cells and neural cells (Review).

Mol Med Rep 2017 Aug 8;16(2):987-993. Epub 2017 Jun 8.

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan, Jeollabuk 54538, Republic of Korea.

Glycosphingolipids are important components of the outer layer of the plasma membrane in the majority of eukaryotic cells. Specifically, gangliosides are sialic acid‑containing glycosphingolipids that participate in cell‑cell recognition, adhesion, proliferation, differentiation and signal transduction, and are integral components of cell surface microdomains and lipid rafts. Stem cells are defined functionally as cells that have the capacity to self‑renewal and differentiate to generate various cell types. Due to different synthesis patterns and locations of gangliosides, they have been used as molecular markers of stem cells. The current review describes the presence of gangliosides in various types of mouse stem cells, including pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) and neural stem cells, and the functional roles of gangliosides in various processes, including cell proliferation and neural differentiation. Thus, this review will aid the understanding of gangliosides patterns and functions in mouse stem cells, and outline markers for the identification of stem cells.
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http://dx.doi.org/10.3892/mmr.2017.6719DOI Listing
August 2017

Erratum to: Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells.

BMB Rep 2017 Jun;50(6):341

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749, Korea

The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".
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June 2017

Upregulation of mitochondrial NAD levels impairs the clonogenicity of SSEA1 glioblastoma tumor-initiating cells.

Exp Mol Med 2017 06 9;49(6):e344. Epub 2017 Jun 9.

Department of Functional Genomics, Korea University of Science &Technology (UST), Daejeon, Korea.

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD) metabolism. However, the functional role of NAD metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD levels affect the characteristics of glioma-driven SSEA1 TICs, including clonogenic growth potential. An increase in the mitochondrial NAD levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.
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http://dx.doi.org/10.1038/emm.2017.74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519015PMC
June 2017

A Multicenter Study Investigating Empathy and Burnout Characteristics in Medical Residents with Various Specialties.

J Korean Med Sci 2016 Apr 2;31(4):590-7. Epub 2016 Mar 2.

Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, Korea .

We assessed empathy in medical residents, including factors modifying empathy and the relationship between empathy and burnout. Participants (n = 317 residents, response rate = 42%) from 4 university hospitals completed a socio-demographic questionnaire, the Jefferson Scale of Empathy (Health Professional version, Korean edition), and the Maslach Burnout Inventory (MBI). Participants were classified by medical specialty: "people-oriented specialty" (POS group) or "technology-oriented specialty" (TOS group), with more women in the POS than in the TOS group, χ(2) = 14.12, P < 0.001. Being female, married, and having children were factors related to higher empathy (gender, t = -2.129, P = 0.034; marriage, t = -2.078, P = 0.038; children, t = 2.86, P = 0.005). Within specialty group, POS residents showed higher empathy scores in the fourth as compared to the first year, F = 3.166, P = 0.026. Comparing POS and TOS groups by year, fourth year POS residents had significantly higher scores than did fourth year TOS residents, t = 3.349, P = 0.002. There were negative correlations between empathy scores and 2 MBI subscales, emotional exhaustion (EE) and depersonalization (DP). Additionally, first year POS residents had higher DP scores than did first year TOS residents, t = 2.183, P = 0.031. We suggest that factors important for empathy are type of medical specialty, marriage, siblings, and children. Burnout state may be related to decreasing empathy.
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http://dx.doi.org/10.3346/jkms.2016.31.4.590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810343PMC
April 2016

Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold?

Am J Sports Med 2015 Jan 27;43(1):176-85. Epub 2014 Oct 27.

Center for Stem Cell and Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Korea

Background: The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions.

Purpose: To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold.

Study Design: Cohort study; Level of evidence, 3.

Methods: This study retrospectively evaluated 54 patients (56 knees) who were examined with second-look arthroscopy after MSC implantation for cartilage lesions in their OA knees. Patients were divided into 2 groups: 37 patients (39 knees) were treated with MSC implantation without a scaffold (group 1), and 17 patients (17 knees) underwent implantation of MSCs loaded in fibrin glue as a scaffold (group 2). Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed with the International Cartilage Repair Society (ICRS) grade. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes.

