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JNK2 silencing and caspase-9 activation by hyperosmotic polymer inhibits tumor progression
Garg, Pankaj,Pandey, Shambhavi,Hoon, Seonwoo,Jang, Kyoung-Je,Lee, Myung Chul,Choung, Yun-Hoon,Choung, Pill-Hoon,Chung, Jong Hoon Elsevier 2018 International journal of biological macromolecules Vol.120 No.2
<P><B>Abstract</B></P> <P>c-Jun N-terminal kinase 2 (JNK2) is primarily responsible for the oncogenic transformation of the transcription factor c-Jun. Expression of the proto-oncogene c-Jun progresses the cell cycle from G1 to S phase, but when its expression becomes awry it leads to uncontrolled proliferation and angiogenesis. Delivering a JNK2 siRNA (siJNK2) in tumor tissue was anticipated to reverse the condition with subsequent onset of apoptosis which predominantly requires an efficient delivering system capable of penetrating through the compact tumor mass. In the present study, it was demonstrated that polymannitol-based vector (PMGT) with inherent hyperosmotic properties was able to penetrate through and deliver the siJNK2 in the subcutaneous tumor of xenograft mice. Hyperosmotic activity of polymannitol was shown to account for the enhanced therapeutic delivery both in vitro and in vivo because of the induction of cyclooxygenase-2 (COX-2) which stimulates caveolin-1 for caveolae-mediated endocytosis of the polyplexes. Further suppression of JNK2 and hence c-Jun expression led to the activation of caspase-9 to induce apoptosis and inhibition of tumor growth in xenograft mice model. The study exemplifies PMGT as an efficient vector for delivering therapeutic molecules in compact tumor tissue and suppression of JNK2 introduces a strategy to inhibit tumor progression.</P> <P><B>Graphical abstract</B></P> <P>Hyperosmotic PMGT driven siJNK2 delivery in compact cancer cells inhibits c-jun phosphorylation resulting in tumor growth arrest via caspase-9 induction and apoptosis.</P> <P>[DISPLAY OMISSION]</P>
Feature Article : Mechanical Stimulation of Mesenchymal Stem Cells for Tissue Engineering
( Jang Ho Kim ),( Chong Su Cho ),( Yun Hoon Choung ),( Ki Taek Lim ),( Hyun Mok Son ),( Hoon Seon Woo ),( Soo Jung Baik ),( Soung Hoo Jeon ),( Joo Young Park ),( Pill Hoon Choung ),( Jong Hoon Chung ) 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.1
Tissue engineering is a rapidly growing field that utilizes cell/scaffolds constructs with chemical signaling molecules as potential therapeutic products for tissue regeneration. Mesenchymal stem cells(MSCs) provide excellent novel strategies for tissue engineering application. Recently, it has been recognized that understanding mechanical stimulation is an important key to the development of efficient and controllable methods as well as chemical signaling for differentiation of MSCs and tissue engineering application. Especially, a number of studies indicated that the mechanical stimuli can enhance the synergy effects for differentiation of MSCs and tissue formation or regeneration. In this review, we introduced the various mechanical stimuli techniques, the effects of mechanical stimuli to MSCs, and tissue engineering applications. Furthermore, we discussed the further research directions of MSCs and mechanical stimuli based on this review for tissue engineering.
( Ki Taek Lim ),( Seon Woo Hoon ),( Hyun Mok Son ),( Soo Jung Baik ),( Jang Ho Kim ),( Soung Hoo Jeon ),( Joo Young Park ),( Yun Hoon Choung ),( Chong Su Cho ),( Pill Hoon Choung ),( Jong Hoon Chung ) 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.14
In the design of perfusion bioreactor system for tissue engineering, design parameters including fluid dynamics and mass transport as well as scaffolds should be optimized to maximize cell growth. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. In particular, perfusion flow systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. In this paper, we reviewed the biomechanical models in relation with fluid dynamics, mass transport, and shear stress with scaffolds. Therefore, obtaining a proper oxygen supply, high cell density, and an uniform cell distribution in a three-dimensional growth support are important. Both experiments and quantitative mathematical models of cell culture in perfusion bioreactors are needed to better understand physical, mechanical, and biochemical conditions and for the design of a suitable bioreactor system the mathematical describes the oxygen mass transfer and cell density within a three-dimensional scaffold. This review focuses on biomechanical models in relation with fluid dynamics, mass transport, and shear stress to cells cultured, and cell growth in perfusion bioreactors for tissue engineering.
