Suppression of tobacco carcinogen-induced lung tumorigenesis by aerosol-delivered glycerol propoxylate triacrylate-spermine copolymer/short hairpin Rab25 rna complexes in female A/J mice

Background: Rab25, a member of Rab family of small guanosine triphosphatase, is associated with progression of various types of human cancers, including lung cancer, the leading cause of cancer-associated deaths around the globe. Methods: In this study, we report the gene therapeutic effect of short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected with single dose of NNK (2mg/0.1mL saline/mouse) by intraperitoneal injection to induce the tumor. Eight weeks later, shRab25 was complexed with glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced lung cancer models through a nose-only inhalation system twice a week for 2 months. Results: GPT-SPE/shRab25 largely decreased the tobacco-induced tumor numbers and tumor volume in the lungs compared to GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab25 significantly decreased the expression level of Rab25 and other prominent apoptosis-related proteins in female A/J mice. The apoptosis in these mice was determined by detecting the expression level of Bcl-2, proliferating cell nuclear antigen, Bax, and further confirmed by TUNEL assay. Conclusions: Our results strongly confirm the tumorigenic role of Rab25 in tobacco carcinogen-induced lung cancer and hence demonstrate aerosol delivery of shRab25 as a therapeutic target for lung cancer treatment.

Suppression of lung cancer progression by biocompatible glycerol triacrylate–spermine-mediated delivery of shAkt1

Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate-spermine (GT-SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy. Methods: The GT-SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance. Results: The GT-SPE successfully protected the DNA from nucleases. The average particle size of the GT-SPE was 121 nm with a zeta potential of +23.45 mV. The GT-SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT-SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-ras(LA1) lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT-SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively. Conclusion: Our data suggest that GT-SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy

Characteristics, Outcomes and Predictors of Long-Term Mortality for Patients Hospitalized for Acute Heart Failure: A Report From the Korean Heart Failure Registry

BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6±14.3 years and 50% of the patients were female. RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5±15.7% and 26.1% of the patients had preserved systolic function (LVEF ≥50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death. CONCLUSION: We present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.ope

First Report for the Seasonal and Annual Prevalence of Flea-Borne Bartonella from Rodents and Soricomorphs in the Republic of Korea

Rodents and soricomorphs are animal hosts of fleas and associated zoonotic microbial pathogens. A total of 4,889 small mammals were collected from Gyeonggi and Gangwon Provinces, Republic of Korea, from 2008 through 2010, including: Apodemus agrarius (4,122, 84.3%), followed by Crocidura lasiura (282, 5.8%), Microtus fortis (257, 5.3%), Myodes regulus (77, 1.6%), Micromys minutus (71, 1.5%), Mus musculus (63, 1.3%), and 4 other species (17, 0.3%). A total of 1,099 fleas belonging to 10 species and 7 genera were collected. Ctenophthalmus congeneroides (724, 65.9%) was the most commonly collected flea, followed by Stenoponia sidimi (301, 27.4%), Neopsylla bidentatiformis (29, 2.6%), and Rhadinopsylla insolita (25, 2.3%). The remaining species accounted for only 1.8% (20, range 1-6) of all fleas collected. The 2 dominant flea species, C. congeneroides and S. sidimi, showed an inverse seasonal pattern, with higher populations of C. congeneroides from January-September, whereas S. sidimi was more frequently collected during October-December. The overall flea infestation rates (FIR) and flea indices (FI) were 14.1% and 0.22, respectively, and were highest during April-June (19.7% and 0.30, respectively). A total of 735 of the 1,099 fleas were assayed for the detection of Bartonella spp. by PCR using Bartonella-specific primers, of which 515 were positive for Bartonella, with an overall maximum likelihood estimate (MLE) of 700.7/1,000. The highest MLE values were observed during April-June (899.2) and July-September (936.2) trapping periods and, although lower, were similar for January-March (566.7) and October-December (574.1). C. congeneroides demonstrated high MLEs for all seasons (range 752.5-934.8), while S. sidimi was positive for Bartonella only during January-March (MLE = 342.1) and October-December (MLE = 497.2) collection periods. Continued long-term surveillance of small mammals and associated ectoparasites is needed to improve our understanding of the prevalence of Bartonella spp. in fleas and the role of fleas in the zoonotic maintenance and transmission of Bartonella to humans.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/5SEQ:5PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:YEMP_ID:A077262DEPT_CD:551CITE_RATE:2.277FILENAME:2013 vbz 13(7)457-467 flea-borne bartonella.pdfDEPT_NM:수의학과SCOPUS_YN:YCONFIRM:

Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical and histopathological findings

The aim of the present study was to assess the clinical and histopathological findings in a canine model of ischemic stroke. Cerebral ischemic stroke was induced by middle cerebral artery occlusion in four healthy beagle dogs using silicone plugs. They showed neurological signs of forebrain dysfunction such as reduced responsiveness, head turning, circling, postural reaction deficits, perceptual deficits, and hemianopsia. These signs gradually regressed within 4 weeks without therapy. On magnetic resonance imaging, T2 hyperintensity and T1 hypointensity were found in the cerebral cortex and basal ganglia. These lesions were well-defined and sharply demarcated from adjacent brain parenchyma with a homogenous appearance. No abnormalities of the cerebrospinal fluid were observed. At necropsy, atrophic and necrotic lesions were observed in the cerebral cortex. The cerebral cortex, basal ganglia, and thalamus were partially unstained with triphenyl-tetrazolium chloride. Histopathologically, typical features of infarction were identified in cortical and thalamic lesions. This study demonstrates that our canine model resembles the conditions of real stroke patients

Sensitization to Aeroallergens in Korean Children: A Population-based Study in 2010

We performed this study to assess the prevalence of sensitization to aeroallergens and to analyze the difference between prevalence rates according to children's ages and residential areas. In this nationwide cross-sectional study, first grade students of 45 elementary schools and 40 middle schools were randomly selected, and skin prick tests were performed for 18 inhalant allergens between October and November 2010. Of 7,829 analyzed subjects, 3,753 (47.9%) were sensitized to at least one aeroallergen. Sensitization to Dermatophagoides farinae was found to be the most prevalent in elementary schoolchildren (32.4%), followed by Dermatophagoides pteronyssinus, Tyrophagus putrescentiae, Japanese hop, and oak. In middle schoolchildren, D. pteronyssinus yielded the highest prevalence (42.7%), followed by D. farinae, T. putrescentiae, Japanese hop, and cat. In middle schoolchildren, the sensitization rate to aeroallergens in metropolitan, urban, and rural areas was 57.2%, 54.3%, and 49.8%, respectively (P = 0.019). In this age group, the sensitization rate in low, middle, high, and very high income groups was 53.8%, 51.8%, 59.0%, and 59.6%, respectively (P = 0.002). In conclusion, the sensitization rate is 47.9% and house dust mite is the most prevalent allergen in the pediatric population in Korea. The rate is higher in metropolitan areas and the highest income group than in rural areas and low income groups

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Steroidogenic effects of Taraxacum officinale extract on the levels of steroidogenic enzymes in mouse Leydig cells

In this study, we investigated the steroidogenic effect of Taraxacum officinale extract on mouse TM3 Leydig cells, which produce male hormones by increasing the levels of steroidogenic enzymes. Steroidogenic enzymes are involved in the production of testosterone in the testis. To date, the steroidogenic effect of T. officinale has not been reported. Therefore, we examined the steroidogenic effects of T. officinale extract (TOE) on mouse Leydig cells in vitro. Traditionally, plants have been used for the treatment of various kinds of ailments. For many years, some medicinal plants have been used to regulate steroidogenesis or late-onset hypogonadism (LOH). In particular, plants belonging to the genus Taraxacum have anti-inflammatory, anti-nociceptive, anti-oxidant, and anti-cancer properties. In this study, we determined whether the TOE exerts steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, such as the steroidogenic acute regulatory protein (STAR), CYP11A1, and translocator protein (TSPO) in the mitochondria and CYP17A1 in the smooth endoplasmic reticulum, in mouse Leydig cells. Our results showed that the TOE significantly increased the mRNA and protein levels of steroidogenic enzymes, thereby increasing the testosterone levels in mouse Leydig cells. Thus, our results indicate that the TOE increases the levels of steroidogenic enzymes, and further studies are required to establish the potential of this plant in regulating steroidogenesis and improving LOH