Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats.

PubMed

Kasote, D M; Badhe, Y S; Zanwar, A A; Hegde, M V; Deshmukh, K K

2012-07-01

to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats. Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl(4) in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl(4) intoxication. Hepatic lipid peroxidation elevated by CCl(4) intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl(4) -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl(4) -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). EPC-BF possesses the significant hepatoprotective activity against CCl(4) induced liver damage, which could be mediated through increase in antioxidant defenses.

Naringin enhances endothelial progenitor cell (EPC) proliferation and tube formation capacity through the CXCL12/CXCR4/PI3K/Akt signaling pathway.

PubMed

Zhao, Zhihu; Ma, Xinlong; Ma, Jianxiong; Sun, Xiaolei; Li, Fengbo; Lv, Jianwei

2018-04-25

Endothelial progenitor cells (EPCs) have been shown to be involved in the process of physiological neovascularization in vivo. Because increasing evidence has indicated that naringin, a major active ingredient in the Chinese herb Drynaria fortunei, can promote angiogenesis and inhibit endothelial cell apoptosis, our study was designed to determine the role of naringin in EPC proliferation and tube formation capacity and examine the potential mechanism for these effects. EPCs were isolated from bone marrow and treated with naringin. An MTT assay was used to investigate EPC proliferation and the tube formation capacity of these EPCs, which were seeded on Matrigel. The protein levels of CXCL12, its receptor (chemokine receptor 4 (CXCR4)) and a downstream signaling molecule (Akt and phosphorylated Akt (pAkt)) were examined using Western blotting. A CXCR4 antagonist (AMD3100) and a phosphatidylinositol 3-kinase (PI3K) antagonist (LY294002) were used to characterize the underlying mechanisms. The results showed that naringin-induced EPC proliferation reached a maximum at day 3 and that the optimal dose of naringin was 500 ng/ml. Treatment with naringin facilitated the EPC tube formation capacity and increased the levels of CXCL12, CXCR4 and pAkt (P < 0.05) relative to those in the control group. Moreover, the naringin-induced EPC tube formation capacity was significantly attenuated by AMD3100 or LY294002. In conclusion, we showed here that the naringin-enhanced EPC proliferation and tube formation were mediated by the activation of the PI3K/Akt signaling pathway via the CXCL12/CXCR4 axis, which suggests that naringin could serve as a new therapeutic medicine and has the potential to be applied for the treatment of ischemic disease. Copyright © 2018 Elsevier B.V. All rights reserved.

A Model for Sustainable Building Energy Efficiency Retrofit (BEER) Using Energy Performance Contracting (EPC) Mechanism for Hotel Buildings in China

NASA Astrophysics Data System (ADS)

Xu, Pengpeng

Hotel building is one of the high-energy-consuming building types, and retrofitting hotel buildings is an untapped solution to help cut carbon emissions contributing towards sustainable development. Energy Performance Contracting (EPC) has been promulgated as a market mechanism for the delivery of energy efficiency projects. EPC mechanism has been introduced into China relatively recently, and it has not been implemented successfully in building energy efficiency retrofit projects. The aim of this research is to develop a model for achieving the sustainability of Building Energy Efficiency Retrofit (BEER) in hotel buildings under the Energy Performance Contracting (EPC) mechanism. The objectives include: • To identify a set of Key Performance Indicators (KPIs) for measuring the sustainability of BEER in hotel buildings; • To identify Critical Success Factors (CSFs) under EPC mechanism that have a strong correlation with sustainable BEER project; • To develop a model explaining the relationships between the CSFs and the sustainability performance of BEER in hotel building. Literature reviews revealed the essence of sustainable BEER and EPC, which help to develop a conceptual framework for analyzing sustainable BEER under EPC mechanism in hotel buildings. 11 potential KPIs for sustainable BEER and 28 success factors of EPC were selected based on the developed framework. A questionnaire survey was conducted to ascertain the importance of selected performance indicators and success factors. Fuzzy set theory was adopted in identifying the KPIs. Six KPIs were identified from the 11 selected performance indicators. Through a questionnaire survey, out of the 28 success factors, 21 Critical Success Factors (CSFs) were also indentified. Using the factor analysis technique, the 21 identified CSFs in this study were grouped into six clusters to help explain project success of sustainable BEER. Finally, AHP/ANP approach was used in this research to develop a model to

Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT-MSCs.

PubMed

Tu, Tran Cam; Yamashita, Toshiharu; Kato, Toshiki; Nagano, Masumi; Trinh, Nhu Thuy; Hamada, Hiromi; Sato, Fujio; Ohneda, Kinuko; Matsuo-Takasaki, Mami; Ohneda, Osamu

2016-08-12

Mesenchymal stem cells (MSCs) are defined as multipotent cells that can give rise to various kinds of differentiated mesenchymal cells, and are thus considered to be useful for clinical therapy. However, the big hurdles of MSC therapy are the inability of MSCs to reach the appropriate tissues or sites with high efficiency and engraftment after transplantation. In this study, we investigated how adipose tissue-derived MSCs (AT-MSCs) improve their homing ability after intravenous injection. We previously found that human endothelial progenitor cells with low aldehyde dehydrogenase activity (Alde-Low EPCs) are suitable for the treatment of ischemic tissues. In addition, we demonstrated that microvesicles (MVs) derived from Alde-Low EPCs possessed the ability to improve the homing ability of non-functional Alde-High EPCs, resulting in wound healing. We initially transfected MVs derived from Alde-Low EPCs (EMVs) to human AT-MSCs, which were originally unable to cure ischemic tissues by intravenous transplantation. Remarkably, AT-MSC transfected EMVs dramatically repaired the ischemic skin flap compared with AT-MSC derived-MV (MMVs) transfected AT-MSCs or control AT-MSCs. We then found that the expression of CXCR4, an important chemokine receptor for cell migration, was highly elevated in EMV-transfected AT-MSCs. Moreover, AT-MSCs transfected with EMVs, but not control AT-MSCs, migrated to wound sites after intravenous injection. Consequently, CD45(+) inflammatory cells were successfully recruited at the wound sites after the injection of EMV-transfected AT-MSCs. These results demonstrate that EMVs are a useful source to improve the homing ability and wound healing ability of MSCs at the wound sites. Copyright © 2016 Elsevier Inc. All rights reserved.

Energy Efficiency Investments in Public Facilities - Developing a Pilot Mechanism for Energy Performance Contracts (EPCs) in Russia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, Meredydd; Roshchanka, Volha; Parker, Steven A.

: Russian public sector buildings tend to be very inefficient, which creates vast opportunities for savings. This report overviews the latest developments in the Russian legislation related to energy efficiency in the public sector, describes the major challenges the regulations pose, and proposes ways to overcome these challenges. Given Russia’s limited experience with energy performance contracts (EPCs), a pilot project can help test an implementation mechanism. This paper discusses how EPCs and other mechanisms can help harness energy savings opportunities in Russia in general, and thus, can be applicable to any Russian region.

Interoperability of Medication Classification Systems: Lessons Learned Mapping Established Pharmacologic Classes (EPCs) to SNOMED CT

PubMed Central

Nelson, Scott D; Parker, Jaqui; Lario, Robert; Winnenburg, Rainer; Erlbaum, Mark S.; Lincoln, Michael J.; Bodenreider, Olivier

2018-01-01

Interoperability among medication classification systems is known to be limited. We investigated the mapping of the Established Pharmacologic Classes (EPCs) to SNOMED CT. We compared lexical and instance-based methods to an expert-reviewed reference standard to evaluate contributions of these methods. Of the 543 EPCs, 284 had an equivalent SNOMED CT class, 205 were more specific, and 54 could not be mapped. Precision, recall, and F1 score were 0.416, 0.620, and 0.498 for lexical mapping and 0.616, 0.504, and 0.554 for instance-based mapping. Each automatic method has strengths, weaknesses, and unique contributions in mapping between medication classification systems. In our experience, it was beneficial to consider the mapping provided by both automated methods for identifying potential matches, gaps, inconsistencies, and opportunities for quality improvement between classifications. However, manual review by subject matter experts is still needed to select the most relevant mappings. PMID:29295234

Feasibility study for the Swaziland/Mozambique interconnector. EPC specifications. Export trade information

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1997-11-01

This study, conducted by Black & Veatch, was funded by the U.S. Trade and Development Agency. The report, produced for the Ministry of National Resources, Energy and Environment (MNRE) of Swaziland, determines the least cost capacity expansion option to meet the future power demand and system reliability criteria of Swaziland, with particular emphasis on the proposed Interconnector between Swaziland and Mozambique. Volume 3 contains EPC Specifications and is divided into the following divisions: (1) Commercial; (2) General Technical Requirements; (3) Transmission Line Technical Requirements; (4) Substation Technical Requirements; (5) Specifications.

Effects of Radiation and Long-Term Thermal Cycling on EPC 1001 Gallium Nitride Transistors

NASA Technical Reports Server (NTRS)

Patterson, Richard L.; Scheick, Leif; Lauenstein, Jean-Marie; Casey, Megan; Hammoud, Ahmad

2012-01-01

Electronics designed for use in NASA space missions are required to work efficiently and reliably under harsh environment conditions. These include radiation, extreme temperatures, and thermal cycling, to name a few. Data obtained on long-term thermal cycling of new un-irradiated and irradiated samples of EPC1001 gallium nitride enhancement-mode transistors are presented. This work was done by a collaborative effort including GRC, GSFC, and support the NASA www.nasa.gov 1 JPL in of Electronic Parts and Packaging (NEPP) Program

Current lineages of the epithelioma papulosum cyprini (EPC) cell line are contaminated with fathead minnow, Pimephales promelas, cells

USGS Publications Warehouse

Winton, J.; Batts, W.; DeKinkelin, P.; LeBerre, M.; Bremont, M.; Fijan, N.

2010-01-01

Initially established from proliferative skin lesions of the common carp, Cyprinus carpio L., the epithelioma papulosum cyprini (EPC) cell line (Fijan, Sulimanovic, Bearzotti, Muzinic, Zwillenberg, Chilmonczyk, Vautherot & de Kinkelin 1983) has become one of the most widely used tools for research on fish viruses and the diagnosis of fish viral diseases.

Single-event Effect Report for EPC Series eGaN FETs: Proton Testing for SEE and TNID Effects

NASA Technical Reports Server (NTRS)

Scheick, Leif

2014-01-01

Previous testing of the Enhanced Power Conversion (EPC) eGaN FETs showed sensitivity to destructive single-event effects (SEE) effects to heavy ions. The presence of tungsten plugs in the gate area raises concerns that the device may be vulnerable to SEE from protons. Irradiation of biased and unbiased devices with heavy ion has results in some damage suspected of being due to total non-ionizing dose (TNID). Proton irradiation is a better radiation type to study this effect. This study presents the results of testing device with protons for SEE and TNID. No SEE in the EPC2012 device, the most sensitive device to SEE, were seen with 53 MeV protons at several angles. The devices continued to function after 1.5 Mrad (Si) of proton dose with only a slight shift in parameters. These results suggest that gross TNID will not be a factor in using these devices nor suffer from SEE due to protons. However, the device should be tested at with 500 MeV protons to guarantee to immunity proton SEE.

Effects of Thermal Cycling on Control and Irradiated EPC 2nd Generation GaN FETs

NASA Technical Reports Server (NTRS)

Patterson, Richard L.; Scheick, Leif; Lauenstein, Jean-Marie; Casey, Megan; Hammoud, Ahmad

2013-01-01

The power systems for use in NASA space missions must work reliably under harsh conditions including radiation, thermal cycling, and exposure to extreme temperatures. Gallium nitride semiconductors show great promise, but information pertaining to their performance is scarce. Gallium nitride N-channel enhancement-mode field effect transistors made by EPC Corporation in a 2nd generation of manufacturing were exposed to radiation followed by long-term thermal cycling in order to address their reliability for use in space missions. Results of the experimental work are presented and discussed.

Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

PubMed

Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

2015-01-01

To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions and myocardial energy expenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of the MEE and cESS was significantly lowered in the treatment group than in the control group after the treatment at 2 weeks (P<0.01), the LVEF and FS was significantly increased in the treatment group than in the control group after the treatment at 4 months (P<0.01). EPC mobilization by G-CSF can effectively improve the cardiac functions, lessen ventricular remodeling and reduce myocardial energy expenditure in patients with heart failure after myocardial infarction.

German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients.

PubMed

Möbus, V; von Minckwitz, G; Jackisch, C; Lück, H-J; Schneeweiss, A; Tesch, H; Elling, D; Harbeck, N; Conrad, B; Fehm, T; Huober, J; Müller, V; Bauerfeind, I; du Bois, A; Loibl, S; Nekljudova, V; Untch, M; Thomssen, C

2017-08-01

Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine. Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1-14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4. From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3-4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% [95% confidence interval (CI) 79.5-83.6] versus 80.2% (95% CI 78.0-82.2). Hazard ratio (HR)=0.95 (95% CI 0.81-1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7-91.0) and 89.0% for iddEPC (95% CI 87.2-90.6), HR = 0.85 (95% CI 0.69-1.04, log-rank P = 0.10). Adding

The development of professional identity and the formation of teams in the Veterans Affairs Connecticut Healthcare System's Center of Excellence in Primary Care Education Program (CoEPCE).

PubMed

Meyer, Emily M; Zapatka, Susan; Brienza, Rebecca S

2015-06-01

The United States Department of Veterans Affairs Connecticut Healthcare System (VACHS) is one of five Centers of Excellence in Primary Care Education (CoEPCE) pilot sites. The overall goal of the CoEPCE program, which is funded by the Office of Academic Affiliations, is to develop and implement innovative approaches for training future health care providers in postgraduate education programs to function effectively in teams to provide exceptional patient care. This longitudinal study employs theoretically grounded qualitative methods to understand the effect of a combined nursing and medical training model on professional identity and team development at the VACHS CoEPCE site. The authors used qualitative approaches to understand trainees' experiences, expectations, and impressions of the program. From September 2011 to August 2012, they conducted 28 interviews of 18 trainees (internal medicine [IM] residents and nurse practitioners [NPs]) and subjected data to three stages of open, iterative coding. Major themes illuminate both the evolution of individual professional identity within both types of trainees and the dynamic process of group identity development. Results suggest that initially IM residents struggled to understand NPs' roles and responsibilities, whereas NP trainees doubted their ability to work alongside physicians. At the end of one academic year, these uncertainties disappeared, and what was originally artificial had transformed into an organic interprofessional team of health providers who shared a strong sense of understanding and trust. This study provides early evidence of successful interprofessional collaboration among NPs and IM residents in a primary care training program.

Performance analysis of different tuning rules for an isothermal CSTR using integrated EPC and SPC

NASA Astrophysics Data System (ADS)

Roslan, A. H.; Karim, S. F. Abd; Hamzah, N.

2018-03-01

This paper demonstrates the integration of Engineering Process Control (EPC) and Statistical Process Control (SPC) for the control of product concentration of an isothermal CSTR. The objectives of this study are to evaluate the performance of Ziegler-Nichols (Z-N), Direct Synthesis, (DS) and Internal Model Control (IMC) tuning methods and determine the most effective method for this process. The simulation model was obtained from past literature and re-constructed using SIMULINK MATLAB to evaluate the process response. Additionally, the process stability, capability and normality were analyzed using Process Capability Sixpack reports in Minitab. Based on the results, DS displays the best response for having the smallest rise time, settling time, overshoot, undershoot, Integral Time Absolute Error (ITAE) and Integral Square Error (ISE). Also, based on statistical analysis, DS yields as the best tuning method as it exhibits the highest process stability and capability.

Ceramide-1-phosphate regulates migration of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) – implications for tissue regeneration

PubMed Central

Kim, ChiHwa; Schneider, Gabriela; Abdel-Latif, Ahmed; Mierzejewska, Kasia; Sunkara, Manjula; Borkowska, Sylwia; Ratajczak, Janina; Morris, Andrew J.; Kucia, Magda; Ratajczak, Mariusz Z.

2012-01-01

Ceramide-1-phosphate (C1P) is a bioactive lipid that, in contrast to ceramide, is an anti-apoptotic molecule released from cells that are damaged and “leaky”. As reported recently, C1P promotes migration of hematopoietic cells. In the current paper, we tested the hypothesis that C1P released upon tissue damage may play an underappreciated role in chemoattraction of various types of stem cells and endothelial cells involved in tissue/organ regeneration. We show for a first time that C1P is upregulated in damaged tissues and chemoattracts BM-derived multipotent stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). Furthermore, compared to other bioactive lipids, C1P more potently chemoattracted human umbilical vein endothelial cells (HUVECs) and stimulated tube formation by these cells. C1P also promoted in vivo vascularization of Matrigel implants and stimulated secretion of stromal derived factor-1 (SDF-1) from BM-derived fibroblasts. Thus, our data demonstrate, for the first time, that C1P is a potent bioactive lipid released from damaged cells that potentially plays an important and novel role in recruitment of stem/progenitor cells to damaged organs and may promote their vascularization. PMID:23193025

Impaired function of endothelial progenitor cells in children with primary systemic vasculitis.

PubMed

Hong, Ying; Eleftheriou, Despina; Klein, Nigel J; Brogan, Paul A

2015-10-16

Previously, we demonstrated that children with active systemic vasculitis (SV) have higher circulating CD34 + CD133 + KDR+ endothelial progenitor cells (EPC); the function of these EPCs, and their relationship with disease activity in vasculitis remains largely unexplored. We hypothesized that although EPC numbers are higher, EPC function is impaired in active SV of the young. The aims of this study were therefore to: 1. investigate the relationship between disease activity and EPC function in children with SV; and 2. study the influence of systemic inflammation on EPC function by investigating the effects of hyperthermia and TNF-α on EPC function. We performed a cross-sectional study of unselected children with SV with different levels of disease activity attending a single center (Great Ormond Street Hospital, London) between October 2008 and December 2014. EPCs were isolated from peripheral blood of children with SV, and healthy child controls. EPC function was assessed by their potential to form colonies (EPC-CFU), and ability to form clusters and incorporate into human umbilical vein endothelial cell (HUVEC) vascular structures in matrigel. The effects of hyperthermia and TNF-α on EPC function were also studied. Twenty children, median age 12-years (5-16.5; nine males) were studied. EPC-CFU and the number of EPC clusters formed on matrigel were significantly reduced in children with active vasculitis compared with healthy controls (p = 0.02 for EPC-CFU; p = 0.01 for EPC cluster formation). Those with active vasculitis had lower EPC-CFU and EPC cluster formation than those with inactive disease, although non-significantly so. In addition, EPC incorporation into matrigel HUVEC networks was lower in children with SV compared with healthy children, irrespective of disease activity. Ex-vivo pre-treatment of EPC with hyperthermia impaired EPC function; TNF-α down-regulated EPC expression of CD18/CD11b and resulted in decreased incorporation into

Overexpression of hypoxia-inducible factor-1 alpha improves vasculogenesis-related functions of endothelial progenitor cells.

PubMed

Kütscher, Christian; Lampert, Florian M; Kunze, Mirjam; Markfeld-Erol, Filiz; Stark, G Björn; Finkenzeller, Günter

2016-05-01

Postnatal vasculogenesis is mediated by mobilization of endothelial progenitor cells (EPCs) from bone marrow and homing to ischemic tissues. This feature emphasizes this cell type for cell-based therapies aiming at the improvement of neovascularization in tissue engineering applications and regenerative medicine. In animal models, it was demonstrated that implantation of EPCs from cord blood (cbEPCs) led to the formation of a complex functional neovasculature, whereas EPCs isolated from adult peripheral blood (pbEPCs) showed a limited vasculogenic potential, which may be attributed to age-related dysfunction. Recently, it was demonstrated that activation of hypoxia-inducible factor-1α (Hif-1α) improves cell functions of progenitor cells of mesenchymal and endothelial origin. Thus, we hypothesized that overexpression of Hif-1α may improve the vasculogenesis-related phenotype of pbEPCs. In the present study, we overexpressed Hif-1α in pbEPCs and cbEPCs by using recombinant adenoviruses and investigated effects on stem cell- and vasculogenesis-related cell parameters. Overexpression of Hif-1α enhanced proliferation, invasion, cell survival and in vitro capillary sprout formation of both EPC populations. Migration was increased in cbEPCs upon Hif-1α overexpression, but not in pbEPCs. Cellular senescence was decreased in pbEPCs, while remained in cbEPCs, which showed, as expected, intrinsically a dramatically lower senescent phenotype in relation to pbEPCs. Similarly, the colony-formation capacity was much higher in cbEPCs in comparison to pbEPCs and was further increased by Hif-1α overexpression, whereas Hif-1α transduction exerted no significant influence on colony formation of pbEPCs. In summary, our experiments illustrated multifarious effects of Hif-1α overexpression on stem cell and vasculogenic parameters. Therefore, Hif-1α overexpression may represent a therapeutic option to improve cellular functions of adult as well as postnatal EPCs. Copyright �

FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs

PubMed Central

Nakayoshi, Takaharu; Sasaki, Ken-ichiro; Kajimoto, Hidemi; Koiwaya, Hiroshi; Ohtsuka, Masanori; Ueno, Takafumi; Chibana, Hidetoshi; Itaya, Naoki; Sasaki, Masahiro; Yokoyama, Shinji; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

2014-01-01

The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. PMID:24663349

Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of akt and increased angiogenesis.

PubMed

Yao, Yuyu; Sheng, Zulong; Li, YeFei; Fu, Cong; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

2013-05-01

Endothelial progenitor cells (EPCs) have been shown to enhance angiogenesis not only by incorporating into the vasculature but also by secreting cytokines, thereby serving as an ideal vehicle for gene transfer. As tissue kallikrein (TK) has pleiotropic effects in inhibiting apoptosis and oxidative stress, and promoting angiogenesis, we evaluated the salutary potential of kallikrein-modified human EPCs (hEPCs; Ad.hTK-hEPCs) after acute myocardial infarction (MI). We genetically modified hEPCs with a TK gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a nude mouse left anterior descending ligation model. hEPCs were manipulated to overexpress the TK gene. In vitro, the antiapoptotic and paracrine effects were assessed under oxidative stress. TK protects hEPCs from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and -9, induction of Akt phosphorylation, and secretion of vascular endothelial growth factor. In vivo, the Ad.hTK-hEPCs were transplanted after MI via intracardiac injection. The surviving cells were tracked after transplantation using near-infrared optical imaging. Left ventricular (LV) function was evaluated by transthoracic echocardiography. Capillary density was quantified using immunohistochemical staining. Engrafted Ad.hTK-hEPCs exhibited advanced protection against ischemia by increasing LV ejection fraction. Compared with Ad.Null-hEPCs, transplantation with Ad.hTK-hEPCs significantly decreased cardiomyocyte apoptosis in association with increased retention of transplanted EPCs in the myocardium. Capillary density and arteriolar density in the infarct border zone was significantly higher in Ad.hTK-hEPC-transplanted mice than in Ad.Null-hEPC-treated mice. Transplanted hEPCs were clearly incorporated into CD31(+) capillaries. These results indicate that implantation of kallikrein-modified EPCs in the heart provides advanced benefits in protection against ischemia-induced MI by

Comparative transcriptomic analysis of endothelial progenitor cells derived from umbilical cord blood and adult peripheral blood: Implications for the generation of induced pluripotent stem cells.

PubMed

Gao, Xiugong; Yourick, Jeffrey J; Sprando, Robert L

2017-12-01

Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs. We also explored differences between CB-EPCs and PB-EPCs at the molecular and cellular levels through a combination of transcriptomic analysis and cell biology techniques. EPC colonies in CB-MNCs emerged 5-7days earlier, were 3-fold higher in number, and consistently larger in size than in PB-MNCs. Similarly, iPSC colonies generated from CB-EPCs was 2.5-fold higher in number than from PB-EPCs, indicating CB-EPCs have a higher reprogramming efficiency than PB-EPCs. Transcriptomic analysis using microarrays found a total of 1133 genes differentially expressed in CB-EPCs compared with PB-EPCs, with 675 genes upregulated and 458 downregulated. Several canonical pathways were impacted, among which the human embryonic stem cell pluripotency pathway was of particular interest. The differences in the gene expression pattern between CB-EPCs and PB-EPCs provide a molecular basis for the discrepancies seen in their derivation and reprogramming efficiencies, and highlight the advantages of using CB as the cellular source for the generation of iPSCs and their derivative tissues for ethnic-related toxicological applications. Published by Elsevier B.V.

Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function.

PubMed

Jung, Seok Yun; Choi, Jin Hwa; Kwon, Sang-Mo; Masuda, Haruchika; Asahara, Takayuki; Lee, You-Mie

2012-05-01

Endothelial progenitor cells (EPCs) contribute to the tumor vasculature during tumor progression. Decursin isolated from the herb Angelica gigas is known to possess potent anti-inflammatory activities. Recently, we reported that decursin is a novel candidate for an angiogenesis inhibitor [Jung et al., 2009]. In this study, we investigated whether decursin regulates EPC differentiation and function to inhibit tumor vasculogenesis. We isolated AC133+ cells from human cord blood and decursin significantly decreased the number of EPC colony forming units of human cord blood-derived AC133+ cells that produce functional EPC progenies. Decursin dose-dependently decreased the cell number of EPC committing cells as demonstrated by EPC expansion studies. Decursin inhibited EPC differentiation from progenitor cells into spindle-shaped EPC colonies. Additionally, decursin inhibited proliferation and migration of early EPCs isolated from mouse bone marrow. Furthermore, decursin suppressed expression of angiopoietin-2, angiopoietin receptor Tie-2, Flk-1 (vascular endothelial growth factor receptor-2), and endothelial nitric oxide synthase in mouse BM derived EPCs in a dose-dependent manner. Decursin suppressed tube formation ability of EPCs in collaboration with HUVEC. Decursin (4 mg/kg) inhibited tumor-induced mobilization of circulating EPCs (CD34 + /VEGFR-2+ cells) from bone marrow and early incorporation of Dil-Ac-LDL-labeled or green fluorescent protein (GFP)+ EPCs into neovessels of xenograft Lewis lung carcinoma tumors in wild-type- or bone-marrow-transplanted mice. Accordingly, decursin attenuated EPC-derived endothelial cells in neovessels of Lewis lung carcinoma tumor masses grown in mice. Together, decursin likely affects EPC differentiation and function, thereby inhibiting tumor vasculogenesis in early tumorigenesis. Copyright © 2012 Wiley Periodicals, Inc.

Adoption of electronic prescribing for controlled substances among providers and pharmacies.

PubMed

Hufstader Gabriel, Meghan; Yang, Yi; Vaidya, Varun; Wilkins, Tricia Lee

2014-11-01

Electronic prescribing for Schedule II through V controlled substances was legalized in the United States by the Drug Enforcement Administration in June 2010. However, little information exists about adoption and use of the electronic prescribing of controlled substances (EPCS) at the national level. Therefore, the objective of this study is to present the first information about national trends surrounding the adoption and use of the newly allowed EPCS by providers and pharmacies in the United States. Trends of EPCS adoption and use were examined for the number of EPCS, number of pharmacies enabled to accept EPCS, and the number of providers prescribing controlled substances electronically. Using nationally representative transactional Surescripts data from July 2012 to December 2013, we examined EPCS trends. During the study period, the total number of EPCS increased from 1535 to 52,423, and the number and percentage of all pharmacies enabled for EPCS increased from 8768 (13%) to 20,498 pharmacies (30%). The proportion of all providers prescribing controlled substances electronically is currently 1%, but increasing steadily each month. There is a positive national growth for EPCS in pharmacy preparedness to accept EPCS, the number of EPCS prescriptions sent each month, and the number of providers with the ability to send EPCS.

Immobilization and Stabilization of Acylase on Carboxylated Polyaniline Nanofibers for Highly Effective Antifouling Application via Quorum Quenching.

PubMed

Lee, Jeongjoon; Lee, Inseon; Nam, Jahyun; Hwang, Dong Soo; Yeon, Kyung-Min; Kim, Jungbae

2017-05-10

Acylase (AC) was immobilized and stabilized on carboxylated polyaniline nanofibers (cPANFs) for the development of antifouling nanobiocatalysts with high enzyme loading and stability. AC was immobilized via three different approaches: covalent attachment (CA), enzyme coating (EC), and magnetically separable enzyme precipitate coating (Mag-EPC). The enzyme activity per unit weight of cPANFs with Mag-EPC was 75 and 300 times higher than that of those with CA and EC, respectively, representing improved enzyme loading in the form of Mag-EPC. After incubation under shaking at 200 rpm for 20 days, Mag-EPC maintained 55% of its initial activity, whereas CA and EC showed 3 and 16% of their initial activities, respectively. The antifouling of highly loaded and stable Mag-EPC against the biofouling/biofilm formation of Pseudomonas aeruginosa was tested under static- and continuous-flow conditions. Biofilm formation in the presence of 40 μg/mL Mag-EPC under static condition was 5 times lower than that under control condition with no addition of Mag-EPC. Under continuous membrane filtration, Mag-EPC delayed the increase of transmembrane pressure (TMP) more effectively as the concentration of added Mag-EPC increased. When separating Mag-EPC and membranes in two different vessels under internal circulation of the culture solution, Mag-EPC maintained a higher permeability than the control with no Mag-EPC addition. It was also confirmed that the addition of Mag-EPC reduced the generation of N-acyl homoserine lactone (AHL) autoinducers. This result reveals that the inhibition of biofilm formation and biofouling in the presence of Mag-EPC is due to the hydrolysis of AHL autoinducers, catalyzed by the immobilized and stabilized AC in the form of Mag-EPC. Mag-EPC of AC with high enzyme loadings and improved stability has demonstrated its great potential as an antifouling agent by reducing biofilm formation and membrane biofouling based on "enzymatic quorum quenching" of autoinducers.

Concise Review: Endothelial Progenitor Cells in Regenerative Medicine: Applications and Challenges

PubMed Central

Chong, Mark Seow Khoon; Ng, Wei Kai

2016-01-01

Endothelial progenitor cells (EPCs) are currently being studied as candidate cell sources for revascularization strategies. Significant advances have been made in understanding the biology of EPCs, and preclinical studies have demonstrated the vasculogenic, angiogenic, and beneficial paracrine effects of transplanted EPCs in the treatment of ischemic diseases. Despite these promising results, widespread clinical acceptance of EPCs for clinical therapies remains hampered by several challenges. The present study provides a concise summary of the different EPC populations being studied for ischemic therapies and their known roles in the healing of ischemic tissues. The challenges and issues surrounding the use of EPCs and the current strategies being developed to improve the harvest efficiency and functionality of EPCs for application in regenerative medicine are discussed. Significance Endothelial progenitor cells (EPCs) have immense clinical value for cardiovascular therapies. The present study provides a concise description of the EPC subpopulations being evaluated for clinical applications. The current major lines of investigation involving preclinical and clinical evaluations of EPCs are discussed, and significant gaps limiting the translation of EPCs are highlighted. The present report could be useful for clinicians and clinical researchers with interests in ischemic therapy and for basic scientists working in the related fields of tissue engineering and regenerative medicine. PMID:26956207

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

PubMed

Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

2015-03-01

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

An affordable method to obtain cultured endothelial cells from peripheral blood

PubMed Central

Bueno-Betí, Carlos; Novella, Susana; Lázaro-Franco, Macarena; Pérez-Cremades, Daniel; Heras, Magda; Sanchís, Juan; Hermenegildo, Carlos

2013-01-01

The culture of endothelial progenitor cells (EPC) provides an excellent tool to research on EPC biology and vascular regeneration and vasculogenesis. The use of different protocols to obtain EPC cultures makes it difficult to obtain comparable results in different groups. This work offers a systematic comparison of the main variables of most commonly used protocols for EPC isolation, culture and functional evaluation. Peripheral blood samples from healthy individuals were recovered and mononuclear cells were cultured. Different recovery and culture conditions were tested: blood volume, blood anticoagulant, coating matrix and percentage of foetal bovine serum (FBS) in culture media. The success of culture procedure, first colonies of endothelial cells appearance time, correlation with number of circulating EPC (cEPC) and functional comparison with human umbilical vein endothelial cells (HUVEC) were studied. The use of heparin, a minimum blood volume of 30 ml, fibronectin as a coating matrix and endothelial growing media-2 supplemented with 20% FBS increased the success of obtaining EPC cultures up to 80% of the processed samples while reducing EPC colony appearance mean time to a minimum of 13 days. Blood samples exhibiting higher cEPC numbers resulted in reduced EPC colony appearance mean time. Cells isolated by using this combination were endothelial cell-like EPCs morphological and phenotypically. Functionally, cultured EPC showed decreased growing and vasculogenic capacity when compared to HUVEC. Thus, above-mentioned conditions allow the isolation and culture of EPC with smaller blood volumes and shorter times than currently used protocols. PMID:24118735

Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.

PubMed

Huang, Po-Hsun; Chen, Yung-Hsiang; Tsai, Hsiao-Ya; Chen, Jia-Shiong; Wu, Tao-Cheng; Lin, Feng-Yen; Sata, Masataka; Chen, Jaw-Wen; Lin, Shing-Jong

2010-04-01

Red wine (RW) consumption has been associated with a reduction of cardiovascular events, but limited data are available on potential mediating mechanisms. This study tested the hypothesis that intake of RW may promote the circulating endothelial progenitor cell (EPC) level and function through enhancement of nitric oxide bioavailability. Eighty healthy, young subjects were randomized and assigned to consume water (100 mL), RW (100 mL), beer (250 mL), or vodka (30 mL) daily for 3 weeks. Flow cytometry was used to quantify circulating EPC numbers, and in vitro assays were used to evaluate EPC functions. After RW ingestion, endothelial function determined by flow-mediated vasodilation was significantly enhanced; however, it remained unchanged after water, beer, or vodka intake. There were significantly increased numbers of circulating EPC (defined as KDR(+)CD133(+), CD34(+)CD133(+), CD34(+)KDR(+)) and EPC colony-forming units only in the RW group (all P<0.05). Only RW ingestion significantly enhanced plasma levels of nitric oxide and decreased asymmetrical dimethylarginine (both P<0.01). Incubation of EPC with RW (but not beer or ethanol) and resveratrol in vitro attenuated tumor necrosis factor-alpha-induced EPC senescence and improved tumor necrosis factor-alpha-suppressed EPC functions and tube formation. Incubation with nitric oxide donor sodium nitroprusside significantly ameliorated the inhibition of tumor necrosis factor-alpha on EPC proliferation, but incubation with endothelial nitric oxide synthase inhibitor l-NAME and PI3K inhibitor markedly attenuated the effect of RW on EPC proliferation. The intake of RW significantly enhanced circulating EPC levels and improved EPC functions by modifying nitric oxide bioavailability. These findings may help explain the beneficial effects of RW on the cardiovascular system. This study demonstrated that a moderate intake of RW can enhance circulating levels of EPC in healthy subjects by increasing nitric oxide

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells

PubMed Central

Hakami, Nora Y.; Ranjan, Amaresh K.; Hardikar, Anandwardhan A.; Dusting, Greg J.; Peshavariya, Hitesh M.

2017-01-01

Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery. NOX4 gene and protein expression in EPCs were measured by real time-PCR and Western blot analysis respectively. NOX4 gene expression was inhibited using an adenoviral vector expressing human NOX4 shRNA (Ad-NOX4i). H2O2 production was measured by Amplex red assay. EPC migration was evaluated using a transwell migration assay. EPC proliferation and viability were measured using trypan blue counts. Results: Inhibition of NOX4 using Ad-NOX4i reduced Nox4 gene and protein expression as well as H2O2 formation in EPCs. Inhibition of NOX4-derived H2O2 decreased both proliferation and migration of EPCs. Interestingly, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) decreased NOX4 expression and reduced survival of EPCs. However, the survival of EPCs was further diminished by TNF-α in NOX4-knockdown cells, suggesting that NOX4 has a protective role in EPCs. Conclusion: These findings suggest that NOX4-type NADPH oxidase is important for proliferation and migration functions of EPCs and protects against pro-inflammatory cytokine induced EPC death. These properties of NOX4 may facilitate the efficient function of EPCs which is vital for successful neovascularization. PMID:28386230

Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus.

PubMed

Hamed, Saher; Brenner, Benjamin; Abassi, Zaid; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

2010-09-01

Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Atrial Natriuretic Peptide Accelerates Human Endothelial Progenitor Cell-Stimulated Cutaneous Wound Healing and Angiogenesis.

PubMed

Lee, Tae Wook; Kwon, Yang Woo; Park, Gyu Tae; Do, Eun Kyoung; Yoon, Jung Won; Kim, Seung-Chul; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Jae Ho

2018-05-26

Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs. Furthermore, small interfering RNA-mediated silencing of natriuretic peptide receptor-1, which is a receptor for ANP, abrogated ANP-induced migration, tube formation, and proliferation of EPCs. In a murine cutaneous wound model, administration of either ANP or EPCs had no significant effect on cutaneous wound healing or angiogenesis in vivo, whereas the co-administration of ANP and EPCs synergistically potentiated wound healing and angiogenesis. In addition, ANP promoted the survival and incorporation of transplanted EPCs into newly formed blood vessels in wounds. These results suggest ANP accelerates EPC-mediated cutaneous wound healing by promoting the angiogenic properties and survival of transplanted EPCs. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner.

PubMed

Abou-Saleh, Haissam; Hachem, Ahmed; Yacoub, Daniel; Gillis, Marc-Antoine; Merhi, Yahye

2015-05-07

The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel(-/-)) mice and their wild-type (WT) counterparts. EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel(-/-) mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel(-/-) mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel(-/-) mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel(-/-) mice as compared to WT mice. This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.

Circulating Endothelial Progenitor Cells Present an Inflammatory Phenotype and Function in Patients With Alcoholic Liver Cirrhosis

PubMed Central

Kaur, Savneet; Sehgal, Rashi; Shastry, Saggere M.; McCaughan, Geoffrey; McGuire, Helen M.; Fazekas St de Groth, Barbara; Sarin, Shiv; Trehanpati, Nirupma; Seth, Devanshi

2018-01-01

Background and Aim: Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Methods: Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients (n = 7) and healthy controls (HC, n = 7). A comprehensive characterization of circulating EPCs using more than 30 phenotype markers was performed by mass cytometer time of flight (CyTOF) in an independent cohort of age and gender matched ALC patients (n = 4) and controls (n = 5). Ex vivo cultures of circulating EPCs from ALC patients (n = 20) and controls (n = 18) were also tested for their functions, including colony formation, LDL uptake, lectin binding and cytokine secretion (ELISA). Results: Three distinct populations of circulating EPCs (CD34+CD133+CD31+) were identified, classified on their CD45 expression (negative: CD45−; intermediate: CD45int; high: CD45hi). CD45int and CD45hi EPCs significantly increased in ALC patients compared to controls (p-val = 0.006). CyTOF data showed that CD45hi EPCs were distinct from CD45− and CD45int EPCs, with higher expression of T cell and myeloid markers, including CD3, CD4, HLA-DR, and chemokine receptors, CCR2, CCR5, CCR7, and CX3CR1. Similar to circulating EPCs, percentage of CD45hiCD34+CD31+ EPCs in ex-vivo cultures from patients, were significantly higher compared to controls (p < 0.05). Cultured EPCs from patients also showed increased LDL uptake, lectin binding and release of TNF-alpha, RANTES, FGF-2, and VEGF. Conclusions: We report the first extensive characterization of circulating human EPCs with distinct EPC subtypes. Increase in CD45hi EPC subtype in ALC patients with enhanced functions

Occludin as a functional marker of vascular endothelial cells on tube-forming activity.

PubMed

Kanayasu-Toyoda, Toshie; Ishii-Watabe, Akiko; Kikuchi, Yutaka; Kitagawa, Hiroko; Suzuki, Hiroko; Tamura, Hiroomi; Tada, Minoru; Suzuki, Takuo; Mizuguchi, Hiroyuki; Yamaguchi, Teruhide

2018-02-01

Cell therapy using endothelial progenitor cells (EPCs) is a promising strategy for the treatment of ischemic diseases. Two types of EPCs have been identified: early EPCs and late EPCs. Late EPCs are able to form tube structure by themselves, and have a high proliferative ability. The functional marker(s) of late EPCs, which relate to their therapeutic potential, have not been fully elucidated. Here we compared the gene expression profiles of several human cord blood derived late EPC lines which exhibit different tube formation activity, and we observed that the expression of occludin (OCLN) in these lines correlated with the tube formation ability, suggesting that OCLN is a candidate functional marker of late EPCs. When OCLN was knocked down by transfecting siRNA, the tube formation on Matrigel, the S phase + G 2 /M phase in the cell cycle, and the spheroid-based sprouting of late EPCs were markedly reduced, suggesting the critical role of OCLN in tube formation, sprouting, and proliferation. These results indicated that OCLN plays a novel role in neovascularization and angiogenesis. © 2017 Wiley Periodicals, Inc.

Endothelial Progenitor Cells and Kidney Diseases.

PubMed

Ozkok, Abdullah; Yildiz, Alaattin

2018-05-10

Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs. © 2018 The Author(s). Published by S. Karger AG, Basel.

Multilayer Membranes of Glycosaminoglycans and Collagen I Biomaterials Modulate the Function and Microvesicle Release of Endothelial Progenitor Cells.

PubMed

Dai, Bingyan; Pan, Qunwen; Li, Zhanghua; Zhao, Mingyan; Liao, Xiaorong; Wu, Keng; Ma, Xiaotang

2016-01-01

Multilayer composite membrane of biomaterials can increase the function of adipose stem cells or osteoprogenitor cells. Recent evidence indicates endothelial progenitor cells (EPCs) and EPCs released microvesicles (MVs) play important roles in angiogenesis and vascular repair. Here, we investigated the effects of biomaterial multilayer membranes of hyaluronic acid (HA) or chondroitin sulfate (CS) and Collagen I (Col I) on the functions and MVs release of EPCs. Layer-by-layer (LBL) technology was applied to construct the multilayer composite membranes. Four types of the membranes constructed by adsorbing either HA or CS and Col I alternatively with different top layers were studied. The results showed that all four types of multilayer composite membranes could promote EPCs proliferation and migration and inhibit cell senility, apoptosis, and the expression of activated caspase-3. Interestingly, these biomaterials increased the release and the miR-126 level of EPCs-MVs. Moreover, the CS-Col I membrane with CS on the top layer showed the most effects on promoting EPCs proliferation, EPCs-MV release, and miR-126 level in EPCs-MVs. In conclusion, HA/CS and Collagen I composed multilayer composite membranes can promote EPCs functions and release of miR-126 riched EPCs-MVs, which provides a novel strategy for tissue repair treatment.

Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

PubMed

Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

2016-10-15

Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Effect of Alloxan-induced diabetes mellitus on the functions of bone marrow-derived and circulating endothelial progenitor cells].

PubMed

Tan, Q; Li, G P; Wang, Q S; Zheng, C H; Zhang, S Y

2017-07-25

Objective: To explore whether diabetes mellitus (DM) impairs functions of bone marrow-derived endothelial progenitor cells (BM-EPC) and circulating EPC. Methods: Diabetic model of rabbit was induced by Alloxan injection and the rabbits were then randomly divided into three groups: BM-EPC group, circulating EPC group, and DM group, with six rabbits in each group. Another 6 normal rabbits were enrolled as normal control group as well. 8 weeks later, BM-EPC and circulating EPC from diabetic and healthy rabbits were isolated and cultured. Colony number, proliferation, adhesion and tube formation function were detected. Exogenous diabetic BM-EPC and circulating EPC were analyzed for therapeutic efficacy in acute ischemia model of diabetic rabbits. Left ventricular (LV) function was assessed using Echocardiography. Capillary density and fibrosis area were evaluated by confocal laser scanning microscope (CLSM) and Masson-trichrome staining. The mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was analyzed using real-time quantitive PCR. Results: Colony number, proliferation, adhesion and tube formation function of diabetic circulating EPC were significantly reduced compared with healthy rabbits. DM impaired tube-forming ability of BM-EPC, but did not influence colony number, proliferation and adhesion function. Compared with circulating EPC and control group, BM-EPC group had fewer fibrosis area (6.98%±0.94% vs 13.03%±2.97% and 15.84%±4.74%, both P =0.001), higher capillary density [(792±87) vs (528±71) and (372±77) vessels/mm(2,) both P <0.001], higher mRNA expression of VEGF (6.25±2.33 vs 2.19±1.01 and 1.55±0.52, both P <0.001) and bFGF (6.38±2.65 vs 1.24±0.76 and 1.18±0.82, both P <0.001), higher left ventricular ejection fraction (LVEF) (61%±4% vs 47%±5% and 50%±10%, both P <0.05). Conclusions: DM not only impaired functions of circulating EPC, but also influenced tube formation function of BM-EPC

Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation.

PubMed

Paul, Jonathan D; Powell, Tiffany M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; Carlow, Andrea; Annavajjhala, Vidhya; Shiva, Sruti; Dejam, Andre; Gladwin, Mark T; McCoy, J Philip; Zalos, Gloria; Press, Beverly; Murphy, Mandy; Hill, Jonathan M; Csako, Gyorgy; Waclawiw, Myron A; Cannon, Richard O

2007-01-01

We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function. Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy > or = 1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133/VEGFR-2 cells) and assayed in culture for EPC colony-forming units (CFUs). In 23 patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite was measured in blood as an indicator of intravascular nitric oxide. Endothelial progenitor cells increased from 35 +/- 5 to 63 +/- 10 cells/mL, and EPC-CFUs increased from 0.9 +/- 0.2 to 3.1 +/- 0.6 per well (both P < .01), but 11 patients had no increase in either measure. Those patients whose EPCs increased from baseline showed significant increases in nitrite and reduction in annexin-V staining (both P < .01) versus no change in patients without increase in EPCs. Over the course of the program, EPCs increased prior to increase in nitrite in the blood. Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood.

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

PubMed

Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

2008-08-01

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

PubMed

Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

2014-01-01

Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

PubMed

Wang, Pei; Yang, Xi; Zhang, Zheng; Song, Jie; Guan, Yun-Feng; Zou, Da-Jin; Miao, Chao-Yu

2016-06-01

The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood

Elevated endothelial progenitor cells during painful sickle cell crisis.

PubMed

van Beem, Rachel T; Nur, Erfan; Zwaginga, Jaap Jan; Landburg, Precious P; van Beers, Eduard J; Duits, Ashley J; Brandjes, Dees P; Lommerse, Ingrid; de Boer, Hetty C; van der Schoot, C Ellen; Schnog, John-John B; Biemond, Bart J

2009-09-01

Circulating endothelial progenitor cells (EPCs) counts were determined in patients with sickle cell disease (SCD) to elucidate their role in SCD-related ischemia-induced angiogenesis and reendothelialization. Circulating EPC counts (KDR(+)/CD34(+)/Cd45(dim) cells) and their relation to serum levels of EPC mobilizing growth factors erythropoietin, vascular endothelial growth factor, and interleukin-8 were investigated in SCD patients during asymptomatic state (n=66) and painful crisis (n=36) and compared to healthy controls (n=13). EPC counts were comparable between controls (0; range, 0-1.1 cells/mL) and patients (0; range, 0-0 cells/mL) in asymptomatic state, but were significantly higher during painful crisis (41.7; range, 0-186 cells/mL; p<0.05). Also in a paired analysis of 12 patients who were included both during asymptomatic state and painful crisis, EPC counts increased significantly during painful crisis (from 0 [range, 0-0] to 26 [range, 0-149 cell/mL; p<0.05). EPC counts were not related to any of the measured growth factors. The higher EPC counts during painful crisis might indicate a role for EPC mobilization in reendothelialization. As a relationship of EPCs with the established mobilizing growth factors, measured in this study was not observed, the mechanism of EPC mobilization in SCD remains to be elucidated.

Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study.

PubMed

Huang, Junhao; Wang, Shen; Xu, Fengpeng; Wang, Dan; Yin, Honggang; Lai, Qinhao; Liao, Jingwen; Hou, Xiaohui; Hu, Min

2017-01-01

Circulating endothelial progenitor cells (EPCs) correlate negatively with obesity. Previous studies have shown that exercise significantly restores circulating EPC levels in obese people; however, the underlying mechanisms have not been elucidated. Recently, irisin has been reported to have a critical role in the regulation of EPCs. This exercise-induced myokine has been demonstrated to play a therapeutic role in obesity. In this study, we hypothesized that the increase in circulating irisin may form a link with increasing EPC levels in obese people after exercise. Seventeen obese adults completed an 8-week program of combined exercise and dietary intervention. Clinical characteristics, blood biochemistry, and circulating irisin levels of subjects were measured before and after eight weeks of training. EPC levels were evaluated via flow cytometry, and EPC migratory and adhesive functions were also determined. Circulating irisin levels significantly increased following the 8-week training program ( P  < 0.05). We furthermore observed an improvement in EPC numbers ( P  < 0.05), and EPC migratory and adhesive functions ( P  < 0.001 and P  < 0.05, respectively) after the intervention. Additionally, we detected a positive correlation between changes in irisin and changes in EPC number ( r  = 0.52, P  < 0.05). For the first time, a positive correlation between increasing irisin levels and increasing EPC levels has been reported after an 8-week program, consisting of exercise and dietary intervention. This result suggests a novel effect of irisin on the regulation of EPC mobilization, which might contribute to improvement of endothelial function in obese people.

Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus.

PubMed

Hamed, Saher; Brenner, Benjamin; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

2009-10-30

The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2-). Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. EPCs from diabetic patients generated more O2-, had higher NAD(P)H oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

In Vivo Serial MR Imaging of Magnetically Labeled Endothelial Progenitor Cells Homing to the Endothelium Injured Artery in Mice

PubMed Central

Chen, Jun; Jia, Zhen-Yu; Ma, Zhan-Long; Wang, Yuan-Yuan; Teng, Gao-Jun

2011-01-01

Background Emerging evidence of histopathological analyses suggests that endothelial progenitor cells (EPCs) play an important role in vascular diseases. Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after vascular injury in mice. Therefore, it would be advantageous to develop an in vivo technique that can explore the temporal and spatial migration of EPCs homing to the damaged endothelium noninvasively. Methodology/Principal Findings The left carotid common artery (LCCA) was injured by removal of endothelium with a flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen-derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to follow-up the injured artery at different time points after intravenous transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI. Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the labeled EPC transfusion group 15 days after LCCA injury, and it was found only in 1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC transfusion group were less than those of unlabeled EPC transfusion group and control group fifteen days after artery injury (p<0.05). Histopathological analyses confirmed accumulation and distribution of transfused EPCs at the injury site of LCCA. Conclusions/Significance These data indicate that MR imaging might be used as an in vivo method for the tracking of EPCs homing to the endothelium injured artery. PMID:21731624

An emerging cell-based strategy in orthopaedics: endothelial progenitor cells.

PubMed

Atesok, Kivanc; Matsumoto, Tomoyuki; Karlsson, Jon; Asahara, Takayuki; Atala, Anthony; Doral, M Nedim; Verdonk, Rene; Li, Ru; Schemitsch, Emil

2012-07-01

The purpose of this article was to analyze the results of studies in the literature, which evaluated the use of endothelial progenitor cells (EPCs) as a cell-based tissue engineering strategy. EPCs have been successfully used in regenerative medicine to augment neovascularization in patients after myocardial infarction and limb ischemia. EPCs' important role as vasculogenic progenitors presents them as a potential source for cell-based therapies to promote bone healing. EPCs have been shown to have prominent effects in promoting bone regeneration in several animal models. Evidence indicates that EPCs promote bone regeneration by stimulating both angiogenesis and osteogenesis through a differentiation process toward endothelial cell lineage and formation of osteoblasts. Moreover, EPCs increase vascularization and osteogenesis by increased secretion of growth factors and cytokines through paracrine mechanisms. EPCs offer the potential to emerge as a new strategy among other cell-based therapies to promote bone regeneration. Further investigations and human trials are required to address current questions with regard to biology and mechanisms of action of EPCs in bone tissue engineering.

Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study.

PubMed

Kaur, Savneet; Kumar, T R Santhosh; Uruno, Akira; Sugawara, Akira; Jayakumar, Karunakaran; Kartha, Chandrasekharan Cheranellore

2009-11-01

Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35-40% of the eNOS-EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected with pcDNA3.0-EGFP, the plasmid vector expressing green fluorescent protein (GFP) were used as control. The untransfected, GFP-transfected and eNOS-transfected EPCs were compared in terms of important functional attributes of angiogenesis such as proliferation, migration, differentiation and adhesion/integration into tube-like structures in vitro. Functional studies revealed that in the presence of defined growth conditions, compared to the untransfected and GFP-transfected cells, eNOS-EPCs from patients with CAD have a significant increase in [3H] thymidine-labeled DNA (P < 0.01), migration (14.6 +/- 1.8 and 16.5 +/- 1.9 vs. 23.5 +/- 3.4 cells/field, P < 0.01), ability to differentiate into endothelial-like spindle-shaped cells (46 +/- 4.5 and 56.5 +/- 2.1 vs. 93.2 +/- 6.6 cells/field, P < 0.001) and also incorporation into tube-like structures on the matrigel (GFP-EPCs: 21.25 +/- 2.9 vs. GFP-eNOS-EPCs: 34.5 +/- 5.5 cells/field, P < 0.05). We conclude that eNOS gene transfection is a valuable approach to augment angiogenic properties of ex vivo expanded EPCs and eNOS-modified EPCs may offer significant advantages than EPCs alone in terms of their clinical use in patients with myocardial ischemia.

Preparation and evaluation of a self-emulsifying drug delivery system of etoposide-phospholipid complex.

