• BMB Reports
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• 제50권8호
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• pp.417-422
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• 2017

Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model. During chemotherapy, NPY mitigates reduction in HSC abundance and destruction of SNS fibers in the bone marrow without blocking the anticancer efficacy of cisplatin, and it results in the restoration of blood cells and amelioration of sensory neuropathy. Therefore, these results suggest that NPY can be used as a potentially effective agent to improve bone marrow dysfunction during cisplatin-based cancer therapy.

• Molecules and Cells
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• 제39권3호
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• pp.186-194
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• 2016

Epidemiological evidence suggests that bone is especially sensitive to oxidative stress, causing bone loss in the elderly. Previous studies indicated that human amnion-derived mesenchymal stem cells (HAMSCs), obtained from human amniotic membranes, exerted osteoprotective effects in vivo. However, the potential of HAMSCs as seed cells against oxidative stress-mediated dysfunction is unknown. In this study, we systemically investigated their antioxidative and osteogenic effects in vitro. Here, we demonstrated that HAMSCs significantly promoted the proliferation and osteoblastic differentiation of $H_2O_2$-induced human bone marrow mesenchymal stem cells (HBMSCs), and down-regulated the reactive oxygen species (ROS) level. Further, our results suggest that activation of the ERK1/2 MAPK signal transduction pathway is essential for both HAMSCs-mediated osteogenic and protective effects against oxidative stress-induced dysfunction in HBMSCs. U0126, a highly selective inhibitor of extracellular ERK1/2 MAPK signaling, significantly suppressed the antioxidative and osteogenic effects in HAMSCs. In conclusion, by modulating HBMSCs, HAMSCs show a strong potential in treating oxidative stress- mediated bone deficiency.

• BMB Reports
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• 제48권12호
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• pp.645-646
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• 2015

The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

• International Neurourology Journal
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• 제22권4호
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• pp.260-267
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• 2018

Purpose: A major question remaining in approaches to tissue engineering and organ replacement is the role of native mobilized native cells in the regeneration process of damaged tissues and organs. The goal of this study was to compare the cell mobilizing effects of the chemokine CXCL12 and cell therapy on the urinary sphincter of nonhuman primates (NHP) with chronic intrinsic urinary sphincter dysfunction. Methods: Either autologous lenti-M-cherry labeled skeletal muscle precursor cells (skMPCs) or CXCL12 were injected directly into the sphincter complex of female NHPs with or without surgery-induced chronic urinary sphincter dysfunction (n=4/treatment condition). All monkeys had partial bone marrow transplantation with autologous lenti-green fluorescent protein (GFP) bone marrow cells prior to treatment. Labeled cells were identified, characterized and quantified using computer-assisted immunohistochemistry 6 months posttreatment. Results: GFP-labeled bone marrow cells (BMCs) were identified in the bone marrow and both BMCs and skMPCs were found in the urinary sphincter at 6-month postinjection. BMCs and skMPCs were present in the striated muscle, smooth muscle, and lamina propria/urothelium of the sphincter tissue. Sphincter injury increased the sphincter content of BMCs when analyzed 6-month postinjection. CXCL12 treatment, but not skMPCs, increased the number of BMCs in all layers of the sphincter complex (P<0.05). CXCL12 only modestly (P=0.15) increased the number of skMPCs in the sphincter complex. Conclusions: This dual labeling methodology now provides us with the tools to measure the relative number of locally injected cells versus bone marrow transplanted cells. The results of this study suggest that CXCL12 promotes mobilization of cells to the sphincter, which may contribute more to sphincter regeneration than injected cells.

• 생명과학회지
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• 제32권6호
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• pp.468-475
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• 2022

