[Show abstract][Hide abstract] ABSTRACT: Combination therapy involving the synergism between different therapeutic approaches seems a promising strategy in anticancer treatment. Immunostimulatory long interfering RNA (liRNA) structure capable of executing specific RNA interference (RNAi) mediated gene silencing task seems a potential candidate for combination approach. Apart from their therapeutic efficacy, unique structural format of liRNA candidates facilitates better association with cationic polymers and significantly improves their intra-cellular delivery. In this study we developed a biocompatible cationic delivery platform based on low molecular weight branched polyethyleneimine-grafted-polyethylene glycol (bPEI-g-PEG) for advanced liRNA based anticancer therapy. With simple guanidine (GU) modification, the bPEI-g-PEG platform could induce strong RNAi mediated response in cancer cells, without induction of any obvious toxicity. Moreover liRNA complexed with GU-bPEI-g-PEG targeting Survivin sensitized cancer cells for effective chemotherapy. Combination strategy involving immunostimulatory RNAi mediators with conventional chemotherapeutic drugs seems an effective approach in advanced anticancer treatment.
Full-text · Article · Oct 2014 · Journal of Materials Chemistry B
[Show abstract][Hide abstract] ABSTRACT: RNA interference (RNAi) triggering oligonucleotides in unconventional structural format can offer advantages over conventional small interfering RNA (siRNA), enhanced cellular delivery and improved target gene silencing. With this concept, we present a well-defined tripodal-interfering RNA (tiRNA) structure that can induce simultaneous silencing of multiple target genes with improved potency. The tiRNA structure, formed by the complementary association of three single stranded RNA units, was optimized for improved gene silencing efficacy. When combined with cationic polymers such as linear polyethyleneimine (PEI), tiRNA assembled to form stable nano-structured complex through electrostatic interactions and induced stronger RNAi response over conventional siRNA-PEI complex. In combination with a liver targeting delivery system tripodal nucleic acid structure demonstrated enhanced fluorescent accumulation in mouse liver, compared to standard duplex nucleic acid format. Tripodal RNA structure complexed with galactose modified PEI could generate effective RNAi mediated gene silencing effect on experimental mice models. Our studies demonstrate that optimized tiRNA structural format with appropriate polymeric carriers have immense potential to become an RNAi-based platform suitable for multi-target gene silencing.
[Show abstract][Hide abstract] ABSTRACT: RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as liRNA, capable of executing RNAi-mediated specific target gene silencing. In this study, we developed a highly effective liRNA based targeted delivery system to apply in the treatment of glioblastoma multiforme. Stable nano-complex was fabricated by complexing multimerized liRNA structures with cross-linked branched poly(ethylene imine) (bPEI) via electrostatic interactions. We show clear evidence that crosslinked bPEI was quite effective in enhancing the cellular uptake of liRNA on U87MG cells. Moreover, liRNA-PEI nano-complex provided strong RNAi mediated target gene silencing, compared to the conventional siRNA-PEI complex. Further, bPEI modification strategy with specific ligand attachment assisted the uptake of liRNA-PEI complex on the mouse brain endothelial cell line (b.End3). Such delivery systems combining the beneficial elements of targeted delivery, controlled immunostimulation, and RNAi mediated target silencing have immense potential in anti-cancer therapy.
Full-text · Article · Feb 2014 · Molecular Pharmaceutics
[Show abstract][Hide abstract] ABSTRACT: We have fabricated a vertical type organic field effect transistor (OFET) using indenofluorenedione derivatives (IF-dione-F) as an n-type organic active material and dimethyldicyanoquinonediimine (DMDCNQI) as an n-type buffer layer. The configuration of the vertical type OFET was ITO (drain)/ IF-dione-F/Metal (gate)/IF-dione-F/DMDCNQI/Metal (source). The characteristics of the vertical type OFET were investigated from the measurements of current-voltage characteristics, contact resistance and device durability. In particular, the device consisting of ITO/TriF-IF-dione/LiAl/ TriF-IF-dione/DMDCNQI/LiAl showed a low turn-on voltage and a high on/off ratio of 6.0 x 10(3).
