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Synergistically Combined Gene Delivery for Enhanced VEGF Secretion and Antiapoptosis
Won, Young-Wook,Lee, Minhyung,Kim, Hyun Ah,Nam, Kihoon,Bull, David A.,Kim, Sung Wan American Chemical Society 2013 MOLECULAR PHARMACEUTICS Vol.10 No.10
<P>With current pharmacological treatments, preventing the remodeling of the left ventricle and the progression to heart failure is a difficult task. Gene therapy is considered to provide a direct treatment to the long-term complications of ischemic heart diseases. Although current gene therapies that use single molecular targets seem potentially possible, they have not achieved success in the treatment of ischemic diseases. With an efficient polymeric gene carrier, PAM-ABP, we designed a synergistically combined gene-delivery strategy to enhance vascular endothelial growth factor (VEGF) secretion and to prolong its antiapoptotic effects. A hypoxia-inducible plasmid expressing both hypoxia-inducible heme oxygenase-1 (HO-1) and the Src homology domain-2 containing tyrosine phosphatase-1 microRNA (miSHP-1) as well as a hypoxia-responsive VEGF plasmid were combined in this study. The positive feedback circuit between HO-1 and VEGF and the negative regulatory role of SHP-1 in angiogenesis enhance VEGF secretion synergistically. The synergy in VEGF secretion as a consequence of the gene combination and prolonged HO-1 activity was confirmed in hypoxic cardiomyocytes and cardiomyocyte apoptosis under hypoxia and was decreased synergistically. These results suggest that the synergistic combination of VEGF, HO-1, and miSHP-1 may be promising for the clinical treatment of ischemic diseases.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2013/mpohbp.2013.10.issue-10/mp400178m/production/images/medium/mp-2013-00178m_0010.gif'></P>
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Transformation behaviour of Ti–Ni and Ti–Ni–Cu alloy ribbons with nano Ti<sub>2</sub>Ni particles
Nam, Tae-hyun,Lee, Jae-hwa,Jung, Dae-won,Yu, Cheol-am,Liu, Yinong,Kim, Yeon-wook Elsevier 2007 Materials science & engineering. properties, micro Vol.449 No.-
<P><B>Abstract</B></P><P>Ti–Ni and Ti–Ni–Cu alloy ribbons have been prepared by single roll melt spinning, and then martensitic transformation behaviours were investigated by means of transmission electron microscopy, differential scanning calorimetry and X-ray diffraction. In 51Ti–49Ni(at.%) alloy ribbons, Ti<SUB>2</SUB>Ni particles of a size less than 50nm with the coherent interface with the matrix were found, while they were not found in 50Ti–50Ni alloy ribbons. In 49Ti–46Ni–5Cu and 50Ti–45Ni–5Cu alloy ribbons, Ti<SUB>2</SUB>Ni particles of size less than 30nm with coherent interface with the matrix were found. Coherent Ti<SUB>2</SUB>Ni particles induced the R phase transformation in Ti–Ni alloys, and consequently transformation occurred in two-stages, i.e., B2–R–B19. Coherent Ti<SUB>2</SUB>Ni particles induced the B19 martensite in a Ti–45Ni–5Cu alloy, and consequently transformation occurred in two-stages, i.e., B2–B19–B19′. The change in transformation behaviour was ascribed to strain fields developed around coherent Ti<SUB>2</SUB>Ni particles.</P>
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Nam, Eun Ji,Lee, Maria,Yim, Ga Won,Kim, Jae Hoon,Kim, Sunghoon,Kim, Sang Wun,Kim, Jae Wook,Kim, Young Tae AlphaMed Press 2013 The oncologist Vol.18 No.7
<P>This study assessed the activity and toxicity of primary carboplatin-based chemoradiotherapy (CarboRT) and compared CarboRT with cisplatin-based chemoradiotherapy (CisRT) in patients with locally advanced cervical cancer and poor general condition. CarboRT was better tolerated than CisRT without compromising tumor response and survival in these patients.</P>
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Ultrastructural Changes of Hepatic Stellate Cells in the Space of Disse in Alcoholic Fatty Liver
(Nam Ik Han),(Kyu Won Chung),(Byung Min Ahn),(Sang Wook Choi),(Young Sok Lee),(Chang Don Lee),(Hee Sik Sun) 대한내과학회 2001 The Korean Journal of Internal Medicine Vol.16 No.3