PubMed

Wu, Zhongbin; Guo, Dan; Deng, Li; Zhang, Yue; Yang, Qiuxia; Chen, Jianming

2011-01-01

The aim of this study was to develop a new phospholipid complex self-emulsifying drug delivery system (PC-SEDDS) to enhance bioavailability of oral etoposide, a drug with poor water solubility. Etoposide-phospholipid complex (EPC) was prepared by reacting etoposide and phospholipid in tetrahydrofuran and confirmed as a phospholipid compound by differential scanning calorimetry (DSC). Solubility of EPC and etoposide was determined in various vehicles. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region of EPC-SEDDS, and the effects of oil concentration, drug loading, and aqueous media on droplet size were investigated. The optimal formulation of EPC-SEDDS was EPC:octyl and decyl monoglyceride (ODO):Cremopher EL:PEG-400 (1:20:48:32) (w/w/w/w). Compared with etoposide-phospholipid complex suspension (EPCS) and etoposide suspension (ES), cumulative release of etoposide from EPC-SEDDS increased by 1.31 and 2.65 fold at 24 hours, respectively. Compared with ES, relative bioavailability of EPC-SEDDS, E-SEDDS, and EPCS after oral administration in rats was enhanced by 60.21-, 44.9-, and 8.44- fold, respectively. The synergistic effect between PC and SEDDS contributed to the enhanced bioavailability of etoposide. It was concluded that PC-SEDDS proved to be a potential system for delivering orally administered hydrophobic compounds including etoposide.

Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus

PubMed Central

Hamed, Saher; Brenner, Benjamin; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

2009-01-01

Background The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2-). Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. Results EPCs from diabetic patients generated more O2-, had higher NAD(P)H oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients. PMID:19878539

Cathepsin L is required for endothelial progenitor cell-induced neovascularization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra

Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sitesmore » of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.« less

The matrix protein CCN1 (CYR61) promotes proliferation, migration and tube formation of endothelial progenitor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Yang; Gao Yu; Wang, Hong

Neovascularization and re-endothelialization relies on circulating endothelial progenitor cells (EPCs), but their recruitment and angiogenic roles are subjected to regulation by the vascular microenvironment, which remains largely unknown. The present study was designed to investigate the effects of mature ECs and matrix protein CCN1 on the properties of EPCs. In a coculture system, effects of ECs on proliferation, migration and participation in tube-like formation of EPCs were evaluated, and functional assays were employed to identify the exact role of CCN1 in EPCs vitality and function. We demonstrated that ECs, as an indispensable part of the cellular milieu, significantly promoted themore » proliferation, migration and tube formation activities of EPCs, and more importantly, CCN1 was potentially involved in such effects of ECs. Expression of CCN1 in EPCs was significantly increased by serum, VEGF, ECs-cocultivation and ECs conditioned medium. Moreover, Ad-CCN1-mediated overexpression of CCN1 directly enhanced migration and tube formation of EPCs, whereas silencing of endogenous CCN1 in EPCs inhibits cell functions. Furthermore, CCN1 induced the expressions of chemokines and growth factors, such as MCP-1 and VEGF, suggesting a complex interaction between those proangiogenic factors. Our data suggest that matrix protein CCN1 may play an important role in microenvironment-mediated biological properties of EPCs.« less

Successful In Vitro Expansion and Differentiation of Cord Blood Derived CD34+ Cells into Early Endothelial Progenitor Cells Reveals Highly Differential Gene Expression

PubMed Central

Topcic, Denijal; Haviv, Izhak; Merivirta, Ruusu-Maaria; Agrotis, Alexander; Leitner, Ephraem; Jowett, Jeremy B.; Bode, Christoph; Lappas, Martha; Peter, Karlheinz

2011-01-01

Endothelial progenitor cells (EPCs) can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU) assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP), PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15) or pro-angiogenic (galectin-3) properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP) was the most up-regulated gene. PMID:21858032

Pericytes and endothelial precursor cells: cellular interactions and contributions to malignancy.

PubMed

Bagley, Rebecca G; Weber, William; Rouleau, Cecile; Teicher, Beverly A

2005-11-01

Tumor vasculature is irregular, abnormal, and essential for tumor growth. Pericytes and endothelial precursor cells (EPC) contribute to the formation of blood vessels under angiogenic conditions. As primary cells in culture, pericytes and EPC share many properties such as tube/network formation and response to kinase inhibitors selective for angiogenic pathways. Expression of cell surface proteins including platelet-derived growth factor receptor, vascular cell adhesion molecule, intercellular adhesion molecule, CD105, desmin, and neural growth proteoglycan 2 was similar between pericytes and EPC, whereas expression of P1H12 and lymphocyte function-associated antigen-1 clearly differentiates the cell types. Further distinction was observed in the molecular profiles for expression of angiogenic genes. Pericytes or EPC enhanced the invasion of MDA-MB-231 breast cancer cells in a coculture assay system. The s.c. coinjection of live pericytes or EPC along with MDA-MB-231 cells resulted in an increased rate of tumor growth compared with coinjection of irradiated pericytes or EPC. Microvessel density analysis indicated there was no difference in MDA-MB-231 tumors with or without EPC or pericytes. However, immunohistochemical staining of vasculature suggested that EPC and pericytes may stabilize or normalize vasculature rather than initiate vasculogenesis. In addition, tumors arising from the coinjection of EPC and cancer cells were more likely to develop lymphatic vessels. These results support the notion that pericytes and EPC contribute to malignancy and that these cell types can be useful as cell-based models for tumor vascular development and selection of agents that may provide therapeutic benefit.

Impact of a cardiac rehabilitation program and inflammatory state on endothelial progenitor cells in acute coronary syndrome patients.

PubMed

Cesari, Francesca; Marcucci, Rossella; Gori, Anna Maria; Burgisser, Costanza; Francini, Sara; Sofi, Francesco; Gensini, Gian Franco; Abbate, Rosanna; Fattirolli, Francesco

2013-09-01

Among the benefits of a cardiac rehabilitation (CR) program for patients after an acute coronary syndrome (ACS) is the mobilization of endothelial progenitor cells (EPCs). However not all patients respond to CR with an increase of EPC. We performed this study to identify the characteristics of patients who will not benefit from an increase of EPCs at the end of a CR program. 112 ACS patients were admitted to a four-week CR program. EPCs, high sensitivity C-reactive protein (hsCRP) and NT-ProBNP levels were determined at the beginning (T1) and at the end (T2) of the CR program. All patients performed a cardiopulmonary exercise test at T1 and at T2. EPCs were defined as CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+. hsCRP and NT-ProBNP were measured by nephelometric and immunometric method, respectively. At T2, we observed a significant increase of EPCs (p=0.001), VO2 peak, Watt max HDL-cholesterol (p<0.0001) and a significant decrease (p<0.001) of hsCRP and NT-ProBNP, triglycerides, HbA1c, systolic blood pressure and waist circumference. Variations of VO2 peak were significantly correlated with the variations of EPCs. Patients with increased EPCs showed significantly (p=0.01) lower baseline levels of CRP and higher basal Watt max (p=0.04). In a multivariate logistic regression analysis, the lowest tertile of baseline hsCRP significantly affected the likelihood of having an increase of EPCs at the end of the CR program. A CR program determines an increase of EPCs with a decrease of CRP and NT-ProBNP. A different trend for EPCs can be detected among patients correlated to CRP levels and exercise tolerance. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Advanced glycation endproducts alter functions and promote apoptosis in endothelial progenitor cells through receptor for advanced glycation endproducts mediate overpression of cell oxidant stress.

PubMed

Chen, Jianfei; Song, Minbao; Yu, Shiyong; Gao, Pan; Yu, Yang; Wang, Hong; Huang, Lan

2010-02-01

Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis. The factors that regulate the function of EPCs are not completely clear. Increased formation of advanced glycation endproducts (AGEs) is generally regarded as one of the main mechanisms responsible for vascular damage in patients with diabetes and atherosclerosis. AGEs lead to the generation of reactive oxygen species (ROS) and part of the regenerative capacity of EPCs seems to be due to their low baseline ROS levels and reduced sensitivity to ROS-induced cell apoptosis. Therefore, we tested the hypothesis that AGEs can alter functions and promote apoptosis in EPCs through overpress cell oxidant stress. EPCs, isolated from bone marrow, were cultured in the absence or presence of AGEs (50, 100, and 200 microg/ml). A modified Boyden's chamber was used to assess the migration of EPCs and the number of recultured EPCs was counted to measure the adhesiveness function. MTT assay was used to determine the proliferation function. ROS were analyzed using the ROS assay kit. A spectrophotometer was used to assess superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, and PCR was used to test mRNA expression of SOD and GSH-PX. SiRNA was used to block receptor for advanced glycation endproducts (RAGEs) expression. Apoptosis was evaluated by Annexin V immunostaining and TUNEL staining. Co-culturing with AGEs increases ROS production, decreases anti-oxidant defenses, overpresses oxidant stress, inhibits the proliferation, migration, and adhesion of EPCs, and induces EPCs apoptosis. In addition, these effects were attenuated during block RAGE protein expression by siRNA. AGEs may serve to impair EPCs functions through RAGE-mediate oxidant stress, and promote EPCs sensitivity toward oxidative-stress-mediated apoptosis, which indicates a new pathophysiological mechanism of disturbed vascular adaptation in atherosclerosis and suggests that lower levels of AGEs might improve the

Store-Operated Ca2+ Entry Is Remodelled and Controls In Vitro Angiogenesis in Endothelial Progenitor Cells Isolated from Tumoral Patients

PubMed Central

Dragoni, Silvia; Bottino, Cinzia; Ong, Hwei Ling; Guerra, Germano; Ganini, Carlo; Massa, Margherita; Manzoni, Mariangela; Ambudkar, Indu S.; Genazzani, Armando A.; Rosti, Vittorio; Pedrazzoli, Paolo; Tanzi, Franco; Moccia, Francesco

2012-01-01

Background Endothelial progenitor cells (EPCs) may be recruited from bone marrow to sustain tumor vascularisation and promote the metastatic switch. Understanding the molecular mechanisms driving EPC proliferation and tubulogenesis could outline novel targets for alternative anti-angiogenic treatments. Store-operated Ca2+ entry (SOCE), which is activated by a depletion of the intracellular Ca2+ pool, regulates the growth of human EPCs, where is mediated by the interaction between the endoplasmic reticulum Ca2+-sensor, Stim1, and the plasmalemmal Ca2+ channel, Orai1. As oncogenesis may be associated to the capability of tumor cells to grow independently on Ca2+ influx, it is important to assess whether SOCE regulates EPC-dependent angiogenesis also in tumor patients. Methodology/Principal Findings The present study employed Ca2+ imaging, recombinant sub-membranal and mitochondrial aequorin, real-time polymerase chain reaction, gene silencing techniques and western blot analysis to investigate the expression and the role of SOCE in EPCs isolated from peripheral blood of patients affected by renal cellular carcinoma (RCC; RCC-EPCs) as compared to control EPCs (N-EPCs). SOCE, activated by either pharmacological (i.e. cyclopiazonic acid) or physiological (i.e. ATP) stimulation, was significantly higher in RCC-EPCs and was selectively sensitive to BTP-2, and to the trivalent cations, La3+ and Gd3+. Furthermore, 2-APB enhanced thapsigargin-evoked SOCE at low concentrations, whereas higher doses caused SOCE inhibition. Conversely, the anti-angiogenic drug, carboxyamidotriazole (CAI), blocked both SOCE and the intracellular Ca2+ release. SOCE was associated to the over-expression of Orai1, Stim1, and transient receptor potential channel 1 (TRPC1) at both mRNA and protein level The intracellular Ca2+ buffer, BAPTA, BTP-2, and CAI inhibited RCC-EPC proliferation and tubulogenesis. The genetic suppression of Stim1, Orai1, and TRPC1 blocked CPA-evoked SOCE in RCC-EPCs

An essential role for the Id1/PI3K/Akt/NFkB/survivin signalling pathway in promoting the proliferation of endothelial progenitor cells in vitro.

PubMed

Li, Wei; Wang, Hang; Kuang, Chun-Yan; Zhu, Jin-Kun; Yu, Yang; Qin, Zhe-Xue; Liu, Jie; Huang, Lan

2012-04-01

The enhancement of re-endothelialisation is a critical therapeutic option for repairing injured blood vessels. Endothelial progenitor cells (EPCs) are the major source of cells that participate in endothelium repair and contribute to re-endothelialisation by reducing neointima formation after vascular injury. The over-expression of the inhibitor of differentiation or DNA binding 1 (Id1) significantly improved EPC proliferation. This study aimed to investigate the effects of Id1 on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor kappa B (NFκB)/survivin signalling pathway and its significance in promoting EPC proliferation in vitro. Spleen-derived EPCs were cultured as previously described. Id1 was presented at low levels in EPCs, and was rapidly up-regulated by stimulation with vascular endothelial growth factor. We demonstrated that transient transfection of Id1 into EPCs activated the PI3K/Akt/NFκB/survivin signalling pathway and promoted EPC proliferation. The proliferation of EPCs was extensively inhibited by silencing of endogenous Id1, and knockdown of Id1 expression led to suppression of PI3K/Akt/NFκB/survivin signalling pathway in EPCs. In addition, blockade by the PI3K-specific inhibitor LY294002, Akt inhibitor, the NFκB inhibitor BAY 11-7082, the survivin inhibitor Curcumin, or the survivin inhibitor YM155 reduced the effects of Id1 transfection. These results suggest that the Id1/PI3K/Akt/NFκB/survivin signalling pathway plays a critical role in EPC proliferation. The Id1/PI3K/Akt/NFκB/survivin signalling pathway may represent a novel therapeutic target in the prevention of restenosis after vascular injury.

A practical and efficient cellular substrate for the generation of induced pluripotent stem cells from adults: blood-derived endothelial progenitor cells.

PubMed

Geti, Imbisaat; Ormiston, Mark L; Rouhani, Foad; Toshner, Mark; Movassagh, Mehregan; Nichols, Jennifer; Mansfield, William; Southwood, Mark; Bradley, Allan; Rana, Amer Ahmed; Vallier, Ludovic; Morrell, Nicholas W

2012-12-01

Induced pluripotent stem cells (iPSCs) have the potential to generate patient-specific tissues for disease modeling and regenerative medicine applications. However, before iPSC technology can progress to the translational phase, several obstacles must be overcome. These include uncertainty regarding the ideal somatic cell type for reprogramming, the low kinetics and efficiency of reprogramming, and karyotype discrepancies between iPSCs and their somatic precursors. Here we describe the use of late-outgrowth endothelial progenitor cells (L-EPCs), which possess several favorable characteristics, as a cellular substrate for the generation of iPSCs. We have developed a protocol that allows the reliable isolation of L-EPCs from peripheral blood mononuclear cell preparations, including frozen samples. As a proof-of-principle for clinical applications we generated EPC-iPSCs from both healthy individuals and patients with heritable and idiopathic forms of pulmonary arterial hypertension. L-EPCs grew clonally; were highly proliferative, passageable, and bankable; and displayed higher reprogramming kinetics and efficiencies compared with dermal fibroblasts. Unlike fibroblasts, the high efficiency of L-EPC reprogramming allowed for the reliable generation of iPSCs in a 96-well format, which is compatible with high-throughput platforms. Array comparative genome hybridization analysis of L-EPCs versus donor-matched circulating monocytes demonstrated that L-EPCs have normal karyotypes compared with their subject's reference genome. In addition, >80% of EPC-iPSC lines tested did not acquire any copy number variations during reprogramming compared with their parent L-EPC line. This work identifies L-EPCs as a practical and efficient cellular substrate for iPSC generation, with the potential to address many of the factors currently limiting the translation of this technology.

Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing.

PubMed

Matsumoto, Tomoyuki; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Shoji, Taro; Iwasaki, Hiroto; Suzuki, Takahiro; Oyamada, Akira; Horii, Miki; Yokoyama, Ayumi; Nishimura, Hiromi; Lee, Sang Yang; Miwa, Masahiko; Doita, Minoru; Kurosaka, Masahiro; Asahara, Takayuki

2008-04-01

We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)-enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)-derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post-fracture, the early phase of endochondral ossifification. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage- (Lin-) cells and PB Sca1+Lin- cells, which are EPC-enriched fractions, significantly increased post-fracture. The Sca1+ EPC-derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell-specific Tie-2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin- Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue. (c) 2008 Wiley-Liss, Inc.

Increase of endothelial progenitor cells in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

PubMed

Medinger, Michael; Heim, Dominik; Gerull, Sabine; Halter, Jörg; Krenger, Werner; Buser, Andreas; Lengerke, Claudia; Bucher, Christoph; Passweg, Jakob

2016-08-01

Circulating endothelial progenitor cells (EPCs; CD31+ CD34(bright)CD133+ CD45(dim) cells) are novel markers of endothelial dysfunction and related to inflammatory processes such as acute graft-versus-host disease (aGvHD). 47 patients with acute myeloid leukaemia (AML) who were in complete remission as they underwent allogeneic hematopoietic stem cell transplantation with myeloablative conditioning with PBSC as stem cell source were enrolled in the study. Blood samples for the quantitative analysis of circulating EPC levels were drawn at different time points in patients with and without aGvHD. CD34+ VEGFR2/KDR+ CD133+ triple-positive cells identified among CD34+ cells by FACS. EPC were quantified and data are presented as cells/ml whole blood. Circulating EPC levels were not significantly different in patients with and without aGvHD prior to conditioning (baseline) and at the time of engraftment. However, at diagnosis of aGvHD≥grade 2, EPC levels increased whereas in patients without aGvHD the EPC levels remained significantly lower (3021±278 versus 2322±195 cells/ml; p<0.001). Patients with steroid-refractory aGvHD had high levels of EPC throughout. EPC levels fell in responding patients. Our results demonstrate that the number of circulating EPCs is increased in patients with aGvHD compared to patients without aGvHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells

PubMed Central

Tan, Kefang; Zheng, Ke; Li, Daiye; Lu, Haiyuan; Wang, Siqi; Sun, Xuan

2017-01-01

The application of autologous endothelial progenitor cell (EPC) transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD)-derived mesenchymal stem cells (MSCs) and umbilical cord (UC)-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC) induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment. PMID:28562647

Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.

PubMed

Yoo, Chae Hwa; Na, Hee-Jun; Lee, Dong-Seol; Heo, Soon Chul; An, Yuri; Cha, Junghwa; Choi, Chulhee; Kim, Jae Ho; Park, Joo-Cheol; Cho, Yee Sook

2013-11-01

Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34(+) EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

PubMed Central

Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2016-01-01

Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

Therapeutic Benefit of Bone Marrow–Derived Endothelial Progenitor Cell Transplantation after Experimental Aneurysm Embolization with Coil in Rats

PubMed Central

Li, Qianyun; Huang, Jun; Chen, Xi; Chen, Xiaoyan; Zhang, Jun; Wang, Yongting; Yang, Guo-Yuan; Zhu, Wei

2014-01-01

Aneurysm embolization with coil is now widely used clinically. However, the recurrence of aneurysms after embolization has always plagued neurosurgeons because the endothelial layer of the aneurysm neck loses its integrity after being embolized by coil. Bone marrow–derived endothelial progenitor cells (BM-EPCs) could be incorporated into injured endothelium and differentiate into mature endothelial cells during vascular repairing processes. The aim of our study is to explore the effects of BM-EPCs on aneurysm repairing and remodeling in a rat embolization model of abdominal aortic aneurysm. BM-EPC proliferation, migration and tube formation were not affected by super-paramagnetic iron oxide nanoparticle (SPIO) labeling compared to the controls (p>0.05). The number of SPIO-labeled cells greatly increased in EPC transplanted rats compared to that of phosphate buffered saline treated rats. SPIO-labeled EPC (SPIO-EPC) are mainly located in the aneurysm neck and surrounded by fibrous tissue. A histology study showed that the aneurysm orifice was closed with neointima and the aneurysm was filled with newly formed fibrous tissue. The SPIO-EPC accumulated in the aneurysm neck, which accelerated focal fibrous tissue remodeling, suggesting that BM-EPCs play a crucial role in repairing and remodeling the aneurysm neck orifice. PMID:24587209

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

PubMed

Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

2016-01-01

Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment.

PubMed

Lee, Jun Hee; Ji, Seung Taek; Kim, Jaeho; Takaki, Satoshi; Asahara, Takayuki; Hong, Young-Joon; Kwon, Sang-Mo

2016-10-28

Although endothelial progenitor cells (EPCs) contribute to wound repair by promoting neovascularization, the mechanism of EPC-mediated wound healing remains poorly understood due to the lack of pivotal molecular targets of dermal wound repair. We found that genetic targeting of the Lnk gene in EPCs dramatically enhances the vasculogenic potential including cell proliferation, migration, and tubule-like formation as well as accelerates in vivo wound healing, with a reduction in fibrotic tissue and improved neovascularization via significant suppression of inflammatory cell recruitment. When injected into wound sites, Lnk -/- EPCs gave rise to a significant number of new vessels, with remarkably increased survival of transplanted cells and decreased recruitment of cytotoxic T cells, macrophages, and neutrophils, but caused activation of fibroblasts in the wound-remodeling phase. Notably, in a mouse model of type I diabetes, transplanted Lnk -/- EPCs induced significantly better wound healing than Lnk +/+ EPCs did. The specific targeting of Lnk may be a promising EPC-based therapeutic strategy for dermal wound healing via improvement of neovascularization but inhibition of excessive inflammation as well as activation of myofibroblasts during dermal tissue remodeling.

Specific role of impaired glucose metabolism and diabetes mellitus in endothelial progenitor cell characteristics and function.

PubMed

Yiu, Kai-Hang; Tse, Hung-Fat

2014-06-01

The disease burden of diabetes mellitus (DM) and its associated cardiovascular complications represent a growing and major global health problem. Recent studies suggest that circulating exogenous endothelial progenitor cells (EPCs) play an important role in endothelial repair and neovascularization at sites of injury or ischemia. Both experimental and clinical studies have demonstrated that hyperglycemia related to DM can induce alterations to EPCs. The reduction and dysfunction of EPCs related to DM correlate with the occurrence and severity of microvascular and macrovascular complications, suggesting a close mechanistic link between EPC dysfunction and impaired vascular function/repair in DM. These alterations to EPCs, likely mediated by multiple pathophysiological mechanisms, including inflammation, oxidative stress, and alterations in Akt and the nitric oxide pathway, affect EPCs at multiple stages: differentiation and mobilization in the bone marrow, trafficking and survival in the circulation, and homing and neovascularization. Several different therapeutic approaches have consequently been proposed to reverse the reduction and dysfunction of EPCs in DM and may represent a novel therapeutic approach to prevent and treat DM-related cardiovascular complications. © 2014 American Heart Association, Inc.

76 FR 82279 - Electronic Delivery of Search Results From the United States Patent and Trademark Office to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... 141 EPC and new Rule 70b EPC--utilisation scheme, OJ EPO 2010, 410. To assist U.S. applicants who... exemption under Rule 141(2) EPC from filing a copy of the search results--utilisation scheme, OJ EPO 2011...

Highly efficient local delivery of endothelial progenitor cells significantly potentiates angiogenesis and full-thickness wound healing.

PubMed

Wang, Chenggui; Wang, Qingqing; Gao, Wendong; Zhang, Zengjie; Lou, Yiting; Jin, Haiming; Chen, Xiaofeng; Lei, Bo; Xu, Huazi; Mao, Cong

2018-03-15

Wound therapy with a rapid healing performance remains a critical clinical challenge. Cellular delivery is considered to be a promising approach to improve the efficiency of healing, yet problems such as compromised cell viability and functionality arise due to the inefficient delivery. Here, we report the efficient delivery of endothelial progenitor cells (EPCs) with a bioactive nanofibrous scaffold (composed of collagen and polycaprolactone and bioactive glass nanoparticles, CPB) for enhancing wound healing. Under the stimulation of CPB nanofibrous system, the viability and angiogenic ability of EPCs were significantly enhanced through the activation of Hif-1α/VEGF/SDF-1α signaling. In vivo, CPB/EPC constructs significantly enhanced the formation of high-density blood vessels by greatly upregulating the expressions of Hif-1α, VEGF, and SDF-1α. Moreover, owing to the increased local delivery of cells and fast neovascularization within the wound site, cell proliferative activity, granulation tissue formation, and collagen synthesis and deposition were greatly promoted by CPB/EPC constructs resulting in rapid re-epithelialization and regeneration of skin appendages. As a result, the synergistic enhancement of wound healing was observed from CPB/EPC constructs, which suggests the highly efficient delivery of EPCs. CPB/EPC constructs may become highly competitive cell-based therapeutic products for efficient impaired wound healing application. This study may also provide a novel strategy to develop bioactive cell therapy constructs for angiogenesis-related regenerative medicine. This paper reported a highly efficient local delivery of EPCs using bioactive glass-based CPB nanofibrous scaffold for enhancing angiogenesis and wound regeneration. In vitro study showed that CPB can promote the proliferation, migration, and tube formation of EPCs through upregulation of the Hif-1α/VEGF/SDF-1α signaling pathway, indicating that the bioactivity and angiogenic ability of

Does external pneumatic compression treatment between bouts of overreaching resistance training sessions exert differential effects on molecular signaling and performance-related variables compared to passive recovery? An exploratory study

PubMed Central

Romero, Matthew A.; Osburn, Shelby C.; Mobley, Christopher B.; Anderson, Richard G.; Goodlett, Michael D.; Pascoe, David D.

2017-01-01

Purpose We sought to compare the effects of external pneumatic compression (EPC) and sham when used concurrently with resistance training on performance-related outcomes and molecular measures related to recovery. Methods Twenty (N = 20) resistance-trained male participants (aged 21.6±2.4 years) were randomized to balanced sham or EPC intervention groups. The protocol consisted of 3 consecutive days of heavy, voluminous back squat exercise followed by EPC/sham treatment (Days2-4) and 3 consecutive days of recovery (Days5-7) with EPC/sham only on Days5-6. On Day1 (PRE), and Days3-7, venipuncture, flexibility and pressure-to-pain threshold (PPT) measures were performed. Vastsus lateralis muscle tissue was biopsied at PRE, 1-h post-EPC/sham treatment on Day2 (POST1) and 24-h post-EPC/sham treatment on Day7 (POST2). Isokinetic peak torque was assessed at PRE and POST2. Results Peak isokinetic strength did not change from PRE to POST2 in either group. The PPT was significantly lower on Days3-6 with sham, indicating greater muscle soreness, though this was largely abolished in the EPC group. A significant decrease in flexibility with sham was observed on Day3 (+16.2±4.6% knee joint angle; P<0.01) whereas there was no change with EPC (+2.8±3.8%; P>0.01). Vastus lateralis poly-ubiquitinated proteins significantly increased at the POST2 time point relative to PRE with sham (+66.6±24.6%; P<0.025) and were significantly greater (P<0.025) than those observed with EPC at the same time point (-18.6±8.5%). 4-hydroxynonenal values were significantly lower at POST2 relative to PRE with EPC (-16.2±5.6%; P<0.025) and were significantly lower (P<0.025) than those observed with sham at the same time point (+11.8±5.9%). Conclusion EPC mitigated a reduction in flexibility and PPT that occurred with sham. Moreover, EPC reduced select skeletal muscle oxidative stress and proteolysis markers during recovery from heavy resistance exercise. PMID:28662152

High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia.

PubMed

Tsai, Hsing-Hua; Lin, Chin-Pu; Lin, Yi-Hui; Hsu, Chih-Chin; Wang, Jong-Shyan

2016-12-01

Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction. Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells. This study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-EPC levels and EPC functionality under hypoxic condition. Sixty healthy sedentary males were randomized to engage in either HIT (3-min intervals at 40 and 80 % VO 2max for five repetitions, n = 20) or MCT (sustained 60 % VO 2max , n = 20) for 30 min/day, 5 days/week for 6 weeks, or to a control group (CTL) that did not received exercise intervention (n = 20). Mon-EPC characteristics and EPC functionality under hypoxic exercise (HE, 100 W under 12 % O 2 ) were determined before and after HIT, MCT, and CTL. The results demonstrated that after the intervention, the HIT group exhibited larger improvements in VO 2peak , estimated peak cardiac output (Q C ), and estimated peak perfusions of frontal cerebral lobe (Q FC ) and vastus lateralis (Q VL ) than the MCT group. Furthermore, HIT (a) increased circulating CD14 ++ /CD16 - /CD34 + /KDR + (Mon-1 EPC) and CD14 ++ /CD16 + /CD34 + /KDR + (Mon-2 EPC) cell counts, (b) promoted the migration and tube formation of EPCs, (c) diminished the shedding of endothelial (CD34 - /KDR + /phosphatidylserine + ) cells, and (d) elevated plasma nitrite plus nitrate, stromal cell-derived factor-1, matrix metalloproteinase-9, and vascular endothelial growth factor-A concentrations at rest or following HE, compared to those of MCT. In addition, Mon-1 and -2 EPC counts were directly related to VO 2peak and estimated peak Q C , Q FC , and Q VL . HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production. Moreover, HIT effectively enhances EPC functionality and suppresses endothelial injury undergoing hypoxia.

GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, impairs neovascularization by decreasing endothelial progenitor cell function.

PubMed

Lin, Yi-Wen; Huang, Chun-Yao; Chen, Yung-Hsiang; Shih, Chun-Ming; Tsao, Nai-Wen; Lin, Cheng-Yen; Chang, Nen-Chung; Tsai, Chien-Sung; Tsai, Hsiao-Ya; Tsai, Jui-Chi; Huang, Po-Hsun; Li, Chi-Yuan; Lin, Feng-Yen

2013-01-01

The number and function of endothelial progenitor cells (EPCs) are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4) mutation) mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS) in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.

The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study

PubMed Central

Brook, Robert D.; Bard, Robert L.; Kaplan, Mariana J.; Yalavarthi, Srilakshmi; Morishita, Masako; Dvonch, J. Timothy; Wang, Lu; Yang, Hui-yu; Spino, Catherine; Mukherjee, Bhramar; Oral, Elif A.; Sun, Qinghua; Brook, Jeffrey R.; Harkema, Jack; Rajagopalan, Sanjay

2015-01-01

Context Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown. Objective We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels. Methods Thirty-two adults (25.9±6.6 years) were exposed to coarse CAP (76.2±51.5 μgm−3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n=21), white blood cell (n=24) and vascular endothelial growth factor (VEGF) (n=16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests. Results Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC mL−1; median (25th–75th percentiles), p=0.052] and 20 h [106.86 (52.91–278.35) EPC mL−1, p=0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC mL−1]. VEGF and white blood cell (WBC) levels did not differ between exposures. Conclusions Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation. PMID:23919441

Immobilization of DNA aptamers via plasma polymerized allylamine film to construct an endothelial progenitor cell-capture surface.

PubMed

Qi, Pengkai; Yan, Wei; Yang, Ying; Li, Yalong; Fan, Yi; Chen, Junying; Yang, Zhilu; Tu, Qiufen; Huang, Nan

2015-02-01

The endothelial progenitor cells (EPCs) capture stent has drawn increasing attentions and become one of the most promising concepts for the next generation vascular stent. In this regard, it is of great significance to immobilize a molecule with the ability to bind EPC for rapid in vivo endothelialization with high specificity. In this work, a facile two-step method aimed at constructing a coating with specific EPC capturing aptamers is reported. The processes involves as the first-step deposition of plasma polymerized allylamine (PPAam) on a substrate to introduce amine groups, followed by the electrostatic adsorption of a 34 bases single strand DNA sequence to the PPAam surface as a second step (PPAam-DNA). Grazing incidence attenuated total reflection Fourier transform infrared spectroscopy (GATR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed the successful immobilization of the aptamers. Quartz crystal microbalance with dissipation (QCM-D) real time monitoring result shows that about 175 ng/cm(2) aptamers were conjugated onto the PPAam surface. The interactions between the modified surfaces and human umbilical vein endothelial cells (ECs), smooth muscle cells (SMCs), and murine induced EPCs derived from mesenchymal stem cells (MSCs) were also investigated. It was demonstrated that PPAam-DNA samples could capture more EPCs, and present a cellular friendly surface for the proliferation of both EPCs and ECs but no effect on the hyperplasia of SMCs. Also, the co-culture results of 3 types of cells confirmed that the aptamer could specifically bond EPCs rather than ECs and SMCs, suggesting the competitive adhesion advantage of EPCs to ECs and SMCs. These data demonstrate that the EPC aptamer has large potential for designing an EPC captured stent and other vascular grafts with targeted in situ endothelialization. Copyright © 2014 Elsevier B.V. All rights reserved.

Early accelerated senescence of circulating endothelial progenitor cells in premature coronary artery disease patients in a developing country - a case control study.

PubMed

Vemparala, Kranthi; Roy, Ambuj; Bahl, Vinay Kumar; Prabhakaran, Dorairaj; Nath, Neera; Sinha, Subrata; Nandi, Pradipta; Pandey, Ravindra Mohan; Reddy, Kolli Srinath; Manhapra, Ajay; Lakshmy, Ramakrishnan

2013-11-19

The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR- ELISA respectively. The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044). We observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.

Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

PubMed Central

Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

2013-01-01

Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

PubMed

Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

2013-01-01

Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter.

PubMed

Hayakawa, Kazuhide; Miyamoto, Nobukazu; Seo, Ji Hae; Pham, Loc-Duyen D; Kim, Kyu-Won; Lo, Eng H; Arai, Ken

2013-04-01

High-mobility group box 1 (HMGB1) was initially described as a damage-associated-molecular-pattern (DAMP) mediator that worsens acute brain injury after stroke. But, recent findings suggest that HMGB1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell (EPC) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine (LPC) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB1 was up-regulated in GFAP-positive reactive astrocytes, along with the accumulation of Flk1/CD34-double-positive EPCs that expressed pro-recovery mediators such as brain-derived neurotrophic factor and basic fibroblast growth factor. Astrocyte-EPC signaling required the HMGB1 receptor RAGE as treatment with RAGE-neutralizing antibody significantly decreased EPC accumulation. Moreover, suppression of HMGB1 with siRNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB1 from reactive astrocytes may attract EPCs to promote recovery after white matter injury. © 2012 International Society for Neurochemistry.

Inhibitor of DNA binding 1 regulates cell cycle progression of endothelial progenitor cells through induction of Wnt2 expression

PubMed Central

Xia, Xi; Yu, Yang; Zhang, Li; Ma, Yang; Wang, Hong

2016-01-01

Endothelial injury is a risk factor for atherosclerosis. Endothelial progenitor cell (EPC) proliferation contributes to vascular injury repair. Overexpression of inhibitor of DNA binding 1 (Id1) significantly promotes EPC proliferation; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated the role of Id1 in cell cycle regulation of EPCs, which is closely associated with proliferation. Overexpression of Id1 increased the proportion of EPCs in the S/G2M phase and significantly increased cyclin D1 expression levels, while knockdown of Id1 arrested the cell cycle progression of EPCs in the G1 phase and inhibited cyclin D1 expression levels. In addition, it was demonstrated that Id1 upregulated wingless-type mouse mammary tumor virus integration site family member 2 (Wnt2) expression levels and promoted β-catenin accumulation and nuclear translocation. Furthermore, Wnt2 knockdown counteracted the effects of Id1 on cell cycle progression of EPCs. In conclusion, the results of the present study indicate that Id1 promoted Wnt2 expression, which accelerated cell cycle progression from G1 to S phase. This suggests that Id1 may promote cell cycle progression of EPCs, and that Wnt2 may be important in Id1 regulation of the cell cycle of EPCs. PMID:27432753

Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xiaoping; Mao, Haian; Chen, Jin-yuan

2013-02-15

Highlights: ► MicroRNA-221 is upregulated in the endothelial progenitor cells of atherosclerosis patients. ► PAK1 is a direct target of microRNA-221. ► MicroRNA-221 inhibits EPCs proliferation through c-Raf/MEK/ERK pathway. -- Abstract: Coronary artery disease (CAD) is associated with high mortality and occurs via endothelial injury. Endothelial progenitor cells (EPCs) restore the integrity of the endothelium and protect it from atherosclerosis. In this study, we compared the expression of microRNAs (miRNAs) in EPCs in atherosclerosis patients and normal controls. We found that miR-221 expression was significantly up-regulated in patients compared with controls. We predicted and identified p21/Cdc42/Rac1-activated kinase 1 (PAK1) asmore » a novel target of miR-221 in EPCs. We also demonstrated that miR-221 targeted a putative binding site in the 3′UTR of PAK1, and absence of this site was inversely associated with miR-221 expression in EPCs. We confirmed this relationship using a luciferase reporter assay. Furthermore, overexpression of miR-221 in EPCs significantly decreased EPC proliferation, in accordance with the inhibitory effects induced by decreased PAK1. Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs.« less

Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice.

PubMed

Asai, Jun; Takenaka, Hideya; Ii, Masaaki; Asahi, Michio; Kishimoto, Saburo; Katoh, Norito; Losordo, Douglas W

2013-10-01

Impaired wound healing leading to skin ulceration is a serious complication of diabetes and may be caused by defective angiogenesis. Endothelial progenitor cells (EPCs) can augment neovascularisation in the ischaemic tissue. Experiments were performed to test the hypothesis that locally administered EPCs can promote wound healing in diabetes. Full-thickness skin wounds were created on the dorsum of diabetic mice. EPCs were obtained from bone marrow mononuclear cells (BMMNCs) and applied topically to the wound immediately after surgery. Vehicle and non-selective BMMNCs were used as controls. Wound size was measured on days 5, 10 and 14 after treatment, followed by resection, histological analysis and quantification of vascularity. Topical application of EPCs significantly promoted wound healing, as assessed by closure rate and wound vascularity. Immunostaining revealed that transplanted EPCs induced increased expression of vascular endothelial growth factor and basic fibroblast growth factor. Few EPCs were observed in the neovasculature based on in vivo staining of the functional vasculature. Ex vivo expanded EPCs promote wound healing in diabetic mice via mechanisms involving increased local cytokine expression and enhanced neovascularisation of the wound. This strategy exploiting the therapeutic capacity of autologously derived EPCs may be a novel approach to skin repair in diabetes. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Research of trace metals as markers of entry pathways in combined sewers.

PubMed

Gounou, C; Varrault, G; Amedzro, K; Gasperi, J; Moilleron, R; Garnaud, S; Chebbo, G

2011-01-01

Combined sewers receive high toxic trace metal loads emitted by various sources, such as traffic, industry, urban heating and building materials. During heavy rain events, Combined Sewer Overflows (CSO) can occur and, if so, are discharged directly into the aquatic system and therefore could have an acute impact on receiving waters. In this study, the concentrations of 18 metals have been measured in 89 samples drawn from the three pollutant Entry Pathways in Combined Sewers (EPCS): i) roof runoff, ii) street runoff, and iii) industrial and domestic effluents and also drawn from sewer deposits (SD). The aim of this research is to identify metallic markers for each EPCS; the data matrix was submitted to principal component analysis in order to determine metallic markers for the three EPCS and SD. This study highlights the fact that metallic content variability across samples from different EPCS and SD exceeds the spatio-temporal variability of samples from the same EPCS. In the catchment studied here, the most valuable EPCS and SD markers are lead, sodium, boron, antimony and zinc; these markers could be used in future studies to identify the contributions of each EPCS to CSO metallic loads.

76 FR 33329 - Energy Performance Contracting-Request for Comments on Proposed Guidance and Policy Clarifications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

... under EPC? c. Should EPCs permit the investments of green building measures if sufficient savings or.... weekdays at the above address. Due to security measures at the HUD Headquarters building, an advance... assessment and auditing protocol for PHA's undertaking self-direct EPCs? Could a Green Physical Needs...

The Promise of Cell Based Therapies for Diabetic Complications: challenges and solutions

PubMed Central

Jarajapu, Yagna P.R.; Grant, Maria B.

2013-01-01

The discovery of endothelial progenitor cells (EPCs) in human peripheral blood advanced the field of cell-based therapeutics for many pathological conditions. Despite the lack of agreement about the existence and characteristics of EPCs, autologous EPC populations represent a novel treatment option for complications requiring therapeutic revascularization and vascular repair. Patients with diabetic complications represent a population of patients that may benefit from cellular therapy yet their broadly dysfunctional cells may limit the feasibility of this approach. Diabetic EPCs have decreased migratory prowess and reduced proliferative capacity and an altered cytokine/ growth factor secretory profile that can accelerates deleterious repair mechanisms rather than support proper vascular repair. Furthermore, the diabetic environment poses additional challenges for the autologous transplantation of cells. The present review is focused on correcting diabetic EPC dysfunction and the challenges involved in the application of cell-based therapies for treatment of diabetic vascular complications. In addition, ex vivo and in vivo functional manipulation(s) of EPCs to overcome these hurdles are discussed. PMID:20299675

Angiogenic function of prostacyclin biosynthesis in human endothelial progenitor cells

PubMed Central

He, Tongrong; Lu, Tong; d’Uscio, Livius V.; Lam, Chen-Fuh; Lee, Hon-Chi; Katusic, Zvonimir S.

2009-01-01

The role of prostaglandins production in the control of regenerative function of endothelial progenitor cells (EPCs) has not been studied. We hypothesized that activation of cyclooxygenase (COX) enzymatic activity and the subsequent production of prostacyclin (PGI2) is an important mechanism responsible for the regenerative function of EPCs. In the present study, we detected high levels of COX-1 protein expression and PGI2 biosynthesis in human EPCs outgrown from blood mononuclear cells. Expression of COX-2 protein was almost undetectable under basal conditions but significantly elevated after treatment with tumor necrosis factor-α. Condition medium derived from EPCs hyperpolarized human coronary artery smooth muscle cells, similar to the effect of the PGI2 analogue iloprost. The proliferation and in vitro tube formation by EPCs were inhibited by the COX inhibitor indomethacin, or by genetic inactivation of COX-1 or PGI2 synthase (PGIS) with small interfering RNA (siRNA). Impaired tube formation and cell proliferation induced by inactivation of COX-1 were rescued by the treatment with iloprost or selective peroxisome-proliferator activated receptor-δ (PPARδ) agonist, GW501516, but not by the selective PGI2 receptor agonist, cicaprost. Down regulation of PPARδ by siRNA also reduced angiogenic capacity of EPCs. Iloprost failed to reverse PPARδ-siRNA-induced impairment of angiogenesis. Furthermore, transfection of PGIS-siRNA, COX-1-siRNA, or PPARδ-siRNA into EPCs decreased the capillary formation in vivo after transplantation of human EPCs into the nude mice. These results suggest that activation of COX-1-PGI2-PPARδ pathway is an important mechanism underlying pro-angiogenic function of EPCs. PMID:18511850

Transplantation of in vitro cultured endothelial progenitor cells repairs the blood-brain barrier and improves cognitive function of APP/PS1 transgenic AD mice.

PubMed

Zhang, Shishuang; Zhi, Yongle; Li, Fei; Huang, Shan; Gao, Huabin; Han, Zhaoli; Ge, Xintong; Li, Dai; Chen, Fanglian; Kong, Xiaodong; Lei, Ping

2018-04-15

To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aβ in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-β (Aβ) transport, and chronic cerebral hypoperfusion causes Aβ deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aβ deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aβ senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aβ clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD. Copyright © 2018 Elsevier B.V. All rights reserved.

On Paperless-ness.

ERIC Educational Resources Information Center

Campbell, Neil A.

1984-01-01

Focusing on F. W. Lancaster's prediction that paperless communication systems are inevitable for science and technology, this article presents an analysis of role of editorial processing centers (EPC) in the development of electronic journals. The traditional scientific journal, the EPC, and the EPC and electronic journal are discussed. (60…

Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells.

PubMed

You, Jinzhi; Sun, Jiacheng; Ma, Teng; Yang, Ziying; Wang, Xu; Zhang, Zhiwei; Li, Jingjing; Wang, Longgang; Ii, Masaaki; Yang, Junjie; Shen, Zhenya

2017-08-03

Neovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells (EPCs). Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs. Streptozotocin-induced type 1 diabetic mice and nondiabetic mice both received unilateral hindlimb ischemic surgery. Curcumin was then administrated to the mice by lavage for 14 days consecutively. Laser Doppler perfusion imaging was conducted to demonstrate the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. In addition, angiogenesis, migration, proliferation abilities, and senescence were determined in EPCs isolated from diabetic and nondiabetic mice. Quantitative PCR was then used to determine the mRNA expression of vascular endothelial growth factor (VEGF) and angiopoetin-1 (Ang-1) in EPCs. Curcumin application to type 1 diabetic mice significantly improved blood reperfusion and increased the capillary density in ischemic hindlimbs. The in-vitro study also revealed that the angiogenesis, migration, and proliferation abilities of EPCs and the number of senescent EPCs were reversed by curcumin application. Quantitative PCR confirmed the overexpression of VEGF-A and Ang-1 in EPCs after curcumin treatment. Curcumin could enhance neovascularization via promoting the function of EPCs in a diabetic mouse hindlimb ischemia model.

Endothelial progenitor cells in mothers of low-birthweight infants: a link between defective placental vascularization and increased cardiovascular risk?

PubMed

King, Thomas F J; Bergin, David A; Kent, Etaoin M; Manning, Fiona; Reeves, Emer P; Dicker, Patrick; McElvaney, Noel G; Sreenan, Seamus; Malone, Fergal D; McDermott, John H

2013-01-01

Offspring birthweight is inversely associated with future maternal cardiovascular mortality, a relationship that has yet to be fully elucidated. Endothelial progenitor cells (EPCs) are thought to play a key role in vasculogenesis, and EPC numbers reflect cardiovascular risk. Our objective was to ascertain whether EPC number or function was reduced in mothers of low-birthweight infants. This was a prospective cohort study in a general antenatal department of a university maternity hospital. Twenty-three mothers of small for gestational age (SGA) infants (birthweight < 10th centile) and 23 mothers of appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile) were recruited. Maternal EPC number and function, conventional cardiovascular risk markers, and cord blood adiponectin were measured. Median EPC count was lower (294 vs. 367, P = 0.005) and EPC migration was reduced (0.91 vs. 1.59, P < 0.001) in SGA compared with AGA infants, with no difference in EPC adhesion (0.221 vs. 0.284 fluorescence units, P = 0.257). Maternal triglyceride levels were higher in SGA than AGA infants (0.98 vs. 0.78 mmol/liter, P = 0.006), but there was no difference in cholesterol, glucose, insulin, glycosylated hemoglobin, adiponectin, or blood pressure. There was a moderate monotone (increasing) relationship between birthweight and umbilical cord blood adiponectin (r = 0.475, P = 0.005). Giving birth to an SGA infant was associated with lower maternal EPC number and reduced migratory function. Cord blood adiponectin was significantly correlated with birthweight.

Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure.

PubMed

Zhang, Han; Feng, Liu; Wan, Qi-Lin; Hong, Yan; Li, Yan-Ming; Cheng, Guan-Chang; Han, Xin-Qiang

2015-07-01

Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hypertension (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = -0.45, P = 0.037) and blood level of OPG (r = -0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

Thymosin β4 promotes endothelial progenitor cell angiogenesis via a vascular endothelial growth factor‑dependent mechanism.

PubMed

Zhao, Yanbo; Song, Jiale; Bi, Xukun; Gao, Jing; Shen, Zhida; Zhu, Junhui; Fu, Guosheng

2018-06-20

Endothelial progenitor cells (EPCs) are a promising cell source for tissue repair and regeneration, predominantly through angiogenesis promotion. Paracrine functions serve a pivotal role in EPC‑mediated angiogenesis, which may be impaired by various cardiovascular risk factors. Therefore, it is important to identify a solution that optimizes the paracrine function of EPCs. Thymosin β4 (Tβ4) is a peptide with the potential to promote tissue regeneration and wound healing. A previous study demonstrated that Tβ4 enhances the EPC‑mediated angiogenesis of the ischemic myocardium. In the present study, whether Tβ4 improved angiogenesis by enhancing the paracrine effects of EPCs was investigated. A tube formation assay was used to assess the effect of angiogenesis, and the paracrine effects were measured using an ELISA kit. The results indicated that Tβ4 improved the paracrine effects of EPCs, evidenced by an increase in the expression of vascular endothelial growth factor (VEGF). EPC‑conditioned medium (EPC‑CM) significantly promoted human umbilical vein endothelial cell angiogenesis in vitro, which was further enhanced by pretreatment with Tβ4. The effect of Tβ4 pretreated EPC‑CM on angiogenesis was abolished by VEGF neutralizing antibody in vitro, indicating that increased VEGF secretion had a pivotal role in Tβ4‑mediated EPC angiogenesis. Furthermore, transplantation of EPCs pretreated with Tβ4 into infarcted rat hearts resulted in significantly higher VEGF expression in the border zone, compared with EPC transplantation alone. To further investigate whether the Akt/eNOS pathway was involved in Tβ4‑induced VEGF secretion in EPCs, the expression levels of VEGF in EPC‑CM were significantly decreased following knockdown of Akt or eNOS by small interfering RNA transfection. In conclusion, Tβ4 significantly increased angiogenesis by enhancing the paracrine effects of EPCs, evidenced by the increased expression of VEGF. The RAC‑α serine

Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase.

PubMed

Li, Xiaoxia; Song, Yimeng; Han, Yingying; Wang, Dawei; Zhu, Yi

2012-08-01

Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μm) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK. © 2012 John Wiley & Sons Ltd.

A Fermented Whole Grain Prevents Lipopolysaccharides-Induced Dysfunction in Human Endothelial Progenitor Cells

PubMed Central

Gabriele, Morena; Del Prato, Stefano; Pucci, Laura

2017-01-01

Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS) orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs), bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG), on early EPCs exposed to LPS. The potential protective effect of LG against LPS-induced alterations was evaluated as cell viability, adhesiveness, ROS production, gene expression, and NF-kB signaling pathway activation. Our results showed that LPS treatment did not affect EPCs viability and adhesiveness but induced endothelial alterations via activation of NF-kB signaling. LG protects EPCs from inflammation as well as from LPS-induced oxidative and endoplasmic reticulum (ER) stress reducing ROS levels, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defense. Moreover, LG pretreatment prevented NF-kB translocation from the cytoplasm into the nucleus caused by LPS exposure. In human EPCs, LPS increases ROS and upregulates proinflammatory tone, proapoptotic factors, and antioxidants. LG protects EPCs exposed to LPS reducing ROS, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defenses possibly by inhibiting NF-κB nuclear translocation. PMID:28386305

Dynamic Adhesion of Umbilical Cord Blood Endothelial Progenitor Cells under Laminar Shear Stress

PubMed Central

Angelos, Mathew G.; Brown, Melissa A.; Satterwhite, Lisa L.; Levering, Vrad W.; Shaked, Natan T.; Truskey, George A.

2010-01-01

Late outgrowth endothelial progenitor cells (EPCs) represent a promising cell source for rapid reendothelialization of damaged vasculature after expansion ex vivo and injection into the bloodstream. We characterized the dynamic adhesion of umbilical-cord-blood-derived EPCs (CB-EPCs) to surfaces coated with fibronectin. CB-EPC solution density affected the number of adherent cells and larger cells preferentially adhered at lower cell densities. The number of adherent cells varied with shear stress, with the maximum number of adherent cells and the shear stress at maximum adhesion depending upon fluid viscosity. CB-EPCs underwent limited rolling, transiently tethering for short distances before firm arrest. Immediately before arrest, the instantaneous velocity decreased independent of shear stress. A dimensional analysis indicated that adhesion was a function of the net force on the cells, the ratio of cell diffusion to sliding speed, and molecular diffusivity. Adhesion was not limited by the settling rate and was highly specific to α5β1 integrin. Total internal reflection fluorescence microscopy showed that CB-EPCs produced multiple contacts of α5β1 with the surface and the contact area grew during the first 20 min of attachment. These results demonstrate that CB-EPC adhesion from blood can occur under physiological levels of shear stress. PMID:21112278

78 FR 56601 - Airworthiness Directives; Fokker Services B.V. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... torque values of nuts on circuit breakers, contactors, and terminal blocks of the EPC and battery relay... blocks of the EPC and battery relay panel, as applicable; and do all applicable adjustments of the torque... contacts and nuts on circuit breakers, contactors, and terminal blocks of the EPC and battery relay panel...

Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease.

PubMed

Chan, Yap-Hang; Lam, Tai-Hing; Lau, Kui-Kai; Yiu, Kai-Hang; Siu, Chung-Wah; Li, Sheung-Wai; Chan, Hiu-Ting; Tam, Sidney; Lau, Chu-Pak; Tse, Hung-Fat

2011-06-01

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133(+) EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133(+) EPC (r = 0.31, p = 0.001). Patients with circulating CD133(+) EPC <10th percentile had significantly lower isoflavone intake than patients with CD133(+)EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133(+) EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133(+) EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.

Adsorption of Egg-PC to an Air/Water and Triolein/Water Bubble Interface: Use of the 2-Dimensional Phase Rule to Estimate the Surface Composition of a Phospholipid/Triolein/Water Surface as a Function of Surface Pressure

PubMed Central

Mitsche, Matthew A.; Wang, Libo; Small, Donald M.

2010-01-01

Phospholipid monolayers play a critical role in the structure and stabilization of biological interfaces including all membranes, the alveoli of the lung, fat droplets in adipose tissue, and lipoproteins. The behavior of phospholipids in bilayers and at an air-water interface is well understood. However, the study of phospholipids at oil-water interfaces is limited due to technical challenges. In this study, egg-phosphatidylcholine (EPC) was deposited from small unilamellar vesicles onto a bubble of either air or triolein (TO) formed in a low salt buffer. The surface tension (γ) was measured using a drop tensiometer. We observed that EPC binds irreversibly to both interfaces and at equilibrium exerts ~12 and 15 mN/m of pressure (Π) at an air and TO interface, respectively. After EPC was bound to the interface, the unbound EPC was washed out of the cuvette and the surface was compressed to study the Π/area relationship. To determine the surface concentration (Γ), which cannot be measured directly, compression isotherms from a Langmuir trough and drop tensiometer were compared. The air-water interfaces had identical characteristics using both techniques, thus Γ on the bubble can be determined by overlaying the two isotherms. TO and EPC are both surface active so in a mixed TO/EPC monolayer both molecules will be exposed to water. Since TO is less surface active than EPC, as Π increases the TO is progressively ejected. To understand the Π/area isotherm of EPC on a TO bubble, a variety of TO-EPC mixtures were spread at the air-water interface. The isotherms show an abrupt break in the curve caused by the ejection of TO from the monolayer into a new bulk phase. By overlaying the compression isotherm above the ejection point with a TO bubble compression isotherm, Γ can be estimated. This allows determination of Γ of EPC on a TO bubble as a function of Π. PMID:20151713

Adsorption of egg phosphatidylcholine to an air/water and triolein/water bubble interface: use of the 2-dimensional phase rule to estimate the surface composition of a phospholipid/triolein/water surface as a function of surface pressure.