No preview · Article · Dec 2013 · Journal of Nanoscience and Nanotechnology
[Show abstract][Hide abstract] ABSTRACT: Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in degradation of the extracellular matrix under physiologic and pathogenic conditions. In a previous study of the roles of MMPs in dental caries, MMP-13 was found to be expressed in both normal and caries pulp, implying its involvement in the pathogenesis of dental caries. Little is known about functions of MMP-13 related to caries progression. Therefore, the objective of this study was to analyze MMP-13 expression in crown and root of normal and caries dentin by western blot analysis. Seven extracted teeth were used. They were categorized into three grades. (Grade 1: Caries limited to enamel, Grade 2: A wide range of caries that invaded dentin, Grade 3: A wide range of caries that invaded pulp). Teeth were divided into crown and root. MMP-13 expression in extracted protein from separated coronal and radicular dentin was analyzed by western blotting. Western blotting revealed that MMP-13 was present in radicular dentin, and was differently expressed as caries progressed. MMP-13 was not expressed in the coronal dentin groups. MMP-13 expression was increased with caries progression in root dentin. This is the first study to determine the presence of MMP-13 in the root of the dentin. We found that it was distinctly increased in the root dentin of widely progressed caries. Future studies with larger sample sizes may be needed to clearly elucidate changes in MMP-13 expression with progression of caries.
Preview · Article · Dec 2013 · Tissue Engineering and Regenerative Medicine
[Show abstract][Hide abstract] ABSTRACT: Malignant mixed müllerian tumor (MMMT) arising from female internal genitalia is rare with the uterine corpus being the most prevalently affected site. It is even more rare when it occurs on both uterus and ovary at the same time. We describe a case of synchronized occurrence of MMMT on ovary and uterine adenosarcoma with review of literature.
[Show abstract][Hide abstract] ABSTRACT: Most traumatic tracheobronchial injuries are fatal and result in death. Some milder cases are not life threatening and are often missed at the initial presentation. Tracheobronchial rupture is difficult to diagnose in the evaluation of severe multiple trauma patients. We reviewed the traumatic tracheobronchial injuries at Konyang University and Eulji University Hospital and analyzed the clinical results.
From January 2001 to December 2011, 23 consecutive cases of traumatic tracheobronchial injury after blunt trauma were reviewed retrospectively. We divided them into two groups by the time to diagnosis: group I was defined as the patients who were diagnosed within 48 hours from trauma and group II was the patients who diagnosed 48 hours after trauma. We compared the clinical parameters of the two groups.
There was no difference in the age and gender between the two groups. The most common cause was traffic accidents (56.5%). The Injury Severity Score (ISS) was 19.6 in group I and 27.5 in group II (p=0.06), respectively. Although the difference in the ISS was not statistically significant, group II tended toward more severe injuries than group I. Computed tomography was performed in 22 cases and tracheobronchial injury was diagnosed in 5 in group I and 6 in group II, respectively (p=0.09). Eighteen patients underwent surgical treatment and all four cases of lung resection were exclusively performed in group II (p=0.03). There were two mortality cases, and the cause of death was shock and sepsis.
We believe that close clinical observation with suspicion and rigorous bronchoscopic evaluation are necessary to perform diagnosis earlier and preserve lung parenchyma in tracheobronchial injuries from blunt trauma.
Preview · Article · Jun 2013 · Korean Journal of Thoracic and Cardiovascular Surgery
[Show abstract][Hide abstract] ABSTRACT: The structural flexibility of RNA interference (RNAi)-triggering nucleic acids suggests that the design of unconventional RNAi trigger structures with novel features is possible. Here, we report a cross-shaped RNA duplex structure, termed quadruple interfering RNA (qiRNA), with multiple target gene silencing activity. qiRNA triggers the simultaneous down-regulation of four cellular target genes via an RNAi mechanism. In addition, qiRNA shows enhanced intracellular delivery and target gene silencing over conventional siRNA when complexed with jetPEI, a linear polyethyleneimine (PEI). We also show that the long antisense strand of qiRNA is incorporated intact into an RNA-induced silencing complex (RISC). This novel RNA scaffold further expands the repertoire of RNAi-triggering molecular structures and could be used in the development of therapeutics for various diseases including viral infections and cancer.
