Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
Tissue engineering requires not only tissue‐specific functionality but also a realistic scale. Decellularized extracellular matrix (dECM) is presently applied to the extrusion‐based 3D printing ...technology. It has demonstrated excellent efficiency as bioscaffolds that allow engineering of living constructs with elaborate microarchitectures as well as the tissue‐specific biochemical milieu of target tissues and organs. However, dECM bioinks have poor printability and physical properties, resulting in limited shape fidelity and scalability. In this study, new light‐activated dECM bioinks with ruthenium/sodium persulfate (dERS) are introduced. The materials can be polymerized via a dityrosine‐based cross‐linking system with rapid reaction kinetics and improved mechanical properties. Complicated constructs with high aspect ratios can be fabricated similar to the geometry of the desired constructs with increased shape fidelity and excellent printing versatility using dERS. Furthermore, living tissue constructs can be safely fabricated with excellent tissue regenerative capacity identical to that of pure dECM. dERS may serve as a platform for a wider biofabrication window through building complex and centimeter‐scale living constructs as well as supporting tissue‐specific performances to encapsulated cells. This capability of dERS opens new avenues for upscaling the production of hydrogel‐based constructs without additional materials and processes, applicable in tissue engineering and regenerative medicine.
New light‐activated decellularized extracellular bioinks with ruthenium/sodium persulfate (dERS) are cured through a rapid dityrosine‐based cross‐linking reaction. dERS enables the bioprinting of complex structures with increased shape fidelity and highly improved printing versatility. The cell‐laden constructs also exhibit excellent tissue regenerative capacity. These capabilities of dERS open new avenues for the production of clinically relevant soft tissues applicable in tissue engineering field.
This paper proposed a triangular inequality-based rewiring method for the rapidly exploring random tree (RRT)-Connect robot path-planning algorithm that guarantees the planning time compared to the ...RRT algorithm, to bring it closer to the optimum. To check the proposed algorithm's performance, this paper compared the RRT and RRT-Connect algorithms in various environments through simulation. From these experimental results, the proposed algorithm shows both quicker planning time and shorter path length than the RRT algorithm and shorter path length than the RRT-Connect algorithm with a similar number of samples and planning time.
Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of ...exercise on these markers as potential mediators between physical activity and breast cancer.
PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.
A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels WMD, -3.46 μU/mL; 95% confidence interval (CI), -5.97 to -0.95;
= 0.007. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, -0.73; 95% CI, -0.54 to 0.13;
= 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, -0.87 to 3.20;
= 0.26), and C-reactive protein (WMD, -1.10 mg/L; 95% CI, -2.39 to 0.20;
= 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, -7.10 μU/mL; 95% CI, -10.31 to -3.90;
< 0.001).
Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.
Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer.
.
Patient-specific ex vivo models of human tumours that recapitulate the pathological characteristics and complex ecology of native tumours could help determine the most appropriate cancer treatment ...for individual patients. Here, we show that bioprinted reconstituted glioblastoma tumours consisting of patient-derived tumour cells, vascular endothelial cells and decellularized extracellular matrix from brain tissue in a compartmentalized cancer-stroma concentric-ring structure that sustains a radial oxygen gradient, recapitulate the structural, biochemical and biophysical properties of the native tumours. We also show that the glioblastoma-on-a-chip reproduces clinically observed patient-specific resistances to treatment with concurrent chemoradiation and temozolomide, and that the model can be used to determine drug combinations associated with superior tumour killing. The patient-specific tumour-on-a-chip model might be useful for the identification of effective treatments for glioblastoma patients resistant to the standard first-line treatment.
This study proposes an interior permanent magnet (IPM) brushless dc (BLDC) motor design strategy that utilizes BLDC control based on Hall sensor signals. The magnetic flux of IPM motors varies ...according to the rotor position and abnormal Hall sensor problems are related to magnetic flux. To find the cause of the abnormality in the Hall sensors, an analysis of the magnetic flux density at the Hall sensor position by finite element analysis is conducted. In addition, an IPM model with a notch structure is proposed to solve abnormal Hall sensor problems and its magnetic equivalent circuit (MEC) model is derived. Based on the MEC model, an optimal rotor design method is proposed and the final model is derived. However, the Hall sensor signal achieved from the optimal rotor is not perfect. To improve the accuracy of the BLDC motor control, a rotor position estimation method is proposed. Finally, experiments are performed to evaluate the performance of the proposed IPM-type BLDC motor and the Hall sensor compensation method.
