종합 건강진단을 실시한 정상성인에서의 혈청지질 분포에 관한 연구

박일환,유선미,정유석 단국대학교 1997 論文集 Vol.31 No.-

Background: Hypercholesterolemia and dyslipidemia are regarded as the risk factors of atherosclerosis of the coronary arteries. The purpose of this study is to measure the serum lipid levels of the normal persons and to calculate the cut-off values of serum lipid levels to predict the occurence of coronary events. Methods: We investigated the serum lipid profiles of the normal adults who had visited the health promotion center of Dankook University Hospital. The mean values of serum lipids were evaluated according to the groups of age, we calculated the percentile values of serum total choleterol. Results: In normal adult persons, the means of total cholesterol increased according to age. The cut-off values of serum total cholesterol for the risk of atherosclerotic coronary events were 189 ㎎/dl for the moderate risk group(75∼90 percentile of normal persons) and 225 ㎎/dl for the high risk group(over 90 percentile of normal persons). Conclusions: This study shows that the mean and the cut-off values of serum lipid in the persons who are not obese and have normal blood pressure are significantly lower than those values of normal Korean adult persons.

Anti-inflammatory effects of novel <i>polygonum multiflorum</i> compound via inhibiting NF-κB/MAPK and upregulating the Nrf2 pathways in LPS-stimulated microglia

Park, Sun Young,Jin, Mei Ling,Kang, Nam Jun,Park, Geuntae,Choi, Young-Whan Elsevier/North-Holland 2017 Neuroscience letters Vol.651 No.-

<P><B>Abstract</B></P> <P>The incorporation of <I>Polygonum multiflorum</I> into the diet can result in anti-aging effects owing to its wide range of biological and pharmaceutical properties. We investigated the anti-neuroinflammatory properties of CRPE56IGIH isolated from <I>P. multiflorum</I> by focusing on its role in the induction of phase II antioxidant enzymes and the modulation of upstream signaling pathways. In microglia, CRPE56IGIH significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide and prostaglandin E<SUB>2</SUB> production with nonspecific cytotoxicity. CRPE56IGIH also markedly inhibited LPS-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein and mRNA expression in the same manner as it inhibited nitric oxide and prostaglandin E<SUB>2</SUB> production. In the control cells, NF-κB transactivation and nuclear translocation occurred at a baseline level, which was significantly increased in response to LPS. However, pretreatment with CRPE56IGIH concentration-dependently inhibited the LPS-induced NF-κB transactivation and nuclear translocation. The phosphorylation of Janus kinase-signal transducers and activators of transcription and mitogen-activated protein kinases was markedly upregulated by LPS, but considerably and dose-dependently inhibited by pretreatment with CRPE56IGIH. Furthermore, CRPE56IGIH induced the expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone-1 (NQO-1). The activation of upstream signaling pathways, such as the Nrf2 pathway, was significantly increased following CRPE56IGIH treatment. Furthermore, the anti-neuroinflammatory effect of CRPE56IGIH was reversed by transfection of Nrf2, HO-1, and NQO-1 siRNA. Our results indicated that CRPE56IGIH isolated from <I>P. multiflorum</I> could be used as a natural anti-neuroinflammatory agent that induces phase II antioxidant enzymes <I>via</I> Nrf2 signaling.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CRPE56IGIH is a natural compound isolated from <I>Polygonum multiflorum.</I>. </LI> <LI> CRPE56IGIH inhibits LPS induced neuroinflammatory response in microglia. </LI> <LI> CRPE56IGIH inhibits LPS-induced NF-κB and JAK-STATs activation in microglia. </LI> <LI> Nrf2 mediates the anti-neuroinflammation of CRPE56IGIH in microglia. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

AMPK/Nrf2 Signaling is Involved in the Anti-Neuroinflammatory Effect of Novel Compound from Petasites japonicus in Microglia against LPS

Sun Young Park,Seon Yeong Chae,Young-Whan Choi,Geun Tae Park 한국환경과학회 2017 한국환경과학회 학술발표회 발표논문집 Vol.2017 No.11

