Aged Tendon Stem/Progenitor Cells Are Less Competent to Form 3D Tendon Organoids Due to Cell Autonomous and Matrix Production Deficits

Tendons are dense connective tissues, which are critical for the integrity and function of our musculoskeletal system. During tendon aging and degeneration, tendon stem/progenitor cells (TSPCs) experience profound phenotypic changes with declined cellular functions that can be linked to the known increase in complications during tendon healing process in elderly patients. Tissue engineering is a promising approach for achieving a complete recovery of injured tendons. However, use of autologous cells from aged individuals would require restoring the cellular fitness prior to implantation. In this study, we applied an established cell sheet model for in vitro tenogenesis and compared the sheet formation of TSPC derived from young/healthy (Y-TSPCs) versus aged/degenerative (A-TSPCs) human Achilles tendon biopsies with the purpose to unravel differences in their potential to form self-assembled three-dimensional (3D) tendon organoids. Using our three-step protocol, 4 donors of Y-TSPCs and 9 donors of A-TSPCs were subjected to cell sheet formation and maturation in a period of 5 weeks. The sheets were then cross evaluated by weight and diameter measurements; quantification of cell density, proliferation, senescence and apoptosis; histomorphometry; gene expression of 48 target genes; and collagen type I protein production. The results revealed very obvious and significant phenotype in A-TSPC sheets characterized by being fragile and thin with poor tissue morphology, and significantly lower cell density and proliferation, but significantly higher levels of the senescence-related gene markers and apoptotic cells. Quantitative gene expression analyses at the mRNA and protein levels, also demonstrated abnormal molecular circuits in the A-TSPC sheets. Taken together, we report for the first time that A-TSPCs exhibit profound deficits in forming 3D tendon tissue organoids, thus making the cell sheet model suitable to investigate the molecular mechanisms involved in tendon aging and degeneration, as well as examining novel pharmacologic strategies for rejuvenation of aged cells

A Collaborative Framework for Privacy Protection in Online Social Networks

With the wide use of online social networks (OSNs), the problem of data privacy has attracted much attention. Several approaches have been proposed to address this issue. One of privacy management approaches for OSN leverages a key management technique to enable a user to simply post encrypted contents so that only users who can satisfy the associate security policy can derive the key to access the data. However, the key management policies of existing schemes may grant access to unaurhorized users and cannot efficiently determine authorized users. In this paper, we propose a collaborative framework which enforces access control for OSN through an innovative key management focused on communities. This framework introduces a community key management based on a new group-oriented convergence cryptosystem, as well as provides an efficient privacy preservation needed in a private OSN. To prove the feasibility of our approach, we also discuss a proof-of-concept implementation of our framework. Experimental results show that our construction can achieve the identified design goals for OSNs with the acceptable performance

Three-dimensional self-assembling nanofiber matrix rejuvenates aged/degenerative human tendon stem/progenitor cells

The poor healing capacity of tendons is known to worsen in the elderly. During tendon aging and degeneration, endogenous human tendon stem/progenitor cells (hTSPCs) experience profound pathological changes. Here, we explored a rejuvenation strategy for hTSPCs derived from aged/degenerated Achilles tendons (A-TSPCs) by providing three-dimensional (3D) nanofiber hydrogels and comparing them to young/healthy TSPCs (Y-TSPCs). RADA peptide hydrogel has a self-assembling ability, forms a nanofibrous 3D niche and can be further functionalized by adding RGD motifs. Cell survival, apoptosis, and proliferation assays demonstrated that RADA and RADA/RGD hydrogels support A-TSPCs in a comparable manner to Y-TSPCs. Moreover, they rejuvenated ATSPCs to a phenotype similar to that of Y-TSPCs, as evidenced by restored cell morphology and cytoskeletal architecture. Transmission electron, confocal laser scanning and atomic force microscopies demonstrated comparable ultrastructure, surface roughness and elastic modulus of A- and Y-TSPC-loaded hydrogels. Lastly, quantitative PCR revealed similar expression profiles, as well a significant upregulation of genes related to tenogenesis and multipotency. Taken together, the RADA-based hydrogels exert a rejuvenating effect by recapitulating in vitro specific features of the natural microenvironment of human TSPCs, which strongly indicates their potential to direct cell behaviour and overcome the challenge of cell aging and degeneration in tendon repair.D.D. acknowledges the EU Twinning Grant Achilles (H2020- WIDESPREAD-05-2017-Twinning Grant Nr. 810850). H.Y. thanks for the support of China Scholarship Council (CSC Grant Nr. 201606200072). S.K. and H.C-S. acknowledge the financial support for CANTER by the Bavarian State Ministry for Science and Education. The authors thank Daniela Drenkard for valuable technical assistance and Dr. Girish Pattappa for English proof-readin