[Show abstract][Hide abstract] ABSTRACT: The aim of this retrospective study is to evaluate the efficacy of adjuvant chemotherapy following radical hysterectomy for intermediate risk stage IB cervical cancer.
From January 1993 to December 2007, a total of 100 patients of stage IB were enrolled in this study who had at least two of the following three intermediate risk factors (deep stromal invasion, lymphovascular space involvement, and large tumor size) after radical hysterectomy and all patients had no high risk factors and no radiotherapy. Of these patients, 22 patients had surgery only and 78 patients had cisplatin-based combination chemotherapy as adjuvant therapy postoperatively to improve survival. Kaplan-Meier survival curves and Cox's proportional-hazards regression model and log-rank test were used for survival analysis and to estimate the impact of prognostic factors on survival.
The mean age was 52 years (range, 28 to 76 years). The overall survival rate of all intermediate tumors are 92% (92/100). Surgery only group is 81.8% (18/22) and adjuvant chemotherapy group is 94.9% (74/78). Comparison of survival between two groups revealed significant statistical difference in both univariant and multivariant survival analysis (P<0.05). The main toxicities of adjuvant chemotherapy were bone marrow suppression (18%), nausea and vomiting (5.2%) and alopecia in etoposide-cisplatin chemotherapy group (100%) but most side effects of postoperative adjuvant chemotherapy were transient, reversible and within acceptable limits to all patients.
Cisplatin based combined adjuvant chemotherapy for intermediate risk tumors after radical hysterectomy is promising with significant improvement of overall survival and with acceptable toxicity profile.
[Show abstract][Hide abstract] ABSTRACT: Thoracic outlet syndrome (TOS) due to thoracic trauma is a rare disorder. Surgical treatment of TOS is especially rare. We report here a case of traumatic TOS caused by right 1st rib and clavicular fracture after a traffic accident. The patient underwent first rib resection and open reduction with fixation of the clavicle through axillary and supraclavicular incisions.
Preview · Article · Dec 2012 · Korean Journal of Thoracic and Cardiovascular Surgery
[Show abstract][Hide abstract] ABSTRACT: High on-off ratio, low turn-on voltage and fast response time are most critical issues in the research and development of organic transistor. In the present work, we have fabricated vertical type organic transistor using 2,8-difluoro-indeno[1,2-b]fluorine-6,12-dione (IF-dione-F) as an organic active semiconductor and DMDCNQI as a n type buffer material. IF-dione-F shows n-type semiconductor property and relatively high electron mobility. The organic light emitting transistor (OLET) configuration is ITO (drain)/PEDOT:PSS/MEH-PPV/IF-dione-F/Metal (gate)/IF-dione-F/DMDCNQI/Metal (source). The characteristics of OLET were investigated from the measurements of current-radiance voltage characteristics, electron mobility and external quantum efficiency
No preview · Article · Nov 2012 · Molecular Crystals and Liquid Crystals
[Show abstract][Hide abstract] ABSTRACT: Soluble oligomers of human islet amyloid polypeptide (h-IAPP) are believed to be the pathogenic species for type 2 diabetes mellitus. In search of the peptide-cleavage agent cleaving oligomers of h-IAPP with low affinity for polymeric aggregates of h-IAPP, a chemical library was constructed by using the Ugi condensation. From the library, a Co(III) complex was discovered to cleave soluble oligomers of h-IAPP in the presence of polymeric aggregates of h-IAPP without being captured by the aggregates considerably. The peptide-cleavage agent inhibited apoptosis of INS-1 cell by h-IAPP even in the presence of preformed polymeric aggregates of h-IAPP. This suggests that target-selective peptide-cleavage agents may be applied clinically not only to diabetes but also to various other amyloid diseases.
