Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

<p>Abstract</p> <p>Background</p> <p>Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O₂) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells.</p> <p>Results</p> <p>After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38.</p> <p>Conclusion</p> <p>Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia.</p

Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p \u3c 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level

Bone regeneration potential of sub-microfibrous membranes with osteogenic induction of rBMSC for tissue engineering

Purpose: To examine the biocompatibility and osteoinductive potential of  sub-microfibrous membranes with cells in vitro and in vivo.Methods: Polylactic acid (PLA) and poly-ε-caprolactone (PCL) were blended at various volume ratios (PLA:PCL = 100:0, 70:30, 50:50, 30:70 and 0:100) and each membrane form was prepared by electrospinning. Cell viability,  biocompatibility, and bone regeneration were measured.Results: The membranes from the PLA/PCL blends prepared by an electrospinning process showed a range of diameter distribution ranging from 1,580 to 550 nm. The cells of 100 % PCL membrane (smallest diameter) exhibited significantly higher adhesion and proliferation than those of the other membranes. Among the  membranes from PLA/PCL blends, PCL membrane showed weak inflammatory changes in the early stages of implantation without acute or chronic inflammation. PCL membranes with osteogenically-induced cells successfully stimulated new bone formation in a rate calvarial defect model.Conclusion: The results indicate that biodegradable PCL sub-microfibrous membrane produced by electrospinning process seems to have excellent biocompatibility, and may be used as a scaffold for bone tissue engineering.Keywords: Biocompatibility, Hard tissue, Biomaterial availability, Bone remodeling, Polylactic acid, Poly-ε-caprolactone, Osteoinductive potential, Sub-microfibrous membrane

Myasthenia Gravis Presenting as Isolated Respiratory Failure: A Case Report

Myasthenia gravis (MG) is often complicated by respiratory failure, known as a myasthenic crisis. However, most of the patients who develop respiratory symptoms do so during the late course of disease and have other neurological signs and symptoms. However, in some patients respiratory failure is the initial presenting symptom. We report the case of a 68-year-old woman with MG who presented with isolated respiratory failure as her first presenting symptom. As illustrated by this case, it is important to consider neuromuscular disorders in cases of unexplained respiratory failure

Ultrahigh-efficiency solution-processed simplified small-molecule organic light-emitting diodes using universal host materials

Although solution processing of small-molecule organic light-emitting diodes (OLEDs) has been considered as a promising alternative to standard vacuum deposition requiring high material and processing cost, the devices have suffered from low luminous efficiency and difficulty of multilayer solution processing. Therefore, high efficiency should be achieved in simple-structured small-molecule OLEDs fabricated using a solution process. We report very efficient solution-processed simple-structured small-molecule OLEDs that use novel universal electron-transporting host materials based on tetraphenylsilane with pyridine moieties. These materials have wide band gaps, high triplet energy levels, and good solution processabilities; they provide balanced charge transport in a mixed-host emitting layer. Orange-red (similar to 97.5 cd/A, similar to 35.5% photons per electron), green (similar to 101.5 cd/A, similar to 29.0% photons per electron), and white (similar to 74.2 cd/A, similar to 28.5% photons per electron) phosphorescent OLEDs exhibited the highest recorded electroluminescent efficiencies of solution-processed OLEDs reported to date. We also demonstrate a solution-processed flexible solid-state lighting device as a potential application of our devices.

Attenuated Age-Related Thinning of Peripapillary Retinal Nerve Fiber Layer in Long Eyes

PURPOSE: To assess the impact of axial length on the age-related peripapillary retinal nerve fiber layer (RNFL) thinning. METHODS: This cross-sectional observational comparative case series included 172 eyes from 172 healthy Korean subjects. Peripapillary RNFL thickness was measured using an Optic Disc Cube 200 x 200 scan of spectral domain Cirrus HD OCT and the axial length was measured using IOL Master Advanced Technology. In age groups based on decade, the normal ranges of peripapillary RNFL thickness for average, quadrant, and clock-hour sectors were determined with 95% confidence intervals. After dividing the eyes into two groups according to axial length (cut-off, 24.50 mm), the degrees of age-related RNFL thinning were compared. RESULTS: Among the eyes included in the study, 53 (30.81%) were considered to be long eyes (axial length, 25.04 +/- 0.48 microm) and 119 (69.19%) were short-to-normal length eyes (axial length, 23.57 +/- 0.60 microm). The decrease in average RNFL thickness with age was less in long eyes (negative slope, -0.12 microm/yr) than in short-to-normal length eyes (negative slope, -0.32 microm/yr) (p < 0.001). CONCLUSIONS: Age-related thinning of peripapillary RNFL thickness is attenuated in long eyes compared to short-to-normal length eyes.ope