Regenerative medicine has been widely researched for the treatment of bone defects. In the field of bone regenerative medicine, signaling molecules and the use of scaffolds are of particular ...importance as drug delivery systems (DDS) or carriers for cell differentiation, and various materials have been explored for their potential use. Although calcium phosphates such as hydroxyapatite and tricalcium phosphate are clinically used as synthetic scaffold material for bone regeneration, biodegradable materials have attracted much attention in recent years for their clinical application as scaffolds due their ability to facilitate rapid localized absorption and replacement with autologous bone. In this review, we introduce the types, features, and performance characteristics of biodegradable polymer scaffolds in their role as DDS for bone regeneration therapy.
With the development of nanotechnology in recent years, there have been concerns about the health effects of nanoparticles. Carbon nanotubes (CNTs) are fibrous nanoparticles with a micro-sized length ...and nano-sized diameter, which exhibit excellent physical properties and are widely studied for their potential application in medicine. However, asbestos has been historically shown to cause pleural malignant mesothelioma and lung cancer by inhalation exposure. Because carbon nanotubes are also fibrous nanotubes, some have raised concerns about its possible carcinogenicity. We have reported that there is no clear evidence of carcinogenicity by local and intravenous administration of multi-walled CNTs to cancer mice models. We firmly believe that CNTs can be a safe, new, and high-performance biomaterials by controlling its type, site of administration, and dosage.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Lysophosphatidylethanolamines (LPEs) are bioactive lysophospholipids that have been suggested to play important roles in several biological processes. We performed a quantitative analysis of ...LPE species and showed their composition in mouse brain. We examined the roles of oleoyl-LPE (18:1 LPE), which is one of the abundant LPE species in brain. In cultured cortical neurons, application of 18:1 LPE-stimulated neurite outgrowth. The effect of 18:1 LPE on neurite outgrowth was inhibited by Gq/11 inhibitor YM-254890, phospholipase C (PLC) inhibitor U73122, protein kinase C (PKC) inhibitor Go6983 or mitogen-activated protein kinase (MAPK) inhibitor U0126. Additionally, 18:1 LPE increased the phosphorylation of MAPK/extracellular signal-regulated kinase 1/2. These results suggest that the action of 18:1 LPE on neurite outgrowth is mediated by the Gq/11/PLC/PKC/MAPK pathway. Moreover, we found that application of 18:1 LPE protects neurons from glutamate-induced excitotoxicity. This effect of 18:1 LPE was suppressed by PKC inhibitor Go6983. These results suggest that 18:1 LPE protects neurons from glutamate toxicity via PKC inhibitor Go6983-sensitive PKC subtype. Collectively, our results demonstrated that 18:1 LPE stimulates neurite outgrowth and protects against glutamate toxicity in cultured cortical neurons. Our findings provide insights into the physiological or pathological roles of 18:1 LPE in the brain.
Graphical Abstract
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.
Titanium fiber plates prepared by molding titanium fibers into plates by simultaneously applying compression and shear stress at normal room temperature can have a Young's modulus similar to that of bone cortex, and stress shielding will not occur. Titanium fibers can form a porous structure suitable for cell adhesion and as a bone‐repair scaffold.
On-machine scanning measurement of workpiece geometry has a strong advantage in its efficiency, compared to conventional discrete measurement using a touch-trigger probe. When a workpiece is rotated ...and tilted, position and orientation errors of the workpiece with respect to the machine’s rotary axes can be a significant contributor to the measurement error. Rotary axis geometric errors also influence the measurement error. To establish the traceability of on-machine measurement with workpiece rotation, this paper kinematically formulates their contribution to measured profiles. As a practical application example, this paper presents the measurement error assessment for an axis-symmetric part. Based on the present kinematic model, this paper compares error contributors to the cases (1) where an axis-symmetric part is placed concentric to the rotary axis, and (2) where it is placed away from the rotary axis.
Purpose
To investigate the effect of a new remnant preservation technique with a focus on remnant continuity on postoperative femoral and tibial tunnel enlargement after anatomical double-bundle ...anterior cruciate ligament reconstruction (ACLR).
Methods
A total of 150 knees were divided into three groups: Preservation Group (Group P: 49 knees), wherein the remnant continuity remained after tunnel creation; Resection Group (Group R: 47 knees), wherein the remaining remnant was resected, and Absent Group (Group A: 54 knees), wherein the remnant had no femoral attachment before tunnel creation. In Group P, the remnant maintained continuity, and the anteromedial (AM) and posterolateral (PL) bundles were positioned anterior and posterior to the remnant, respectively. Computed tomographic scans were performed at 1 week and 1 year after surgery, and the cross-sectional area of each tunnel aperture was measured. Tunnel enlargement was compared among the three groups by one-way analysis of variance (ANOVA) and the Bonferroni test. Univariate and multivariate logistic analyses were performed to identify the risk factors for tunnel enlargement in demographic and radiographic data.
Result
For femoral AM tunnels, the tunnel enlargement of Group P was significantly smaller than Groups R and A (
p
< 0.001), femoral PL (
p
< 0.001 vs. R and A), tibial AM (
p
< 0.001 vs. R, 0.002 vs. A), and tibial PL (
p
< 0.001 vs. R, 0.002 vs. A). There was no significant difference between Groups R and A. Multivariate logistic analysis showed that remnant preservation was a significant factor in reducing tunnel enlargement in the femoral AM, femoral PL, tibial AM, and tibial PL.
Conclusion
The new remnant-preserving anatomical double-bundle ACLR, which preserves the continuity of the remnant, prevented all bone tunnel enlargement at 1 year postoperatively.
Level of evidence
Level III.
Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved ...over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.
Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and ...osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials.
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