Results: At final follow-up (mean, 28.6 months; range, 24-34 months), the mean IKDC score and Tegner activity scale in each group significantly improved: group 1, from 38.1±7.7 to 62.0±11.7 (IKDC) and from 2.5±0.9 to 3.5±0.8 (Tegner); group 2, from 36.1±6.2 to 64.4±11.5 (IKDC) and from 2.2±0.8 to 3.8±0.8 (Tegner) (P<.001 for all). According to the overall ICRS cartilage repair grades, 9 of the 39 lesions (23%) in group 1 and 12 of the 17 lesions (58%) in group 2 achieved a grade of I or II. There was a significant difference in ICRS grades between the groups (P=.028). Overweight (body mass index≥27.5 kg/m2) and large lesion size (≥5.7 cm2) were significant predictors of poor clinical and arthroscopic outcomes in group 1 (P<.05 for both). There was a similar trend in group 2, but the differences were not significant, possibly owing to the smaller sample size.

Conclusion: Clinical and arthroscopic outcomes of MSC implantation were encouraging for OA knees in both groups, although there were no significant differences in outcome scores between groups. However, at second-look arthroscopy, there were better ICRS grades in group 2.
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http://dx.doi.org/10.1177/0363546514554190DOI Listing
January 2015

Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells.

Biochem Biophys Res Commun 2014 Aug 15;450(4):1593-9. Epub 2014 Jul 15.

Center for Stem Cell & Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea. Electronic address:

Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs.
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http://dx.doi.org/10.1016/j.bbrc.2014.07.045DOI Listing
August 2014

A novel feeder-free culture system for expansion of mouse spermatogonial stem cells.

Mol Cells 2014 Jun 23;37(6):473-9. Epub 2014 May 23.

Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea ; Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701, Korea.

Spermatogonial stem cells (SSCs, also called germline stem cells) are self-renewing unipotent stem cells that produce differentiating germ cells in the testis. SSCs can be isolated from the testis and cultured in vitro for long-term periods in the presence of feeder cells (often mouse embryonic fibroblasts). However, the maintenance of SSC feeder culture systems is tedious because preparation of feeder cells is needed at each subculture. In this study, we developed a Matrigel-based feeder-free culture system for long-term propagation of SSCs. Although several in vitro SSC culture systems without feeder cells have been previously described, our Matrigel-based feeder-free culture system is time- and cost- effective, and preserves self-renewability of SSCs. In addition, the growth rate of SSCs cultured using our newly developed system is equivalent to that in feeder cultures. We confirmed that the feeder-free cultured SSCs expressed germ cell markers both at the mRNA and protein levels. Furthermore, the functionality of feeder-free cultured SSCs was confirmed by their transplantation into germ cell-depleted mice. These results suggest that our newly developed feeder-free culture system provides a simple approach to maintaining SSCs in vitro and studying the basic biology of SSCs, including determination of their fate.
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http://dx.doi.org/10.14348/molcells.2014.0080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086341PMC
June 2014

Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes.

Biochem Biophys Res Commun 2014 May 21;447(4):715-20. Epub 2014 Apr 21.

Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, 478-3, Bangbae-dong, Seocho-gu, 137-820 Seoul, Republic of Korea. Electronic address:

Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.
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http://dx.doi.org/10.1016/j.bbrc.2014.04.077DOI Listing
May 2014

Plant-derived mAbs have effective anti-cancer activities by increasing ganglioside expression in colon cancers.

Biotechnol Lett 2013 Dec;35(12):2031-8

An epithelial cell adhesion molecule (EpCAM) was selectively expressed in human colorectal carcinoma. Treatment with plant-derived anti-EpCAM mAb (mAbP CO17-1A) and RAW264.7 cells inhibited cell growth in the human colorectal cancer cell line SW620. In SW620 treated with mAbP CO17-1A and RAW264.7 cells, expression of p53 and p21 increased, whereas the expression of G1 phase-related proteins, cyclin D1, CDK4, cyclin E, and CDK2, decreased, similar to mammalian-derived mAb (mAbM) CO17-1A. Similar to mAbM CO17-1A, treatment with mAbP CO17-1A and RAW264.7 cell decreased the expression of anti-apoptotic protein, Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-α, caspase-3, caspase-6, caspase-8 and caspase-9, increased. Cells treated with mAbP CO17-1A and RAW264.7 cells expressed metastasis-related gangliosides, GM1 and GD1a, similar to mAbM CO17-1A. These results suggest that mAbP CO17-1A is as effective on anti-cancer activity as mAbM CO17-1A.
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http://dx.doi.org/10.1007/s10529-013-1318-zDOI Listing
December 2013

Intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody.

