106 research outputs found

    Vascular endothelial growth factor B (VEGF-B) is up-regulated and exogenous VEGF-B is neuroprotective in a culture model of Parkinson's disease

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    Parkinson's disease (PD) results from the degeneration of dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine released in the striatum. Current oral dopamine replacement or surgical therapies do not address the underlying issue of neurodegeneration, they neither slow nor halt disease. Neurotrophic factors have shown preclinical promise, but the choice of an appropriate growth factor as well as the delivery has proven difficult. In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1) We challenged rat midbrain cultures with rotenone (20 nM), a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B) was evident, while vascular endothelial growth factor A (VEGF-A) levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using Ī²-actin as the internal standard. (2) We have also found evidence that exogenously applied VEGF-B performed as a neuroprotective agent facilitating neuron survival in an even more severe rotenone culture model of PD (40 nM rotenone). VEGF-B has very recently been added to the list of trophic factors that reduce effects of neurodegeneration, as was shown in an in vivo model of motor neuron degeneration, while lacking potential adverse angiogenic activity. The data of an in vivo protective effect on motor neurons taken together with the presented results demonstrate that VEGF-B is a new candidate trophic factor distinct from the GDNF family of trophic factors. VEGF-B is activated by neurodegenerative challenges to the midbrain, and exogenous application of VEGF-B has a neuroprotective effect in a culture model of PD. Strengthening this natural protective response by either adding exogenous VEGF-B or up-regulating the endogenous VEGF-B levels may have the potential to be a disease modifying therapy for PD. We conclude that the growth factor VEGF-B can improve neuronal survival in a culture model of PD

    Statistical model for intergranular corrosion growth kinetics

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    A statistical model has been developed to predict the anisotropy of intergranular corrosion (IGC) kinetics and effect of microstructure on IGC kinetics in high strength AA2024-T3 alloys. The methodology is to estimate the statistical distribution of minimum IGC path length that will be found through the thickness of a given thickness ST sample using the principle of order statistics. A brick-wall model is adopted for wrought Al alloy microstructure and different distributions of grain dimension are assumed for the purpose of the estimation of total IGC path length. Numerical stimulation using a gamma distribution model stimulated the anisotropy of localized corrosion in AA2024-T3 alloys, which quite agrees with the growth rate anisotropy experimentally determined by the foil penetration technique. Some limitations regarding the statistical model are discussed. The statistical model provides a new approach to predicting and quantifying localized corrosion kinetics on basis of the alloy microstructure.This work was supported by the United States Air Force Office of Scientific Research through Grant no. F49620-99-1-0103

    The Influence of Social Isolation and Medical Comorbidities on Geriatric Congestive Heart Failure Hospital Readmissions

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    CONTEXT Social isolation and comorbidities are likely to have a significant level of influence on the healthcare use patterns of geriatric patients with ongoing congestive heart failure (CHF)-related needs. METHODS A retrospective study was conducted in a specialized emergency department (ED) with a sample of 286 geriatric CHF patients who initially received CHF-related care over a six-month period. Social isolation levels were assessed using a pre-existing four-point screening tool used in the study setting and composite comorbidity was gauged using the Charlson Comorbidity Index method. Subjects were categorized into either ā€œless than 30-day readmissionā€ or ā€œgreater than 30-day readmission/non-readmittedā€ sample subgroups. The setting was a single 304-bed community hospital with approximately 45,000 annual ED visits. The analytic sample was comprised of geriatric patients 65+ years of age with an ICD-9 code corresponding to CHF. RESULTS There were no statistically significant differences between earlier hospital readmission versus later/non-readmitted sample patients when grouped by age, race, gender or level of measured social isolation. However, composite comorbidity scores were significantly lower for patients in the \u3e30-day/non-readmitted subgroup compared to earlier readmission patients. CONCLUSIONS These initial study results suggest that a larger proportion of CHF hospital readmissions may be more heavily influenced by clinical factors than social living arrangements. Future studies with larger samples and validated measures of social isolation are needed to inform the development and testing of programs for geriatric CHF patients striving to avoid unnecessary hospital readmissions and adverse health outcomes

    PEDF and VEGF-A Output from Human Retinal Pigment Epithelial Cells Grown on Novel Microcarriers

