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1.  Draft Genome Sequence and Annotation of the Insect Pathogenic Bacterium Xenorhabdus nematophila Strain C2-3, Isolated from Nematode Steinernema carpocapsae in the Republic of Korea 
Genome Announcements  2015;3(1):e01521-14.
Xenorhabdus nematophila strain C2-3, which belongs to the family Enterobacteriaceae, was isolated from entomopathogenic nematodes collected in the Republic of Korea. Herein, we report a 4.38-Mbp draft genome sequence of X. nematophila strain C2-3, with a 43.6% G+C content. The RAST annotation analysis revealed 4,994 protein-coding sequences in the draft genome.
doi:10.1128/genomeA.01521-14
PMCID: PMC4333654  PMID: 25676754
2.  Draft Genome Sequence of Chryseobacterium sp. Strain P1-3, a Keratinolytic Bacterium Isolated from Poultry Waste 
Genome Announcements  2014;2(6):e01237-14.
Chryseobacterium sp. strain P1-3, harboring keratin degrading activity, has recently been isolated from poultry waste. Here, we report the 4.6-Mbp draft genome sequence of the keratinolytic bacterium with a G+C content of 37.0% and 4,087 protein-coding genes.
doi:10.1128/genomeA.01237-14
PMCID: PMC4246171  PMID: 25428979
3.  Microbial production of lactate-containing polyesters 
Microbial biotechnology  2013;6(6):621-636.
Due to our increasing concerns on environmental problems and limited fossil resources, biobased production of chemicals and materials through biorefinery has been attracting much attention. Optimization of the metabolic performance of microorganisms, the key biocatalysts for the efficient production of the desired target bioproducts, has been achieved by metabolic engineering. Metabolic engineering allowed more efficient production of polyhydroxyalkanoates, a family of microbial polyesters. More recently, non-natural polyesters containing lactate as a monomer have also been produced by one-step fermentation of engineered bacteria. Systems metabolic engineering integrating traditional metabolic engineering with systems biology, synthetic biology, protein/enzyme engineering through directed evolution and structural design, and evolutionary engineering, enabled microorganisms to efficiently produce natural and non-natural products. Here, we review the strategies for the metabolic engineering of microorganisms for the in vivo biosynthesis of lactate-containing polyesters and for the optimization of whole cell metabolism to efficiently produce lactate-containing polyesters. Also, major problems to be solved to further enhance the production of lactate-containing polyesters are discussed.
doi:10.1111/1751-7915.12066
PMCID: PMC3815930  PMID: 23718266
4.  Draft Genome Sequence of Entomopathogenic Bacterium Photorhabdus temperata Strain M1021, Isolated from Nematodes 
Genome Announcements  2013;1(5):e00747-13.
Photorhabdus temperata strain M1021 is an entomopathogenic bacterium belonging to the family Enterobacteriaceae and is symbiotically associated with nematodes. The draft genome sequence of P. temperata strain M1021 consists of 5,598,253 bp with a G+C content of 43.7%, and it has 6,120 protein-coding genes.
doi:10.1128/genomeA.00747-13
PMCID: PMC3772151  PMID: 24029767
5.  Impact of epiphora on vision-related quality of life 
BMC Ophthalmology  2015;15:6.
Background
The study aimed to evaluate vision-related quality of life (QOL) in epiphora (excessive tear production) patients.
Methods
A total of 342 epiphora patients who visited ophthalmology clinics at 21 general hospitals during a 1-week period were enrolled; 245 females and 97 males with a mean age of 52 ± 13 years. Participants completed a self-administered questionnaire on the extent to which epiphora limited their daily activities. Questions on frequency of discomfort with daily activities were answered on scale of a 0–4. Daily activities that were assessed included reading, daytime and nighttime driving, working at a computer, watching TV, work-related activities, household activities, outdoor activities, interpersonal relations, and general happiness. A correlation analysis was performed between the scores and patient ages. Scores were compared with the clinical factors of gender, bilaterality, and lacrimal irrigation pattern. Presurgical and postsurgical scores in a subset of epiphora patients who underwent surgery were compared.
