Meniscus is a semilunar fibrocartilaginous tissue, serving important roles in load buffering, stability, lubrication, proprioception, and nutrition of the knee joint. The degeneration and damage of meniscus has been proved to be a risk factor of knee osteoarthritis. Mechanical stimulus is a critical factor of the development, maintenance and repair of the meniscus fibrochondrocytes. However, the mechanism of the mechano-transduction process remains elusive. Here we reported that cyclic hydrostatic compress force (CHCF) treatment promotes proliferation and inhibits apoptosis of the isolated primary meniscus fibrochondrocytes (PMFs), via upregulating the expression level of integrin ?5ß1. Consequently, increased phosphorylated-ERK1/2 and phosphorylated-PI3K, and decreased caspase-3 were detected. These effects of CHCF treatment can be abolished by integrin ?5ß1 inhibitor or specific siRNA transfection. These data indicate that CHCF regulates apoptosis of PMFs via integrin ?5ß1-FAK-PI3K/ERK pathway, which may be an important candidate approach during meniscus degeneration.
- MeSH
- Apoptosis physiology drug effects MeSH
- Mechanotransduction, Cellular physiology MeSH
- Chondrocytes metabolism drug effects MeSH
- Fibroblasts metabolism drug effects MeSH
- Hydrostatic Pressure MeSH
- Integrin alpha5beta1 antagonists & inhibitors metabolism MeSH
- Rats MeSH
- Cells, Cultured MeSH
- RNA, Small Interfering administration & dosage MeSH
- Meniscus cytology metabolism MeSH
- Compressive Strength physiology MeSH
- Rats, Sprague-Dawley MeSH
- Cell Proliferation physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The main goal of this study is to develop a micromechanical model of a particle-filled dental composite focused on the residual stress (RS) field developed during the curing process in its microstructure. A finite element model of a representative volume element of filler and resin was developed, and volumetric shrinkage was simulated during the curing process. Four material models (von Mises plasticity model, Drucker-Prager plasticity model, von Mises plasticity model with stress relaxation and Drucker-Prager plasticity with stress relaxation) of the polymer resin were built to assess the influence of the material model on the resulting internal stress. The relationship between the curing process and the magnitude of the stress components will be described, and an analysis of the post-curing state of the material in particular microstructure locations will be conducted in this study. Obtained RS is comparable to the stresses developed in the material under the external load. The substantial dependence on the choice of material model for resin is to be observed, and the suitability of particular models is discussed.
Adoptive T cell transfer has been shown to be an effective method used to boost tumor-specific immune responses in several types of malignancies. In this study, we set out to optimize the ACT protocol for the experimental treatment of prostate cancer. The protocol includes a pre-stimulation step whereby T cells were primed with autologous dendritic cells loaded with the high hydrostatic pressure-treated prostate cancer cell line, LNCaP. Primed T cells were further expanded in vitro with anti-CD3/CD28 Dynabeads in the WAVE bioreactor 2/10 system and tested for cytotoxicity. Our data indicates that the combination of pre-stimulation and expansion steps resulted in the induction and enrichment of tumor-responsive CD4(+) and CD8(+) T cells at clinically relevant numbers. The majority of both CD4(+) and CD8(+) IFN-γ producing cells were CD62L, CCR7 and CD57 negative but CD28 and CD27 positive, indicating an early antigen experienced phenotype in non-terminal differentiation phase. Expanded T cells showed significantly greater cytotoxicity against LNCaP cells compared to the control SKOV-3, an ovarian cancer line. In summary, our results suggest that the ACT approach together with LNCaP-loaded dendritic cells provides a viable way to generate prostate cancer reactive T cell effectors that are capable of mounting efficient and targeted antitumor responses and can be thus considered for further testing in a clinical setting.
- MeSH
- Lymphocyte Activation MeSH
- Antigens, Neoplasm immunology MeSH
- Bioreactors MeSH
- Dendritic Cells immunology MeSH
- Epitopes, T-Lymphocyte immunology MeSH
- Immunotherapy, Adoptive methods MeSH
- Interferon-gamma biosynthesis immunology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms immunology MeSH
- Ovarian Neoplasms immunology MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Case-Control Studies MeSH
- T-Lymphocyte Subsets immunology MeSH
- T-Lymphocytes immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
... B.i Pseudonremic and pseudorachitics syndromes evoked by enduance load and nutrition 229 -- 4BartftAková ... ... S. - Havlíčková L. - Jetek P. - Paŕizkovi J.: Drinking regime daring an extreme endurance load 2 -- ... ... JUrlmäe T. - Jagomägl C.: The new apparatuses for measurement body density by hydrostatic weighing 2 ...
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