Although radiotherapy plays a crucial in the management of pelvic tumors, its toxicity on surrounding healthy tissues such as the small intestine, colon, and rectum is one of the major limitations ...associated with its use. In particular, proctitis is a major clinical complication of pelvic radiotherapy. Recent evidence suggests that endothelial injury significantly affects the initiation of radiation-induced inflammation. The damaged endothelial cells accelerate immune cell recruitment by activating the expression of endothelial adhesive molecules, which participate in the development of tissue damage. Pravastatin, a cholesterol lowering drug, exerts persistent anti-inflammatory and anti-thrombotic effects on irradiated endothelial cells and inhibits the interaction of leukocytes and damaged endothelial cells. Here, we aimed to investigate the effects of pravastatin on radiation-induced endothelial damage in human umbilical vein endothelial cell and a murine proctitis model. Pravastatin attenuated epithelial damage and inflammatory response in irradiated colorectal lesions. In particular, pravastatin improved radiation-induced endothelial damage by regulating thrombomodulin (TM) expression. In addition, exogenous TM inhibited leukocyte adhesion to the irradiated endothelial cells. Thus, pravastatin can inhibit endothelial damage by inducing TM, thereby alleviating radiation proctitis. Therefore, we suggest that pharmacological modulation of endothelial TM may limit intestinal inflammation after irradiation.
The upsurge in prevalence of obesity has spawned an epidemic of nonalcoholic fatty liver disease (NAFLD). Previously, we identified a sequence variant (I148M) in patatin-like phospholipase ...domain-containing protein 3 (PNPLA3) that confers susceptibility to both hepatic triglyceride (TG) deposition and liver injury. To glean insights into the biological role of PNPLA3, we examined the molecular mechanisms by which nutrient status controls hepatic expression of PNPLA3. PNPLA3 mRNA levels, which were low in fasting animals, increased ∼90-fold with carbohydrate feeding. The increase was mimicked by treatment with a liver X receptor (LXR) agonist and required the transcription factor SREBP-1c. The site of SREBP-1c binding was mapped to intron 1 of Pnpla3 using chromatin immunoprecipitation and electrophoretic mobility shift assays. SREBP-1c also promotes fatty acid synthesis by activating several genes encoding enzymes in the biosynthetic pathway. Addition of fatty acids (C16:0, C18:1, and C18:2) to the medium of cultured hepatocytes (HuH-7) increased PNPLA3 protein mass without altering mRNA levels. The posttranslational increase in PNPLA3 levels persisted after blocking TG synthesis with triascin C. Oleate (400 μM) treatment prolonged the half-life of PNPLA3 from 2.4 to 6.7 h. These findings are consistent with nutritional control of PNPLA3 being effected by a feed-forward loop; SREBP-1c promotes accumulation of PNPLA3 directly by activating Pnpla3 transcription and indirectly by inhibiting PNPLA3 degradation through the stimulation of fatty acid synthesis.
Summary
Nanocellulose materials are promising sustainable and environmentally friendly candidates for green and renewable energy storage applications. Herein, hierarchical Co3O4@CNC nanohybrid ...structure was fabricated in conjunction with cobalt acetate tetrahydrate and cellulose nanocrystals (CNC) as a bio‐carbon source using green ball‐milling pathway for the first time. For comparison, pristine Co3O4 nanostructure was prepared using a similar method without adding CNC. The structural and morphological characteristics of nanohybrid composites were investigated using X‐ray diffractometer (XRD), Raman, X‐ray photoelectron spectroscopy (XPS), Fourier‐transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer‐Emmett‐Teller (BET) techniques. Furthermore, the electrochemical properties of the nanohybrid composites evaluated using cyclic voltammetry (CV), Galvanostatic Charge‐Discharge (GCD), and electrochemical impedance spectroscopy (EIS) techniques. The hierarchical Co3O4@CNC nanohybrid electrode showed the highest specific capacitance of 396 F/g that of pristine Co3O4 nanostructure electrode (was 268 F/g) at a current density of 1.0 A/g for a three‐electrode assembly. The hierarchical Co3O4@CNC nanohybrid electrode showed appreciable capacitive behavior with 96% cyclic retention even after 5,000 cycles at 1.0 A/g with energy density of 12.5 Wh k−1 at a power density of 230.5 W k−1. Thus, it is suitable for improving and/or designing active electrocatalysts for enhanced supercapacitor applications.
Nanocellulose based composite materials has attracted much attention in the fabrication of supercapacitor electrodes. Green ball‐milling technique was set forth for the fabrication of hierarchical Co3O4 nano‐hybrid structures in connotation with cellulose nanocrystals (CNCs). The nano‐hybrid hierarchical electrode (Co3O4@CNC) showed excellent specific capacitance of 396 F/g than its pristine Co3O4 nanostructure electrode (268 F/g) at a current density of 1.0 A/g for three‐electrode cell assembly.
Abstract The cellular fate of nanoparticles in the liver is not fully understood. Because the effectiveness and safety of nanoparticles in liver therapy depends on targeting nanoparticles to the ...right cell populations, this study aimed to determine a relative distribution of PLGA-nanoparticles (sizes 271±1.4 nm) among liver cells in vivo . We found that Kupffer cells were the major cells that took up nanoparticles, followed by liver sinusoidal endothelial cells and hepatic stellate cells. Nanoparticles were found in only 7% of hepatocytes. Depletion of Kupffer cells by clodronate liposomes increased nanoparticle retention in liver sinusoidal endothelial cells and hepatic stellate cells, but not in hepatocytes. It is importantly suggested that studies of drug-loaded nanoparticle delivery to the liver have to demonstrate not only uptake of nanoparticles by the target cell type but also non-uptake by other cell types to assess their effect as well as ensure their safety.
