Medical visits of childhood cancer survivors in Japan: A cross‐sectional survey

Background: Although more children with cancer continue to be cured, these survivors experience various late effects. Details of the medical visit behaviors of childhood cancer survivors (CCS) in adulthood remain to be elucidated. Methods: In order to examine medical visits in the past and future of CCS, we performed a cross‐sectional survey with self‐rating questionnaires on medical visits of CCS compared with control groups (their siblings and the general population). Results: Questionnaires were completed by 185 CCS, 72 of their siblings and 1000 subjects from the general population and the results were analyzed. Mean ages at this survey and the duration after therapy completions of CCS were 23 and 12 years, respectively. We found that the previous treatment hospitals (where CCS were treated for their cancer) were the most commonly visited medical facilities for the CCS group (74% for female patients and 64% for male patients) and more than half of the CCS preferred to continue visiting the previous treatment hospital with enough satisfaction in Japan. The multivariate analysis showed that female sex and relapse were significantly associated with the past visits to the previous treatment hospital and that the CCS with brain tumors or bone/soft tissue sarcomas and CCS with any late effects tended to continue the relationships with the hospital. In addition female sex was also significantly associated with desired future visits to the previous treatment hospital. On the other hand, the married CCS tended to be disinclined to visit the hospital it in the future. Conclusions: In order to optimize risk‐based care and promote health for CCS after adulthood, we should discuss the medical transition with CCS and their parents.     

A natural lipopeptide of surfactin for oral delivery of insulin

Abstract

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and β-turn, but with increased flexible β-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.     

Size-Dependent Persistent Luminescence of YAGG:Cr3+ Nanophosphors

In the current work, YAGG:Cr³⁺ nanophosphors were synthesized by the Pechini method and then annealed at different temperatures in the range 800–1300 °C. The structure and morphology of the samples were characterized by X-ray Powder Diffraction (XRPD). The lattice parameters and average crystalline sizes as site occupation by Al³⁺ and Ga³⁺ ions were calculated from the Rietveld refinement data. To investigate the effect of crystalline size of the materials on their optical properties: excitation and emission spectra were recorded and analyzed. Finally, the effect of crystalline size on the probability of carrier recombination leading to PersL was determined experimentally with thermoluminescence analyses. The T_max-T_stop method was applied to determine the trap type and particle size (calcination temperature) effect on their redistribution. A correlation between structural changes and trap redistribution was found. In particular, the extinction of high-temperature TL maximum with increasing annealing temperatures is observed, while low-temperature TL maximum increases and reaches a maximum when the lattice parameter reaches saturation.     

Investigation of the Thermodynamic Transformation and Rare Earth Microalloying of a Medium Carbon-Medium Alloy Steel for Large Ball Mill Liners

The medium carbon-medium alloy steel was developed for the manufacture of large ball mill liners and sports equipment. In this study, the continuous cooling transformation curve of a novel type of medium carbon-medium alloy steel was measured with a thermal simulation machine; based on this curve, the hardening and tempering processes were optimized. The steel was then complex modified with alkaline earth and rare earth alloys. The mechanical properties of the treated steel were tested. The microstructure of the steel was analyzed by metallographic microscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy, and the wear surface of the steel was analyzed by a three-dimensional morphometer. After high-temperature tempering, the microstructure transformed into tempered sorbite, which possesses good mechanical properties and can adapt to working conditions that require high strength and toughness. Rare earth or alkaline earth modification of the medium carbon-medium alloy steel promoted microstructural uniformity and grain refinement and improved the mechanical and anti-wear properties.     

Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway

Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

Corosolic acid analogue,a natural triterpenoid saponin,induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro

Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine.

Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines.

Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40?μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4′-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays.

Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24?h, the IC₅₀ values were 34.6, 30.8 and 30.5?μg/mL, respectively. TEO (40?μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio.

Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.     

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Aim： To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium （DSS）-induced colitis and to determine the mechanism of the balsalazine-induced changes.
Methods： Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index （DAI） score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde （MDA） in the colon was determined, along with the activity of myeloperoxidase （MPO）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）. Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor （TNF）-α and interferon （IFN）-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results： Balsalazine was found to reduce the DAI score and the histological index （HI） score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion： In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine＇s antioxidative and anti-inflammatory effects.     

白三烯拮抗剂ONO-1078对电刺激迷走神经、辣椒素和P物质引起的豚鼠心血管反应的作用(英文)

阐明ONO-1078(ONO,4-氧-8-[对-(4-苯丁氧基)苯甲酰氨基]-2-(5-四唑基)-4H-1-苯并毗喃)对神经原性刺激诱导心血管反应的作用.方法:观察豚鼠心房和心室伊文思蓝渗出以及平均主动脉压(MAP)变化.结果:在阿托品(1 mg·kg~(-1),iv)预先处理后,电刺激迷走神经(ESV,10 Hz,5 ms,2或10 V,90 s)显著增高伊文思蓝渗出;辣椒素和P物质也增加染料渗出并降低平均动脉压(MAP).ONO(0.03,0.1 mg·kg~(-1),iv)抑制ESV的反应,在刺激强度低(2 V)时更明显;ONO 0.03 mg·kg~(-1)减弱辣椒素引起的微血管渗漏和低血压,但对P物质无影响.结论:ONO-1078可能通过抑制感觉神经肽释放而调节神经原性炎症时的心血管反应.     

Novel Electromagnetic Characterization Methods for New Materials and Structures in Aerospace Platforms

The tendency over the last decades in the aerospace industry is to substitute classic metallic materials with new composite materials such as carbon fiber composites (CFC), fiber glass, etc., as well as adding electronic devices to ensure the safety and proper platform operation. Due to this, to protect the aircraft against the Electromagnetic Environmental Effects (E3), it is mandatory to develop accurate electromagnetic (EM) characterization measurement systems to analyze the behavior of new materials and electronic components. In this article, several measurement methods are described to assess the EM behavior of the samples under test: microstrip transmission line for a surface current analysis, free space to obtain intrinsic features of the materials and shielding effectiveness (SE) approaches to figure out how well they isolate from EM fields. The results presented in this work show how the different facilities from the National Institute of Aerospace Technology (INTA) are suitable for such purposes, being capable of measuring a wide variety of materials, depending on the type of test to be carried out.