An examination of the mechanisms driving the therapeutic effects of an AAV expressing a soluble variant of VEGF receptor-1.

In previous animal model studies, we demonstrated the potential of rAAV2-sVEGFRv-1, which encodes a truncated variant of the alternatively spliced soluble version of VEGF receptor-1 (VEGFR1), as a human gene therapy for age-related macular degeneration (AMD) and diabetic retinopathy (DR). Here, we elucidate in vitro some of the mechanisms by which rAAV2-sVEGFRv-1 exerts its therapeutic effects. Human umbilical vein endothelial cells (HUVECs) were infected with rAAV2-sVEGFRv-1 or a control virus vector in the presence of members of the VEGF family to identify potential binding partners via ELISA, which showed that VEGF-A, VEGF-B, and placental growth factor (PlGF) are all ligands of its transgene product.

scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3).

Biokinetics of subacutely co-inhaled same size gold and silver nanoparticles.

Background: Toxicokinetics of nanomaterials, including studies on the absorption, distribution, metabolism, and elimination of nanomaterials, are essential in assessing their potential health effects. The fate of nanomaterials after inhalation exposure to multiple nanomaterials is not clearly understood.

Methods: Male Sprague-Dawley rats were exposed to similar sizes of silver nanoparticles (AgNPs, 10.

The Acute and Short-Term Inhalation of Carbon Nanofiber in Sprague-Dawley Rats.

The inhalation toxicity of carbon nanofibers (CNFs) is not clearly known due to relatively few related studies reported. An acute inhalation study and short-term inhalation study (5 days) were therefore conducted using Sprague-Dawley rats. In the acute inhalation study, the rats were grouped and exposed to a fresh air control or to low (0.

Lung retention and particokinetics of silver and gold nanoparticles in rats following subacute inhalation co-exposure.

Background: Inhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics.

Methods And Results: Rats were exposed to biosoluble silver nanoparticles (AgNPs, 10.

Even lobar deposition of poorly soluble gold nanoparticles (AuNPs) is similar to that of soluble silver nanoparticles (AgNPs).

Background: Information on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health. The revised Organization Economic Cooperation and Development (OECD) inhalation toxicity test guidelines now require lung burden measurements of nanomaterials after rodent subacute and sub-chronic inhalation exposure (OECD 412, OECD 413) to inform on lung clearance behavior and translocation after exposure and during post-exposure observation (PEO). Lung burden measurements are particularly relevant when the testing chemical is a solid poorly soluble nanomaterial.

Mode of silver clearance following 28-day inhalation exposure to silver nanoparticles determined from lung burden assessment including post-exposure observation periods.

Recently revised OECD inhalation toxicity testing guidelines require measurements of lung burden immediately after and for periods following exposure for nanomaterials. Lung burden is a function of pulmonary deposition and retention of nanoparticles. Using lung burden studies as per OECD guidelines, it may be possible to assess clearance mechanisms of nanoparticles.

28-Day inhalation toxicity study with evaluation of lung deposition and retention of tangled multi-walled carbon nanotubes.

Lung deposition and retention measurements are now required by the newly revised OECD inhalation toxicity testing guidelines 412 and 413 when evaluating the clearance and biopersistence of poorly soluble nanomaterials, such as multi-walled carbon nanotubes (MWCNTs). However, evaluating the lung deposition concentration is challenging with certain nanomaterials, such as carbon-based and iron-based nanomaterials, as it is difficult to differentiate them from endogenous elements. Therefore, the current 28-day inhalation toxicity study investigated the lung retention kinetics of tangled MWCNTs.

Derivation of occupational exposure limits for multi-walled carbon nanotubes and graphene using subchronic inhalation toxicity data and a multi-path particle dosimetry model.

In this study, we aimed to provide the recommended occupational exposure limits (OELs) for multi-walled carbon nanotubes (MWCNTs) and graphene nanomaterials based on data from a subchronic inhalation toxicity study using a lung dosimetry model. We used a no observed adverse effect level (NOAEL) of 0.98 mg m and 3.

Lobar evenness of deposition/retention in rat lungs of inhaled silver nanoparticles: an approach for reducing animal use while maximizing endpoints.

Background: Information on particle deposition, retention and clearance are important for the evaluation of the risk of inhaled nanomaterials to human health. Recent revised OECD inhalation toxicity test guidelines require to evaluate the lung burden of nanomaterials after rodent subacute and subchronic inhalation exposure (OECD 412, OECD 413). These revised test guidelines require additional post-exposure observation (PEO) periods that include lung burden measurements that can inform on lung clearance behavior and translocation.

Subacute inhalation toxicity study of synthetic amorphous silica nanoparticles in Sprague-Dawley rats.

Synthetic amorphous silica nanoparticles (SiNPs) are one of the most applied nanomaterials and are widely used in a broad variety of industrial and biomedical fields. However, no recent long-term inhalation studies evaluating the toxicity of SiNPs are available and results of acute studies are limited. Thus, we conducted a subacute inhalation toxicity study of SiNPs in Sprague-Dawley rats using a nose-only inhalation system.