Results
Outdoor activities were among those that epiphora most significantly hindered. Age had a negative correlation with interpersonal relations scores. Female patients tended to have more discomfort than males in conducting household activities, outdoor activities, and interpersonal relations. Bilaterality showed no differences in QOL. Patients with complete obstruction of lacrimal irrigation recorded higher scores in all daily activities than those with partial or no obstruction. For vision-related QOL, post-surgical scores were improved significantly compared with pre-surgical scores.
Conclusion
Epiphora can affect a broad array of daily activities. Corrective measures for epiphora can improve vision-related QOL, and this may provide guidance for physicians in managing epiphora patients.
doi:10.1186/1471-2415-15-6
PMCID: PMC4320496  PMID: 25613683
Dacryocystorhinostomy; Epiphora; Self-assessment questionnaire; Vision-related quality of life
6.  Effect of zinc oxide nanoparticles on dams and embryo–fetal development in rats 
International Journal of Nanomedicine  2014;9(Suppl 2):145-157.
This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[−] NPs; negatively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(−) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnOSM20(−) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day.
doi:10.2147/IJN.S57931
PMCID: PMC4279755  PMID: 25565833
nanotoxicology; nanoparticles; zinc oxide; maternal toxicity; developmental toxicity; teratogenicity
7.  Prenatal development toxicity study of zinc oxide nanoparticles in rats 
International Journal of Nanomedicine  2014;9(Suppl 2):159-171.
This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group.
doi:10.2147/IJN.S57932
PMCID: PMC4279776  PMID: 25565834
developmental toxicity; maternal toxicity; nanotoxicology; teratogenicity
8.  Metabolic engineering of microorganisms for the production of L-arginine and its derivatives 
Microbial Cell Factories  2014;13(1):166.
L-arginine (ARG) is an important amino acid for both medicinal and industrial applications. For almost six decades, the research has been going on for its improved industrial level production using different microorganisms. While the initial approaches involved random mutagenesis for increased tolerance to ARG and consequently higher ARG titer, it is laborious and often leads to unwanted phenotypes, such as retarded growth. Discovery of L-glutamate (GLU) overproducing strains and using them as base strains for ARG production led to improved ARG production titer. Continued effort to unveil molecular mechanisms led to the accumulation of detailed knowledge on amino acid metabolism, which has contributed to better understanding of ARG biosynthesis and its regulation. Moreover, systems metabolic engineering now enables scientists and engineers to efficiently construct genetically defined microorganisms for ARG overproduction in a more rational and system-wide manner. Despite such effort, ARG biosynthesis is still not fully understood and many of the genes in the pathway are mislabeled. Here, we review the major metabolic pathways and its regulation involved in ARG biosynthesis in different prokaryotes including recent discoveries. Also, various strategies for metabolic engineering of bacteria for the overproduction of ARG are described. Furthermore, metabolic engineering approaches for producing ARG derivatives such as L-ornithine (ORN), putrescine and cyanophycin are described. ORN is used in medical applications, while putrescine can be used as a bio-based precursor for the synthesis of nylon-4,6 and nylon-4,10. Cyanophycin is also an important compound for the production of polyaspartate, another important bio-based polymer. Strategies outlined here will serve as a general guideline for rationally designing of cell-factories for overproduction of ARG and related compounds that are industrially valuable.
doi:10.1186/s12934-014-0166-4
PMCID: PMC4258820  PMID: 25467280
Metabolic engineering; L-Arginine; L-Ornithine; Putrescine; Biopolymers; Polyaspartate
9.  A biochemically active MCM-like helicase in Bacillus cereus 
Nucleic Acids Research  2009;37(13):4441-4452.