PubMed

Mitsche, Matthew A; Wang, Libo; Small, Donald M

2010-03-11

Phospholipid monolayers play a critical role in the structure and stabilization of biological interfaces, including all membranes, the alveoli of the lungs, fat droplets in adipose tissue, and lipoproteins. The behavior of phospholipids in bilayers and at an air-water interface is well understood. However, the study of phospholipids at oil-water interfaces is limited due to technical challenges. In this study, egg phosphatidylcholine (EPC) was deposited from small unilamellar vesicles onto a bubble of either air or triolein (TO) formed in a low-salt buffer. The surface tension (gamma) was measured using a drop tensiometer. We observed that EPC binds irreversibly to both interfaces and at equilibrium exerts approximately 12 and 15 mN/m of pressure (Pi) at an air and TO interface, respectively. After EPC was bound to the interface, the unbound EPC was washed out of the cuvette, and the surface was compressed to study the Pi/area relationship. To determine the surface concentration (Gamma), which cannot be measured directly, compression isotherms from a Langmuir trough and drop tensiometer were compared. The air-water interfaces had identical characteristics using both techniques; thus, Gamma on the bubble can be determined by overlaying the two isotherms. Both TO and EPC are surface-active, so in a mixed TO/EPC monolayer, both molecules will be exposed to water. Since TO is less surface-active than EPC, as Pi increases, the TO is progressively ejected. To understand the Pi/area isotherm of EPC on a TO bubble, a variety of TO-EPC mixtures were spread at the air-water interface. The isotherms show an abrupt break in the curve caused by the ejection of TO from the monolayer into a new bulk phase. By overlaying the compression isotherm above the ejection point with a TO bubble compression isotherm, Gamma can be estimated. This allows determination of Gamma of EPC on a TO bubble as a function of Pi.

Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates.

PubMed

Qin, Meng; Guan, Xin; Zhang, Yu; Shen, Bin; Liu, Fang; Zhang, Qingyu; Ma, Yupo; Jiang, Yongping

2018-01-22

Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34 + cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34 + cells for the therapeutic potential of autologous transplantation. The human and nonhuman primate EPCs from mobilized PB CD34 + cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury. The mobilized PB CD34 + cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 10 8 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 10 6  ± 3.39 × 10 5 CD34 + cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs. We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34 + cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that

Adherence to lifestyle modifications after a cardiac rehabilitation program and endothelial progenitor cells. A six-month follow-up study.

PubMed

Cesari, F; Marcucci, R; Gori, A M; Burgisser, C; Francini, S; Roberts, A T; Sofi, F; Gensini, G F; Abbate, R; Fattirolli, F

2014-07-03

An increase of endothelial progenitor cells (EPCs) among acute myocardial infarction (AMI) patients participating in a cardiac rehabilitation (CR) program has been reported, but no data on the impact of adherence to lifestyle recommendations provided during a CR program on EPCs are available. It was our aim to investigate the effect of adherence to lifestyle recommendations on EPCs, inflammatory and functional parameters after six months of a CR program in AMI patients. In 110 AMI patients (90 male/20 female; mean age 57.9 ± 9.4 years) EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we administered a questionnaire assessing dietary habits and physical activity. At T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP (p<0.0001). Patient population was divided into three categories by Healthy Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle recommendations). We observed a significant association between adherence to lifestyle recommendations, increase in EPCs and exercise capacity between T1 and T2 (Δ EPCs p for trend <0.05; ΔWatt max p for trend=0.004). In a multivariate logistic regression analyses, being in the highest tertile of HL score affected the likelihood of an increase of EPC levels at T2 [OR (95% confidence interval): 3.36 (1.0-10.72) p=0.04]. In conclusion, adherence to lifestyle recommendations provided during a CR program positively influences EPC levels and exercise capacity.

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

PubMed

Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

2013-10-01

Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

PubMed

Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

2016-02-01

Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

Effect of intensive glycaemic control on endothelial progenitor cells in patients with long-standing uncontrolled type 2 diabetes.

PubMed

Lev, Eli I; Singer, Joel; Leshem-Lev, Dorit; Rigler, Merav; Dadush, Oshrat; Vaduganathan, Muthiah; Battler, Alexander; Kornowski, Ran

2014-09-01

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. However, in patients with diabetes, EPC number and function are markedly reduced. It is unclear whether intensive glycaemic control can modify EPC properties in diabetic patients. We aimed to examine whether glycaemic control can improve EPC number and function in patients with long-standing uncontrolled type 2 diabetes. Thirty-five patients with treated type 2 diabetes and HgA1c ≥ 8.5% were included. Patients were tested at baseline and after 3-4 months of an intensive glycaemic control programme, with the aim of achieving HgA1c of 7%. The diabetes group was compared to 20 patients without diabetes (control). Circulating EPC levels were assessed by flow cytometry for expression of VEGFR2, CD133, and CD34. The capacity of the cells to form colony-forming units (CFUs), and their migration and viability were quantified after 1 week of culture. Patients with diabetes (mean age 61.1 ± 7 years, 28.6% women, disease duration of 19.2 ± 8 years) had a baseline HgA1c of 9.4 ± 0.8%. After the glycaemic control period, HgA1c decreased to 8 ± 0.8%. Circulating EPC levels increased significantly after the intensive control period and reached a level similar to the control group. The number of EPC CFUs also increased significantly after glycaemic control but remained lower than the control group. All EPC functional assays improved following the glycaemic control. In patients with uncontrolled long-standing type 2 diabetes, intensive glycaemic control was associated with an increase in the levels of circulating EPCs, and improvement in their functional properties. © The European Society of Cardiology 2013 Reprints and permissions:sagepub.co.uk/journalsPermissions.nav.

Endothelial progenitor cells proliferated via MEK-dependent p42 MAPK signaling pathway.

PubMed

Sandra, Ferry; Oktaviono, Yudi Her; Widodo, Mohammad Aris; Dirgantara, Yanni; Chouw, Angliana; Sargowo, Djanggan

2015-02-01

Endothelial progenitor cells (EPCs) clinical applications have been well reported. However, due to low number of EPCs that could be isolated, EPCs expansion study became one of the main focuses. Some optimized mediums to culture EPCs were currently available. However, the proliferation signaling pathway is not clearly disclosed yet. Peripheral blood was collected from eight healthy subjects, followed by mononuclear cells (MNCs) isolation. MNCs were then prepared and cultured for 2 days. After that, non-adherent cells were harvested and further cultured for 3 days. Resulted colony-forming unit (CFU)-Hill colonies were documented and enumerated under an inverted light microscope. To detect membrane markers, immunofluorescence was performed to detect CD34, VEGFR-2, and CD133. Cell documentation was conducted under a fluorescence microscope. To check cell proliferation, XTT Cell Proliferation Assay Kit was used according to kit insert. To detect possible activation of p44/42 MAPK, western blot was performed to detect p44/42 MAPK and phosphorylated p44/42 MAPK. All visualized bands were captured and quantified. Our results showed that EPCs markers (CD34, CD133 and VEGFR-2) were detected in 3 days culture. From XTT cell proliferation assay and CFU enumeration results, we found that EPCs proliferated significantly (p = 0.012) with addition of supplement. Phosphorylated-p42 MAPK expression of EPCs treated with supplement was significantly higher than the one of EPCs without treatment. Significant inhibition of p42 MAPK phosphorylation by U0126 was observed (p = 0.012). By pretreatment of U0126, number of viable cells and CFUs treated with supplement was significantly decreased (p = 0.012). Our results showed that MEK-dependent p42 MAPK pathway might play an important role in EPCs proliferation.

Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations.

PubMed

Kötting, J; Berger, M R; Unger, C; Eibl, H

1992-01-01

Hexadecylphosphocholine (HPC) and octadecylphosphocholine (OPC) show very potent antitumor activity against autochthonous methylnitrosourea-induced mammary carcinomas in rats. The longer-chain and unsaturated homologue erucylphosphocholine (EPC) forms lamellar structures rather than micelles, but nonetheless exhibits antineoplastic activity. Methylnitrosourea was used in the present study to induce autochthonous mammary carcinomas in virgin Sprague-Dawley rats. At 6 and 11 days following oral therapy, the biodistribution of HPC, OPC and EPC was analyzed in the serum, tumor, liver, kidney, lung, small intestine, brain and spleen of rats by high-performance thin-layer chromatography. In contrast to the almost identical tumor response noted, the distribution of the three homologues differed markedly. The serum levels of 50 nmol/ml obtained for OPC and EPC were much lower than the value of 120 nmol/ml measured for HPC. Nevertheless, the quite different serum levels resulted in similar tumor concentrations of about 200 nmol/g for all three of the compounds. Whereas HPC preferably accumulated in the kidney (1 mumol/g), OPC was found at increased concentrations (400 nmol/g) in the spleen, kidney and lung. In spite of the high daily dose of 120 mumol/kg EPC as compared with 51 mumol/kg HPC or OPC, EPC concentrations (100-200 nmol/g) were low in most tissues. High EPC concentrations were found in the small intestine (628 nmol/g). Values of 170 nmol/g were found for HPC and OPC in the brain, whereas the EPC concentration was 120 nmol/g. Obviously, structural modifications in the alkyl chain strongly influence the distribution pattern of alkylphosphocholines in animals. Since EPC yielded the highest tissue-to-serum concentration ratio in tumor tissue (5.1) and the lowest levels in other organs, we conclude that EPC is the most promising candidate for drug development in cancer therapy.

Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome.

PubMed

Sonnenschein, Kristina; Horváth, Tibor; Mueller, Maja; Markowski, Andrea; Siegmund, Tina; Jacob, Christian; Drexler, Helmut; Landmesser, Ulf

2011-06-01

Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p < 0.05) and improved endothelium-dependent vasodilation. Nitric oxide production of EPCs was substantially increased after exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with

Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

PubMed

Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

2015-01-01

Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase.

PubMed

Di Santo, Stefano; Seiler, Stefanie; Fuchs, Anna-Lena; Staudigl, Jennifer; Widmer, Hans Rudolf

2014-01-01

Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

[VEGF165 transfected endothelial progenitor cells mediated by lentivirus alleviated ALI in rats].

PubMed

He, Zhaohui; He, Huiwei; Lu, Yuanhua; Chen, Zhi; Xu, Fanghua; Wang, Rongsheng; Yang, Chunli

2017-11-01

To investigate the protective effects of vascular endothelial growth factor-165 (VEGF165) transfected the endothelial progenitor cells (EPCs) mediated by lentivirus on acute lung injury (ALI) in rats. The mononuclear cells from the male Sprague-Dawley (SD) rats were isolated and cultured to get the EPCs for study. The lentivirus vector carrying the human VEGF165 gene was constructed. According to the random number table method, 90 male SD rats were divided into ALI model group, phosphate buffer solution (PBS) group, EPCs treatment group, none transfected EPCs treatment group and VEGF165 transfected EPCs treatment group, and the rats in each group were subdivided into 4, 12 and 48 hours subgroups, with 6 rats in each subgroup. The rat model of ALI was reproduced by intravenous injection of oleic acid (0.15 μL/g). Then each treatment group was given PBS, EPCs, none transfected EPCs and VEGF165 transfected EPCs respectively with the same volume of 0.2 mL. For the groups with cells, about 1×10 6 cells were contained. Abdominal aortic blood and lung tissue were harvested at 4, 12 and 48 hours. Arterial blood gas analysis was performed. The lung wet/dry weight ratio (W/D) was calculated. The expressions of induced nitric oxide synthase (iNOS), endothelin-1 (ET-1) and VEGF165 were determined by enzyme-linked immunosorbent assay (ELISA). After dyed with hematoxylin-eosin (HE), the lung tissue pathology was observed and the lung injury score was performed. Compared with the ALI model group, the arterial partial pressure of oxygen (PaO 2 ) in EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups was significantly increased from 4 hours, and lung W/D, expressions of iNOS and ET-1 were significantly decreased, and VEGF165 expression was significantly increased. Compared with the EPCs treatment group, the increase in PaO 2 , the decrease in lung W/D and expressions of iNOS and ET-1, and the increase in VEGF165 expression in VEGF165 transfected EPCs

The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: a randomized clinical trial.

PubMed

Chiva-Blanch, Gemma; Condines, Ximena; Magraner, Emma; Roth, Irene; Valderas-Martínez, Palmira; Arranz, Sara; Casas, Rosa; Martínez-Huélamo, Miriam; Vallverdú-Queralt, Anna; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Estruch, Ramon

2014-04-01

Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sun Ginseng Protects Endothelial Progenitor Cells From Senescence Associated Apoptosis

PubMed Central

Im, Wooseok; Chung, Jin-Young; Bhan, Jaejun; Lim, Jiyeon; Lee, Soon-Tae; Chu, Kon; Kim, Manho

2012-01-01

Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verified that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms. PMID:23717107

Desensitization shortens the high-quantal-content endplate current time course in frog muscle with intact cholinesterase.

PubMed

Giniatullin, R A; Talantova, M; Vyskocil, F

1997-08-01

1. The desensitization induced by bath-applied carbachol or acetylcholine (ACh) and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with intact synaptic acetylcholinesterase (AChE). 2. The reduction in the density and number of postsynaptic receptors produced by desensitization lowered the amplitude of the endplate currents (EPCs) and shortened the EPC decay when the quantal content (m) of the EPC was about 170 and when multiple release of quanta at single active zones was highly probably. The shortening of high-quantal-content EPCs persisted for at least 15 min after the wash-out of agonists, at a time when the amplitude had recovered fully. 3. The decay times of the low-quantal-content EPCs recorded from preparations pretreated with 5 mM Mg2+ (m approximately 70) and single-quantum miniature endplate currents (MEPCs) were not affected by carbachol, ACh or proadifen. 4. The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE. 5. It is assumed that high-quantal-content EPCs increase the incidence of multiple quanta release at single active zones and the probability of repetitive binding of ACh molecules which leads to EPC prolongation. The shortening which persists after complete recovery of the amplitude during wash-out of the exogenous agonist is probably due to 'trapping' of ACh molecules onto rapidly desensitized receptors and the reduced density of functional AChRs during the quantum action.

Protective effects of bone marrow-derived endothelial progenitor cells and Houttuynia cordata in lipopolysaccharide-induced acute lung injury in rats.

PubMed

Cai, Da-Sheng; Zhou, Heng; Liu, Wei-Wei; Pei, Ling

2013-01-01

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a serious health problem, and an effective treatment is needed for use in the clinical setting. In this study, we first constructed ALI models in Adult Sprague-Dawley rats. We then used an herbal medicine, Houttuynia cordata (HC), to enhance the effect of endothelial progenitor cells (EPCs) on ALI. (1) HC improved the therapeutic effects of EPCs on lipopolysachharide-induced ALI in the rat model; (2) HC down-regulated the anti-inflammatory response by suppressing inflammatory cytokines; (3) the combination of EPC and HC reduced expression of iNOS and ET-1 and subsequently prevented lung injury. Combined EPC and HC therapy was more effective than either therapy alone. EPC and HC could be used in the clinical treatment of ALI. © 2013 S. Karger AG, Basel.

Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities.

PubMed

Kim, Yeon-Ju; Ji, Seung Taek; Kim, Da Yeon; Jung, Seok Yun; Kang, Songhwa; Park, Ji Hye; Jang, Woong Bi; Yun, Jisoo; Ha, Jongseong; Lee, Dong Hyung; Kwon, Sang-Mo

2018-06-12

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

The molecular characterization of porcine egg precursor cells

PubMed Central

Tsai, Te-Sha; Johnson, Jacqueline; White, Yvonne; John, Justin C.

2017-01-01

Female-factor infertility can be caused by poor oocyte quality and depleted ovarian reserves. Egg precursor cells (EPCs), isolated from the ovarian cortex, have the potential to be used to overcome female infertility. We aimed to define the origins of EPCs by analyzing their gene expression profiles and mtDNA content using a mini-pig model. We characterized FAC-sorted DDX4+-derived porcine EPCs by performing RNA-sequencing and determined that they utilize pathways important for cell cycle and proliferation, which supports the existence of adult mitotically active oogonial cells. Expression of the pluripotent markers Sox2 and Oct4, and the primitive germ cell markers Blimp1 and Stella were not detected. However, Nanog and Ddx4 were expressed, as were the primitive germ cell markers Fragilis, c-Kit and Tert. Moreover, porcine EPCs expressed self-renewal and proliferation markers including Myc, Esrrb, Id2, Klf4, Klf5, Stat3, Fgfr1, Fgfr2 and Il6st. The presence of Zp1, Zp2, Zp3 and Nobox were not detected, indicating that porcine EPCs are not indicative of mature primordial oocytes. We performed mitochondrial DNA Next Generation Sequencing and determined that one mtDNA variant harbored by EPCs was present in oocytes, preimplantation embryos and somatic tissues over three generations in our mini-pig model indicating the potential germline origin of EPCs. PMID:28969006

Chronic heart failure and aging - effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study.

PubMed

Sandri, Marcus; Viehmann, Manuel; Adams, Volker; Rabald, Kristin; Mangner, Norman; Höllriegel, Robert; Lurz, Philipp; Erbs, Sandra; Linke, Axel; Kirsch, Katharina; Möbius-Winkler, Sven; Thiery, Joachim; Teupser, Daniel; Hambrecht, Rainer; Schuler, Gerhard; Gielen, Stephan

2016-03-01

A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age. We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed. As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls. Four weeks of exercise training are effective in improving EPC number

Concomitant external pneumatic compression treatment with consecutive days of high intensity interval training reduces markers of proteolysis.

PubMed

Haun, Cody T; Roberts, Michael D; Romero, Matthew A; Osburn, Shelby C; Healy, James C; Moore, Angelique N; Mobley, Christopher B; Roberson, Paul A; Kephart, Wesley C; Mumford, Petey W; Goodlett, Michael D; Pascoe, David D; Martin, Jeffrey S

2017-12-01

To compare the effects of external pneumatic compression (EPC) and sham when used concurrently with high intensity interval training (HIIT) on performance-related outcomes and recovery-related molecular measures. Eighteen recreationally endurance-trained male participants (age: 21.6 ± 2.4 years, BMI: 25.7 ± 0.5 kg/m 2 , VO 2peak : 51.3 ± 0.9 mL/kg/min) were randomized to balanced sham and EPC treatment groups. Three consecutive days of HIIT followed by EPC/sham treatment (Days 2-4) and 3 consecutive days of recovery (Days 5-7) with EPC/sham only on Days 5-6 were employed. Venipuncture, flexibility and pressure-to-pain threshold (PPT) measurements were made throughout. Vastus lateralis muscle was biopsied at PRE (i.e., Day 1), 1-h post-EPC/sham treatment on Day 2 (POST1), and 24-h post-EPC/sham treatment on Day 7 (POST2). 6-km run time trial performance was tested at PRE and POST2. No group × time interaction was observed for flexibility, PPT, or serum measures of creatine kinase (CK), hsCRP, and 8-isoprostane. However, there was a main effect of time for serum CK (p = 0.005). Change from PRE in 6-km run times at POST2 were not significantly different between groups. Significant between-groups differences existed for change from PRE in atrogin-1 mRNA (p = 0.018) at the POST1 time point (EPC: - 19.7 ± 8.1%, sham: + 7.7 ± 5.9%) and atrogin-1 protein concentration (p = 0.013) at the POST2 time point (EPC: - 31.8 ± 7.5%, sham: + 96.0 ± 34.7%). In addition, change from PRE in poly-Ub proteins was significantly different between groups at both the POST1 (EPC: - 26.0 ± 10.3%, sham: + 34.8 ± 28.5%; p = 0.046) and POST2 (EPC: - 33.7 ± 17.2%, sham: + 21.4 ± 14.9%; p = 0.037) time points. EPC when used concurrently with HIIT and in subsequent recovery days reduces skeletal muscle markers of proteolysis.

Endothelial progenitor cells bind and inhibit platelet function and thrombus formation.

PubMed

Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

2009-12-01

Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride-induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Peripheral blood mononuclear cell-derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and

Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression

PubMed Central

Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

2015-01-01

Aims Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Methods and results Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1–CXCR2 and CX3CL1–CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. Conclusion CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. PMID:25765938

Evidence synthesis activities of a hospital evidence-based practice center and impact on hospital decision making.

PubMed

Jayakumar, Kishore L; Lavenberg, Julia A; Mitchell, Matthew D; Doshi, Jalpa A; Leas, Brian; Goldmann, David R; Williams, Kendal; Brennan, Patrick J; Umscheid, Craig A

2016-03-01

Hospital evidence-based practice centers (EPCs) synthesize and disseminate evidence locally, but their impact on institutional decision making is unclear. To assess the evidence synthesis activities and impact of a hospital EPC serving a large academic healthcare system. Descriptive analysis of the EPC's database of rapid systematic reviews since EPC inception (July 2006-June 2014), and survey of report requestors from the EPC's last 4 fiscal years. Descriptive analyses examined requestor and report characteristics; questionnaire examined report usability, impact, and requestor satisfaction (higher scores on 5-point Likert scales reflected greater agreement). The EPC completed 249 evidence reviews since inception. The most common requestors were clinical departments (29%, n = 72), chief medical officers (19%, n = 47), and purchasing committees (14%, n = 35). The most common technologies reviewed were drugs (24%, n = 60), devices (19%, n = 48), and care processes (12%, n = 31). Mean report completion time was 70 days. Thirty reports (12%) informed computerized decision support interventions. More than half of reports (56%, n = 139) were completed in the last 4 fiscal years for 65 requestors. Of the 64 eligible participants, 46 responded (72%). Requestors were satisfied with the report (mean = 4.4), and agreed it was delivered promptly (mean = 4.4), answered the questions posed (mean = 4.3), and informed their final decision (mean = 4.1). This is the first examination of evidence synthesis activities by a hospital EPC in the United States. Our findings suggest hospital EPCs can efficiently synthesize and disseminate evidence addressing a range of clinical topics for diverse stakeholders, and can influence local decision making. © 2015 Society of Hospital Medicine.

Aerobic exercise modulation of mental stress-induced responses in cultured endothelial progenitor cells from healthy and metabolic syndrome subjects.

PubMed

Rocha, Natalia G; Sales, Allan R K; Miranda, Renan L; Silva, Mayra S; Silva, Jemima F R; Silva, Bruno M; Santos, Aline A; Nóbrega, Antonio C L

2015-02-15

Numerous studies have demonstrated that exercise acutely prevents the reduction in flow-mediated dilation induced by mental stress in subjects with metabolic syndrome (MetS). However, it is unknown whether a similar effect occurs in endothelial progenitors cells (EPCs). This study investigated whether exercise protects from the deleterious effect of mental stress on cultured EPCs in healthy subjects and those with MetS. Ten healthy subjects (aged 31±2) and ten subjects with MetS (aged 36±2) were enrolled. Subjects underwent a mental stress test, followed immediately by either 40 min of leg cycling or rest across two randomized sessions: mental stress+non-exercise control (MS) and mental stress+exercise (MS+EXE). The Stroop Color-Word Test was used to elicit mental stress. Blood samples were drawn at baseline and following sessions to isolate mononuclear cells. These cells were cultured in fibronectin-coated plates for seven days, and EPCs were identified by immunofluorescence (acLDL(+)/ UEA-I Lectin(+)). All subjects presented similar increases in mean blood pressure and heart rate during the mental stress test (P<0.01) in both the MS and MS+EXE sessions. Number of EPCs was not different between groups at baseline in both sessions (P>0.05). The EPC response to MS and MS+EXE was increased in healthy subjects, whereas it was decreased in subjects with MetS (P<0.04). In healthy subjects, the EPC response to MS+EXE was greater than the response to MS alone (P=0.03). An exercise session increased EPCs in healthy subjects but did not prevent the EPC reduction induced by mental stress among subjects with MetS. © 2015.

Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves

PubMed Central

Mettler, Bret A.; Engelmayr, George C.; Aikawa, Elena; Bischoff, Joyce; Martin, David P.; Exarhopoulos, Alexis; Moses, Marsha A.; Schoen, Frederick J.; Sacks, Michael S.

2010-01-01

Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not α-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves. PMID:19698056

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

Endothelial progenitor cells dysfunction and impaired tissue reparation: The missed link in diabetes mellitus development.

PubMed

Berezin, Alexander E

Diabetes mellitus (DM) is considered a leading cause of premature cardiovascular (CV) mortality and morbidity in general population and in individuals with known CV disease. Recent animal and clinical studies have shown that reduced number and weak function of endothelial progenitor cells (EPCs) may not only indicate to higher CV risk, but contribute to the impaired heart and vessels reparation in patients with DM. Moreover, EPCs having a protective impact on the vasculature may mediate the functioning of other organs and systems. Therefore, EPCs dysfunction is probably promising target for DM treatment strategy, while the role of restoring of EPCs number and functionality in CV risk diminish and reduce of DM-related complications is not fully clear. The aim of the review is summary of knowledge regarding EPCs dysfunction in DM patients. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Endothelial progenitor cells--an evolving story.

PubMed

Pearson, Jeremy D

2010-05-01

The first description of endothelial progenitor cells (EPC) in 1997 led rapidly to substantial changes in our understanding of angiogenesis, and within 5 years to the first clinical studies in humans using bone marrow derived EPC to enhance coronary neovascularisation and cardiac function after myocardial ischemia. However, to improve the success of this therapy a clearer understanding of the biology of EPC is needed. This article summarises recent data indicating that most EPC are not, in fact, endothelial progenitors but can be better described as angiogenic monocytes, and explores the implications this has for their future therapeutic use. Copyright 2009 Elsevier Inc. All rights reserved.

How to utilize Ca²⁺ signals to rejuvenate the repairative phenotype of senescent endothelial progenitor cells in elderly patients affected by cardiovascular diseases: a useful therapeutic support of surgical approach?

PubMed

Moccia, Francesco; Dragoni, Silvia; Cinelli, Mariapia; Montagnani, Stefania; Amato, Bruno; Rosti, Vittorio; Guerra, Germano; Tanzi, Franco

2013-01-01

Endothelial dysfunction or loss is the early event that leads to a host of severe cardiovascular diseases, such as atherosclerosis, hypertension, brain stroke, myocardial infarction, and peripheral artery disease. Ageing is regarded among the most detrimental risk factor for vascular endothelium and predisposes the subject to atheroscleorosis and inflammatory states even in absence of traditional comorbid conditions. Standard treatment to restore blood perfusion through stenotic arteries are surgical or endovascular revascularization. Unfortunately, ageing patients are not the most amenable candidates for such interventions, due to high operative risk or unfavourable vascular involvement. It has recently been suggested that the transplantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) might constitute an alternative and viable therapeutic option for these individuals. Albeit pre-clinical studies demonstrated the feasibility of EPC-based therapy to recapitulate the diseased vasculature of young and healthy animals, clinical studies provided less impressive results in old ischemic human patients. One hurdle associated to this kind of approach is the senescence of autologous EPCs, which are less abundant in peripheral blood and display a reduced pro-angiogenic activity. Conversely, umbilical cord blood (UCB)-derived EPCs are more suitable for cellular therapeutics due to their higher frequency and sensitivity to growth factors, such as vascular endothelial growth factor (VEGF). An increase in intracellular Ca(2+) concentration is central to EPC activation by VEGF. We have recently demonstrated that the Ca(2+) signalling machinery driving the oscillatory Ca(2+) response to this important growth factor is different in UCB-derived EPCs as compared to their peripheral counterparts. In particular, we focussed on the so-called endothelial colony forming cells (ECFCs), which are the only EPC population belonging to the endothelial lineage and able

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielsen, Nathalie; Laustsen, Christoffer; Bertelsen, Lotte Bonde, E-mail: Lotte@clin.au.dk

Endothelial progenitor cells (EPCs) represent a heterogeneous cell population that is believed to be involved in vasculogenesis. With the purpose of enhancing endothelial repair, EPCs could have a potential for future cell therapies. Due to the low amount of EPCs in the peripheral circulating blood, in vitro expansion is needed before administration to recipients and the effects of in vitro culturing is still an under-evaluated field with little knowledge of how the cells change over time in culture. The aim of this study was to use hyperpolarised carbon-13 magnetic resonance spectroscopy to profile important metabolic pathways in a population ofmore » progenitor cells and to show that cell culturing in 3D scaffolds seem to block the metabolic processes that leads to cell senescence. The metabolic breakdown of hyperpolarized [1-{sup 13}C]pyruvate was followed after injection of the substrate to a bioreactor system with EPCs either adhered to 3D printed scaffolds or kept in cell suspension. The pyruvate-to-lactate conversion was elevated in suspension of EPCs compared to the EPCs adhered to scaffolds. Furthermore in the setup with EPCs in suspension, an increase in lactate production was seen over time indicating that the older the cultures of EPCs was before using the cells for cell suspension experiments, the more lactate they produce, compared to a constant lactate level in the cells adhered to scaffolds. It could therefore be stated that cells grown first in 2D culture and subsequent prepared for cell suspension show a metabolism with higher lactate production consistent with cells senescence processes compared to cells grown first at 2D culture and subsequent in the 3D printed scaffolds, where metabolism shows no sign of metabolic shifting during the monitored period. - Highlights: • Hyperpolarized 13C MRS detects EPCs metabolic changes associated with ageing and cultivating conditions. • Increased lactate production in EPC’s correlates positively with

Circulating Bone Marrow-Derived CD45-/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn's Disease.

PubMed

Boltin, Doron; Kamenetsky, Zvi; Perets, Tsachi Tsadok; Snir, Yifat; Sapoznikov, Boris; Schmilovitz-Weiss, Hemda; Ablin, Jacob Nadav; Dickman, Ram; Niv, Yaron

2017-03-01

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. To determine whether the circulating levels of EPCs are changed in the context of CD. CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

Obstructive sleep apnea and endothelial progenitor cells.

PubMed

Wang, Qing; Wu, Qi; Feng, Jing; Sun, Xin

2013-10-18

Obstructive sleep apnea (OSA) occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow-derived endothelial progenitor cells (EPCs) within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has emerged. The possible mechanisms underlying the decrease in the number or function of EPCs include prolonged inflammation response, oxidative stress, increased sympathetic activation, physiological adaptive responses of tissue to hypoxia, reduced EPC mobilization, EPC apoptosis, and functional impairment in untreated OSA. Continuous positive airway pressure (CPAP) therapy for OSA affects the mobilization, apoptosis, and function of EPCs through preventing intermittent hypoxia episodes, improving sleep quality, and reducing systemic inflammation, oxidative stress levels, and sympathetic overactivation. To improve

Fabrication of endothelial progenitor cell capture surface via DNA aptamer modifying dopamine/polyethyleneimine copolymer film

NASA Astrophysics Data System (ADS)

Li, Xin; Deng, Jinchuan; Yuan, Shuheng; Wang, Juan; Luo, Rifang; Chen, Si; Wang, Jin; Huang, Nan

2016-11-01

Endothelial progenitor cells (EPCs) are mainly located in bone marrow and circulate, and play a crucial role in repairmen of injury endothelium. One of the most promising strategies of stents designs were considered to make in-situ endothelialization in vivo via EPC-capture biomolecules on a vascular graft to capture EPCs directly from circulatory blood. In this work, an EPC specific aptamer with a 34 bases single strand DNA sequence was conjugated onto the stent surface via dopamine/polyethyleneimine copolymer film as a platform and linker. The assembled density of DNA aptamer could be regulated by controlling dopamine percentage in this copolymer film. X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) and fluorescence test confirmed the successful immobilization of DNA aptamer. To confirm its biofunctionality and cytocompatibility, the capturing cells ability of the aptamer modified surface and the effects on the growth behavior of human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs) were investigated. The aptamer functionalized sample revealed a good EPC-capture ability, and had a cellular friendly feature for both EPC and EC growth, while not stimulated the hyperplasia of SMCs. And, the co-culture experiment of three types of cells confirmed the specificity capturing of EPCs to aptamer modified surface, rather than ECs and SMCs. These data suggested that this aptamer functionalized surface may have a large potentiality for the application of vascular grafts with targeted endothelialization.

PSGL-1–mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells

PubMed Central

Foubert, Philippe; Silvestre, Jean-Sébastien; Souttou, Boussad; Barateau, Véronique; Martin, Coralie; Ebrahimian, Téni G.; Leré-Déan, Carole; Contreres, Jean Olivier; Sulpice, Eric; Levy, Bernard I.; Plouët, Jean; Tobelem, Gérard; Le Ricousse-Roussanne, Sophie

2007-01-01

Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization; however, only a small proportion of injected cells home to the lesion and incorporate into the neocapillaries. Consequently, this type of cell therapy requires substantial improvement to be of clinical value. Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors and their ephrin ligands are key regulators of vascular development. We postulated that activation of the EphB4/ephrin-B2 system may enhance EPC proangiogenic potential. In this report, we demonstrate in a nude mouse model of hind limb ischemia that EphB4 activation with an ephrin-B2–Fc chimeric protein increases the angiogenic potential of human EPCs. This effect was abolished by EphB4 siRNA, confirming that it is mediated by EphB4. EphB4 activation enhanced P selectin glycoprotein ligand-1 (PSGL-1) expression and EPC adhesion. Inhibition of PSGL-1 by siRNA reversed the proangiogenic and adhesive effects of EphB4 activation. Moreover, neutralizing antibodies to E selectin and P selectin blocked ephrin-B2–Fc–stimulated EPC adhesion properties. Thus, activation of EphB4 enhances EPC proangiogenic capacity through induction of PSGL-1 expression and adhesion to E selectin and P selectin. Therefore, activation of EphB4 is an innovative and potentially valuable therapeutic strategy for improving the recruitment of EPCs to sites of neovascularization and thereby the efficiency of cell-based proangiogenic therapy. PMID:17510705

In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor.

PubMed

Melchiorri, Anthony J; Bracaglia, Laura G; Kimerer, Lucas K; Hibino, Narutoshi; Fisher, John P

2016-07-01

A critical challenge to the success of biodegradable vascular grafts is the establishment of a healthy endothelium. To establish this monolayer of endothelial cells (ECs), a variety of techniques have been developed, including cell seeding. Vascular grafts may be seeded with relevant cell types and allowed to mature before implantation. Due to the low proliferative ability of adult ECs and issues with donor site morbidity, there has been increasing interest in using endothelial progenitor cells (EPCs) for vascular healing procedures. In this work, we combined the proliferative and differentiation capabilities of a commercial cell line of early EPCs with an established bioreactor system to support the maturation of cell-seeded vascular grafts. All components of the vascular graft and bioreactor setup are commercially available and allow for complete customization of the scaffold and culturing system. This bioreactor setup enables the control of flow through the graft, imparting fluid shear stress on EPCs and affecting cellular proliferation and differentiation. Grafts cultured with EPCs in the bioreactor system demonstrated greatly increased cell populations and neotissue formation compared with grafts seeded and cultured in a static system. Increased expression of markers for mature endothelial tissues were also observed in bioreactor-cultured EPC-seeded grafts. These findings suggest the distinct advantages of a customizable bioreactor setup for the proliferation and maturation of EPCs. Such a strategy may be beneficial for utilizing EPCs in vascular tissue engineering applications.

Influence of depression and anxiety on circulating endothelial progenitor cells in patients with acute coronary syndromes.

PubMed

Felice, Francesca; Di Stefano, Rossella; Pini, Stefano; Mazzotta, Gianfranco; Bovenzi, Francesco M; Bertoli, Daniele; Abelli, Marianna; Borelli, Lucia; Cardini, Alessandra; Lari, Lisa; Gesi, Camilla; Michi, Paola; Morrone, Doralisa; Gnudi, Luigi; Balbarini, Alberto

2015-05-01

Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders. Copyright © 2015 John Wiley & Sons, Ltd.

Anthocyans-rich Aronia melanocarpa extract possesses ability to protect endothelial progenitor cells against angiotensin II induced dysfunction.

PubMed

Parzonko, Andrzej; Oświt, Aleksandra; Bazylko, Agnieszka; Naruszewicz, Marek

2015-12-15

Endothelial progenitor cells (EPC) may provide protection against atherosclerosis and plaque rupture by their innate ability to replace dysfunctional or damaged endothelial cells in plaque microvessels. There is evidence that angiotensin II may impair the angiogenic functions of EPCs in the atherosclerotic plaque by accelerating senescence and inhibiting their proliferation through oxidative stress induction. In this study, we examined whether chokeberry (Aronia melanocarpa) fruit extract, containing mainly anthocyanins with potent antioxidative properties, could protect EPCs against angiotensin-induced oxidative stress. EPCs were isolated from peripheral blood of young healthy volunteers and cultivated on fibronectin-coated plates in the presence or absence of angiotensin II (1 µM) and chokeberry extract (1-25 µg/ml). EPCs exposed to chokeberry extract prior to angiotensin II showed a significant increase of proliferation and telomerase activity, and a decrease in the percentage of senescent cells and intracellular ROS formation in comparison to angiotensin II treated cells. Furthermore, extract increased migration ability, adhesion to fibronectin and the angiogenic potential of EPC in vitro diminished by angiotensin II in a concentration-dependent manner. That effect was related to the activation of the Nrf2 transcription factor and the increase of HO-1 expression. Our results suggested that chokeberry extract may protect EPCs against angiotensin II-induced dysfunction and could play a potential role in the prevention of coronary artery disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Eastland Prostate Cancer Survey: instrument development and psychometric testing.

PubMed

Eastland, Taryn Y; Dancy, Barbara L

2013-03-01

African-American (AA) women could be instrumental in communicating positive prostate screening behavior to the significant males in their lives. However, little is known about AA women's prostate cancer attitudes, perceived behavioral control, subjective norms, intentions, behaviors, and knowledge regarding prostate cancer screening. This study describes the development and psychometric testing of the Eastland Prostate Cancer Survey (EPCS). A nonexperimental, correlational study with 200 AA women was used to test the psychometric properties of the six-subscale EPCS with 66 items. Construct validity, internal consistency, and test-retest reliability for the EPCS were acceptable and resulted in an eight-subscale EPCS with 56 items. Cronbach's alphas for the subscales ranged from 0.69 to 0.92. The EPCS is a culturally sensitive, gender-relevant instrument that could be used by community health providers to develop community health programs aimed at engaging AA women in the promotion of prostate cancer screening for AA men.

Nucleosome-free DNA regions differentially affect distant communication in chromatin

PubMed Central

Nizovtseva, Ekaterina V.; Clauvelin, Nicolas; Todolli, Stefjord; Kulaeva, Olga I.; Wengrzynek, Scott

2017-01-01

Abstract Communication between distantly spaced genomic regions is one of the key features of gene regulation in eukaryotes. Chromatin per se can stimulate efficient enhancer-promoter communication (EPC); however, the role of chromatin structure and dynamics in this process remains poorly understood. Here we show that nucleosome spacing and the presence of nucleosome-free DNA regions can modulate chromatin structure/dynamics and, in turn, affect the rate of EPC in vitro and in silico. Increasing the length of internucleosomal linker DNA from 25 to 60 bp results in more efficient EPC. The presence of longer nucleosome-free DNA regions can positively or negatively affect the rate of EPC, depending upon the length and location of the DNA region within the chromatin fiber. Thus the presence of histone-free DNA regions can differentially affect the efficiency of EPC, suggesting that gene regulation over a distance could be modulated by changes in the length of internucleosomal DNA spacers. PMID:27940560

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

Metastatic eccrine porocarcinoma: report of a case and review of the literature

PubMed Central

2011-01-01

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported. We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT). EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread. PMID:21410982

Metastatic eccrine porocarcinoma: report of a case and review of the literature.

PubMed

Marone, Ugo; Caracò, Corrado; Anniciello, Anna Maria; Di Monta, Gianluca; Chiofalo, Maria Grazia; Di Cecilia, Maria Luisa; Mozzillo, Nicola

2011-03-16

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported.We report a case of patient with EPC of the left arm, with axillary nodal involvement and subsequent local relapse, treated by complete lymph node dissection and electrochemotherapy (ECT).EPC is an unusual tumor to diagnose. Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating metastatic disease. Although in the current case the short follow-up period is a limitation, we consider in the management of EPC a therapeutic approach involving surgery and ECT, because of its aggressive potential for loregional metastatic spread.

Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension.

PubMed

Zhao, Qiang; Liu, Zixiong; Wang, Zhe; Yang, Cheng; Liu, Jun; Lu, Jun

2007-08-01

Calcitonin gene-related peptide (CGRP) is a potent smooth muscle cell proliferation inhibitor and vasodilator. It is now believed that CGRP plays an important role in maintaining a low pulmonary vascular resistance. We evaluated the therapeutic effect of intravenously administered CGRP-expressing endothelial progenitor cells (EPCs) on left-to-right shunt-induced pulmonary hypertension in rats. Endothelial progenitor cells were obtained from cultured human peripheral blood mononuclear cells. The genetic sequence for CGRP was subcloned into cultured EPCs by human expression plasmid. Pulmonary hypertension was established in immunodeficient rats with an abdominal aorta to inferior vena cava shunt operation. The transfected EPCs were injected through the left jugular vein at 10 weeks after the shunt operation. Mean pulmonary artery pressure and total pulmonary vascular resistance were detected with right cardiac catheterization at 4 weeks. The distribution of EPCs in the lung tissue was examined with immunofluorescence technique. Histopathologic changes in the structure of the pulmonary arteries was observed with electron microscopy and subjected to computerized image analysis. The lungs of rats transplanted with CGRP-expressing EPCs demonstrated a decrease in both mean pulmonary artery pressure (17.64 +/- 0.79 versus 22.08 +/- 0.95 mm Hg; p = 0.018) and total pulmonary vascular resistance (1.26 +/- 0.07 versus 2.45 +/- 0.18 mm Hg x min/mL; p = 0.037) at 4 weeks. Immunofluorescence revealed that intravenously administered cells were incorporated into the pulmonary vasculature. Pulmonary vascular remodeling was remarkably attenuated with the administration of CGRP-expressing EPCs. The transplantation of CGRP-expressing EPCs may effectively attenuate established pulmonary hypertension and exert reversal effects on pulmonary vascular remodeling. Our findings suggest that the therapy based on the combination of both CGRP transfection and EPCs may be a potentially useful

Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

PubMed

Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

2017-10-01

Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Loss of the Liver X Receptors Disrupts the Balance of Hematopoietic Populations, With Detrimental Effects on Endothelial Progenitor Cells.

PubMed

Rasheed, Adil; Tsai, Ricky; Cummins, Carolyn L

2018-05-08

The liver X receptors (LXRs; α/β) are nuclear receptors known to regulate cholesterol homeostasis and the production of select hematopoietic populations. The objective of this study was to determine the importance of LXRs and a high-fat high-cholesterol diet on global hematopoiesis, with special emphasis on endothelial progenitor cells (EPCs), a vasoreparative cell type that is derived from bone marrow hematopoietic stem cells. Wild-type and LXR double-knockout ( Lxr αβ -/- ) mice were fed a Western diet (WD) to increase plasma cholesterol levels. In WD-fed Lxr αβ -/- mice, flow cytometry and complete blood cell counts revealed that hematopoietic stem cells, a myeloid progenitor, and mature circulating myeloid cells were increased; EPC numbers were significantly decreased. Hematopoietic stem cells from WD-fed Lxr αβ -/- mice showed increased cholesterol content, along with increased myeloid colony formation compared with chow-fed mice. In contrast, EPCs from WD-fed Lxr αβ -/- mice also demonstrated increased cellular cholesterol content that was associated with greater expression of the endothelial lineage markers Cd144 and Vegfr2 , suggesting accelerated differentiation of the EPCs. Treatment of human umbilical vein endothelial cells with conditioned medium collected from these EPCs increased THP-1 monocyte adhesion. Increased monocyte adhesion to conditioned medium-treated endothelial cells was recapitulated with conditioned medium from Lxr αβ -/- EPCs treated with cholesterol ex vivo, suggesting cholesterol is the main component of the WD inducing EPC dysfunction. LXRs are crucial for maintaining the balance of hematopoietic cells in a hypercholesterolemic environment and for mitigating the negative effects of cholesterol on EPC differentiation/secretome changes that promote monocyte-endothelial adhesion. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation

PubMed Central

Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean-François; Gillis, Marc-Antoine; Neagoe, Paul-Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G.; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye

2013-01-01

Background Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation. Methods and Results Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride–induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow. Conclusions Peripheral blood mononuclear cell– derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential

Experimentally Identify the Effective Plume Chimney over a Natural Draft Chimney Model

NASA Astrophysics Data System (ADS)

Rahman, M. M.; Chu, C. M.; Tahir, A. M.; Ismail, M. A. bin; Misran, M. S. bin; Ling, L. S.

2017-07-01

The demands of energy are in increasing order due to rapid industrialization and urbanization. The researchers and scientists are working hard to improve the performance of the industry so that the energy consumption can be reduced significantly. Industries like power plant, timber processing plant, oil refinery, etc. performance mainly depend on the cooling tower chimney’s performance, either natural draft or forced draft. Chimney is used to create sufficient draft, so that air can flow through it. Cold inflow or flow reversal at chimney exit is one of the main identified problems that may alter the overall plant performance. The presence Effective Plume Chimney (EPC) is an indication of cold inflow free operation of natural draft chimney. Different mathematical model equations are used to estimate the EPC height over the heat exchanger or hot surface. In this paper, it is aim to identify the EPC experimentally. In order to do that, horizontal temperature profiling is done at the exit of the chimneys of face area 0.56m2, 1.00m2 and 2.25m2. A wire mesh screen is installed at chimneys exit to ensure cold inflow chimney operation. It is found that EPC exists in all modified chimney models and the heights of EPC varied from 1 cm to 9 cm. The mathematical models indicate that the estimated heights of EPC varied from 1 cm to 2.3 cm. Smoke test is also conducted to ensure the existence of EPC and cold inflow free option of chimney. Smoke test results confirmed the presence of EPC and cold inflow free operation of chimney. The performance of the cold inflow free chimney is increased by 50% to 90% than normal chimney.

Hematopoietic Substrate-1-Associated Protein X-1 Regulates the Proliferation and Apoptosis of Endothelial Progenitor Cells Through Akt Pathway Modulation.

PubMed

Guo, Xin-Bin; Deng, Xin; Wei, Ying

2018-03-01

Endothelial precursor cells (EPCs) are involved in vasculogenesis of various physiological and pathological processes. The proliferation and survival mechanism of EPCs needs to be explored further for the purpose of developing an effective glioma treatment. Hematopoietic substrate-1-associated protein X-1 (HAX-1) has been reported as an anti-apoptotic protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 on EPCs remains unknown. This study aims to investigate the effect of HAX-1 on the proliferation and apoptosis of EPCs and explore its mechanism. According to our results, HAX-1 was overexpressed in EPCs. The results of clone formation and 5-ethynyl-2'-deoxyuridine proliferation assay showed that HAX-1 promoted multiplication of EPCs. Flow cytometry showed HAX-1 knockout cell cycle arrest mainly in G0/G1 phase. Apoptosis analysis showed that HAX-1 could protect EPCs from apoptosis in oxidative stress. Western blot assay indicated that HAX-1 could inhibit the activation of caspase cascade and reduce the expression of p21, Bcl-2-associated X protein, and p53. HAX-1 also enhanced the degradation rate and ubiquitination of p53 through the promotion of phosphorylation of proteins MDM-2 and Akt1. Co-immunoprecipitation and immunofluorescent colocalization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and heat shock protein 90 (Hsp90), which is crucial for the activity of Akt1. In conclusion, this novel study suggests that HAX-1 could facilitate the Akt1 pathway through Hsp90, which led to a decline in the levels of p53, and finally promoted the proliferation and inhibited the apoptosis of EPCs. Stem Cells 2018;36:406-419. © 2017 AlphaMed Press.

Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression.

PubMed

Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

2015-05-01

Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1-CXCR2 and CX3CL1-CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Red wine consumption improves in vitro migration of endothelial progenitor cells in young, healthy individuals.

PubMed

Hamed, Saher; Alshiek, Jonia; Aharon, Anat; Brenner, Benjamin; Roguin, Ariel

2010-07-01

Endothelial progenitor cells (EPCs) contribute to the maintenance of vascular endothelial function. The moderate consumption of red wine provides cardiovascular protection. We investigated the underlying molecular mechanism of EPC migration in young, healthy individuals who drank red wine. Fourteen healthy volunteers consumed 250 mL red wine daily for 21 consecutive days. Vascular endothelial function, plasma stromal cell-derived factor 1alpha (SDF1alpha) concentrations, and the number, migration, and nitric oxide production of EPCs were determined before and after the daily consumption of red wine. EPCs were glucose stressed to study the effect of red wine on EPC migration, proliferation, and senescence and to study the expressions of CXC chemokine receptor 4 (CXCR4) and members of the Pi3K/Akt/eNOS (phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase) signaling pathway by Western blotting. Daily red wine consumption for 21 consecutive days significantly enhanced vascular endothelial function. Although plasma SDF1alpha concentrations were unchanged, EPC count and migration were significantly increased after this 21-d consumption period. Red wine increased the migration, proliferation, CXCR4 expression, and activity of the Pi3K/Akt/eNOS signaling pathway and decreased the extent of apoptosis in glucose-stressed EPCs. The results of the present study indicate that red wine exerts its effect through the up-regulation of CXCR4 expression and activation of the SDF1alpha/CXCR4/Pi3K/Akt/eNOS signaling pathway, which results in increased EPC migration and proliferation and decreased extent of apoptosis. Our findings suggest that these effects could be linked to the mechanism of cardiovascular protection that is associated with the regular consumption of red wine.

Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.

PubMed

Rehman, Jalees; Li, Jingling; Orschell, Christie M; March, Keith L

2003-03-04

Endothelial progenitor cells (EPCs) have been isolated from peripheral blood and can enhance angiogenesis after infusion into host animals. It is not known whether the proangiogenic effects are a result of such events as endothelial differentiation and subsequent proliferation of EPCs or secondary to secretion of angiogenic growth factors. Human EPCs were isolated as previously described, and their phenotypes were confirmed by uptake of acetylated LDL and binding of ulex-lectin. EPC proliferation and surface marker expression were analyzed by flow cytometry, and conditioned medium was assayed for growth factors. The majority of EPCs expressed monocyte/macrophage markers such as CD14 (95.7+/-0.3%), Mac-1 (57.6+/-13.5%), and CD11c (90.8+/-4.9%). A much lower percentage of cells expressed the specific endothelial marker VE-cadherin (5.2+/-0.7%) or stem/progenitor-cell markers AC133 (0.16+/-0.05%) and c-kit (1.3+/-0.7%). Compared with circulating monocytes, cultured EPCs showed upregulation of monocyte activation and macrophage differentiation markers. EPCs did not demonstrate any significant proliferation but did secrete the angiogenic growth factors vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Our findings suggest that acetylated LDL(+)ulex-lectin(+) cells, commonly referred to as EPCs, do not proliferate but release potent proangiogenic growth factors. The majority of acetylated LDL(+)ulex-lectin(+) cells are derived from monocyte/macrophages. The findings of low proliferation and endothelial differentiation suggest that their angiogenic effects are most likely mediated by growth factor secretion. These findings may allow for development of novel angiogenic therapies relying on secreted growth factors or on recruitment of endogenous monocytes/macrophages to sites of ischemia.

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

Generating para-water from para-hydrogen: A Gedankenexperiment.

PubMed

Ivanov, Konstantin L; Bodenhausen, Geoffrey

2018-07-01

A novel conceptual approach is described that is based on the transfer of hyperpolarization from para-hydrogen in view of generating a population imbalance between the two spin isomers of H 2 O. The approach is analogous to SABRE (Signal Amplification By Reversible Exchange) and makes use of the transfer of spin order from para-hydrogen to H 2 O in a hypothetical organometallic complex. The spin order transfer is expected to be most efficient at avoided level crossings. The highest achievable enrichment levels of para- and ortho-water are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population.

PubMed

Fadini, Gian Paolo; Coracina, Anna; Baesso, Ilenia; Agostini, Carlo; Tiengo, Antonio; Avogaro, Angelo; de Kreutzenberg, Saula Vigili

2006-09-01

Disruption of the endothelial layer is the first step in the atherogenic process. Experimental studies have shown that endothelial progenitor cells (EPCs) are involved in endothelial homeostasis and repair. Conversely, EPC depletion has been demonstrated in the setting of established atherosclerotic diseases. With this background, we evaluated whether variations in the number of EPCs are associated with subclinical atherosclerosis in healthy subjects. Carotid intima-media thickness (IMT), high-sensitive C-reactive protein (hsCRP), levels of circulating EPCs, and cardiovascular risk were compared in 137 healthy subjects. Six subpopulations of progenitor cells were determined by flow cytometry on the basis of the surface expression of CD34, CD133, and KDR antigens: CD34(+), CD133(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+). Among different antigenic profiles of EPCs, only CD34(+)KDR(+) cells were significantly reduced in subjects with increased IMT. Specifically, CD34(+)KDR(+) cells were inversely correlated with IMT, even after adjustment for hsCRP and 10-year Framingham risk and independently of other cardiovascular parameters. Depletion of CD34(+)KDR(+) EPCs is an independent predictor of early subclinical atherosclerosis in healthy subjects and may provide additional information beyond classic risk factors and inflammatory markers.