This study aimed to validate body composition analysis using bioelectrical impedance analysis (BIA) against dual‐energy X‐ray absorptiometry (DXA) in children with obesity and to compare agreement ...between BIA and DXA according to their degree of obesity. Three hundred and sixteen children aged 6‐17 years participated in the Intervention for Childhood and Adolescents Obesity via Activity and Nutrition study. We divided participants by body mass index (BMI) percentile (group 1: mild to moderate obesity; group 2: severe obesity) and compared body composition variables, eg, percentage of body fat (%BF), fat mass (FM), and fat‐free mass (FFM) using BIA and DXA. The %BF and FM of BIA were significantly lower (−1.8% and −0.8 kg, respectively), and the FFM of BIA was significantly higher (1.4 kg) than those of DXA. There were significant negative relationships between the absolute value of differences from BIA and DXA and BMI z‐scores in %BF, FM, and FFM (regression coefficient β: −1.39, 95% confidence interval CI: −1.81 to −0.97; β: −0.34, 95%CI: −0.61 to −0.06; β: −0.73, 95%CI: −1.03 to −0.44, respectively). The gap of body compositions between BIA and DXA decreased as participants became more obese, and the differences of FM in boys with severe obesity and the differences of %BF and FFM in girls with severe obesity were much less than those in children with mild to moderate obesity. In conclusion, the agreement between DXA and BIA was better for children with severe obesity than for children with mild to moderate obesity.
Isolating total DNA from small samples using traditional methods is difficult and inefficient mainly due to loss of DNA during filtration and precipitation. With advances in molecular pathology, DNA ...extraction from micro-dissected cells has become essential in handling clinical samples. Genomic DNA extraction using small numbers of cells can be very important to successfully PCR amplify DNA from small biopsy specimens. We compared our experimental genomic DNA extraction method (A) with two other commercially available methods: using spin columns (B), and conventional resins (C), and determined the efficacy of DNA extraction from small numbers of cells smeared on a glass slide. Approximately 50, 100, 200, 500 and 1000 cells were isolated from fine needle aspiration biopsy (FNAB) slides aspirated from histologically proven papillary thyroid carcinoma masses. DNA was extracted using the three techniques. After measuring DNA quantity, PCR amplification was performed to detect the b-globin and BRAF V600E gene mutations. DNA extracted by method (A) showed better yield than the other methods in all cell groups. With our method, a suitable amount of genomic DNA to produce amplification was extracted from as few as 50 cells, while more than 100 to 200 cells were required when methods (B) or (C) were applied. Our genomic DNA extraction method provides high quality and improved yields for molecular analysis. It will be especially useful for paucicellular clinical samples which molecular pathologists often confront when handling fine needle aspiration cytology, exfoliative cytology and small biopsy specimens.
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► SBA-15 grafted with aminopropyl, hydroxymethyl, and trimethylsilyl groups as sorbents. ► Sorbents for removal of a mixture of 12 pharmaceuticals from water. ► Hydroxymethyl-SBA-15 ...shows similar adsorption efficiency like SBA-15. ► Aminopropyl-SBA-15 makes increase for clofibric acid, diclofenac, decrease for atenolol, estrone, trimethoprim. ► Trimethylsilyl-SBA-15 makes increase for 9 compounds; 7 compounds from 70.6% to 98.9%.
Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N
2 adsorption–desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5–7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals from aqueous phase, especially for the treatment of wastewater from drug manufacturers.
Abstract Background Half of all stroke patients experience depression, which adversely affects functional recovery. To improve functional outcomes, post-stroke depressive symptoms require more ...effective management strategies. Objective This study examined whether repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) can manage post-stroke depression and improve motor function. Methods This study was a single-center, prospective, double blind, sham-controlled preliminary study. Twenty-four patients with chronic stroke were randomly assigned to two groups: (1) the rTMS group, in which patients received ten sessions of high-frequency (10 Hz) stimulation; and (2) the sham group, in which patients received ten sessions of sham stimulation. Functional recovery was assessed at two time points before the intervention (four weeks and one day) and two time points after the intervention (one day and four weeks), using the Beck Depression Inventory (BDI), 17-item version of the Hamilton Depression Rating Scale (HAM-D17), upper (MI-UE) and lower limb Motricity Indices (MI-LE), modified Brunnstrom Classification (MBC), and Functional Ambulatory Category (FAC) assessments. Results At both post-intervention time points, BDI and HAM-D17 in the rTMS group were significantly decreased compared to those in the sham group (Mann–Whitney U test, p < 0.05) and compared to pre-intervention time points (Wilcoxon’s test, p < 0.017). However, no significant changes in MI-UE, MI-LE, MBC, and FAC were found. Conclusions Our results suggest that rTMS is a beneficial therapeutic modality for managing depression after stroke.
The authors compared performance management in different local governments in South Korea looking for the best systems. Two separate, consecutive processes (adoption and implementation) were ...examined. This article will help policy-makers and managers develop efficient and effective performance management policies, not only in local government but also in central government. This study was conducted with all basic local governments in South Korea, making the results highly reliable.
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