The mini-chromosome maintenance (MCM) proteins serve as the replicative helicases in archaea and eukaryotes. Interestingly, an MCM homolog was identified, by BLAST analysis, within a phage integrated in the bacterium Bacillus cereus (Bc). BcMCM is only related to the AAA region of MCM-helicases; the typical amino-terminus is missing and is replaced by a segment with weak homology to primases. We show that BcMCM displays 3′→5′ helicase and ssDNA-stimulated ATPase activity, properties that arise from its conserved AAA domain. Isolated BcMCM is a monomer in solution but likely forms the functional oligomer in vivo. We found that the BcMCM amino-terminus can bind ssDNA and harbors a zinc atom, both hallmarks of the typical MCM amino-terminus. No BcMCM-catalyzed primase activity could be detected. We propose that the divergent amino-terminus of BcMCM is a paralog of the corresponding region of MCM-helicases. A divergent amino terminus makes BcMCM a useful model for typical MCM-helicases since it accomplishes the same function using an apparently unrelated structure.
doi:10.1093/nar/gkp376
PMCID: PMC2715239  PMID: 19474351
10.  Full-Genome Sequence Analysis of a Variant Strain of Porcine Epidemic Diarrhea Virus in South Korea 
Genome Announcements  2014;2(6):e01116-14.
In March of 2014, a variant of novel porcine epidemic diarrhea virus (PEDV) was first identified in South Korea and found to be most closely related to the U.S. variant strain OH851. The complete genome of the KOR/KNU-1406/2014 strain was sequenced and analyzed to investigate the U.S.-strain-like variant circulating in South Korea.
doi:10.1128/genomeA.01116-14
PMCID: PMC4239346  PMID: 25414491
11.  Identification and Characterization of the Insecticidal Toxin “Makes Caterpillars Floppy” in Photorhabdus temperata M1021 Using a Cosmid Library 
Toxins  2014;6(7):2024-2040.
Photorhabdus temperata is an entomopathogenic enterobacterium; it is a nematode symbiont that possesses pathogenicity islands involved in insect virulence. Herein, we constructed a P. temperata M1021 cosmid library in Escherichia coli XL1-Blue MRF` and obtained 7.14 × 105 clones. However, only 1020 physiologically active clones were screened for insect virulence factors by injection of each E. coli cosmid clone into Galleria mellonella and Tenebrio molitor larvae. A single cosmid clone, PtC1015, was consequently selected due to its characteristic virulent properties, e.g., loss of body turgor followed by death of larvae when the clone was injected into the hemocoel. The sequence alignment against the available sequences in Swiss-Prot and NCBI databases, confirmed the presence of the mcf gene homolog in the genome of P. temperata M1021 showing 85% homology and 98% query coverage with the P. luminescens counterpart. Furthermore, a 2932 amino acid long Mcf protein revealed limited similarity with three protein domains. The N-terminus of the Mcf encompassed consensus sequence for a BH3 domain, the central region revealed similarity to toxin B, and the C-terminus of Mcf revealed similarity to the bacterial export domain of ApxIVA, an RTX-like toxin. In short, the Mcf toxin is likely to play a role in the elimination of insect pests, making it a promising model for use in the agricultural field.
doi:10.3390/toxins6072024
PMCID: PMC4113739  PMID: 25014195
insecticidal toxin; Galleria mellonella; makes caterpillar floppy; Photorhabdus temperata; Tenebrio molitor
12.  Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats 
Nutrition Research and Practice  2014;8(3):272-277.
BACKGROUND/OBJECTIVES
This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.
MATERIALS/METHODS
Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection.
RESULTS
Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC).
CONCLUSIONS
Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.
doi:10.4162/nrp.2014.8.3.272
PMCID: PMC4058560  PMID: 24944771
Schisandra chinensis baillon; Tert-butyl hydroperoxide; endogenous antioxidant capacity; hepatotoxicity
13.  Relationship between 15-hydroxyprostaglandin dehydrogenase and gastric adenocarcinoma 
Purpose
Prostaglandin E2 (PGE2) is a contributory carcinogen in gastric adenocarcinoma. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catabolizes PGE2 by oxidizing its 15(s)-hydroxy group. The aim of this study was to investigate the expression of 15-PGDH in gastric adenocarcinoma tissue and the relationship between 15-PGDH expression and clinicopathologic features of gastric adenocarcinoma.
Methods
Ninety-nine patients who underwent surgical resection for gastric adenocarcinoma between January 2007 and December 2007 were enrolled and evaluated retrospectively.
