Korean Byungkyul - Citrus platymamma Hort.et Tanaka flavonoids induces cell cycle arrest and apoptosis, regulating MMP protein expression in Hep3B hepatocellular carcinoma cells

Hong, G. E.,Lee, H. J.,Kim, J. A.,Yumnam, S.,Raha, S.,Saralamma, V. Venkatarame Gowda,Heo, J. D.,Lee, S. J.,Kim, E. H.,Won, C. K. Lychnia 2017 International journal of oncology Vol.50 No.2

<P>Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cycl in B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.</P>

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells

Heo, S.K.,Noh, E.K.,Yoon, D.J.,Jo, J.C.,Koh, S.,Baek, J.H.,Park, J.H.,Min, Y.J.,Kim, H. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.747 No.-

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b<SUP>+</SUP> and CD14<SUP>+</SUP> cells depended on ERK-NF-κB axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL.

Mirror pattern of cerebral artery atherosclerosis in patients with ischaemic stroke

Kim, Y. D.,Choi, H. Y.,Jung, Y. H.,Nam, C. M.,Yang, J. H.,Cho, H. J.,Nam, H. S.,Lee, K-Y.,Heo, J. H. Blackwell Publishing Ltd 2009 European Journal of Neurology Vol.16 No.10

<P>Background and purpose: </P><P>Although it has been suggested that bilateral symmetry of atherosclerosis can be found in paired arteries, including external carotid arteries and femoral arteries, it has remained unknown in intracranial arteries. We determined whether bilateral symmetry (a mirror pattern) of atherosclerosis presents in the entire cerebral arterial system.</P><P>Methods: </P><P>Angiographic findings of 795 consecutive patients with ischaemic stroke, after excluding those with cardiac sources of embolism or other causes of stroke, were reviewed retrospectively. The presence (location) and severity (the degree of stenosis) of atherosclerosis were compared between left and right sides at 26 predetermined arteries/segments.</P><P>Results: </P><P>We found 2230 lesions in predetermined segments/arteries from 669 patients. Amongst 509 patients with atherosclerotic lesions at two or more arteries/segments, mirror patterns were observed in 312 patients (61.3%). The mirror pattern increased steeply as the number of atherosclerotic arteries increased and was most frequently found in the carotid bulb (C1, 26.7%), followed by the middle cerebral artery (M1, 14.1%). The severity of stenosis was also correlated between left and right sides, and the correlation was highest in the C1 (<I>r</I> = 0.40, <I>P </I>< 0.001). Multiple logistic regression analyses revealed that the mirror patterns of atherosclerosis were more obvious in C1 and associated with a past history of ischaemic stroke and the number of stenotic lesions.</P><P>Conclusion: </P><P>Atherosclerosis in cerebral arteries may develop and progress in a mirror pattern. In patients with cerebral artery atherosclerosis, the occurrence and progression of atherosclerosis in the contralateral cerebral artery should be considered during follow-up examination.</P>

Wound healing potential of antibacterial microneedles loaded with green tea extracts

Park, S.Y.,Lee, H.U.,Lee, Y.C.,Kim, G.H.,Park, E.C.,Han, S.H.,Lee, J.G.,Choi, S.,Heo, N.S.,Kim, D.L.,Huh, Y.S.,Lee, J. Elsevier 2014 Materials Science and Engineering C Vol.42 No.-

This study evaluates the utility of an antibacterial microneedle composed of green tea (GT) extract and hyaluronic acid (HA), for the efficient delivery of GT. These microneedles have the potential to be a patient-friendly method for the conventional sustained release of drugs. In this study, a fabrication method using a mold-based technique to produce GT/HA microneedles with a maximum area of ~50mm<SUP>2</SUP> with antibacterial properties was used to manufacture transdermal drug delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out to observe the potential modifications in the microneedles, when incorporated with GT. The degradation rate of GT in GT/HA microneedles was controlled simply by adjusting the HA composition. The effects of different ratios of GT in the HA microneedles were determined by measuring the release properties. In HA microneedles loaded with 70% GT (GT70), a continuous higher release rate was sustained for 72h. The in vitro cytotoxicity assays demonstrated that GT/HA microneedles were not generally cytotoxic to Chinese hamster ovary cells (CHO-K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which were treated for 12 and 24h. Antimicrobial activity of the GT/HA microneedles was demonstrated by ~95% growth reduction of gram negative [Escherichia coli (E. coli), Pseudomonas putida (P. putida), and Salmonella typhimurium (S. typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles reduced bacterial growth of infected wound sites in the skin and improved wound healing process of skin in rat model.

