Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases

Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95–104, 2018. © 2017 Wiley Periodicals, Inc.     

Regulation of tumor angiogenesis by microRNAs: State of the art

MicroRNAs (miRNAs, miRs) are small (21–25 nucleotides) endogenous and noncoding RNAs involved in many cellular processes such as apoptosis, development, proliferation, and differentiation via binding to the 3′-untranslated region of the target mRNA and inhibiting its translation. Angiogenesis is a hallmark of cancer, which provides oxygen and nutrition for tumor growth while removing deposits and wastes from the tumor microenvironment. There are many angiogenesis stimulators, among which vascular endothelial growth factor (VEGF) is the most well known. VEGF has three tyrosine kinase receptors, which, following VEGF binding, initiate proliferation, invasion, migration, and angiogenesis of endothelial cells in the tumor environment. One of the tumor microenvironment conditions that induce angiogenesis through increasing VEGF and its receptors expression is hypoxia. Several miRNAs have been identified that affect different targets in the tumor angiogenesis pathway. Most of these miRNAs affect VEGF and its tyrosine kinase receptors expression downstream of the hypoxia-inducible Factor 1 (HIF-1). This review focuses on tumor angiogenesis regulation by miRNAs and the mechanism underlying this regulation.     

Toward community predictions: Multi‐scale modelling of mountain breeding birds' habitat suitability,landscape preferences,and environmental drivers

Across a large mountain area of the western Swiss Alps, we used occurrence data (presence‐only points) of bird species to find suitable modelling solutions and build reliable distribution maps to deal with biodiversity and conservation necessities of bird species at finer scales. We have performed a multi‐scale method of modelling, which uses distance, climatic, and focal variables at different scales (neighboring window sizes), to estimate the efficient scale of each environmental predictor and enhance our knowledge on how birds interact with their complex environment. To identify the best radius for each focal variable and the most efficient impact scale of each predictor, we have fitted univariate models per species. In the last step, the final set of variables were subsequently employed to build ensemble of small models (ESMs) at a fine spatial resolution of 100 m and generate species distribution maps as tools of conservation. We could build useful habitat suitability models for the three groups of species in the national red list. Our results indicate that, in general, the most important variables were in the group of bioclimatic variables including “Bio11” (Mean Temperature of Coldest Quarter), and “Bio 4” (Temperature Seasonality), then in the focal variables including “Forest”, “Orchard”, and “Agriculture area” as potential foraging, feeding and nesting sites. Our distribution maps are useful for identifying the most threatened species and their habitat and also for improving conservation effort to locate bird hotspots. It is a powerful strategy to improve the ecological understanding of the distribution of bird species in a dynamic heterogeneous environment.     

Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta

The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the active site.     

Life cycle assessment of winter road maintenance

Purpose

Winter road maintenance in the Nordic climate is demanding due to challenging weather conditions, high precipitation, and icy conditions. As a leading country in the transition to low-emission transport, Norway must work to reduce their emissions while providing a safe level of service through winter maintenance operations. This article investigates the environmental impacts of winter road maintenance (WRM) in Norway both today and under a climate change scenario predicted for 2050.

Methods

Life cycle assessment (LCA) is used to evaluate the environmental impact of the functional unit “average winter road maintenance in Norway on national and county roads per km.lane.” The ReCiPe (hierarchy) method was used to identify and categorize emissions related to WRM to show how different factors affect the system and to reveal hidden emissions hotspots. Real-time data from WRM vehicles were used to determine how fuel consumption is affected by gradient and weather. Producers and operators provided other relevant information on WRM vehicles. Official reports supplied information on deicer quantities used and the total distance driven by WRM vehicles in Norway.

Results and discussion

The quantity of deicer used is the main source of emissions contributing toward all impact categories. The effect of deicer is likely to be even higher in certain impact categories. The environmental impact of the deicer after application is not included. The representation of WRM in existing emissions data is limited despite the considerable amount of deicer applied and the long distances that WRM vehicles travel. The results document how energy use throughout the system is another important source of emissions. Various parameters, such as road gradient, vehicle properties, driver behavior, and weather, affect the fuel consumption of WRM vehicles, with weather being the most important of these.