Development and characterization of acoustically efficient cementitious materials

NASA Astrophysics Data System (ADS)

Neithalath, Narayanan

Tire-pavement interaction noise is one of the significant environmental issues in highly populated urban areas situated near busy highways. The understanding that methodologies to reduce the sound at the source itself is necessary, has led to the development of porous paving materials. This thesis outlines the systematic research effort conducted in order to develop and characterize two different types of sound absorbing cementitious materials---Enhanced Porosity Concrete (EPC), that incorporates porosity in the non-aggregate component of the mixture, and Cellulose-Cement Composites, where cellulose fibers are used as porous inclusions. The basic tenet of this research is that carefully introduced porosity of about 15%--25% in the material structure of concrete will allow sound waves to pass through and dissipate its energy. The physical, mechanical, and acoustic properties of EPC mixtures are discussed in detail. Methods are developed to determine the porosity of EPC. The total pore volume, pore size, and pore connectivity are the significant features that influence the behavior of EPC. Using a shape-specific model, and incorporating the principle of acoustic wave propagation through semi-open cells, the acoustic absorption in EPC has been modeled. The pore structure and performance of EPC is characterized using Electrical Impedance Spectroscopy. Using a multi-phase conducting model, a pore connectivity factor has been developed, that correlates well with the acoustic absorption coefficient. A falling head permeameter has been designed to ascertain the water permeability of EPC mixtures. A hydraulic connectivity factor is proposed, which could be used to classify EPC mixtures based on their permeability. Electrical conductivity is shown to be a single measurable parameter that defines the performance of EPC. Preliminary studies conducted on the freezing and thawing response of EPC are also reported. From several porous, compliant materials, morphologically altered

Ca2+ signalling in endothelial progenitor cells: a novel means to improve cell-based therapy and impair tumour vascularisation.

PubMed

Moccia, Francesco; Lodola, Francesco; Dragoni, Silvia; Bonetti, Elisa; Bottino, Cinzia; Guerra, Germano; Laforenza, Umberto; Rosti, Vittorio; Tanzi, Franco

2014-01-01

Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may sustain tumour vascularisation and provide an additional target for anticancer therapies. CBT is limited by the paucity of cells harvested from peripheral blood and suffers from several pitfalls, including the low rate of engrafted EPCs, whereas classic antiangiogenic treatments manifest a number of side effects and may induce resistance into the patients. CBT will benefit of a better understanding of the signal transduction pathway(s) which drive(s) EPC proliferation, trafficking, and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to impair tumor neovascularisation and improve the therapeutic outcome of antiangiogenic strategies. An increase in intracellular Ca(2+) concentration is the key signal in the regulation of cellular replication, migration, and differentiation. In particular, Ca(2+) signalling may regulate cellcycle progression, due to the Ca(2+)-sensitivity of a number of cycline-dependent kinases, and gene expression, owing to the Ca(2+)-dependence of several transcription factors. Recent work has outlined the role of the so-called store-operated Ca(2+) entry in driving EPC proliferation and migration. Unravelling the mechanisms guiding EPC engraftment into neovessels might supply the biological bases required to improve CBT and anticancer treatments. For example, genetic manipulation of the Ca(2+) signalling machinery could provide a novel approach to increase the extent of limb regeneration or preventing tumour vascularisation by EPCs.

Electronic Power Conditioner for Ku-band Travelling Wave Tube

NASA Astrophysics Data System (ADS)

Kowstubha, Palle; Krishnaveni, K.; Ramesh Reddy, K.

2017-04-01

A highly sophisticated regulated power supply is known as electronic power conditioner (EPC) is required to energise travelling wave tubes (TWTs), which are used as RF signal amplifiers in satellite payloads. The assembly consisting of TWT and EPC together is known as travelling wave tube amplifier (TWTA). EPC is used to provide isolated and conditioned voltage rails with tight regulation to various electrodes of TWT and makes its RF performance independent of solar bus variations which are caused due to varying conditions of eclipse and sunlit. The payload mass and their power consumption is mainly due to the existence of TWTAs that represent about 35 % of total mass and about 70-90 % (based on the type of satellite application) of overall dc power consumption. This situation ensures a continuous improvement in the design of TWTAs and their associated EPCs to realize more efficient and light products. Critical technologies involved in EPCs are design and configuration, closed loop regulation, component and material selection, energy limiting of high voltage (HV) outputs and potting of HV card etc. This work addresses some of these critical technologies evolved in realizing and testing the state of art of EPC and it focuses on the design of HV supply with a HV and high power capability, up to 6 kV and 170 WRF, respectively required for a space TWTA. Finally, an experimental prototype of EPC with a dc power of 320 W provides different voltages required by Ku-band TWT in open loop configuration.

Initial Experience of an Anesthesiology-based Service for Perioperative Management of Pacemakers and Implantable Cardioverter Defibrillators.

PubMed

Rooke, G Alec; Lombaard, Stefan A; Van Norman, Gail A; Dziersk, Jörg; Natrajan, Krishna M; Larson, Lyle W; Poole, Jeanne E

2015-11-01

Management of cardiovascular implantable electronic devices (CIEDs), including pacemakers and implantable cardioverter defibrillators, for surgical procedures is challenging due to the increasing number of patients with CIEDs and limited availability of trained providers. At the authors' institution, a small group of anesthesiologists were trained to interrogate CIEDs, devise a management plan, and perform preoperative and postoperative programming and device testing whenever necessary. Patients undergoing surgery between October 1, 2009 and June 30, 2013 at the University of Washington Medical Center were included in a retrospective chart review to determine the number of devices actively managed by the Electrophysiology/Cardiology Service (EPCS) versus the Anesthesiology Device Service (ADS), changes in workload over time, surgical case delays due to device management, and errors and problems encountered in device programming. The EPCS managed 254 CIEDs, the ADS managed 548, and 227 by neither service. Over time, the ADS providers managed an increasing percentage of devices with decreasing supervision from the EPCS. Only two CIEDs managed by the ADS required immediate assistance from the EPCS. Patients who were unstable postoperatively were referred to the EPCS. Although numerous issues in programming were encountered, primarily when restoring demand pacing after programming asynchronous pacing for surgery, no patient harm resulted from ADS or EPCS management of CIEDs. An ADS can provide safe CIED management for surgery, but it requires specialized provider training and strong support from the EPCS. Due to the complexity of CIED management, an ADS will likely only be feasible in high-volume settings.

Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

PubMed

Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

2011-04-01

Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects. Copyright © 2011 Elsevier Inc. All rights reserved.

Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

2012-01-01

The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

Biologic properties of endothelial progenitor cells and their potential for cell therapy.

PubMed

Young, Pampee P; Vaughan, Douglas E; Hatzopoulos, Antonis K

2007-01-01

Recent studies indicate that portions of ischemic and tumor neovasculature are derived by neovasculogenesis, whereby bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) home to sites of regenerative or malignant growth and contribute to blood vessel formation. Recent data from animal models suggest that a variety of cell types, including unfractionated BM mononuclear cells and those obtained by ex vivo expansion of human peripheral blood or enriched progenitors, can function as EPCs to promote tissue vasculogenesis, regeneration, and repair when introduced in vivo. The promising preclinical results have led to several human clinical trials using BM as a potential source of EPCs in cardiac repair as well as ongoing basic research on using EPCs in tissue engineering or as cell therapy to target tumor growth.

Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

PubMed

Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

2005-02-01

Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair

Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.

PubMed

Liu, Norika Mengchia; Siu, Kin Lung; Youn, Ji Youn; Cai, Hua

2017-03-01

Restenosis after angioplasty is a serious clinical problem that can result in re-occlusion of the coronary artery. Although current drug-eluting stents have proved to be more effective in reducing restenosis, they have drawbacks of inhibiting reendothelialization to promote thrombosis. New treatment options are in urgent need. We have shown that netrin-1, an axon-guiding protein, promotes angiogenesis and cardioprotection via production of nitric oxide (NO). The present study examined whether and how netrin-1 attenuates neointimal formation in a femoral wire injury model. Infusion of netrin-1 into C57BL/6 mice markedly attenuated neointimal formation following wire injury of femoral arteries, measured by intimal to media ratio (from 1.94 ± 0.55 to 0.45 ± 0.86 at 4 weeks). Proliferation of VSMC in situ was largely reduced. This protective effect was absent in DCC +/- animals. NO production was increased by netrin-1 in both intact and injured femoral arteries, indicating netrin-1 stimulation of endogenous NO production from intact endothelium and remaining endothelial cells post-injury. VSMC migration was abrogated by netrin-1 via a NO/cGMP/p38 MAPK pathway, while timely EPC homing was induced. Injection of netrin-1 preconditioned wild-type EPCs, but not EPCs of DCC +/- animals, substantially attenuated neointimal formation. EPC proliferation, NO production, and resistance to oxidative stress induced apoptosis were augmented by netrin-1 treatment. In conclusion, our data for the first time demonstrate that netrin-1 is highly effective in reducing neointimal formation following vascular endothelial injury, which is dependent on DCC, and attributed to inhibition of VSMC proliferation and migration, as well as improved EPC function. These data may support usage of netrin-1 and netrin-1 preconditioned EPCs as novel therapies for post angioplasty restenosis. Netrin-1 attenuates neointimal formation following post endothelial injury via DCC and NO. Netrin-1 inhibits

The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

NASA Astrophysics Data System (ADS)

Liberda, Eric N.

Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

Fifty-three years' experience with randomized clinical trials of emergency portacaval shunt for bleeding esophageal varices in Cirrhosis: 1958-2011.

PubMed

Orloff, Marshall J

2014-02-01

Emergency treatment of bleeding esophageal varices (BEV) consists mainly of endoscopic and pharmacologic measures, with transjugular intrahepatic portal-systemic shunt (TIPS) performed when bleeding is not controlled. Surgical shunt has been relegated to salvage. At the University of California, San Diego, Medical Center, our group has conducted 10 studies of emergency portacaval shunt (EPCS) during 46 years. To describe 2 randomized clinical trials (RCTs) conducted from 1988 to 2011 in unselected consecutive patients who received emergency treatment for BEV. In RCT No. 1, a total of 211 unselected consecutive patients with cirrhosis and acute BEV were randomized to emergency endoscopic sclerotherapy (EEST) (n=106) or EPCS (n=105). In RCT No. 2, a total of 154 unselected consecutive patients with cirrhosis and acute BEV were randomized to TIPS (n=78) or EPCS (n=76). Diagnostic workup was completed within 6 hours of initial contact, and primary treatment was initiated within 8 to 12 hours. Regular follow-up for up to 10 years was accomplished in 100% of the patients. In RCT No. 1, EEST or EPCS; in RCT No. 2, TIPS or EPCS. The 2 groups were compared with regard to survival, control of bleeding, portal-systemic encephalopathy, and direct cost of care. RESULTS Distribution in Child risk classes was almost identical. One-third of patients were in Child class C. Permanent control of bleeding was achieved by EEST in only 20% of the patients and by TIPS in only 22%. In contrast, EPCS permanently controlled bleeding in 97% and 100% of the patients in RCT No. 2 and RCT No. 1, respectively (P<.001). Survival was significantly greater following EPCS than after EEST and TIPS (P<.001). Median survival was more than 10 years following EPCS compared with 1.99 years after TIPS. Occlusion of TIPS was demonstrated in 84% of the patients, 63% of whom underwent TIPS revision, which failed in 80% of the cases. Recurrent portal-systemic encephalopathy developed in 35% of the patients who

Endothelial and circulating progenitor cells in hematological diseases and allogeneic hematopoietic stem cell transplantation.

PubMed

Ruggeri, Annalisa; Paviglianiti, Annalisa; Volt, Fernanda; Kenzey, Chantal; Rafii, Hanadi; Rocha, Vanderson; Gluckman, Eliane

2017-10-12

Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells which are not associated with vessel walls, and that are detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and some other diseases. Consequently, CECs and EPCs represent a potential biomarker in several clinical conditions involving endothelial turnover and remodeling, such as hematological diseases. These cells may be involved in disease progression and the neoplastic angiogenesis process. Moreover, CESs and EPCs are probably involved in endothelial damage that is a marker of several complications following allogeneic hematopoietic stem cell transplantation. This review aims to provide an overview on the characterization of CECs and EPCs, describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Endothelial Progenitor Cells as Shuttle of Anticancer Agents.

PubMed

Laurenzana, Anna; Margheri, Francesca; Chillà, Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario

2016-10-01

Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining cell-based therapy with gene therapy or with nanomedicine. The first approach is based on the possibility of engineering EPCs to express different transgenes, and the second is based on the capacity of EPCs to take up nanomaterials. Here we review the most important progress covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularization and metastasis, and preclinical data about their use in cell-based tumor therapy, considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in terms of plasmonic-dependent thermoablation and molecular imaging.

Processing of CXCL12 impedes the recruitment of endothelial progenitor cells in diabetic wound healing.

PubMed

Feng, Guang; Hao, Daifeng; Chai, Jiake

2014-11-01

High blood sugar levels result in defective wound healing processes in diabetic patients. Endothelial progenitor cells (EPCs) play an important role in vasculogenesis, and thereby contribute to reconstitution of the microcirculation and healing. This study aimed to determine the possible mechanism by which the numbers of circulating EPCs are regulated in response to tissue wounding. In the streptozotocin-induced diabetic mouse model, we found that phagocytes activated by local inflammatory cytokines in the wound interfere with the mobilization and recruitment of EPCs to the lesion area. Specifically, the activated macrophages inactivate CXCL12, the major chemokine for EPC recruitment, via matrix metalloproteinases (MMPs), and thereby prevent local chemotaxis and subsequent homing of EPCs to the wound. The wound healing process is delayed by local administration of inflammatory cytokines, and its rate is increased by MMP inhibitors. This study indicates that local inhibition of MMPs is beneficial for regeneration of damaged vessels, and may explain poor wound healing in diabetic patients, thus demonstrating its potential utility as a local treatment therapy to promote diabetic wound healing. © 2014 FEBS.

Arabinogalactans from Mimosa tenuiflora (Willd.) Poiret bark as active principles for wound-healing properties: specific enhancement of dermal fibroblast activity and minor influence on HaCaT keratinocytes.

PubMed

Zippel, Janina; Deters, Alexandra; Hensel, Andreas

2009-07-30

Aqueous extracts from the bark of Mimosa tenuiflora (Willd.) Poirett (Mimosaceae), tradionally known as "tepescohuite", are widely used for wound-healing and burns in middle and South America. No pharmacological data are available on the influence of aqueous extracts and high molecular constituents on human skin cells. Tests were performed on human primary dermal fibroblasts and human HaCaT keratinocytes by quantification of mitochondrial activity (MTT, WST-1), proliferation (BrdU incorporation), necrosis (LDH) and gene expression profiling (RT-PCR). Water extract WE (10 and 100 microg/mL) expressed loss of cell viability and proliferation in dermal fibroblasts. Ethanol-precipitated compounds EPC (10 microg/mL), isolated from WE significantly stimulated mitochondrial activity and proliferation of dermal fibroblasts. Minor stimulation of human kerationocytes by EPC was found only at 100 microg/mL level. The differentiation behavior of keratinocytes was not influenced by EPC. EPC had no influence on the expression of specific proliferation and differentiation related genes so that the mode of action remains unclear. By bioactivity-guided fractionation two arabinogalactan-enriched fractions (F2, F3) were isolated from EPC and identified as the stimulating principles of EPC against fibroblasts. A significant in vitro stimulation of dermal fibroblast activity and proliferation by arabinogalactans from Mimosa tenuiflora provides a rational for the traditional use of the bark material for wound healing.

Activation of Cell Surface Bound 20S Proteasome Inhibits Vascular Cell Growth and Arteriogenesis

PubMed Central

Ito, Wulf D.; Lund, Natalie; Zhang, Ziyang; Buck, Friedrich; Lellek, Heinrich; Horst, Andrea; Machens, Hans-Günther; Schunkert, Heribert; Schaper, Wolfgang; Meinertz, Thomas

2015-01-01

Arteriogenesis is an inflammatory process associated with rapid cellular changes involving vascular resident endothelial progenitor cells (VR-EPCs). Extracellular cell surface bound 20S proteasome has been implicated to play an important role in inflammatory processes. In our search for antigens initially regulated during collateral growth mAb CTA 157-2 was generated against membrane fractions of growing collateral vessels. CTA 157-2 stained endothelium of growing collateral vessels and the cell surface of VR-EPCs. CTA 157-2 bound a protein complex (760 kDa) that was identified as 26 kDa α7 and 21 kDa β3 subunit of 20S proteasome in mass spectrometry. Furthermore we demonstrated specific staining of 20S proteasome after immunoprecipitation of VR-EPC membrane extract with CTA 157-2 sepharose beads. Functionally, CTA 157-2 enhanced concentration dependently AMC (7-amino-4-methylcoumarin) cleavage from LLVY (N-Succinyl-Leu-Leu-Val-Tyr) by recombinant 20S proteasome as well as proteasomal activity in VR-EPC extracts. Proliferation of VR-EPCs (BrdU incorporation) was reduced by CTA 157-2. Infusion of the antibody into the collateral circulation reduced number of collateral arteries, collateral proliferation, and collateral conductance in vivo. In conclusion our results indicate that extracellular cell surface bound 20S proteasome influences VR-EPC function in vitro and collateral growth in vivo. PMID:26146628

Characterization of the activity of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-be nzopyran-6-yl-hydrogen phosphate] potassium salt in hydroxyl radical elimination.

PubMed

Tomita, T; Kashima, M; Tsujimoto, Y

2000-03-01

The effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1) on hydroxyl radical (*OH) elimination was studied using electron spin resonance (ESR) and spectrophotometric experiments. The addition of EPC-K, and *OH scavengers eliminated the *OH generated from Cu2+/H2O2, Fe2+/H2O2 and H2O2/UV-irradiation reaction systems. However, in competitive reactions using different concentrations of a spin-trap agent, the addition of the *OH scavenger altered the IC50 values, whereas the addition of EPC-K1 and a metal chelater did not change the value in the Cu2+/H2O2 and Fe2+/H2O2 reaction systems. The addition of EPC-K1 and metal chelater changed the ESR signal for free Cu2+. The spectrophotometric experiments confirmed that the addition of EPC-K1 and metal chelater altered the absorption spectra due to CuCl2 and FeSO4, whereas the *OH scavenger did not alter the spectra. Therefore, it was demonstrated that EPC-K, has the ability both to scavenge *OH directly and to inhibit the generation of *OH by the chelation of Cu2+ and Fe2+.

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer.

PubMed

Lowery, William J; Lowery, Ashlei W; Barnett, Jason C; Lopez-Acevedo, Micael; Lee, Paula S; Secord, Angeles Alvarez; Havrilesky, Laura

2013-09-01

To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) <$50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY. Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer. Published by Elsevier Inc.

Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

PubMed Central

Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

2009-01-01

Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

Combination of endophytic Bacillus and Beauveria for the management of Fusarium wilt and fruit borer in tomato.

PubMed

Prabhukarthikeyan, Rathinam; Saravanakumar, Duraisamy; Raguchander, Thiruvengadam

2014-11-01

Most of the approaches for biocontrol of pests and diseases have used a single biocontrol agent as antagonist to a single pest or pathogen. This accounts for the inconsistency in the performance of biocontrol agents. The development of a bioformulation possessing a mixture of bioagents could be a viable option for the management of major pests and diseases in crop plants. A bioformulation containing a mixture of Beauveria bassiana (B2) and Bacillus subtilis (EPC8) was tested against Fusarium wilt and fruit borer in tomato under glasshouse and field conditions. The bioformulation with B2 and EPC8 isolates effectively reduced the incidence of Fusarium wilt (Fusarium oxysporum f. sp. lycopersici) and fruit borer (Helicoverpa armigera) under glasshouse and field conditions compared with the individual application of B2 and EPC8 isolates and control treatments. In vitro studies showed a higher larval mortality of H. armigera when fed with B2 + EPC8-treated leaves. Further, plants treated with the B2 + EPC8 combination showed a greater accumulation of defence enzymes such as lipoxygenase, peroxidase and polyphenol oxidase against wilt pathogen and fruit borer pest than the other treatments. Moreover, a significant increase in growth parameters and yield was observed in tomato plants treated with B2 + EPC8 compared with the individual bioformulations and untreated control. The combined application of Beauveria and Bacillus isolates B2 and EPC8 effectively reduced wilt disease and fruit borer attack in tomato plants. Results show the possibility of synchronous management of tomato fruit borer pest and wilt disease in a sustainable manner. © 2013 Society of Chemical Industry.

White Paper: Unleashing Energy Efficiency Retrofits Through Energy Performance Contracts in China and the United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Bo; Price, Lynn; Liu, Manzhi

2015-09-15

Energy performance contracting (EPC) is a mechanism that uses private sector investment and expertise to deploy energy efficiency retrofits in buildings, industries, and other types of facilities. China and the United States both have large, growing EPC markets. This White Paper shares key insights on each market, including strengths and barriers inherent to these markets, compares the two markets, and sets forth options for enhancing EPC markets in each country. The White Paper concludes with recommendations structured around common goals of both countries.

The influence of nitroglycerin on the proliferation of endothelial progenitor cells from peripheral blood of patients with coronary artery disease.

PubMed

Wang, Xin; Zeng, Caiyu; Gong, Huiping; He, Hong; Wang, Mengxin; Hu, Qin; Yang, Falin

2014-10-01

Endothelial progenitor cells (EPCs) are associated with vascular repairing and progression of atherosclerotic lesion. It may lead to coronary artery disease (CAD) if circulating EPCs lose their function. Continuous nitroglycerin (NTG) therapy causes increased vascular oxidative stress and endothelial dysfunction. The aim of this study was to investigate the effects of NTG on the proliferation of human peripheral blood-derived EPCs. EPC cultures, collected from 60 CAD patients and cultured for 7-12 days, were treated with different concentrations of NTG (0.0, 0.3, 1.0, 2.0, 7.5, 15.0, and 20.0 mg/l) for 72 h, respectively. The cell counts and proliferative activities of EPC; the levels of vascular endothelial growth factor-A (VEGF-A), nitric oxide (NO) and peroxynitrite (ONOO(-)) in culture medium; and the level of reactive oxygen species (ROS) in adherent cells were measured. Compared with control (0.0 mg/l NTG), the cell number and proliferative activities of EPCs were increased when treated with 1.0 mg/l NTG and reached maximum level when NTG concentration was 7.5 mg/l. However, there was a significant reduction when treated with higher doses of NTG (≥15.0 mg/l). Meanwhile, VEGF-A expression reached its maximal expression with 7.5 mg/l NTG, but gradually declined by incubation with higher doses of NTG. There was a linear relationship between NO level and NTG concentration, but no changes of ONOO(-) and ROS levels were found when EPCs were incubated with 0.3-7.5 mg/l NTG. However, ONOO(-) and ROS levels were significantly increased when incubated with 15 and 20 mg/l NTG. Our data demonstrated that moderate dose of NTG may stimulate the proliferative activities of EPCs isolated from CAD patients. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility.

PubMed

Nonaka, Mayumi I; Zsigmond, Eva; Kudo, Akihiko; Kawakami, Hayato; Yoshida, Kaoru; Yoshida, Manabu; Kawano, Natsuko; Miyado, Kenji; Nonaka, Masaru; Wetsel, Rick A

2015-04-01

C4b-binding protein (C4BP) is known as one of the circulating complement regulators that prevents excessive activation of the host-defense complement system. We have reported previously that C4BP is expressed abundantly in the rodent epididymis, one of the male reproductive organs connecting the testis and vas deferens, where immature spermatozoa acquire their motility and fertilizing ability during their transit through the duct. Epididymal C4BP (EpC4BP) is synthesized androgen-dependently by the epithelial cells, secreted into the lumen, and bound to the outer membrane of the passing spermatozoa. In this study, we found that EpC4BP is secreted as a large oligomer, similar to the serum C4BP, but is digested during the epididymal transit and is almost lost from both the luminal fluid and the sperm surface in the vas deferens. Such a processing pattern is not known in serum C4BP, suggesting that EpC4BP and serum C4BP might have different functional mechanisms, and that there is a novel function of EpC4BP in reproduction. In addition, the disappearance of EpC4BP from the sperm surface prior to ejaculation suggests that EpC4BP works only in the epididymis and would not work in the female reproductive tract to protect spermatozoa from complement attack. Next, we generated C4BP-deficient (C4BP-/-) mice to examine the possible role of EpC4BP in reproduction. However, the C4BP-/- mice were fertile and no significant differences were observed between the C4BP-/- and wild-type mouse spermatozoa in terms of morphology, motility, and rate of the spontaneous acrosome reaction. These results suggest that EpC4BP is involved in male reproduction, but not essential for sperm maturation. Copyright © 2014 Elsevier GmbH. All rights reserved.

Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist.

PubMed

Yu, Peng; Li, Shengjie; Zhang, Zhifei; Wen, Xiaolong; Quan, Wei; Tian, Qilong; Gao, Chuang; Su, Wanqiang; Zhang, Jianning; Jiang, Rongcai

2017-10-01

Progesterone (P4) has the potential therapeutic effects for traumatic brain injury (TBI) whose recovery depended on the enhanced angiogenesis. Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We previously demonstrated that P4 administration improved circulating EPC level and neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented angiogenic potential of EPC and the angiogenesis-related neurorestoration after TBI through classical progesterone receptor (PR). EPC derived from rats were stimulated with graded concentrations (0, 10 -10 , 10 -9 , 5 × 10 -9 , 10 -8 , 10 -7  mol/L) of P4 or 10 -6  mol/L ulipristal acetate (UPA, a PR antagonist). Male rats were subjected to cortical impact injury and treated with (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. It showed that P4 improved the angiogenic potential of EPC, including tube formation, adhesion, migration and vascular endothelial growth factor secretion, in a dose-dependent fashion with the maximal effect achieved at 10 -9  mol/L P4. High concentration (10 -7  mol/L) of P4 impaired the angiogenic potential of EPC. Notably, 10 -6  mol/L UPA antagonized the stimulatory effects of 10 -9  mol/L P4. After administrating P4, a significant improvement of neurological function and the restoration of the leaked blood-brain barrier were observed as well as a reduction of the brain water content. Both vessel density and expression of occludin of vessels were increased. When UPA was administered with P4, the neural restoration and angiogenesis were all reversed. Western blot showed that 10 -9  mol/L P4 increased the content of PRA and PRB of EPC, while 10 -7  mol/L P4 reduced the content of both PR isoforms, but there was no change found in the TBI rats. It may suggest that P4-mediated angiogenic activity of EPC and angiogenesis in TBI rats were antagonized by PR antagonist. © 2017 John Wiley & Sons Ltd.

May the remodeling of the Ca²⁺ toolkit in endothelial progenitor cells derived from cancer patients suggest alternative targets for anti-angiogenic treatment?

PubMed

Moccia, Francesco; Poletto, Valentina

2015-09-01

Endothelial progenitor cells (EPCs) may be recruited from bone marrow to sustain the metastatic switch in a number of solid cancers, including breast cancer (BC) and renal cellular carcinoma (RCC). Preventing EPC mobilization causes tumor shrinkage. Novel anti-angiogenic treatments have been introduced in therapy to inhibit VEGFR-2 signaling; unfortunately, these drugs blocked tumor angiogenesis in pre-clinical murine models, but resulted far less effective in human patients. Understanding the molecular mechanisms driving EPC proliferation and tubulogenesis in cancer patients could outline novel targets for alternative anti-angiogenic treatments. Store-operated Ca²⁺ entry (SOCE) regulates the growth of human EPCs, and it is mediated by the interaction between the endoplasmic reticulum Ca²⁺-sensor, Stim1, and the plasmalemmal Ca²⁺ channels, Orai1 and TRPC1. EPCs do not belong to the neoplastic clone: thus, unlike tumor endothelium and neoplastic cells, they should not remodel their Ca²⁺ toolkit in response to tumor microenvironment. However, our recent work demonstrated that EPCs isolated from naïve RCC patients (RCC-EPCs) undergo a dramatic remodeling of their Ca²⁺ toolkit by displaying a remarkable drop in the endoplasmic reticulum Ca²⁺ content, by down-regulating the expression of inositol-1,4,5-receptors (InsP3Rs), and by up-regulating Stim1, Orai1 and TRPC1. Moreover, EPCs are dramatically less sensitive to VEGF stimulation both in terms of Ca²⁺ signaling and of gene expression when isolated from tumor patients. Conversely, the pharmacological abolition of SOCE suppresses proliferation in these cells. These results question the suitability of VEGFR-2 as a therapeutically relevant target for anti-angiogenic treatments and hint at Orai1 and TRPC1 as more promising alternatives. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. Copyright © 2014 Elsevier B.V. All rights reserved.

Validation of Metrics as Error Predictors

NASA Astrophysics Data System (ADS)

Mendling, Jan

In this chapter, we test the validity of metrics that were defined in the previous chapter for predicting errors in EPC business process models. In Section 5.1, we provide an overview of how the analysis data is generated. Section 5.2 describes the sample of EPCs from practice that we use for the analysis. Here we discuss a disaggregation by the EPC model group and by error as well as a correlation analysis between metrics and error. Based on this sample, we calculate a logistic regression model for predicting error probability with the metrics as input variables in Section 5.3. In Section 5.4, we then test the regression function for an independent sample of EPC models from textbooks as a cross-validation. Section 5.5 summarizes the findings.

78 FR 18364 - Electronic Prescriptions for Controlled Substances Notice of Approved Certification Process

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. DEA-364] Electronic... certification processes for providers of Electronic Prescriptions for Controlled Substances (EPCS) applications... established by Congress. Electronic Prescriptions for Controlled Substances (EPCS) Historically, where federal...

Simulating Asymmetric Top Impurities in Superfluid Clusters: A para-Water Dopant in para-Hydrogen.

PubMed

Zeng, Tao; Li, Hui; Roy, Pierre-Nicholas

2013-01-03

We present the first simulation study of bosonic clusters doped with an asymmetric top molecule. The path-integral Monte Carlo method with the latest methodological advance in treating rigid-body rotation [Noya, E. G.; Vega, C.; McBride, C. J. Chem. Phys.2011, 134, 054117] is employed to study a para-water impurity in para-hydrogen clusters with up to 20 para-hydrogen molecules. The growth pattern of the doped clusters is similar in nature to that of pure clusters. The para-water molecule appears to rotate freely in the cluster. The presence of para-water substantially quenches the superfluid response of para-hydrogen with respect to the space-fixed frame.

Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients: a partially double-blind, randomized, three-arm unicenter study.

PubMed

Oikonomou, Dimitrios; Kopf, Stefan; von Bauer, Rüdiger; Djuric, Zdenka; Cebola, Rita; Sander, Anja; Englert, Stefan; Vittas, Spiros; Hidmark, Asa; Morcos, Michael; Korosoglou, Grigorios; Nawroth, Peter P; Humpert, Per M

2014-10-11

Endothelial progenitor cells (EPC) are bone marrow-derived cells which can undergo differentiation into endothelial cells and participate in endothelial repair and angiogenesis. Insulin facilitates this in vitro mediated by the IGF-1 receptor. Clinical trials showed that the number of circulating EPCs is influenced by glucose control and EPC are a predictor of cardiovascular death. To study direct effects of insulin treatment on EPCs in type 2 diabetes patients, add-on basal insulin treatment was compared to an escalation of oral medication aiming at similar glucose control between the groups. 55 patients with type 2 diabetes (61.6±5.9 years) on oral diabetes medication were randomized in a 2:2:1 ratio in 3 groups. Patients were treated additionally with insulin glargine (n=20), NPH insulin (n=22) or escalated with oral medication (n=13). Number of circulating EPC, EPC-outgrowth, intima media thickness, skin microvascular function and HbA1c were documented at baseline and/or after 4 weeks and 4 months. HbA1c at baseline was, 7.3+/-0.7% in the oral group, 7.3+/-0.9% and 7.5+/-0.7% in the glargine and NPH insulin respectively (p=0.713). HbA1c after 4 months decreased to 6.8+/-0.8%, 6.6+/-0.7% and 6.7+/-0.6%, in the oral, glargine and NPH insulin group respectively (p=0.61). FACS analysis showed no difference in number of circulating EPC between the groups after 4 weeks and 4 months. However, the outgrowth of EPCs as detected by colony forming assay was increased in the NPH insulin and glargine groups (29.2+/-6.4 and 29.4+/- 6.7 units respectively) compared to the group on oral medication (23.2+/-6.3, p=0.013) after 4 months of treatment. A significant decrease of IMT from 0.80mm (+/-0.14) at baseline to 0.76mm (+/-0.12) after 4 months could be observed in all patients only (p=0.03) with a trend towards a reduction of IMT after 4 months when all patients on insulin treatment were compared to the oral treatment group (p=0.06). Skin microvascular function revealed no

Adhesion behavior of endothelial progenitor cells to endothelial cells in simple shear flow

NASA Astrophysics Data System (ADS)

Gong, Xiao-Bo; Li, Yu-Qing; Gao, Quan-Chao; Cheng, Bin-Bin; Shen, Bao-Rong; Yan, Zhi-Qiang; Jiang, Zong-Lai

2011-12-01

The adhesion of endothelial progenitor cells (EPCs) on endothelial cells (ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases. Here, the rolling and adhesion behavior of EPCs on ECs was studied numerically. A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow. The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model. The effect of tumor necrosis factor alpha (TNF- α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally. A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs. Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiffness of the cell and shear rate of the flow. It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered. Experimental results demonstrate that TNF- α enhanced the expressions of VCAM, ICAM, P-selectin and E-selectin in ECs, which supports the numerical results that the rolling velocity of EPC on TNF- α treated EC substrate decreases obviously compared with its velocity on the untreated one. It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell, an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.

Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure.

PubMed

Van Craenenbroeck, Emeline M; Hoymans, Vicky Y; Beckers, Paul J; Possemiers, Nadine M; Wuyts, Kurt; Paelinck, Bernard P; Vrints, Christiaan J; Conraads, Viviane M

2010-09-01

Alterations in circulating angiogenic cells (CAC) and endothelial progenitor cells (EPC), known to contribute to endothelial repair, could explain the reversal of endothelial function in response to exercise training. Moreover, training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout. We studied the impact of exercise training on CAC function and numbers of CD34(+)/KDR(+) EPC in patients with chronic heart failure (CHF) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients. Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group (n = 17) and 10 healthy age-matched subjects. At baseline and follow-up, flow-mediated dilation was assessed and graded exercise testing (GXT) was performed. Before and immediately after GXT, CAC migratory capacity was assessed in vitro and circulating CD34(+)/KDR(+) EPC were quantified using flow cytometry. At baseline, CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT. Training corrected endothelial dysfunction, which coincided with a 77% increase in CAC migration (P = 0.0001). Moreover, the GXT-induced improvement detected at baseline was no longer observed after training. Numbers of CD34(+)/KDR(+) EPC increased following 6-month exercise training (P = 0.021), but were not affected by GXT, either prior or post-training. In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34(+)/KDR(+) EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair.

Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

PubMed

Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

2016-06-01

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis

PubMed Central

McCracken, James P.; Bhatnagar, Aruni; Conklin, Daniel J.

2016-01-01

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1+/Sca-1+ cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/particulate-matter-induced-vascular-insulin-resistance/. PMID:27016579

Induction of Endothelial Phenotype From Wharton's Jelly-Derived MSCs and Comparison of Their Vasoprotective and Neuroprotective Potential With Primary WJ-MSCs in CA1 Hippocampal Region Ex Vivo.

PubMed

Obtulowicz, Patrycja; Lech, Wioletta; Strojek, Lukasz; Sarnowska, Anna; Domanska-Janik, Krystyna

2016-01-01

Ischemic stroke results in violent impairment of tissue homeostasis leading to severe perturbation within the neurovascular unit (NVU) during the recovery period. The aim of this study was to assess the potential of mesenchymal stem cells (MSCs) originating from Wharton's jelly (WJ) to differentiate into functionally competent cells of endothelial lineage (WJ-EPCs). The protective effect(s) of either primary WJ-MSCs or induced WJ-EPCs was investigated and compared after oxygen-glucose deprivation (OGD) of hippocampal organotypic slices (OHC) in the indirect coculture model. WJ-MSCs, primed in EGM-2 (Lonza commercial medium) under 5% O2, acquired cobblestone endothelial-like morphology, formed capillary-like structures and actively took up DiI-Ac-LDL. Both cell types (WJ-MSCs and WJ-EPCs) were positive for CD73, CD90, CD105, VEGFR-2, and VEGF, but only endothelial-like culture expressed vWF and PECAM-1 markers at significant levels. In the presence of either WJ-MSCs or WJ-EPCs in the compartment below OGD-injured slices, cell death and vascular atrophy in the hypoxia-sensitive CA1 region were substantially decreased. This suggests that a paracrine mechanism may mediate WJ-MSC- and WJ-EPC-dependent protection. Thus, finally, we estimated secretion of the neuro/angio/immunomodulatory molecules IL-6, TGF-β1, and VEGF by these cell cultures. We have found that release of TGF-β1 and IL-6 was TLR ligand [LPS and Poly(I:C)] concentration dependent and stronger in WJ-EPC than WJ-MSC cultures. Simultaneously, the uneven pattern of TLR receptors and modulatory cytokine gene expression was confirmed also on qRT-PCR level, but no significant differences were noticed between WJ-EPC and primary WJ-MSC cultures.

Increased Circulating Endothelial Apoptotic Microparticle to Endothelial Progenitor Cell Ratio Is Associated with Subsequent Decline in Glomerular Filtration Rate in Hypertensive Patients

PubMed Central

Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2013-01-01

Background Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear. Methods and Results We enrolled totally 100 hypertensive out-patients with eGFR ≥30 mL/min/1.73 m2. The mean annual rate of GFR decline (△GFR/y) was −1.49±3.26 mL/min/1.73 m2 per year during the follow-up period (34±6 months). Flow cytometry was used to assess circulating EPC (CD34+/KDR+) and EMP levels (CD31+/annexin V+) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r = −0.465, p<0.001), microalbuminuria (r = −0.329, p = 0.001), and the Framingham risk score (r = −0.245, p = 0.013). When we divided the patients into 4 groups according to the EMP to EPC ratio, there was an association between the EMP to EPC ratio and the ΔGFR/y (mean ΔGFR/y: 0.08±3.04 vs. −0.50±2.84 vs. −1.25±2.49 vs. −4.42±2.82, p<0.001). Multivariate analysis indicated that increased EMP to EPC ratio is an independent predictor of ΔeGFR/y. Conclusions An increased circulating EMP to EPC ratio is associated with subsequent decline in GFR in hypertensive patients, which suggests endothelial damage with reduced vascular repair capacity may contribute to further deterioration of renal function in patients with hypertension. PMID:23874701

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head.

PubMed

Liao, Yun; Su, Rui; Zhang, Ping; Yuan, Bo; Li, Ling

2017-10-18

ANFH is a major health problem, to which long lasting and definitive treatments are lacking. The aim of this study is to study RNA alterations attributed to cortisol-induced ANFH. Rat models were stratified into three groups: in vitro group (n = 20) for molecular biological assays, control group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were extracted from the rats. An RNA expression array was performed on BM-EPCs, and enriched genes were subject to pathway analysis. In vitro studies following findings of array results were also performed using the isolated BM-EPCs. Significant alterations in mammalian target of rapamycin (mTOR) and HIF signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were identified. The alteration of HIF pathways appeared to be downstream of mTOR signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid-dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR stimulation. Decreased mTOR signaling in response to GR stimulation leading to downregulated HIF pathway as well as increased apoptosis could be the pathophysiology.

Peroxisome proliferator-activated receptor-δ activates endothelial progenitor cells to induce angio-myogenesis through matrix metallo-proteinase-9-mediated insulin-like growth factor-1 paracrine networks.

PubMed

Han, Jung-Kyu; Kim, Hack-Lyoung; Jeon, Ki-Hyun; Choi, Young-Eun; Lee, Hyun-Sook; Kwon, Yoo-Wook; Jang, Ja-June; Cho, Hyun-Jai; Kang, Hyun-Jae; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

2013-06-01

The roles of peroxisome proliferator-activated receptor (PPAR)-δ in vascular biology are mainly unknown. We investigated the effects of PPAR-δ activation on the paracrine networks between endothelial progenitor cells (EPCs) and endothelial cells (ECs)/skeletal muscle. Treatment of EPCs with GW501516, a PPAR-δ agonist, induced specifically matrix metallo-proteinase (MMP)-9 by direct transcriptional activation. Subsequently, this increased-MMP-9 broke down insulin-like growth factor-binding protein (IGFBP)-3, resulting in IGF-1 receptor (IGF-1R) activation in surrounding target cells. Treatment of conditioned medium from GW501516-stimulated EPCs enhanced the number and functions of human umbilical vein ECs and C2C12 myoblasts via MMP-9-mediated IGF-1R activation. Systemic administration of GW501516 in mice increased MMP-9 expression in EPCs, and augmented IGFBP-3 degradation in serum. In a mouse hindlimb ischaemia model, systemic treatment of GW501516 or local transplantation of GW501516-treated EPCs induced IGF-1R phosphorylation in ECs and skeletal muscle in the ischaemic limbs, leading to augmented angiogenesis and skeletal muscle regeneration. It also enhanced wound healing with increased angiogenesis in a mouse skin punch wound model. These pro-angiogenic and muscle-regenerating effects were abolished by MMP-9 knock-out. Our results suggest that PPAR-δ is a crucial modulator of angio-myogenesis via the paracrine effects of EPCs, and its agonist is a good candidate as a therapeutic drug for patients with peripheral vascular diseases.

tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis

PubMed Central

Day, Yuan-Ji

2016-01-01

We examined the role of tissue plasminogen activator- (tPA-) matrix metalloproteinase- (MMP-) 9 in mobilizing endothelial progenitor cells (EPCs) from bone marrow to circulation and critical limb ischemia (CLI) region. Male C57BL/6J mice having been irradiated were categorized into wild-type mice (WT) receiving WT bone marrow cell (BMC) transfusion (group 1), WT mice receiving MMP-9 knockout (MMP-9−/−) BMC (group 2), MMP-9−/− receiving MMP-9−/− BMC (group 3), and MMP-9−/− receiving WT BMC (group 4), each of which was subdivided into sham control (SC), CLI, SC-tPA, and CLI-tPA. In groups 1 and 4, by post-CLI 18 h and day 14, circulating EPC (C-kit+/CD31+, Sca-1+/KDR+) levels were highest in CLI-tPA subgroup. In groups 2 and 3, EPC levels did not differ among all subgroups. The EPC levels in bone marrow were higher in groups 2 and 3 than those in groups 1 and 4. By day 14, in animals with CLI, expression levels of proangiogenic factors (CXCR4, SDF-1α, and VEGF) showed similar trends as circulating EPC levels. Moreover, the number of infiltrated neutrophils and macrophages in quadriceps was higher in groups 1 and 4 than groups in 2 and 3. In conclusion, tPA-MMP-9 axis plays a crucial role in EPC mobilization and angiogenesis in experimental CLI. PMID:27610138

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro

PubMed Central

Peters, Erica B.; Liu, Betty; Christoforou, Nicolas; West, Jennifer L.; Truskey, George A.

2015-01-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p <0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications. PMID:25777295

Evidence-based practice center network and health technology assessment in the United States: bridging the cultural gap.

PubMed

Sarría-Santamera, Antonio; Matchar, David B; Westermann-Clark, Emma V; Patwardhan, Meenal B

2006-01-01

The purpose of this study was to identify the Evidence-Based Practice Center (EPC) network participants' perceptions of the characteristics of the EPC process and the relationship of the process to the success of EPC reports. Semistructured interviews were conducted with the three groups involved in the EPC: EPC staff, Agency for Healthcare Research and Quality (AHRQ) staff, and representatives of partner organizations. The analysis of the coded transcripts revealed three related major themes, which form the conceptual basis for the interpretation presented here: the definition of a successful report, the determinants of a successful report, and the role of AHRQ in the process. A successful report is a report that is used. The ultimate success of the core health technology assessment objective, moving from research to policy, depends on balancing two values: excellence and relevance. Our findings are consistent with the "two communities thesis," which postulates the existence of two camps that confer different values to excellence and relevance, with resulting tension. A promising model for approaching this tension is integration or collaboration, which requires linking researchers and policy makers, promoting productive dialogues about the formulation and timing of analysis, and early consideration of how the resulting analysis will be used. This effort suggests that actively blurring the frontiers between these two groups will enhance their interaction. Furthermore, enhancing the role of the AHRQ as scientific broker will maximize the potential of the EPC network.

Increased endothelial progenitor cell circulation and VEGF production in a rat model of noise-induced hearing loss.

PubMed

Yang, Dong; Zhou, Huifang; Zhang, Jianning; Liu, Li

2015-06-01

The vascular endothelial growth factor (VEGF)-mediated mechanism of endothelial progenitor cell (EPC) mobilization, migration, and differentiation may occur in response to noise-induced acoustic trauma of the cochlea, leading to the protection of cochlear function. The purpose of this study was to analyze changes in the cochlear vessel under an intensive noise environment. Sixty male Sprague-Dawley rats were randomly divided into six groups. Acoustic trauma was induced by 120 dB SPL white noise for 4 h. Auditory function was evaluated by the auditory brainstem response threshold. Morphological changes of the cochleae, the expression of VEGF, and the circulation of EPCs in the peripheral blood were studied by immunohistochemistry, Western blotting analysis, scanning electron microscopy, and flow cytometry. Vascular recovery of the cochlea began after noise exposure. The change in the number of EPCs was consistent with the expression of VEGF at different time points after noise exposure. We propose that VEGF evokes specific permeable and chemotactic effects on the vascular endothelial cells. These effects can mobilize EPCs into the peripheral blood, leading the EPCs to target damaged sites and to exert a neoangiogenic effect.

Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.

PubMed

Weech, Michelle; Altowaijri, Hana; Mayneris-Perxachs, Jordi; Vafeiadou, Katerina; Madden, Jacqueline; Todd, Susan; Jackson, Kim G; Lovegrove, Julie A; Yaqoob, Parveen

2018-06-01

Endothelial progenitor cells (EPCs) and microparticles are emerging as novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fatty acids (SFAs) with monounsaturated or n-6 (ω-6) polyunsaturated fatty acids (MUFAs or PUFAs, respectively) improved lipid biomarkers, blood pressure, and markers of endothelial activation, but their effects on circulating EPCs and microparticles are unclear. The Dietary Intervention and VAScular function (DIVAS) Study investigated the replacement of 9.5-9.6% of total energy (%TE) contributed by SFAs with MUFAs or n-6 PUFAs for 16 wk on EPC and microparticle numbers in United Kingdom adults with moderate CVD risk. In this randomized, controlled, single-blind, parallel-group dietary intervention, men and women aged 21-60 y (n = 190) with moderate CVD risk (≥50% above the population mean) consumed 1 of three 16-wk isoenergetic diets. Target compositions for total fat, SFAs, MUFAs, and n-6 PUFAs (%TE) were as follows: SFA-rich diet (36:17:11:4; n = 64), MUFA-rich diet (36:9:19:4; n = 62), and n-6 PUFA-rich diet (36:9:13:10; n = 66). Circulating EPC, endothelial microparticle (EMP), and platelet microparticle (PMP) numbers were analyzed by flow cytometry. Dietary intake, vascular function, and other cardiometabolic risk factors were determined at baseline. Relative to the SFA-rich diet, MUFA- and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) respectively and PMP (-36.8%, -39.1%) numbers (overall diet effects, P < 0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P = 0.023). Additional analyses that used stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse-wave analysis) as an independent predictor of baseline EPC and microparticle numbers. Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6

Prescribers' expectations and barriers to electronic prescribing of controlled substances

PubMed Central

Kim, Meelee; McDonald, Ann; Kreiner, Peter; Kelleher, Stephen J; Blackman, Michael B; Kaufman, Peter N; Carrow, Grant M

2011-01-01

Objective To better understand barriers associated with the adoption and use of electronic prescribing of controlled substances (EPCS), a practice recently established by US Drug Enforcement Administration regulation. Materials and methods Prescribers of controlled substances affiliated with a regional health system were surveyed regarding current electronic prescribing (e-prescribing) activities, current prescribing of controlled substances, and expectations and barriers to the adoption of EPCS. Results 246 prescribers (response rate of 64%) represented a range of medical specialties, with 43.1% of these prescribers current users of e-prescribing for non-controlled substances. Reported issues with controlled substances included errors, pharmacy call-backs, and diversion; most prescribers expected EPCS to address many of these problems, specifically reduce medical errors, improve work flow and efficiency of practice, help identify prescription diversion or misuse, and improve patient treatment management. Prescribers expected, however, that it would be disruptive to practice, and over one-third of respondents reported that carrying a security authentication token at all times would be so burdensome as to discourage adoption. Discussion Although adoption of e-prescribing has been shown to dramatically reduce medication errors, challenges to efficient processes and errors still persist from the perspective of the prescriber, that may interfere with the adoption of EPCS. Most prescribers regarded EPCS security measures as a small or moderate inconvenience (other than carrying a security token), with advantages outweighing the burden. Conclusion Prescribers are optimistic about the potential for EPCS to improve practice, but view certain security measures as a burden and potential barrier. PMID:21946239

Calcein AM release-based cytotoxic cell assay for fish leucocytes.

PubMed

Iwanowicz, Luke R; Densmore, Christine L; Ottinger, Christopher A

2004-02-01

A non-specific cytotoxic cell assay for fish is presented that is based on the release of the activated fluorochrome calcein AM from lysed carp epithelioma papulosum cyprini (EPC) cells. To establish the suitability of treating EPC cells with calcein AM the uptake and spontaneous release of the calcein AM by the EPC cells was evaluated. Incubation of 5 microM calcein AM in culture medium with 1x10(5)EPC cells well(-1)for a minimum of 3 h provided sufficient labelling. Spontaneous release of fluorescence from the labelled EPC cells during 10 h of post labelling incubation ranged from 30 to 39% of the total observed fluorescence. Cytotoxic activity of trout leucocytes was evaluated at three leucocyte to target cell ratios (10:1, 2:1 and 1:1) following incubation (4, 6, 8, and 10 h) with calcein AM-labelled EPC cells at 15 degrees C. In some instances, the monoclonal antibody specific for the NCC surface receptor NCCRP-1 (MAb5C.6) was included in the cultures. The activity of NCC cells was significantly inhibited in the presence of 0.25 microg well(-1)of MAb5C.6 relative to no antibody (P

Circulating endothelial cells and their progenitors in acute myeloid leukemia

PubMed Central

Zahran, Asmaa Mohammed; Aly, Sanaa Shaker; Altayeb, Hanan Ahmed; Ali, Arwa Mohammed

2016-01-01

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management. PMID:27602121

Effects of Hypoglycemia on Circulating Stem and Progenitor Cells in Diabetic Patients.

PubMed

Fadini, Gian Paolo; Boscari, Federico; Cappellari, Roberta; Galasso, Silvia; Rigato, Mauro; Bonora, Benedetta Maria; D'Anna, Marianna; Bruttomesso, Daniela; Avogaro, Angelo

2018-03-01

Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2). Tertiary referral inpatient clinic. Type 1 diabetic patients (Study 1, n = 19); diabetic patients hospitalized for severe iatrogenic hypoglycemia, matched inpatient and outpatient controls (Study 2, n = 22/group). Type 1 diabetic patients underwent two in-hospital sessions of glucose monitoring during a breakfast meal with or without induction of hypoglycemia in random order. In Study 2, patients hospitalized for hypoglycemia and matched controls were compared. Circulating stem cells and EPCs were measured by flow cytometry based on the expression of CD34 and kinase insert domain receptor (KDR). In Study 1, the physiologic decline of CD34+KDR+ EPCs from 8 am to 2 pm was abolished by insulin-induced hypoglycemia in type 1 diabetic patients. In Study 2, diabetic patients hospitalized for severe iatrogenic hypoglycemia had significantly lower levels of CD34+ stem cells and CD34+KDR+ EPCs compared with diabetic inpatients or outpatient controls. In diabetic patients, a single mild hypoglycemic episode can compromise the physiologic EPC fluctuation, whereas severe hypoglycemia is associated with a marked reduction in stem cells and EPCs. These data provide a possible link between hypoglycemia and adverse outcomes of diabetes.

Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy

PubMed Central

Grisar, Johannes; Aletaha, Daniel; Steiner, Carl W; Kapral, Theresa; Steiner, Sabine; Säemann, Marcus; Schwarzinger, Ilse; Buranyi, Barbara; Steiner, Günter; Smolen, Josef S

2007-01-01

Objectives To study the effects of short‐term intermediate dose glucocorticoid (GC) therapy in patients with active rheumatoid arthritis (RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA. Methods EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF. Results After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 (SD 0.010)% (p<0.01), and from 12 (SD 4) to 27 (SD 7) CFU/well (p<0.02); CAC also increased from 7 (SD 2) to 29 (SD 8) cells/high power field (p<0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 (SD 10) to 14 (SD 6) pg/ml (p<0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU. Conclusions Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC. PMID:17293363

Number of circulating endothelial progenitor cells and intratumoral microvessel density in non-small cell lung cancer patients: differences in angiogenic status between adenocarcinoma histologic subtypes.

PubMed

Maeda, Ryo; Ishii, Genichiro; Ito, Masami; Hishida, Tomoyuki; Yoshida, Junji; Nishimura, Mitsuyo; Haga, Hironori; Nagai, Kanji; Ochiai, Atsushi

2012-03-01

Angiogenesis plays a significant role in tumor progression. This study examined the association between the number of circulating endothelial progenitor cells (EPCs), intratumoral microvessel density (MVD) (both of which may be markers for neovascularization), and lung cancer histological types, particularly adenocarcinoma histological subtypes. A total of 83 stage I non-small cell lung cancer (NSCLC) patients underwent complete tumor resection between November 2009 and July 2010. The number of EPCs from the pulmonary artery of the resected lungs was measured by assaying CD34/vascular endothelial growth factor receptor 2 positive cells, and the MVD was assessed immunohistochemically in tumor specimens by staining for CD34. A statistically significant correlation between the number of EPCs from pulmonary artery and intratumoral MVD was found (p < 0.001). No statistically significant differences in the number of EPCs and the MVD were observed between the adenocarcinomas and the squamous cell carcinomas. Among the adenocarcinoma histological subtypes, a higher number of EPCs and MVD were found significantly more frequently in solid adenocarcinomas than in nonsolid adenocarcinomas (p < 0.001 and p = 0.011, respectively). In addition, solid adenocarcinomas showed higher levels of vascular endothelial growth factor using quantitative real-time polymerase chain reaction in the tumor tissue samples than in the nonsolid adenocarcinomas (p = 0.005). The higher number of circulating EPCs and the MVD of solid adenocarcinoma may indicate the presence of differences in the tumor angiogenic status between early-stage adenocarcinoma histological subtypes. Among adenocarcinoma patients, patients with solid adenocarcinoma may be the best candidates for antiangiogenic therapies.

Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice

PubMed Central

Yu, Jiawen; Sun, Yuannan; Ren, Guofei; Zhu, Jianjun

2017-01-01

Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway. PMID:28373902

Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice.

PubMed

Han, Xue; Deng, Yaping; Yu, Jiawen; Sun, Yuannan; Ren, Guofei; Cai, Jian; Zhu, Jianjun; Jiang, Guojun

2017-01-01

Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O 2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway.

Epilepsia partialis continua responsive to neocortical electrical stimulation.

PubMed

Valentin, Antonio; Ughratdar, Ismail; Cheserem, Beverly; Morris, Robert; Selway, Richard; Alarcon, Gonzalo

2015-08-01

Epilepsia partialis continua (EPC), defined as a syndrome of continuous focal jerking, is a rare form of focal status epilepticus that usually affects a distal limb, and when prolonged, can produce long-lasting deficits in limb function. Substantial electrophysiologic evidence links the origin of EPC to the motor cortex; thus surgical resection carries the risk of significant handicap. We present two patients with focal, drug-resistant EPC, who were admitted for intracranial video-electroencephalography monitoring to elucidate the location of the epileptogenic focus and identification of eloquent motor cortex with functional mapping. In both cases, the focus resided at or near eloquent motor cortex and therefore precluded resective surgery. Chronic cortical stimulation delivered through subdural strips at the seizure focus (continuous stimulation at 60-130 Hz, 2-3 mA) resulted in >90% reduction in seizures and abolition of the EPC after a follow-up of 22 months in both patients. Following permanent implantation of cortical stimulators, no adverse effects were noted. EPC restarted when intensity was reduced or batteries depleted. Battery replacement restored previous improvement. This two-case report opens up avenues for the treatment of this debilitating condition. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Induction of viral interference by IPNV-carrier cells on target cells: A cell co-culture study.

PubMed

Parreño, Ricardo; Torres, Susana; Almagro, Lucía; Belló-Pérez, Melissa; Estepa, Amparo; Perez, Luis

2016-11-01

IPNV is a salmonid birnavirus that possesses the ability to establish asymptomatic persistent infections in a number of valuable fish species. The presence of IPNV may interfere with subsequent infection by other viruses. In the present study we show that an IPNV-carrier cell line (EPC IPNV ) can induce an antiviral state in fresh EPC by co-cultivating both cell types in three different ways: a "droplet" culture system, a plastic chamber setup, and a transmembrane (Transwell ® ) system. All three cell co-culture methods were proven useful to study donor/target cell interaction. Naïve EPC cells grown in contact with EPC IPNV cells develop resistance to VHSV superinfection. The transmembrane system seems best suited to examine gene expression in donor and target cells separately. Our findings point to the conclusion that one or more soluble factors produced by the IPNV carrier culture induce the innate immune response within the target cells. This antiviral response is associated to the up-regulation of interferon (ifn) and mx gene expression in target EPC cells. To our knowledge this is the first article describing co-culture systems to study the interplay between virus-carrier cells and naive cells in fish. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Neural Correlates of Emotional Prosody Comprehension: Disentangling Simple from Complex Emotion

PubMed Central

Alba-Ferrara, Lucy; Hausmann, Markus; Mitchell, Rachel L.; Weis, Susanne

2011-01-01

Background Emotional prosody comprehension (EPC), the ability to interpret another person's feelings by listening to their tone of voice, is crucial for effective social communication. Previous studies assessing the neural correlates of EPC have found inconsistent results, particularly regarding the involvement of the medial prefrontal cortex (mPFC). It remained unclear whether the involvement of the mPFC is linked to an increased demand in socio-cognitive components of EPC such as mental state attribution and if basic perceptual processing of EPC can be performed without the contribution of this region. Methods fMRI was used to delineate neural activity during the perception of prosodic stimuli conveying simple and complex emotion. Emotional trials in general, as compared to neutral ones, activated a network comprising temporal and lateral frontal brain regions, while complex emotion trials specifically showed an additional involvement of the mPFC, premotor cortex, frontal operculum and left insula. Conclusion These results indicate that the mPFC and premotor areas might be associated, but are not crucial to EPC. However, the mPFC supports socio-cognitive skills necessary to interpret complex emotion such as inferring mental states. Additionally, the premotor cortex involvement may reflect the participation of the mirror neuron system for prosody processing particularly of complex emotion. PMID:22174872

Bone engineering in dog mandible: Coculturing mesenchymal stem cells with endothelial progenitor cells in a composite scaffold containing vascular endothelial growth factor.

PubMed

Khojasteh, Arash; Fahimipour, Farahnaz; Jafarian, Mohammad; Sharifi, Davoud; Jahangir, Shahrbanoo; Khayyatan, Fahimeh; Baghaban Eslaminejad, Mohamadreza

2017-10-01

We sought to assess the effects of coculturing mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) in the repair of dog mandible bone defects. The cells were delivered in β-tricalcium phosphate scaffolds coated with poly lactic co-glycolic acid microspheres that gradually release vascular endothelial growth factor (VEGF). The complete scaffold and five partial scaffolds were implanted in bilateral mandibular body defects in eight beagles. The scaffolds were examined histologically and morphometrically 8 weeks after implantation. Histologic staining of the decalcified scaffolds demonstrated that bone formation was greatest in the VEGF/MSC scaffold (63.42 ± 1.67), followed by the VEGF/MSC/EPC (47.8 ± 1.87) and MSC/EPC (45.21 ± 1.6) scaffolds, the MSC scaffold (34.59 ± 1.49), the VEGF scaffold (20.03 ± 1.29), and the untreated scaffold (7.24 ± 0.08). Hence, the rate of new bone regeneration was highest in scaffolds containing MSC, either mixed with EPC or incorporating VEGF. Adding both EPC and VEGF with the MSC was not necessary. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1767-1777, 2017. © 2016 Wiley Periodicals, Inc.

The effectiveness of behavioural interventions in the primary prevention of Hepatitis C amongst injecting drug users: a randomised controlled trial and lessons learned

PubMed Central

Abou-Saleh, Mohammed; Davis, Paul; Rice, Philip; Checinski, Ken; Drummond, Colin; Maxwell, Douglas; Godfrey, Christine; John, Christopher; Corrin, Betsy; Tibbs, Christopher; Oyefeso, Adenekan; de Ruiter, Marian; Ghodse, Hamid

2008-01-01

Aim To develop and evaluate the comparative effectiveness of behavioural interventions of enhanced prevention counselling (EPC) and simple educational counselling (SEC) in reducing hepatitis C viral (HCV) infection in sero-negative injecting drug users (IDU). Design Randomised controlled trial (RCT) of EPC intervention in comparison with simple educational counselling (SEC). Setting Specialised Drug services in London and Surrey, United Kingdom. Participants and Measurements Ninety five IDUs were recruited and randomised to receive EPC (n = 43) or SEC (n = 52). Subjects were assessed at baseline using the Addiction Severity Index (ASI), the Injecting Risk Questionnaire (IRQ), and Drug Injecting Confidence Questionnaire (DICQ). The primary outcome was measured by the rate of sero-conversion at 6 months and 12 months from baseline and by the ASI, IRQ and DICQ at 6 months from baseline. Hepatitis C testing was undertaken by the innovative test of the dried blood spot (DBS) test which increased the rate of testing by 4 fold compared to routine blood testing. Findings Seventy Eighty two subjects (82%) out of the 95 recruited were followed up at 6 months and 62 (65%) were followed up at 12 months. On the primary outcome measure of the rate of seroconversion, 8 out of 62 patients followed-up at twelve months seroconverted, three in the EPC group and five in the SEC group, indicating incidence rates of 9.1 per 100 person years for the EPC group, 17.2 per 100 person years for the SEC group, and 12.9 per 100 person years for the cohort as a whole. Analysis of the secondary outcome measures on alcohol use, risk behaviour, psychological measures, quality of life, showed no significant differences between the EPC and the SEC groups. However, there were significant changes on a number of measures from baseline values indicating positive change for both groups. Conclusion We were not able to prove the efficacy of EPC in comparison with SEC in the prevention of hepatitis C in IDUs

The effectiveness of behavioural interventions in the primary prevention of hepatitis C amongst injecting drug users: a randomised controlled trial and lessons learned.

PubMed

Abou-Saleh, Mohammed; Davis, Paul; Rice, Philip; Checinski, Ken; Drummond, Colin; Maxwell, Douglas; Godfrey, Christine; John, Christopher; Corrin, Betsy; Tibbs, Christopher; Oyefeso, Adenekan; de Ruiter, Marian; Ghodse, Hamid

2008-07-31

To develop and evaluate the comparative effectiveness of behavioural interventions of enhanced prevention counselling (EPC) and simple educational counselling (SEC) in reducing hepatitis C viral (HCV) infection in sero-negative injecting drug users (IDU). Randomised controlled trial (RCT) of EPC intervention in comparison with simple educational counselling (SEC). SETTING SPECIALISED: Drug services in London and Surrey, United Kingdom. Ninety five IDUs were recruited and randomised to receive EPC (n = 43) or SEC (n = 52). Subjects were assessed at baseline using the Addiction Severity Index (ASI), the Injecting Risk Questionnaire (IRQ), and Drug Injecting Confidence Questionnaire (DICQ). The primary outcome was measured by the rate of sero-conversion at 6 months and 12 months from baseline and by the ASI, IRQ and DICQ at 6 months from baseline. Hepatitis C testing was undertaken by the innovative test of the dried blood spot (DBS) test which increased the rate of testing by 4 fold compared to routine blood testing. FINDINGS SEVENTY: Eighty two subjects (82%) out of the 95 recruited were followed up at 6 months and 62 (65%) were followed up at 12 months. On the primary outcome measure of the rate of seroconversion, 8 out of 62 patients followed-up at twelve months seroconverted, three in the EPC group and five in the SEC group, indicating incidence rates of 9.1 per 100 person years for the EPC group, 17.2 per 100 person years for the SEC group, and 12.9 per 100 person years for the cohort as a whole. Analysis of the secondary outcome measures on alcohol use, risk behaviour, psychological measures, quality of life, showed no significant differences between the EPC and the SEC groups. However, there were significant changes on a number of measures from baseline values indicating positive change for both groups. We were not able to prove the efficacy of EPC in comparison with SEC in the prevention of hepatitis C in IDUs. This was related to low recruitment and

77 FR 16486 - Airworthiness Directives; Fokker Services B.V. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

... values of nuts on circuit breakers, contactors and terminal blocks of the EPC and battery relay panel... battery relay panel]. The required actions include doing a general visual inspection to determine if... and circuit breakers, contactors, and terminal blocks of the EPC and battery relay panel, as...

Extra-pair copulations in Black Brant

USGS Publications Warehouse

Welsh, Daniel; Sedinger, James S.

1990-01-01

Monogamy is the primary mating system among waterfowl, but extra-pair copulations (EPCs) have been documented in at least 39 species (McKinney et al. 1983). Extra-pair copulations occur in most Holarctic species of dabbling ducks (Anas spp.), but have been recorded in only three species of geese: Lesser Snow Geese, Chen caerulescens caerulescens (Mineau and Cooke 1979a), Ross’ Geese, C. rossii (J. Ryder in McKinney et al. 1984), and Greater White-fronted Geese, Anser albifrons frontalis (C.R. Ely, pers. comm.).In colonial Lesser Snow Geese, the close proximity of nesting conspecifics may enable males to pursue EPCs as a secondary reproductive strategy (Mineau and Cooke, 1979a, 1979b). Copulatory behavior of other geese has not been studied in sufficient detail to permit comparison with Lesser Sone Geese. Here we report on timing and rates of pair copulations (PCs) and EPCs, and describe behaviors associated with EPCs in colonially nesting Black Brant (Branta bernicla nigricans).

Expanding Energy Performance Contracting in china: policy solutions and market mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Bo; Price, Lynn; Liu, Xu

Energy performance contracting is an important market mechanism that uses energy savings to pay over time for the upfront costs of energy efficiency retrofits in buildings, industries, and other types of facilities. Through energy performance contracts (EPCs), Energy Service Companies (ESCOs) play an important role in implementing energy efficiency retrofits. Both China and the United States have large markets for EPCs and significant opportunities for growth. The Chinese government has made great efforts in promoting the country’s ESCO business and expanding its EPC markets. This paper makes a series of recommendations for China to adopt more ambitious policy measures tomore » encourage deep energy savings projects via EPCs. These recommendations are built on initial insights from a white paper developed by researchers at the Pacific Northwest National Laboratory and the Lawrence Berkeley National Laboratory with the assistance from the ESCO Committee of China’s Energy Conservation Association (EMCA). Key recommendations are listed below.« less

Antibacterial activity of selected Malaysian honey

PubMed Central

2013-01-01

Background Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Methods Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. Results The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p > 0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r = -0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r = -0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r = 0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r = -0.1482). Conclusions Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other

Fish oil-enriched diet protects against ischemia by improving angiogenesis, endothelial progenitor cell function and postnatal neovascularization.

PubMed

Turgeon, Julie; Dussault, Sylvie; Maingrette, Fritz; Groleau, Jessika; Haddad, Paola; Perez, Gemma; Rivard, Alain

2013-08-01

Fish oil consumption has been associated with a reduced incidence of cardiovascular diseases. However, the precise mechanisms involved are not completely understood. Here we tested the hypothesis that a fish oil-enriched diet improves neovascularization in response to ischemia. C57Bl/6 mice were fed a diet containing either 20% fish oil, rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), or 20% corn oil, rich in n-6 PUFAs. After 4 weeks, hindlimb ischemia was surgically induced by femoral artery removal. We found that blood flow recovery was significantly improved in mice fed a fish oil diet compared to those fed a corn oil diet (Doppler flow ratio (DFR) at day 21 after surgery 78 ± 5 vs. 56 ± 4; p < 0.01). Clinically, this was associated with a significant reduction of ambulatory impairment and ischemic damage in the fish oil group. At the microvascular level, capillary density was significantly improved in ischemic muscles of mice fed a fish oil diet. This correlated with increased expression of VEGF and eNOS in ischemic muscles, and higher NO concentration in the plasma. Endothelial progenitor cells (EPCs) have been shown to have an important role for postnatal neovascularization. We found that the number of EPCs was significantly increased in mice fed a fish oil diet. In addition, oxidative stress levels (DCF-DA, DHE) were reduced in EPCs isolated from mice exposed to fish oil, and this was associated with improved EPC functional activities (migration and integration into tubules). In vitro, treatment of EPCs with fish oil resulted in a significant increase of cellular migration. In addition, the secretion of angiogenic growth factors including IL6 and leptin was significantly increased in EPCs exposed to fish oil. Fish oil-enriched diet is associated with improved neovascularization in response to ischemia. Potential mechanisms involved include activation of VEGF/NO pathway in ischemic tissues together with an increase in the number and the

Comparative analysis of circulating endothelial progenitor cells in age-related macular degeneration patients using automated rare cell analysis (ARCA) and fluorescence activated cell sorting (FACS).

PubMed

Say, Emil Anthony T; Melamud, Alex; Esserman, Denise Ann; Povsic, Thomas J; Chavala, Sai H

2013-01-01

Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs), defined as CD34(+)VEGR2(+) using traditional fluorescence activated cell sorting (FACS), are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA), a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and p<0.2 was considered indicative of a trend for this proof of concept study, while statistical significance was established at 0.05. We measured levels of CD34(+)VEGFR2(+) EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17) using ARCA. Interestingly, CD34(+)VEGR2(+) EPC analysis using FACS did not produce similar results (p = 0.94). CD34(+)VEGR2(+) may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample size were suggestive of a trend in ARMD using

Antibacterial activity of selected Malaysian honey.

PubMed

Zainol, Mohd Izwan; Mohd Yusoff, Kamaruddin; Mohd Yusof, Mohd Yasim

2013-06-10

Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p > 0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r = -0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r = -0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r = 0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r = -0.1482). Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other constituents are mutually important as contributing factors

Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals.

PubMed

Tian, L; Prior, C; Dempster, J; Marshall, I G

1997-11-01

1. The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/ hemidiaphragm preparations. 2. Hexamethonium (200 microM), but not MLA (0.4-2.0 microM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. 3. At low frequencies of stimulation (0.5-2 Hz), hexamethonium (200 microM) and MLA (2.0 microM) increased e.p.c. quantal content by 30-40%. At high frequencies (50-150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. 4. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. 5. At the concentrations studied, MLA and hexamethonium produced a small (10-20%) decrease in the peak amplitude of m.e.p.cs. 6. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca(2+)-activated K(+)-channels. 7. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the alpha-bungarotoxin-insensitive neuronal type.

Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals

PubMed Central

Tian, >Lijun; Prior, Chris; Dempster, John; Marshall, Ian G

1997-01-01

The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/hemidiaphragm preparations. Hexamethonium (200 μM), but not MLA (0.4–2.0 μM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. At low frequencies of stimulation (0.5–2 Hz), hexamethonium (200 μM) and MLA (2.0 μM) increased e.p.c. quantal content by 30–40%. At high frequencies (50–150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. At the concentrations studied, MLA and hexamethonium produced a small (10–20%) decrease in the peak amplitude of m.e.p.cs. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca2+-activated K+-channels. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the α-bungarotoxin-insensitive neuronal type. PMID:9401765

microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

PubMed

Zhang, Junfeng; Zhang, Zongqi; Zhang, David Y; Zhu, Jianbing; Zhang, Tiantian; Wang, Changqian

2013-01-01

Endothelial progenitor cells (EPCs) are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGFβ1). EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL) for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin) and to maintain the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell functional capacity.

PubMed

Yao, Yuyu; Sheng, Zulong; Li, Yefei; Yan, Fengdi; Fu, Cong; Li, Yongjun; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

2012-08-01

Tissue kallikrein (TK) has been demonstrated to improve neovasculogenesis after myocardial infarction (MI). In the present study, we examined the role and underlying mechanisms of TK in peripheral endothelial progenitor cell (EPC) function. Peripheral blood-derived mononuclear cells containing EPCs were isolated from rat. The in vitro effects of TK on EPC differentiation, apoptosis, migration, and vascular tube formation capacity were studied in the presence or absence of TK, kinin B(2) receptor antagonist (icatibant), and phosphatidylinositol-3 kinase inhibitor (LY294002). Apoptosis was evaluated by flow-cytometry analysis using Annexin V-FITC/PI staining, as well as western-blot analysis of Akt phosphorylation and cleaved caspase-3. Using an MI mouse model, we then examined the in vivo effects of human TK gene adenoviral vector (Ad.hTK) administration on the number of CD34(+)Flk-1(+) progenitors in the peripheral circulation, heart tissue, extent of vasculogenesis, and heart function. Administration of TK significantly increased the number of Dil-LDL/UEA-lectin double-positive early EPCs, as well as their migration and tube formation properties in vitro. Transduction of TK in cultured EPCs attenuated apoptosis induced by hypoxia and led to an increase in Akt phosphorylation and a decrease in cleaved caspase-3 levels. The beneficial effects of TK were blocked by pretreatment with icatibant and LY294002. The expression of recombinant human TK in the ischemic mouse heart significantly improved cardiac contractility and reduced infarct size 7 days after gene delivery. Compared with the Ad.Null group, Ad.hTK reduced mortality and preserved left ventricular function by increasing the number of CD34(+)Flk-1(+) EPCs and promoting the growth of capillaries and arterioles in the peri-infarct myocardium. These data provide direct evidence that TK promotes vessel growth by increasing the number of EPCs and enhancing their functional properties through the kinin B(2) receptor

Comparative Analysis of Circulating Endothelial Progenitor Cells in Age-Related Macular Degeneration Patients Using Automated Rare Cell Analysis (ARCA) and Fluorescence Activated Cell Sorting (FACS)

PubMed Central

Say, Emil Anthony T.; Melamud, Alex; Esserman, Denise Ann; Povsic, Thomas J.; Chavala, Sai H.

2013-01-01

Background Patients with age-related macular degeneration (ARMD) begin with non-neovascular (NNV) phenotypes usually associated with good vision. Approximately 20% of NNV-ARMD patients will convert to vision debilitating neovascular (NV) ARMD, but precise timing of this event is unknown. Developing a clinical test predicting impending conversion to NV-ARMD is necessary to prevent vision loss. Endothelial progenitor cells (EPCs), defined as CD34+VEGR2+ using traditional fluorescence activated cell sorting (FACS), are rare cell populations known to be elevated in patients with NV-ARMD compared to NNV-ARMD. FACS has high inter-observer variability and subjectivity when measuring rare cell populations precluding development into a diagnostic test. We hypothesized that automated rare cell analysis (ARCA), a validated and FDA-approved technology for reproducible rare cell identification, can enumerate EPCs in ARMD patients more reliably. This pilot study serves as the first step in developing methods for reproducibly predicting ARMD phenotype conversion. Methods We obtained peripheral venous blood samples in 23 subjects with NNV-ARMD or treatment naïve NV-ARMD. Strict criteria were used to exclude subjects with known angiogenic diseases to minimize confounding results. Blood samples were analyzed in masked fashion in two separate laboratories. EPCs were independently enumerated using ARCA and FACS within 24 hours of blood sample collection, and p<0.2 was considered indicative of a trend for this proof of concept study, while statistical significance was established at 0.05. Results We measured levels of CD34+VEGFR2+ EPCs suggestive of a trend with higher values in patients with NV compared to NNV-ARMD (p = 0.17) using ARCA. Interestingly, CD34+VEGR2+ EPC analysis using FACS did not produce similar results (p = 0.94). Conclusions CD34+VEGR2+ may have predictive value for EPC enumeration in future ARCA studies. EPC measurements in a small sample size were

Evidence for CXCL16 as a potent angiogenic mediator and endothelial progenitor cell chemotactic factor

PubMed Central

Isozaki, Takeo; Arbab, Ali S.; Haas, Christian S.; Amin, M. Asif; Arendt, Monica D.; Koch, Alisa E.; Ruth, Jeffrey H.

2013-01-01

Background We examined the possibility that CXCL16 recruits endothelial cells (ECs) to developing neovasculature in rheumatoid arthritis (RA) synovium. Methods We utilized the RA synovial tissue (ST) severe combined immunodeficient (SCID) mouse chimera system to examine human dermal microvascular endothelial cell (HMVEC) and human endothelial progenitor cell (EPC) recruitment into engrafted human synovium injected intragraft with RA synovial fluid (SF) immunodepleted of CXCL16. CXCR6 deficient (CXCR6−/−) and wild-type (Wt) C57BL/6 mice were primed to develop K/BxN serum induced arthritis and evaluated for angiogenesis. HMVECs and EPCs from human cord blood were also examined for CXCR6 expression by immunofluorescence and signaling activity for CXCL16. Results We found that CXCR6 is prominently expressed on human EPCs and HMVECs and can be upregulated by interleukin-1β (IL-1β). SCID mice injected intragraft with RA SF immunodepleted of CXCL16 showed a significant reduction in EPC recruitment. Using the K/BxN serum induced inflammatory arthritis model, CXCR6−/− mice showed profound reductions in hemoglobin (Hb) levels that correlated with reductions in monocyte and T-cell recruitment to arthritic joint tissue in CXCR6−/− compared to wildtype (Wt) mice. We also found that HMVECs and EPCs respond to CXCL16 stimulation but have unique signal transduction pathways and homing properties. Conclusion These results indicate that CXCL16 and its receptor CXCR6 may be a central ligand-receptor pair that can be highly correlated with EPC recruitment and blood vessel formation in the RA joint. PMID:23633118

Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway.

PubMed

Deng, Song-Bai; Jing, Xiao-Dong; Wei, Xiao-Ming; Du, Jian-Lin; Liu, Ya-Jie; Qin, Qin; She, Qiang

2017-04-29

Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3'-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 μmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 μmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells.

PubMed

Wang, Z-C; Qi, J; Liu, L-M; Li, J; Xu, H-Y; Liang, B; Li, B

2017-03-01

Valsartan has been reported to have the function of treating hypertension and improving the prognosis of patients. Many studies indicated that valsartan can also increase angiotensin II, andosterone and plasma renin activity (PRA). Autoantibodies against the angiotensin II type 1 receptor (AT1-AA) have been showed to increase reactive oxygen species (ROS) and calcium (Ca2+) and result in apoptosis in vascular smooth muscle cells. In this study, we attempted to explore the effect of valsartan on AT1-AA-induced apoptosis in endothelial progenitor cells. Endothelial progenitor cells (EPCs) were cultured. The cytotoxicity was determined by MTT assay. EPCs apoptosis was determined by DAPI staining and flow cytometry. Reactive oxygen species, intracellular calcium concentration and calpain activity were measured using Fluostar Omega Spectrofluorimeter. The expression of p-ERK, p-eIF-2a, CHOP, Bcl-2 and caspase-3 were detected by Western blot. MTT assays showed valsartan significantly inhibited AT1-AA- induced decline of the viability of EPCs. DAPI staining and flow cytometry results indicated valsartan inhibited AT1-AA-induced decline of the viability of EPCs via inhibiting AT1-AA-induced apoptosis. Furthermore, the increasing of reactive oxygen species, intracellular calcium and calpain activity induced by AT1-AA in EPCs were also recovered after pre-treated with valsartan. Meanwhile, the upregulation of p-ERK, p-eIF-2a and CHOP, downregulation of Bcl-2, and activation of Caspase-3 caused by AT1-AA were reversed after pre-incubated with valsartan. Valsartan could inhibit AT1-AA-induced apoptosis through inhibiting oxidative stress mediated ER stress in EPCs.

Study of the Effectiveness of OCR for Decentralized Data Capture and Conversion. Final Report.

ERIC Educational Resources Information Center

Liston, David M.; And Others

The ERIC network conversion to an OCR (Optical Character Recognition) mode of data entry was studied to analyze the potential effectiveness of OCR data entry for future EPC/s (Editorial Processing Centers). Study results are also applicable to any other system involving decentralized bibliographic data capture and conversion functions. The report…

Specific Cleavage of the Nucleoprotein of Fish Rhabdovirus.

PubMed

Zhou, G-Z; Yi, Y-J; Chen, Z-Y; Zhang, Q-Y

2015-11-01

Siniperca chuatsi rhabdovirus (SCRV) is one of myriad rhabdoviruses recorded in fish. Preliminary data show that inhibition of the SCRV nucleoprotein (N) could significantly reduce the progeny virus titers in infected Epithelioma papulosum cyprinid (EPC) cells. Here, the authors propose that cleavage of the viral 47-kDa N protein is caspase-mediated based on caspase inhibition experiments, transient expression in EPC transfection, and analysis of cleavage sites. Cleavage of the SCRV N protein in culture was prevented by a pan-caspase inhibitor, z-VAD-FMK (z-Val-Ala-DL-Asp-fluoromethyl ketone). Subsequently, N was transiently expressed in EPC cells, the results of which indicated that the specific cleavage of N also occurred in the cells transfected with N-GFP plasmid. Several truncated fragments of the N gene were constructed and transiently transfected into EPC cells. Immunoblotting results indicated that D324 and D374 are the cleavage sites of N by caspases. The authors also found that z-VAD-FMK could inhibit the cytopathic effect in SCRV-infected EPC cells but not affect the production of infectious progeny, suggesting that the caspase-mediated cleavage of N protein is not required for in vitro SCRV replication. To the authors' knowledge, this is the first report on the cleavage of rhabdovirus proteins. © The Author(s) 2015.

Inhibition of CYP4A by a novel flavonoid FLA-16 prolongs survival and normalizes tumor vasculature in glioma.

PubMed

Wang, Chenlong; Li, Ying; Chen, Honglei; Zhang, Jie; Zhang, Jing; Qin, Tian; Duan, Chenfan; Chen, Xuewei; Liu, Yanzhuo; Zhou, Xiaoyang; Yang, Jing

2017-08-28

Glioblastomas rapidly become refractory to anti-VEGF therapies. We previously showed that cytochrome P450 (CYP) 4A-derived 20-hydroxyeicosatetraenoic acid (20-HETE) promotes angiogenesis. Here, we tested whether a novel flavonoid (FLA-16) prolongs survival and normalizes tumor vasculature in glioma through CYP4A inhibition. FLA-16 improved survival, reduced tumor burden, and normalized vasculature, accompanied with the decreased secretion of 20-HETE, VEGF and TGF-β in tumor-associated macrophages (TAMs) and endothelial progenitor cells (EPCs) in C6 and U87 gliomas. FLA-16 attenuated vascular abnormalization induced by co-implantation of GL261 glioma cells with CYP4A10 high macrophages or EPCs. Mechanistically, the conditional medium from TAMs and EPCs treated with FLA-16 enhanced the migration of pericyte cells, and decreased the proliferation and migration of endothelial cells, which were reversed by CYP4A overexpression or exogenous addition of 20-HETE, VEGF and TGF-β. Furthermore, FLA-16 prevented crosstalk between TAMs and EPCs during angiogenesis. These results suggest that CYP4A inhibition by FLA-16 prolongs survival and normalizes vasculature in glioma through decreasing production of TAMs and EPCs-derived VEGF and TGF-β. This may represent a potential therapeutic strategy to overcome resistance to anti-VEGF treatment by effects on vessels and immune cells. Copyright © 2017 Elsevier B.V. All rights reserved.

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients.

PubMed

Patry, Christian; Stamm, Daniela; Betzen, Christian; Tönshoff, Burkhard; Yard, Benito A; Beck, Grietje Ch; Rafat, Neysan

2018-01-01

Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome. Peripheral blood mononuclear cells from septic patients ( n  = 30), ICU control patients ( n  = 11) and healthy volunteers ( n  = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and - 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays. EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival. Our data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis.

Effect of hyperglycemia on the number of CD117+ progenitor cells and their differentiation toward endothelial progenitor cells in young and old ages.

PubMed

Pierpaoli, Elisa; Moresi, Raffaella; Orlando, Fiorenza; Malavolta, Marco; Provinciali, Mauro

2016-10-01

Dysfunction of endothelial progenitor cells (EPCs) has been reported either in aging or diabetes, though the influence of an "old" environment on numerical and functional changes of diabetes associated EPCs is not known. We evaluated the effect of both aging and early stage of streptozotocin-induced diabetes on the number of bone marrow-derived CD117 + progenitor cells, and on their differentiation in vitro toward EPCs. The phenotype of progenitor cells and the uptake of acetylated-low density lipoprotein (Ac-LDL) were evaluated after cell culture in VEGF, FGF-1, and IGF-1 supplemented medium. Hyperglycemia similarly reduced the number of CD117 + cells both in young and old mice. CD117 + cells from young mice differentiated better than those from old animals "in vitro", with a greater reduction of CD117 + cells and an higher increase of CD184 + VEGFR-2 + cells. In diabetic mice, in vitro CD117 + cells differentiation was significantly reduced in young animals. Diabetes did not impact on the scarce differentiation of CD117 + cells from old mice. Hyperglycemia reduced the uptake of acLDL by EPCs greatly in young than in old mice. These findings indicate that part of the EPCs functional alterations induced by hyperglicemia in young mice are observed in normal aged mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Superoxide reaction with tyrosyl radicals generates para-hydroperoxy and para-hydroxy derivatives of tyrosine.

PubMed

Möller, Matías N; Hatch, Duane M; Kim, Hye-Young H; Porter, Ned A

2012-10-10

Tyrosine-derived hydroperoxides are formed in peptides and proteins exposed to enzymatic or cellular sources of superoxide and oxidizing species as a result of the nearly diffusion-limited reaction between tyrosyl radical and superoxide. However, the structure of these products, which informs their reactivity in biology, has not been unequivocally established. We report here the complete characterization of the products formed in the addition of superoxide, generated from xanthine oxidase, to several peptide-derived tyrosyl radicals, formed from horseradish peroxidase. RP-HPLC, LC-MS, and NMR experiments indicate that the primary stable products of superoxide addition to tyrosyl radical are para-hydroperoxide derivatives (para relative to the position of the OH in tyrosine) that can be reduced to the corresponding para-alcohol. In the case of glycyl-tyrosine, a stable 3-(1-hydroperoxy-4-oxocyclohexa-2,5-dien-1-yl)-L-alanine was formed. In tyrosyl-glycine and Leu-enkephalin, which have N-terminal tyrosines, bicyclic indolic para-hydroperoxide derivatives were formed ((2S,3aR,7aR)-3a-hydroperoxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indole-2-carboxylic acid) by the conjugate addition of the free amine to the cyclohexadienone. It was also found that significant amounts of the para-OH derivative were generated from the hydroxyl radical, formed on exposure of tyrosine-containing peptides to Fenton conditions. The para-OOH and para-OH derivatives are much more reactive than other tyrosine oxidation products and may play important roles in physiology and disease.

Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

PubMed

Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

2015-01-01

Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

Permeability of lipid bilayers to amino acids and phosphate

NASA Technical Reports Server (NTRS)

Chakrabarti, A. C.; Deamer, D. W.

1992-01-01

Permeability coefficients for amino acid classes, including neutral, polar, hydrophobic, and charged species, were measured and compared with values for other ionic solutes such as phosphate. The rates of efflux of glycine, lysine, phenylalanine, serine and tryptophan were determined after they were passively entrapped in large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine (EPC) or dimyristoylphosphatidylcholine (DMPC). The following permeability coefficients were obtained for: glycine, 5.7 x 10(-12) cm s-1 (EPC), 2.0 x 10(-11) cm s-1 (DMPC); serine, 5.5 x 10(-12) cm s-1 (EPC), 1.6 x 10(-11) cm s-1 (DMPC); lysine, 5.1 x 10(-12) cm s-1 (EPC), 1.9 x 10(-11) cm s-1 (DMPC); tryptophan, 4.1 x 10(-10) cm s-1 (EPC); and phenylalanine, 2.5 x 10(-10) cm s-1 (EPC). Decreasing lipid chain length increased permeability slightly, while variations in pH had only minor effects on the permeability coefficients of the amino acids tested. Phosphate permeability was in the range of 10(-12)-10(-13) cm s-1 depending on the pH of the medium. The values for the polar and charged amino acids were surprisingly similar to those previously measured for monovalent cations such as sodium and potassium, which are in the range of 10(-12)-10(-13) cm s-1, depending on conditions and the lipid species used. This observation suggests that the permeation rates for the neutral, polar and charged amino acids are controlled by bilayer fluctuations and transient defects, rather than partition coefficients and Born energy barriers. The results are relevant to the permeation of certain peptides into lipid bilayers during protein translocation and membrane biogenesis.

Vasculogenesis and Diabetic Erectile Dysfunction: How Relevant Is Glycemic Control?

PubMed

Castela, Angela; Gomes, Pedro; Silvestre, Ricardo; Guardão, Luísa; Leite, Liliana; Chilro, Rui; Rodrigues, Ilda; Vendeira, Pedro; Virag, Ronald; Costa, Carla

2017-01-01

Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human endothelial progenitor cells rescue cortical neurons from oxygen-glucose deprivation induced death.

PubMed

Bacigaluppi, Susanna; Donzelli, Elisabetta; De Cristofaro, Valentina; Bragazzi, Nicola Luigi; D'Amico, Giovanna; Scuteri, Arianna; Tredici, Giovanni

2016-09-19

Cerebral ischemia is characterized by both acute and delayed neuronal injuries. Neuro-protection is a major issue that should be properly addressed from a pharmacological point of view, and cell-based treatment approaches are of interest due to their potential pleiotropic effects. Endothelial progenitor cells have the advantage of being mobilized from the bone marrow into the circulation, but have been less studied than other stem cells, such as mesenchymal stem cells. Therefore, the comparison between human endothelial progenitor cells (hEPC) and human mesenchymal progenitor cells (hMSC) in terms of efficacy in rescuing neurons from cell death after transitory ischemia is the aim of the current study, in the effort to address further directions. In vitro model of oxygen-glucose deprivation (OGD) on a primary culture of rodent cortical neurons was set up with different durations of exposure: 1, 2 and 3hrs with assessment of neuron survival. The 2hrs OGD was chosen for the subsequent experiments. After 2hrs OGD neurons were either placed in indirect co-culture with hMSC or hEPC or cultured in hMSC or hEPC conditioned medium and cell viability was evaluated by MTT assay. At day 2 after 2hrs OGD exposure, mean neuronal survival was 47.9±24.2%. In contrast, after treatment with hEPC and hMSC indirect co-culture was 74.1±27.3%; and 69.4±18.8%, respectively. In contrast, treatment with conditioned medium did not provide any advantage in terms of survival to OGD neurons The study shows the efficacy of hEPC in indirect co-culture to rescue neurons from cell death after OGD, comparable to that of hMSC. hEPC deserve further studies given their potential interest for ischemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Loss of Sirt3 Limits Bone Marrow Cell-Mediated Angiogenesis and Cardiac Repair in Post-Myocardial Infarction

PubMed Central

Zeng, Heng; Li, Lanfang; Chen, Jian-Xiong

2014-01-01

Sirtuin-3 (Sirt3) has a critical role in the regulation of human aging and reactive oxygen species (ROS) formation. A recent study has identified Sirt3 as an essential regulator of stem cell aging. This study investigated whether Sirt3 is necessary for bone marrow cell (BMC)-mediated cardiac repair in post-myocardial infarction (MI). In vitro, BMC-derived endothelial progenitor cells (EPCs) from wild type (WT) and Sirt3KO mice were cultured. EPC angiogenesis, ROS formation and apoptosis were assessed. In vivo, WT and Sirt3 KO mice were subjected to MI and BMCs from WT and Sirt3 KO mice were injected into ischemic area immediately. The expression of VEGF and VEGFR2 was reduced in Sirt3KO-EPCs. Angiogenic capacities and colony formation were significantly impaired in Sirt3KO-EPCs compared to WT-EPCs. Loss of Sirt3 further enhanced ROS formation and apoptosis in EPCs. Overexpression of Sirt3 or treatment with NADPH oxidase inhibitor apocynin (Apo, 200 and 400 microM) rescued these abnormalities. In post-MI mice, BMC treatment increased number of Sca1+/c-kit+ cells; enhanced VEGF expression and angiogenesis whereas Sirt3KO-BMC treatment had little effects. BMC treatment also attenuated NADPH oxidase subunits p47phox and gp91phox expression, and significantly reduced ROS formation, apoptosis, fibrosis and hypertrophy in post-MI mice. Sirt3KO-BMC treatment did not display these beneficial effects. In contrast, Sirt3KO mice treated with BMCs from WT mice attenuated myocardial apoptosis, fibrosis and improved cardiac function. Our data demonstrate that Sirt3 is essential for BMC therapy; and loss of Sirt3 limits BMC-mediated angiogenesis and cardiac repair in post-MI. PMID:25192254

Construction of a multifunctional coating consisting of phospholipids and endothelial progenitor cell-specific peptides on titanium substrates

NASA Astrophysics Data System (ADS)

Chen, Huiqing; Li, Xiaojing; Zhao, Yuancong; Li, Jingan; Chen, Jiang; Yang, Ping; Maitz, Manfred F.; Huang, Nan

2015-08-01

A phospholipid/peptide polymer (PMMDP) with phosphorylcholine groups, endothelial progenitor cell (EPC)-specific peptides and catechol groups was anchored onto a titanium (Ti) surface to fabricate a biomimetic multifunctional surface. The PMMDP coating was characterized by X-ray photoelectron spectroscopy (XPS), water contact angle measurements and atomic force microscopy (AFM), respectively. The amount of PMMDP coating on the Ti surface was quantified by using the quartz crystal microbalance with dissipation (QCM-D). Interactions between blood components and the coated and bare Ti substrates were evaluated by platelet adhesion and activation assays and fibrinogen denaturation test using platelet rich plasma (PRP). The results revealed that the PMMDP-modified surface inhibited fibrinogen denaturation and reduced platelet adhesion and activation. EPC cell culture on the PMMDP-modified surface showed increased adhesion and proliferation of EPCs when compared to the cells cultured on untreated Ti surface. The inhibition of fibrinogen denaturation and platelet adhesion and support of EPCs attachment and proliferation indicated that this coating might be beneficial for future applications in blood-contacting implants, such as vascular stents.

Effects of Stress Relaxation Aging with Electrical Pulses on Microstructures and Properties of 2219 Aluminum Alloy

PubMed Central

Tan, Jingsheng; Zhan, Lihua; Zhang, Jiao; Yang, Zhan; Ma, Ziyao

2016-01-01

To realize the high-efficiency and high-performance manufacture of complex high-web panels, this paper introduced electric pulse current (EPC) into the stress relaxation aging forming process of 2219 aluminum alloy and systematically studied the effects of EPC, stress, and aging time upon the microstructure and properties of 2219 aluminum alloy. It is discovered that: (a) EPC greatly enhanced the mechanical properties after stress relaxation aging and reduced the sensitivity of the yield strength for the initial stress under the aging system of 165 °C/11 h; (b) compared with general aging, stress relaxation aging instead delayed the aging process of 2219 aluminum alloy and greatly increased the peak strength value; (c) EPC accelerated the aging precipitation behavior of 2219 aluminum alloy and reduced transgranular and grain-boundary energy difference, thus leading to a more diffused distribution of the transgranular precipitated phase and the absence of a significant precipitation-free zone (PFZ) and grain-boundary stable phase in the grain boundary, further improving the mechanical properties of the alloy. PMID:28773660

Catalytic Ketone Hydrodeoxygenation Mediated by Highly Electrophilic Phosphonium Cations.

PubMed

Mehta, Meera; Holthausen, Michael H; Mallov, Ian; Pérez, Manuel; Qu, Zheng-Wang; Grimme, Stefan; Stephan, Douglas W

2015-07-06

Ketones are efficiently deoxygenated in the presence of silane using highly electrophilic phosphonium cation (EPC) salts as catalysts, thus affording the corresponding alkane and siloxane. The influence of distinct substitution patterns on the catalytic effectiveness of several EPCs was evaluated. The deoxygenation mechanism was probed by DFT methods. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Confirmation of Non-Impacted Status (TA16-280 Complex)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruedig, Elizabeth

2017-12-07

EPC-ES finds that the materials associated with TA16-280 complex (see Figure 1) are candidates for release to the public for recycle or as sanitary/commercial waste. This finding is consistent with the requirements of DOE Order 458.1 Radiation Protection of the Public and the Environment and LANL Policy 412 Environmental Radiation Protection.

Expression of Angiogenic MicroRNAs in Endothelial Progenitor Cells From Type 1 Diabetic Patients With and Without Diabetic Retinopathy.

PubMed

García de la Torre, Nuria; Fernández-Durango, Raquel; Gómez, Raquel; Fuentes, Manuel; Roldán-Pallarés, Manuela; Donate, Juan; Barabash, Ana; Alonso, Bárbara; Runkle, Isabelle; Durán, Alejandra; Rubio, Miguel Angel; Calle-Pascual, Alfonso L

2015-06-01

MicroRNA (miR) expression in endothelial progenitor cells (EPCs) in type 1 diabetes (DM1) and its relation with different stages of diabetic retinopathy (DR) have not been reported to date. Our aim was to analyze miR-222, miR-221, and miR-126 expression in EPCs from DM1 patients with and without DR. We included 41 patients with DR, 35 without DR, and 38 controls. Blood was collected for flow cytometry and EPC culture. Total RNA was extracted and purified and real-time quantitative PCR was performed for miR expression in cultured EPCs. Relative changes in miR expression were analyzed with the 2-ΔΔCT method. Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls (0.030 [interquartile range [IQR], 0.020-0.050] vs. 0.060 [IQR, 0.030-0.110], P = 0.004; 1.740 [IQR, 0.890-4.120] vs. 0.990 [IQR, 0.487-3.015], P = 0.047 respectively) without differences between patients with and without DR. Patients with DR had higher expression of miR-221 than those without DR (1.405 [IQR, 0.820-2.867] vs. 0.915 [IQR, 0.507-1.292], P = 0.019) without differences among degrees of DR. Circulating EPCs were reduced in patients on statins (0.010 [IQR, 0.010-0.050] vs. 0.045 [IQR, 0.020-0.087], P = 0.008), and miR-221 expression increased in patients on angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) II (1.430 [IQR, 1.160-2.705] vs. 1.000 [IQR, 0.520-1.330], P = 0.021) compared to those without treatment. MicroRNA-126 expression was associated with body mass index (BMI; ρ = -0.267, P = 0.026) and diastolic blood pressure (ρ = -0.267, P = 0.034). MicroRNA-221 was associated with triglyceride concentration (ρ = 0.296, P = 0.012). Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls. Patients with DR had higher expression of miR-221 than those without DR. The identification of biomarkers of diabetic complications might be useful for monitoring disease progression and potential

Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation.

PubMed

Bou Khzam, Lara; Bouchereau, Olivier; Boulahya, Rahma; Hachem, Ahmed; Zaid, Younes; Abou-Saleh, Haissam; Merhi, Yahye

2015-11-09

Endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs). We aimed at characterizing these two EPC subtypes and at identifying their role in platelet aggregation. EOCs and ECFCs were generated from human peripheral blood mononuclear cells (PBMCs) seeded in conditioned media on fibronectin and collagen, respectively. The morphological, phenotypical and functional characteristics of EOCs and ECFCs were assessed by optical and confocal laser scanning microscopes, cell surface markers expression, and Matrigel tube formation. The impact of EOCs and ECFCs on platelet aggregation was monitored in collagen-induced optical aggregometry and compared with PBMCs and human umbilical vein endothelial cells (HUVECs). The levels of the anti-platelet agents' nitric oxide (NO) and prostacyclin (PGI2) released from cultured cells as well as the expression of their respective producing enzymes NO synthases (NOS) and cyclooxygenases (COX) were also assessed. We showed that EOCs display a monocytic-like phenotype whereas ECFCs have an endothelial-like phenotype. We demonstrated that both EOCs and ECFCs and their supernatants inhibited platelet aggregation; however ECFCs were more efficient than EOCs. This could be related to the release of significantly higher amounts of NO and PGI2 from ECFCs, in comparison to EOCs. Indeed, ECFCs, like HUVECs, constitutively express the endothelial (eNOS)-and inducible (iNOS)-NOS isoforms, and COX-1 and weakly express COX-2, whereas

Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004-2008.

PubMed

Menz, Hylton B

2009-10-30

In 2004, as an extension of the Enhanced Primary Care (EPC) program, the Australian Government introduced a policy of providing Medicare rebates for allied health services provided to patients with chronic or complex health conditions. The objective of this study was to evaluate the utilisation of podiatry services provided under this scheme between 2004 and 2008. Data pertaining to the Medicare item 10962 for the calendar years 2004-2008 were extracted from the Australian Medicare Benefits Schedule (MBS) database and cross-tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number of consultations provided and to assess for temporal trends over the five-year assessment period. The total cost to Medicare over this period was also determined. During the 2004-2008 period, a total of 1,338,044 EPC consultations were provided by podiatrists in Australia. Females exhibited higher utilisation than males (63 versus 37%), and those aged over 65 years accounted for 75% of consultations. There was a marked increase in the number of consultations provided from 2004 to 2008, and the total cost of providing EPC podiatry services during this period was $62.9 M. Podiatry services have been extensively utilised under the EPC program by primary care patients, particularly older women, and the number of services provided has increased dramatically between 2004 and 2008. Further research is required to determine whether the EPC program enhances clinical outcomes compared to standard practice.

Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis.

PubMed

Li, Xiaogang; Gou, Shanmiao; Liu, Zhiqiang; Ye, Zeng; Wang, Chunyou

2018-03-01

Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014). Overall survival was analyzed using Kaplan-Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan-Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Manaresi, Elisabetta; Gallinella, Giorgio

2016-07-15

Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved permeability of acyclovir: optimization of mucoadhesive liposomes using the phospholipid vesicle-based permeation assay.

PubMed

Naderkhani, Elenaz; Erber, Astrid; Škalko-Basnet, Nataša; Flaten, Gøril Eide

2014-02-01

The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations' mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Dark gap solitons in exciton-polariton condensates in a periodic potential.

PubMed

Cheng, Szu-Cheng; Chen, Ting-Wei

2018-03-01

We show that dark spatial gap solitons can occur inside the band gap of an exciton-polariton condensate (EPC) in a one-dimensional periodic potential. The energy dispersions of an EPC loaded into a periodic potential show a band-gap structure. Using the effective-mass model of the complex Gross-Pitaevskii equation with pump and dissipation in an EPC in a periodic potential, dark gap solitons are demonstrated near the minimum energy points of the band center and band edge of the first and second bands, respectively. The excitation energies of dark gap solitons are below these minimum points and fall into the band gap. The spatial width of a dark gap soliton becomes smaller as the pump power is increased.

Dark gap solitons in exciton-polariton condensates in a periodic potential

NASA Astrophysics Data System (ADS)

Cheng, Szu-Cheng; Chen, Ting-Wei

2018-03-01

We show that dark spatial gap solitons can occur inside the band gap of an exciton-polariton condensate (EPC) in a one-dimensional periodic potential. The energy dispersions of an EPC loaded into a periodic potential show a band-gap structure. Using the effective-mass model of the complex Gross-Pitaevskii equation with pump and dissipation in an EPC in a periodic potential, dark gap solitons are demonstrated near the minimum energy points of the band center and band edge of the first and second bands, respectively. The excitation energies of dark gap solitons are below these minimum points and fall into the band gap. The spatial width of a dark gap soliton becomes smaller as the pump power is increased.

A new heterometallic hybrid based on polymeric iodoplumbate and lanthanide metal-carboxylic coordination polycation

NASA Astrophysics Data System (ADS)

Gong, An-Weng; Wu, Hong-Yan; Lian, Zhao-Xun; Dong, Hai-Jun; Li, Hao-Hong; Chen, Zhi-Rong

2013-03-01

A 3-D supramolecular hybrid {[La(EPC)3(H2O)3]2(Pb6I18)}n (EPC+ = N-ethyl-pyridium-4-carboxylate) (1) has been structurally determined, which assume significance for its incorporating lanthanide metal-carboxylic coordination polycation into polymeric iodoplumbate to get heterometallics. 1 consists of 1-D (PbI)n6n- zigzag-like anion chains with lanthanide metalcarboxylic [La(EPC)3(HO)3]n3n+ polycations, which arrange in a criss-cross configuration. C-H⋯I and C-H⋯O hydrogen bonds among inorganic anions and polycations contribute to the formation of a 3-D supramolecular framework. Moreover, the framework displays an absorption edge at 2.46 eV which is comparable to PbI2's absorption edge.

Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis.

PubMed

Chou, Chen-Pin; Jiang, Shih Sheng; Pan, Huay-Ben; Yen, Yi-Chen; Tseng, Hui-Hwa; Hung, Yu-Ting; Wang, Ssu-Han; Chen, Yu-Lin; Chen, Ya-Wen

2016-11-24

Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34 + VEGFR2 + EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.

Publication rates following pancreas meetings.

PubMed

Timmer, A; Blum, T; Lankisch, P G

2001-08-01

Publication rates and determinants of publication were studied based on abstracts presented at pancreatic meetings. All abstracts presented at the 1994 and 1995 annual meetings of the European Pancreatic Club (EPC) and the American Pancreatic Association (APA) were followed up by searching MEDLINE. Publication rates were compared using log-rank tests and multiple logistic regression. The prestige of the publishing journals was compared using Kruskal-Wallis tests on scientific impact factors (SIF). Overall, 340 abstracts were presented at the EPC, and 254 were presented at the APA. Of these, 203 (59.7%, EPC) and 138 (54.3%, APA) were later published in peer-reviewed journals. Publication rates did not differ by study type or country region of origin. In addition, median SIFs were similar by conference (APA vs. EPC) and research type (basic science vs. clinical studies) (overall, 1.7). However, North American and North/West European articles were published in higher impact journals as compared with those from other countries. Publication rates and median journal SIFs in pancreas research are similar to those reported from other medical specialty meetings. There is no difference by conference, type of research, or origin (North American vs. European).

Endothelial progenitor cells and rheumatic disease modifying therapy.

PubMed

Lo Gullo, Alberto; Aragona, Caterina Oriana; Michele, Scuruchi; Versace, Antonio Giovanni; Antonino, Saitta; Egidio, Imbalzano; Loddo, Saverio; Campo, Giuseppe Maurizio; Giuseppe, Mandraffino

2018-05-26

Rheumatic diseases are associated with accelerated atherosclerosis and with increased risk of cardiovascular morbidity and mortality. The mechanisms underlying the higher prevalence of cardiovascular disease are not completely clarified, but it is likely that a pivotal role is played by vascular inflammation and consequently to altered vascular endothelium homeostasis. Also, high prevalence of traditional risk factors, proatherogenic activation and endothelial dysfunction further contribute to vascular damage. Circulating endothelial progenitor cells (EPCs) can restore dysfunctional endothelium and protect against atherosclerotic vascular disease. However, abnormalities in number and function of these cells in patients with rheumatic condition have been extensively reported. During the last years, growing interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD has been shown; in addition, pioneering studies show that EPC dysfunction might be improved with pharmacological strategies. However, how to restore EPC function, and whether achieving this aim may be effective in preventing cardiovascular complications in rheumatic disease, remain to be established. In this review we report an overview on the current stand of knowledge on the effect of pharmaceutical and lifestyle intervention in improving EPCs number and function in rheumatic disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamic optical resource allocation for mobile core networks with software defined elastic optical networking.

PubMed

Zhao, Yongli; Chen, Zhendong; Zhang, Jie; Wang, Xinbo

2016-07-25

Driven by the forthcoming of 5G mobile communications, the all-IP architecture of mobile core networks, i.e. evolved packet core (EPC) proposed by 3GPP, has been greatly challenged by the users' demands for higher data rate and more reliable end-to-end connection, as well as operators' demands for low operational cost. These challenges can be potentially met by software defined optical networking (SDON), which enables dynamic resource allocation according to the users' requirement. In this article, a novel network architecture for mobile core network is proposed based on SDON. A software defined network (SDN) controller is designed to realize the coordinated control over different entities in EPC networks. We analyze the requirement of EPC-lightpath (EPCL) in data plane and propose an optical switch load balancing (OSLB) algorithm for resource allocation in optical layer. The procedure of establishment and adjustment of EPCLs is demonstrated on a SDON-based EPC testbed with extended OpenFlow protocol. We also evaluate the OSLB algorithm through simulation in terms of bandwidth blocking ratio, traffic load distribution, and resource utilization ratio compared with link-based load balancing (LLB) and MinHops algorithms.