Detection of Serum Free DNA Hypermethylation in Surgically Resected Adenocarcinoma of the Lung

Park, Sun Jung,Kim, Young Tae,Park, Ju-Yeon,Wi, Hyun Cho,Kang, Chang Hyun,Sung, Sook-Whan,Kim, Joo Hyun 대한폐암연구회 2008 Journal of Lung Cancer Vol.7 No.2

Purpose: Aberrant DNA methylation patterns have been commonly associated with human cancers. We have investigated the frequency of DNA hypermethylation in promoter regions from adenocarcinomas of the lung and then attempted to detect the same epigenetic changes from patient serum samples. Materials and Methods: We collected tissues from 72 cases of lung adenocarcinomas. The cancer and normal lung tissues were tested for DNA hypermethylation using methylation-specific PCR (MSP). The genes investigated were DAPK, RARβP2 and p16. We selected 12 patients where promoter hypermethylation was present for all three genes and four patients where hypermethylation was not seen for any of the three genes. Serum-free DNA was extracted and was tested for promoter hypermethylation. The status of serum-free DNA methylation was analyzed; the hypermethylation status was compared to clinical variables and cancer outcomes. Results: DNA hypermethylation was observed in 32% of samples for DAPK, 63% of samples for RARβP2 and 83% of samples for p16 from the cancer tissues. Among the 12 matched serum samples where the primary tumor showed hypermethylation in all three gene promoter regions, we were able to detect five incidences of serum DNA hypermethylation in four patients. The four patients had TNM stage II or higher disease. None of the patients with stage I disease showed serum-free DNA hypermethylation. Conclusion: Aberrant promoter hypermethylation was frequently observed in surgically resected adenocarcinoma of the lung. Concurrent serum-free DNA hypermethylation was detected in 34% of patients where the primary tumor showed hypermethylation in all three gene promoter regions. The findings suggest that the serum-free DNA methylation status might be used as a potential target for the diagnosis of lung cancer. However, the low sensitivity should be improved for use in a clinical application.

α-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta 1-42 fibril-induced microglial activation : α-Iso-cubebenol inhibits neuroinflammation

Park, Sun Young,Park, Tae Gyeong,Lee, Sang-Joon,Bae, Yoe-Sik,Ko, Min J.,Choi, Young-Whan Pharmaceutical Society of Great Britain 2014 Journal of pharmacy and pharmacology Vol.66 No.1

3,3′-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions

PARK, HONGZOO,LEE, DAE-SUNG,YIM, MI-JIN,CHOI, YUNG HYUN,PARK, SAEGWANG,SEO, SU-KIL,CHOI, JUNG SIK,JANG, WON HEE,YEA, SUNG SU,PARK, WON SUN,LEE, CHANG-MIN,JUNG, WON-KYO,CHOI, IL-WHAN UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.36 No.1

<P>Oxidative stress in the retinal pigment epithelium (RPE) can lead to the pathological causes of age-related macular degeneration (AMD). Hypoxia induces oxidative damage in retinal pigment epithelial cells (RPE cells). In this study, we investigated the capacity of 3,3-diindolyl-methane (DIM) to reduce the expression of vascular endothelial growth factor (VEGF) under hypoxic conditions, as well as the molecular mechanisms involved. Human RPE cells (ARPE-19 cells) were treated with cobalt chloride (CoCl2, 200 mu M) and/or DIM (10 and 20 mu M). The production of VEGF was measured by enzyme-linked immunosorbent assay. The trans-location of hypoxia-inducible factor-1 (HIF-1) and nuclear factor-B (NF-B) was determined by western blot analysis. The binding activity of HIF-1 and NF-B was analyzed by electrophoretic mobility shift assay. The phosphorylation levels of mitogen-activated protein kinases (MAPKs) were measured by western blot analysis. The levels of mitochondrial reactive oxygen species (ROS) were detected by fluorescence microplate assay. The results revealed that DIM significantly attenuated the CoCl2-induced expression of VEGF in the ARPE-19 cells. The CoCl2-induced translocation and activation of HIF-1 and NF-B were also attenuated by treatment with DIM. In addition, DIM inhibited the CoCl2-induced activation of p38 MAPK in the ARPE-19 cells. Pre-treatment with YCG063, a mitochondrial ROS inhibitor, led to the downregulation of the CoCl2-induced production of VEGF by suppressing HIF-1 and NF-B activity. Taken together, the findings of our study demonstrate that DIM inhibits the CoCl2-induced production of VEGF by suppressing mitochondrial ROS production, thus attenuating the activation of HIF-1 and p38 MAPK/NF-B.</P>

