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To investigate the effects of meniscectomy on degenerative osteoarthritis, a three-dimensional (3D) finite element (FE) model of the human lower limb is constructed from a combination of magnetic resonance (MR) images and computed tomographic (CT) images that can provide anatomically suitable boundary conditions for a knee joint. Four cases, i.e., the intact meniscus, and the partial, sub-total, and total meniscectomy of the medial meniscus are modeled and simulated. We consider that the cartilage-to-cartilage contact area and the peak contact pressure in the meniscus may be significant parameters in evaluating degenerative osteoarthritis. Partial meniscectomy can be regarded as a better treatment than sub-total/total meniscectomy, and a high possibility of degenerative osteoarthritis is anticipated after total meniscectomy. Moreover, medial meniscectomy has the potential to bring about degenerative osteoarthritis in both the medial compartment and the lateral compartment of a knee joint.

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Background Natural killer (NK) cells are an emerging new tool for cancer immunotherapy. To develop NK cell therapeutics from peripheral blood mononuclear cells (PBMCs) of healthy donors, substantial expansion of primary NK cells is necessary because of the very low number of these cells in peripheral blood. In this study, we aimed to investigate the effect of various cytokine alone or combinations, in expanded NK cells and to analyze the synergetic effect of cytokine combinations. Methods Human NK cells were isolated from healthy donor PBMC. Purified NK cells were stimulated with single cytokines or combinations of IL-2, IL-15, IL-18, and IL-27. The expanded NK cells were characterized by flow cytometry, cytotoxicity assay, calcein AM assay and Western blot. Results We investigated the synergistic effects of each cytokine, namely, IL-2, IL-15, IL-18, and IL-27, on human NK cells isolated from PBMCs of healthy donors and cultured for 21 days. We identified that IL-15/IL-18/IL-27-mediated activation of NK cells most potently increased NK cell proliferation, cytotoxicity, and IFN-ɣ secretion compared with the activation observed with other treatments, including IL-2, IL-15, and IL-15/IL-18. Additionally, the expression of DNAM-1, NKG2D, CD69, and natural cytotoxicity receptors (NCRs; NKp30 and NKp44) increased on day 21 compared to that on day 0, demonstrating the activation of NK cells. In vitro, expanded NK cells were highly cytotoxic against cancer cells, displaying increased perforin and granzyme B accumulation. Conclusions Taken together, these results indicated that IL-27 can synergize on NK cell expansion and activation with IL-15 and IL-18. In addition, we described an improved culture method for ex vivo expansion of human NK cells with IL-15/IL-18/IL-27 stimulation and characterized the response of NK cells to this stimulation. Electronic supplementary material The online version of this article (10.1186/s40425-019-0652-7) contains supplementary material, which is available to authorized users.

Background Early stage osteonecrosis of the femoral head (ONFH) has many treatment options including core decompression with implantation of a tantalum rod. The purpose of this study was to evaluate clinical and radiological outcomes and potential complications during conversion total hip arthroplasty (THA) in such patients. Methods Six male patients (8 hips) underwent THA subsequent to removing a tantalum rod (group I) from April 2010 to November 2011. We retrospectively reviewed the medical records of these patients. We enrolled 12 age- and sex-matched patients (16 hips) during the same period, who had undergone primary THA without a previous operation as the control group (group II). All patients were followed for at least 3 years. We checked the Harris hip score (HHS), operative time, and volume of blood loss. Radiological results, including inclination, anteversion of the acetabular cup, presence of periprosthetic osteolysis, and subsidence of femoral stem were checked at the last follow-up. Results The mean preoperative HHS values were 56.5 (range, 50 to 62) and 59.1 (range, 42 to 70) in groups I and II, respectively. The HHS improved to 96.0 (range, 93 to 100) and 97.6 (range, 93 to 100), respectively, at the 3-year follow-up ( p = 0.172). Mean operation time was 98.8 minutes (range, 70 to 120 minutes) in group I and 77.5 minutes (range, 60 to 115 minutes) in group II ( p = 0.006). Total blood loss volumes were 1,193.8 mL (range, 960 to 1,360 mL) and 944.1 mL (range, 640 to 1,280 mL) in groups I and II, respectively ( p = 0.004). No significant differences in inclination or anteversion of acetabular cup and no evidence of osteolysis or subsidence of the femoral stem were reported in either group in radiological follow-up results. However, one case of squeaking occurred in group I during the follow-up. Conclusions The two groups showed no clinical or radiological differences except extended operative time and increased blood loss. However, the incidence of squeaking (1 of 8 hips) was higher, as compared to the control group or previously reported values.

BackgroundGiven the usefulness of rats as an experimental system, an efficient method for generating rat induced pluripotent stem (iPS) cells would provide researchers with a powerful tool for studying human physiology and disease. Here, we report direct reprogramming of rat neural precursor (NP) cells and rat embryonic fibroblasts (REF) into iPS cells by retroviral transduction using either three (Oct3/4, Sox2, and Klf4), four (Oct3/4, Sox2, Klf4, and c-Myc), or five (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) genes.Methodology and Principal FindingsiPS cells were generated from both NP and REF using only three (Oct3/4, Sox2, and Klf4) genes without c-Myc. Two factors were found to be critical for efficient derivation and maintenance of rat iPS cells: the use of rat instead of mouse feeders, and the use of small molecules specifically inhibiting mitogen-activated protein kinase and glycogen synthase kinase 3 pathways. In contrast, introduction of embryonic stem cell (ESC) extracts induced partial reprogramming, but failed to generate iPS cells. However, when combined with retroviral transduction, this method generated iPS cells with significantly higher efficiency. Morphology, gene expression, and epigenetic status confirmed that these rat iPS cells exhibited ESC-like properties, including the ability to differentiate into all three germ layers both in vitro and in teratomas. In particular, we found that these rat iPS cells could differentiate to midbrain-like dopamine neurons with a high efficiency.Conclusions/SignificanceGiven the usefulness of rats as an experimental system, our optimized method would be useful for generating rat iPS cells from diverse tissues and provide researchers with a powerful tool for studying human physiology and disease.

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The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.