The aims of this study were to improve in vitro dissolution property of poorly water-soluble everolimus (EVR) for enhanced bioavailability without using organic solvents and characterize the effects ...of microfluidization and freeze-drying on physicochemical properties of EVR nanosuspension and nanoparticle, respectively. EVR nanosuspension was prepared using microfluidization with various types and concentrations of stabilizers. After that, it was solidified into nanoparticle using freeze-drying with various concentrations of xylitol, a cryoprotectant. The particle size, zeta potential, physical stability, and chemical stability of EVR nanosuspension and nanoparticle were measured. In vitro release of EVR nanoparticle was also measured and compared with that of physical mixture. Zero point five percent (w/w) poloxamer 407 (P407) was chosen as the stabilizer considering particle size, zeta potential, and yield of EVR nanosuspension. Freeze-drying with 1% (w/w) xylitol improved both physical and chemical stability of EVR nanoparticle. In vitro release test showed improved dissolution property compared to that of physical mixture, implying enhanced bioavailability.
Tumor-targeting strategies for nanoparticles have been predominantly based on optimization of physical properties or conjugation with biological ligands. However, their tumor-targeting abilities ...remain limited and insufficient. Furthermore, traditional biological binding molecules have intrinsic limitations originating from the limited amount of cellular receptors and the heterogeneity of tumor cells. Our two-step in vivo tumor-targeting strategy for nanoparticles is based on metabolic glycoengineering and click chemistry. First, an intravenous injection of precursor-loaded glycol chitosan nanoparticles generates azide groups on tumor tissue specifically by the enhanced permeation and retention (EPR) effect followed by metabolic glycoengineering. These ‘receptor-like’ chemical groups then enhance the tumor-targeting ability of drug-containing nanoparticles by copper-free click chemistry in vivo during a second intravenous injection. The advantage of this protocol over traditional binding molecules is that there are significantly more binding molecules on the surface of most tumor cells regardless of cell type. The subsequent enhanced tumor-targeting ability can significantly enhance the cancer therapeutic efficacy in animal studies.
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IJS, KILJ, NUK, PNG, UL, UM
Here, we report a simple yet reliable method for bonding poly(methyl methacrylate) (PMMA) to polyethylene terephthalate (PETE) track-etched membranes using (3-glycidyloxypropyl)trimethoxysilane ...(GLYMO), which enables reliable cytotoxicity tests in a microfluidic device impermeable to small molecules, such as anti-cancer drugs. The porous PETE membranes treated with 5% GLYMO were assembled with microfluidic channel-engraved PMMA substrates after air plasma treatment for 1 minute, followed by heating at 100 °C for 2 minutes, which permits irreversible and complete bonding to be achieved within 1 h. The bonding strength between the two substrates (1.97 × 10
7
kg m
−2
) was robust enough to flow culture medium through the device without leakage even at a gauge pressure of above 135 kPa. For validation of its utility in drugs testing, we successfully demonstrated that human lung adenocarcinoma cells cultured in the PMMA devices show more reliable cytotoxicity results for vincristine in comparison to conventional polydimethylsiloxane (PDMS) devices due to the inherent property of PMMA of it being impervious to small molecules. Given that the current organ-on-a-chip fabrication methods mostly rely on PDMS, this bonding strategy will expand simple fabrication capability using various thermoplastics and porous track-etched membranes, and allow us to create 3D-micro-constructs that more precisely mimic organ-level physiological conditions.
A GLYMO-based method enables robust fabrication of PMMA-PETE cell-culturing microfluidic devices, which permits more precise cytotoxicity response to lipophilic drugs.
Stair ascent is one of the most important and challenging activities of daily living to maintain mobility and independence in elderly adults. Recently, various types of wearable walking assist robots ...have been developed to improve gait function and metabolic efficiency for elderly adults. Several studies have shown that walking assist robots can improve cardiopulmonary metabolic efficiency during level walking in elderly. However, there is limited evidence demonstrating the effect of walking assist robots on cardiopulmonary metabolic efficiency during stair walking in elderly adults. Therefore, the aim of this study was to investigate the assistance effect of a newly developed wearable hip assist robot on cardiopulmonary metabolic efficiency during stair ascent in elderly adults.