Human endothelial progenitor cells-derived exosomes accelerate cutaneous wound healing in diabetic rats by promoting endothelial function.

PubMed

Li, Xiaocong; Jiang, Chunyu; Zhao, Jungong

2016-08-01

Wound healing is deeply dependent on neovascularization to restore blood flow. The neovascularization of endothelial progenitor cells (EPCs) through paracrine secretion has been reported in various tissue repair models. Exosomes, key components of cell paracrine mechanism, have been rarely reported in wound healing. Exosomes were isolated from the media of EPCs obtained from human umbilical cord blood. Diabetic rats wound model was established and treated with exosomes. The in vitro effects of exosomes on the proliferation, migration and angiogenic tubule formation of endothelial cells were investigated. We revealed that human umbilical cord blood EPCs derived exosomes transplantation could accelerate cutaneous wound healing in diabetic rats. We also showed that exosomes enhanced the proliferation, migration and tube formation of vascular endothelial cells in vitro. Furthermore, we found that endothelial cells stimulated with these exosomes would increase expression of angiogenesis-related molecules, including FGF-1, VEGFA, VEGFR-2, ANG-1, E-selectin, CXCL-16, eNOS and IL-8. Taken together, our findings indicated that EPCs-derived exosomes facilitate wound healing by positively modulating vascular endothelial cells function. Copyright © 2016 Elsevier Inc. All rights reserved.

Producing and quantifying enriched para-H2.

PubMed

Tom, Brian A; Bhasker, Siddhartha; Miyamoto, Yuki; Momose, Takamasa; McCall, Benjamin J

2009-01-01

The production of enriched para-H(2) is useful for many scientific applications, but the technology for producing and measuring para-H(2) is not yet widespread. In this note and in the accompanying auxiliary material, we describe the design, construction, and use of a versatile standalone converter that is capable of producing para-H(2) enrichments of up to > or = 99.99% at continuous flow rates of up to 0.4 SLM. We also discuss para-H(2) storage and back conversion rates, and improvements to three techniques (thermal conductance, NMR, and solid hydrogen impurity spectroscopy) used to quantify the para-H(2) enrichment.

Moderate Hypoxia Exhibits Increased Endothelial Progenitor Vessel-forming Ability However Gestational Diabetes Caused to Impede Compensatory Defense Reaction.

PubMed

Dincer, U Deniz

2016-05-30

Endothelium represents a defense barrier and responds and integrates neuro humoral stimulus which describes as a compensatory mechanism. Endothelium formed with endothelial cells (ECs) and their progenitors. Endothelial progenitor cells (EPCs) represent minor subpopulation of mononuclear cells in the blood. During acute hypoxia, larger amount of EPCs mobilize into the peripheral blood and they directly contribute revascularization process. One of the subtypes of EPC is termed endothelial colony forming cells (ECFCs) which they possess de novo vessel-forming ability. The present study aims to investigate the role of hypoxia in EPCs functional and vessel-forming ability. Furthermore, it was investigated whether fetal exposure to a diabetic intrauterine environment influence EPCs adaptation ability. Human umbilical cord blood (HUCB) derived ECFCs were selected in all experimental procedures obtained from normal and gestational diabetes mellitus (GDM) subjects via in vitro cell culture methods. Early passage (<5) HUCB ECFCs obtain from GDM (n; 5) and control (n; 5) subjects were cultured with plates pre-coated with collagen in vitro 72 h hypoxic as well as normoxic condition. Endothelial, angiogenic and hypoxia associated gene specific primers designed to perform Real-time PCR. Senescenes assay conducted onto HUCB ECFCs to investigate their functional clonogenic ability. To quantify their vessel forming ability matrigel assay was applied. These data demonstrates that moderate hypoxia results increased vessel-forming ability and VEGFA expression in HUCB ECFCs obtained from control subjects. However, GDM caused to impede compensatory defense reaction against hypoxia which observed in control subjects. Thus, it illuminates beneficial information related future therapeutic modalities.

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

PubMed

Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

2015-10-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

Possible involvement of miRNAs in tropism of Parvovirus B19.

PubMed

Anbarlou, Azadeh; AkhavanRahnama, Mahshid; Atashi, Amir; Soleimani, Masoud; Arefian, Ehsan; Gallinella, Giorgio

2016-03-01

Human Parvovirus B19 (PVB19) is one of the most important pathogens that targets erythroid lineage. Many factors were mentioned for restriction to erythroid progenitor cells (EPCs). Previous studies showed that in non-permissive cells VP1 and VP2 (structural proteins) mRNAs were detected but could not translate to proteins. A bioinformatics study showed that this inhibition might be due to specific microRNAs (miRNAs) present in non-permissive cells but not in permissive EPCs. To confirm the hypothesis, we evaluated the effect of miRNAs on VP expression. CD34(+) HSCs were separated from cord blood. Then, CD34(+) cells were treated with differentiation medium to obtain CD36(+) EPCs. To evaluate the effect of miRNAs on VP expression in MCF7 and HEK-293 cell lines (non-permissive cells) and CD36(+) EPCs, dual luciferase assay was performed in presence of shRNAs against Dicer and Drosha to disrupt miRNA biogenesis. QRT-PCR was performed to check down-regulation of Dicer and Drosha after transfection. All measurements were done in triplicate. Data means were compared using one-way ANOVAs. MicroRNA prediction was done by the online microRNA prediction tools. No significant difference was shown in luciferase activity of CD36(+) EPCs after co-transfection with shRNAs, while it was significant in non-permissive cells. Our study revealed that miRNAs may be involved in inhibition of VP expression in non-permissive cells, although further studies are required to demonstrate which miRNAs exactly are involved in regulation of PVB19 replication.

[Manufacture and application of laparoscopic extraperitoneal sigmoid colostomy].

PubMed

Jin, Hei-ying; DU, Yong-hong; Wang, Xiao-feng; Yao, Hang; Wu, Kun-lan; Zhang, Bei; Zhang, Jin-hao

2013-10-01

To investigate the safety and feasibility of laparoscopic extraperitoneal sigmoid colostomy. Thirty-six patients with low rectal cancer undergoing laproscopic abdominoperineal resection from July 2011 to July 2012 were prospectively enrolled in the study and randomly divided into extraperitoneal colostomy group(EPC, n=18) and internal peritoneal colostomy group(IPC, n=18). Follow-up period was 4-16 (median, 7) months and postoperative complications were compared between two groups. One case in EPC group was converted to IPC because of poor blood supply of the proximal sigmoid, who was eliminated from the subsequent analysis. Compared with the IPC group, the surgery time was longer in EPC group [(25.3±8.5) min vs. (14.7±6.4) min], while the difference was not statistically significant(P>0.05). Each group had 1 case of stoma ischemia, who both received the colostomy reconstructive surgery. The incidence of stoma edema was significantly higher in EPC group[35.3%(6/17) vs. 0, P<0.05). The early postoperative complications rate did not significantly different between the two groups[58.8%(10/17) vs. 27.8%(5/18), P>0.05]. The late postoperative complications rate was 22.2%(4/18) in IPC group, including 1 case of stoma prolapse, 1 case of stoma stenosis and 2 cases of parastomal hernia. No later postoperative complication occurred in EPC group. Extraperitoneal sigmoid colostomy is an easy and safe procedure with lower late complications as compared to internal peritoneal sigmoid colostomy.

Enhanced detection of infectious hematopoietic necrosis virus by pretreatment of cell monolayers with polyethylene glycol

USGS Publications Warehouse

Batts, W.N.; Winton, J.R.

1989-01-01

To improve quantification of very low levels of infectious hematopoietic necrosis virus (IHNV) in samples of tissue, ovarian fluid, or natural water supplies, we tested the ability of polyethylene glycol (PEG) to enhance the sensitivity and speed of the plaque assay system. We compared 4, 7, and 10% solutions of PEG of molecular weight 6,000, 8,000, or 20,000 applied at selected volumes and for various durations. When cell monolayers of epithelioma papulosum cyprini (EPC), fathead minnow (FHM), chinook salmon embryo (CHSE-214), and bluegill fry (BF2) were pretreated with 7% PEG-20,000, they produced 4-17-fold increases in plaque assay titers of IHNV. The plaque assay titers of viral hemorrhagic septicemia virus, chum salmon reovirus, and chinook salmon paramyxovirus were also enhanced by exposure of CHSE-214 cells to PEG, but the titers of infectious pancreatic necrosis virus and Oncorhynchus masou virus were not substantially changed. Plaques formed by IHNV on PEG-treated EPC cells incubated at 15°C had a larger mean diameter at 6 d than those on control cells at 8 d; this suggests the assay could be shortened by use of PEG. Pretreatment of EPC cell monolayers with PEG enabled detection of IHNV in some samples that appeared negative with untreated cells. For example, when ovarian fluid samples from chinook salmon Oncorhynchus tshawytscha were inoculated onto untreated monolayers of EPC cells, IHNV was detected in only 11 of 51 samples; 17 of the samples were positive when PEG-treated EPC cells were used.PDF

Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts

PubMed Central

Chen, Xiaofang; Aledia, Anna S.; Popson, Stephanie A.; Him, Linda; Hughes, Christopher C.W.

2010-01-01

To ensure survival of engineered implantable tissues thicker than approximately 2–3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, before implantation (prevascularization), is one potential strategy to achieve this aim. In this study, we developed three-dimensional engineered vessel networks in vitro by coculture of endothelial cells (ECs) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial progenitor cell–derived ECs (EPC-ECs) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared with 5–7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein ECs (HUVECs) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immune-compromised mice, however, revealed a dramatic difference in the ability of EPC-ECs and HUVECs to form anastomoses with the host vasculature. Vascular beds derived from EPC-ECs were perfused within 1 day of implantation, whereas no HUVEC vessels were perfused at day 1. Further, while almost 90% of EPC-EC–derived vascular beds were perfused at day 3, only one-third of HUVEC-derived vascular beds were perfused. In both cases, a high density of fibroblasts accelerated anastomosis by 2–3 days. We conclude that both EPC-ECs and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo. PMID:19737050

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study.

PubMed

Ahmed, Fahad W; Rider, Rachel; Glanville, Michael; Narayanan, Kilimangalam; Razvi, Salman; Weaver, Jolanta U

2016-08-26

Type 1 diabetes is associated with increased cardiovascular disease (CVD). Decreased endothelial progenitor cells (EPCs) number plays a pivotal role in reduced endothelial repair and development of CVD. We aimed to determine if cardioprotective effect of metformin is mediated by increasing circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and decreasing circulating endothelial cells (cECs) count whilst maintaining unchanged glycemic control. This study was an open label and parallel standard treatment study. Twenty-three type 1 diabetes patients without overt CVD were treated with metformin for 8 weeks (treatment group-TG). They were matched with nine type 1 diabetes patients on standard treatment (SG) and 23 age- and sex-matched healthy volunteers (HC). Insulin dose was adjusted to keep unchanged glycaemic control. cEPCs and cECs counts were determined by flow cytometry using surface markers CD45(dim)CD34(+)VEGFR-2(+) and CD45(dim)CD133(-)CD34(+)CD144(+) respectively. Peripheral blood mononuclear cells were cultured to assess changes in PACs number, function and colony forming units (CFU-Hill's colonies). At baseline TG had lower cEPCs, PACs, CFU-Hills' colonies and PACs adhesion versus HC (p < 0.001-all variables) and higher cECs versus HC (p = 0.03). Metformin improved cEPCs, PACs, CFU-Hill's colonies number, cECs and PACs adhesion (p < 0.05-all variables) to levels seen in HC whilst HbA1c (one-way ANOVA p = 0.78) and glucose variability (average glucose, blood glucose standard deviation, mean amplitude of glycaemic excursion, continuous overall net glycaemic action and area under curve) remained unchanged. No changes were seen in any variables in SG. There was an inverse correlation between CFU-Hill's colonies with cECs. Metformin has potential cardio-protective effect through improving cEPCs, CFU-Hill's colonies, cECs, PACs count and function independently of hypoglycaemic effect. This finding needs to be confirmed by long

Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

PubMed

Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

2016-10-01

Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and endothelial dysfunction in resistant hypertension.

PubMed

Magen, Eli; Feldman, Arie; Cohen, Ziona; Alon, Dora Ben; Minz, Evegeny; Chernyavsky, Alexey; Linov, Lina; Mishal, Joseph; Schlezinger, Menacham; Sthoeger, Zev

2010-02-01

A possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies. To compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH). Blood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning. RAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7 cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/- 88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/- 63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma transforming growth factor-beta1 levels were significantly higher in the RAH group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/- 0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls (10.1 +/- 1.1%; P < 0.001). RAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-beta1 levels.

Association of endothelial progenitor cells and peptic ulcer treatment in patients with type 2 diabetes mellitus.

PubMed

Nie, Zhihong; Xu, Limin; Li, Chuanyuan; Tian, Tao; Xie, Pingping; Chen, Xia; Li, Bojing

2016-05-01

The present study aimed to investigate the association between endothelial progenitor cells (EPCs) and peptic ulcers in patients with or without type 2 diabetes mellitus (T2DM), in association with the efficiency of peptic ulcer treatment. The study recruited healthy subjects and peptic ulcer patients with or without T2DM. All the ulcer patients, including those with and without T2DM, were administered omeprazole for 8 weeks. Peptic ulcer patients with T2DM were additionally treated with glipizide and novolin. Blood samples were then obtained from the three groups following ulcer treatment. CD133 + cells were isolated from the blood samples using magnetic bead selection, and cultured in complete medium 199. Morphological and quantity changes in EPCs were observed by light and fluorescence microscopy. In addition, flow cytometric analysis was used to quantify the number of vascular endothelial cells. The treatment was partially effective in 7 of the 32 peptic ulcer patients without T2DM and 12 of the 32 peptic ulcer patients with T2DM. However, this treatment was ineffective in 20 of the 32 peptic ulcer patients with T2DM. Notably, 25 peptic ulcer patients without T2DM were defined as completely recovered following treatment. In addition, the number of circulating EPCs as well as their colony forming ability was significantly reduced (P<0.05) in the peptic ulcer patients with T2DM following ulcer treatment, compared with the other groups. Circulating EPC counts were significantly increased in peptic ulcer patients without T2DM, as compared with the healthy controls. With regards to colony formation, peptic ulcer patients without T2DM did not exhibit improved colony formation ability. In conclusion, the number of circulating EPCs and their colony-forming ability was significantly reduced in peptic ulcer patients with T2DM following ulcer treatment when compared with the other groups. This suggests that the poor curative effect of peptic ulcer treatment in these

Association of endothelial progenitor cells and peptic ulcer treatment in patients with type 2 diabetes mellitus

PubMed Central

NIE, ZHIHONG; XU, LIMIN; LI, CHUANYUAN; TIAN, TAO; XIE, PINGPING; CHEN, XIA; LI, BOJING

2016-01-01

The present study aimed to investigate the association between endothelial progenitor cells (EPCs) and peptic ulcers in patients with or without type 2 diabetes mellitus (T2DM), in association with the efficiency of peptic ulcer treatment. The study recruited healthy subjects and peptic ulcer patients with or without T2DM. All the ulcer patients, including those with and without T2DM, were administered omeprazole for 8 weeks. Peptic ulcer patients with T2DM were additionally treated with glipizide and novolin. Blood samples were then obtained from the three groups following ulcer treatment. CD133+ cells were isolated from the blood samples using magnetic bead selection, and cultured in complete medium 199. Morphological and quantity changes in EPCs were observed by light and fluorescence microscopy. In addition, flow cytometric analysis was used to quantify the number of vascular endothelial cells. The treatment was partially effective in 7 of the 32 peptic ulcer patients without T2DM and 12 of the 32 peptic ulcer patients with T2DM. However, this treatment was ineffective in 20 of the 32 peptic ulcer patients with T2DM. Notably, 25 peptic ulcer patients without T2DM were defined as completely recovered following treatment. In addition, the number of circulating EPCs as well as their colony forming ability was significantly reduced (P<0.05) in the peptic ulcer patients with T2DM following ulcer treatment, compared with the other groups. Circulating EPC counts were significantly increased in peptic ulcer patients without T2DM, as compared with the healthy controls. With regards to colony formation, peptic ulcer patients without T2DM did not exhibit improved colony formation ability. In conclusion, the number of circulating EPCs and their colony-forming ability was significantly reduced in peptic ulcer patients with T2DM following ulcer treatment when compared with the other groups. This suggests that the poor curative effect of peptic ulcer treatment in these

Moderate-to-high-intensity training and a hypocaloric Mediterranean diet enhance endothelial progenitor cells and fitness in subjects with the metabolic syndrome.

PubMed

Fernández, Juan Marcelo; Rosado-Álvarez, Daniel; Da Silva Grigoletto, Marzo Edir; Rangel-Zúñiga, Oriol Alberto; Landaeta-Díaz, Leslie Lorena; Caballero-Villarraso, Javier; López-Miranda, José; Pérez-Jiménez, Francisco; Fuentes-Jiménez, Francisco

2012-09-01

A reduction in EPC (endothelial progenitor cell) number could explain the development and progression of atherosclerosis in the MetS (metabolic syndrome). Although much research in recent years has focused on the Mediterranean dietary pattern and the MetS, the effect of this diet with/without moderate-to-high-intensity endurance training on EPCs levels and CrF (cardiorespiratory fitness) remains unclear. In the present study, the objective was to assess the effect of a Mediterranean diet hypocaloric model with and without moderate-to-high-intensity endurance training on EPC number and CrF of MetS patients. Thus 45 MetS patients (50-66 years) were randomized to a 12-week intervention with the hypocaloric MeD (Mediterranean diet) or the MeDE (MeD plus moderate-to-high-intensity endurance training). Training included two weekly supervised sessions [80% MaxHR (maximum heart rate); leg and arm pedalling] and one at-home session (65-75% MaxHR; walking controlled by heart rate monitors). Changes in: (i) EPC number [CD34(+)KDR(+) (kinase insert domain-containing receptor)], (ii) CrF variables and (iii) MetS components and IRH (ischaemic reactive hyperaemia) were determined at the end of the study. A total of 40 subjects completed all 12 weeks of the study, with 20 in each group. The MeDE led to a greater increase in EPC numbers and CrF than did the MeD intervention (P ≤ 0.001). In addition, a positive correlation was observed between the increase in EPCs and fitness in the MeDE group (r=0.72; r(2)=0.52; P ≤ 0.001). Body weight loss, insulin sensitivity, TAGs (triacylglycerols) and blood pressure showed a greater decrease in the MeDE than MeD groups. Furthermore, IRH was only improved after the MeDE intervention. In conclusion, compliance with moderate-to-high-intensity endurance training enhances the positive effects of a model of MeD on the regenerative capacity of endothelium and on the fitness of MetS patients.

Toxicity of Pb and of Pb/Cd combination on the springtail Folsomia candida in natural soils: reproduction, growth and bioaccumulation as indicators.

PubMed

Bur, T; Crouau, Y; Bianco, A; Gandois, L; Probst, A

2012-01-01

The toxicity of Pb and Cd+Pb was assessed on the Collembola F. candida in two cultivated soils (SV and AU) with low organic matter (OM) content and circumneutral to basic pH, and an acid forested soil (EPC) with high OM content. Collembola reproduction and growth as well as metal content in Collembola body, in soil, exchangeable fraction and soil solutions, pH and DOC were investigated. Pb and Cd+Pb were the highest in exchangeable fraction and soil solution of the acidic soils. Soil solution pH decreased after metal spiking in every soil due to metal adsorption, which was similar for Cd and the highest in AU for Pb. With increasing Pb and Cd+Pb, the most important reproduction decrease was in EPC soil. The LOEC for reproduction after metal addition was 2400 (Pb) and 200/2400 (Cd/Pb), 1200 and 100/1200, 300 and 100/1200 μg g(-1) for AU, SV and EPC, respectively. The highest and the lowest Pb toxicity was observed for EPC and AU bulk soil, respectively. The metal in Collembola increased with increasing soil concentration, except in AU, but the decreasing BF(solution) with increasing concentrations indicates a limited metal transfer to Collembola or an increased metal removal. Loading high Pb concentrations decreases Cd absorption by the Collembola, but the reverse was not true. The highest Pb toxicity in EPC can be explained by pH and OM content. Because of metal complexation, OM might have a protective role but its ingestion by Collembola lead to higher toxicity. Metal bioavailability in Collembola differs from soil solution indicating that soil solution is not sufficient to evaluate toxicity in soil organisms. The toxicity as a whole decreased when metals were combined, except for Pb in AU, due to adsorption competition between Cd and Pb on clay particles and OM sites in AU and EPC soils, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

Ortho-para-hydrogen equilibration on Jupiter

NASA Technical Reports Server (NTRS)

Carlson, Barbara E.; Lacis, Andrew A.; Rossow, William B.

1992-01-01

Voyager IRIS observations reveal that the Jovian para-hydrogen fraction is not in thermodynamic equilibrium near the NH3 cloud top, implying that a vertical gradient exists between the high-temperature equilibrium value of 0.25 at depth and the cloud top values. The height-dependent para-hydrogen profile is obtained using an anisotropic multiple-scattering radiative transfer model. A vertical correlation is found to exist between the location of the para-hydrogen gradient and the NH3 cloud, strongly suggesting that paramagnetic conversion on NH3 cloud particle surfaces is the dominant equilibration mechanism. Below the NH3 cloud layer, the para fraction is constant with depth and equal to the high-temperature equilibrium value of 0.25. The degree of cloud-top equilibration appears to depend on the optical depth of the NH3 cloud layer. Belt-zone variations in the para-hydrogen profile seem to be due to differences in the strength of the vertical mixing.

Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits.

PubMed

Xiao, Mingyue; Lu, Xiao; Li, Jianan; Li, Ling; Li, Yongxue

2014-04-01

Ischaemia-induced angiogenesis promises to improve neovascularization by delivery of angiogenic factors or endothelial progenitor cells (EPCs) to cardiac ischaemic areas. In order to avoid the risk of excessive myocardial ischaemia, therefore, we hypothesized that physiological ischaemic training (PIT) of normal skeletal muscle might contribute to myocardial angiogenesis via nitric oxide mediated mobilization of EPCs from the bone marrow in the established rabbit model of controllable myocardial ischaemia. The rabbits were grouped by sham-operation, myocardial ischaemia without PIT, PIT and PIT with pretreatment with the endothelial nitric oxide synthase (eNOS) inhibitor L-nitroarginine methyl ester (L-NAME). Controlled myocardial ischaemia was modelled by a water balloon constrictor implanted on the left ventricular branch in a rabbit. The PIT procedure included three cycles of 3 min of cuff inflation followed by 5 min of deflation on hind limbs of the rabbits for 4 weeks. At the endpoints, circulating EPCs (CD34/Flk-1) were measured by fluorescence-activated cell sorter; capillary density, by immunohistochemistry; blood flow, by a microsphere technique; endothelial nitric oxide synthase (eNOS) mRNA and protein, by real-time reverse transcriptase (RT)-PCR and Western blotting. The mRNA levels of eNOS were significantly higher in the PIT and L-NAME groups than in the sham-operation group (P < 0.05). Phospho-eNOS protein expression was higher in the PIT group than in the sham-operation and myocardial ischaemia without PIT groups (P < 0.05), and the effect was inhibited by L-NAME pretreatment (P < 0.05). Compared with sham-operation and myocardial ischaemia without PIT groups, the PIT group had the highest EPC count (P < 0.001), and the increase of capillary density (P < 0.01) and collateral blood flow (P < 0.05) in the ischaemic myocardium was consistent with the finding of EPC count. These effects were also inhibited by pretreatment with

Employment, Production and Consumption model: Patterns of phase transitions

NASA Astrophysics Data System (ADS)

Lavička, H.; Lin, L.; Novotný, J.

2010-04-01

We have simulated the model of Employment, Production and Consumption (EPC) using Monte Carlo. The EPC model is an agent based model that mimics very basic rules of industrial economy. From the perspective of physics, the nature of the interactions in the EPC model represents multi-agent interactions where the relations among agents follow the key laws for circulation of capital and money. Monte Carlo simulations of the stochastic model reveal phase transition in the model economy. The two phases are the phase with full unemployment and the phase with nearly full employment. The economy switches between these two states suddenly as a reaction to a slight variation in the exogenous parameter, thus the system exhibits strong non-linear behavior as a response to the change of the exogenous parameters.

Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma.

PubMed

Sun, Xi-Tai; Yuan, Xian-Wen; Zhu, Hai-Tao; Deng, Zheng-Ming; Yu, De-Cai; Zhou, Xiang; Ding, Yi-Tao

2012-09-21

To investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) in the angiogenesis of hepatocellular carcinoma (HCC). The bone marrow of HCC mice was reconstructed by transplanting green fluorescent protein (GFP) + bone marrow cells. The concentration of circulating EPCs was determined by colony-forming assays and fluorescence-activated cell sorting. Serum and tissue levels of vascular endothelial growth factor (VEGF) and colony-stimulating factor (CSF) were quantified by enzyme-linked immunosorbent assay. The distribution of EPCs in tumor and tumor-free tissues was detected by immunohistochemistry and real-time polymerase chain reaction. The incorporation of EPCs into hepatic vessels was examined by immunofluorescence and immunohistochemistry. The proportion of EPCs in vessels was then calculated. The HCC model was successful established. The flow cytometry analysis showed the mean percentage of CD133CD34 and CD133VEGFR2 double positive cells in HCC mice was 0.45% ± 0.16% and 0.20% ± 0.09% respectively. These values are much higher than in the sham-operation group (0.11% ± 0.13%, 0.05% ± 0.11%, n = 9) at 14 d after modeling. At 21 d, the mean percentage of circulating CD133CD34 and CD133VEGFR2 cells is 0.23% ± 0.19%, 0.25% ± 0.15% in HCC model vs 0.05% ± 0.04%, 0.12% ± 0.11% in control. Compared to the transient increase observed in controls, the higher level of circulating EPCs were induced by HCC. In addition, the level of serum VEGF and CSF increased gradually in HCC, reaching its peak 14 d after modeling, then slowly decreased. Consecutive sections stained for the CD133 and CD34 antigens showed that the CD133+ and CD34+ VEGFR2 cells were mostly recruited to HCC tissue and concentrated in tumor microvessels. Under fluorescence microscopy, the bone-marrow (BM)-derived cells labeled with GFP were concentrated in the same area. The relative levels of CD133 and CD34 gene expression were elevated in tumors, around 5.0 and 3.8 times that

Tiempo para un cambio

NASA Astrophysics Data System (ADS)

Woltjer, L.

1987-06-01

En la reunion celebrada en diciembre dei ano pasado informe al Consejo de mi deseo de terminar mi contrato como Director General de la ESO una vez que fuera aprobado el proyecto dei VLT, que se espera sucedera hacia fines de este aAo. Cuando fue renovada mi designacion hace tres aAos, el Consejo conocia mi intencion de no completar los cinco aAos dei contrato debido a mi deseo de disponer de mas tiempo para otras actividades. Ahora, una vez terminada la fase preparatoria para el VLT, Y habiendose presentado el proyecto formalmente al Consejo el dia 31 de marzo, y esperando su muy probable aprobacion antes dei termino de este ano, me parece que el 10 de enero de 1988 presenta una excelente fecha para que se produzca un cambio en la administracion de la ESO.

Nonclassical and semiclassical para-Bose states

NASA Astrophysics Data System (ADS)

Huerta Alderete, C.; Villanueva Vergara, Liliana; Rodríguez-Lara, B. M.

2017-04-01

Motivated by the proposal to simulate para-Bose oscillators in a trapped-ion setup [C. Huerta Alderete and B. M. Rodríguez-Lara, Phys. Rev. A 95, 013820 (2017), 10.1103/PhysRevA.95.013820], we introduce an overcomplete, nonorthogonal basis for para-Bose Hilbert spaces. The states spanning these bases can be experimentally realized in the trapped-ion simulation via time evolution. The para-Bose states show both nonclassical and semiclassical statistics on their Fock state distribution, asymmetric field quadrature variances, and do not minimize the uncertainty relation for the field quadratures. These properties are analytically controlled by the para-Bose order and the evolution time; both parameters might be feasible for fine tuning in the trapped-ion quantum simulation.

A plasma-based biomatrix mixed with endothelial progenitor cells and keratinocytes promotes matrix formation, angiogenesis, and reepithelialization in full-thickness wounds.

PubMed

Vermeulen, Pieter; Dickens, Stijn; Degezelle, Karlien; Van den Berge, Stefaan; Hendrickx, Benoit; Vranckx, Jan Jeroen

2009-07-01

In search of an autologous vascularized skin substitute, we treated full-thickness wounds (FTWs) with autologous platelet-rich plasma gel (APG) in which we embedded endothelial progenitor cells (EPCs) and basal cell keratinocytes (KCs). We cultivated autologous KCs in low-serum conditions and expanded autologous EPCs from venous blood. FTWs (n = 55) were created on the backs of four pigs, covered with wound chambers, and randomly assigned to the following treatments: (1) APG, (2) APG + KCs, (3) APG + EPCs, (4) APG + KCs + EPCs, and (5) saline. All wounds were biopsied to measure neovascularization (lectin Bandeiraea Simplicifolia-1 (BS-1), alpha smooth muscle actin [alphaSMA], and membrane type 1 matrix metalloproteinase (MT1-MMP)), matrix deposition (fibronectin, collagen type I/III, and alphavbeta3), and reepithelialization. Wound fluids were analyzed for protein expression. All APG-treated wounds showed more vascular structures (p < 0.001), and the addition of EPCs further improved neovascularization, as confirmed by higher lectin, alphaSMA, and MT1-MMP. APG groups had higher collagen I/III (p < 0.05), alphavbeta3, and fibronectin content (p < 0.001), and they exhibited higher concentrations of platelet-derived growth factor subunit bb, basic fibroblast growth factor, hepatocyte growth factor, insulin growth factor-1, transforming growth factor-beta1 and -beta3, matrix metalloproteinase-1 and -z9, and tissue-inhibiting matrix metalloproteinase-1 and -2. Applying APG + KCs resulted in the highest reepithelialization rates (p < 0.001). No differences were found for wound contraction by planimetry. In this porcine FTW model, APG acts as a supportive biomatrix that, along with the embedded cells, improves extracellular matrix organization, promotes angiogenesis, and accelerates reepithelialization.

Quality‐Quantity Control Culture Enhances Vasculogenesis and Wound Healing Efficacy of Human Diabetic Peripheral Blood CD34+ Cells

PubMed Central

Masuda, Haruchika; Fujimura, Satoshi; Ito‐Hirano, Rie; Arita, Kayo; Kakinuma, Yusuke; Hagiwara, Hiroko; Kado, Makiko; Hayashi, Ayato; Mita, Tomoya; Ogawa, Takasuke; Watada, Hirotaka; Mizuno, Hiroshi; Sawada, Naoki; Asahara, Takayuki

2018-01-01

Abstract Autologous endothelial progenitor cell (EPC) therapy is commonly used to stimulate angiogenesis in ischemic repair and wound healing. However, low total numbers and functional deficits of EPCs make autologous EPC therapy ineffective in diabetes. Currently, no known ex vivo culture techniques can expand and/or ameliorate the functional deficits of EPCs for clinical usage. Recently, we showed that a quality‐quantity culture (QQc) system restores the vasculogenic and wound‐healing efficacy of murine diabetic EPCs. To validate these results and elucidate the mechanism in a translational study, we evaluated the efficacy of this QQc system to restore the vasculogenic potential of diabetic human peripheral blood (PB) CD34+ cells. CD34+ cells purified from PB of diabetic and healthy patients were subjected to QQc. Gene expression, vascular regeneration, and expression of cytokines and paracrine mediators were analyzed. Pre‐ or post‐QQc diabetic human PB‐CD34+ cells were transplanted into wounded BALB/c nude mice and streptozotocin‐induced diabetic mice to assess functional efficacy. Post‐QQc diabetic human PB‐CD34+ cell therapy significantly accelerated wound closure, re‐epithelialization, and angiogenesis. The higher therapeutic efficacy of post‐QQc diabetic human PB‐CD34+ cells was attributed to increased differentiation ability of diabetic CD34+ cells, direct vasculogenesis, and enhanced expression of angiogenic factors and wound‐healing genes. Thus, QQc can significantly enhance the therapeutic efficacy of human PB‐CD34+ cells in diabetic wounds, overcoming the inherent limitation of autologous cell therapy in diabetic patients, and could be useful for treatment of not only wounds but also other ischemic diseases. Stem Cells Translational Medicine 2018;7:428–438 PMID:29573563

Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.

PubMed

Su, Shiau-Tsz; Yeh, Chiu-Li; Hou, Yu-Chen; Pai, Man-Hui; Yeh, Sung-Ling

2017-02-01

Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue ischemia may occur with diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral glutamine (GLN) supplementation on circulating EPC mobilization and expression of tissue EPC-releasing markers in diabetic mice subjected to limb ischemia. Diabetes was induced by a daily intraperitoneal injection of streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9 and the circulating EPC percentage increased after limb ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia-inducible factor-1 and vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and Application of a Novel Environmental Preference Chamber for Assessing Responses of Laboratory Mice to Atmospheric Ammonia

PubMed Central

Green, Angela R; Wathes, Christopher M; Demmers, Theo GM; Clark, Judy MacArthur; Xin, Hongwei

2008-01-01

A novel environmental preference chamber (EPC) was developed and used to assess responses of laboratory mice to atmospheric ammonia. The EPC features 1) a test chamber with 4 individually ventilated, mutually accessible compartments; b) automated tracking of mouse movements by using paired infrared sensors; c) identification of individual mice by using photosensors; d) monitoring and regulation of the NH3 concentration in each compartment; and e) personal-computer–based data acquisition. In an initial preference study with the EPC, 4 groups of 4 laboratory mice (BALB/c/Bkl; body weight, 13.4 to 18.4 g) were each given a choice among 4 NH3 concentrations (mean ± SE) of 4 ± 2, 30 ± 2, 56 ± 4, and 110 ± 6 ppm for 2 d after a 2-d familiarization period. Once trained to use the intercompartment tunnels, the mice made extensive use of the EPC, with each group making more than 2000 intercompartment movements during 48 h. Video recording verified the results of the automatic tracking system, which detected and correctly determined mouse location for 79% of the moves. The use of photosensors proved to be ineffective in recognizing individual mice. Although the EPC would benefit from refinement and further development, it simplified analysis of locomotion behavioral data. Results of the preference study indicated that the mice exhibited no clear preference for, or aversion to, any of the experimental concentrations of ammonia and that the mice clearly preferred the upper 2 compartments of the chamber over the lower 2 compartments. Further investigation should be conducted to verify these preliminary results and explore other preferences of laboratory mice for environmental conditions and resources. PMID:18351722

Brain-Mediated Dysregulation of the Bone Marrow Activity in Angiotensin II-induced Hypertension

PubMed Central

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B.; Mocco, J; Raizada, Mohan K

2012-01-01

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus (PVN) of the hypothalamus, is driven by mitochondrial reactive oxygen species (ROS) and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II (Ang II) infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the PVN. This was associated with 46% decrease in BM EPCs and 250% increase in BM ICs, resulting in 5 fold decrease of EPCs/ICs ratio in the BM. Treatment with mitoTEMPO, a scavenger of mitochondrial O2−• intracerebroventricularly but not subcutaneously, attenuated Ang II-induced hypertension, decreased activation of microglia in the PVN, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with GFP-tagged pseudorabies virus (PRV). Administration of GFP-PRV into the BM resulted in predominant labeling of PVN neurons within 3 days, with some fluorescence in the NTS, RVLM and SFO. Taken together, these data demonstrate that inhibition of mitochondrial ROS attenuates Ang II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension. PMID:23045460

Characterizing the freezing behavior of liposomes as a tool to understand the cryopreservation procedures.

PubMed

Siow, Lee Fong; Rades, Thomas; Lim, Miang Hoong

2007-12-01

Freezing behaviors of egg yolk l-alpha-phosphatidylcholine (EPC) and 1,2-dipalmitoyl-rac-glycero-3-phosphocholine (DPPC) large unilamellar vesicles (LUV) were quantitatively characterized in relation to freezing temperatures, cooling rates, holding time, presence of sodium chloride and phospholipid phase transition temperature. Cooling of the EPC LUV showed an abrupt increase in leakage of the encapsulated carboxyfluorescein (CF) between -5 degrees C and -10 degrees C, which corresponded with the temperatures of the extraliposomal ice formation at around -7 degrees C. For the DPPC LUV, CF leakage started at -10 degrees C, close to the temperature of the extraliposomal ice formation; followed by a subsequent rapid increase in leakage between -10 degrees C and -25 degrees C. Scanning electron microscopy showed that both of these LUV were freeze-concentrated and aggregated at sub-freezing temperatures. We suggest that the formation of the extraliposomal ice and the decrease of the unfrozen fraction causes freeze-injury and leakage of the CF. The degree of leakage, however, differs between EPC LUV and DPPC LUV that inherently vary in their phospholipid phase transition temperatures. With increasing holding time, the EPC LUV were observed to have higher leakage when they were held at -15 degrees C compared to at -30 degrees C whilst leakage of the DPPC LUV was higher when holding at -40 degrees C than at -15 degrees C and -50 degrees C. At slow cooling rates, osmotic pressure across the bilayers may cause an additional stress to the EPC LUV. The present work elucidates freeze-injury mechanisms of the phospholipid bilayers through the liposomal model membranes.

Effect of Saxagliptin on Circulating Endothelial Progenitor Cells and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients.

PubMed

Li, Fang; Chen, Jiachao; Leng, Fei; Lu, Zhiqiang; Ling, Yan

2017-06-01

Endothelial dysfunction is associated with the risk of cardiovascular complications in diabetic patients. Endothelial progenitor cells (EPCs) and flow-mediated dilation (FMD) are common markers of endothelial function. In this study, we aim to investigate whether the DPP-4 inhibitor saxagliptin modulate EPCs number and FMD in newly diagnosed, treatment-naive type 2 diabetic patients. This was a controlled, randomized, open-label clinical trial. Saxagliptin group and metformin group consumed either saxagliptin 5 mg per day or metformin 1 500 mg per day respectively for 12 weeks. Changes of FMD and EPCs number after 12-week intervention were the primary endpoints. 31 patients were initially enrolled and randomized to saxagliptin group (n=16) and metformin group (n=15). 27 patients completed the trial (saxagliptin group n=14 and metformin group n=13), and 4 patients dropped out during the study. FMD and EPCs number increased significantly in both saxagliptin group and metformin group, and there was no significant difference between groups. 2-h postprandial plasma glucose, HbA1c and diastolic blood pressure improved significantly in both groups, and there was no significant difference between groups. Saxagliptin and metformin had comparable beneficial effects on endothelial function. © Georg Thieme Verlag KG Stuttgart · New York.

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration.

PubMed

Zhou, Jian; Rogers, Jason H; Lee, Scott H; Sun, DongMing; Yao, Hai; Mao, Jeremy J; Kong, Kimi Y

2017-01-15

Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration.

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

PubMed Central

Zhou, Jian; Rogers, Jason H.; Lee, Scott H.; Sun, DongMing; Yao, Hai; Mao, Jeremy J.

2017-01-01

Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration. PMID:27832737

Why inclusive fitness can make it adaptive to produce less fit extra-pair offspring

PubMed Central

Lehtonen, Jussi; Kokko, Hanna

2015-01-01

Social monogamy predominates in avian breeding systems, but most socially monogamous species engage in promiscuous extra-pair copulations (EPCs). The reasons behind this remain debated, and recent empirical work has uncovered patterns that do not seem to fit existing hypotheses. In particular, some results seem to contradict the inbreeding avoidance hypothesis: females can prefer extra-pair partners that are more closely related to them than their social partners, and extra-pair young can have lower fitness than within-pair young. Motivated by these studies, we show that such results can become explicable when an asymmetry in inbreeding tolerance between monogamy and polygamy is extended to species that combine both strategies within a single reproductive season. Under fairly general conditions, it can be adaptive for a female to choose an unrelated social partner, but inbreed with an extra-pair partner. Inbreeding depression is compensated for by inclusive fitness benefits, which are only fully realized in EPCs. We also show that if a female has already formed a suboptimal social bond, there are scenarios where it is beneficial to engage in EPCs with less related males, and others where EPCs with more related males increase her inclusive fitness. This has implications for detecting general relatedness or fitness trends when averaged over several species. PMID:25589605

The para-HK/QK correspondence

NASA Astrophysics Data System (ADS)

Dyckmanns, Malte; Vaughan, Owen

2017-06-01

We generalise the hyper-Kähler/quaternionic Kähler (HK/QK) correspondence to include para-geometries, and present a new concise proof that the target manifold of the HK/QK correspondence is quaternionic Kähler. As an application, we construct one-parameter deformations of the temporal and Euclidean supergravity c-map metrics and show that they are para-quaternionic Kähler.

Phonon-driven electron scattering and magnetothermoelectric effect in two-dimensional tin selenide

NASA Astrophysics Data System (ADS)

Yang, Kaike; Ren, Ji-Chang; Qiu, Hongfei; Wang, Jian-Sheng

2018-02-01

The bulk tin selenide (SnSe) is the best thermoelectric material currently with the highest figure-of-merit due to strong phonon-phonon interactions. We investigate the effect of electron-phonon coupling (EPC) on the transport properties of a two-dimensional (2D) SnSe sheet. We demonstrate that EPC plays a key role in the scattering rate when the constant relaxation time approximation is deficient. The EPC strength is especially large in contrast to that of pristine graphene. The scattering rate depends sensitively on the system temperatures and the carrier densities when the Fermi energy approaches the band edge. We also investigate the magnetothermoelectric effect of the 2D SnSe. It is found that at low temperatures there is enormous magnetoelectrical resistivity and magnetothermal resistivity above 200%, suggesting possible potential applications in device design. Our results agree qualitatively well with the experimental data.

Characterization of Circulating and Endothelial Progenitor Cells in Patients With Extreme-Duration Type 1 Diabetes

PubMed Central

Hernandez, Sonia L.; Gong, Jennifer H.; Chen, Liming; Wu, I-Hsien; Sun, Jennifer K.; Keenan, Hillary A.; King, George L.

2014-01-01

OBJECTIVE We characterized and correlated endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) with lack of vascular complications in the Joslin Medalist Study in patients with type 1 diabetes for 50 years or longer. RESEARCH DESIGN AND METHODS EPC and CPC levels were ascertained by flow cytometry and compared among Medalists (n = 172) with or without diabetic retinopathy (DR; n = 84 of 162), neuropathy (n = 94 of 165), diabetic nephropathy (DN; n = 18 of 172), cardiovascular disease (CVD; n = 63 of 168), age-matched controls (n = 83), type 2 diabetic patients (n = 36), and younger type 1 diabetic patients (n = 31). Mitogens, inflammatory cytokines, and oxidative markers were measured in blood or urine. Migration of cultured peripheral blood mononuclear cells (PBMCs) from Medalists and age-matched controls were compared. RESULTS Medalists’ EPC and CPC levels equaled those of their nondiabetic age-matched controls, were 10% higher than those in younger type 1 diabetic patients, and were 20% higher than those in age-matched type 2 diabetic patients. CPC levels were 15% higher in Medalists without CVD and nephropathy than in those affected, whereas EPC levels were significantly higher in those without peripheral vascular disease (PVD) than those with PVD. Stromal-derived factor 1 (SDF-1) levels were higher in Medalists with CVD, DN, and DR than in those not affected and their controls. IGF-I levels were lower in Medalists and correlated inversely with CPC levels. Additionally, cultured PBMCs from Medalists migrated more than those from nondiabetic controls. CONCLUSIONS Normal levels of EPC and CPC in the Medalists, unlike other groups with diabetes, especially those without CVD, support the idea that endogenous factors exist to neutralize the adverse effects of metabolic abnormalities of diabetes on vascular tissues. PMID:24780357

Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

PubMed Central

2012-01-01

Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF). Methods High fat diet (45 Kcal% fat) was given to 8-week-old C57BL/6 J mice (n = 8) for 20 weeks to induce obesity (group 1). Another age-matched group (n = 8) were fed with control diet for 20 weeks as controls (group 2). The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p<0.01). The circulating level of EPCs (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) was significantly lower in group 1 than in group 2 (p<0.03) at 18 h after critical limb ischemia induction. The angiogenesis and migratory ability of bone marrow-derived EPCs was remarkably impaired in group 1 compared to that in group 2 (all p<0.01). The repair ability of aortic endothelium damage by lipopolysaccharide was notably attenuated in group 1 compared with that in group 2 (p<0.01). Collagen deposition (Sirius red staining) and fibrotic area (Masson's Trichrome staining) in LV myocardium were notably increased in group 1 compared with group 2 (p<0.001). LVEF was notably lower, whereas LV end-diastolic and end-systolic dimensions were remarkably higher in group 1 than in group 2 (all p<0.001). Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling. PMID:22747715

Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.

PubMed

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

2012-11-01

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Separating para and ortho water.

PubMed

Horke, Daniel A; Chang, Yuan-Pin; Długołęcki, Karol; Küpper, Jochen

2014-10-27

Water exists as two nuclear-spin isomers, para and ortho, determined by the overall spin of its two hydrogen nuclei. For isolated water molecules, the conversion between these isomers is forbidden and they act as different molecular species. Yet, these species are not readily separated, and no pure para sample has been produced. Accordingly, little is known about their specific physical and chemical properties, conversion mechanisms, or interactions. The production of isolated samples of both spin isomers is demonstrated in pure beams of para and ortho water in their respective absolute ground state. These single-quantum-state samples are ideal targets for unraveling spin-conversion mechanisms, for precision spectroscopy and fundamental symmetry-breaking studies, and for spin-enhanced applications, for example laboratory astrophysics and astrochemistry or hypersensitized NMR experiments. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capsaicin modulates acetylcholine release at the myoneural junction.

PubMed

Thyagarajan, Baskaran; Potian, Joseph G; Baskaran, Padmamalini; McArdle, Joseph J

2014-12-05

Transient receptor potential (TRP) proteins are non-selective cation channel proteins that are expressed throughout the body. Previous studies demonstrated the expression of TRP Vanilloid 1 (TRPV1), capsaicin (CAP) receptor, in sensory neurons. Recently, we reported TRPV1 expression in mouse motor nerve terminals [MNTs; (Thyagarajan et al., 2009)], where we observed that CAP protected MNTs from botulinum neurotoxin A (BoNT/A). Phrenic nerve diaphragm nerve muscle preparations (NMP) isolated from isoflurane anesthetized adult mice were analyzed for twitch tension, spontaneous (mEPCs) and nerve stimulus evoked (EPCs) acetylcholine release. When acutely applied to isolated NMP, CAP produced a concentration-dependent decline of twitch tension and produced a significant decline in the amplitude of EPCs and quantal content without any effect on the mEPCs. The suppression of nerve stimulus evoked acetylcholine release by CAP was antagonized by capsazepine (CPZ), a TRPV1 antagonist. CAP did not suppress phrenic nerve stimulus evoked acetylcholine release in TRPV1 knockout mice. Also, CAP treatment, in vitro, interfered with the localization of adapter protein 2 in cholinergic Neuro 2a cells. Wortmannin, (WMN; non-selective phosphoinositol kinase inhibitor), mimicked the effects of CAP by inhibiting the acetylcholine exocytosis. Our data suggest that TRPV1 proteins expressed at the MNT are coupled to the exo-endocytic mechanisms to regulate neuromuscular functions. Copyright © 2014 Elsevier B.V. All rights reserved.

High order methods for the integration of the Bateman equations and other problems of the form of y‧ = F(y,t)y

NASA Astrophysics Data System (ADS)

Josey, C.; Forget, B.; Smith, K.

2017-12-01

This paper introduces two families of A-stable algorithms for the integration of y‧ = F (y , t) y: the extended predictor-corrector (EPC) and the exponential-linear (EL) methods. The structure of the algorithm families are described, and the method of derivation of the coefficients presented. The new algorithms are then tested on a simple deterministic problem and a Monte Carlo isotopic evolution problem. The EPC family is shown to be only second order for systems of ODEs. However, the EPC-RK45 algorithm had the highest accuracy on the Monte Carlo test, requiring at least a factor of 2 fewer function evaluations to achieve a given accuracy than a second order predictor-corrector method (center extrapolation / center midpoint method) with regards to Gd-157 concentration. Members of the EL family can be derived to at least fourth order. The EL3 and the EL4 algorithms presented are shown to be third and fourth order respectively on the systems of ODE test. In the Monte Carlo test, these methods did not overtake the accuracy of EPC methods before statistical uncertainty dominated the error. The statistical properties of the algorithms were also analyzed during the Monte Carlo problem. The new methods are shown to yield smaller standard deviations on final quantities as compared to the reference predictor-corrector method, by up to a factor of 1.4.

Expansion of Endothelial Progenitor Cells in High Density Dot Culture of Rat Bone Marrow Cells

PubMed Central

Wang, Ling; Kretlow, James D.; Zhou, Guangdong; Cao, Yilin; Liu, Wei; Zhang, Wen Jie

2014-01-01

In vitro expansion of endothelial progenitor cells (EPCs) remains a challenge in stem cell research and its application. We hypothesize that high density culture is able to expand EPCs from bone marrow by mimicking cell-cell interactions of the bone marrow niche. To test the hypothesis, rat bone marrow cells were either cultured in high density (2×105 cells/cm2) by seeding total 9×105 cells into six high density dots or cultured in regular density (1.6×104 cells/cm2) with the same total number of cells. Flow cytometric analyses of the cells cultured for 15 days showed that high density cells exhibited smaller cell size and higher levels of marker expression related to EPCs when compared to regular density cultured cells. Functionally, these cells exhibited strong angiogenic potentials with better tubal formation in vitro and potent rescue of mouse ischemic limbs in vivo with their integration into neo-capillary structure. Global gene chip and ELISA analyses revealed up-regulated gene expression of adhesion molecules and enhanced protein release of pro-angiogenic growth factors in high density cultured cells. In summary, high density cell culture promotes expansion of bone marrow contained EPCs that are able to enhance tissue angiogenesis via paracrine growth factors and direct differentiation into endothelial cells. PMID:25254487

Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.

PubMed

Caizhen, Guo; Yan, Gao; Ronron, Chang; Lirong, Yang; Panpan, Chu; Xuemei, Hu; Yuanbiao, Qiao; Qingshan, Li

2015-04-10

An essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78 nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7 Å to 7.4 and 7.9 nm, respectively. In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24 mg/kg bw in NIH/KM/ICR mice. The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life. Copyright © 2015 Elsevier B.V. All rights reserved.

Transduction of cultured fish cells with recombinant baculoviruses.

PubMed

Leisy, Douglas J; Lewis, Teresa D; Leong, Jo-Ann C; Rohrmann, George F

2003-05-01

Five fish cell lines were tested for their ability to be transduced by Ac-CAlacZ, a recombinant baculovirus that is capable of expressing a beta-galactosidase reporter gene from the CAG promoter (consisting of a cytomegalovirus enhancer element, a chicken actin promoter and rabbit beta-globin termination sequences). TO (Tilapia ovary), EPC (carp), CHH-1 (Chum salmon heart fibroblast) and CHSE-214 (chinook salmon embryo) cells were transducible, as demonstrated by an in situ beta-galactosidase assay, whereas RTG-2 (rainbow trout gonad) cells were not. The EPC cell line was used for more detailed studies on baculovirus transduction. The transduction frequency was found to be higher at 28 degrees C than at 21 degrees C. Addition of the histone deacetylase inhibitor sodium butyrate increased the number of blue cells detected 5- to 7-fold. The m.o.i. was positively correlated with transduction frequency, although the relationship did not appear to be strictly linear, as has been observed with mammalian cells. The temperature at which baculoviruses were adsorbed to EPC cells did not affect levels of beta-galactosidase expression. We also examined expression levels of beta-galactosidase in EPC cells after infection with a baculovirus construct that overexpresses the vesicular stomatitis virus G protein and displays it on the virion surface. Expression levels with this virus were approximately 15-fold higher than were observed with Ac-CAlacZ.

Energy Efficiency Investments in Public Facilities - Developing a Pilot Mechanism for Russia and Chelyabinsk Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, Meredydd; Roshchanka, Volha; Parker, Steven A.

Russian public sector buildings tend to be very inefficient, which creates vast opportunities for savings. This paper reviews opportunities to implement energy efficiency projects in Russian public buildings, created by new Russian legislation and regulations. Given Russia's limited experience with energy performance contracts (EPCs), a pilot project can help test an implementation mechanism. The authors use Chelyabinsk Region as an example to discuss opportunities, challenges and solutions to financing and implementing an EPC in Russia, navigating through federal requirements and specific local conditions.

[Proangiogenic cell-based therapy for treatment of ischemic diseases].

PubMed

Silvestre, Jean-Sébastien

2009-11-01

The application of endothelial progenitor cells (EPC) cell-based therapy for regenerative medicine constitutes a promising therapeutic avenue for the treatment of cardiovascular diseases. Based on experimental studies demonstrating that bone marrow-, blood- or tissue-derived stem/progenitor cells improve the functional recovery after ischemia, clinical trials were initiated to address this new therapeutic concept. Although autolougous cell therapy was shown to improve perfusion and function of ischemic tissues, a number of issues remain to be adressed. The nature of the mobilizing, migratory and homing signals, and the mechanisms of action need to be identified and further defined. In addition, strategies to enhance homing, survival and therapeutic potential of EPC need to be developped to improve therapeutic effect and counteract EPC dysfunction in aged patients with cardiovascular risk factors. The present review article will discuss the mechanisms of action of different types of adult stem cells and several approaches to improve their therapeutic efficiency.

Veteran Affairs Centers of Excellence in Primary Care Education: transforming nurse practitioner education.

PubMed

Rugen, Kathryn Wirtz; Watts, Sharon A; Janson, Susan L; Angelo, Laura A; Nash, Melanie; Zapatka, Susan A; Brienza, Rebecca; Gilman, Stuart C; Bowen, Judith L; Saxe, JoAnne M

2014-01-01

To integrate health care professional learners into patient-centered primary care delivery models, the Department of Veterans Affairs has funded five Centers of Excellence in Primary Care Education (CoEPCEs). The main goal of the CoEPCEs is to develop and test innovative structural and curricular models that foster transformation of health care training from profession-specific "silos" to interprofessional, team-based educational and care delivery models in patient-centered primary care settings. CoEPCE implementation emphasizes four core curricular domains: shared decision making, sustained relationships, interprofessional collaboration, and performance improvement. The structural models allow interprofessional learners to have longitudinal learning experiences and sustained and continuous relationships with patients, faculty mentors, and peer learners. This article presents an overview of the innovative curricular models developed at each site, focusing on nurse practitioner (NP) education. Insights on transforming NP education in the practice setting and its impact on traditional NP educational models are offered. Preliminary outcomes and sustainment examples are also provided. Published by Mosby, Inc.

A Pragmatic Randomized Trial Comparing Telephone-Based Enhanced Pharmacy Care and Usual Care to Support Smoking Cessation.

PubMed

Gong, Jason; Baker, Christine L; Zou, Kelly H; Bruno, Marianna; Jumadilova, Zhanna; Lawrence, David; Wilson, Beth; Ewel, Cynthia

2016-12-01

Smoking is the leading preventable cause of death, and tobacco control professionals continue to make progress in cessation efforts. Pharmacists can assist smokers seeking to quit by offering counseling on smoking cessation pharmacotherapies. Pragmatic randomized trials are useful for investigating practical questions about an intervention's risks, benefits, and costs in routine clinical practice. To evaluate an enhanced pharmacy care (EPC) program involving personalized pharmacist-provided telephone counseling for supporting prescription smoking cessation medications compared with usual care (UC). Cigarette smokers filling a newly prescribed smoking cessation pharmacotherapy and with pharmacy benefits managed by Express Scripts were recruited. Qualified subjects were randomized 1:1 to EPC and UC. Subjects in EPC received 3 telephone-counseling sessions from specialist pharmacists during the early course of the study, while subjects in UC did not receive any counseling sessions. Study outcomes were collected through telephone contact and using the Express Scripts prescription database. The primary outcome assessed the 1-week point prevalence (PP) of smoking abstinence at the end of the trial (week 12). Secondary outcomes included 4-week PP at week 12 and adherence, evaluated by proportion of days covered (PDC), to prescribed smoking cessation pharmacotherapies. There were 1,017 randomized subjects. Among them, 1,002 subjects were included in the analysis, and 513 were randomized into EPC and 489 into UC. Baseline demographics, smoking history, and prescribed smoking cessation pharmacotherapies were comparable. Varenicline and nicotine replacement therapy (NRT) were most frequently prescribed for smoking cessation. In EPC, 46.0% received all 3 counseling sessions; 29.4% received 2 sessions; and 14.6% received 1 session. Overall, 353 subjects in EPC and 383 subjects in UC completed the week 12 assessment. In the analysis for 1-week PP of smoking abstinence at week 12

Life cycle cost-based risk model for energy performance contracting retrofits

NASA Astrophysics Data System (ADS)

Berghorn, George H.

Buildings account for 41% of the primary energy consumption in the United States, nearly half of which is accounted for by commercial buildings. Among the greatest energy users are those in the municipalities, universities, schools, and hospitals (MUSH) market. Correctional facilities are in the upper half of all commercial building types for energy intensity. Public agencies have experienced reduced capital budgets to fund retrofits; this has led to the increased use of energy performance contracts (EPC), which are implemented by energy services companies (ESCOs). These companies guarantee a minimum amount of energy savings resulting from the retrofit activities, which in essence transfers performance risk from the owner to the contractor. Building retrofits in the MUSH market, especially correctional facilities, are well-suited to EPC, yet despite this potential and their high energy intensities, efficiency improvements lag behind that of other public building types. Complexities in project execution, lack of support for data requests and sub-metering, and conflicting project objectives have been cited as reasons for this lag effect. As a result, project-level risks must be understood in order to support wider adoption of retrofits in the public market, in particular the correctional facility sub-market. The goal of this research is to understand risks related to the execution of energy efficiency retrofits delivered via EPC in the MUSH market. To achieve this goal, in-depth analysis and improved understanding was sought with regard to ESCO risks that are unique to EPC in this market. The proposed work contributes to this understanding by developing a life cycle cost-based risk model to improve project decision making with regard to risk control and reduction. The specific objectives of the research are: (1) to perform an exploratory analysis of the EPC retrofit process and identify key areas of performance risk requiring in-depth analysis; (2) to construct a

CYP96T1 of Narcissus sp. aff. pseudonarcissus Catalyzes Formation of the Para-Para' C-C Phenol Couple in the Amaryllidaceae Alkaloids

PubMed Central

Kilgore, Matthew B.; Augustin, Megan M.; May, Gregory D.; Crow, John A.; Kutchan, Toni M.

2016-01-01

The Amaryllidaceae alkaloids are a family of amino acid derived alkaloids with many biological activities; examples include haemanthamine, haemanthidine, galanthamine, lycorine, and maritidine. Central to the biosynthesis of the majority of these alkaloids is a C-C phenol-coupling reaction that can have para-para', para-ortho', or ortho-para' regiospecificity. Through comparative transcriptomics of Narcissus sp. aff. pseudonarcissus, Galanthus sp., and Galanthus elwesii we have identified a para-para' C-C phenol coupling cytochrome P450, CYP96T1, capable of forming the products (10bR,4aS)-noroxomaritidine and (10bS,4aR)-noroxomaritidine from 4′-O-methylnorbelladine. CYP96T1 was also shown to catalyzed formation of the para-ortho' phenol coupled product, N-demethylnarwedine, as less than 1% of the total product. CYP96T1 co-expresses with the previously characterized norbelladine 4′-O-methyltransferase. The discovery of CYP96T1 is of special interest because it catalyzes the first major branch in Amaryllidaceae alkaloid biosynthesis. CYP96T1 is also the first phenol-coupling enzyme characterized from a monocot. PMID:26941773

Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.

PubMed

Park, Angela; Barrera-Ramirez, Juliana; Ranasinghe, Indee; Pilon, Sophie; Sy, Richmond; Fergusson, Dean; Allan, David S

2016-06-01

Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with

The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study.

PubMed

Gartlehner, Gerald; Dobrescu, Andreea; Evans, Tammeka Swinson; Bann, Carla; Robinson, Karen A; Reston, James; Thaler, Kylie; Skelly, Andrea; Glechner, Anna; Peterson, Kimberly; Kien, Christina; Lohr, Kathleen N

2016-02-01

To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial variation in sediment-water exchange of phosphorus in Florida Bay: AMP as a model organic compound.

PubMed

Huang, Xiao-Lan; Zhang, Jia-Zhong

2010-10-15

Dissolved organic phosphorus (DOP) has been recognized as dominant components in total dissolved phosphorus (TDP) pools in many coastal waters, and its exchange between sediment and water is an important process in biogeochemical cycle of phosphorus. Adenosine monophosphate (AMP) was employed as a model DOP compound to simulate phosphorus exchange across sediment-water interface in Florida Bay. The sorption data from 40 stations were fitted to a modified Freundlich equation and provided a detailed spatial distribution both of the sediment's zero equilibrium phosphorus concentration (EPC(0-T)) and of the distribution coefficient (K(d-T)) with respect to TDP. The K(d-T) was found to be a function of the index of phosphorus saturation (IPS), a molar ratio of the surface reactive phosphorus to the surface reactive iron oxide content in the sediment, across the entire bay. However, the EPC(0-T) was found to correlate to the contents of phosphorus in the eastern bay only. Sediment in the western bay might act as a source of the phosphorus in the exchange process due to their high EPC(0-T) and low K(d-T), whereas sediments in the eastern bay might act as a sink because of their low EPC(0-T) and high K(d-T). These results strongly support the hypothesis that both phosphorus and iron species in calcareous marine sediments play a critical role in governing the sediment-water exchange of both phosphate and DOP in the coastal and estuarine ecosystems.

Endothelial remodelling and intracellular calcium machinery.

PubMed

Moccia, F; Tanzi, F; Munaron, L

2014-05-01

Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

Cooling by Para-to-Ortho-Hydrogen Conversion

NASA Technical Reports Server (NTRS)

Sherman, A.; Nast, T.

1983-01-01

Catalyst speeds conversion, increasing capacity of solid hydrogen cooling system. In radial-flow catalytic converter, para-hydrogen is converted to equilibrium mixture of para-hydrogen and ortho-hydrogen as it passes through porous cylinder of catalyst. Addition of catalyst increases capacity of hydrogen sublimation cooling systems for radiation detectors.

ParaChoice Model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heimer, Brandon Walter; Levinson, Rebecca Sobel; West, Todd H.

Analysis with the ParaChoice model addresses three barriers from the VTO Multi-Year Program Plan: availability of alternative fuels and electric charging station infrastructure, availability of AFVs and electric drive vehicles, and consumer reluctance to purchase new technologies. In this fiscal year, we first examined the relationship between the availability of alternative fuels and station infrastructure. Specifically, we studied how electric vehicle charging infrastructure affects the ability of EVs to compete with vehicles that rely on mature, conventional petroleum-based fuels. Second, we studied how the availability of less costly AFVs promotes their representation in the LDV fleet. Third, we used ParaChoicemore » trade space analyses to help inform which consumers are reluctant to purchase new technologies. Last, we began analysis of impacts of alternative energy technologies on Class 8 trucks to isolate those that may most efficaciously advance HDV efficiency and petroleum use reduction goals.« less

Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells

PubMed Central

Bua, Gloria; Manaresi, Elisabetta; Bonvicini, Francesca; Gallinella, Giorgio

2016-01-01

The pathogenic Parvovirus B19 (B19V) is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi) and lower levels at day 18 (+1.5 Log from 2 to 48 hpi). B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18). Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6–15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. PMID:26845771

Study on cross-reactivity to the para group.

PubMed

Picardo, M; Cannistraci, C; Cristaudo, A; De Luca, C; Santucci, B

1990-01-01

In 80 patients, positive to at least one hapten of the para group (para-phenylenediamine, diaminodiphenylmethane, benzocaine, PPD mix), patch tests were carried out with freshly prepared solutions of para-phenylenediamine (PPD) and of 3 selected aromatic compounds related structurally to PPD (para-aminophenol, ortho-aminophenol, hydroquinone). The number of positive reactions correlated with the rate of decomposition of the substances as evaluated by high-pressure liquid chromatography. PPD, which was almost decomposed after 24 h, gave the highest number of positive reactions, followed by ortho-aminophenol and by para-aminophenol, while hydroquinone, which was oxidized to the extent of 35%, did not give any reactions. To evaluate if a different rate of oxidation can modify the patch test response, in the same patients and in 10 normal volunteers, tests were carried out with PPD solutions containing the oxidizing agent silver oxide (0.1%). By this procedure a significant increase in the number of positive responses was observed. The results suggest that the rate of decomposition and therefore the amount of quinone(s) generated, might be the key to eliciting patch test responses to oxidizable aromatic haptens.

Programa de conservacion para aves migratorias neotropicales

Treesearch

Deborah Finch; Marcia Wilson; Roberto Roca

1992-01-01

Mas de 250 especies de aves terrestres migran a Norte America durante la epoca reproductiva para aprovechar los sistemas templados. No obstante, las aves migratorias neotropicales pasan la mayor parte de su ciclo de vida en los habitat tropicales y subtropicales de paises latinoamericanos y caribefios donde viven en una asociacion cercana con las aves residentes. Para...

Polymorphism and Modulation of Para-Substituted l-Phenylalanine.

PubMed

Sögütoglu, Leyla-Cann; Lutz, Martin; Meekes, Hugo; de Gelder, René; Vlieg, Elias

2017-12-06

The crystal structure of para -methyl-l-phenylalanine at 230 K resembles that of the para-fluorinated analogue from the literature but is commensurately modulated with seven molecules in the asymmetric unit ( Z ' = 7). At 100 K, the superstructure loses its modulation, leading to a unit cell with Z ' = 1, with clear disorder in the phenyl ring orientations. The methyl-substituent in para -methyl-l-phenylalanine has, in contrast to fluorine, no polar interactions with protons of neighboring molecules, which might allow for the well-defined modulation of the crystal structure at 230 K.

On Orbital Elements of Extrasolar Planetary Candidates and Spectroscopic Binaries

NASA Technical Reports Server (NTRS)

Stepinski, T. F.; Black, D. C.

2001-01-01

We estimate probability densities of orbital elements, periods, and eccentricities, for the population of extrasolar planetary candidates (EPC) and, separately, for the population of spectroscopic binaries (SB) with solar-type primaries. We construct empirical cumulative distribution functions (CDFs) in order to infer probability distribution functions (PDFs) for orbital periods and eccentricities. We also derive a joint probability density for period-eccentricity pairs in each population. Comparison of respective distributions reveals that in all cases EPC and SB populations are, in the context of orbital elements, indistinguishable from each other to a high degree of statistical significance. Probability densities of orbital periods in both populations have P(exp -1) functional form, whereas the PDFs of eccentricities can he best characterized as a Gaussian with a mean of about 0.35 and standard deviation of about 0.2 turning into a flat distribution at small values of eccentricity. These remarkable similarities between EPC and SB must be taken into account by theories aimed at explaining the origin of extrasolar planetary candidates, and constitute an important clue us to their ultimate nature.

Substance P accelerates wound healing in type 2 diabetic mice through endothelial progenitor cell mobilization and Yes-associated protein activation

PubMed Central

Um, Jihyun; Yu, Jinyeong; Park, Ki-Sook

2017-01-01

Wound healing is delayed in diabetes due to a number of factors, including impaired angiogenesis and poor dermal healing. The present study demonstrated that subcutaneous administration of substance P (SP) accelerates wound healing in db/db type 2 diabetic mice (db/db mice). SP injection (10 nM/kg, subcutaneously) enhanced angiogenesis, induced the mobilization of endothelial progenitor cells (EPCs) and increased the number of EPC-colony forming units (EPC-CFUs) in the bone marrow of db/db mice. Immunohistochemistry was performed to check the effects of SP on the cellular proliferation and the subcellular localization of Yes-associated protein (YAP) in the wound dermis. SP also upregulated cellular proliferation in the injured dermis of db/db mice. Compared with the control group, an increased number of cells in the wound dermis of SP-treated mice exhibited nuclear localization of YAP, which induces cellular proliferation. The results of the current study indicate that subcutaneous administration of SP may be a promising therapeutic strategy to treat diabetic wounds exhibiting impaired angiogenesis and dysfunctional dermal wound healing. PMID:28339006

Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice

PubMed Central

Kwon, Yi-Hong; Jung, Seok-Yun; Kim, Jae-Won; Lee, Sang-Hun; Lee, Jun-Hee; Lee, Boo-Yong; Kwon, Sang-Mo

2012-01-01

Background There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. Methodology/Principal Findings This is the first report on phloroglucinol's ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45−/CD34+ progenitor mobilization into peripheral blood in vivo in the LLC-tumor-bearing mouse model. Conclusions/Significance These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidate compound for biosafe drugs that target tumor angiogenesis. PMID:22496756

Para hydrogen equilibration in the atmospheres of the outer planets

NASA Technical Reports Server (NTRS)

Conrath, Barney J.

1986-01-01

The thermodynamic behavior of the atmospheres of the Jovian planets is strongly dependent on the extent to which local thermal equilibration of the ortho and para states of molecular hydrogen is achieved. Voyager IRIS data from Jupiter imply substantial departures of the para hydrogen fraction from equilibrium in the upper troposphere at low latitudes, but with values approaching equilibrium at higher latitudes. Data from Saturn are less sensitive to the orth-para ratio, but suggest para hydrogen fractions near the equilibrium value. Above approximately the 200 K temperature level, para hydrogen conversion can enhance the efficiency of convection, resulting in a substantial increase in overturning times on all of the outer planets. Currently available data cannot definitively establish the ortho-para ratios in the atmospheres of Uranus and Neptune, but suggest values closer to local equilibrium than to the 3.1 normal ratio. Modeling of sub-millimeter wavelength measurements of these planets suggest thermal structures with frozen equilibrium lapse rates in their convective regions.

The Ratio of Ortho- to Para-H2 in Photodissociation Regions

NASA Technical Reports Server (NTRS)

Sternberg, Amiel; Neufeld, David A.

1999-01-01

We discuss the ratio of ortho- to para-H2 in photodissociation regions (PDRs). We draw attention to an apparent confusion in the literature between the ortho-to-para ratio of molecules in FUV-pumped vibrationally excited states and the total H2 ortho-to-para abundance ratio. These ratios are not the same because the process of FUV pumping of fluorescent H2 emission in PDRs occurs via optically thick absorption lines. Thus gas with an equilibrium ratio of ortho- to para-H2 equal to 3 will yield FUV-pumped vibrationally excited ortho-to-para ratios smaller than 3, because the ortho-H2 pumping rates are preferentially reduced by optical depth effects. Indeed, if the ortho and para pumping lines are on the "square root" part of the curve of growth, then the expected ratio of ortho and para vibrational line strengths is 3(sup 1/2) approximately 1.7, close to the typically observed value. Thus, contrary to what has sometimes been stated in the literature, most previous measurements of the ratio of ortho- to para-H2 in vibrationally excited states are entirely consistent with a total ortho-to-para ratio of 3, the equilibrium value for temperatures greater than 200 K. We present an analysis and several detailed models that illustrate the relationship between the total ratios of ortho- to para-H2 and the vibrationally excited ortho-to-para ratios in PDRs. Recent Infrared Space Observatory measurements of pure rotational and vibrational H2 emissions from the PDR in the star-forming region S140 provide strong observational support for our conclusions.

Towards a double field theory on para-Hermitian manifolds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaisman, Izu

In a previous paper, we have shown that the geometry of double field theory has a natural interpretation on flat para-Kähler manifolds. In this paper, we show that the same geometric constructions can be made on any para-Hermitian manifold. The field is interpreted as a compatible (pseudo-)Riemannian metric. The tangent bundle of the manifold has a natural, metric-compatible bracket that extends the C-bracket of double field theory. In the para-Kähler case, this bracket is equal to the sum of the Courant brackets of the two Lagrangian foliations of the manifold. Then, we define a canonical connection and an action ofmore » the field that correspond to similar objects of double field theory. Another section is devoted to the Marsden-Weinstein reduction in double field theory on para-Hermitian manifolds. Finally, we give examples of fields on some well-known para-Hermitian manifolds.« less

Fixture for forming evaporative pattern (EPC) process patterns

DOEpatents

Turner, Paul C.; Jordan, Ronald R.; Hansen, Jeffrey S.

1993-01-01

A method of casting metal using evaporative pattern casting process patterns in combination with a fixture for creating and maintaining a desired configuration in flexible patterns. A pattern is constructed and gently bent to the curvature of a suitable fixture. String or thin wire, which burns off during casting, is used to tie the pattern to the fixture. The fixture with pattern is dipped in a commercially available refractory wash to prevent metal adherence and sticking to the fixture. When the refractory wash is dry, the fixture and pattern are placed in a flask, and sand is added and compacted by vibration. The pattern remains in position, restrained by the fixture. Metal that is poured directly into the pattern replaces the pattern exactly but does not contact or weld to the fixture due to the protective refractory layer. When solid, the casting is easily separated from the fixture. The fixture can be cleaned for reuse in conventional casting cleaning equipment.

Trust and British Gas partner in EPC scheme.

PubMed

Bevan, Patrick

2015-02-01

In late August last year the St George's Healthcare NHS Trust in south-west London signed what the Trust's Estates and Facilities team described as 'a historic partnership' with British Gas for a £12 m Energy Performance Contract energy reduction scheme--via which the energy company has guaranteed to deliver £1.1 m in annual savings over the next 15 years. The agreement will see British Gas replace four 35-year-old gas-powered steam boilers and an ageing CHP plant in the boiler house at the Trust's main acute facility, the StGeorge's Hospital in Tooting, and upgrade some of the associated infrastructure. British Gas will also maintain the new plant to ensure that the projected savings are achieved while the Trust owns the new assets. The Trust should gain financially--via lower energy costs and carbon emissions, while estates personnel will be better able to complete the many other estate maintenance issues that would otherwise be contracted out at one of London's biggest acute hospitals.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, F.H.; Moore, J.C.

1999-05-25

A method is disclosed for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase. 43 figs.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, Frances H.; Moore, Jeffrey C.

1998-01-01

A method for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, Frances H.; Moore, Jeffrey C.

1999-01-01

A method for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, F.H.; Moore, J.C.

1998-04-21

A method is disclosed for isolating and identifying modified para-nitrobenzyl esterases. These enzymes exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase. 43 figs.

Para-hydrogen perspectives in hyperpolarized NMR.

PubMed

Glöggler, Stefan; Colell, Johannes; Appelt, Stephan

2013-10-01

The first instance of para-hydrogen induced polarization (PHIP) in an NMR experiment was serendipitously observed in the 1980s while investigating a hydrogenation reaction (Seldler et al., 1983; Bowers and Weitekamp, 1986, 1987; Eisenschmid et al., 1987) [1-4]. Remarkably a theoretical investigation of the applicability of para-hydrogen as a hyperpolarization agent was being performed in the 1980's thereby quickly providing a theoretical basis for the PHIP-effect (Bowers and Weitekamp, 1986) [2]. The discovery of signal amplification by a non-hydrogenating interaction with para-hydrogen has recently extended the interest to exploit the PHIP effect, as it enables investigation of compounds without structural alteration while retaining the advantages of spectroscopy with hyperpolarized compounds [5]. In this article we will place more emphasis of the future applications of the method while only briefly discussing the efforts that have been made in the understanding of the phenomenon and the development of the method so far. Copyright © 2013 Elsevier Inc. All rights reserved.

[Spanish version of the Cancer Worry Scale (CWS). Cross cultural adaptation and validity and reliability analysis].

PubMed

Cabrera, Esther; Zabalegui, Adelaida; Blanco, Ignacio

2011-01-15

The worry for falling ill has been described as a key element in the change of preventive attitudes. Levels of cancer worry not well fitted have been associated with inadequate adherence to preventive strategies. There is not a Spanish validated scale to evaluate the degree of worry for the cancer in our population. The aim of the present study was to perform the cross cultural adaptation and validation of the Cancer Worry Scale described by Lerman. A translation, re-translation of the Cancer Worry Scale to Spanish was done. Validation of the Spanish scale was performed by means of the factorial analysis of principal components with the rotation varimax test in a sample of 200 healthy women with family history of breast cancer. The Escala de Preocupación por el Cáncer (EPC) is the Spanish version of the Cancer Worry Scale and it contains 6 items with a total value ranging from 6 (minimal worry) to 24 (maximum worry). The analysis of content validity demonstrated that the EPC is conceptually equivalent to the original scale. The factorial analysis showed a unique factor that explains 53.07% of the variance confirming the unique dimension. The EPC presented good reliability test - re-test with an Intraclass Correlation Coefficient of 0.777. The Cronbach's alpha was 0.835 for the complete of the scale. The EPC is a validated Spanish scale to measure the cancer worry in healthy individuals, which shows a correct content validity and reliability. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Expression and characterization of hydrophobin HGFI fused with the cell-specific peptide TPS in Pichia pastoris.

PubMed

Niu, Baolong; Huang, Yujian; Zhang, Suai; Wang, Dandan; Xu, Haijin; Kong, Deling; Qiao, Mingqiang

2012-05-01

The cell-specific peptide TPS (TPSLEQRTVYAK) has been proposed as a potential candidate for fabricating tissue engineering scaffolds based on its ability of binding to human endothelial progenitor cells (EPC) with high affinity and specificity. In this study, the class I hydrophobin hgfI gene from Grifola frondosa and the tps were fused and cloned into pPIC9. The fusion gene was expressed in Pichia pastoris under the control of alcohol oxidase 1 promoter. Tricine-SDS-PAGE and Western blotting confirmed that the fusion protein TPS-linker-HGFI (TLH) was successfully secreted into the culture medium. The fusion protein TLH was purified by ultrafiltration and reverse-phase high performance liquid chromatography (RP-HPLC). Water contact angle (WCA) demonstrated that similar to recombinant HGFI (rHGFI), the purified TLH could convert the surface wettability of polystyrene and mica. X-ray photoelectron spectroscopy (XPS) measurements indicated that the purified TLH could form stable films on the hydrophobic siliconized glass surface. The cell adhesion examination showed that the TLH modified poly(ε-caprolactone) (PCL) could specially facilitate the EPC (particularly EPC derived from human) binding, while rHGFI modified PCL could nonselectively enhance cells adhesion. To the best of our knowledge, this is the first report that demonstrates that the TPS peptide was immobilized on biomaterial-PCL surface by fusion with hydrophobin. The potential application of this finding in combination with biomedical devices for EPC culture, will facilitate the current techniques used for cell-based therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Effective charges and virial pressure of concentrated macroion solutions

DOE PAGES

Boon, Niels; Guerrero-García, Guillermo Ivan; van Roij, René; ...

2015-07-13

The stability of colloidal suspensions is crucial in a wide variety of processes, including the fabrication of photonic materials and scaffolds for biological assemblies. The ionic strength of the electrolyte that suspends charged colloids is widely used to control the physical properties of colloidal suspensions. The extensively used two-body Derjaguin-Landau-Verwey-Overbeek (DLVO) approach allows for a quantitative analysis of the effective electrostatic forces between colloidal particles. DLVO relates the ionic double layers, which enclose the particles, to their effective electrostatic repulsion. Nevertheless, the double layer is distorted at high macroion volume fractions. Therefore, DLVO cannot describe the many-body effects that arisemore » in concentrated suspensions. In this paper, we show that this problem can be largely resolved by identifying effective point charges for the macroions using cell theory. This extrapolated point charge (EPC) method assigns effective point charges in a consistent way, taking into account the excluded volume of highly charged macroions at any concentration, and thereby naturally accounting for high volume fractions in both salt-free and added-salt conditions. We provide an analytical expression for the effective pair potential and validate the EPC method by comparing molecular dynamics simulations of macroions and monovalent microions that interact via Coulombic potentials to simulations of macroions interacting via the derived EPC effective potential. The simulations reproduce the macroion-macroion spatial correlation and the virial pressure obtained with the EPC model. Finally, our findings provide a route to relate the physical properties such as pressure in systems of screened Coulomb particles to experimental measurements.« less

In vivo growth and genomic characterization of rickettsia-like organisms isolated from farmed Chinook salmon (Oncorhynchus tshawytscha) in New Zealand.

PubMed

Gias, E; Brosnahan, C L; Orr, D; Binney, B; Ha, H J; Preece, M A; Jones, B

2018-05-28

A rickettsia-like organism, designated NZ-RLO2, was isolated from Chinook salmon (Oncorhynchus tshawytscha) farmed in the South Island, New Zealand. In vivo growth showed NZ-RLO2 was able to grow in CHSE-214, EPC, BHK-21, C6/36 and Sf21 cell lines, while Piscirickettsia salmonis LF-89 T grew in all but BHK-21 and Sf21. NZ-RLO2 grew optimally in EPC at 15°C, CHSE-214 and EPC at 18°C. The growth of LF-89 T was optimal at 15°C, 18°C and 22°C in CHSE-24, but appeared less efficient in EPC cells at all temperatures. Pan-genome comparison of predicted proteomes shows that available Chilean strains of P. salmonis grouped into two clusters (p-value = 94%). NZ-RLO2 was genetically different from previously described NZ-RLO1, and both strains grouped separately from the Chilean strains in one of the two clusters (p-value = 88%), but were closely related to each other. TaqMan and Sybr Green real-time PCR targeting RNA polymerase (rpoB) and DNA primase (dnaG), respectively, were developed to detect NZ-RLO2. This study indicates that the New Zealand strains showed a closer genetic relationship to one of the Chilean P. salmonis clusters; however, more Piscirickettsia genomes from wider geographical regions and diverse hosts are needed to better understand the classification within this genus. © 2018 John Wiley & Sons Ltd.

Scaling up the energy service company business: market status and company feedback in the Russian Federation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roshchanka, Volha; Evans, Meredydd

Many energy efficiency professionals have proposed using Energy Performance Contracts (EPCs) as a mechanism to improve public sector energy efficiency in countries with restrictive government budgets. However, in practice, most middle-income countries have used this mechanism only in a limited way. Russia offers an interesting case study because of its huge energy savings opportunities, increasing energy prices, robust political backing for public sector energy efficiency, and evolving legislation that supports EPCs. In 2009, the Russian Federation launched a program to reduce the energy intensity of the country’s large public sector, which accounts for 9 percent of Russia’s total energy consumption.more » To achieve energy efficiency goals, Russia experimented with its public procurement rules, adjusting them to encourage EPCs. We conducted structured interviews with Energy Service Companies (ESCOs) in Russia and supplemented them with online research. Our review shows that, to date, nearly 50 ESCOs signed about 150 contracts in public facilities. Most ESCO contracts in Russia are for 5 years, and they generally are small (under $100,000). ESCOs in Russia face a challenging environment, which leads to smaller projects. ESCOs also are concerned about costly and risky tender procedures, uncertainty regarding repayment from public facilities, the inability to expand projects, and financing. We discuss these challenges and propose potential solutions at policy and company levels. The ESCOs feedback regarding Russia’s experimental model can inform the country’s program for public sector energy efficiency and offer lessons for other countries attempting to develop the EPC mechanism.« less

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

PubMed

Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

2015-09-01

Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Coincidence of moderately elevated N-terminal pro-B-type natriuretic peptide, endothelial progenitor cells deficiency and propensity to exercise-induced myocardial ischemia in stable angina.

PubMed

Surdacki, Andrzej; Marewicz, Ewa; Rakowski, Tomasz; Szumańska, Monika; Szastak, Grzegorz; Pryjma, Juliusz; Dubiel, Jacek S

2010-01-01

To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors - N-terminal pro-B-type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia - in stable coronary artery disease (CAD) with preserved LV systolic function. We studied 30 non-diabetic men with one-vessel CAD, LV ejection fraction 60% and normal LV diastolic function (n=16) or impaired LV relaxation (by ultrasound including tissue Doppler) (n=14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry. CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP-CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score. Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors.

Selective detection of hyperpolarized NMR signals derived from para-hydrogen using the Only Para-hydrogen SpectroscopY (OPSY) approach.

PubMed

Aguilar, Juan A; Adams, Ralph W; Duckett, Simon B; Green, Gary G R; Kandiah, Rathika

2011-01-01

A new family of NMR pulse sequences is reported for the recording of para-hydrogen enhanced NMR spectra. This Only Para-hydrogen SpectroscopY (OPSY) approach uses coherence selection to separate hyperpolarized signals from those of fully relaxed and thermally equilibrated protons. Sequence design, performance, practical aspects and applicability to other hyperpolarization techniques are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

A case of schizencephaly has a normal surface EEG but abnormal intracranial EEG: epilepsia partialis continua or dystonia?

PubMed

Lv, Yudan; Ma, Dihui; Meng, Hongmei; Zan, Wang; Li, Cui

2013-10-01

Schizencephaly is a congenital malformation of the cerebral hemispheres, with communication between the lateral ventricle and the subarachnoid space. Marinelli reported that schizencephaly may be associated with continuous involuntary hand movements, such as dystonia or epilepsia partialis continua (EPC). We describe a young Chinese patient with continuous involuntary movements of the contralateral hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG) but abnormal intracranial EEG, with synchronized periodic lateralized epileptiform discharges. The results obtained from these EEG investigations and the clinical features of the involuntary movements are in favor of a diagnosis of secondary EPC.

ORTHO-PARA SELECTION RULES IN THE GAS-PHASE CHEMISTRY OF INTERSTELLAR AMMONIA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faure, A.; Hily-Blant, P.; Le Gal, R.

The ortho-para chemistry of ammonia in the cold interstellar medium is investigated using a gas-phase chemical network. Branching ratios for the primary reaction chain involved in the formation and destruction of ortho- and para-NH{sub 3} were derived using angular momentum rules based on the conservation of the nuclear spin. We show that the 'anomalous' ortho-to-para ratio of ammonia ({approx}0.7) observed in various interstellar regions is in fact consistent with nuclear spin selection rules in a para-enriched H{sub 2} gas. This ratio is found to be independent of temperature in the range 5-30 K. We also predict an ortho-to-para ratio ofmore » {approx}2.3 for NH{sub 2}. We conclude that a low ortho-to-para ratio of H{sub 2} naturally drives the ortho-to-para ratios of nitrogen hydrides below the statistical values.« less

[The induction and cryopreservation of erythroid progenitor cells derived from umbilical cord blood mononuclear cells].

PubMed

Chen, Lin; Xie, Xiaoyan; Xi, Jiafei; Lyu, Yang; Tian, Yu; Liu, Daqing; Yue, Wen; Li, Yanhua; Nan, Xue; Li, Siting; Fan, Zeng; Pei, Xuetao

2016-01-01

To discover the techniques for ex vivo generation and cryopreservation of erythroid progenitor cells (EPCs)derived from umbilical cord blood (UCB)mononuclear cells (MNCs). UCB was chosen as the source of EPCs. Erythrocytes were precipitated by hydroxyethyl starch (HES). MNCs were separated by Ficoll density gradient centrifugation. Erythroid progenitor cell were generated from MNC ex vivo in suspension culture supplemented with stem cell growth factor, insulin growth factor, erythropoietin, Fms- liketyrosinekinase ligand, transferrin and dexamethasone. Cell maturation was evaluated by morphologic analysis and CD71/CD235a expression profiling. In vitro induced cells were cryopreserved using different cryopreservation media. The cell survival rate, phenotype and proliferation curves were detected after cell thawing. With the extension of culture time, the total number of cells increased significantly accompanied with the elevation of CD71 and CD235 positive populations. After 14- day inducing, the cells reached to approximately 110 times of the starting number with the cell viability as (88.92±0.95)%. The percentages of cell surface markers were (86.77±9.11)% for CD71 and (64.47±16.67)% for CD71/CD235, respectively. With the extension of inducing time, wright- Giemsa staining showed that the middle erythroblasts appeared mostly at day 10, and the late erythroblasts were seen at day 14. The red pellets were present at day 14, which indicated the more production of hemoglobin. Colony forming assay showed that erythroid colonies at induction day 7 were higher than that for non-induced cells (326.00±97.96vs 61.60±20.03 per 2 000 cells). With the extension of culture time, the number of erythroid colonies decreased. Induced EPCs were preserved with different cryopreservation solutions, in which 10% DMSO were better than 5% DMSO. Additionally, 10% DMSO + 2% HSA showed no different with 10% DMSO + 5% HSA. Combined 50% plasma with 2% HSA was more effective. This non

Men's Sexual Faithfulness Judgments May Contain a Kernel of Truth.

PubMed

Leivers, Samantha; Simmons, Leigh W; Rhodes, Gillian

2015-01-01

Mechanisms enabling men to identify women likely to engage in extra-pair copulations (EPCs) would be advantageous in avoiding cuckoldry. Men's judgments of female sexual faithfulness often show high consensus, but accuracy appears poor. We examined whether accuracy of these judgments made to images of women could be improved through i) employing a forced choice task, in which men were asked to select the more faithful of two women and/or ii) providing men with full person images. In Experiment 1, men rated 34 women, for whom we had self-reported EPC behavior, on faithfulness, trustworthiness or attractiveness from either face or full person photographs. They then completed a forced choice task, selecting the more faithful of two woman from 17 pairs of images, each containing one woman who had reported no EPCs and one who had reported two or more EPCs. Men were unable to rate faithfulness with any accuracy, replicating previous findings. However, when asked to choose the more faithful of two women, they performed significantly above chance, although the ability to judge faithfulness at above-chance levels did not generalize to all pairs of women. Although there was no significant difference in accuracy for face and full person image pairs, only judgments from faces were significantly above chance. In Experiment 2, we showed that this accuracy for faces was repeatable in a new sample of men. We also showed that individual variation in accuracy was unrelated to variation in preferences for faithfulness in a long-term partner. Overall, these results show that men's judgments of faithfulness made from faces of unfamiliar women may contain a kernel of truth.

Phase 1-2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells.

PubMed

D'Avola, Delia; Fernández-Ruiz, Verónica; Carmona-Torre, Francisco; Méndez, Miriam; Pérez-Calvo, Javier; Prósper, Felipe; Andreu, Enrique; Herrero, José Ignacio; Iñarrairaegui, Mercedes; Fuertes, Carmen; Bilbao, José Ignacio; Sangro, Bruno; Prieto, Jesús; Quiroga, Jorge

2017-10-01

The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

Engaging patients and families to create a feasible clinical trial integrating palliative and heart failure care: results of the ENABLE CHF-PC pilot clinical trial.

PubMed

Bakitas, Marie; Dionne-Odom, J Nicholas; Pamboukian, Salpy V; Tallaj, Jose; Kvale, Elizabeth; Swetz, Keith M; Frost, Jennifer; Wells, Rachel; Azuero, Andres; Keebler, Konda; Akyar, Imatullah; Ejem, Deborah; Steinhauser, Karen; Smith, Tasha; Durant, Raegan; Kono, Alan T

2017-08-31

Early palliative care (EPC) is recommended but rarely integrated with advanced heart failure (HF) care. We engaged patients and family caregivers to study the feasibility and site differences in a two-site EPC trial, ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends Comprehensive Heartcare for Patients and Caregivers). We conducted an EPC feasibility study (4/1/14-8/31/15) for patients with NYHA Class III/IV HF and their caregivers in academic medical centers in the northeast and southeast U.S. The EPC intervention comprised: 1) an in-person outpatient palliative care consultation; and 2) telephonic nurse coach sessions and monthly calls. We collected patient- and caregiver-reported outcomes of quality of life (QOL), symptom, health, anxiety, and depression at baseline, 12- and 24-weeks. We used linear mixed-models to assess baseline to week 24 longitudinal changes. We enrolled 61 patients and 48 caregivers; between-site demographic differences included age, race, religion, marital, and work status. Most patients (69%) and caregivers (79%) completed all intervention sessions; however, we noted large between-site differences in measurement completion (38% southeast vs. 72% northeast). Patients experienced moderate effect size improvements in QOL, symptoms, physical, and mental health; caregivers experienced moderate effect size improvements in QOL, depression, mental health, and burden. Small-to-moderate effect size improvements were noted in patients' hospital and ICU days and emergency visits. Between-site demographic, attrition, and participant-reported outcomes highlight the importance of intervention pilot-testing in culturally diverse populations. Observations from this pilot feasibility trial allowed us to refine the methodology of an in-progress, full-scale randomized clinical efficacy trial. Clinicaltrials.gov NCT03177447 (retrospectively registered, June 2017).

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

PubMed

Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

Potential impacts of urban land expansion on Asian airborne pollutant outflows

NASA Astrophysics Data System (ADS)

Tao, Wei; Liu, Junfeng; Ban-Weiss, George A.; Zhang, Lin; Zhang, Jiachen; Yi, Kan; Tao, Shu

2017-07-01

Eastern part of China (EPC) has experienced rapid urbanization during the past few decades. Here we investigate the impacts of urban land expansion over EPC on the export of Asian pollutants to the western Pacific during January, April, July, and October of 2009 using the Weather Research and Forecasting model coupled to Chemistry (WRF/Chem) and a single-layer urban canopy scheme. Over urbanizing areas, increases in the urban land fraction result in a linearly enhanced uplift of surface primary pollutants to higher altitudes. We further examine how this local effect would change outflows of Asian pollutants to the western Pacific using the tagged black carbon (BC) and carbon monoxide (CO) tracers emitted from EPC (denoted by BCt and COt, respectively). Overall, a 0.1 increase in the fraction of land area that is urban over EPC would linearly (R2 = 0.70-0.96) increase the mean tropospheric eastward export of BCt and COt across meridional planes (i.e., 135°E and 150°E) by 4-40% and 1-6% in different months, respectively. The relative perturbation in exporting efficiency generally maximizes during July while minimizes during April. The urbanization-export relationship is largely driven by the elevation effect and is also impacted by urbanization-forced changes in zonal winds. The spatial pattern of the response of BCt over the downwind Pacific differs from that of COt mainly due to aerosol-cloud interactions. Our findings demonstrate that extensive urban land expansion could substantially impact climate and air quality from a local scale to a regional scale, especially for shorter-lived air pollutants such as BC and other aerosols.

Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.

PubMed

Vouga, Alexandre; Gregg, Ryan A; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K; Tallarida, Christopher S; Grizzanti, David; Raffa, Robert B; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

2015-04-01

Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own. Copyright © 2014 Elsevier Ltd. All rights reserved.

Emergence of an Out-of-Plane Optical Phonon (ZO) Kohn Anomaly in Quasifreestanding Epitaxial Graphene.

PubMed

Politano, Antonio; de Juan, Fernando; Chiarello, Gennaro; Fertig, Herbert A

2015-08-14

In neutral graphene, two prominent cusps known as Kohn anomalies are found in the phonon dispersion of the highest optical phonon at q=Γ (LO branch) and q=K (TO branch), reflecting a significant electron-phonon coupling (EPC) to undoped Dirac electrons. In this work, high-resolution electron energy loss spectroscopy is used to measure the phonon dispersion around the Γ point in quasifreestanding graphene epitaxially grown on Pt(111). The Kohn anomaly for the LO phonon is observed at finite momentum q~2k_{F} from Γ, with a shape in excellent agreement with the theory and consistent with known values of the EPC and the Fermi level. More strikingly, we also observe a Kohn anomaly at the same momentum for the out-of-plane optical phonon (ZO) branch. This observation is the first direct evidence of the coupling of the ZO mode with Dirac electrons, which is forbidden for freestanding graphene but becomes allowed in the presence of a substrate. Moreover, we estimate the EPC to be even greater than that of the LO mode, making graphene on Pt(111) an optimal system to explore the effects of this new coupling in the electronic properties.

Suppression of microbial metabolic pathways inhibits the generation of the human body odor component diacetyl by Staphylococcus spp.

PubMed

Hara, Takeshi; Matsui, Hiroshi; Shimizu, Hironori

2014-01-01

Diacetyl (2,3-butanedione) is a key contributor to unpleasant odors emanating from the axillae, feet, and head regions. To investigate the mechanism of diacetyl generation on human skin, resident skin bacteria were tested for the ability to produce diacetyl via metabolism of the main organic acids contained in human sweat. L-lactate metabolism by Staphylococcus aureus and Staphylococcus epidermidis produced the highest amounts of diacetyl, as measured by high-performance liquid chromatography. Glycyrrhiza glabra root extract (GGR) and α-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), a phosphate diester of α-tocopherol and ascorbic acid, effectively inhibited diacetyl formation without bactericidal effects. Moreover, a metabolic flux analysis revealed that GGR and EPC-K1 suppressed diacetyl formation by inhibiting extracellular bacterial conversion of L-lactate to pyruvate or by altering intracellular metabolic flow into the citrate cycle, respectively, highlighting fundamentally distinct mechanisms by GGR and EPC-K1 to suppress diacetyl formation. These results provide new insight into diacetyl metabolism by human skin bacteria and identify a regulatory mechanism of diacetyl formation that can facilitate the development of effective deodorant agents.

An endocannabinoid hypothesis of drug reward and drug addiction.

PubMed

Onaivi, Emmanuel S

2008-10-01

Pharmacologic treatment of drug and alcohol dependency has largely been disappointing, and new therapeutic targets and hypotheses are needed. There is accumulating evidence indicating a central role for the previously unknown but ubiquitous endocannabinoid physiological control system (EPCS) in the regulation of the rewarding effects of abused substances. Thus an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and are involved in the regulation of synaptic transmission to suppress neurotransmitter release by the presynaptic cannabinoid receptors (CB-Rs). This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Our data, along with those from other investigators, provide strong new evidence for a role for EPCS modulation in the effects of drugs of abuse, and specifically for involvement of cannabinoid receptors in the neural basis of addiction. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs. The results suggest that the EPCS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.

AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions--agency for healthcare research and quality and the effective health-care program.

PubMed

Owens, Douglas K; Lohr, Kathleen N; Atkins, David; Treadwell, Jonathan R; Reston, James T; Bass, Eric B; Chang, Stephanie; Helfand, Mark

2010-05-01

To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality. Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose-response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence. EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence.

Interprofessional transformation of clinical education: The first six years of the Veterans Affairs Centers of Excellence in Primary Care Education.

PubMed

Harada, Nancy D; Traylor, Laural; Rugen, Kathryn Wirtz; Bowen, Judith L; Smith, C Scott; Felker, Bradford; Ludke, Deborah; Tonnu-Mihara, Ivy; Ruberg, Joshua L; Adler, Jayson; Uhl, Kimberly; Gardner, Annette L; Gilman, Stuart C

2018-02-20

This paper describes the Centers of Excellence in Primary Care Education (CoEPCE), a seven-site collaborative project funded by the Office of Academic Affiliations (OAA) within the Veterans Health Administration of the United States Department of Veterans Affairs (VA). The CoEPCE was established to fulfill OAA's vision of large-scale transformation of the clinical learning environment within VA primary care settings. This was accomplished by funding new Centers within VA facilities to develop models of interprofessional education (IPE) to teach health professions trainees to deliver high quality interprofessional team-based primary care to Veterans. Using reports and data collected and maintained by the National Coordinating Center over the first six years of the project, we describe program inputs, the multicomponent intervention, activities undertaken to develop the intervention, and short-term outcomes. The findings have implications for lessons learned that can be considered by others seeking large-scale transformation of education within the clinical workplace and the development of interprofessional clinical learning environments. Within the VA, the CoEPCE has laid the foundation for IPE and collaborative practice, but much work remains to disseminate this work throughout the national VA system.

Prediction of phonon-mediated superconductivity in hole-doped black phosphorus.

PubMed

Feng, Yanqing; Sun, Hongyi; Sun, Junhui; Lu, Zhibin; You, Yong

2018-01-10

We study the conventional electron-phonon mediated superconducting properties of hole-doped black phosphorus by density functional calculations and get quite a large electron-phonon coupling (EPC) constant λ ~ 1.0 with transition temperature T C ~ 10 K, which is comparable to MgB 2 when holes are doped into the degenerate and nearly flat energy bands around the Fermi level. We predict that the softening of low-frequency [Formula: see text] optical mode and its phonon displacement, which breaks the lattice nonsymmorphic symmetry of gliding plane and lifts the band double degeneracy, lead to a large EPC. These factors are favorable for BCS superconductivity.

Prediction of phonon-mediated superconductivity in hole-doped black phosphorus

NASA Astrophysics Data System (ADS)

Feng, Yanqing; Sun, Hongyi; Sun, Junhui; Lu, Zhibin; You, Yong

2018-01-01

We study the conventional electron-phonon mediated superconducting properties of hole-doped black phosphorus by density functional calculations and get quite a large electron-phonon coupling (EPC) constant λ ~ 1.0 with transition temperature T C ~ 10 K, which is comparable to MgB2 when holes are doped into the degenerate and nearly flat energy bands around the Fermi level. We predict that the softening of low-frequency B3g1 optical mode and its phonon displacement, which breaks the lattice nonsymmorphic symmetry of gliding plane and lifts the band double degeneracy, lead to a large EPC. These factors are favorable for BCS superconductivity.

Key Nutritional Strategies to Optimize Performance in Para Athletes.

PubMed

Scaramella, Jacque; Kirihennedige, Nuwanee; Broad, Elizabeth

2018-05-01

Para athletes are a high-risk population for inadequate dietary intake leading to insufficiencies in nutrients important to athletic performance. This is partly due to minimal support and resources, especially in sport nutrition education, combined with limited prior nutrition knowledge and risks associated with different impairment types. Inadequate energy, carbohydrate, protein, iron, and vitamin D status are of particular concern in Para athletes. Assessment of these key nutrients, along with sport nutrition education, is needed to empower Para athletes with the knowledge to understand their individual nutrition needs and maximize athletic performance. Copyright © 2018 Elsevier Inc. All rights reserved.

Probing the Superfluid Response of para-Hydrogen with a Sulfur Dioxide Dopant.

PubMed

Zeng, Tao; Guillon, Grégoire; Cantin, Joshua T; Roy, Pierre-Nicholas

2013-07-18

We recently presented the first attempt at using an asymmetric top molecule (para-water) to probe the superfluidity of nanoclusters (of para-hydrogen) [ Zeng , T. ; Li , H. ; Roy , P.-N. J. Phys. Chem. Lett. 2013 , 4 , 18 - 22 ]. Unfortunately, para-water could not be used to probe the para-hydrogen superfluid response. We now report a theoretical simulation of sulfur dioxide rotating in para-hydrogen clusters and show that this asymmetric top can serve as a genuine probe of superfluidity. With this probe, we predict that as few as four para-hydrogen molecules are enough to form a superfluid cluster, the smallest superfluid system to date. We also propose the concept of "exchange superfluid fraction" as a more precise measurement. New superfluid scenarios brought about by an asymmetric top dopant and potential experimental measurements are discussed.

Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters.

PubMed

Zhang, Huixian; Ravi, Vydianathan; Tay, Boon-Hui; Tohari, Sumanty; Pillai, Nisha E; Prasad, Aravind; Lin, Qiang; Brenner, Sydney; Venkatesh, Byrappa

2017-08-22

ParaHox genes ( Gsx , Pdx , and Cdx ) are an ancient family of developmental genes closely related to the Hox genes. They play critical roles in the patterning of brain and gut. The basal chordate, amphioxus, contains a single ParaHox cluster comprising one member of each family, whereas nonteleost jawed vertebrates contain four ParaHox genomic loci with six or seven ParaHox genes. Teleosts, which have experienced an additional whole-genome duplication, contain six ParaHox genomic loci with six ParaHox genes. Jawless vertebrates, represented by lampreys and hagfish, are the most ancient group of vertebrates and are crucial for understanding the origin and evolution of vertebrate gene families. We have previously shown that lampreys contain six Hox gene loci. Here we report that lampreys contain only two ParaHox gene clusters (designated as α- and β-clusters) bearing five ParaHox genes ( Gsxα , Pdxα , Cdxα , Gsxβ , and Cdxβ ). The order and orientation of the three genes in the α-cluster are identical to that of the single cluster in amphioxus. However, the orientation of Gsxβ in the β-cluster is inverted. Interestingly, Gsxβ is expressed in the eye, unlike its homologs in jawed vertebrates, which are expressed mainly in the brain. The lamprey Pdxα is expressed in the pancreas similar to jawed vertebrate Pdx genes, indicating that the pancreatic expression of Pdx was acquired before the divergence of jawless and jawed vertebrate lineages. It is likely that the lamprey Pdxα plays a crucial role in pancreas specification and insulin production similar to the Pdx of jawed vertebrates.

Ortho- and para-hydrogen in dense clouds, protoplanets, and planetary atmospheres

NASA Technical Reports Server (NTRS)

Decampli, W. M.; Cameron, A. G. W.; Bodenheimer, P.; Black, D. C.

1978-01-01

If ortho- and para-hydrogen achieve a thermal ratio on dynamical time scales in a molecular hydrogen cloud, then the specific heat is high enough in the temperature range 35-70 K to possibly induce hydrodynamic collapse. The ortho-para ratio in many interstellar cloud fragments is expected to meet this condition. The same may have been true for the primitive solar nebula. Detailed hydrodynamic and hydrostatic calculations are presented that show the effects of the assumed ortho-para ratio on the evolution of Jupiter during its protoplanetary phase. Some possible consequences of a thermalized ortho-para ratio in the atmospheres of the giant planets are also discussed.

Cooling by conversion of para to ortho-hydrogen

NASA Technical Reports Server (NTRS)

Sherman, A. (Inventor)

1983-01-01

The cooling capacity of a solid hydrogen cooling system is significantly increased by exposing vapor created during evaporation of a solid hydrogen mass to a catalyst and thereby accelerating the endothermic para-to-ortho transition of the vapor to equilibrium hydrogen. Catalyst such as nickel, copper, iron or metal hydride gels of films in a low pressure drop catalytic reactor are suitable for accelerating the endothermic para-to-ortho conversion.

Influence of Molecular Oxygen on Ortho-Para Conversion of Water Molecules

NASA Astrophysics Data System (ADS)

Valiev, R. R.; Minaev, B. F.

2017-07-01

The mechanism of influence of molecular oxygen on the probability of ortho-para conversion of water molecules and its relation to water magnetization are considered within the framework of the concept of paramagnetic spin catalysis. Matrix elements of the hyperfine ortho-para interaction via the Fermi contact mechanism are calculated, as well as the Maliken spin densities on water protons in H2O and O2 collisional complexes. The mechanism of penetration of the electron spin density into the water molecule due to partial spin transfer from paramagnetic oxygen is considered. The probability of ortho-para conversion of the water molecules is estimated by the quantum chemistry methods. The results obtained show that effective ortho-para conversion of the water molecules is possible during the existence of water-oxygen dimers. An external magnetic field affects the ortho-para conversion rate given that the wave functions of nuclear spin sublevels of the water protons are mixed in the complex with oxygen.

Carbon Monoxide and Nitric Oxide Mediate Cytoskeletal Reorganization in Microvascular Cells via Vasodilator-Stimulated Phosphoprotein Phosphorylation

PubMed Central

Li Calzi, Sergio; Purich, Daniel L.; Chang, Kyung Hee; Afzal, Aqeela; Nakagawa, Takahiko; Busik, Julia V.; Agarwal, Anupam; Segal, Mark S.; Grant, Maria B.

