Callesenhwang5158

Among these 23 genes, six genes with "sequence-specific DNA binding" annotation were significantly enriched, including three Homeobox genes-HMX2, TLX2, and HOXA9-that may be involved in the tumourigenesis of canine malignant melanoma. This study revealed widespread alterations in DNA methylation and a large number of hypermethylated genes in canine malignant melanoma.Autosomal recessive Stargardt disease is the most common cause of inherited retinal disease. In this report, we describe the generation and characterization of two human induced pluripotent stem cell (iPSC) lines from a patient with compound heterozygous mutations in the ABCA4 gene (c.[768G>T];[6079C>T]). Patient dermal fibroblasts were reprogrammed using episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, LIN28, mir302/367 microRNA and shRNA for P53. The clonal iPSC lines LEIi012-A and LEIi012-B were established. Both lines had a normal karyotype, displayed iPSC morphology, expressed pluripotency genes at similar levels to control iPSC and displayed trilineage differentiation potential during embryoid body differentiation.

Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in case of recurrent, or high-grade tumours. To date, chemotherapy has proven ineffective in meningioma patients, reinforcing the need for novel therapeutic targets and molecular biomarkers.

Using meningioma tissues and in vitro models, we investigated microRNA levels in meningioma samples of different grades, as well as their regulation. Based on this, we also investigated candidate miRNAs expression in serum, and their potential as biomarkers.

We found that miR-497~195 cluster expression in meningioma decreases with increasing malignancy grade, and that Cyclin D1 overexpression correlated with downregulation of the miR-497~195 cluster. GPCR antagonist GATA binding protein 4, a transcription factor upregulated in malignant meningioma, caused increased cell viability by controlling the expression of the miR-497~195 cluster, resulting in increased Cyclin D1 expression. Accordingly, GATA-4 inhibition via the small-molecule inhibitor NSC140905 restored miR-497~195 cluster expression, resulting in decreased viability, and Cyclin D1 downregulation. Analysis of the miR-497~195 cluster expression in serum exosomes derived from high-grade meningioma patients, revealed lower levels of miR-497 compared to those of benign origin.

Our data suggest that GATA-4 could be a novel potential therapeutic target, and miR-497 could serve as a potential non-invasive biomarker for high-grade meningioma.

Our data suggest that GATA-4 could be a novel potential therapeutic target, and miR-497 could serve as a potential non-invasive biomarker for high-grade meningioma.

Progressive neuronal death in monoaminergic nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson's disease (PD). Given that α-synuclein may be an early mediator of the pathological cascade that ultimately leads to neurodegeneration, decreased α-synuclein synthesis will abate neurotoxicity if delivered to the key affected neurons.

We used a non-viral gene therapy based on a new indatraline-conjugated antisense oligonucleotide (IND-ASO) to disrupt the α-synuclein mRNA transcription selectively in monoamine neurons of a PD-like mouse model and elderly nonhuman primates. Molecular, cell biology, histological, neurochemical and behavioral assays were performed.