In Vitro Comparison of 2D-Cell Culture and 3D-Cell Sheets of Scleraxis-Programmed Bone Marrow Derived Mesenchymal Stem Cells to Primary Tendon Stem/Progenitor Cells for Tendon Repair

The poor and slow healing capacity of tendons requires novel strategies to speed up the tendon repair process. Hence, new and promising developments in tendon tissue engineering have become increasingly relevant. Previously, we have established a tendon progenitor cell line via ectopic expression of the tendon-related basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) in human bone marrow mesenchymal stem cells (hMSC-Scx). The aim of this study was to directly compare the characteristics of hMSC-Scx cells to that of primary human tendon stem/progenitors cells (hTSPCs) via assessment of self-renewal and multipotency, gene marker expression profiling, in vitro wound healing assay and three-dimensional cell sheet formation. As expected, hTSPCs were more naive than hMSC-Scx cells because of higher clonogenicity, trilineage differentiation potential, and expression of stem cell markers, as well as higher mRNA levels of several gene factors associated with early tendon development. Interestingly, with regards to wound healing, both cell types demonstrate a comparable speed of scratch closure, as well as migratory velocity and distance in various migration experiments. In the three-dimensional cell sheet model, hMSC-Scx cells and hTSPCs form compact tendinous sheets as histological staining, and transmission electron microscopy shows spindle-shaped cells and collagen type I fibrils with similar average diameter size and distribution. Taken together, hTSPCs exceed hMSC-Scx cells in several characteristics, namely clonogenicity, multipotentiality, gene expression profile and rates of tendon-like sheet formation, whilst in three-dimensional cell sheets, both cell types have comparable in vitro healing potential and collagenous composition of their three-dimensional cell sheets, making both cell types a suitable cell source for tendon tissue engineering and healing

Effectiveness of 18F-FDG PET/CT in the diagnosis, staging and recurrence monitoring of Ewing sarcoma family of tumors: A meta-analysis of 23 studies

Background: To investigate the value of positron emission tomography (PET) and PET/computed tomography (CT) using fluorine-18-fluorodeoxyglucose (F-18-FDG) in the diagnosis, staging, restaging and recurrence monitoring of Ewing sarcoma family of tumors (ESFTs), a meta-analysis was performed through systematically searching PubMed, Embase, and Cochrane Central library to retrieve articles. Methods: After screening and diluting out the articles that met inclusion criteria to be used for statistical analysis the pooled evaluation indexes including sensitivity, specificity, and diagnostic odd ratio (DOR) as well as the summary receiver operating characteristic curve (SROC) were calculated involving diagnostic data (true positive, false positive, false negative, and true negative) extracted from original studies. Results: Screening determined that out of 2007, 23 studies involving a total of 524 patients were deemed viable for inclusion in the meta-analysis. The results of the analysis showed that the sensitivity and specificity were at 86% and 80%, respectively. Additionally, a satisfactory accuracy of F-18-FDG PET and PET/CT was observed in detecting ESFT recurrence, lung metastasis, and osseous metastasis. Conclusion: This meta-analysis suggests that F-18-FDG PET and PET/CT with an extremely high accuracy could be considered a valuable method for detecting distant metastasis and post-operational recurrence of ESFT, which might have a profound impact on the development of treatment protocols for ESFT