Fifteen healthy elderly adults participated. The Gait Enhancing Mechatronic System (GEMS), developed by Samsung Electronics Co., Ltd., Korea, was used in the present study. The metabolic energy expenditure was measured using a K4b
while participants performed randomly assigned two conditions consecutively: free ascending stairs without the GEMS or robot-assisted ascending stair with the GEMS.
There were significant differences in the oxygen consumption per unit mass (ml/min/kg), metabolic power per unit mass (W/kg) and metabolic equivalents (METs) values between the GEMS and NoGEMS conditions. A statistically significant difference was found between the two conditions in net oxygen consumption and net metabolic power, with a reduction of 8.59% and 10.16% respectively in GEMS condition (p < 0.05). The gross oxygen consumption while climbing stairs under the GEMS and NoGEMS conditions was equivalent to 6.38 METs and 6.85 METs, respectively.
This study demonstrated that the GEMS was helpful for reducing cardiopulmonary metabolic energy expenditure during stair climbing in elderly adults. The use of the GEMS allows elderly adults to climb stairs with less metabolic energy, therefore, they may experience more endurance in stair climbing while using the GEMS.
NCT03389165 , Registered 26 December 2017 - retrospectively registered.
In this study, experiments, simulations, and optimization were performed to evaluate heat transfer performance of ferrofluids. Ferrofluids are colloidal suspensions containing magnetic-nano particles ...with a diameter of 5 to 15 nm in a base fluid such as oil or water. Recently, as many devices are miniaturized, the design of heat dissipation systems are being diversified to consider cost and safety, and it is becoming important to separate an ancillary device for cooling from main unit. In ferrofluids, the behavior and vortex of magnetic-nano particles are actively generated by an external magnetic field, and the cooling system can be designed in a simplified manner by using this characteristic. The main design parameter is the arrangement of permanent magnets, and the output variable is the temperature inside the magnetic nanofluid. The permanent magnet can be moved up and down, and the temperature inside the magnetic nanofluid was measured at various locations. A predictive model was created using a design of experiments (DOE) and response surface method (RSM) using selected design and temperature variables. Based on the generated regression model, an optimization was applied to find a permanent magnet arrangement that maximizes heat transfer performance. Through the optimization technique used in this study, economic efficiency in terms of time and cost was obtained by reducing the number of experiments.
Licochalcone A (LCA) is a chalcone that is predominantly found in the root of
species, which is widely used as an herbal medicine. Although previous studies have reported that LCA has a wide range of ...pharmacological effects, evidence for the underlying molecular mechanism of its anti-cancer efficacy is still lacking. In this study, we investigated the anti-proliferative effect of LCA on human bladder cancer cells, and found that LCA induced cell cycle arrest at G2/M phase and apoptotic cell death. Our data showed that LCA inhibited the expression of cyclin A, cyclin B1, and Wee1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdc2 and Cdk2. LCA activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, LCA increased the Bax/Bcl-2 ratio, and reduced the integrity of mitochondria, which contributed to the discharge of cytochrome
from the mitochondria to the cytoplasm. Moreover, LCA enhanced the intracellular levels of reactive oxygen species (ROS); however, the interruption of ROS generation using ROS scavenger led to escape from LCA-mediated G2/M arrest and apoptosis. Collectively, the present data indicate that LCA can inhibit the proliferation of human bladder cancer cells by inducing ROS-dependent G2/M phase arrest and apoptosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ...ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy.
The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed.
The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients.
The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.