[Show abstract][Hide abstract] ABSTRACT: The development of gene interfering RNA (iRNA) molecules such as small interfering RNAs (siRNAs) and antagomirs provides promising therapeutic modalities for targeting specific mRNAs and microRNAs (miRNAs) involved in disease mechanisms. Therapeutic iRNA strategy against cancer or hypermutable viruses prefers targeting multiple genes simultaneously to achieve synergistic inhibition and to prevent resistance.
In the present study, we report chemically synthesized, multi-target gene interfering RNA structures based upon branched, tripodal interfering RNAs (termed T-tiRNAs).
The T-tiRNAs could simultaneously inhibit up to three different mRNAs or miRNAs by harboring three siRNA or antagomir units. Moreover, when complexed with cationic delivery vehicles, T-tiRNAs showed enhanced gene interfering activity over conventional siRNAs or antagomirs as a result of increased intracellular delivery.
The data obtained in the present study provide an example of synthetic multi-functional RNA structures that enable multiple gene interference in mammalian cells, which could become powerful tools for an efficient combinatorial iRNA strategy.
No preview · Article · Feb 2012 · The Journal of Gene Medicine
[Show abstract][Hide abstract] ABSTRACT: Structural modifications could provide classical small interfering RNA (siRNA) structure with several advantages, including reduced off-target effects and increased silencing activity. Thus, RNA interference (RNAi)-triggering molecules with diverse structural modifications have been investigated by introducing variations on duplex length and overhang structure. However, most of siRNA structural variants are based on the linear duplex structure. In this study, we introduce a branched, non-linear tripartite-interfering RNA (tiRNA) structure that could induce silencing of multiple target genes. Surprisingly, the gene silencing by tiRNA structure does not require Dicer-mediated processing into smaller RNA units, and the 38-nt-long guide strands can trigger specific gene silencing through the RNAi machinery in mammalian cells. tiRNA also shows improved gene silencing potency over the classical siRNA structure when complexed with cationic delivery vehicles due to the enhanced intracellular delivery. These results demonstrate that tiRNA is a novel RNA nanostructure for executing multi-target gene silencing with increased potency, which could be utilized as a structural platform to develop efficient anticancer or antiviral RNAi therapeutics.
[Show abstract][Hide abstract] ABSTRACT: In most applications, small interfering RNAs are designed to execute specific gene silencing via RNA interference (RNAi) without triggering nonspecific responses such as immunostimulation. However, in anticancer therapeutics, immunostimulation combined with specific oncogene silencing could be beneficial, resulting in the synergistic inhibition of cancer cell growth. In this study, we report an immunostimulatory long double-stranded RNA (dsRNA) structure with the ability to trigger RNAi-mediated specific target gene silencing, termed as long interfering dsRNA (liRNA). liRNA targeting Survivin mRNA not only efficiently and specifically triggered target gene silencing via RNAi, but also stimulated the protein kinase R pathway to induce the expression of interferon β. As a result, the ability of Survivin-targeting liRNA to inhibit cancer cell growth was superior over conventional small interfering RNA or nontargeting dsRNA structures. Our results thus provide a simple yet efficient dual function immunostimulatory RNAi-triggering structure, which is potentially applicable for the development of anticancer therapeutics.
[Show abstract][Hide abstract] ABSTRACT: We analyzed the results of surgical reduction and fixation of ribs under thoracic epidural anesthesia and analgesia (TEA) in patients who had no more than 3 consecutive rib fractures with severe displacement to examine the clinical usefulness of this method.
From May 2008 to March 2010, 35 patients underwent surgical reduction and fixation of ribs under TEA. We reviewed the indications for this technique, number of fixed ribs, combined surgical procedures for thoracic trauma, intraoperative cardiopulmonary events, postoperative complications, reestablishment of enteral nutrition, and ambulation.