줄기세포와 전구세포 사이의 기능 분석은 여러 조직 특히 혈액에서 잘 확립되어 있다. 특히 조혈줄기세포는 골수 니쉬에서 자가재생능 및 재구성능을 가지고 있으며, 골수 내 기질세포는 조직 기능 조절에 큰 영향을 미친다. 최근 연구에서는 포유동물 줄기세포의 기능은 니쉬 세포 내에서 실험적으로 처음 증명되었고, 특히 미세환경에 의해 종양발생이 가능하다는 증거를 나타내고 있다. 고대에서부터 뼈와 피의 관계는 생체 내 필수불가결인 관계로 진화 과정을 거쳐 포유류의 줄기세포에 대해 최초로 제안되었고, 실험적으로 증명된 니쉬세포를 포함한 미세환경과의 복잡한 상호 관계를 규명하였다. 여러 골수 기질세포는 조혈줄기세포의 기능 조절을 하며, 일부의 기능장애는 골수 이형성 및 백혈병을 유발할 수 있다. 현재까지 여러 기질세포에 대한 맵핑이 되지 않아 현재 많은 연구자들이 단일 분자 수준에서 개개의 기질세포 유형을 파악하는 데이터가 필요하다고 주장하고 있으며 이를 바탕으로 골수 내 조혈줄기세포의 특정 기능을 파악할 수 있다고 볼 수 있다. 따라서 본 총설을 통해 조혈줄기세포 및 미세환경에 대한 이전 연구들의 흥미로운 문제를 논의하고, 조혈줄기세포와 골수 니쉬에 대한 현재 및 새로운 개념을 요약하고자 한다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제34권6호
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• pp.484-487
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• 2012

Skull base osteomyelitis is a very rare disease that affects the bone marrow of the temporal bone, sphenoid bone, occipital bone. It occurs typically chronic ear canal infections by malignant otitis externa, but some of atypical osteomyelitis have been reported. It most commonly presents old diabetic patients, and have high morbidity and mortality rate if diagnosis and treatment are delayed. However with respect to pain or dysfunction, it appeared similar to the initial symptoms of temporomandibular joint disorder. So frequently, definitive diagnosis is tend to delayed. We have clinical experience that a patient who presented with symptom similar to temporomandibular disorder, and differential diagnosised by skull base osteomyelitis. We will report this case with literature review.

• Clinical and Experimental Pediatrics
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• 제46권10호
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• pp.1029-1031
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• 2003

본 저자들은 전신성 홍반성 루푸스와 미만성 증식성 사구체신염으로 진단된 남아의 치료과정 중 발열과 혈구 감소증이 지속된 환아에서 이차성 혈구 탐식성 조직구 증식증을 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Genomics & Informatics
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• 제2권2호
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• pp.75-80
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• 2004

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ TCDD/kg body weight at various time intervals: gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7): P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than $\pm$2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure: smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.

• BMB Reports
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• 제49권5호
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• pp.288-292
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• 2016

Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity.

• Clinical and Experimental Pediatrics
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• 제53권3호
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• pp.420-427
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• 2010

목 적 : 소아와 청소년기에 골수이식을 받은 환자들은 여러 가지 조기 또는 후기 합병증이 발생할 수 있다. 본 연구에서는 이식 후 발생할 수 있는 내분비 기능 부전에 대해 분석하여 이식 후 추적 관리에 도움이 되고자 하였다. 방 법 : 골수이식을 받은 100명(남자 61명, 여자 39명)의 환자들을 대상으로 진단명, 이식 당시 연령, 전처치 방법, 만성 이식편대 숙주병 유무, 성장 패턴, 갑상샘 기능, 사춘기 발달 상태 등을 후향적으로 조사하여 내분비 기능 부전과 관련이 있는 위험 인자가 있는지 분석하였다. 결 과 : 이식 당시, 이식 1년후, 최종 내원시의 신장 표준편차 점수는 각각 $0.08{\pm}1.04$, $-0.09{\pm}1.02$, $-0.27{\pm}1.18$로 의미있게 감소하였다(P =0.001). 전처치로 TBI를 받은 경우 TBI를 받지 않은 군에 비하여 이식 전보다 신장 표준편차 점수가 더 많이 감소하였다(P =0.017). TBI를 시행한 환자 중 1명에서 성장 호르몬 결핍을 보였다. 갑상샘 기능 검사를 시행한 94명 중 30명(31.9%)이 보상성 갑상샘저하증이었고 만성 이식편대 숙주병이 있었던 환자에서 보상성 갑상샘저하증의 빈도가 높았다(odds ratio=2.82, P =0.025). 최종 내원 시 만 14세 이상 남자 17명, 만 13세 이상 여자 15명 중에서 비정상적인 LH 또는 FSH의 상승을 보인 경우는 남자 3명, 여자 13명으로 여아가 의미 있게 많았다(odds ratio=30.3, P =0.001). 결 론 : 소아나 청소년기에 골수이식을 받은 환자에서 가장 흔한 내분비 기능 이상은 난소 기능 부전이며 그 외 높은 빈도의 내분비 기능 이상을 보이므로 정기적인 내분비 기능 검사가 필요하다.