Titanium plates are widely used in clinical settings because of their high bone affinity. However, owing to their high elastic modulus, these plates are not suitable for bone repair since their proximity to the bone surface for prolonged periods can cause stress shielding, leading to bone embrittlement. In contrast, titanium fiber plates prepared by molding titanium fibers into plates by simultaneously applying compression and shear stress at normal room temperature can have an elastic modulus similar to that of bone cortex, and stress shielding will not occur even when the plate lies flush against the bone's surface. Titanium fibers can form a porous structure suitable for cell adhesion and as a bone repair scaffold. A titanium fiber plate is combined with osteoblasts and shown that the titanium fiber plate is better able to facilitate bone tissue repair than the conventional titanium plate when implanted in rat bone defects. Capable of being used in close contact with bone for a long time, and even capable of promoting bone repair, titanium fiber plates have a wide range of applications, and are expected to make great contributions to clinical management of increasing bone diseases, including bone fracture repair and bone regenerative medicine.

Background: There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods: In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results: We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions: Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg-we anticipate that our findings will lead to the development of new methods for cancer treatment.

Purpose Although both anti-PD-1 antibody and treatments using anti-PD-L1 antibody are currently in clinical use, their therapeutic effects vary according to cancer type. One of the factors accounting for this variability is the expression level of the immune checkpoint molecule that differs between cancer types; thus, it is important to clarify the relationship between clinical outcomes and immune checkpoint molecules for all types of human cancer. The purpose of this study is to evaluate the clinical outcome of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. Methods Using 19 clinical specimens of osteosarcoma, we examined the expression of PD-L1, PRF, GZMB, and IFNγ in relation to their clinical outcomes. Results PD-L1 expression correlated with early metastatic formation in clinical specimens of osteosarcoma, and the group with highly expressed functional markers for T cells such as PRF and GZMB resulted in a long overall survival time. Conclusion This is the first study to elucidate the clinical outcomes of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. This study provides valuable information regarding the clinical indication and prediction of effect for anti-PD-1 antibody in osteosarcoma.

BackgroundSpinocerebellar degeneration (SCD) mainly manifests a cerebellar ataxic gait, leading to marked postural sway and the risk of falling down. Gait support using a wearable robot is expected to be an effective solution to maintaining the status quo and/or delaying symptom progression. The aim of this study was to evaluate the effects of gait support in patients with SCD by using a wearable robotic system called curara ®; while undergoing walking tests.MethodsThe curara system assists both the hip and knee joints and supports the wearer’s rhythmic gait using a synchronization control based on a central pattern generator. The system reflects the wearer’s intended motion in response to the gait support by detecting an interactive force that is generated from slight movements of the wearer. The degree of coordinated motion between the robot and the wearer can be adjusted by modifying the synchronization gain. In this study, we provided gait support using three high-gain conditions (A, B, C) to more easily follow the wearer’s movement in each joint. The synchronization gains for both the hip and knee joints (i.e., Ch and Ck) were set at 0.5 for condition A and at 0.4 for condition B. Condition C had different gains for the hip and knee joints (i.e., Ch=0.4 and Ck=0.5). With the walking test, we assessed the effects of the gait support provided by the curara system on walking smoothness (measured using the harmonic ratio: HR) and spatiotemporal parameters (gait speed, stride length, cadence) in SCD patients (n=12). We compared the performance between the three high-gain conditions and without assistance from the robot.ResultsUnder condition C, the HRs in the anteroposterior, mediolateral, and vertical directions (HR-AP, HR-ML, and HR-V) were especially high compared with those under conditions A and B. The results of the statistical analyses using repeated measures analysis of variance followed by Tukey’s test showed that gait support with condition C results in a statistically significant increase in the HR-AP (2.04 ±0.52; p=0.025) and HR-V (2.06 ±0.37; p=0.032) when compared with walking without assistance from the system. In contrast, the gait speed, stride length, and cadence under condition C were no major changes in most patients, compared with the patient’s walking without assistance.ConclusionsThe significantly increased HR indicates that gait support under condition C achieved smoother walking than when not wearing the power unit of the system. Consequently, we suggest that gait support using the curara system has the potential to improve walking smoothness in patients with SCD.

IntroductionCarbon nanotubes (CNTs) have various shapes, including needle-like shapes and curled shapes, and the cytotoxicity and carcinogenicity of CNTs differ depending on their shapes and surface modifications. However, the biological responses induced by CNTs and related mechanisms according to the dispersion state of CNTs have not been extensively studied.Materials and methodsWe prepared multiwalled CNTs (MWCNTs) showing different dispersions and evaluated these MWCNTs in RAW264 cells to determine cytotoxicity, cellular uptake, and immune responses. Furthermore, RAW264 cells were also used to compare the cellular uptake and cytotoxicity of fibrous MWCNTs and spherical carbon nanohorns (CNHs) exhibiting the same degree of dispersion.ResultsOur analysis showed that the cellular uptake, localization, and inflammatory responses of MWCNTs differed depending on the dispersion state. Moreover, there were differences in uptake between MWCNTs and CNHs, even showing the same degree of dispersion. These findings suggested that receptors related to cytotoxicity and immune responses differed depending on the aggregated state of MWCNTs and surface modification with a dispersant. Furthermore, our results suggested that the receptors recognized by the cells differed depending on the particle shape.ConclusionTherefore, to apply MWCNTs as a biomaterial, it is important to determine the carcinogenicity and toxicity of the CNTs and to examine different biological responses induced by varying shapes, dispersion states, and surface modifications of particles.