The possible role of ribosomal protein S6 kinase 4 in the senescence of endothelial progenitor cells in diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>The decrease and dysfunction of endothelial progenitor cells (EPCs) has been assumed as an important cause/consequence of diabetes mellitus (DM) and its complications, in which the senescence of EPCs induced by hyperglycemia may play an immensurable role. However, the mechanisms of EPCs senescence has not been fully investigated. Recently, ribosomal protein S6 kinase 4 (RSK4), a member of serine/threomine (Ser/Thr) kinase family and p53-related gene, is reported to regulate the replicative and stress-induced senescence of different cells.</p> <p>Presentation of the hypothesis</p> <p>These above lead to consideration of an evidence-based hypothesis that RSK4 may serve as a mediator of EPCs senescence in DM.</p> <p>Testing the hypothesis</p> <p>EPCs of healthy subjects and DM patients are isolated from peripheral blood and incubated with high glucose (HG). Then, the EPCs senescence would be detected by senescence associated β-galactosides (SA-β-gal) staining. Meanwhile, the RSK4 expression is assessed by RT-PCR and western blot. Moreover, overexpressing or RNA interfering of RSK4 in EPCs to investigate the relationship between RSK4 expression and the senescence of EPCs are necessary to substantiate this hypothesis. Also, studies on possible upstream and downstream factors of RSK4 would be explored to reveal the RSK4-mediated senescence pathway in EPCs.</p> <p>Implications of the hypothesis</p> <p>If proved, this hypothesis will provide another mediator of EPCs senescence, and may establish a novel pathogenesis for DM and further benefit to the management of DM.</p

A Comparative Analysis of Strategic Values of Four Silk-Road International Transport Corridors Based on a Fuzzy Integral Method with Comprehensive Weights

This paper carries out a comparative analysis of the strategic values of four silk-road international transport corridors, “China-Pakistan-Iran-Turkey” (CPIT), “China-Mongolia-Russia” (CMR), “Bangladesh-China-India-Myanmar” (BCIM), and “China-Singapore-Egypt-Greece” (CSEG). These corridors aim to reactivate the Northwest, North, South, and Marine Silk Road during the period of the “Belt and Road” (B&R), reflect China’s overarching strategic goal of “furnishing land-sea internal and external linkage and achieving east-west mutual aid,” and possess important strategic values. To facilitate the comparison, this paper constructs a hierarchical model and evaluation index system for assessing the strategic value of international transport corridors (SVITC). From China’s perspective, this paper uses a fuzzy integral method with comprehensive weights to evaluate and compare the SVITC of the four international corridors as fuzzy integrals can handle interdependent indices and comprehensive weights can accommodate both subjective and objective weights. In the evaluation process, we first clarify the strategic attributes and characteristics of each corridor and identify its corresponding missions so that the overseas infrastructure projects along the four corridors can be carried out smoothly. By assessing their strategic values and ranking them accordingly, we offer the policy maker with useful information to prioritize investment opportunities and deploy limited resources in the construction of these corridors. Finally, this comparative study identifies the weaknesses and strengths in different corridors, which allow them to learn from each other, make joint progress, and strengthen linkages and integrations, thereby providing a set of feasible solutions for the construction of B&R international corridors

@Robust enhancing stability and fructose tolerance of sucrose phosphorylase by immobilization on Ni-NTA functionalized agarose microspheres for the biosynthesis of 2-alpha-glucosylglycerol

Sucrose phosphorylase (SPase) is a carbohydrate-active enzyme with outstanding potential for the biocatalytic conversion of sucrose and glycerol into 2-alpha-glucosylglycerol (2-alpha-GG) with attractive properties. However, poor stability, lack of appropriate immobilization strategy and serious inhibition of fructose by-products significantly restrict the industrial application of SPase. In this study, a new recombinant SPase from the Bifidobacterium Magian was specifically immobilized by agarose microspheres with Ni2+-nitrotriacetic acid for significantly enhancing its stability and fructose tolerance. Agarose immobilization greatly improved the stability of SPase. At 50 degrees C, the relative activity of the immobilized SPase (95%) was obviously greater than that of the free SPase (55%). Moreover, immobilized SPase exhibited excellent reusability and storage stability, retaining over 60% of its initial activity after 15 cycles, maintaining 70% relative activity after 15 days. It was first found that SPase immobilized by agamse still hold 98% activity even under 0.6 M fructose. Based on Raman spectrum analysis, agarose immobilization significantly enhanced the beta-sheet structures of SPase, which helped to maintain its efficient catalytic performance under extreme environment and high inhibitor concentration. Immobilized SPase based on agamse would have a brilliant future in the production of 2-alpha-GG

Luteolin Limits Infarct Size and Improves Cardiac Function after Myocardium Ischemia/Reperfusion Injury in Diabetic Rats

Background: The present study was to investigate the effects and mechanism of Luteolin on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in diabetic rats with myocardial ischemia/reperfusion (I/R) injury. Methodology/Principal Findings: Diabetic rats underwent 30 minutes of ischemia followed by 3 h of reperfusion. Animals were pretreated with or without Luteolin before coronary artery ligation. The severity of myocardial I/R induced LDH release, arrhythmia, infarct size, cardiac function impairment, cardiomyocyte apoptosis were compared. Western blot analysis was performed to elucidate the target proteins of Luteolin. The inflammatory cytokine production were also examined in ischemic myocardium underwent I/R injury. Our results revealed that Luteolin administration significantly reduced LDH release, decreased the incidence of arrhythmia, attenuated myocardial infarct size, enhanced left ventricular ejection fraction and decreased myocardial apoptotic death compared with I/R group. Western blot analysis showed that Luteolin treatment up-regulated anti-apoptotic proteins FGFR2 and LIF expression, increased BAD phosphorylation while decreased the ratio of Bax to Bcl-2. Luteolin treatment also inhibited MPO expression and inflammatory cytokine production including IL-6, IL-1a and TNF-a. Moreover, co-administration of wortmannin and Luteolin abolished the beneficial effects of Luteolin. Conclusions/Significance: This study indicates that Luteolin preserves cardiac function, reduces infarct size and cardiomyocyte apoptotic rate after I/R injury in diabetic rats. Luteolin exerts its action by up-regulating of anti-apoptoti

Multifunctional graphene-based nano-additives toward high-performance polymer nanocomposites with enhanced mechanical, thermal, flame retardancy and smoke suppressive properties

Despite many important industrial applications, the acrylonitrile–butadienestyrene copolymer (ABS) suffers from an inherent flammability, extremely hampering its practical use. Current flame retardants can effectively reduce the flammability issue but give rise to degraded mechanical and thermal properties of ABS. To address this intractable challenge, a graphene-derived flame retardant (Mo5/PN-rGO) was designed by introducing the functional elements (phosphorus, nitrogen and molybdate) onto the graphene oxides nanosheets. The resultant ABS nanocomposite containing 1.0 wt% of Mo5/PN-rGO exhibits a 28% increase in the tensile strength and a 58% enhancement in the Young’s modulus as compared to the ABS host. Furthermore, the glass transition temperature (Tg) increases by ca. 12 °C while the onset thermal decomposition temperature is significantly delayed by ca. 21 °C. In addition, the final ABS nanomaterial shows a 20% reduction in the total heat release and a 45% decrease in the total smoke production in comparison to the ABS bulk. This work paves a new way for the creation of high-performance flame retardants towards advanced flame-retardant polymer nanocomposites with expandable industrial applications

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro

Background/Aims: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. Methods: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated β-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. Results: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. Conclusion: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro