• Title/Summary/Keyword: Biomedical technology

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BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types

  • Ryoo, Soyoon;Choi, Jida;Kim, Jaemyung;Bae, Suyoung;Hong, Jaewoo;Jo, Seunghyun;Kim, Soohyun;Lee, Youngmin
    • IMMUNE NETWORK
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    • v.13 no.6
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    • pp.283-288
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    • 2013
  • The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

  • Lee, Ji Eun;Woo, Min Gyu;Jung, Kyung Hee;Kang, Yeo Wool;Shin, Seung-Min;Son, Mi Kwon;Fang, Zhenghuan;Yan, Hong Hua;Park, Jung Hee;Yoon, Young-Chan;Kim, Yong-Sung;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.274-283
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    • 2022
  • KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Characterization of Thickness and Electrical Properties of Ni-Cr Thin Films via Terahertz Time-domain Spectroscopy

  • Sunghun Kim;Inhee Maeng;Hyeon Sang Bark;Jungsup Byun;Jae Hun, Na;Seho Kim;Myeong Suk Yim;Byung-Youl Cha;Youngbin Ji;Seung Jae Oh
    • Current Optics and Photonics
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    • v.7 no.5
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    • pp.569-573
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    • 2023
  • We utilized terahertz time-domain spectroscopy (THz-TDS) to measure the thickness and electrical properties of nickel-chromium (Ni-Cr) films. This technique not only aligns well with traditional methods, such as haze-meter and transmission-densitometer measurements, but it also reveals the electrical properties and thickness of films down to a few tens of nanometers. The complex conductivity of the Ni-Cr thin films was extracted using the Tinkham formula. The experimental values closely aligned with the Drude model, indicating the reliability of our Ni-Cr film's electrical and optical constants. The thickness of Ni-Cr was estimated using the complex conductivity. These findings emphasize the potential of THz-TDS in quality control of metallic nanofilms, pointing toward an efficient and nondestructive test (NDT) for such analyses.

NOVEL CATIONIC POLYMERS DESIGNED FOR NON-VIRAL GENE DELIVERY

  • Zhong Zhiyuan;Lin, Chao;Song, Yan;Lok Martin C.;Jiang Xulin;Christensen Lane V.;Engbersen Johan F.J.;Kim, Sung-Wan;Hennink Wim E.;Feijen Jan
    • Proceedings of the Polymer Society of Korea Conference
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    • 2006.10a
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    • pp.44-45
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    • 2006
  • Gene therapy holds great promise for treating various forms of diseases with a genetic origin including cystic fibrosis, different forms of cancer, and cardiovascular disorders. The clinical use of gene therapy treatments is however restricted, mainly because of the absence of safe and efficient gene delivery technologies. In our group, with an aim of developing efficient and nontoxic polymeric gene delivery systems, several novel types of polymeric gene carriers have been designed, synthesized, and evaluated. Herein, I will mainly present our recent work on low molecular weight linear PEI-PEG-PEI triblock copolymers, degradable hyperbranched poly(ester amine)s, and reduction-sensitive poly(amido amine)s.

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Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals

  • Reshma, Cherian Sebastian;Sruthi, Sudhakaran;Syama, Santhakumar;Gayathri, Vishwanath;Mohanan, Parayanthala Valappil
    • Toxicological Research
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    • v.31 no.1
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    • pp.49-59
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    • 2015
  • Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

Vitrification, in vitro fertilization, and development of Atg7 deficient mouse oocytes