Thermodynamic Modeling and Analysis of an Optical Electric-Field Sensor

The stability of the optical electric field sensor (OEFS) in actual operation is affected by environmental factors such as temperature and SF6 (sulfur hexafluoride). To analyze the operational environment parameters affecting the optical properties of crystals, a thermodynamic model of the OEFS in which the optical properties of the crystal are changed by the first-order effects and the second-order effects was established. The intensity parameters such as electric, stress and temperature fields were introduced. The theoretical analysis results show that under temperature, stress and electric field conditions, the optical properties of the sensing crystals are no longer changed only by the electro-optic effect, but also by the temperature and the stress fields. Further synthesis suggests the expected optical property changes under the effect of the environment fields. OEFS tests show that the accuracy of OEFS is dependent on temperature with a ratio error of −0.8%~1.5% in the temperature range from −25 °C to +40 °C

CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy

Abstract Background: Serum tumor markers are of great importance in diagnosis, prognostic predicting and recurrence monitoring in gastrointestinal malignancy, including AFU, AFP, CEA, CA199, CA125 and CA724. However, their significances in gastric cancer (GC) patients with neoadjuvant therapy (NCT) are still uncertain. The aim of this study is to evaluate the predictive value of these six tumor markers in locally advanced GC patients with NCT and curative surgery. Methods: 290 locally advanced GC patients with NCT and D2 radical gastrectomy were retrospectively analyzed. Their tumor markers before (pre-) and after (post-) NCT and pathological characters were exacted from the database in our hospital. The optimal cutoff values of six tumor markers were calculated by ROC and Youden index. Their predictive significances were analyzed and survival curves on overall survival (OS) were obtained by Kaplan-Meier method. Associations between categorical variables were explored by Chi-square test or Fisher's exact method. Multivariate analyses were performed by Cox regression model. Results: Not only the pre- and post- CA199, CA125 and CA724 could predict the overall survival respectively, but also the changes (diff-) between post- and pre- groups were related to the prognosis (P &lt; 0.05). In multivariable analysis, only pre- (P = 0.016) and post-CA724 (P = 0.033) remained significant, and the significance of diff-CA724 was on borderline (P = 0.085). Besides, pre- and post-CA199, CA125 and CA724 were associated with the metastasis of lymph node (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (P &lt; 0.05). Post-CA724 was related to the invasion of vascular or lymphatic vessels (P = 0.019), and pre-CA724 was nearly remarkable (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P &gt; 0.05). Conclusions: CA724 is an independent factor to prognosis, and could be used to predict the ypN and ypTNM stage in locally advanced GC patients undergone NCT and curative resection.</jats:p

CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy&amp;nbsp;

Abstract Background: Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery. Methods: In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model. Results: Pre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P &lt; 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (all P &lt; 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P &gt; 0.05). Conclusions: CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.</jats:p

CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy

Abstract Background: Serum tumor markers are of great importance in diagnosis, prognostic predicting and recurrence monitoring in gastrointestinal malignancy, including AFU, AFP, CEA, CA199, CA125 and CA724. However, their significances in gastric cancer (GC) patients with neoadjuvant therapy (NCT) are still uncertain. The aim of this study is to evaluate the predictive value of these six tumor markers in locally advanced GC patients with NCT and curative surgery. Methods: 290 locally advanced GC patients with NCT and D2 radical gastrectomy were retrospectively analyzed. Their tumor markers before (pre-) and after (post-) NCT and pathological characters were exacted from the database in our hospital. The optimal cutoff values of six tumor markers were calculated by ROC and Youden index. Their predictive significances were analyzed and survival curves on overall survival (OS) were obtained by Kaplan-Meier method. Associations between categorical variables were explored by Chi-square test or Fisher's exact method. Multivariate analyses were performed by Cox regression model. Results: Not only the pre- and post- CA199, CA125 and CA724 could predict the OS respectively, but also the changes (diff-) between post- and pre- groups were related to the prognosis (P &lt; 0.05). In multivariable analysis, only pre- (P = 0.016) and post-CA724 (P = 0.033) remained significant, and the significance of diff-CA724 was on borderline (P = 0.085). Besides, pre- and post-CA199, CA125 and CA724 were associated with the metastasis of lymph node (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (P &lt; 0.05). Post-CA724 was related to the invasion of vascular or lymphatic vessels (P = 0.019), and pre-CA724 was nearly remarkable (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P &gt; 0.05). Conclusions: CA724 is an independent factor to prognosis, and could be used to predict the ypN and ypTNM stage in locally advanced GC patients undergone NCT and curative resection.</jats:p