Hyperosmotic polydixylitol for crossing the blood brain barrier and efficient nucleic acid delivery
Garg, P.,Pandey, S.,Seonwoo, Hoon,Yeom, Seungmin,Choung, Yun-Hoon,Cho, Chong-Su,Choung, Pill-Hoon,Hoon Chung, Jong The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.17
<P>Here, we introduce a polydixylitol based highly osmotic polymer that not only transmigrates the BBB by intra-arterial infusion of osmotic polyol but also triggers cellular uptake <I>via</I> modulation of caveolae mediated endocytosis.</P> <P>Graphic Abstract</P><P>We report that the incorporation of a hyperosmotic molecule, dixylitol, into the backbone of a delivery vector can enhance its blood brain barrier transmigration. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc09871d'> </P>
Feature Article : Novel Perfusion Bioreactor Systems for Tissue Engineering
( Ki Taek Lim ),( Chong Su Cho ),( Yun Hoon Choung ),( Jang Ho Kim ),( Hyun Mok Son ),( Hoon Seon Woo ),( Soo Jung Baik ),( Soung Hoo Jeon ),( Joo Young Park ),( Pill Hoon Choung ),( Jong Hoon Chung ) 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.1
Bioreactor systems that use a new aeration concept have recently been introduced. Bioreactors can assist in the development of new tissues in vitro by providing appropriate stimuli to the cell cultures. The design of bioreactors for tissue engineering is very complex and is often tailored to individual cell- engineered-tissue products. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. Flow perfusion systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. The beneficial effects of fluid flow induced convective transport and shear stress have been exploited in various types of bioreactors because fluid flow-through cell and tissue engineered constructs increase nutrient transport. These systems are called flow-perfusion bioreactors. In this paper, we review the characteristics of bioreactor systems used for cell culture in tissue engineering, and provide a schematic design for a novel bioreactor system that incorporates the elements we deem critical for such systems.
( Kyoung Je Jang ),( Woo Jae Cho ),( Hoon Seonwoo ),( Jangho Kim ),( Ki Taek Lim ),( Pill Hoon Chung ),( Jong Hoon Chung ) 한국농업기계학회 2014 바이오시스템공학 Vol.39 No.2
Purpose: This study was to develop an effective process for fabricating biocompatible calcium phosphate powders (CPPs) using horse bones, and to investigate the characteristics of them. Methods: The characteristics of horse bone powders (HBPs) were investigated according to the different osseous tissue types (compact bone and cancellous bone), bone types (spine and tibia), pretreatment methods (cold water, H2O2, and hot water), sintering time (4, 8 and 12h), and sintering temperature (600, 900, 1100 and1300°C). In addition, the grinding methods were compared based on the wet grinding (ball mill) and dry grinding (blade grinder) method to make it as powders. Finally, their cytotoxicity and cell viability were checked. Results: Regardless of the types of osseous tissues and bones, HBPs were well fabricated as biocompatible CPPs. It was also found that the pretreatment methods did not influence on the resultants, showing well-fabricated HBPs. Considering the processing time, the hot water method was the most suitable compared to other pretreatment methods. Further, 12h-sintering time was sufficient to remove residual organic compounds. The sintering temperatures greatly affected the properties of bone powders fabricated. The x-ray diffraction (XRD) peak of horse bone sintered at 600°C was most closed to that of hydroxyapatite (HA). Our bioactivity study demonstrated that the HBPs fabricated by sintering horse bones at 1300°C showed the best performance in terms of cell viability whereas the HBPs 1100°C showed the cytotoxicity. Conclusions: Using various types of horse bone tissues, biocompatible CPPs were successfully developed. We conclude that the HBPs may have a great potential as biomaterials for various biological applications including bone tissue engineering.
Development and Characterization of Horse Bone-derived Natural Calcium Phosphate Powders
Jang, Kyoung-Je,Cho, Woo Jae,Seonwoo, Hoon,Kim, Jangho,Lim, Ki Taek,Chung, Pill-Hoon,Chung, Jong Hoon Korean Society for Agricultural Machinery 2014 바이오시스템공학 Vol.39 No.2
Purpose: This study was to develop an effective process for fabricating biocompatible calcium phosphate powders (CPPs) using horse bones, and to investigate the characteristics of them. Methods: The characteristics of horse bone powders (HBPs) were investigated according to the different osseous tissue types (compact bone and cancellous bone), bone types (spine and tibia), pretreatment methods (cold water, $H_2O_2$, and hot water), sintering time (4, 8 and 12h), and sintering temperature (600, 900, 1100 and $1300^{\circ}C$). In addition, the grinding methods were compared based on the wet grinding (ball mill) and dry grinding (blade grinder) method to make it as powders. Finally, their cytotoxicity and cell viability were checked. Results: Regardless of the types of osseous tissues and bones, HBPs were well fabricated as biocompatible CPPs. It was also found that the pretreatment methods did not influence on the resultants, showing well-fabricated HBPs. Considering the processing time, the hot water method was the most suitable compared to other pretreatment methods. Further, 12h-sintering time was sufficient to remove residual organic compounds. The sintering temperatures greatly affected the properties of bone powders fabricated. The x-ray diffraction (XRD) peak of horse bone sintered at $600^{\circ}C$ was most closed to that of hydroxyapatite (HA). Our bioactivity study demonstrated that the HBPs fabricated by sintering horse bones at $1300^{\circ}C$ showed the best performance in terms of cell viability whereas the HBPs $1100^{\circ}C$ showed the cytotoxicity. Conclusions: Using various types of horse bone tissues, biocompatible CPPs were successfully developed. We conclude that the HBPs may have a great potential as biomaterials for various biological applications including bone tissue engineering.