• Title/Summary/Keyword: human stem cell

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Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population

  • Lee, Jun-Ho;Song, Hye-Rim;Kim, Hee Nam;Kweon, Sun-Seog;Yun, Yong-Woon;Choi, Jin-Su;Jung, Seung-Il;Kwon, Dong Deuk;Kim, Soo Hyun;Choi, Yoo-Duk;Shin, Min-Ho
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8901-8904
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    • 2014
  • Background: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. Materials and Methods: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. Results: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT =1.58, 95% CI= 1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. Conclusions: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

Altered Gene Expression Profiles in the Lungs of Streptozotocin-induced Diabetic Mice

  • Kim, Jung-Hyun;Rasaei, Roya;Park, Sujin;Kim, Ji-Young;Na, Sunghun;Hong, Seok-Ho
    • Development and Reproduction
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    • v.24 no.3
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    • pp.197-205
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    • 2020
  • Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

Disruption of the Tff1 gene in mice using CRISPR/Cas9 promotes body weight reduction and gastric tumorigenesis

  • Kim, Hyejeong;Jeong, Haengdueng;Cho, Yejin;Lee, Jaehoon;Nam, Ki Taek;Lee, Han-Woong
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.257-263
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    • 2018
  • Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. Tff1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated Tff1-knockout (KO) mice, without a neomycin resistant ($Neo^R$) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our Tff1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established Tff1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that Tff1 expression influences gender differences.

Growth hormone treatment for children with mucopolysaccharidosis I or II

  • Minji Im;Chiwoo Kim;Juyoung Sung;Insung Kim;Ji-Hoon Hwang;Min-Sun Kim;Sung Yoon Cho
    • Journal of Genetic Medicine
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    • v.20 no.2
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    • pp.60-69
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    • 2023
  • Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients-four with MPS I and five with MPS II-underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from -4.09±0.83 to -3.68±0.43 after 1 year of hGH treatment, and to -3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion: This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.

NOX4 and its association with myeloperoxidase and osteopontin in regulating endochondral ossification

  • Kayoung Ko;Seohee Choi;Miri Jo;Chaeyoung Kim;Napissara Boonpraman;Jihyun Youm;Sun Shin Yi
    • Journal of Veterinary Science
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    • v.25 no.4
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    • pp.49.1-49.15
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    • 2024
  • Importance: Endochondral ossification plays an important role in skeletal development. Recent studies have suggested a link between increased intracellular reactive oxygen species (ROS) and skeletal disorders. Moreover, previous studies have revealed that increasing the levels of myeloperoxidase (MPO) and osteopontin (OPN) while inhibiting NADPH oxidase 4 (NOX4) can enhance bone growth. This investigation provides further evidence by showing a direct link between NOX4 and MPO, OPN in bone function. Objective: This study investigates NOX4, an enzyme producing hydrogen peroxide, in endochondral ossification and bone remodeling. NOX4's role in osteoblast formation and osteogenic signaling pathways is explored. Methods: Using NOX4-deficient (NOX4-/-) and ovariectomized (OVX) mice, we identify NOX4's potential mediators in bone maturation. Results: NOX4-/- mice displayed significant differences in bone mass and structure. Compared to the normal Control and OVX groups. Hematoxylin and eosin staining showed NOX4-/- mice had the highest trabecular bone volume, while OVX had the lowest. Proteomic analysis revealed significantly elevated MPO and OPN levels in bone marrow-derived cells in NOX4-/- mice. Immunohistochemistry confirmed increased MPO, OPN, and collagen II (COLII) near the epiphyseal plate. Collagen and chondrogenesis analysis supported enhanced bone development in NOX4-/- mice. Conclusions and Relevance: Our results emphasize NOX4's significance in bone morphology, mesenchymal stem cell proteomics, immunohistochemistry, collagen levels, and chondrogenesis. NOX4 deficiency enhances bone development and endochondral ossification, potentially through increased MPO, OPN, and COLII expression. These findings suggest therapeutic implications for skeletal disorders.

Photoprotective Effect of Grape Pruning Stem Extracts on the UVB Induced HR-1 Mice Skin (포도전정가지 추출물이 UVB에 유도된 HR-1 mice의 피부손상에 대한 광보호 효과)

  • Kim, Joung-Hee;Kim, Jong Guk;Kim, Sun-Gun;Jeong, Seung-IL;Jang, Min-Jung;Kim, Kil-Soo;Kim, Keuk-Jun;Kwack, Seung-Jun
    • Journal of Life Science
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    • v.27 no.4
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    • pp.383-389
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    • 2017
  • This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.

STAT3 is Activated in a Subset of Benign and Malignant Chondroid Tumors (양성 및 악성 연골 종양에서의 STAT3 활성화)

  • Park, Hye-Rim;Park, Yong-Koo
    • The Journal of the Korean bone and joint tumor society
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    • v.15 no.2
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    • pp.130-137
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    • 2009
  • Purpose: STAT3 is an oncogene that regulates critical cellular processes, and its constitutive activation has been demonstrated to correlate with biological and clinical features in many types of human malignancy. Materials and Methods: In this study, STAT3 activation was assessed in variable benign and malignant chondroid tumors in bone by immunohistochemistry using a monoclonal antibody specific for $tyrosine^{705}$-phosphorylated STAT3 ($pSTAT3^{tyr705}$). Results: Among conventional chondrosarcomas (n=17), three cases(50%) of grade III chondrosarcomas were pSTAT3-positive. All grade I and II chondrosarcomas were pSTAT3-negative. This pSTAT3 positivity according to the histologic grade was statistically significant (p=0.0432). Two cases(50%) of clear cell chondrosarcomas were pSTAT3-positive. Six cases (50%) among 12 benign chondroid tumors(6 enchondromas, 3 chondroblastomas, and 3 chondromyxoid fibromas) were also $pSTAT3^{tyr705}$-positive. Conclusion: In conclusion, STAT3 activation is associated with higher tumor grade in conventional chondrosarcomas. Our results suggest that STAT3 is activated in a subset of benign and malignant chondroid tumors, and may support the extension of the cancer stem cell hypothesis to include tumors of cartilaginous lineage.

