Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth

Bak, Dong Ho,Choi, Mi Ji,Kim, Soon Re,Lee, Byung Chul,Kim, Jae Min,Jeon, Eun Su,Oh, Wonil,Lim, Ee Seok,Park, Byung Cheol,Kim, Moo Joong,Na, Jungtae,Kim, Beom Joon The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ${\beta}-catenin$; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy

BAK, DONG-HO,KANG, SEONG HEE,CHOI, DU RI,GIL, MI NA,YU, KWANG SIK,JEONG, JI HEUN,LEE, NAM-SEOB,LEE, JE-HUN,JEONG, YOUNG-GIL,KIM, DONG KWAN,KIM, DO-KYUNG,KIM, JWA-JIN,HAN, SEUNG-YUN D.A. Spandidos 2016 Experimental and therapeutic medicine Vol.11 No.6

<P>Temozolomide (TMZ), an alkylating agent, is recommended as the initial treatment for high-grade glioblastoma. TMZ is widely used, but its short half-life and the frequency of tumor resistance limit its therapeutic efficacy. In the present study, the anticancer effect of vitamin D (VD) combined with TMZ upon glioblastoma was determined, and the underlying mechanism of this effect was identified. Through cell viability, clonogenic and wound healing assays, the current study demonstrated that treatment of a C6 glioblastoma cell line with TMZ and VD resulted in significantly increased <I>in vitro</I> antitumor effects compared with either VD or TMZ alone. Autophagy, hypothesized to be the dominant mechanism underlying TMZ-based tumor cell death, was maximally activated in TMZ and VD co-treated C6 cells. This was demonstrated by ultrastructural observations of autophagosomes, increased size and number of microtubule-associated protein 1 light chain 3 (LC3) puncta and increased conversion of LC3-I to LC3-II. However, the extent of apoptosis was not significantly different between cells treated with TMZ and VD and those treated with TMZ alone. Addition of the autophagy inhibitor 3-methyladenine markedly inhibited the anticancer effect of TMZ and VD treatment, indicating that the chemosensitizing effect of VD in TMZ-based glioblastoma therapy is generated through enhancement of cytotoxic autophagy. TMZ and VD co-treatment also significantly inhibited tumor progression and prolonged survival duration in rat glioblastoma orthotopic xenograft models when compared with TMZ treatment alone. These <I>in vivo</I> results are concordant with the aforementioned <I>in vitro</I> results, together revealing that the combined use of TMZ and VD exerts synergistic antitumor effects on rat models of glioblastoma and may represent an effective therapeutic strategy.</P>

Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth

Dong Ho Bak,Mi Ji Choi,Soon Re Kim,Byung Chul Lee,Jae Min Kim,Eun Su Jeon,Wonil Oh,Ee Seok Lim,Byung Cheol Park,Moo Joong Kim,Jungtae Na,Beom Joon Kim 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs coculture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the colocalization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

Anti-apoptotic effects of human placental hydrolysate against hepatocyte toxicity <i>in vivo</i> and <i>in vitro</i>

Bak, Dong-Ho,Na, Jungtae,Choi, Mi Ji,Lee, Byung Chul,Oh, Chang Taek,Kim, Jeom-Yong,Han, Hae Jung,Kim, Moo Joong,Kim, Tae Ho,Kim, Beom Joon D.A. Spandidos 2018 International journal of molecular medicine Vol.42 No.5

<P>Apoptosis and oxidative stress are essential for the pathogenesis of acute liver failure and fulminant hepatic failure. Human placental hydrolysate (hPH) has been reported to possess antioxidant and anti-inflammatory properties. In the present study, the protective effects of hPH against D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced hepatocyte apoptosis were investigated <I>in vivo</I>. In addition, the molecular mechanisms underlying the anti-apoptotic activities of hPH against D-GalN-induced cell death <I>in vitro</I> were examined. Male Sprague-Dawley rats were injected with D-GaIN/LPS with or without the administration of hPH. Rats were sacrificed 24 h after D-GaIN/LPS intraperitoneal injection, and the blood and liver samples were collected for future inflammation and hepatotoxicity analyses. Changes in cell viability, apoptosis protein expression, mitochondrial mass, mitochondrial membrane potential, reactive oxygen species generation, and the levels of proteins and mRNA associated with a protective mechanism were determined in HepG2 cells pretreated with hPH for 2 h prior to D-GalN exposure. The findings suggested that hPH treatment effectively protected against D-GalN/LPS-induced hepatocyte apoptosis by reducing the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, interleukin-6, and tumor necrosis factor-α, and increasing the level of proliferating cell nuclear antigen. It was also found that hPH inhibited the apoptotic cell death induced by D-GalN. hPH activated the expression of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase, which were further upregulated by the Kelch-like ECH2-associated protein 1-p62-nuclear factor-erythroid 2-related factor 2 pathway, a component of oxidative stress defense mechanisms. Furthermore, hPH markedly reduced cytosolic and mitochondrial reactive oxygen species and rescued mitochondrial loss and dysfunction through the reduction of damage-regulated autophagy modulator, p53, and C/EBP homologous protein. Collectively, hPH exhibited a protective role in hepatocyte apoptosis by inhibiting oxidative stress and maintaining cell homeostasis. The underlying mechanisms may be associated with the inhibition of endoplasmic reticulum stress and minimization of the autophagy progress.</P>