PLoS One 2013 15;8(8):e68772. Epub 2013 Aug 15.

Department of Medicine, Medical Research Institute, College of Medicine, Chung-Ang University, Seoul, Korea.

Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar levels of binding activity to the FcγRI receptor (CD64). The mAb(P)K had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAb(P) had mainly Golgi type glycans (96.8%) similar to those seen with mAb(H). Confocal analysis showed that the mAb(P)K was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAb(P) with KDEL in the ER. Both mAb(P) and mAb(P)K disappeared with similar trends to mAb(H) in BALB/c mice. In addition, mAb(P)K was as effective as mAb(H) at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAb(P) by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0068772PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744537PMC
September 2014

A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block.

Korean J Pain 2013 Apr 3;26(2):148-53. Epub 2013 Apr 3.

Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Seoul, Korea.

Background: C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB).

Methods: This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop.

Results: There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 ± 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 ± 0.71, P = 0.042) and beside the table (5.69 ± 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 ± 19.0, 0.97 ± 0.92, and 9.53 ± 8.16), resepectively.

Conclusions: Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.
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http://dx.doi.org/10.3344/kjp.2013.26.2.148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629341PMC
April 2013

The Survey about the Degree of Damage of Radiation-Protective Shields in Operation Room.

Korean J Pain 2013 Apr 3;26(2):142-7. Epub 2013 Apr 3.

Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Seoul, Korea.

Background: Medical doctors who perform C-arm fluoroscopy-guided procedures are exposed to X-ray radiation. Therefore, radiation-protective shields are recommended to protect these doctors from radiation. For the past several years, these protective shields have sometimes been used without regular inspection. The aim of this study was to investigate the degree of damage to radiation-protective shields in the operating room.

Methods: This study investigated 98 radiation-protective shields in the operation rooms of Konkuk University Medical Center and Jeju National University Hospital. We examined whether these shields were damaged or not with the unaided eye and by fluoroscopy.

Results: There were seventy-one aprons and twenty-seven thyroid protectors in the two university hospitals. Fourteen aprons (19.7%) were damaged, whereas no thyroid protectors (0%) were. Of the twenty-six aprons, which have been used since 2005, eleven (42.3%) were damaged. Of the ten aprons, which have been used since 2008, none (0%) was damaged. Of the twenty-three aprons that have been used since 2009, two (8.7%) of them were damaged. Of the eight aprons used since 2010, one (12.3%) was damaged. Of the four aprons used since 2011, none (0%) of them were damaged. The most common site of damage to the radiation-protective shields was at the waist of the aprons (51%).

Conclusions: As a result, aprons that have been used for a long period of time can have a higher risk of damage. Radiation-protective shields should be inspected regularly and exchanged for new products for the safety of medical workers.
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http://dx.doi.org/10.3344/kjp.2013.26.2.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629340PMC
April 2013

Radiation Exposure of the Hand and Chest during C-arm Fluoroscopy-Guided Procedures.

Korean J Pain 2013 Jan 4;26(1):51-6. Epub 2013 Jan 4.

Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Seoul, Korea.

Background: The C-arm fluoroscope is an essential tool for the intervention of pain. The aim of this study was to investigate the radiation exposure experienced by the hand and chest of pain physicians during C-arm fluoroscopy-guided procedures.

Methods: This is a prospective study about radiation exposure to physicians during transforaminal epidural steroid injection (TFESI) and medial branch block (MBB). Four pain physicians were involved in this study. Data about effective dose (ED) at each physician's right hand and left side of the chest, exposure time, radiation absorbed dose (RAD), and the distance from the center of the X-ray field to the physician during X-ray scanning were collected.

Results: Three hundred and fifteen cases were included for this study. Demographic data showed no significant differences among the physicians in the TFESIs and MBBs. In the TFESI group, there was a significant difference between the ED at the hand and chest in all the physicians. In physician A, B and C, the ED at the chest was more than the ED at the hand. The distance from the center of the X-ray field to physician A was more than that of the other physicians, and for the exposure time, the ED and RAD in physician A was less than that of the other physicians. In the MBB group, there was no difference in the ED at the hand and chest, except for physician D. The distance from the center of the X-ray field to physician A was more than that of the other physicians and the exposure time in physician A was less than that of the other physicians.

Conclusions: In conclusion, the distance from the radiation source, position of the hand, experience and technique can correlate with the radiation dose.
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http://dx.doi.org/10.3344/kjp.2013.26.1.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546211PMC
January 2013

Human leukocytes regulate ganglioside expression in cultured micro-pig aortic endothelial cells.