Results
In 62 patients (62.6%), 15-PGDH expression was lower in gastric adenocarcinoma tissue than in nonneoplastic tissue. Regarding the relationship between 15-PGDH expression and clinicopathological features, 15-PGDH expression was significantly lower in tissues with poor differentiation (P = 0.002), advanced T stage (P = 0.0319), a higher number of lymph node metastases (P = 0.045), lymphatic invasion (P = 0.031), and vascular invasion (P = 0.036).
Conclusion
15-PGDH expression was associated with a subset of clinicopathologic features such as differentiation grade, T stage, lymphatic invasion, and vascular invasion.
doi:10.4174/astr.2014.86.6.302
PMCID: PMC4062450  PMID: 24949321
Gastric neoplasms; 15-Hydroxyprostaglandin dehydrogenase; Differentiation; Staging
14.  Culturable Fungal Endophytes Isolated from the Roots of Coastal Plants Inhabiting Korean East Coast 
Mycobiology  2014;42(2):100-108.
Twelve plant species were collected from the east coast of Korea to identify culturable endophytes present in their roots. The fungal internal transcribe spacer (ITS) region (ITS1-5.8SrRNA-ITS2) was used as a DNA barcode for identification of fungi. A total of 194 fungal strains were identified and categorized into 31 genera. The genus Penicillium accounted for the largest number of strains, followed by the genus Aspergillus. Furthermore, using 5 statistical methods, the diversity indices of the fungi were calculated at the genus level. After comprehensive evaluation, the endophytic fungal group from Phragmites australis ranked highest in diversity analyses. Several strains responsible for plant growth and survival (Penicillium citrinum, P. funiculosum, P. janthinellum, P. restrictum, and P. simplicissimum), were also identified. This study provides basic data on the sheds light on the symbiotic relationship between coastal plants and fungi.
doi:10.5941/MYCO.2014.42.2.100
PMCID: PMC4112224  PMID: 25071377
Coastal plants; Fungal diversity; Fungal endophytes; Korean East Coast
15.  Biocompatible Materials for Continuous Glucose Monitoring Devices 
Chemical reviews  2013;113(4):2528-2549.
doi:10.1021/cr300387j
PMCID: PMC3624030  PMID: 23387395
16.  Silicon mitigates heavy metal stress by regulating P-type heavy metal ATPases, Oryza sativa low silicon genes, and endogenous phytohormones 
BMC Plant Biology  2014;14:13.
Background
Silicon (Si) application has been known to enhance the tolerance of plants against abiotic stresses. However, the protective mechanism of Si under heavy metals contamination is poorly understood. The aim of this study was to assess the role of Si in counteracting toxicity due to cadmium (Cd) and copper (Cu) in rice plants (Oryza sativa).
Results
Si significantly improved the growth and biomass of rice plants and reduced the toxic effects of Cd/Cu after different stress periods. Si treatment ameliorated root function and structure compared with non-treated rice plants, which suffered severe root damage. In the presence of Si, the Cd/Cu concentration was significantly lower in rice plants, and there was also a reduction in lipid peroxidation and fatty acid desaturation in plant tissues. The reduced uptake of metals in the roots modulated the signaling of phytohormones involved in responses to stress and host defense, such as abscisic acid, jasmonic acid, and salicylic acid. Furthermore, the low concentration of metals significantly down regulated the mRNA expression of enzymes encoding heavy metal transporters (OsHMA2 and OsHMA3) in Si-metal-treated rice plants. Genes responsible for Si transport (OsLSi1 and OsLSi2), showed a significant up-regulation of mRNA expression with Si treatment in rice plants.
Conclusion
The present study supports the active role of Si in the regulation of stresses from heavy metal exposure through changes in root morphology.
doi:10.1186/1471-2229-14-13
PMCID: PMC3893592  PMID: 24405887
Silicon; Heavy metal stress; Root physiology; Phytohormones; P-type heavy metal ATPase; Oryza sativa; Low silicon
17.  Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4-dependent cytokine production in rat model of endotoxic shock 
Nutrition Research and Practice  2013;7(6):460-465.