This study investigated how Fe substitution with Ni, Co, Cu, Mn, and Cr affected the first hydrogenation behavior of air-exposed TiFe-based hydrogen storage alloys. The alloy ingots were crushed into ...powders and exposed to air for 1 h to analyze the first hydrogenation kinetics. Although Fe was substituted with up to 30% of Ni, Co, and Cu, the alloys had a single TiFe phase. In addition, the TiFe0·7Ni0·2Co0.1 and TiFe0·7Co0·2Ni0.1 alloys also had a single TiFe phase in spite of the simultaneous substitution. The composition of the oxide layer changed by the addition of Ni, Co, and Cu, but the alloys did not absorb hydrogen. In the TiFe0·8Mn0.2 and TiFe0·8Cr0.2 alloys, a dual-phase microstructure consisting of TiFe and Mn/Cr-rich C14 Laves phase was formed, with a larger amount in TiFe0·8Cr0.2. Both samples absorbed hydrogen after air exposure without any thermal activation process. Comparing the first hydrogenation kinetics, TiFe0·8Cr0.2 had a shorter incubation time and faster hydrogen absorption rate than TiFe0·8Mn0.2.
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•The alloys where Fe was substituted by Ni, Co, and Cu had a single TiFe phase.•Above substitutions changed the oxide film composition but alloys did not hydrogenate.•The TiFe0·8Mn0.2 and TiFe0·8Cr0.2 alloys were composed of TiFe and C14 Laves phases.•TiFe0·8Mn0.2 and TiFe0·8Cr0.2 absorbed hydrogen even after air exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rotator cuff tear (RCT) is a challenging and common musculoskeletal disease. Magnetic resonance imaging (MRI) is a commonly used diagnostic modality for RCT, but the interpretation of the results is ...tedious and has some reliability issues. In this study, we aimed to evaluate the accuracy and efficacy of the 3-dimensional (3D) MRI segmentation for RCT using a deep learning algorithm.
A 3D U-Net convolutional neural network (CNN) was developed to detect, segment, and visualize RCT lesions in 3D, using MRI data from 303 patients with RCTs. The RCT lesions were labeled by two shoulder specialists in the entire MR image using in-house developed software. The MRI-based 3D U-Net CNN was trained after the augmentation of a training dataset and tested using randomly selected test data (training: validation: test data ratio was 6:2:2). The segmented RCT lesion was visualized in a three-dimensional reconstructed image, and the performance of the 3D U-Net CNN was evaluated using the Dice coefficient, sensitivity, specificity, precision, F1-score, and Youden index.
A deep learning algorithm using a 3D U-Net CNN successfully detected, segmented, and visualized the area of RCT in 3D. The model's performance reached a 94.3% of Dice coefficient score, 97.1% of sensitivity, 95.0% of specificity, 84.9% of precision, 90.5% of F1-score, and Youden index of 91.8%.
The proposed model for 3D segmentation of RCT lesions using MRI data showed overall high accuracy and successful 3D visualization. Further studies are necessary to determine the feasibility of its clinical application and whether its use could improve care and outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Amorphous form and its characterization using a wide variety of analytical techniques have been known for decades. However, there is no single superior method because of similarities between ...crystalline mesophases and amorphous forms. The aim of the present study was to characterize and identify solid-state of CKD-519, a new cholesteryl ester transfer protein inhibitor, using a combination of analytical techniques. CKD-519 was analyzed via scanning electron microscope, thermogravimetric/differential thermal analysis (TG/DTA), differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSPLM), and variable temperature x-ray powder diffraction (VT-XRPD). Endothermic shifts in the baseline before and after the peak with no mass change were observed via TG/DTA and conventional DSC. Enthalpy recovery experiments and modulated-temperature DSC (MDSC) measurement revealed enthalpy recovery superimposed on glass transition. The absence of birefringence in HSPLM micrographs as well as the glass transition and presence of diffuse scattering (halo) in the VT-XRPD pattern of micron-sized particles up to 200 µm indicate that CKD-519 exists in an amorphous form. This combination of analytical techniques may be used to distinguish amorphous forms from crystalline mesophases.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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