Lab Anim Res 2012 Dec 26;28(4):255-63. Epub 2012 Dec 26.

Department of Biological Science, College of National Sciences, Wonkwang University, Iksan, Korea.

Gangliosides are ubiquitous components of the membranes of mammalian cells that are thought to play important roles in various cell functions such as cell-cell interaction, cell adhesion, cell differentiation, growth control, and signaling. However, the role that gangliosides play in the immune rejection response after xenotransplantation is not yet clearly understood. In this study, the regulatory effects of human leukocytes on ganglioside expression in primary cultured micro-pig aortic endothelial cells (PAECs) were investigated. To determine the impact of human leukocytes on the expression of gangliosides in PAECs, we performed high-performance thin layer chromatography (HPTLC) in PAECs incubated with FBS, FBS containing human leukocytes, human serum containing human leukocytes, and FBS containing TNF-α. Both HPTLC and immunohistochemistry analyses revealed that PAECs incubated with FBS predominantly express the gangliosides GM3, GM1, and GD3. However, the expression of GM1 significantly decreased in PAECs incubated for 5 h with TNF-α (10 ng/mL), 10% human serum containing human leukocytes, and 10% FBS containing human leukocytes. Taken together, these results suggest that human leukocytes induced changes in the expression profile of ganglioside GM1 similar to those seen upon treatment of PAECs with TNF-α. This finding may be relevant for designing future therapeutic strategies intended to prolong xenograft survival.
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http://dx.doi.org/10.5625/lar.2012.28.4.255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542384PMC
December 2012

Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells.

BMB Rep 2012 Dec;45(12):713-8

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749, Korea.

Gangliosides play important roles in the control of several biological processes, including proliferation and transmembrane signaling. In this study, we demonstrate the effect of ganglioside GM1 on the proliferation of mouse induced pluripotent stem cells (miPSCs). The proliferation rate of miPSCs was lower than in mouse embryonic stem cells (mESCs). Fluorescence activated cell sorting analysis showed that the percentage of cells in the G2/M phase in miPSCs was lower than that in mESCs. GM1 was expressed in mESCs, but not miPSCs. To confirm the role of GM1 in miPSC proliferation, miPSCs were treated with GM1. GM1-treated miPSCs exhibited increased cell proliferation and a larger number of cells in the G2/M phase. Furthermore, phosphorylation of mitogen-activated protein kinases was increased in GM1- treated miPSCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133816PMC
http://dx.doi.org/10.5483/bmbrep.2012.45.12.138DOI Listing
December 2012

Prevalence of dementia and its correlates among participants in the National Early Dementia Detection Program during 2006-2009.

Psychiatry Investig 2012 Jun 30;9(2):134-42. Epub 2012 Apr 30.

Department of Psychiatry and Institute of Medical Science, Jeju National University School of Medicine, Jeju, Korea.

Objective: To investigate the prevalence of dementia and its correlates among people with poor socioeconomic status, poor social support systems, and poor performance on the Korean version of the Mini-Mental Status Exam (MMSE-KC).

Methods: We used 2006-2009 data of the National Early Dementia Detection Program (NEDDP) conducted on Jeju Island. This program included all residents >65 years old who were receiving financial assistance. We examined those who performed poorly (standard deviation from the norm of <-1.5) on the MMSE-KC administered as part of the NEDDP, using age-, gender-, and education-adjusted norms for Korean elders. A total of 1708 people were included in this category.

Results: The prevalence of dementia in this group was 20.5%. Multivariate logistic regression analysis revealed that the following factors were statistically significantly associated with dementia: age of 80 or older, no education, nursing home residence, and depression.

Conclusion: The prevalence of dementia is very high among those with lower MMSE-KC scores, and significant correlates include older age, no education, living in a nursing home, and depression. Enhancing lifetime education to improve individuals' cognitive reserves by providing intellectually challenging activities, encouraging living at home rather than in a nursing home, and preventing and treating depression in its early phase could reduce the prevalence of dementia in this population.
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http://dx.doi.org/10.4306/pi.2012.9.2.134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372560PMC
June 2012

Abrupt formation of intracardiac thrombus during cardiopulmonary bypass with full heparinization -A case report-.

Korean J Anesthesiol 2012 Feb 20;62(2):175-8. Epub 2012 Feb 20.