The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/10 µg/kg body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.
doi:10.4162/nrp.2013.7.6.460
PMCID: PMC3865268  PMID: 24353831
Acanthopanax koreanum Nakai; acanthoic acid; toll-like receptor 4; inflammation; hepatotoxicity
18.  Association Between a Close Distal Resection Margin and Recurrence After a Sphincter-Saving Resection for T3 Mid- or Low-Rectal Cancer Without Radiotherapy 
Annals of Coloproctology  2013;29(6):231-237.
Purpose
To maintain the patient's quality of life, surgeons strive to preserve the sphincter during rectal cancer surgery. This study evaluated the oncologic safety of a sphincter-saving resection with a distal resection margin (DRM) <1 cm without radiotherapy in T3, mid- or low-rectal cancer.
Methods
This retrospective study enrolled 327 patients who underwent a sphincter-saving resection for proven T3 rectal cancer located <10 cm from the anal verge and without radiotherapy between January 1995 and December 2011. The oncologic outcomes included the 5-year cancer-specific survival, the local recurrence, and the systemic recurrence rates.
Results
In groups A (DRM ≤1 cm) and B (DRM >1 cm), the 5-year cancer-specific survival rates were 81.57% and 80.03% (P = 0.8543), the 5-year local recurrence rates were 6.69% and 9.52% (P = 0.3981), and the 5-year systemic recurrence rates were 19.46% and 23.11% (P = 0.5750), respectively.
Conclusion
This study showed that the close DRM itself should not be a contraindication for a sphincter-saving resection for T3 mid- or low-rectal cancer without radiotherapy. However, a prospective randomized controlled trial including the effect of adjuvant therapy will be needed.
doi:10.3393/ac.2013.29.6.231
PMCID: PMC3895546  PMID: 24466537
Rectal neoplasms; Distal resection margin; Recurrence
19.  Draft Genome Sequence of an Anaerobic and Extremophilic Bacterium, Caldanaerobacter yonseiensis, Isolated from a Geothermal Hot Stream 
Genome Announcements  2013;1(6):e00923-13.
Caldanaerobacter yonseiensis is a strictly anaerobic, thermophilic, spore-forming bacterium, which was isolated from a geothermal hot stream in Indonesia. This bacterium utilizes xylose and produces a variety of proteases. Here, we report the draft genome sequence of C. yonseiensis, which reveals insights into the pentose phosphate pathway and protein degradation metabolism in thermophilic microorganisms.
doi:10.1128/genomeA.00923-13
PMCID: PMC3820782  PMID: 24201201
20.  Hemogenic endocardium contributes to transient definitive hematopoiesis 
Nature communications  2013;4:1564.
Hematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here we examine the hemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the hemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors.
doi:10.1038/ncomms2569
PMCID: PMC3612528  PMID: 23463007
21.  Inorganic/Organic Hybrid Silica Nanoparticles as a Nitric Oxide Delivery Scaffold 
The preparation and characterization of nitric oxide (NO)-releasing silica particles formed following the synthesis of N-diazeniumdiolate-modified aminoalkoxysilanes are reported. Briefly, an aminoalkoxysilane solution was prepared by dissolving an appropriate amount of aminoalkoxysilane in a mixture of ethanol, methanol, and sodium methoxide (NaOMe) base. The silane solution was reacted with NO (5 atm) to form N-diazeniumdiolate NO donor moieties on the amino-alkoxysilanes. Tetraethoxy- or tetramethoxysilane (TEOS or TMOS) was then mixed with different ratios of N-diazeniumdiolate-modified aminoalkoxysilane (10 – 75 mol%, balance TEOS or TMOS). Finally, the silane mixture was added into ethanol in the presence of an ammonia catalyst to form NO donor silica nanoparticles via a sol–gel process. This synthetic approach allows for the preparation of NO delivery silica scaffolds with remarkably improved NO storage and release properties, surpassing all macromolecular NO donor systems reported to date with respect to NO payload (11.26μmol·mg−1), maximum NO release amount (357000 ppb·mg−1), NO release half-life (253 min), and NO release duration (101 h). The N-diazeniumdiolate-modified silane monomers and the resulting silica nanoparticles were characterized by 29Si nuclear magnetic resonance (NMR) spectroscopy, UV-visible spectroscopy, chemiluminescence, atomic force microscopy (AFM), gas adsorption-desorption isotherms, and elemental analysis.
doi:10.1021/cm702526q
PMCID: PMC3699884  PMID: 23833394
22.  Prognostic Significance of the Decreased Rate of Perioperative Serum Carcinoembryonic Antigen Level in the Patients With Colon Cancer After a Curative Resection 
Annals of Coloproctology  2013;29(3):115-122.