Neuroprotective effects of 20(S)-protopanaxadiol against glutamate-induced mitochondrial dysfunction in PC12 cells

BAK, DONG-HO,KIM, HYUNG DON,KIM, YOUNG OCK,PARK, CHUN GEUN,HAN, SEUNG-YUN,KIM, JWA-JIN D.A. Spandidos 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.2

<P>Ginseng (<I>Panax ginseng</I> C.A. Mey.) is commonly used in traditional oriental medicine for its wide spectrum of medicinal properties, including anti-inflammatory, antitumorigenic, adaptogenic and anti-aging properties. 20(S)-Protopanaxadiol (PPD), the main intestinal metabolite of ginsenosides, is one of the active ingredients in ginseng. In this study, we aimed to investigate the neuroprotective effects of PPD on PC12 cells; however, the underlying mechanisms remain elusive. We examined cell viability by MTT assay and the morphological changes of PC12 cells following glutamate-induced cell damage and evaluated the anti-apoptotic effects of PPD using Hoechst 33258 staining, western blot analysis and Muse™ Cell Analyzer and the antioxidant effects of PPD using FACS analysis and immunofluorescence. Furthermore, PPD exerted protective effects on PC12 cells via the inhibition of mitochondrial damage against glutamate-induced excitotoxicity using immunofluorescence, electron microscopy and FACS analysis. We demonstrate that treatment with PPD suppresses apoptosis, which contributes to the neuroprotective effects of PPD against glutamate-induced excitotoxicity in PC12 cells. Treatment with PPD inhibited nuclear condensation and decreased the number of Annexin V-positive cells. In addition, PPD increased antioxidant activity and mitochondrial homeostasis in the glutamate-exposed cells. These antioxidant effects were responsible for the neuroprotection and enhanced mitochondrial function following treatment with PPD. Furthermore, PD inhibited the glutamate-induced morphological changes in the mitochondria and scavenged the mitochondrial and cytosolic reactive oxygen species (ROS) induced by glutamate. In addition, mitochondrial function was significantly improved in terms of mitochondrial membrane potential (MMP) and enhanced mitochondrial mass compared with the cells exposed to glutamate and not treated with PPD. Taken together, the findings of our study indicate that the antioxidant effects and the enhanced mitochondrial function triggered by PPD contribute to the inhibition of apoptosis, thus leading to a neuroprotective response, as a novel survival mechanism.</P>

Stability of Equivalent Control Based Discrete Sliding-Mode Controller

Dong-Jun Kim,Moon-Ho Son,Kang-Bak Park 제어로봇시스템학회 2007 제어로봇시스템학회 국내학술대회 논문집 Vol.2007 No.5

농촌매립지 주변환경영향조사

김관호 ( Kwan-ho Kim ),오영인 ( Young-in Oh ),이동건 ( Dong-geon Lee ),조숙희 ( Sook-hee Cho ),박은숙 ( Eun-suk Bak ) 한국농공학회 2010 한국농공학회 학술대회초록집 Vol.2010 No.-