N/A Background: Hepatic stellate cell (HSC) has been suggested to play a role in fibrogenesis in alcoholic liver disease. We evaluate the correlation with fibrogenesis and ultrastructure of hepatic stellate cells in alcoholic fatty liver. Methods: We studied 6 patients with alcoholic fatty liver and 5 non-alcoholic fatty liver. The numbers off at droplets in hepatic stellate cell was determined by electron microscopy. We also studied the grading of deposition of collagen fibers in the space of Disse. We were to evaluate the structure of hepatic stellate cells in the space of Disse by light and electron microscopy. Results: Wider distribution of fat droplets in hepatic stellate cells in alcoholic fatty liver than in normal liver. The hypertrophied endoplasmic reticulum in hepatic stellate cells is a prominent findings in alcoholic fatty liver. We observed basement membrane-like materials in patients with alcoholic fatty liver with hepatic fibrosis. Conclusion: The results demonstrate that, in patients with alcoholic fatty liver by alcoholic liver injury, the hepatic stellate cells may play an important role in the fibrogenesis of perisinusoidal spaces in the liver.
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NAM, Sung Min,HWANG, In Koo,YI, Sun Shin,YOO, Ki-Yeon,PARK, Ok Kyu,YAN, Bingchun,SONG, Wook,WON, Moo-Ho,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2011 The Journal of veterinary medical science Vol.73 No.8
<P>In this study, we investigated the effects of treadmill exercise on calretinin (CR), a marker of early postmitotic neurons, immunoreactivity in the dentate gyrus (DG) of Zucker diabetic fatty (ZDF) rats, before or after diabetes onset, and Zucker lean control (ZLC) rats. For this study, 6-week-old ZLC and prediabetic ZDF rats, and 22-week-old ZLC and ZDF rats were exercised on the treadmill. Sedentary ZLC and ZDF rats of the same age were used as exercise experiment controls. The exercised prediabetic ZDF rats did not show diabetes onset, while the sedentary prediabetic ZDF rats showed significantly increased blood glucose levels. The exercised diabetic ZDF rats exhibited a decrease in their blood glucose levels compared to the sedentary diabetic ZDF rats, but the levels were still above 20 mmol/<I>l</I>. ZLC rats of both ages were in the normoglycemic range. CR immunoreactivity was detected throughout the DG, including the subgranular zone and the polymorphic layer. Diabetic rats exhibited a significant decrease in the number of CR-immunoreactive cells and fibers in the DG. Exercise in the prediabetic ZDF rats significantly increased the number of CR-immunoreactive cells and fibers in the subgranular zone of the DG. In the ZLC and ZDF rats of chronic diabetic phase, exercise increased CR-immunoreactive neurons in the hilar region. These results suggest that diabetes significantly reduces the number of postmitotic CR-immunoreactive neurons and the intensity of immunoreactivity and that exercise increases these CR-related parameters in a diabetic stage-dependent manner.</P>
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Nam, Hyun,Kim, Ji-Hye,Kim, Jae-Won,Seo, Byoung-Moo,Park, Joo-Cheol,Kim, Jung-Wook,Lee, Gene Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.7
Human Hertwig's epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cells are epithelial remnants of teeth residing in the periodontium. Although the functional roles of HERS/ERM cells have yet to be elucidated, they are a unique epithelial cell population in adult teeth and are reported to have stem cell characteristics. Therefore, HERS/ERM cells might play a role as an epithelial component for the repair or regeneration of dental hard tissues; however, they are very rare population in periodontium and the primary isolation of them is considered to be difficult. To overcome these problems, we immortalized primary HERS/ERM cells isolated from human periodontium using SV40 large T antigen (SV40 LT) and performed a characterization of the immortalized cell line. Primary HERS/ERM cells could not be maintained for more than 6 passages; however, immortalized HERS/ERM cells were maintained for more than 20 passages. There were no differences in the morphological and immunophenotypic characteristics of HERS/ERM cells and immortalized HERS/ERM cells. The expression of epithelial stem cell and embryonic stem cell markers was maintained in immortalized HERS/ERM cells. Moreover, immortalized HERS/ERM cells could acquire mesenchymal phenotypes through the epithelial-mesenchymal transition via TGF-${\beta}1$. In conclusion, we established an immortalized human HERS/ERM cell line with SV40 LT and expect this cell line to contribute to the understanding of the functional roles of HERS/ERM cells and the tissue engineering of teeth.