This paper discusses a motor that was designed to satisfy the size constraints of system by using ferrite magnet and has the same performance as rare-earth magnet motor. In general, the size of the ...motor is increased in order to meet the same performance of motor using a ferrite magnet, because of its very low energy density compared to the rare-earth magnet. In order to compensate for these drawbacks, spoke structures capable of generating maximum magnetic flux at the same rotor size have been frequently studied. However, the spoke type motor structure has a drawback that demagnetization occurs in a magnet-specific portion. However, because it affects harmonics of the airgap flux density by demagnetization, it affects mechanical torque ripple and vibration. Therefore, in this paper, the changed air-gap flux density due to the demagnetization phenomenon and the changed mechanical vibration are analyzed by the finite-element method. In addition, we proposed an optimal rotor structure that can reduce the demagnetization phenomenon of magnets in spoke interior permanent magnet synchronous motor. Experiments were performed to evaluate the reliability of the optimized design.
Tissue‐specific decellularized extracellular matrix recapitulates the complexity of natural ECMs, creating an organ‐specific microenvironment based on its intrinsic characteristics. Here, hydrogels ...containing uterus‐derived decellularized extracellular matrix (UdECMs) from the endometrium‐specific layer or the entire uterus are developed. UdECMs serve as effective organ‐specific biomaterials, displaying that intrauterine UdECM administration induces endometrial regeneration and fertility enhancement. Moreover, UdECM administration alters the profile of natural killer cell subpopulations to exhibit more mature and less cytotoxic features, providing a favorable uterine environment for successful implantation and decidualization. Interestingly, insulin‐like growth factor 1 and insulin‐like growth factor‐binding protein 3 as key regulatory factors that contribute to UdECM‐mediated endometrial regeneration are discovered. Furthermore, ex vivo culture of human uterine tissues reveals that UdECMs of different origins exhibit distinct therapeutic effects based on the endometrial conditions of patients, suggesting their uses as a therapeutic intervention providing personalized regenerative medicine for infertile patients with a poor uterine environment.
Intrauterine administration of uterus‐derived decellularized extracellular matrix (UdECMs) induces regeneration of the endometrium and fertility enhancement. UdECM treatments Endo‐ or Whole‐UdECM‐induced regenerative effects are mediated by a shared regulatory mechanism of downregulated‐insulin‐like growth factor 1 (IGF1) and/or upregulated‐insulin‐like growth factor binding protein 3 (IGFBP3). Furthermore, an ex vivo culture of human uterine tissues in each UdECM reveals that UdECMs with different origins show distinct therapeutic effects depending on the endometrial conditions of patients.
Several studies have focused on the regeneration of liver tissue in a two-dimensional (2D) planar environment, whereas actual liver tissue is three-dimensional (3D). Cell printing technology has been ...successfully utilized for building 3D structures; however, the poor mechanical properties of cell-laden hydrogels are a major concern. Here, we demonstrate the printing of a 3D cell-laden construct and its application to liver tissue engineering using 3D cell printing technology through a multi-head tissue/organ building system. Polycaprolactone (PCL) was used as a framework material because of its excellent mechanical properties. Collagen bioink containing three different types of cells-hepatocytes (HCs), human umbilical vein endothelial cells , and human lung fibroblasts--was infused into the canals of a PCL framework to induce the formation of capillary--like networks and liver cell growth. A co-cultured 3D microenvironment of the three types of cells was successfully established and maintained. The vascular formation and functional abilities of HCs (i.e., albumin secretion and urea synthesis) demonstrated that the heterotypic interaction among HCs and nonparenchymal cells increased the survivability and functionality of HCs within the collagen gel. Therefore, our results demonstrate the prospect of using cell printing technology for the creation of heterotypic cellular interaction within a structure for liver tissue engineering.
Three-dimensional (3D) cell printing systems allow the controlled and precise deposition of multiple cells in 3D constructs. Hydrogel materials have been used extensively as printable bioinks owing ...to their ability to safely encapsulate living cells. However, hydrogel-based bioinks have drawbacks for cell printing, e.g. inappropriate crosslinking and liquid-like rheological properties, which hinder precise 3D shaping. Therefore, in this study, we investigated the influence of various factors (e.g. bioink concentration, viscosity, and extent of crosslinking) on cell printing and established a new 3D cell printing system equipped with heating modules for the precise stacking of decellularized extracellular matrix (dECM)-based 3D cell-laden constructs. Because the pH-adjusted bioink isolated from native tissue is safely gelled at 37 °C, our heating system facilitated the precise stacking of dECM bioinks by enabling simultaneous gelation during printing. We observed greater printability compared with that of a non-heating system. These results were confirmed by mechanical testing and 3D construct stacking analyses. We also confirmed that our heating system did not elicit negative effects, such as cell death, in the printed cells. Conclusively, these results hold promise for the application of 3D bioprinting to tissue engineering and drug development.
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