Phosphodiesterase Ⅲ Inhibitor Cilostazol Protects Amyloid β-Induced Neuronal Cell Injury via Peroxisome Proliferator-Activated Receptor-γ Activation

Sun Haeng Park(박선행),Ji Hyun Kim(김지현),Sun Sik Bae(배순식),Ki Whan Hong(홍기환),Byung Tae Choi(최병태),Hwa Kyoung Shin(신화경) 한국생명과학회 2011 생명과학회지 Vol.21 No.5

Amyloid β (Aβ)의 신경독성은 알츠하이머병의 주된 원인이 되고 이러한 신경독성은 일련의 신경세포 사멸반응에 의해 일어난다고 알려져 있다. 본 연구에서는 알츠하이머병의 실험모델로 mouse primary neuronal cell에 Aβ25-35를 처리하여 세포독성을 유도하는 세포실험모델과 C57BL/6J mouse 뇌실에 Aβ25-35를 주입하여 인지장애를 일으키는 동물실험모델을 이용하여 phosphodiesterase Ⅲ 억제제인 cilostazol의 신경보호 효과에 대해 조사하였다. Aβ25-35를 신경세포에 처리하면 세포생존율이 감소되었고, 세포사멸이 일어난 세포의 수도 증가되었다. 이러한 Aβ25-35에 의한 세포독성이 cilostazol처리에 의해 회복되었으며, peroxisome proliferator-activated receptor (PPAR)-γ 항진제인 rosiglitazone 또한 동일한 회복효과를 나타내었다. Cilostazol과 rosiglitazone에 의한 이러한 회복효과가 PPAR-γ 길항제인 GW9662에 의해 다시 억제되는 결과를 통해 cilostazol의 효과는 PPAR-γ가 매개하는 신호전달이 관여함을 알 수 있었다. 직접 PPAR-γ 활성화 정도를 측정한 결과, Aβ25-35 처리에 의해 감소된 PPAR-γ 활성화 정도가 cilostazol과 rosiglitazone에 의해 증가함을 관찰할 수 있었고, 이는 GW9662에 의해 다시 억제됨을 확인하였다. 게다가, cilostazol은 세포사멸이 일어난 세포의 수와 세포사멸 조절단백질인 Bax/Bcl-2의 비율도 감소시켰다. Cilostazol (20 ㎎/㎏, 구강투여)을 C57BL/6J mice 뇌실에 Aβ25-35를 주입하기 2주 동안 전처리하고, Aβ25-35 주입 후 4주 동안 처리하면, 기억력과 학습능력을 증진시킨다는 결과를 water maze 실험을 통해 알 수 있었으며, rosiglitazone (10 ㎎/㎏)을 먹인 동물에서도 동일한 결과를 얻을 수 있었다. 본 연구를 통해서 cilostazol이 PPAR-γ 활성화를 통해 Aβ25-35로 인한 신경세포 손상과 세포사멸을 약화시켜, 신경세포의 생존을 증진시키고, 알츠하이머에서 인지장애를 개선할 것으로 생각된다. 따라서, phosphodiesterase Ⅲ 억제제인 cilostazol은 알츠하이머 질병 치료에 새로운 전략이 될 수 있을 것이다. The neurotoxicity of aggregated amyloid β (Aβ) has been implicated as a critical cause in the pathogenesis of Alzheimer’s disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase Ⅲ inhibitor, on Aβ25-35-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-γ activation. Aβ25-35 significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from Aβ-induced cell death as well as rosiglitazone, a PPAR-γ activator. These effects were suppressed by GW9662, an antagonist of PPAR-γ activity, indicative of a PPAR-γ -mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-γ activity levels that had been altered as a result of Aβ25-35 treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of Aβ25-35 in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 ㎎/㎏) for 2 weeks before Aβ25-35 injection and once a day for 4 weeks post-surgery almost completely prevented the Aβ25-35-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate Aβ25-35-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-γ activation. The phosphodiesterase Ⅲ inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.

