Human embryonic stem cells (hESCs) are ideal seed cells for tissue regeneration, but no research has yet been reported concerning their potential for tendon regeneration. This study investigated the strategy and efficacy of using hESCs for tendon regeneration as well as the mechanism involved. hESCs were first induced to differentiate into mesenchymal stem cells (MSCs), which had the potential to differentiate into the three mesenchymal lineages and were positive for MSC surface markers. hESC-derived MSCs (hESC-MSCs) regenerated tendon tissues in both an in vitro tissue engineering model and an in vivo ectopic tendon regeneration model, as confirmed by the expression of tendon-specific genes and structure. In in-situ rat patellar tendon repair, tendon treated with hESC-MSCs had much better structural and mechanical properties than did controls. Furthermore, hESC-MSCs remained viable at the tendon wound site for at least 4 weeks and secreted human fetal tendon-specific matrix components and differentiation factors, which then activated the endogenous regeneration process in tendon. Moreover, no teratoma was found in any samples. These findings demonstrate a safe and practical strategy of applying ESCs for tendon regeneration and may assist in future strategies to treat tendon diseases. STEM

Background:Corneal stromal cells (CSCs) are components of the corneal endothelial microenvironment that can be induced to form a functional tissue-engineered corneal endothelium. Adipose-derived mesenchymal stem cells (ADSCs) have been reported as an important component of regenerative medicine and cell therapy for corneal stromal damage. We have demonstrated that the treatment with ADSCs leads to phenotypic changes in CSCs in vitro. However, the underlying mechanisms of such ADSC-induced changes in CSCs remain unclear.Methods:ADSCs and CSCs were isolated from New Zealand white rabbits and cultured in vitro. An Exosome Isolation Kit, Western blotting, and nanoparticle tracking analysis (NTA) were used to isolate and confirm the exosomes from ADSC culture medium. Meanwhile, the optimal exosome concentration and treatment time were selected. Cell Counting Kit-8 and annexin V-fluorescein isothiocyanate/propidium iodide assays were used to assess the effect of ADSC- derived exosomes on the proliferation and apoptosis of CSCs. To evaluate the effects of ADSC- derived exosomes on CSC invasion activity, Western blotting was used to detect the expression of matrix metalloproteinases (MMPs) and collagens.Results:ADSCs and CSCs were successfully isolated from New Zealand rabbits. The optimal concentration and treatment time of exosomes for the following study were 100 μg/ml and 96 h, respectively. NTA revealed that the ADSC-derived exosomes appeared as nanoparticles (40–200 nm), and Western blotting confirmed positive expression of CD9, CD81, flotillin-1, and HSP70 versus ADSC cytoplasmic proteins (all P < 0.01). ADSC-derived exosomes (50 μg/ml and 100 μg/ml) significantly promoted proliferation and inhibited apoptosis (mainly early apoptosis) of CSCs versus non-exosome-treated CSCs (all P < 0.05). Interestingly, MMPs were downregulated and extracellular matrix (ECM)-related proteins including collagens and fibronectin were upregulated in the exosome-treated CSCs versus non-exosome-treated CSCs (MMP1: t = 80.103, P < 0.01; MMP2: t = 114.778, P < 0.01; MMP3: t = 56.208, P < 0.01; and MMP9: t = 60.617, P < 0.01; collagen I: t = −82.742, P < 0.01; collagen II: t = −72.818, P < 0.01; collagen III: t = −104.452, P < 0.01; collagen IV: t = −133.426, P < 0.01, and collagen V: t = −294.019, P < 0.01; and fibronectin: t = −92.491, P < 0.01, respectively).Conclusion:The findings indicate that ADSCs might play an important role in CSC viability regulation and ECM remodeling, partially through the secretion of exosomes.

We have reported that nuclear translocation of Receptor-interacting protein 3 (RIP3) involves in neuronal programmed necrosis after 20-min global cerebral ischemia/reperfusion (I/R) injury. Herein, the underlying mechanisms and the nuclear role of RIP3 were investigated further. The necroptosis inhibitor necrostatin-1 (Nec-1), the autophagy inhibitor 3-methyladenine (3-MA), and the caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspart-1-al (Ac-DMQD-CHO) were administered intracerebroventricularly 1 h before ischemia. Protein expression, location and interaction was determined by western blot, immunofluorescence or immunoprecipitation. Most CA1 neuronal death induced by 20-min global cerebral I/R injury was TUNEL-positive. Neuronal death and rat mortality rates were greatly inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. And no activation of caspase-3 was detected after I/R injury. Caspase-8 was expressed richly in GFAP-positive astrocytes and Iba-1-positive microglia, but was not detected in Neun-positive neurons. The nuclear translocation and co-localization of RIP3 and AIF, and their interaction were detected after I/R injury. These processes were inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. The formation of an RIP3-AIF complex and its nuclear translocation are critical to ischemic neuronal DNA degradation and programmed necrosis. Neurons are more likely to enter the programmed necrosis signal pathway for the loss of caspase-8 suppression.

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To increase continuing education accessibility, nurses around the world are turning to Web-based instruction. However, for Internet education to be successful, particularly in developing countries, nurses must have access to computers and the Internet as well as positive attitudes toward this form of learning. As part of a distance education project for nurses of the Tianjin Municipality in China, a survey of nurses was conducted to examine their sources of professional knowledge as well as their computer and Internet access and attitudes. The attitudes of the nurses were generally positive, and there was evidence of rapidly increasing use of and access to computers and the Internet. This article reports the results of that survey and their implications for Web-based teaching of Chinese nurses.

Background: Higher tumor expression of CD44, a marker of cancer stem cells (CSCs), is associated with poor overall survival (OS) in various cancers. However, the association between CD44 and poor OS remains inconsistent in glioma. We aimed to evaluate the potential predictive role of CD44 for prognosis of glioma patients in a meta-analysis. Methods: Observational studies comparing OS of glioma patients according to the level of CD44 were identified through searching PubMed, Embase, and Cochrane’s Library databases. Meta-analyses were performed with a random- or fixed-effect model according to the heterogeneity. Subgroup analyses were performed to evaluate the influences of study characteristics. Results: Eleven retrospective cohort studies were included. Results showed that increased CD44 expression in tumor predicted poor OS in glioma patients (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.02–1.97, P=0.04). Subgroup analyses showed that higher tumor CD44 expression significantly predicted poor OS in patients with World Health Organization (WHO) stages II–III glioma (HR: 2.99, 95% CI: 1.53–5.89, P=0.002), but not in patients with glioblastoma (HR: 1.26, 95% CI: 0.76–2.08, P=0.47; P for subgroup difference = 0.03). Results were not statistically different between subgroups according to patient ethnicity, sample size, CD44 detection method, CD44 cutoff, HR estimation, univariate or multivariate analysis, or median follow-up durations (P-values for subgroup difference all &gt;0.10). Conclusion: Higher tumor expression of CD44 may predict poor survival in patients with glioma, particularly in those with WHO stage II–III glioma.

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