Department of Anesthesiology and Pain Medicine, Konkuk University Hospital, Seoul, Korea.

Intracardiac thrombus during cardiopulmonary bypass (CPB) with full heparinization is very rare but fatal. A 60-year-old woman was scheduled for aortic and mitral valve repairs with a maze procedure for mixed aortic and mitral valvular heart disease with atrial fibrillation. Preoperative transthoracic echocardiography and cardiac computed tomography showed moderate aortic regurgitation and moderate mitral stenosis with regurgitation. There was no intracardiac thrombus. Aortic and mitral valve repairs with the maze procedure were successfully performed without unexpected events. During CPB weaning, a mobile hyper-echogenic mass in the left atrium was detected on transesophageal echocardiography. After cardiac arrest, it was surgically removed. On completion of the operation, weaning from CPB was accomplished uneventfully. The patient fully recovered and was discharged from the intensive care unit on her third postoperative day.
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http://dx.doi.org/10.4097/kjae.2012.62.2.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284742PMC
February 2012

Regulatory roles of ganglioside GQ1b in neuronal cell differentiation of mouse embryonic stem cells.

BMB Rep 2011 Dec;44(12):799-804

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749 Korea.

Gangliosides play an important role in neuronal differentiation processes. The regulation of ganglioside levels is related to the induction of neuronal cell differentiation. In this study, the ST8Sia5 gene was transfected into mESCs and then differentiated into neuronal cells. Interestingly, ST8Sia5 gene transfected mESCs expressed GQ1b by HPTLC and immunofluorescence analysis. To investigate the effects of GQ1b over-expression in neurogenesis, neuronal cells were differentiated from GQ1b expressing mESCs in the presence of retinoic acid. In GQ1b expressing mESCs, increased EBs formation was observed. After 4 days, EBs were co-localized with GQ1b and nestin, and GFAP. Moreover, GQ1b co-localized with MAP-2 expressing cells in GQ1b expressing mESCs in 7-day-old EBs. Furthermore, GQ1b expressing mESCs increased the ERK1/2 MAP kinase pathway. These results suggest that the ST8Sia5 gene increases ganglioside GQ1b and improves neuronal differentiation via the ERK1/2 MAP kinase pathway.
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http://dx.doi.org/10.5483/bmbrep.2011.44.12.799DOI Listing
December 2011

Relationship between ganglioside expression and anti-cancer effects of the monoclonal antibody against epithelial cell adhesion molecule in colon cancer.

Exp Mol Med 2011 Dec;43(12):693-701

Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea.

The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti- cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression of GM1 and GD1a significantly increased in the ability of anti-EpCAM to inhibit cell growth in SW620 cells. Anti-EpCAM mAb treatment increased the expression of anti-apoptotic proteins such as Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-α, caspase-3, cleaved caspase-3, and cleaved caspase-8 were unaltered. We observed that anti-EpCAM mAb significantly inhibited the growth of colon tumors, as determined by a decrease in tumor volume and weight. The expression of anti-apoptotic protein was inhibited by treatment with anti-EpCAM mAb, whereas the expression of pro-apoptotic proteins was increased. These results suggest that GD1a and GM1 were closely related to anticancer effects of anti-EpCAM mAb. In light of these results, further clinical investigation should be conducted on anti-EpCAM mAb to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.
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http://dx.doi.org/10.3858/emm.2011.43.12.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256297PMC
December 2011

Inhibition of ganglioside GD1a synthesis suppresses the differentiation of human mesenchymal stem cells into osteoblasts.

Dev Growth Differ 2011 Apr;53(3):323-32

Department of Biological Science, College of Natural Sciences, Institute of Biotechnology Wonkwang University, Iksan, Jeonbuk 570-749, Korea.