Influence of growth temperature and post-annealing on an n-ZnO/p-GaN heterojunction diode

Sharma, S.K.,Heo, S.,Lee, B.,Lee, H.,Kim, C.,Kim, D.Y. Elsevier 2014 Current Applied Physics Vol.14 No.12

We report on an n-ZnO/p-GaN heterojunction diode fabricated from zinc oxide (ZnO) films at various growth temperatures (450, 500, 550, and 600 <SUP>o</SUP>C) by RF sputtering. The films were subsequently annealed at 700 <SUP>o</SUP>C in N<SUB>2</SUB> ambient. To investigate the influence of the growth temperature of n-ZnO films, the microstructural, optical, and electrical properties were measured using scanning electron microscopy (SEM), X-ray diffraction (XRD), photoluminescence (PL), and Hall measurements. The XRD pattern showed the preferred orientation along the c-axis (002) regardless of growth temperature. The PL spectra showed a dominant sharp near-band-edge (NBE) emission. Current-voltage (I-V) curves showed excellent rectification behavior. The turn-on voltage of the diode was observed to be 3.2 V for the films produced at 500 <SUP>o</SUP>C. The ideality factor of ZnO film was observed to be 1.37, which showed the best performance of the diode.

Protective effect and mechanism of action of diallyl disulfide against acetaminophen-induced acute hepatotoxicity

Ko, J.W.,Park, S.H.,Shin, N.R.,Shin, J.Y.,Kim, J.W.,Shin, I.S.,Moon, C.,Heo, J.D.,Kim, J.C.,Lee, I.C. Pergamon ; Elsevier Science Ltd 2017 Food and chemical toxicology Vol.109 No.1

The aim of this study was to investigate the potential protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute hepatotoxicity and elucidate the molecular mechanisms underlying these protective effects in rats. Treatment with AAP caused acute hepatotoxicity manifested by elevated levels of aspartate aminotransferase and alanine aminotransferase with corresponding histopathological changes and high levels of oxidative stress in the livers. AAP treatment also caused hepatocellular apoptosis with phosphorylation of c-Jun-N-terminal protein kinase (JNK). In addition, AAP caused activation of nuclear factor kappaB (NF-κB) concurrent with induction of inflammatory mediators. In contrast, pretreatment with DADS effectively attenuated acute liver injury and oxidative stress caused by AAP. DADS pretreatment suppressed cytochrome P450 2E1 (CYP2E1) levels in a dose-dependent manner and inhibited elevation of CYP2E1 activity induced by AAP. DADS pretreatment suppressed the phosphorylation of JNK and attenuated hepatocellular apoptotic changes. In addition, DADS inhibited the nuclear translocation of NF-κB and subsequent induction of inflammatory mediators. Overall, these results indicate that DADS confers a protective effect against oxidative stress-mediated JNK activation and apoptotic changes caused by AAP in the rat livers. This may be due to its ability to inhibit CYP2E1, enhance antioxidant enzymes activities, and suppress NF-κB activation.

A prospective multicentre phase II study of cisplatin and weekly docetaxel as first-line treatment for recurrent or metastatic nasopharyngeal cancer (KCSG HN07-01)

Korean Cancer Study Group,Ji, J.H.,Yun, T.,Kim, S.B.,Kang, J.H.,Park, J.C.,Cho, I.S.,Sohn, C.H.,Heo, D.S.,Jang, J.S.,Shin, S.W.,Hwang, D.W.,Sun, J.M.,Park, K.,Ahn, M.J. Pergamon Press 2012 European journal of cancer Vol.48 No.17

Background: The purpose of this phase II study was to determine the efficacy and toxicity of cisplatin and weekly docetaxel combination chemotherapy as a first-line treatment in patients with recurrent or metastatic nasopharyngeal cancer. Patients and Methods: Recurrent or metastatic nasopharyngeal cancer patients were enrolled and received a combination of weekly docetaxel (35mg/m<SUP>2</SUP> on Day1 and Day8) and cisplatin (70mg/m<SUP>2</SUP> D1) every 21days, for up to a maximum of 6 cycles. The primary endpoint was objective response rate, and the secondary endpoints included toxicity of combination chemotherapy, progression-free survival, overall survival and 1-year survival rate. Results: In total, 47 patients were enrolled and analysed, and 46 patients (97.9%) completed the planned protocol. In an intent-to-treat analysis, 6 patients (12.8%) achieved complete response (CR) and 27 patients (57.4%) showed partial response (PR), with an objective response rate of 70.2%. The median progression-free survival and overall survival were 9.6months (95% C.I. 5.7-13.5months) and 28.5months (95% C.I. 16.9-40.1months), respectively, and the 1-year survival rate was 89.9%. The common grade 3 adverse events were stomatitis (1.2%), neutropenia (0.8%), anaemia (0.8%), infection (0.8%) and diarrhoea (0.8%). Grade 4 adverse events were not observed in this study. Conclusions: The combination chemotherapy of cisplatin and weekly docetaxel is highly effective and shows favourable toxicity as a first-line chemotherapy in patients with recurrent or metastatic nasopharyngeal cancer.