Intracerebroventricular and intranasal IND-ASO administration for four weeks in a mouse model with AAV-mediated wild-type human α-synuclein overexpression in dopamine neurons prevented the synthesis and accumulation of α-synuclein in the connected brain regions, improving dopamine neurotransmission. Likewise, entres for Networked Biomedical Research on Mental Health (CIBERSAM), and on Neurodegenerative Diseases (CIBERNED).When proteins interact with solvent or co-solutes with a high specificity and affinity, protein-ligand complexes may be formed. Such phenomenon may involve the processes like intra- and intermolecular interactions, which result in interaction based protein folding. In this study, cytochrome c (cyt c) was treated with different concentrations of ethylene glycol (EG) in crowded and confined media to check its structural stability using various spectroscopic techniques at pH 7.0 and 25 °C. The various spectroscopic techniques including circular dichroism (Soret, far- and near-UV regions), Fourier transform infrared (FTIR), absorption (UV and visible) and Trp fluorescence shows both secondary and tertiary structure of cyt c increases when treated with EG. The investigations using dynamic light scattering (DLS), time resolved fluorescence and isothermal titration calorimetry (ITC) for binding studies shows weak interaction between EG and cyt c. Small increase in the structure of the protein and insignificant decrease in hydrodynamic radii of the protein was observed from the studies. Molecular docking studies showed that EG has binding site on the protein and interact with few amino acid residues by weak interactions such as van der Waals and hydrogen bonding. This study helps in understanding the protein-ligand interactions, provides facts and the mechanisms that mediates the recognition of binding site for specific ligand to the receptor protein, which make possible of the discovery, design, and development of drugs at molecular level without affecting proteins within an organism.Dermoscopic images are widely used for melanoma detection. Many existing works based on traditional classification methods and deep learning models have been proposed for automatic skin lesion analysis. The traditional classification methods use hand-crafted features as input. However, due to the strong visual similarity between different classes of skin lesions and complex skin conditions, the hand-crafted features are not discriminative enough and fail in many cases. Recently, deep convolutional neural networks (CNN) have gained popularity since they can automatically learn optimal features during the training phase. Different from existing works, a novel mid-level feature learning method for skin lesion classification task is proposed in this paper. In this method, skin lesion segmentation is first performed to detect the regions of interest (ROI) of skin lesion images. Next, pretrained neural networks including ResNet and DenseNet are used as the feature extractors for the ROI images. Instead of using the extracted features directly as input of classifiers, the proposed method obtains the mid-level feature representations by utilizing the relationships among different image samples based on distance metric learning. The learned feature representation is a soft discriminative descriptor, having more tolerance to the hard samples and hence is more robust to the large intra-class difference and inter-class similarity. Experimental results demonstrate advantages of the proposed mid-level features, and the proposed method obtains state-of-the-art performance compared with the existing CNN based methods.Long-term air pollution exposure has been suggested to increase the risk of attention-deficit/hyperactivity disorder (ADHD). However, the association between short-term air pollution exposure and ADHD-related outcomes is still unknown. We investigated the associations between short-term exposure to particulate matter with an aerodynamic diameter ≤10 μm (PM10), nitrogen oxide (NO2), and sulfur dioxide (SO2) and hospital admissions with a principal diagnosis of ADHD among adolescents (age 10-19 years) in 16 regions of the Republic of Korea from 2013 to 2015. We estimated the region-specific relative risks (RRs) and 95% confidence intervals (CIs) from quasi-Poisson regressions adjusted for potential confounders, considering single-day and moving average lag. Consequently, we performed meta-analyses to pool the region-specific estimates. The risks of ADHD-related hospital admissions were increased in the single-day and moving average lag models for PM10 (largest association for lag 1 in the single-day lag model, RR = 1.12, 95% CI 1.05, 1.20; lag 0-2 in the moving average lag model, RR = 1.17, 95% CI 1.07, 1.27), NO2 (lag 3, RR = 1.47, 95% CI 1.25, 1.73; lag 1-3, RR = 1.68, 95% CI 1.38, 2.04), and SO2 (lag 1, RR = 1.27, 95% CI 1.14, 1.41; lag 1-3, RR = 1.29, 95% CI 1.12, 1.49). The associations were similar between boys and girls, but they were stronger among adolescents aged 15-19 years than those aged 10-14 years for NO2 and SO2. In conclusion, the results indicate that short-term exposure to PM10, NO2, and SO2 may be a risk factor for the exacerbation of ADHD symptoms, leading to hospitalization.This study aimed to evaluate the mutagenicity and oral acute toxicity of winter mushroom powder (PW) treated by atmospheric non-thermal plasma (ANP). Winter mushroom powder without plasma treatment (CW) containing an equivalent amount of sodium nitrite as PW was used as a control. The Ames test revealed that the number of revertant colonies did not significantly increase compared to that in the control. Acute toxicity was assessed in rats that were fed a single dose of winter mushroom powder (5000 mg/kg body weight). Results of the acute toxicity test revealed no remarkable clinical symptoms in any of the rats. No significant difference was observed in of the serum biochemical parameters between the treatments. Regardless of the ANP treatment, mild histological changes were observed in few rats in all groups. Therefore, it is concluded that ANP treatment did not cause any mutagenicity or acute toxicity in the winter mushroom.Four soluble dietary fibers (SDFs) were fortified with corn starch (CS) at different concentrations to match the same viscosity equivalents. The mixtures were subjected to a simulated digestion procedure to study the effects of SDFs on viscosity properties and digestion kinetics of CS. Results showed that SDFs increased the hydration property and decreased the water mobility of digesta. During digestion process, SDFs increased the apparent viscosity of digesta to some extent, and showed significant difference to delay the decay of digesta viscosity (kv). The amylolysis inhibitory ability was similar when each SDF was present at the same viscosity equivalent, however, significant differences were found on the digestion rate constant of k2. Linear correlations between kv and k2 were established for 1 and 2 equivalent groups. These results demonstrated that SDFs could delay the digestion process as chemistry differences, which related to their ability on delaying the change of digesta viscosity.In this study, a potential of covalent linkage approach for developing active edible coatings was examined. Vanillin and trans-cinnamaldehyde were bound to chitosan by Schiff base reaction and reductive amination. The modified polysaccharides were comprehensively characterized and applied as active coatings on fresh-cut melon. The covalent linkage allowed overcoming solubility problems with the lipophilic vanillin and cinnamaldehyde and neutralizing their volatility, producing well-adhered coatings that enhanced fruit quality and storability without sensorial impairment. The attached hydrophobic moieties also provided new polysaccharides with self-assembling ability. Their aggregates were loaded with antimicrobial citral and added to mandarin juice, resulting in up to 6 log CFU/mL microbial count reduction. Thus, the covalent linkage concept offers several advantages, especially when hydrophobic or volatile active agents are used. Further developed, it may become a safe and effective tool for the formation of advanced active edible coatings and delivery vehicles for direct applications on food products.