농촌지역 사용종료 매립지에 의한 주변환경영향종합조사에 필요한 폐기물의 분해정도, 발생가스, 지반침하도 및 지하수 수질, 토양오염도등을 종합적으로 조사한 후 계획적이고 합리적인 사후관리 방안을 제시하여, 사용종료매립지로부터 발생 가능한 2차 환경오염을 예방하고자 한다. 1) 토양오염도 ○○ 사용종료매립장 주변지점의 토양오염도 분석결과 카드뮴(Cd) 2.07 ~ 4.20 mg/kg, 구리(Cu) 0.77 ~ 27.97 mg/kg, 비소(As) 9.80 ~ 21.00 mg/kg, 납(Pb) 6.77 ~ 11.53 mg/kg, 6가크롬(Cr6+) 0.02 ~ 0.42mg/kg, 아연(Zn) 불검출 ~ 28.10 mg/kg, 니켈(Ni) 2.37 ~ 25.63 mg/kg, 불소(F) 170.8 ~ 311.9 mg/kg, 톨루엔 불검출 ~ 0.13 mg/kg, TPH 45.419 ~ 58.069 mg/kg으로 나타나 기준 이하로 조사되었으며, 그 외의 항목에서는 불검출 되었음 2) 침출수 원수에 대한 수질조사 결과를 각 항목별로 살펴보면, BOD 6.9 ∼ 9.7 ㎎/L, CODcr 27.08 ∼ 83.25 ㎎/L, SS(부유물질) 4.8 ∼ 18.9 ㎎/L, pH 6.4 ∼ 7.1, n-Hexane(광유류) 0.3226 ∼ 0.6452 ㎎/L, n-Hexane(동식물)2.2581 ∼ 3.3871 ㎎/L, 용해성 철(s-Fe) 불검출 ∼ 0.259 ㎎/L, 아연(Zn) 0.017 ∼ 0.170 ㎎/L, 구리(Cu) 불검출 ∼ 0.036 ㎎/L, 용해성 망간(s-Mn) 0.109 ∼ 1.851 ㎎/L, 불소(F) 0.080 ∼ 0.210㎎/L, 대장균군수 478 ∼ 1,300 군수/100mL, 색도 23 ∼ 57 , 총인(T-P) 0.607 ∼ 2.772 ㎎/L, 질산성질소(NO3-N) 2.236 ∼ 17.530 ㎎/L, 아질산성질소(NO2-N) 0.766 ∼ 1.060 ㎎/L로 나타나 침출수 배출허용기준을 만족하는 것으로 나타났음. 시안(CN)을 비롯한 나머지 항목은 검출되지 않았음 3) 발생가스 각 측정지점 및 시기별로 차이는 있지만 항목별 성분비를 살펴보면, 메탄(CH4) 4.0 ∼ 74.6 %, 이산화탄소(CO2) 1.6 ∼ 20.7 %, 산소(O2) 2.4 ∼ 19.4 %, 질소(N2) 2.3 ∼ 75.0 % 로 조사되었음. 또한, 악취유발물질인 황화수소(H2S)와 암모니아(NH3)성분이 검출되지 않아 악취로 인한 대기질의 오염은 미미할 것으로 판단되며, 그 이외의 물질은 검출되지 않았음 4)지하수 항목별로 분석결과를 살펴보면, pH는 5.9 ~ 6.9, 대장균군수 162 ~ 1,410 군수/100mL, 염소(Cl) 20.3 ~ 72.3 ㎎/L, CODcr 1.37 ~ 19.79 ㎎/L, BOD 0.36 ~ 3.94 ㎎/L, 암모니아성질소(NH3-N) 불검출 ~ 17.880 ㎎/L, 아질산성질소(NO2-N) 불검출 ~ 0.028 ㎎/L로 기준을 만족하는 것으로 나타났으며, 카드뮴(Cd)을 비롯한 나머지 항목은 검출되지 않았음.

3차원 입체조형치료에 의한 아교모세포종의 방사선 선량증가 연구

조재호(Jae Ho Cho),이창걸(Chang Geol Lee) 김경주(Kyoung Ju Kim),박진호(Jino Bak),이세병(Se Byeoung Lee),조삼주(Sam Ju Cho),심수정(Su Jung Shim),윤덕현(Dok Hyun Yoon),장종희(Jong Hee Chang),김태곤(Tae Gon Kim),김동석(Dong Suk Kim),서장옥 대한방사선종양학회 2004 Radiation Oncology Journal Vol.22 No.4