In this study, we investigated the regulatory role of ganglioside GD1a in the differentiation of osteoblasts from human mesenchymal stem cells (hMSCs) by using lentivirus-containing short hairpin (sh)RNA to knockdown ST3 β-galactoside α-2, 3-sialyltransferase 2 (ST3Gal II) mRNA expression. After hMSCs were infected for 72 h with the lentivirus constructed with ST3Gal II shRNAs, the puromycin-resistant cells were selected and subcultured to produce hMSCs with ST3Gal II mRNA knockdown. The hMSCs established from human dental papilla abundantly expressed CD44 and CD105, but not CD45 and CD117. Osteoblasts that differentiated from normal hMSCs showed a significant increase in alkaline phosphatase (ALP) activity and ganglioside GD1a expression level compared with those in hMSCs. Lentiviral infection of hMSCs successfully induced a marked inhibition of ST3Gal II mRNA expression and caused a significant decrease in ALP activity and ganglioside GD1a expression. During osteoblastic differentiation, the increased ALP activity remarkably reduced by suppression of ganglioside GD1a expression by ST3Gal II shRNA. Ganglioside GD1a and ALP were mainly expressed in the cell body of hMSCs and osteoblasts with colocalization. The phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 mitogen-activated protein (MAP) kinase and epidermal growth factor receptor (EGFR) was significantly reduced in the osteoblasts that had differentiated from the hMSCs with ST3Gal II mRNA knockdown. These results suggest that ganglioside GD1a plays an important role in the regulation of osteoblastic differentiation of hMSCs through the activation of ERK 1/2 MAP kinase and EGFR.
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http://dx.doi.org/10.1111/j.1440-169X.2010.01240.xDOI Listing
April 2011

Comparison of ganglioside expression between human adipose- and dental pulp-derived stem cell differentiation into osteoblasts.

Arch Pharm Res 2010 Apr 27;33(4):585-91. Epub 2010 Apr 27.

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan, 570-749, Korea.

Human adipose-derived stem cells (hADSCs) and dental pulp-derived stem cells (hDPSCs) have been considered alternative sources of adult stem cells because of their potential to trans-differentiate into multiple cell lineages. This study investigated the possible role of gangliosides in the osteoblast differentiation of hADSCs and hDPSCs. First, we investigated characterization of hADSCs and hDPSCs using FACS analysis. Mesenchymal stem cell specific markers, CD44 and CD105, were expressed but not hematopoietic markers, CD45 and CD117 in both of hADSCs and hDPSCs. High-performance thin-layer chromatography analysis showed that increased gangliosides were associated with differentiation of hADSCs and hDPSCs into osteoblasts. RT-PCR analysis confirmed that osteoblast specific genes, ALP, BMP-2, collagen were expressed in differentiated osteoblasts, however, the another osteoblast specific gene, osteocalcin, was not expressed. When hADSCs and hDPSCs were cultured under osteoblast-differentiation conditions, alkaline phosphatase (ALP) activity was increased in comparison to hADSCs and hDPSCs. Furthermore, specifically both ALP activity and ganglioside expression increased more in hDPSCs-derived osteoblasts than hADSCs-derived osteoblasts. These results suggest that gangliosides play a more important role in regulating the osteoblast-differentiation of hDPSCs compared to hADSCs.
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http://dx.doi.org/10.1007/s12272-010-0413-0DOI Listing
April 2010

Estrogenic activity produced by aqueous extracts of silkworm (Bombyx mori) pupae in ovariectomized rats.

Am J Chin Med 2010 ;38(1):89-97

Department of Biological Science, Wonkwang University, Iksan, Jeonbuk, Korea.

This study examined the estrogenic activity produced by aqueous extracts of silkworm (Bombyx mori) pupae in ovariectomized (OVX) rats. The components of silkworm pupae were extracted in distilled water at room temperature for 6 hours. The ovaries of six-week old female rats were then bilaterally removed. One week after OVX, the animals were treated with 200, 400 or 600 mg/kg/day of silkworm pupae extracts. The body weights of the OVX rats increased remarkably compared to the control rats, however their relative uterus weights to body weights decreased significantly. Treatment with the aqueous extracts of silkworm pupae dramatically improved the decreased uterus weights of OVX rats, with the highest increase observed in treatment with 200 mg/kg/day of the aqueous extracts. Additionally, treatment with aqueous extracts (200 mg/kg/day) of silkworm pupae significantly elevated the serum 17beta-estradiol contents of OVX rats when compared to the control animals. To examine the toxic effects of silkworm pupae on the hepatic functions of OVX rats, the levels of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were measured. The serum GOT and GPT levels did not change in response to the administration of aqueous extracts (200, 400 and 600 mg/kg/day) for 4-weeks. Taken together, these results suggest that the aqueous extracts of silkworm pupae may have estrogenic activity, which suggests that silkworm pupae may be useful in the prevention and/or treatment of menopausal disorders caused by deficiencies in female sexual hormones, including estrogen.
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http://dx.doi.org/10.1142/S0192415X10007683DOI Listing
April 2010
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