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( Nam Kyu Kang ),( Jung Wha Chung ),( Hee Yoon Jang ),( Dong Won Park ),( Eun Sun Jang ),( Jin-wook Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Hepatitis B virus (HBV) DNA levels and HBsAg titer have been implicated as a predictor of the risk for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). Potent nucleos(t)ide analog therapy improves not only biochemical and virologic profiles but also the long-term prognosis of CHB. However, it is not certain whether HBV DNA and HBsAg titer still retain prognostic value in CHB on potent NA therapy. This study investigated whether pre-treatment HBsAg titer and HBV DNA levels can predict the risk of HCC development in CHB patients receiving entecavir therapy. Methods: This retrospective cohort study included 1,246 CHB patients who received entecavir and HCC surveillance from three referral centres in Korea. Baseline HBsAg titers and HBV DNA levels were analyzed by Kaplan-Meier method and log-rank test to calculate the cumulative incidence rates of HCC and compare them according to HBsAg and HBV DNA levels. Independent risk predictors of HCC were identified by Cox proportional hazard modeling. Results: The cumulative incidence of HCC during observation period was 1 %, 10.2%, and 51.8 % at 1, 5 and 9 years, respectively (9.6 per 1000 person-years). The baseline HBsAg titer and HBV DNA levels were 4311.4 (IQR = 2.9 - 9683) and 5.7 logIU/ml (IQR = 1.4 - 8.8461), respectively. The risk of HCC was higher in patients with HBsAg titer ≥ 5000 IU/L than in those with HBsAg titer < 5000 IU/L (P=0.002), whereas higher baseline DNA levels were not associated with higher risk for HCC ( > 5.7 vs <5.7 LogIU/ml; p = 0.166). Old age, male sex and presence of cirrhosis were also associated with increased HCC risk. Multivariate Cox analysis showed that HBsAg lost significance [HR = 1.26 (0.59-2.65)], whereas old age, male sex and presence of cirrhosis still predicted HCC risk as independent factors. Conclusions: In the era of potent NA therapy, baseline virologic parameters no longer have significant impact on the prediction of HCC development in addition to conventional clinical predictors. Additional predictors are needed for correct prediction of the HCC risk in CHB.