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Resolvin D5, a Lipid Mediator, Inhibits Production of Interleukin-6 and CCL5 Via the ERK-NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated THP-1 Cells

  • Chun, Hyun-Woo;Lee, Jintak;Pham, Thu-Huyen;Lee, Jiyon;Yoon, Jae-Hwan;Lee, Jin;Oh, Deok-Kun;Oh, Jaewook;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.30 no.1
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    • pp.85-92
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    • 2020
  • One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.

Comparison of biological activities of essential oils from Foeniculum vulgare Mill, Boswellia carteii Birew and Juniperus rigida Sieb. by a supercritical fluid extraction system (초임계 추출 공법을 이용해 회향, 유향 및 노간주나무로부터 분리한 정유 성분의 생리활성 비교)

  • Lee, Hyun-Soo;Mun, Chul-Hyung;Park, Jin-Hong;Kim, Dae-Ho;Yoo, Jae-Eun;Park, Young-Sik;Ryu, Lee-Ha;Choi, Keun-Pyo;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.11 no.2
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    • pp.115-121
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    • 2003
  • Essential oils from Fennel fruit(Foeniculum vulgare Mill), Olibanum resin(Boswellia carteii Birew) and Needl Juniperus stem(Juniperus rigida Sieb.) were extracted by a supercritical fluid extraction system(SFE) and biological activity of each essential oils were observed. SFE technique was applied for the isolation and purification of nonpolar biologically active essential oils from each samples. The quantitative analysis of essential oils was carried out by gas chromatography-mass spectrometer(GC/MS). About 60% of the growth of AGS and A549 cells were inhibited by adding 1.0g/l of the crude essential oils and below 40% was observed by the control. Cytotoxicity on human normal lung cell(HEL299) was scored as $15{\sim}18%$ for the crude essential oils and 12% for control, respectively. It meant that the essential oils were more effective than the control in anti-mutagenecity tested by CHO V79 cells. The effect of the essential oils on the growth of nerve cells, PC12 was observed as follows: The viable cell density was about two times higher than control.

Treatment of Phalangeal Bone Defect Using Autologous Stromal Vascular Fraction from Lipoaspirated Tissue (자가기질혈관분획을 이용한 수지골 결손 환자의 치료)

  • Jeong, Tae-Won;Ji, Yi-Hwa;Kim, Deok-Woo;Dhong, Eun-Sang;Yoon, Eul-Sik
    • Archives of Plastic Surgery
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    • v.38 no.4
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    • pp.438-444
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    • 2011
  • Purpose: Adipose-derived stromal cells (ASCs) are readily harvested from lipoaspirated tissue or subcutaneous adipose tissue fragments. The stromal vascular fraction (SVF) is a heterogeneous set of cell populations that surround and support adipose tissue, which includes the stromal cells, ASCs, that have the ability to differentiate into cells of several lineages and contains cells from the microvasculature. The mechanisms that drive the ASCs into the osteoblast lineage are still not clear, but the process has been more extensively studied in bone marrow stromal cells. The purpose of this study was to investigate the osteogenic capacity of adipose derived SVF cells and evaluate bone formation following implantation of SVF cells into the bone defect of human phalanx. Methods: Case 1 a 43-year-old male was wounded while using a press machine. After first operation, segmental bone defects of the left 3rd and 4th middle phalanx occurred. At first we injected the SVF cells combined with demineralized bone matrix (DBM) to defected 4th middle phalangeal bone lesion. We used P (L/DL)LA [Poly (70L-lactide-co-30DL-lactide) Co Polymer P (L/DL)LA] as a scaffold. Next, we implanted the SVF cells combined with DBM to repair left 3rd middle phalangeal bone defect in sequence. Case 2 was a 25-year-old man with crushing hand injury. Three months after the previous surgery, we implanted the SVF cells combined with DBM to restore right 3rd middle phalangeal bone defect by syringe injection. Radiographic images were taken at follow-up hospital visits and evaluated radiographically by means of computerized analysis of digital images. Results: The phalangeal bone defect was treated with autologous SVF cells isolated and applied in a single operative procedure in combination with DBM. The SVF cells were supported in place with mechanical fixation with a resorbable macroporous sheets acting as a soft tissue barrier. The radiographic appearance of the defect revealed a restoration to average bone density and stable position of pharyngeal bone. Densitometric evaluations for digital X-ray revealed improved bone densities in two cases with pharyngeal bone defects, that is, 65.2% for 4th finger of the case 1, 60.5% for 3rd finger of the case 1 and 60.1% for the case 2. Conclusion: This study demonstrated that adipose derived stromal vascular fraction cells have osteogenic potential in two clinical case studies. Thus, these reports show that cells from the SVF cells have potential in many areas of clinical cell therapy and regenerative medicine, albeit a lot of work is yet to be done.