Prostaglandin E<inf>2</inf> (PGE<inf>2</inf>) exerts biphasic effects on human tendon stem cells

Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE 2 ( >1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo. © 2014 Zhang, Wang

Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer

Subcellular distribution of nuclear import-defective isoforms of the promyelocytic leukemia protein

<p>Abstract</p> <p>Background</p> <p>The promyelocytic leukemia (PML) protein participates in a number of cellular processes, including transcription regulation, apoptosis, differentiation, virus defense and genome maintenance. This protein is structurally organized into a tripartite motif (TRIM) at its N-terminus, a nuclear localization signal (NLS) at its central region and a C-terminus that varies between alternatively spliced isoforms. Most PML splice variants target the nucleus where they define sub-nuclear compartments termed PML nuclear bodies (PML NBs). However, PML variants that lack the NLS are also expressed, suggesting the existence of PML isoforms with cytoplasmic functions. In the present study we expressed PML isoforms with a mutated NLS in U2OS cells to identify potential cytoplasmic compartments targeted by this protein.</p> <p>Results</p> <p>Expression of NLS mutated PML isoforms in U2OS cells revealed that PML I targets early endosomes, PML II targets the inner nuclear membrane (partially due to an extra NLS at its C-terminus), and PML III, IV and V target late endosomes/lysosomes. Clustering of PML at all of these subcellular locations depended on a functional TRIM domain.</p> <p>Conclusions</p> <p>This study demonstrates the capacity of PML to form macromolecular protein assemblies at several different subcellular sites. Further, it emphasizes a role of the variable C-terminus in subcellular target selection and a general role of the N-terminal TRIM domain in promoting protein clustering.</p

The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cowpea: a legume crop for a challenging environment

Running title: Cowpea for a challenging environmentCowpea is a grain legume native from Africa and is a primary source of protein for millions of people in sub-Saharan Africa and other parts of the developing world. The main important characteristics of this crop include a good protein quality with a high nutritional value, its nitrogen-fixing ability, and an ability to be more drought- and heat-tolerant than most of its legume relatives. In a research perspective, studies of cowpea are relatively scarce, despite its relevance to agriculture in the developing world and its resilience to stress. The present review provides an overview of different aspects of cowpea, with a special emphasis on the molecular markers for assessing genetic diversity, as well as on biochemical and transcriptomic data with respect to evaluating cowpea drought stress tolerance. The integration of both datasets will be useful for the improvement of cowpea because research on drought stress tolerance is of major interest for this crop in a challenging environment. © 2017 Society of Chemical Industry.This work is supported by European Investment Funds by FEDER/COMPETE/POCI—Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT—Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013.info:eu-repo/semantics/publishedVersio

Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E₂ signaling in fat stromal cells

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms of dietary oils (such as fish oil) and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E₂ (PGE₂)-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE₂ receptors and an HEK293 cell line specifically expressing the recombinant human PGE₂ receptor subtype-1 (EP₁) were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE₂.</p> <p>Results</p> <p>It was identified that fish oil best inhibited the PGE₂ signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA), found in abundance in fish oil, was identified as a key factor of inhibition of PGE₂ signaling. Eicosapentaenoic acid (EPA), another major fatty acid found in fish oil and tested in this study was found to have small effect on EP₁ signaling. The study suggested one of the four PGE₂ subtype receptors, EP₁ as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP₁ expressed in HEK293 cells as a target.</p> <p>Conclusion</p> <p>This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP₁-mediated PGE₂ receptor signaling, and that the inflammatory response stimulated by PGE₂ in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart disease, pain, and cancer resulted from inflammatory PGE_2.</p