Conclusions

Significant potential for emissions reductions from WRM was found, and WRM operations should be included in cold-climate road LCA studies. The environmental impacts of deicer application are especially high compared to the mechanical clearing of roads and contribute strongly to impact categories such as terrestrial, freshwater, and human toxicity and to the formation of particulate matter.

     

Integrated electronic detection of biomolecules

Electronics offers several unique opportunities for the detection and characterization of biomolecules such as oligonucleotides and proteins. Solid-state microfabrication technology, similar to that used to make integrated circuits, can be employed to make integrated electronic sensing systems that are capable of simultaneously detecting multiple molecules. Here, we review some of the capabilities afforded by electronics for rapid and sensitive detection of biomolecules and discuss a recent demonstration of a multi-marker electronic sensing system for detection of uropathogens in clinical samples.     

CD4+CD25+/highCD127low/- regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints—analysis of frequency and phenotype in synovial membrane,synovial fluid and peripheral blood

Introduction

CD4⁺CD25^+/highCD127^low/- regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients.

Methods

Treg frequency in a total of 40 patients (18 RA and 22 OA) matched for age and sex was assessed by flow cytometry. Functional status was assessed by analysis of cell surface markers representative of activation, memory and regulation.

Results

CD4⁺ T cells infiltrate the SM to higher frequencies in RA joints than in OA joints (P = 0.0336). In both groups, Tregs accumulate more within the SF and SM than concurrently in PB (P < 0.0001). Relative Treg frequencies were comparable in all compartments of RA and OA, but Treg concentration was significantly higher in the SM of RA patients (P = 0.025). Both PB and SM Tregs displayed a memory phenotype (CD45RO⁺RA^-), but significantly differed in activation status (CD69 and CD62L) and markers associated with Treg function (CD152, CD154, CD274, CD279 and GITR) with only minor differences between RA and OA.

Conclusions

Treg enrichment into the joint compartment is not specific to inflammatory arthritis, as we found that it was similarly enriched in OA. RA pathophysiology might not be due to a Treg deficiency, because Treg concentration in SM was significantly higher in RA. Synovial Tregs represent a distinct phenotype and are activated effector memory cells (CD62L^-CD69⁺), whereas peripheral Tregs are resting central memory cells (CD62L⁺CD69^-).     

D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet

LDL receptor-null (LDLR(-/-)) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR(-/-)mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their drinking water. The control mice (ScD-4F) developed glomerular changes, increased immunostaining for MCP-1/CCL2 chemokine, increased macrophage CD68 and F4/80 antigens, and increased oxidized phospholipids recognized by the EO6 monoclonal antibody in both glomerular and tublo-interstitial areas. All of these parameters were significantly reduced by D-4F treatment, approaching levels found in wild-type C57BL/6J or LDLR(-/-) mice fed a chow diet. Sterol-regulatory element binding protein-1c (SREBP-1c) mRNA levels and triglyceride levels were elevated in the kidneys of the control mice (ScD-4F) fed the WD compared with C57BL/6J and LDLR(-/-) mice on chow (P < 0.001 and P < 0.001, respectively) and compared with D-4F-treated mice on the WD (P < 0.01). There was no significant difference in plasma lipids, lipoproteins, glucose, blood pressure, or renal apoB levels between D-4F- and ScD-4F-treated mice. We conclude that D-4F reduced renal oxidized phospholipids, resulting in lower expression of SREBP-1c, which, in turn, resulted in lower triglyceride content and reduced renal inflammation.     

TGF-beta1 is a negative regulator of lymphatic regeneration during wound repair

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -beta1 (TGF-beta1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-beta1 on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-beta1 expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-beta1 on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-beta1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-beta1 to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-beta1 inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-beta1 caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-beta1 during wound repair resulted in lymphatic fibrosis and the coexpression of alpha-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-beta1 expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-beta1 expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-beta1 expression may be useful in promoting more rapid lymphatic regeneration.