The indications of TEA were malunion or nonunion of fractured ribs in 29 (82.9%; first operation) and incompletely ribs under previous general anesthesia in 6 (17.1%; second operation). The average number of fixed ribs per patient was 1.7 (range: 1~3). As a combined operation for thoracic trauma, 17 patients (48.6%) underwent removal of intrathoracic hematomas, and we performed repair of lung parenchyma (2), wedge resection of lung (1) for accompanying lung injury and pericardiostomy (1) for delayed hemopericardium. No patient had any intraoperative cardiopulmonary event nor did any need to switch to general anesthesia. We experienced 3 postoperative complications (8.6%): 2 extrapleural hematomas that spontaneously resolved without treatment and 1 wound infection treated with secondary closure of the wound. All patients reestablished oral feeding immediately after awakening and resumed walking ambulation the day after operation.
Thoracic epidural anesthesia and analgesia (TEA) may positively affect cardiopulmonary function in the perioperative period. Moreover, this technique leads to an earlier return of gastrointestinal function and early ambulation without severe postoperative complications, resulting in a shortened hospital stay and lowered costs.
Preview · Article · Apr 2011 · Korean Journal of Thoracic and Cardiovascular Surgery
[Show abstract][Hide abstract] ABSTRACT: Photodissociation dynamics of allyl alcohol (H2C=CH-CH2OH) has been investigated at 205 -213 nm along the UV ab-sorption band by measuring rotationally-resolved laser-induced fluorescence spectra of OH radicals. Observed energy par-titioning of the available energy among products at all photon energies investigated was similar and the barrier energy for OH production is about 574.7 kJ/mol from the OH yield measurements. The potential energy surfaces for the S0, T1, and S1 excited states along the dissociation coordinate were obtained by ab initio quantum chemical calculations. The observed energy partitioning was successfully modeled by the "barrier-impulsive model" with the reverse barrier and the geometry obtained by the calculated potential energy surfaces. The dissociation takes place on the T1 excited state potential energy surface with an energy barrier in the exit channel and a large portion of the photon energy is distributed in the internal degrees of freedom of the polyatomic products.
Preview · Article · Feb 2011 · Bulletin- Korean Chemical Society
[Show abstract][Hide abstract] ABSTRACT: Organic field effect transistor (OFET) having advantages such as simple fabrication process, large area coverage, structural flexibility and low cost have been much attention because of the feasibility of application in flexible display, information tag, smart card and e-paper etc. . High on-off ratio, low turn-on voltage and fast response time are most critical issues in the research and development of organic transistor. Recently, the charge injection process through metal / organic interface has been widely studied by a variety of methods. Especially, contact resistance and electrical properties of the conventional lateral type OFET were improved by using various metals and charge transfer materials .
[Show abstract][Hide abstract] ABSTRACT: To design soluble artificial proteases that cleave peptide backbones of a wide range of proteins with high reactivity, artificial active sites comprising the Cu(II) complex of 1-oxa-4,7,10-triazacyclodedecane (oxacyclen) and the aldehyde group were synthesized. The aldehyde group was employed as the binding site in view of its ability to reversibly form imine bonds with ammonium groups exposed on the surfaces of proteins, and Cu(II) oxacyclen was exploited as the catalytic group for peptide hydrolysis. The artificial metalloproteases synthesized in the present study cleaved all of the protein substrates examined (albumin, γ-globulin, myoglobin, and lysozyme). In addition, the activity of the best soluble artificial protease was enhanced by up to 190-fold in terms of k
m. When the temperature was raised to 80 °C, the activities of the artificial proteases were significantly enhanced. The activity of the artificial protease was not greatly affected by surfactants, including sodium dodecyl sulfate. The intermediacy of the imine complex formed between the artificial protease and the protein substrate was supported by an experiment using sodium cyanoborohydride. Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, high thermal and chemical stabilities, and small molecular weights were thus synthesized by positioning the aldehyde group in proximity to Cu(II) oxacyclen.
No preview · Article · Sep 2010 · European Journal of Biochemistry
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.