Session 2. 곤충매개 인수공통전염병: Vectorborne Zoonotic Diseases : S2-2 ; Severe Fever with Thrombocytopenia Syndrome: Molecular and Serological Diagnosis

( Sun Whan Park ),( Jung Sang Ryou ),( Seok Min Yun ),( Chan Park ),( Won Ja Lee ),한명국 ( Myung Guk Han ) 대한인수공통전염병학회 2014 창립총회 및 학술대회 초록집 Vol.2014 No.1

Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging viral infectious disease, first reported in China in 2010. Patients with SFTS have been reported recently in South Korea and Japan in 2013. Totally 36 cases of SFTS were identified in Korea in 2013 with case fatality rate of 47%. The SFTS is characterized by acute febrile illness, thrombocytopenia, leucopenia, gastrointestinal symptoms, elevated serum enzymes and multi-organ failure which are not specific signs and symptoms for SFTS. The SFTS virus (SFTSV) causing SFTS belongs to the genus Phlebovirus in the family Bunyaviridae. Heartland viruses and Hunter Island Group virus (HIGV) which are related to but distinctly different from SFTSV were isolated from patients in the US and ticks in Australia, respectively. The patients infected with Heartland virus presented a similar signs and symptoms to SFTS. HIGV was isolated from ticks collected from shy albatross on Albatross Island, a small island in the Hunter Island Group in northwestern Tasmania, Australia. The SFTSV has been detected in Haemaphysalis longicornis and Rhipicephalus microplus ticks suggesting that the causative agent of SFTS, SFTSV is transmitted possibly to humans by ticks, such as H. longicornis which is considered as the principal vector of SFTSV. Recently Amblyomma testudinarium and Ixodes nipponensis are also implicated as the vector of SFTSV. Although cases of person-to-person transmission through contact with infected patient’s blood or mucous have also been reported in China, transmission of SFTSV takes place by biting of ticks infected with SFTSV. The SFTS presents with clinical manifestations similar to those of other infectious vector-borne diseases, such as hemorrhagic fever with renal syndrome (HFRS), scrub typhus, leptospirosis and anaplasmosis, strongly suggesting the need for differential diagnosis of SFTS from other infectious diseases. HFRS, leptospirosis and anaplasmosis are caused by Hantavirus, Leptospira interrogans and Anaplasma phagocytophilum, respectively. Wild rodents (Apodemus agrarius) play the role of the primary natural reservoir for these pathogens. HFRS, scrub typhus and leptospirosis are endemic in eastern and south-east Asia including Korea. In terms of distribution of hosts and reservoirs of vector-borne pathogens in the environment, and current coexistence of these diseases in the same epidemic area, concurrent infections of these vector-borne diseases can occur. Therefore, a reliable SFTSV detection tool is urgently required to provide early diagnosis of SFTS to support clinical care, infection control and epidemiological surveillance. Laboratory diagnosis of SFTSV infection is carried out by various ways, including nucleic acid amplification, detection of viral antigen, virus isolation and antibody detection to SFTSV using by real-time RT-PCR, Vero E6 cell culture, enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent assay (IFA). Conventional RT-PCR and real-time RT-PCR was developed in our laboratory and applied to detect SFTSV from hospitalized patients who presented SFTS symptoms. The SFTSVs were detected from 35 specimens among more than 300 serum specimens in 2013 and the nucleotide sequence was analyzed for identification of the SFTSV. The Korean isolates of SFTSV showed 93-98% similarityof the nucleotide sequences to Chinese and Japanese isolates of SFTSV and were distinctly different from Heartland virus. SFTSVs were also isolated by Vero E6 cell culture and identified by the nucleotide sequence, IFA using monoclonal antibodies, and electron microscopy. As reported, antibody to SFTSV can be detected as early as 2 to 4 days after illness onsets by serological assays and persists in some patients even one year after recovery. Seroconversion against SFTS V in patients with SFTS occurs mostly more than 3 weeks after onsets of illness. We developed IFA for laboratory diagnosis and determined serologic cross reactivity of SFTSV to Hantavirus and rickets. Slides for IFA were prepared with Vero E6 cells infected with SFTSV and Hantaan virus (HTNV). Commercial IFA kits for Anaplasma, Ehrlichia, Leptosira and Origentia spp were also used in the study. Serum specimens of SFTSV patients, sera of HTNV IgG antibody of more than 512 and paired sera of scrub typhus patients were tested with IFA. None of sera specimens showed specific antibody reaction to SFTSV infected cells and antigens assayed by IFA. IgG titers to each homogeneous antigen of HTNV and O.tsutsugamushi assayed by IFA were ranged from 512 to 4,096 and from 0 to 8,192. These results suggest that SFTSV does not have cross reactivity to at least, HTNV and O. tsutsugamushi. Considered currently occurrence of SFTSV, HTNV and O. tsutsugamushi in the same epidemic of the country, concurrent infection can be identified by serological assays. In the presentation, we report a case of coinfection with SFTSV and Hantavirus in humans. To the best of our knowledge, this is the first case report of coinfection with SFTSV and Hantavirus. A 66-year-old farm-dwelling woman was admitted to the hospital with a 6-day history of worsening fever and myalgia. Neutropenia and thrombocytopenia were evident on admission to the intensive care unit. SFTSV infection was suspected based on clinical findings and laboratory test results, although the patient had no recollection of a tick bite and there was no evidence of tick bites. She was treated with plasma exchange and oral ribavirin (4.0g/day) after 10 days of illness onset and had fully recovered at 15 days after illness onset Considering the concurrence of SFTS, HFRS and ricketiisial diseases in the endemic area and the higher possibility of exposure to pathogens due to the patient’s area of residence and occupation as a farmer, coinfection with SFTSV, hantavirus and ricketiisial agents in the patient is suggested. Determining the effects of coinfection on disease prognosis and laboratory diagnosis could be helpful in deciding patient treatment and management.