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( Nam Kyung Roh ),( Soo Young Kim ),( Ho Jung Jung ),( Yu Ri Kim ),( Yu Na Lee ),( Jae Wook Jung ),( Hyung Jin Hahn ),( Hyun Jung Park ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2
Background: The level of serum inflammatory cytokines and LL-37 is known to be elevated in patients with psoriasis compared to healthy controls. However, researches of level of serum inflammatory cytokines and LL-37 according to phenotypic heterogeneity in psoriasis have been scarcely reported. We demonstrate that interleukin(IL)-1 receptor antagonist and IL-17A were more increased in the eruptive inflammatory state when compared with the chronic stable state in the previous study. Objectives: We aimed to clarify difference of the circulating Th1, Th17 cytokines and LL-37 between guttate and plaque psoriasis and correlation between disease severity and serum level of inflammatory cytokines. Methods: A total of 74 patients with psoriasis(32 guttate psoriasis, 42 plaque psoriasis) were evaluated and serum samples were obtained. Multiple cytokine assay was used to measure Th1 and Th17 derived cytokines. Data were analyzed using the SPSS 17.0 for Windows program (SPSS, Chicago, IL, USA) Results: We observed no difference of the level of serum inflammatory cytokines and LL-37 according to clinical phenotype in patients with psoriasis. Psoriasis Area and Severity Index(PASI) is significantly correlated with serum cytokine level in patients with plaque psoriasis but not in patients with guttate psoriasis. Conclusion: There is no difference of the level of serum inflammatory cytokine and LL-37 according to clinical phenotype. Clinical severity was correlated with serum inflammatory cytokines but not LL-37
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( Nam Kyung Roh ),( Soo Young Kim ),( Ho Jung Jung ),( Yu Ri Kim ),( Jae Wook Jung ),( Yu Na Lee ),( Hyung Jin Hahn ),( Hyun Jung Park ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2
Background: Photoaging is clinical and histological skin alteration caused by sun exposure. In vitro, previous studies have shown that both UVA and UVB exert effect on collagen formation and degradation. However, the light source of UVB used has been broadband UV, which contains other wavelengths besides UVB. There was no study conducted on the subject matter using monochromatic filtered UV. Objectives: The aim of this study was to evaluate the effect of UVA and UVB with monochromatic filter on human dermal fibroblasts and to elucidate the difference between previous studies using broadband UVB and present monochromatic UVB result. Methods: Solar UV simulator(ORIEL corporation, USA) was used for the light source of UVA and UVB. After irradiating UVA and 300nm monochromatic filtered UVB on human dermal fibroblasts, gene expressions of MMP-1, MMP-3, Collagen-Iα1, Collagen-Iα2 and TIMP-1 were assessed by RT-PCR. When irradiating monochromatic UVB, we adjusted different amount of energy of UVB (50mJ, 100mJ, 200mJ). Results: In vitro, UVA and UVB irradiation induced significant upregulation of MMP-1, MMP-3, collagen-Iα1 and collagen-Iα2, as previous studies have been shown. Expression of those genes was inversely decreased proportional to the amount of UVB energy above 50mJ. Conclusion: Although UVA and UVB exert different effect on choromophores, both UVA and UVB are able to induce MMPs expression in vitro. Also, it is necessary to demonstrate the specific spectrum of light source.
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Hypersensitivity to RF fields emitted from CDMA cellular phones: A provocation study
Nam, Ki Chang,Lee, Ju Hyung,Noh, Hyung Wook,Cha, Eun Jong,Kim, Nam Hyun,Kim, Deok Won Wiley Subscription Services, Inc., A Wiley Company 2009 Bioelectromagnetics Vol.30 No.8
<P><B>Abstract</B></P><P>With the number of cellular phone users rapidly increasing, there is a considerable amount of public concern regarding the effects that electromagnetic fields (EMFs) from cellular phones have on health. People with self‐attributed electromagnetic hypersensitivity (EHS) complain of subjective symptoms such as headaches, insomnia, and memory loss, and attribute these symptoms to radio frequency (RF) radiation from cellular phones and/or base stations. However, EHS is difficult to diagnose because it relies on a person's subjective judgment. Various provocation studies have been conducted on EHS caused by Global System for Mobile Communications (GSM) phones in which heart rate and blood pressure or subjective symptoms were investigated. However, there have been few sham‐controlled provocation studies on EHS with Code Division Multiple Access (CDMA) phones where physiological parameters, subjective symptoms, and perception of RF radiation for EHS and non‐EHS groups were simultaneously investigated. In this study, two volunteer groups of 18 self‐reported EHS and 19 non‐EHS persons were tested for both sham and real RF exposure from CDMA cellular phones with a 300 mW maximum exposure that lasted half an hour. We investigated not only the physiological parameters such as heart rate, respiration rate, and heart rate variability (HRV), but also various subjective symptoms and the perception of EMF. In conclusion, RF exposure did not have any effects on physiological parameters or subjective symptoms in either group. As for EMF perception, there was no evidence that the EHS group better perceived EMF than the non‐EHS group. Bioelectromagnetics 30:641–650, 2009. © 2009 Wiley‐Liss, Inc.</P>
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