  • Bang, Soyoung;Lee, Geun-Kyung;Shin, Hyejin;Suh, Chang Suk;Lim, Hyunjung Jade
    • Clinical and Experimental Reproductive Medicine
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    • v.43 no.1
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    • pp.9-14
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    • 2016
  • Objective: Autophagy contributes to the clearance and recycling of macromolecules and organelles in response to stress. We previously reported that vitrified mouse oocytes show acute increases in autophagy during warming. Herein, we investigate the potential role of Atg7 in oocyte vitrification by using an oocyte-specific deletion model of the Atg7 gene, a crucial upstream gene in the autophagic pathway. Methods: Oocyte-specific Atg7 deficient mice were generated by crossing Atg7 floxed mice and Zp3-Cre transgenic mice. The oocytes were vitrified-warmed and then subjected to in vitro fertilization and development. The rates of survival, fertilization, and development were assessed in the Atg7 deficient oocytes in comparison with the wildtype oocytes. Light chain 3 (LC3) immunofluorescence staining was performed to determine whether this method effectively evaluates the autophagy status of oocytes. Results: The survival rate of vitrified-warmed $Atg7^{f/f}$;Zp3-Cre ($Atg7^{d/d}$) metaphase II (MII) oocytes was not significantly different from that of the wildtype ($Atg7^{f/f}$) oocytes. Fertilization and development in the $Atg7^{d/d}$ oocytes were significantly lower than the $Atg7^{f/f}$ oocytes, comparable to the $Atg5^{d/d}$ oocytes previously described. Notably, the developmental rate improved slightly in vitrified-warmed $Atg7^{d/d}$ MII oocytes when compared to fresh $Atg7^{d/d}$ oocytes. LC3 immunofluorescence staining showed that this method can be reliably used to assess autophagic activation in oocytes. Conclusion: We confirmed that the LC3-positive signal is nearly absent in $Atg7^{d/d}$ oocytes. While autophagy is induced during the warming process after vitrification of MII oocytes, the Atg7 gene is not essential for survival of vitrified-warmed oocytes. Thus, induction of autophagy during warming of vitrified MII oocytes seems to be a natural response to manage cold or other cellular stresses.

Methylation Pattern of H19 Gene at Various Preimplantation Development Stages of In Vitro Fertilized and Cloned Porcine Embryos

  • Im, Young-Bin;Han, Dong-Wook;Gupta, Mukesh Kumar;Uhm, Sang-Jun;Heo, Young-Tae;Kim, Jin-Hoi;Park, Chan-Kyu;Lee, Hoon-Taek
    • Reproductive and Developmental Biology
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    • v.31 no.2
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    • pp.83-90
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    • 2007
  • Insulin-like growth factor II (IGF2) and H19 genes are mutually imprinted genes which may be responsible for abnormalities in the cloned fetuses and offspring. This study was performed to identify putative differentially methylated regions (DMRs) of porcine H19 locus and to explore its genomic imprinting in in vitro fertilized (IVF) and somatic cell nuclear transferred (SCNT) embryos. Based on mice genomic data, we identified DMRs on H19 and found porcine H19 DMRs that included three CTCF binding sites. Methylation patterns in IVF and SCNT embryos at the 2-, 4-, $8{\sim}16$-cells and blastocyst stages were analyzed by BS (Bisulfite Sequencing)-PCR. The CpGs in CTCF1 was significantly unmethylated in the 2-cell stage IVF embryos. However, the 4- (29.1%) and $8{\sim}16$-cell (68.2%) and blastocyst (48.2%) stages showed higher methylation levels (p<0.01). On the other hand, SCNT embryos were unmethylayted ($0{\sim}2%$) at all stages of development. The CpGs in CTCF2 showed almost unmethylation levels at the 2-,4- and $8{\sim}16$-cell and blastocyst stages of development in both IVF ($0{\sim}14.1%$) and SCNT ($0{\sim}6.4%$) embryos. At all stages of development, CTCF3 was unmethylated in IVF ($0{\sim}17.3%$) and SCNT ($0{\sim}1.2%$) embryos except at the blastocyst stage (54.5%) of IVF embryos. In conclusion, porcine SCNT embryos showed an aberrant methylation pattern comprised to IVF embryos. Therefore, we suggest that the aberrant methylation pattern of H19 loci may be a reason for increased abnormal fetus after embryo transfer of porcine SCNT embryos.