Severe Fever with Thrombocytopenia Syndrome Virus, South Korea, 2013

Park, Sun-Whan,Han, Myung-Guk,Yun, Seok-Min,Park, Chan,Lee, Won-Ja,Ryou, Jungsang U.S. Department of Health and Human Services * Cen 2014 Emerging Infectious Diseases Vol.20 No.11

<P>During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.</P>

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome during an Outbreak in South Korea, 2013–2015

Park, Sun-Whan,Ryou, Jungsang,Choi, Woo-Young,Han, Myung-Guk,Lee, Won-Ja Allen Press, etc 2016 The American journal of tropical medicine and hygi Vol.95 No.6

<P>Since the first reported case of severe fever with thrombocytopenia syndrome (SFTS) in South Korea in 2013, between 2013 and 2015, we collected 1,697 serum samples from suspected patients who experienced symptoms of SFTS. We performed reverse transcriptase polymerase chain reaction using total RNA extracted from the patients' sera. When viral RNA was detected in the sera, SFTS was diagnosed. Among the 1,697 samples, 170 were positive for SFTS virus. We then analyzed the epidemiologic features of these 170 cases. As a result, we found that the annual number of cases increased steadily. However, the annual case fatality rate exhibited a downward trend. The majority of patients were aged ≥ 60 years, and most cases occurred during May–October in the eastern and southern parts of the country. These results may be useful for effective SFTS control by describing the clinical and epidemiologic features of the disease in South Korea.</P>