Comparison of inflammatory markers between diabetic and nondiabetic ST segment elevation myocardial infarction

Heo, J.M.,Park, J.H.,Kim, J.H.,You, S.H.,Kim, J.S.,Ahn, C.M.,Hong, S.J.,Shin, K.H.,Lim, D.S. Japanese College of Cardiology 2012 Journal of cardiology Vol.60 No.3

Background: Inflammation plays a significant role in acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM). There may be similar inflammatory changes in non-DM patients with ST elevation myocardial infarction (STEMI) and DM patients with stable angina (SA), and DM patients with STEMI may have more severe changes than the former two groups. The objectives of this study were to investigate whether the level of inflammation was similar in patients with non-DM STEMI and DM SA, and to evaluate whether the changes in the level of inflammation were more severe in patients with DM STEMI compared to the other two groups. Methods and results: A variety of inflammatory markers including: highly sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), IL-18, vascular cell adhesion molecule-1 (VCAM-1), and matrix metallopeptidase-9 (MMP-9) as well as insulin resistance were compared among the three groups: DM STEMI (90 patients), DM SA (91 patients), and non-DM STEMI (76 patients). Inflammatory marker levels were not significantly different between the DM SA and non-DM STEMI groups. However, hsCRP and IL-6 were increased in the DM STEMI compared to the DM SA patients (p=0.005 and p=0.004, respectively). In addition, hsCRP, ESR, and IL-18 were increased in the DM STEMI compared to the non-DM STEMI patients (p=0.017, p=0.020, and p=0.033, respectively). Furthermore, the fasting insulin and the homeostasis model assessment were significantly increased in the DM STEMI compared to the DM SA patients (p=0.04 and p=0.004, respectively). Conclusions: DM SA and non-DM STEMI may have similar inflammatory changes. DM STEMI may be a more severe inflammatory condition compared to patients with DM SA or non-DM STEMI.

플랜지가 있는 제품에서 부분패드의 영향에 관한 연구

고관영,허주환,문정효,장재석,김동윤,정민섭,김주찬,박기용,이강연,조명우,이권진,조영호,이효걸,김주호,이경희 울산과학대학 2000 연구논문집 Vol.27 No.1

본 논문에서는 기존의 Motion-JPEG 기반 감시시스템에서 낮은 동영상 압축성능 문제를 해결하기 위한 새로운 동영상 압축기법을 제안하였다. 제안된 방법에서는 현재 프레임의 JPEG 데이터 중 변화된 압축 데이터만이 실시간으로 추출하고 저장된다. 제안된 방법에 의해 저장된 데이터는 기존의 JPEG과는 다른 고유의 포맷을 가지기 때문에, 동영상 데이터는 더욱 안전하게 유지될 수 있다. 실험을 통해, 제안된 동영상 압축기법의 압축률이 기존의 Motion-JPEG 기반 감시시스템에 비해 3배정도 높다는 것을 확인할 수 있었다.

결정질 태양전지에서 니켈 전극 상요을 위한 열처리 방안

정우원(W.W. Jung),김성철(S.C. Kim),경도현(D.H. Kyung),권태영(T.Y. Kwon),이영석(Y.S. Lee),허윤성(Y.S. Heo),박승일(S.I. Park),이준신(J.S. Yi) 대한전기학회 2009 대한전기학회 학술대회 논문집 Vol.2009 No.4

고효율 태양전지를 위한 결정질 태양전지의 구조 중 UNSW에서 개발한 BCSC(buried contact solar cell)가 있는데, 이는 전면 전극을 laser 처리 후 무전해니켈 도금으로 형성한 것이다. 이같은 진면 전극을 형성하기 위해서는 무전해 nickel 도금 후 열처리가 필수적이다. 우리는 이 공정을 확립하기 위해 결정질 wafer에 후연을 PECVD로 SiNx막을 형성하여 30Ω/□로 도핑한 후 후면을 불산으로 제거한 상태에서 양면을 니켈 무전해 도금으로 전극을 형성하여 300℃, 350℃, 400℃에 서 각각 3,6,9분간 진행하였다. 그 결과 400℃에서 3분간 열처리된 sample이 상대적으로 가장 명확한 IV curve를 형성하였다. 이 실험의 결과는 PN 접합 구조에서 전극을 nickel로 사용할 때 유용하게 사용될 수 있다.