Purpose
The serum level of carcinoembryonic antigen (CEA) is a clinical prognostic factor in the follow-up evaluation of patients with colon cancer. We aimed to evaluate the prognostic significance of the rate of decrease of the perioperative serum CEA level in patients with colon cancer after a curative resection.
Methods
A total of 605 patients who underwent a curative resection for colon cancer between January 2000 and December 2007 were enrolled retrospectively. The rate of decrease was calculated using the following equation: ([preoperative CEA - postoperative CEA]/[preoperative CEA] ×100).
Results
In the group with a preoperative serum CEA level of >5 ng/mL, the normalized group with a postoperative serum CEA level of ≤5 ng/mL showed a better overall survival (OS) rate and disease-free survival (DFS) rate than those of the non-normalized group (P ≤ 0.0001). The "cutoff values" of the rate of decrease in the perioperative serum CEA that determined the OS and the DFS were 48.9% and 50.8%, respectively. In the multivariate analysis of preoperative serum CEA levels >5 ng/mL, the prognostic factors for the OS and the DFS were the cutoff value (P < 0.0001) and the pN stage (P < 0.0001).
Conclusion
A rate of decrease of more than 50% in the perioperative serum CEA level, as well as the normalization of the postoperative serum CEA level, may be useful factors for determining a prognosis for colon cancer patients with high preoperative CEA levels.
doi:10.3393/ac.2013.29.3.115
PMCID: PMC3710772  PMID: 23862129
Colon neoplasms; Carcinoembryonic antigen; Prognostic factor
23.  Bactericidal efficacy of nitric oxide-releasing silica nanoparticles 
ACS nano  2008;2(2):235-246.
The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.
doi:10.1021/nn700191f
PMCID: PMC3571086  PMID: 19206623
nitric oxide; silica nanoparticle; antibacterial; bactericidal; cytotoxicity; reactive nitrogen species; reactive oxygen species
24.  Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth 
Molecular pharmaceutics  2010;7(3):775-785.
Although the potent anti-tumor activity of nitric oxide (NO) supports its promise as an anti-neoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their anti-tumor efficacy against human ovarian tumor and nontumor cells. The NO-releasing nanoparticles exhibited enhanced growth inhibition of ovarian tumor cells when compared to both control nanoparticles and a previously reported small molecule NO donor, PYRRO/NO. In addition, the NO-releasing nanoparticles showed greater inhibition of the anchorage-independent growth of tumor-derived and Ras-transformed ovarian cells. Confocal microscopy analysis revealed that fluorescently-labeled NO-releasing nanoparticles entered the cytosol of the cell and localized to late endosomes and lysosomes. Furthermore, we observed a nanoparticle size dependency on efficacy against normal versus transformed ovarian cells. Our study provides the first application of nanoparticle-derived NO as an antitumor therapy and supports the merit for future studies examining nanoparticle formulation for in vivo applications.
doi:10.1021/mp9002865
PMCID: PMC3569608  PMID: 20205473
Nanoparticle; silica; nitric oxide; ovarian cancer; Ras
25.  Tutorial Review: Electrochemical Nitric Oxide Sensors for Physiological Measurements 
Chemical Society reviews  2010;39(6):1925-1935.
Summary
The important biological roles of nitric oxide (NO) have prompted the development of analytical techniques capable of sensitive and selective detection of NO. Electrochemical sensing, more than any other NO-detection method, embodies the parameters necessary for quantifying NO in challenging physiological environments such as blood and the brain. Herein, we provide a broad overview of the field of electrochemical NO sensors, including design, fabrication, and analytical performance characteristics. Both electrochemical sensors and biological applications are detailed.
doi:10.1039/b701906h
PMCID: PMC3569000  PMID: 20502795

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