목 적: 아교모세포종의 방사선치료에서 국소제어율과 생존율을 향상시켜 보고자 3차원 입체조형치료기법을 이용 한 방사선선량 증가 연구를 전향적으로 시행하였다. 대상 및 방법: 1997년 1월부터 2002년 7월까지 아교모세포종으로 조직학적 진단이 되고 전신수행도(KPS)가 60 이상으로 수술 후 방사선치료를 받은 환자를 대상으로 하였다. 프로토콜에 따라 전향적으로 연구에 참여한 42예의 고선량군과 후향적 대조군인 33예의 저선량군을 비교 분석하였다. 고선량군은 3차원 입체조형치료법에 의해 63.0∼70.2 Gy (중앙값 66 Gy)의 고선량 방사선을 조사받았으며, 저선량군은 2차원 치료방식으로 현재 표준선량으로 여겨지고 있는 59.4 Gy 정도(최소선량 50.4 Gy, 중앙선량 59.4 Gy)의 계획된 방사선치료를 종료할 수 있었던 환자들을 대상으로 하였다. 수술절제범위에 따라 나누어보면 전절제술 30예(40%), 준전절제술 30예(40%), 부분절제술 8예(11%), 그리고 조직생검만 시행된 환자가 7예(9%)였다. 각 환자의 육안종양체적은 CT 혹은 MRI상 수술절제연 및 잔류종양에 의해 정의되었다. 종양주변 부종은 저선량군에서는 임상표적체적에 포함되었지만, 고선량군에서는 재발양상 및 선량증가에 따른 합병증 증가의 가능성을 고려하여 제외하였다. 환자의 전체 및 무진행생존기간은 수 술 받은 날을 기준으로 Kaplan-Meier법으로 산출하였고, 기존 문헌에 보고되고 있는 예후인자들과 각 환자에 조사 된 방사선 선량, 표적체적 등이 생존율에 미치는 영향을 Log rank test 및 Cox regression analysis로 분석하였다. 추 적관찰을 위해 정기적으로 MRI가 시행되었다. 결 과: 전체환자의 중앙 생존기간 및 무진행 생존기간은 각각 15±1.65, 11±0.95개월이었다. 중앙생존기간은 저선량군 및 고선량군이 각각 14±0.94개월, 21±5.03개월로 고선량군에서 보다 나은 치료성적을 보여주었으며, 중앙무진행생존기간은 저선량군 10±1.63개월, 고선량군 12±1.59개월이었다. 특히 2년 생존율에 있어서 고선량군은 44.7%로 19.2%인 저선량군에 비해 훨씬 좋은 예후를 보였다. 단변량분석에서 예후에 영향을 미치는 중요인자로는 환자의 나이, 전신수행도, 종양의 위치, 수술절제범위, 표적체적, 방사선총선량 등이었다. 다변량분석에서 통계적으로 유의한 인자는 환자의 나이(p=0.012), 수술절제범위(p=0.000), 방사선선량군(p=0.049)이었다. 방사선괴사와 같은 방사선으로 인한 직접적인 만성합병증은 추적관찰기간 동안 발생하지 않았다. 결 론: 3차원 입체조형치료기법을 통하여 70 Gy까지의 방사선을 부작용 없이 조사할 수 있었고, 근치적 국소요법의 일환으로 방사선 선량증가가 전체 생존기간 및 무진행 생존기간을 향상시킬 수 있을 것으로 기대한다. Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received 63∼70 Gy (Median 66 Gy, fraction size 1.8∼2 Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were 15±1.65 and 11±0.95 months, respectively. There was a significantly longer survivaltime for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were 21±5.03 and 12±1.59 months, respectively, while for Arm 2 patients they were 14±0.94 and 10±1.63 months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; 44.7% versus 19.2%. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

만성췌장염에서 발생한 진단이 어려웠던 가성동맥류 2 예 : 천자와 hemosuccus pancreaticus 로 확인된 가성동맥류

박연호,김지훈,김재선,이창홍,공휘,박영태,김효정,정길만,고동욱,조남영 대한소화기내시경학회 2001 Clinical Endoscopy Vol.23 No.4

Pseudoaneurysm is a rare life-threatening complication of chronic pancreatitis. It can be diagnosed by various imaging modalities including computerized tomography (CT), ultrasound, and angiography. Early diagnosis and radiologic or surgical treatment can promise better outcomes. However, pseudoaneurysm is not easily diagnosed. It can be misdiagnosed as a pseudocyst with secondary infection. Rarely, the correct diagnosis is made by an inadvertent trial with percutaneous drainage. The endoscopically identified hemosuccus pancreaticus is also a rare finding. Recently, we experienced two cases of pseudoaneurysm in patients with chronic pancreatitis. They did not have any evidence of bleeding in the initial eddoscopy or evidence of pseudoaneurysms in the initial ultrasound and CT scan. In one case, the pseudoaneurysm was identified during a percutaneous drainage procedure, performed to diagnose and manage a cystic lesion which apperared to be an infected cyst. In the other case, the pseudoaneurysm was suspected after the hemosuccus pancreaticus was found during endoscopy performed due to recurrent hematemesis. Both cases were successfully treated with arterial embolization of the pseudoaneurysms.

肛門 및 直腸에 發生한 惡性黑色腫 1例

李章博(Jang Bak Lee),安東浩(Dong Ho Ahn),崔鳳洛(Bong Rhak Choi),李鐵(Chul Lee) 대한외과학회 1972 Annals of Surgical Treatment and Research Vol.14 No.10