Cardiac tissue engineering and regeneration using cell-cased therapy

Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells

Application of graphene nanoplatelets and graphene magnetite for the removal of emulsified oil from produced water.

Graphene and its magnetite derivative were used as adsorbents for removal of emulsified oil from produced water. The experimental parameters for maximum emulsified oil removal efficiency and effective regeneration of these adsorbents were determined. The best parameters in terms of dosage, contact time, pH, salinity and temperature were 3.00 g/L, 60.0 minutes, 10.0, 1500 ppm and 25.0{deg}C for graphene nanoplatelets, and 4.00 g/L, 30.0 minutes, 3.5, 1000 ppm and 25.0{deg}C, for graphene magnetite, respectively. Packed column studies were carried out utilizing graphene magnetite as adsorbent for the removal of oil from produced water. The packed column operation was assessed using Thomas, Yan et al., Clark, Bohart and Adams and Yoon and Nelson models. Thomas model was found to best describe the column experimental data. The column was regenerated using n-Hexane and reused several times for produced water treatment with negligible decrease in its initial capacity

Corrigendum: NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells.

Nature Communications 7 Article number: 11724 doi: 10.1038/ncomms11724(2016); Published: 25 May 2016; Updated: 2 August 2016. The affiliation details for Amiya K. Patra are incomplete in this Article. The correct affiliations are given below: Institute of Translational and Stratified Medicine, Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth Science Park, Research Way, Plymouth PL6 8BU, UK

Diurnal Variations of Mouse Plasma and Hepatic Bile Acid Concentrations as well as Expression of Biosynthetic Enzymes and Transporters

Diurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis.The current study depicted diurnal variations of individual BAs detected by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) in serum and livers collected from C57BL/6 mice fed a regular chow or a chow containing cholestyramine (resin). Circadian rhythms of mRNA of vital BA-related nuclear receptors, enzymes, and transporters in livers and ilea were determined in control- and resin-fed mice, as well as in farnesoid X receptor (FXR) null mice. The circadian profiles of BAs showed enhanced bacterial dehydroxylation during the fasting phase and efficient hepatic reconjugation of BAs in the fed phase. The resin removed more than 90% of BAs with β-hydroxy groups, such as muricholic acids and ursodeoxycholic acid, from serum and livers, but did not exert as significant influence on CA and CDCA in both compartments. Both resin-fed and FXR-null mouse models indicate that BAs regulate their own biosynthesis through the FXR-regulated ileal fibroblast growth factor 15. BA flux also influences the daily mRNA levels of multiple BA transporters.BA concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum. The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals

Coronary Artery Bypass grafting (CABG) versus Percutaneous Coronary Intervention (PCI) in the treatment of multivessel coronary disease

BackgroundRevascularization for patients who suffer multivessel coronary artery disease is a common procedure around the world. Taking United about 700,000 patients have multivessel coronary revascularization per year ¼ of these patients are diagnosed with diabetes. AimsTo summarize the current evidence that compare CABG to PCI in multivessel coronary disease‎ in form of ‎cardiac death, stroke, MI and unplanned devascularization.‎Methods This is a systematic review was carried out, including PubMed, Google Scholar, and EBSCO that examining randomized trials of treatment of multivessel coronary disease to summarize the major RCT concerning this topic.Results The review included five randomized studies that compare coronary artery bypass grafting and percutaneous coronary intervention. The findings showed that CABG show better result with less mortality rate.ConclusionThis review concluded that there revascularization in treating coronary artery disease could be conducted either by CABG or PCI, CABG show better result as it cause less death, MI and revascularization rates, but the usage of new additions such as second generation DES, can also improve the safety and efficacy of PCI when added to it

Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

The stock market responses of MENA countries to major global shocks

This thesis investigates whether the Middle East and North Africa (MENA) stock markets are susceptible to various global shocks, in particular of financial and geopolitical crises. The purpose of this research is to improve our understanding of the effect and consequences of turbulent global events on the MENA equity markets. The recent attempts of emerging markets, including the MENA equity markets to integrate have profound implications for asset pricing, diversification opportunities, and susceptibility to future global market turbulence and geopolitical unrest. Existing studies on MENA equity markets are characterized by a limited number of countries under examination; this thesis in contrast examines eleven equity markets from the MENA region. Furthermore, the majority of studies have failed to examine the country risk over time and their exposure to external shocks. This failure may stem from the fact that these markets are completely segmented and, therefore, considered safe haven for international investors. This raises a question of why the empirical literature does not provide comprehensive results to justify this supposed immunity. To solve this problem, this thesis employs several econometric models such as the Kalman filter, the Bai and Perron (2003) model, and the Johansen cointegration model, in addition to panel regression analysis. The first chapter examines the country beta instability using unconditional ICAPM. The chapter also examines the impact of the war on Iraq of 2003 using the statespace model and the Kalman filter approach. The outcomes reveal that the country betas are not stable and that the effect of the war on Iraq is limited to only four markets in the MENA region. The second chapter employs the multiple structural breakpoints model of Bai and Perron (2003). The results show that the country betas have coped with regional and global crises such as the Asian, Russian, and Turkish financial crises, and geopolitical unrest such as that brought on by the September 11, 2001 attacks. The Bai and Perron (2003) model shows that more MENA markets have experienced structural breaks due to the war on Iraq than what is found from the Kalman filter. The third chapter examines whether economic variables can explain the variation of country beta in a panel analysis. The results show that money supply and inflation have significant positive impacts on the country beta of MENA equity markets, whereas the accumulation of foreign currency reserves helps to alleviate it over time. In the fourth chapter, the thesis examines the integration of MENA equity markets with four major developed markets: Germany, Japan, UK, and USA, using the Johansen cointegration. The outcomes show that the integration of the MENA equity markets has significantly increased since the global financial crisis, indicating more market exposure to the global financial system