Short-term inhalation study of graphene oxide nanoplates.

Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague-Dawley rats.

Case study on risk evaluation of printed electronics using nanosilver ink.

Background: With the ever-increasing development of nanotechnology, our society is being surrounded by possible risks related to exposure to manufactured nanomaterials. The consumer market already includes many products that contain silver nanoparticles (AgNPs), including various household products, such as yoga mats, cutting boards, running shirts, and socks. There is a growing concern over the release of AgNPs in workplaces related to the manufacture and application of nanomaterials.

Down-regulation of MicroRNA-126 in Glioblastoma and its Correlation with Patient Prognosis: A Pilot Study.

Glioblastoma is the most common primary malignant tumor of the adult human brain. Although microRNA-126 (miR-126) has been reported to exhibit expression abnormalities in various types of cancer, to date very few studies have examined changes in miR-126 level in glioblastoma. In this pilot study, we investigated the changes in miR-126 expression in newly-dissected primary glioblastoma to explore possible roles of miR-126 in patient prognosis.

Exposure monitoring of graphene nanoplatelets manufacturing workplaces.

Graphenes have emerged as a highly promising, two-dimensional engineered nanomaterial that can possibly substitute carbon nanotubes. They are being explored in numerous R&D and industrial applications in laboratories across the globe, leading to possible human and environmental exposures to them. Yet, there are no published data on graphene exposures in occupational settings and no readily available methods for their detection and quantitation exist.

28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period.

Pulmonary Responses of Sprague-Dawley Rats in Single Inhalation Exposure to Graphene Oxide Nanomaterials.

Graphene is receiving increased attention due to its potential widespread applications in future. However, the health effects of graphene have not yet been well studied. Therefore, this study examined the pulmonary effects of graphene oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation technique.

Aquatic Toxicity Comparison of Silver Nanoparticles and Silver Nanowires.

To better understand the potential ecotoxicological impact of silver nanoparticles (AgNPs) and silver nanowires (AgNWs) released into freshwater environments, the toxicities of these nanomaterials were assessed and compared using Organization for Economic Cooperation and Development (OECD) test guidelines, including a "Daphnia sp., acute immobilization test," "Fish, acute toxicity test," and "freshwater alga and cyanobacteria, growth inhibition test." Based on the estimated median lethal/effective concentrations of AgNPs and AgNWs, the susceptibility to the nanomaterials was different among test organisms (daphnia > algae > fish), suggesting that the AgNPs are classified as "category acute 1" for Daphnia magna, "category acute 2" for Oryzias latipes, and "category acute 1" for Raphidocelis subcapitata, while the AgNWs are classified as "category acute 1" for Daphnia magna, "category acute 2" for Oryzias latipes, and "category acute 2" for Raphidocelis subcapitata, according to the GHS (Globally Harmonized System of Classification and Labelling of Chemicals).

5-Day repeated inhalation and 28-day post-exposure study of graphene.

Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats.

Acute toxicity comparison of single-walled carbon nanotubes in various freshwater organisms.

While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R.

Postoperative flat back: contribution of posterior accessed lumbar interbody fusion and spinopelvic parameters.

Objective: Posterior accessed lumbar interbody fusion (PALIF) has a clear objective to restore disc height and spinal alignment but surgeons may occasionally face the converse situation and lose lumbar lordosis. We analyzed retrospective data for factors contributing to a postoperative flat back.

Methods: A total of 105 patients who underwent PALIF for spondylolisthesis and stenosis were enrolled.

The sundt encircling clip as a vascular rescue: a case report and a review of repair methods for arterial tearing.

The Sundt encircling clip was developed to repair defects of the vessel wall. With the advent of microvascular techniques, most parts of the damaged vessel wall during aneurysm surgery can be repaired by primary closure or by the bypass technique. However, these methods are not always successful.

Interplay between polymorphisms in the endothelial nitric oxide synthase (eNOS) gene and metabolic syndrome in determining the risk of ischemic stroke in Koreans.

Background: Endothelial nitric oxide synthase (eNOS) gene variants are known to play a role in atherosclerotic development. However, whether interplay between eNOS polymorphisms and metabolic syndrome (MetS) affects ischemic stroke (IS) risk has yet to be discovered. We investigated whether the combined effects of eNOS polymorphisms and MetS influence ischemic stroke risk in Koreans.

Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure.

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.

The e-health landscape: current status and future prospects in Korea.

The e-health infrastructure in Korea has come a long way within a short period since the establishment of the Korea e-Health Association in 2003 by the Korean Ministry of Commerce, Industry and Energy. Since then, four related government departments in the Ministry of Health and Welfare, Ministry of Information and Communication, Ministry of National Defense, and the Ministry of Science and Technology have also started planning and promoting their own strategies for e-Health applications. We have defined standardization, law and policy planning, human resources development, research and development for e-health products, and international collaboration as the five core pillars for the development of a successful e-health industry.