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    Human retinal pigment epithelial (hRPE) cells have been tested as a cell-based therapy for Parkinson's disease but will require additional study before further clinical trials can be planned. We now show that the long-term survival and neurotrophic potential of hRPE cells can be enhanced by the use of FDA-approved plastic-based microcarriers compared to a gelatin-based microcarrier as used in failed clinical trials. The hRPE cells grown on these plastic-based microcarriers display several important characteristics of hRPE found in vivo: (1) characteristic morphological features, (2) accumulation of melanin pigment, and (3) high levels of production of the neurotrophic factors pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A). Growth of hRPE cells on plastic-based microcarriers led to sustained levels (>1ā€‰ng/ml) of PEDF and VEGF-A in conditioned media for two months. We also show that the expression of VEGF-A and PEDF is reciprocally regulated by activation of the GPR143 pathway. GPR143 is activated by L-DOPA (1ā€‰Ī¼M) which decreased VEGF-A secretion as opposed to the previously reported increase in PEDF secretion. The hRPE microcarriers are therefore novel candidate delivery systems for achieving long-term delivery of the neuroprotective factors PEDF and VEGF-A, which could have a value in neurodegenerative conditions such as Parkinson's disease

    3-Cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one ameliorates diabetic peripheral neuropathy in type 2 diabetes mellitus rats via PI3K/Akt signaling pathway

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    Purpose: To investigate the curative effects of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHMP) on streptozotocin (STZ)-induced model of diabetic SD rats, and the underlying mechanism. Method: Diabetes was induced in rats using single intraperitoneal injection of STZ. Subsequently, diabetic and non-diabetic rats were randomly grouped into five experimental groups. Six weeks after the STZ-injection, the diabetic animals were orally administered test compound (CHMP) at two doses of 10 and 20 mg/kg body weight for 6 weeks. Thereafter, the rats were anesthetised, and body weight, blood sugar, and motor nerve conduction velocity (MNCV) were determined. Moreover, real time-polymerase chain reaction (RT-PCR) and western blot analysis were used to assay the expression levels of genes in PIK3/Akt pathway and Glut4. Results: Treatment of diabetic rats with CHMP significantly reduced levels of fasting blood glucose and enhanced average rat body weight, relative to diabetic control (p Ė‚ 0.05). Motor nerve conduction velocity (MNCV) was remarkably increased in CHMP-treated rats (54.2 Ā± 2.2), when compared to the diabetic control rats (46 Ā± 4.1, p < 0.01). Results from RT-PCR and western blot indicated increased expressions of PI3K, Akt and IRS-1, and down regulation of GSK-3B expression in skeletal muscle. The CHMP treatment also upregulated the Glut4 expression in skeletal muscle. Conclusion: These findings show that CHMP may be beneficial in the management of diabetic neuropath

    Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy

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    Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats

    NTIRE 2023 Quality Assessment of Video Enhancement Challenge

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    This paper reports on the NTIRE 2023 Quality Assessment of Video Enhancement Challenge, which will be held in conjunction with the New Trends in Image Restoration and Enhancement Workshop (NTIRE) at CVPR 2023. This challenge is to address a major challenge in the field of video processing, namely, video quality assessment (VQA) for enhanced videos. The challenge uses the VQA Dataset for Perceptual Video Enhancement (VDPVE), which has a total of 1211 enhanced videos, including 600 videos with color, brightness, and contrast enhancements, 310 videos with deblurring, and 301 deshaked videos. The challenge has a total of 167 registered participants. 61 participating teams submitted their prediction results during the development phase, with a total of 3168 submissions. A total of 176 submissions were submitted by 37 participating teams during the final testing phase. Finally, 19 participating teams submitted their models and fact sheets, and detailed the methods they used. Some methods have achieved better results than baseline methods, and the winning methods have demonstrated superior prediction performance

    Configuration and Stability of HF/SF6 and HF/N2 Standard Gases

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    In this paper, the analysis methods of HF components in two background series of nitrogen and sulfur hexafluoride were established and optimized. The uncertainty contribution in the weighing process was evaluated. The configuration of HF/SF6 and HF/N2 standard gases was established, that is, the packaging volume was 4L and 8L, and the content range of HF component was (50-100)Ɨ10-6 mol/mol. Then, the stability of the value of the standard gas is investigated, that is, the stability of the value with time and pressure, the fixed value and performance investigation. The relative expanded uncertainty of two series HF standard gas prediction is less than 6% (k=2)
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