2008-01-01

OBJECTIVE— We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) on the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation. RESEARCH DESIGN AND METHODS— We examined the effect of donor-released CO and NO in endothelial progenitor cells (EPCs) and platelets from nondiabetic and diabetic subjects and in human microvascular endothelial cells (HMECs) cultured under low (5.5 mmol/l) or high (25 mmol/l) glucose conditions. VASP phosphorylation was evaluated using phosphorylation site-specific antibodies. RESULTS— In control platelets, CO selectively promotes phosphorylation at VASP Ser-157, whereas NO promotes phosphorylation primarily at Ser-157 and also at Ser-239, with maximal responses at 1 min with both agents on Ser-157 and at 15 min on Ser-239 with NO treatment. In diabetic platelets, neither agent resulted in VASP phosphorylation. In nondiabetic EPCs, NO and CO increased phosphorylation at Ser-239 and Ser-157, respectively, but this response was markedly reduced in diabetic EPCs. In endothelial cells cultured under low glucose conditions, both CO and NO induced phosphorylation at Ser-157 and Ser-239; however, this response was completely lost when cells were cultured under high glucose conditions. In control EPCs and in HMECs exposed to low glucose, VASP was redistributed to filopodia-like structures following CO or NO exposure; however, redistribution was dramatically attenuated under high glucose conditions. CONCLUSIONS— Vasoactive gases CO and NO promote cytoskeletal changes through site- and cell type–specific VASP phosphorylation, and in diabetes, blunted responses to these agents may lead to reduced vascular repair and tissue perfusion. PMID:18559661

Formulation and characterization of boanmycin-loaded liposomes prepared by pH gradient experimental design.

PubMed

Liu, Yu; Yoo, Sun Dong; Li, Li; Fang, Liang; Wen, Ziyi; Li, Tiefu

2012-02-01

This study reports the development of a novel liposomal formulation containing boanmycin (BAM) by the pH-gradient, spherical symmetric experimental design. DSC was used to elucidate the thermotropic transition of the soybean egg phosphatidylcholine (EPCS) bilayers. The DSC analysis showed that the incorporation of cholesterol into the EPCS bilayers caused a reduction in the cooperativity of the bilayer phase transition, leading to a dense and more stable structure. To further explore the possibility of the facilitated molecular interaction between BAM and lipids, the effective chemical shift anisotropy (Δδ) of EPCS was measured by (31)P-NMR spectroscopy in the presence and absence of BAM at 25 °C. The results revealed that the amino group of BAM interacted with the hydrophilic head group of EPCS by electrostatic attraction. Effects of the lipid concentration, pH of the outside buffer and incubation temperature on the encapsulation efficiency of the liposomes were investigated by the spherical symmetric design. Multiple nonlinear regression and second-order polynomial model were fitted to the data, and the resulting equations were used to produce the three dimensional response graphs. The actual response values were in good agreement with the predicted values calculated by the visual FoxPro software. To determine the plasma pharmacokinetics and tissue distribution characteristics of BAM, mice were i.v. injected with BAM-loaded liposomes and the commercial injection solution. The BAM-loaded liposomes exhibited significantly different t(1/2), CL and AUC in plasma and tissues. The MTT assay showed that the BAM-loaded liposomes effectively inhibited the cell proliferation by inducing apoptosis of HepG2 cells in a dose- and time-dependent manner. Compared to the control group, the BAM-loaded liposomes induced marked apoptotic morphologic alterations, including cell shrinkage and granular apoptotic bodies. © 2012 Informa Healthcare USA, Inc.

Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: Follow-up of a randomized trial.

PubMed

Maiorino, Maria Ida; Bellastella, Giuseppe; Petrizzo, Michela; Gicchino, Maurizio; Caputo, Mariangela; Giugliano, Dario; Esposito, Katherine

2017-03-01

Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet ( n = 108) or a low-fat diet ( n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34 + KDR + and CD34 + KDR + CD133 + counts had increased with the Mediterranean diet compared with the low-fat diet ( p < 0.05 for both). At the EOT evaluation, there was a significant ( p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) ( p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34 + KDR + , r = -0.24, p = 0.020; CD34 + KDR + CD133 + , r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

Induction of intestinalization in human esophageal keratinocytes is a multistep process.

PubMed

Kong, Jianping; Nakagawa, Hiroshi; Isariyawongse, Brandon K; Funakoshi, Shinsuke; Silberg, Debra G; Rustgi, Anil K; Lynch, John P

2009-01-01

Barrett's esophagus (BE) is the replacement of normal squamous esophageal mucosa with an intestinalized columnar epithelium. The molecular mechanisms underlying its development are not understood. Cdx2 is an intestine-specific transcription factor that is ectopically expressed in BE, but its role in this process is unclear. Herein, we describe a novel cell culture model for BE. Retroviral-mediated Cdx2 expression in immortalized human esophageal keratinocytes [EPC-human telomerase reverse transcriptase (hTERT)] could transiently be established but not maintained and was associated with a reduction in cell proliferation. Coexpression of cyclin D1, but not a dominant-negative p53, rescued proliferation in the Cdx2-expressing cells. Cdx2 expression in the EPC-hTERT.D1 cells decreased cell proliferation but did not induce intestinalization. We investigated for other treatments to enhance intestinalization and found that acidic culture conditions uniformly killed EPC-hTERT.D1.Cdx2 cells. However, treatment with 5-aza-2-deoxycytidine (5-AzaC) to demethylate epigenetically silenced genes did appear to be tolerated. Multiple Cdx2 target genes, markers of intestinal differentiation and markers of BE, were induced by this 5-AzaC treatment. More interestingly, the expression level of several of these genes was enhanced only in the EPC-hTERT.D1-Cdx2 cells treated with 5-AzaC. Two of these, SLC26a3/DRA (downregulated in adenoma) and Na+/H+ exchanger 2 (NHE2), were not previously known to be elevated in BE; however, we confirmed their elevation in BE tissue samples. 5-AzaC treatment also induced cell senescence, even at low doses. We conclude that ectopic proliferation signals, alterations in epigenetic gene regulation and the inhibition of tumor suppressor mechanisms are required for Cdx2-mediated intestinalization of human esophageal keratinocytes in BE.

Induction of intestinalization in human esophageal keratinocytes is a multistep process

PubMed Central

Kong, Jianping; Nakagawa, Hiroshi; Isariyawongse, Brandon K.; Funakoshi, Shinsuke; Silberg, Debra G.; Rustgi, Anil K.; Lynch, John P.

2009-01-01

Barrett's esophagus (BE) is the replacement of normal squamous esophageal mucosa with an intestinalized columnar epithelium. The molecular mechanisms underlying its development are not understood. Cdx2 is an intestine-specific transcription factor that is ectopically expressed in BE, but its role in this process is unclear. Herein, we describe a novel cell culture model for BE. Retroviral-mediated Cdx2 expression in immortalized human esophageal keratinocytes [EPC-human telomerase reverse transcriptase (hTERT)] could transiently be established but not maintained and was associated with a reduction in cell proliferation. Coexpression of cyclin D1, but not a dominant-negative p53, rescued proliferation in the Cdx2-expressing cells. Cdx2 expression in the EPC-hTERT.D1 cells decreased cell proliferation but did not induce intestinalization. We investigated for other treatments to enhance intestinalization and found that acidic culture conditions uniformly killed EPC-hTERT.D1.Cdx2 cells. However, treatment with 5-aza-2-deoxycytidine (5-AzaC) to demethylate epigenetically silenced genes did appear to be tolerated. Multiple Cdx2 target genes, markers of intestinal differentiation and markers of BE, were induced by this 5-AzaC treatment. More interestingly, the expression level of several of these genes was enhanced only in the EPC-hTERT.D1-Cdx2 cells treated with 5-AzaC. Two of these, SLC26a3/DRA (downregulated in adenoma) and Na+/H+ exchanger 2 (NHE2), were not previously known to be elevated in BE; however, we confirmed their elevation in BE tissue samples. 5-AzaC treatment also induced cell senescence, even at low doses. We conclude that ectopic proliferation signals, alterations in epigenetic gene regulation and the inhibition of tumor suppressor mechanisms are required for Cdx2-mediated intestinalization of human esophageal keratinocytes in BE. PMID:18845559

Apoptosis regulator through modulating IAP expression (ARIA) controls the PI3K/Akt pathway in endothelial and endothelial progenitor cells.

PubMed

Koide, Masahiro; Ikeda, Koji; Akakabe, Yoshiki; Kitamura, Youhei; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Okigaki, Mitsuhiko; Matsubara, Hiroaki

2011-06-07

Endothelial and endothelial progenitor cells (ECs and EPCs) play a fundamental role in angiogenesis that is essential for numerous physiological and pathological processes. The phosphatase and tensin homolog (PTEN)/ phosphoinositide 3-kinase (PI3K) pathway has been implicated in angiogenesis, but the mechanism in the regulation of this pathway in ECs and EPCs is poorly understood. Here we show that ARIA (apoptosis regulator through modulating IAP expression), a transmembrane protein that we recently identified, regulates the PTEN/PI3K pathway in ECs and EPCs and controls developmental and postnatal angiogenesis in vivo. We found that ARIA is abundantly expressed in EPCs and regulates their angiogenic functions by modulating PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling. Genetic deletion of ARIA caused nonfatal bleeding during embryogenesis, in association with increased small vessel density and altered expression of various vascular growth factors including angiopoietins and VEGF receptors. Postnatal neovascularization induced by critical limb ischemia was substantially enhanced in ARIA-null mice, in conjunction with more bone marrow (BM)-derived ECs detected in ischemic muscles. Administration of PI3K or NO synthase inhibitor completely abolished the enhanced neovascularization in ARIA(-/-) mice. Mechanistically, we identified that ARIA interacts with PTEN at the intracellular domain independently of the PTEN phosphorylation in its C-terminal tail. Overexpressed ARIA increased PTEN in the membrane fraction, whereas ARIA-silencing reduced the membrane-associated PTEN, resulting in modified PI3K/Akt signaling. Taken together, our findings establish a previously undescribed mode of regulation of the PTEN/PI3K/Akt pathway by ARIA, and reveal a unique mechanism in the control of angiogenesis. These functions of ARIA might offer a unique therapeutic potential.

Family Caregiver Depressive Symptom and Grief Outcomes from the ENABLE III Randomized Controlled Trial

PubMed Central

Dionne-Odom, J. Nicholas; Azuero, Andres; Lyons, Kathleen D.; Hull, Jay G.; Prescott, Anna T.; Tosteson, Tor; Frost, Jennifer; Dragnev, Konstantin H.; Bakitas, Marie A

2016-01-01

Context Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die. Objectives To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. Methods We conducted a randomized controlled trial (RCT) (10/2010-9/2013) of an EPC telehealth intervention for CGs (n=123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression scale (CESD) and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between-group differences were estimated and tested using general linear models. Results For care recipients who died (n=70), 44 CGs (early: n=19; delayed: n=25) completed after-death questionnaires. Mean depressive symptom scores (CESD) for the early group was 14.6 (standard deviation [SD]=10.7) and for the delayed group was 17.6 (SD=11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD=4.9) and for the delayed group was 24.9 (SD=6.9). Adjusted between-group differences were not statistically significant (CESD: d=0.07, P=0.88; PG13: d=-0.21, P=0.51). Conclusion CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation. PMID:27265814

[Circulating endothelial progenitor cell levels in treated hypertensive patients].

PubMed

Maroun-Eid, C; Ortega-Hernández, A; Abad, M; García-Donaire, J A; Barbero, A; Reinares, L; Martell-Claros, N; Gómez-Garre, D

2015-01-01

Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP<140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

TA-60 Warehouse and Salvage SWPPP Rev 2 Jan 2017-Final

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgin, Jillian Elizabeth

The Stormwater Pollution Prevention Team (PPT) for the TA-60-0002 Salvage and Warehouse Area consists of operations and management personnel from the facility, Multi-Sector General Permitting (MSGP) stormwater personnel from Environmental Compliance Programs (EPC-CP) organization, and Deployed Environmental Professionals. The EPC-CP representative is responsible for Laboratory compliance under the National Pollutant Discharge Elimination System (NPDES) permit regulations. The team members are selected on the basis of their familiarity with the activities at the facility and the potential impacts of those activities on stormwater runoff. The Warehouse and Salvage Yard are a single shift operation; therefore, a member of the PPT ismore » always present during operations.« less

Baseline tests of the EPC Hummingbird electric passenger vehicle

NASA Technical Reports Server (NTRS)

Slavik, R. J.; Maslowski, E. A.; Sargent, N. B.; Birchenough, A. G.

1977-01-01

The rear-mounted internal combustion engine in a four-passenger Volkswagen Thing was replaced with an electric motor made by modifying an aircraft generator and powered by 12 heavy-duty, lead-acid battery modules. Vehicle performance tests were conducted to measure vehicle maximum speed, range at constant speed, range over stop-and-go driving schedules, maximum acceleration, gradeability limit, road energy consumption, road power, indicated energy consumption, braking capability, battery charger efficiency, and battery characteristics. Test results are presented in tables and charts.

The Ortho-to-para Ratio of Water Molecules Desorbed from Ice Made from Para-water Monomers at 11 K

NASA Astrophysics Data System (ADS)

Hama, Tetsuya; Kouchi, Akira; Watanabe, Naoki

2018-04-01

Water has two nuclear-spin isomers: ortho- and para-H2O. Some observations of interstellar space and cometary comae have reported the existence of gaseous H2O molecules with anomalous ortho-to-para ratios (OPRs) less than the statistical value of three. This has been often used to estimate the formation temperature of ice on dust, which is inferred to be below 50 K. The relation between the nuclear-spin dynamics of H2O in ice at low temperatures and the OPR of gaseous H2O desorbed from the ice has yet to be explored in a laboratory. Consequently, the true meaning of the observed OPRs remains debated. We measure the OPR of H2O photodesorbed from ice made from para-H2O monomers at 11 K, which was prepared by the sublimation of Ne from a para-H2O/Ne matrix. The photodesorbed H2O molecules from the ice have the statistical OPR value of three, demonstrating the immediate nuclear-spin-state mixing of H2O toward the statistical value of ice even at 11 K. The OPR of H2O thermally desorbed from the ice also shows the expected statistical value. Our results indicate that the OPR of H2O desorbed from interstellar ice should be the statistical value regardless of the formation process of the ice, which cannot be used to deduce the ice-formation temperature. This study highlights the importance of interstellar gas-phase processes in understanding anomalous abundance ratios of nuclear-spin isomers of molecules in space.

Detection of the MW Transition Between Ortho and Para States

NASA Astrophysics Data System (ADS)

Kanamori, Hideto; Dehghani, Zeinab Tafti; Mizoguchi, Asao; Endo, Yasuki

2017-06-01

Thorough the detailed analysis of the hyperfine resolved rotational transitions, we have been pointed out that there exists not a little interaction between ortho and para states in the molecular Hamiltonian of S_2Cl_2. Using the ortho-para mixed molecular wavefunctions derived from the Hamiltonian, we calculated the transition moment and frequency of the ortho-para forbidden transitions in the cm- and mm-wave region, and picked up some promising candidate transitions for the spectroscopic detection. In the experiment, the S_2Cl_2 vapor with Ar buffer gas in a supersonic jet condition was used with FTMW spectrometer at National Chiao Tung University. As a result, seven hyperfine resolved rotational transitions in the cm-wave region were detected as the ortho-para transition at the predicted frequency within the experimental error range. The observed intensity was 10^{-3} smaller than that of an allowed transition, which is also consistent with the prediction. This is the first time the electric dipole transition between ortho and para states has been detected in a free isolated molecule. A. Mizoguchi, S. Ota, H. Kanamori, Y. Sumiyoshi, and Y. Endo, J. Mol. Spectrosc, 250, 86 (2008) Z. T. Dehghani, S. Ota, A. Mizoguchi and H. Kanamori, J. Phys. Chem. A, 117(39), 10041, (2013)

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

PubMed Central

Doñate, F; Juarez, J C; Burnett, M E; Manuia, M M; Guan, X; Shaw, D E; Smith, E L P; Timucin, C; Braunstein, M J; Batuman, O A; Mazar, A P

2008-01-01

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development. PMID:18253124

Patent prosecution at the European Patent Office: what is new for life sciences applicants?

PubMed

Lidén, Camilla; Setréus, Ellen

2011-06-01

During the last couple of years, the European Patent Office (EPO) has gradually implemented the so-called 'Raising the Bar' initiative, which is aimed at improving the quality of European patents and, in combination with speeding up the procedure for grant, reducing uncertainty for third parties. As a part of this initiative, a series of changes to the implementing regulations of the European Patent Convention (EPC) were introduced last year. Applicants now need to be sure of their position with regard to supportive experimental data and a thorough argumentation at an earlier stage in the prosecution of a patent application. When evaluating the criteria of inventive step (Art 56 EPC) and sufficiency of disclosure (Art 83 EPC), the EPO frequently refers to two decisions issued by the Boards of Appeal. These decisions are also used to determine whether it is appropriate to further support a disclosed technical effect or a scope of protection with experimental data produced after the date of filing of the patent application. In view of recent case law, it is evident that applicants cannot rely on post-filed experimental data as the only evidence for a technical effect or a certain scope of protection claimed in the application.

A Comparative Usage-Based Approach to the Reduction of the Spanish and Portuguese Preposition "Para"

ERIC Educational Resources Information Center

Gradoville, Michael Stephen

2013-01-01

This study examines the frequency effect of two-word collocations involving "para" "to," "for" (e.g. "fui para," "para que") on the reduction of "para" to "pa" (in Spanish) and "pra" (in Portuguese). Collocation frequency effects demonstrate that language speakers…

Preparation of ortho-para ratio controlled D2 gas for muon-catalyzed fusion.

PubMed

Imao, H; Ishida, K; Kawamura, N; Matsuzaki, T; Matsuda, Y; Toyoda, A; Strasser, P; Iwasaki, M; Nagamine, K

2008-05-01

A negative muon in hydrogen targets, e.g., D2 or D-T mixture, can catalyze nuclear fusions following a series of atomic processes involving muonic hydrogen molecular formation (muon-catalyzed fusion, muCF). The ortho-para state of D2 is a crucial parameter not only for enhancing the fusion rate but also to precisely investigate various muonic atom processes. We have developed a system for controlling and measuring the ortho-para ratio of D2 gas for muCF experiments. We successfully collected para-enriched D2 without using liquid-hydrogen coolant. Ortho-enriched D2 was also obtained by using a catalytic conversion method with a mixture of chromium oxide and alumina. The ortho-para ratio of D2 gas was measured with a compact Raman spectroscopy system. We produced large volume (5-30 l at STP), high-purity (less than ppm high-Z contaminant) D2 targets with a wide range of ortho-para ratios (ortho 20%-99%). By using the ortho-para controlled D2 in muCF experiments, we observed the dependence of muCF phenomena on the ortho-para ratio.

Rotational excitation of HCN by para- and ortho-H₂.

PubMed

Vera, Mario Hernández; Kalugina, Yulia; Denis-Alpizar, Otoniel; Stoecklin, Thierry; Lique, François

2014-06-14

Rotational excitation of the hydrogen cyanide (HCN) molecule by collisions with para-H2(j = 0, 2) and ortho-H2(j = 1) is investigated at low temperatures using a quantum time independent approach. Both molecules are treated as rigid rotors. The scattering calculations are based on a highly correlated ab initio 4-dimensional (4D) potential energy surface recently published. Rotationally inelastic cross sections among the 13 first rotational levels of HCN were obtained using a pure quantum close coupling approach for total energies up to 1200 cm(-1). The corresponding thermal rate coefficients were computed for temperatures ranging from 5 to 100 K. The HCN rate coefficients are strongly dependent on the rotational level of the H2 molecule. In particular, the rate coefficients for collisions with para-H2(j = 0) are significantly lower than those for collisions with ortho-H2(j = 1) and para-H2(j = 2). Propensity rules in favor of even Δj transitions were found for HCN in collisions with para-H2(j = 0) whereas propensity rules in favor of odd Δj transitions were found for HCN in collisions with H2(j ⩾ 1). The new rate coefficients were compared with previously published HCN-para-H2(j = 0) rate coefficients. Significant differences were found due the inclusion of the H2 rotational structure in the scattering calculations. These new rate coefficients will be crucial to improve the estimation of the HCN abundance in the interstellar medium.

Analyzing and Visualizing Cosmological Simulations with ParaView

NASA Astrophysics Data System (ADS)

Woodring, Jonathan; Heitmann, Katrin; Ahrens, James; Fasel, Patricia; Hsu, Chung-Hsing; Habib, Salman; Pope, Adrian

2011-07-01

The advent of large cosmological sky surveys—ushering in the era of precision cosmology—has been accompanied by ever larger cosmological simulations. The analysis of these simulations, which currently encompass tens of billions of particles and up to a trillion particles in the near future, is often as daunting as carrying out the simulations in the first place. Therefore, the development of very efficient analysis tools combining qualitative and quantitative capabilities is a matter of some urgency. In this paper, we introduce new analysis features implemented within ParaView, a fully parallel, open-source visualization toolkit, to analyze large N-body simulations. A major aspect of ParaView is that it can live and operate on the same machines and utilize the same parallel power as the simulation codes themselves. In addition, data movement is in a serious bottleneck now and will become even more of an issue in the future; an interactive visualization and analysis tool that can handle data in situ is fast becoming essential. The new features in ParaView include particle readers and a very efficient halo finder that identifies friends-of-friends halos and determines common halo properties, including spherical overdensity properties. In combination with many other functionalities already existing within ParaView, such as histogram routines or interfaces to programming languages like Python, this enhanced version enables fast, interactive, and convenient analyses of large cosmological simulations. In addition, development paths are available for future extensions.

Determination of inadvertent atrial capture during para-Hisian pacing.

PubMed

Obeyesekere, Manoj; Leong-Sit, Peter; Skanes, Allan; Krahn, Andrew; Yee, Raymond; Gula, Lorne J; Bennett, Matthew; Klein, George J

2011-08-01

Inadvertent capture of the atrium will lead to spurious results during para-Hisian pacing. We sought to establish whether the stimulation-to-atrial electrogram interval at the proximal coronary sinus (stim-PCS) or high right atrium (stim-HRA) could signal inadvertent atrial capture. Para-Hisian pacing with and without intentional atrial capture was performed in 31 patients. Stim-HRA and stim-PCS intervals were measured with atrial capture, His plus para-Hisian ventricular (H+V) capture, and para-Hisian ventricular (V) capture alone. The mean stim-HRA interval was significantly shorter with atrial capture (66 ± 18 ms) than with H+V (121 ± 27 ms, P < 0.001) or V capture alone (174 ± 38 ms, P < 0.001). The mean stim-PCS interval was significantly shorter with atrial capture (51 ± 16 ms) than with H+V (92 ± 22 ms, P<0.001) or V capture alone (146 ± 33 ms, P < 0.001). A stim-PCS < 60 ms (stim-HRA < 70 ms) was observed only with atrial capture. A stim-PCS >90 ms (stim-HRA >100 ms) was observed only in the absence of atrial capture. A stim-HRA of < 85 ms was highly specific and stim-PCS of < 85 ms highly sensitive at identifying atrial capture. Stim-HRA intervals of 75 to 97 ms and stim-PCS intervals of 65 to 88 ms were observed with either atrial, His, or para-Hisian ventricular capture without atrial capture. In this overlap zone, all patients demonstrated a stim-PCS or stim-HRA interval prolongation of at least 20 ms when the catheter was advanced to avoid deliberate atrial pacing. The QRS morphology was of limited value in distinguishing atrial capture due to concurrent ventricular or H+V capture, as observed in 20 of 31 (65%) patients. Stim-PCS and stim-HRA intervals can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS < 60 ms (or stim-HRA < 70 ms) and stim-PCS > 90 ms (or stim-HRA > 100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate

Norma para la Certificación de Aplicadores de Plaguicidas Revisada

EPA Pesticide Factsheets

La EPA emitió una propuesta para la revisión de la norma para la Certificación de Aplicadores de Plaguicidas. La norma ayudará a mantener nuestras comunidades seguras, salvaguardar el medio ambiente y reducir el riesgo a los que aplican los plaguicidas.

Conformational explosion: Understanding the complexity of short chain para-dialkylbenzene potential energy surfaces

NASA Astrophysics Data System (ADS)

Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

2018-05-01

The single-conformation ultraviolet and infrared spectroscopy of three short-chain para-dialkylbenzenes (para-diethylbenzene, para-dipropylbenzene, and para-dibutylbenzene) is reported for the jet-cooled, isolated molecules. The present study builds off previous work on single-chain n-alkylbenzenes, where an anharmonic local mode Hamiltonian method was developed to account for stretch-bend Fermi resonance in the alkyl CH stretch region [D. P. Tabor et al., J. Chem. Phys. 144, 224310 (2016)]. The jet-cooled molecules are interrogated using laser-induced fluorescence (LIF) excitation, fluorescence dip infrared spectroscopy, and dispersed fluorescence. The LIF spectra in the S1 ← S0 origin region show a dramatic increase in the number of resolved transitions with increasing length of the alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an "egg carton" shaped potential energy surface. A combination of electronic frequency shift and alkyl CH stretch infrared spectra is used to generate a consistent set of conformational assignments. Using these experimental techniques in conjunction with computational methods, subsets of origin transitions in the LIF excitation spectrum can be classified into different conformational families. Two conformations are resolved in para-diethylbenzene, seven in para-dipropylbenzene, and about nineteen in para-dibutylbenzene. These chains are largely independent of each other as there are no new single-chain conformations induced by the presence of a second chain. A cursory LIF excitation scan of para-dioctylbenzene shows a broad congested spectrum at frequencies consistent with interactions of alkyl chains with the phenyl π cloud.

Conformational explosion: Understanding the complexity of short chain para-dialkylbenzene potential energy surfaces.

PubMed

Mishra, Piyush; Hewett, Daniel M; Zwier, Timothy S

2018-05-14

The single-conformation ultraviolet and infrared spectroscopy of three short-chain para-dialkylbenzenes (para-diethylbenzene, para-dipropylbenzene, and para-dibutylbenzene) is reported for the jet-cooled, isolated molecules. The present study builds off previous work on single-chain n-alkylbenzenes, where an anharmonic local mode Hamiltonian method was developed to account for stretch-bend Fermi resonance in the alkyl CH stretch region [D. P. Tabor et al., J. Chem. Phys. 144, 224310 (2016)]. The jet-cooled molecules are interrogated using laser-induced fluorescence (LIF) excitation, fluorescence dip infrared spectroscopy, and dispersed fluorescence. The LIF spectra in the S 1 ← S 0 origin region show a dramatic increase in the number of resolved transitions with increasing length of the alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an "egg carton" shaped potential energy surface. A combination of electronic frequency shift and alkyl CH stretch infrared spectra is used to generate a consistent set of conformational assignments. Using these experimental techniques in conjunction with computational methods, subsets of origin transitions in the LIF excitation spectrum can be classified into different conformational families. Two conformations are resolved in para-diethylbenzene, seven in para-dipropylbenzene, and about nineteen in para-dibutylbenzene. These chains are largely independent of each other as there are no new single-chain conformations induced by the presence of a second chain. A cursory LIF excitation scan of para-dioctylbenzene shows a broad congested spectrum at frequencies consistent with interactions of alkyl chains with the phenyl π cloud.

Kit para aplicar la metodología de Lean en el gobierno

EPA Pesticide Factsheets

Este Kit para comenzar a aplicar la metodología Lean (Gobierno optimizado) ofrece información para ayudar a las agencias de protección ambiental a planificar e implementar iniciativas Lean exitosas.

Phosphorus sorption and buffering mechanisms in suspended sediments from the Yangtze Estuary and Hangzhou Bay, China

NASA Astrophysics Data System (ADS)

Li, M.; Whelan, M. J.; Wang, G.; White, S. M.

2012-12-01

The adsorption isotherm and the mechanism of the buffering effect are important controls on phosphorus behaviors in estuaries and are important for estimating phosphate concentrations in aquatic environments. In this paper, we derive phosphate adsorption isotherms in order to investigate sediment adsorption and buffering capacity for phosphorus discharged from sewage outfalls in the Yangtze Estuary and Hangzhou Bay near Shanghai, China. Experiments were also carried out at different temperatures in order to explore the buffering effects for phosphate. The results show that P sorption in sediments with low fine particle fractions was best described using exponential equations. Some P interactions between water and sediment may be caused by the precipitation of CaHPO4 from Ca2+ and HPO42- when the phosphate concentration in the liquid phase is high. Results from the buffering experiments suggest that the Zero Equilibrium Phosphate Concentrations (EPC0) vary from 0.014 mg l-1 to 0.061 mg l-1, which are consistent with measured phosphate concentrations in water samples collected at the same time as sediment sampling. Values of EPC0 and linear sorption coefficients (K) in sediments with high fine particle and organic matter contents are relatively high, which implies that they have high buffering capacity. Both EPC0 and K increase with increasing temperature, indicating a higher P buffering capacity at high temperatures.

Phosphorus sorption and buffering mechanisms in suspended sediments from the Yangtze Estuary and Hangzhou Bay, China

NASA Astrophysics Data System (ADS)

Li, M.; Whelan, M. J.; Wang, G. Q.; White, S. M.

2013-05-01

The adsorption isotherm and the mechanism of the buffering effect are important controls on phosphorus (P) behaviors in estuaries and are important for estimating phosphate concentrations in aquatic environments. In this paper, we derive phosphate adsorption isotherms in order to investigate sediment adsorption and buffering capacity for phosphorus discharged from sewage outfalls in the Yangtze Estuary and Hangzhou Bay near Shanghai, China. Experiments were also carried out at different temperatures in order to explore the buffering effects for phosphate. The results show that P sorption in sediments with low fine particle fractions was best described using exponential equations. Some P interactions between water and sediment may be caused by the precipitation of CaHPO4 from Ca2+ and HPO42- when the phosphate concentration in the liquid phase is high. Results from the buffering experiments suggest that the Zero Equilibrium Phosphate Concentrations (EPC0) vary from 0.014 mg L-1 to 0.061 mg L-1, which are consistent with measured phosphate concentrations in water samples collected at the same time as sediment sampling. Values of EPC0 and linear sorption coefficients (K) in sediments with high fine particle and organic matter contents are relatively high, which implies that they have high buffering capacity. Both EPC0 and K increase with increasing temperature, indicating a higher P buffering capacity at high temperatures.

The evolution of postpairing male mate choice.

PubMed

Lyu, Nan; Servedio, Maria R; Lloyd, Huw; Sun, Yue-Hua

2017-06-01

An increasing number of empirical studies in animals have demonstrated male mate choice. However, little is known about the evolution of postpairing male choice, specifically which occurs by differential allocation of male parental care in response to female signals. We use a population genetic model to examine whether such postpairing male mate choice can evolve when males face a trade-off between parental care and extra-pair copulations (EPCs). Specifically, we assume that males allocate more effort to providing parental care when mated to preferred (signaling) females, but they are then unable to allocate additional effort to seek EPCs. We find that both male preference and female signaling can evolve in this situation, under certain conditions. First, this evolution requires a relatively large difference in parental investment between males mated to preferred versus nonpreferred females. Second, whether male choice and female signaling alleles become fixed in a population versus cycle in their frequencies depends on the additional fecundity benefits from EPCs that are gained by choosy males. Third, less costly female signals enable both signaling and choice alleles to evolve under more relaxed conditions. Our results also provide a new insight into the evolution of sexual conflict over parental care. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Distinctive effects of CD34- and CD133-specific antibody-coated stents on re-endothelialization and in-stent restenosis at the early phase of vascular injury

PubMed Central

Wu, Xue; Yin, Tieying; Tian, Jie; Tang, Chaojun; Huang, Junli; Zhao, Yinping; Zhang, Xiaojuan; Deng, Xiaoyan; Fan, Yubo; Yu, Donghong; Wang, Guixue

2015-01-01

It is not clear what effects of CD34- and CD133-specific antibody-coated stents have on re-endothelialization and in-stent restenosis (ISR) at the early phase of vascular injury. This study aims at determining the capabilities of different coatings on stents (e.g. gelatin, anti-CD133 and anti-CD34 antibodies) to promote adhesion and proliferation of endothelial progenitor cells (EPCs). The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flow-induced shear stress, so that allowing for the growth of the cells on the slides for 48 h. The in vivo experiment using a rabbit model in which the coated stents with different substrates were implanted showed that anti-CD34 and anti-CD133 antibody-coated stents markedly reduced the intima area and restenosis than bare mental stents (BMS) and gelatin-coated stents. Compared with the anti-CD34 antibody-coated stents, the time of cells adhesion was longer and earlier present in the anti-CD133 antibody-coated stents and anti-CD133 antibody-coated stents have superiority in re-endothelialization and inhibition of ISR. In conclusion, this study demonstrated that anti-CD133 antibody as a stent coating for capturing EPCs is better than anti-CD34 antibody in promoting endothelialization and reducing ISR. PMID:26813006

Single- and double-walled carbon nanotubes enhance atherosclerogenesis by promoting monocyte adhesion to endothelial cells and endothelial progenitor cell dysfunction.

PubMed

Suzuki, Yuka; Tada-Oikawa, Saeko; Hayashi, Yasuhiko; Izuoka, Kiyora; Kataoka, Misa; Ichikawa, Shunsuke; Wu, Wenting; Zong, Cai; Ichihara, Gaku; Ichihara, Sahoko

2016-10-13

The use of carbon nanotubes has increased lately. However, the cardiovascular effect of exposure to carbon nanotubes remains elusive. The present study investigated the effects of pulmonary exposure to single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs) on atherosclerogenesis using normal human aortic endothelial cells (HAECs) and apolipoprotein E-deficient (ApoE -/- ) mice, a model of human atherosclerosis. HAECs were cultured and exposed to SWCNTs or DWCNTs for 16 h. ApoE -/- mice were exposed to SWCNTs or DWCNTs (10 or 40 μg/mouse) once every other week for 10 weeks by pharyngeal aspiration. Exposure to CNTs increased the expression level of adhesion molecule (ICAM-1) and enhanced THP-1 monocyte adhesion to HAECs. ApoE -/- mice exposed to CNTs showed increased plaque area in the aorta by oil red O staining and up-regulation of ICAM-1 expression in the aorta, compared with vehicle-treated ApoE -/- mice. Endothelial progenitor cells (EPCs) are mobilized from the bone marrow into the circulation and subsequently migrate to the site of endothelial damage and repair. Exposure of ApoE -/- mice to high-dose SWCNTs or DWCNTs reduced the colony-forming units of EPCs in the bone marrow and diminished their migration function. The results suggested that SWCNTs and DWCNTs enhanced atherosclerogenesis by promoting monocyte adhesion to endothelial cells and inducing EPC dysfunction.

The effect of long-term lithium treatment of bipolar disorder on stem cells circulating in peripheral blood.

PubMed

Ferensztajn-Rochowiak, Ewa; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy; Ratajczak, Mariusz Z; Michalak, Michal; Rybakowski, Janusz K

2017-02-01

To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD). The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8-40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis. In BD subjects not taking lithium the number of CD34 +  VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34 +  VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34 +  VSELs correlated negatively with the duration of lithium treatment and serum lithium concentration. Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress.

Mapping momentum-dependent electron-phonon coupling and nonequilibrium phonon dynamics with ultrafast electron diffuse scattering

NASA Astrophysics Data System (ADS)

Stern, Mark J.; René de Cotret, Laurent P.; Otto, Martin R.; Chatelain, Robert P.; Boisvert, Jean-Philippe; Sutton, Mark; Siwick, Bradley J.

2018-04-01

Despite their fundamental role in determining material properties, detailed momentum-dependent information on the strength of electron-phonon and phonon-phonon coupling (EPC and PPC, respectively) across the entire Brillouin zone has remained elusive. Here we demonstrate that ultrafast electron diffuse scattering (UEDS) directly provides such information. By exploiting symmetry-based selection rules and time resolution, scattering from different phonon branches can be distinguished even without energy resolution. Using graphite as a model system, we show that UEDS patterns map the relative EPC and PPC strength through their profound sensitivity to photoinduced changes in phonon populations. We measure strong EPC to the K -point TO phonon of A1' symmetry (K -A1' ) and along the entire TO branch between Γ -K , not only to the Γ -E2 g phonon. We also determine that the subsequent phonon relaxation of these strongly coupled optical phonons involve three stages: decay via several identifiable channels to TA and LA phonons (1 -2 ps), intraband thermalization of the non-equilibrium TA/LA phonon populations (30 -40 ps) and interband relaxation of the TA/LA modes (115 ps). Combining UEDS with ultrafast angle-resolved photoelectron spectroscopy will yield a complete picture of the dynamics within and between electron and phonon subsystems, helping to unravel complex phases in which the intertwined nature of these systems has a strong influence on emergent properties.

Vasculogenic and Angiogenic Pathways in Moyamoya Disease.

PubMed

Bedini, Gloria; Blecharz, Kinga G; Nava, Sara; Vajkoczy, Peter; Alessandri, Giulio; Ranieri, Michela; Acerbi, Francesco; Ferroli, Paolo; Riva, Daria; Esposito, Silvia; Pantaleoni, Chiara; Nardocci, Nardo; Zibordi, Federica; Ciceri, Elisa; Parati, Eugenio A; Bersano, Anna

2016-01-01

Moyamoya disease (MMD) is a slowly progressing steno-occlusive cerebrovascular disease. The typical moyamoya vessels, which originate from an initial stenosis of the internal carotid, highlight that increased and/or abnormal angiogenic, vasculogenic and arteriogenic processes are involved in the disease pathophysiology. Herein, we summarize the current knowledge on the most important signaling pathways involved in MMD vessel formation, particularly focusing on the expression of growth factors and function of endothelial progenitor cells (EPCs). Higher plasma concentrations of vascular endothelial growth factor, matrix metalloproteinase, hepatocyte growth factor, and interleukin-1β were reported in MMD. A specific higher level of basic fibroblast growth factor was also found in the cerebrospinal fluid of these patients. Finally, the number and the functionality of EPCs were found to be increased. In spite of the available data, the approaches and findings reported so far do not give an evident correlation between the expression levels of the aforementioned growth factors and MMD severity. Furthermore, the controversial results provided by studies on EPCs, do not permit to understand the true involvement of these cells in MMD pathophysiology. Further studies should thus be implemented to extend our knowledge on processes regulating both the arterial stenosis and the excessive formation of collateral vessels. Moreover, we suggest advances of integrated approaches and functional assays to correlate biological and clinical data, arguing for the development of new therapeutic applications for MMD.

Monitoring Environmental Performance Commitments in Construction Projects.

DOT National Transportation Integrated Search

2007-05-01

EPCs are measures implemented during project construction to reduce environmental impacts. These commitments are directed toward the Projects performance period only and focus primarily on reducing the impacts of construction equipment and trucks....

Sistemas Correctores de Campo Para EL Telescopio Cassegrain IAC80

NASA Astrophysics Data System (ADS)

Galan, M. J.; Cobos, F. J.

1987-05-01

El proyecto de instrumentación de mayor importancia que ha tenido el Instituto de Astrofisica de Canarias en los últimos afios ha sido el diseflo y construcción del te1escopio IAC8O. Este requería del esfuerzo con junto en mec´nica, óptica y electrónica, lo que facilitó la estructuración y el crecimiento de los respectivos grupos de trabajo, que posteriormente se integraron en departamentos En su origen (1977), el telescopio IAC80 fue concebido como un sistema clásico tipo Cassegrain, con una razón focal F/i 1.3 para el sistema Casse grain y una razón focal F/20 para el sistema Coudé. Posteriormente, aunque se mantuvo la filosofia de que el sistema básico fuera el F/11.3, se consideró conveniente el diseño de secundarios para razones focales F/16 y F/32, y se eliminó el de F/20. Sin embargo, dada la importancia relativa que un foco estrictamente fotográfico tiene en un telescopio moderno, diseñado básicamente para fotometría fotoeléctrica y con un campo util mínimamente de 40 minutos de arco, se decídió Ilevar a cabo el diseño de un secundario F/8 con un sistema corrector de campo, pero que estuviera formado únicamente por lentes con superficies esféricas para que asl su construcción fuera posible en España ó en México. La creciente utilización de detectores bidimensionales para fines de investigación astron6mica y la viabilidad de que en un futuro cercano éstos tengan un área sensible cada vez mayor, hicieron atractiva la idea de tener diseñado un sistema corrector de campo para el foco primario (F/3), con un campo útil mínimo de un grado, y también con la limitante de que sus componentes tuvieron sólamente supérficies esféricas. Ambos diseños de los sis-temas correctores de campo se llevaron a cabo, en gran medida, como parte de un proyecto de colaboración e intercambio en el área de diseño y evaluación de sistemas ópticos.

Quantum fluctuations increase the self-diffusive motion of para-hydrogen in narrow carbon nanotubes.

PubMed

Kowalczyk, Piotr; Gauden, Piotr A; Terzyk, Artur P; Furmaniak, Sylwester

2011-05-28

Quantum fluctuations significantly increase the self-diffusive motion of para-hydrogen adsorbed in narrow carbon nanotubes at 30 K comparing to its classical counterpart. Rigorous Feynman's path integral calculations reveal that self-diffusive motion of para-hydrogen in a narrow (6,6) carbon nanotube at 30 K and pore densities below ∼29 mmol cm(-3) is one order of magnitude faster than the classical counterpart. We find that the zero-point energy and tunneling significantly smoothed out the free energy landscape of para-hydrogen molecules adsorbed in a narrow (6,6) carbon nanotube. This promotes a delocalization of the confined para-hydrogen at 30 K (i.e., population of unclassical paths due to quantum effects). Contrary the self-diffusive motion of classical para-hydrogen molecules in a narrow (6,6) carbon nanotube at 30 K is very slow. This is because classical para-hydrogen molecules undergo highly correlated movement when their collision diameter approached the carbon nanotube size (i.e., anomalous diffusion in quasi-one dimensional pores). On the basis of current results we predict that narrow single-walled carbon nanotubes are promising nanoporous molecular sieves being able to separate para-hydrogen molecules from mixtures of classical particles at cryogenic temperatures. This journal is © the Owner Societies 2011

Preparation of ortho-para ratio controlled D{sub 2} gas for muon-catalyzed fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imao, H.; Ishida, K.; Matsuzaki, T.

2008-05-15

A negative muon in hydrogen targets, e.g., D{sub 2} or D-T mixture, can catalyze nuclear fusions following a series of atomic processes involving muonic hydrogen molecular formation (muon-catalyzed fusion, {mu}CF). The ortho-para state of D{sub 2} is a crucial parameter not only for enhancing the fusion rate but also to precisely investigate various muonic atom processes. We have developed a system for controlling and measuring the ortho-para ratio of D{sub 2} gas for {mu}CF experiments. We successfully collected para-enriched D{sub 2} without using liquid-hydrogen coolant. Ortho-enriched D{sub 2} was also obtained by using a catalytic conversion method with a mixturemore » of chromium oxide and alumina. The ortho-para ratio of D{sub 2} gas was measured with a compact Raman spectroscopy system. We produced large volume (5-30 l at STP), high-purity (less than ppm high-Z contaminant) D{sub 2} targets with a wide range of ortho-para ratios (ortho 20%-99%). By using the ortho-para controlled D{sub 2} in {mu}CF experiments, we observed the dependence of {mu}CF phenomena on the ortho-para ratio.« less

Relative Contributions of Agricultural Drift, Para-Occupational ...

EPA Pesticide Factsheets

Background: Increased pesticide concentrations in house dust in agricultural areas have been attributed to several exposure pathways, including agricultural drift, para-occupational, and residential use. Objective: To guide future exposure assessment efforts, we quantified relative contributions of these pathways using meta-regression models of published data on dust pesticide concentrations. Methods: From studies in North American agricultural areas published from 1995-2015, we abstracted dust pesticide concentrations reported as summary statistics (e.g., geometric means (GM)). We analyzed these data using mixed-effects meta-regression models that weighted each summary statistic by its inverse variance. Dependent variables were either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use). Results: For the drift pathway, predicted GMs decreased sharply and nonlinearly, with GMs 64% lower in homes 250 m versus 23 m from fields (inter-quartile range of published data) based on 52 statistics from 7 studies. For the para-occupational pathway, GMs were 2.3 times higher (95% confidence interval [CI]: 1.5-3.3; 15 statistics, 5 studies) in homes of farmers who applied pesticides more versus less recently or frequently. For the residential use pathway, GMs were 1.3 (95%CI: 1.1-1.4) and 1.5 (95%CI: 1.2-1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for

Sistemas Correctores de Campo Para EL Telescopio Ritchey-Chretien UNAM212

NASA Astrophysics Data System (ADS)

Cobos, F. J.; Galan, M. J.

1987-05-01

El telescopio UNAM2l2 fue inaugurado hace siete años y concebido para trabajar en las razones focales: f/7.5, F/13.5, F/27 y F/98. El diseño Ritchey-Chretién corresponde a la razón focal F/7.5 y el foco primario (F/2.286) no se consideró como utilizable para fotografía directa. En el Instituto de Astronomía de la UNAM, se diseñó y construyó un sistema corrector de campo para la razón focal F/7.5, que actualmente está en funcionamiento. Dentro de un programa de colaboración en diseflo y evaluación de sistemas ópticos, entre el Instituto de Astrofísica de Canarias y el Instituto de Astronomía de la UNAM, decidimos intentar el diseño de una correctora de campo para el foco primario del tȩlescopio UNAM212 bajo la consideración de que no son insalvables los problemas que implicaría su instalación y de que es muy posible que, en un futuro relativamente cercano, podamom tener un detector bidimenmional tipo Mepsicrón cuya área sensible haga tentadora la idea de construir la cámara directa para foco primario

Para Sport Athletic Identity from Competition to Retirement: A Brief Review and Future Research Directions.

PubMed

Guerrero, Michelle; Martin, Jeffrey

2018-05-01

The primary purpose of this article is to review the literature on para sport athletic identity and provide avenues for future research direction. First, the authors briefly describe the existing quantitative and qualitative research on para sport athletic identity and, thereby, illustrate the complexities para sport athletes experience regarding the way they describe their participation in competitive sport. Next, the authors describe how para sport athletes with acquired permanent disabilities and congenital disabilities face similar, yet unique, identity-related challenges. Finally, the authors argue that future researchers should consider examining para sport athletes' identity through narrative identity. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of new alternatives in wastewater treatment plants based on dynamic modelling and life cycle assessment (DM-LCA).

PubMed

Bisinella de Faria, A B; Spérandio, M; Ahmadi, A; Tiruta-Barna, L

2015-11-01

With a view to quantifying the energy and environmental advantages of Urine Source-Separation (USS) combined with different treatment processes, five wastewater treatment plant (WWTP) scenarios were compared to a reference scenario using Dynamic Modelling (DM) and Life Cycle Assessment (LCA), and an integrated DM-LCA framework was thus developed. Dynamic simulations were carried out in BioWin(®) in order to obtain a realistic evaluation of the dynamic behaviour and performance of plants under perturbation. LCA calculations were performed within Umberto(®) using the Ecoinvent database. A Python™ interface was used to integrate and convert simulation data and to introduce them into Umberto(®) to achieve a complete LCA evaluation comprising foreground and background processes. Comparisons between steady-state and dynamic simulations revealed the importance of considering dynamic aspects such as nutrient and flow peaks. The results of the evaluation highlighted the potential of the USS scenario for nutrient recovery whereas the Enhanced Primary Clarification (EPC) scenario gave increased biogas production and also notably decreased aeration consumption, leading to a positive energy balance. Both USS and EPC scenarios also showed increased stability of plant operation, with smaller daily averages of total nitrogen and phosphorus. In this context, USS and EPC results demonstrated that the coupled USS + EPC scenario and its combinations with agricultural spreading of N-rich effluent and nitritation/anaerobic deammonification could present an energy-positive balance with respectively 27% and 33% lower energy requirements and an increase in biogas production of 23%, compared to the reference scenario. The coupled scenarios also presented lesser environmental impacts (reduction of 31% and 39% in total endpoint impacts) along with effluent quality well within the specified limits. The marked environmental performance (reduction of global warming) when nitrogen is used

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

PubMed Central

Tsakiris, Ioannis; Torocsik, Daniel; Gyongyosi, Adrienn; Dozsa, Aniko; Szatmari, Istvan; Szanto, Attila; Soos, Gyorgyike; Nemes, Zoltan; Igali, Laszlo; Marton, Ildiko; Takats, Zoltan; Nagy, Laszlo; Dezso, Balazs

2012-01-01

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and

Family Caregiver Depressive Symptom and Grief Outcomes From the ENABLE III Randomized Controlled Trial.

PubMed

Dionne-Odom, J Nicholas; Azuero, Andres; Lyons, Kathleen D; Hull, Jay G; Prescott, Anna T; Tosteson, Tor; Frost, Jennifer; Dragnev, Konstantin H; Bakitas, Marie A

2016-09-01

Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die. To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. We conducted a randomized controlled trial (10/2010-9/2013) of an EPC telehealth intervention for CGs (n = 123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression (CES-D) scale and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between-group differences were estimated and tested using general linear models. For care recipients who died (n = 70), 44 CGs (early: n = 19; delayed: n = 25) completed after-death questionnaires. Mean depressive symptom scores (CES-D) for the early group was 14.6 (SD = 10.7) and for the delayed group was 17.6 (SD = 11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD = 4.9) and for the delayed group was 24.9 (SD = 6.9). Adjusted between-group differences were not statistically significant (CES-D: d = 0.07, P = 0.88; PG13: d = -0.21, P = 0.51). CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease.

PubMed

Marlicz, Wojciech; Zuba-Surma, Ewa; Kucia, Magda; Blogowski, Wojciech; Starzynska, Teresa; Ratajczak, Mariusz Z

2012-09-01

Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue/organ injury. We sought to determine whether these cells are mobilized into PB in patients with Crohn's disease (CD). Twenty-five patients with active CD, 20 patients in clinical remission, and 25 age-matched controls were recruited and PB samples harvested. The circulating CD133+/Lin-/CD45+ and CD34+/Lin-/CD45+ cells enriched for HSPCs, CD105+/STRO-1+/CD45- cells enriched for MSCs, CD34+/KDR+/CD31+/CD45-cells enriched for EPCs, and small CXCR4+CD34+CD133+ subsets of Lin-CD45- cells that correspond to the population of VSELs were counted by fluorescence-activated cell sorting (FACS) and evaluated by direct immunofluorescence staining for pluripotency embryonic markers and by reverse-transcription polymerase chain reaction (RT-PCR) for expression of messenger (m)RNAs for a panel of genes expressed in intestine epithelial stem cells. The serum concentration of factors involved in stem cell trafficking, such as stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were measured by enzyme-linked immunosorbent assay (ELISA). Our data indicate that cells expressing markers for MSCs, EPCs, and small Oct-4+Nanog+SSEA-4+CXCR4+lin-CD45- VSELs are mobilized into PB in CD. The mobilized cells also expressed at the mRNA level genes playing a role in development and regeneration of gastrointestinal epithelium. All these changes were accompanied by increased serum concentrations of VEGF and HGF. CD triggers the mobilization of MSCs, EPCs, and VSELs, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

NASA Astrophysics Data System (ADS)

Fuhrmann, A.; Staunton, J. R.; Nandakumar, V.; Banyai, N.; Davies, P. C. W.; Ros, R.

2011-02-01

The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their ability to 'bend and flex'.

Extra-pair copulation in the greater white-fronted goose

USGS Publications Warehouse

Ely, Craig R.

1989-01-01

Controlled experiments and quantitative field studies with both captive and wild waterfowl (Family Anatidae) have demonstrated that extra-pair copulations (EPCs, both forced and unforced) may be a viable alternative reproductive strategy for males (Mineau and Cooke 1979; Burns et al. 1980; Cheng et al. 1982, 1983; Afron 1985; Evarts and Williams 1987). In a review of EPCs in waterfowl, McKinney et al. (1983) stressed the need for additional information on the extent of such behavior in seemingly monogamous species of birds. Such information would increase our understanding of the extent of mixed reproductive strategies as formally hypothesized by Trivers (1972). Extra-pair copulations have been reported for only three of 22 (14%) species of geese and swans (Tribe Anserini), but are known to occur in 37 of 122 (30%) of the remaining species of waterfowl (McKinney et al. 1983, 1984; Welsh 1988). Socioecological differences between Anserini and most other anatids may provide insight into the evolution of extra-pair copulatory behavior, as male Anserini (unlike most other Anatidae) provide extensive parental care and maintain long-term pair bonds (Owen 1980, p. 76). Cuckolded male Anserini thus stand to lose more in the form of reproductive investment than other male anatids, which may invest less in a given clutch and generally have short-term pair bonds.I describe here an observation of extra-pair copulation in wild Greater White-fronted Geese (Anser albifrons frontalis). The observation is significant not only because it augments our meager documentation of this behavior within the Anserini, but it is the first observation of such behavior in a noncolonial goose (Mineau and Cooke 1979, McKinney et al. 1983). The occurrence of EPC behavior in a dispersal-nesting goose is important, as proximity to potential mates has been hypothesized as a factor possibly selecting for EPC behavior in geese (McKinney et al. 1983) and other species of monogamous birds (Gladstone 1979

Concentrating Solar Power Projects - Dadri ISCC Plant | Concentrating Solar

Science.gov Websites

Fresnel reflector Turbine Capacity: Gross: 14.0 MW Status: Under construction Start Year: 2017 Do you have , 2016 Start Production: September 2017 Participants Developer(s): Frenell Owner(s) (%): NTCP EPC

Astronomia para/com crianças carentes em Limeira

NASA Astrophysics Data System (ADS)

Bretones, P. S.; Oliveira, V. C.

2003-08-01

Em 2001, o Instituto Superior de Ciências Aplicadas (ISCA Faculdades de Limeira) iniciou um projeto pelo qual o Observatório do Morro Azul empreendeu uma parceria com o Centro de Promoção Social Municipal (CEPROSOM), instituição mantida pela Prefeitura Municipal de Limeira para atender crianças e adolescentes carentes. O CEPROSOM contava com dois projetos: Projeto Centro de Convivência Infantil (CCI) e Programa Criança e Adolescente (PCA), que atendiam crianças e adolescentes em Centros Comunitários de diversas áreas da cidade. Esses projetos têm como prioridades estabelecer atividades prazerosas para as crianças no sentido de retirá-las das ruas. Assim sendo, as crianças passaram a ter mais um tipo de atividade - as visitas ao observatório. Este painel descreve as várias fases do projeto, que envolveu: reuniões de planejamento, curso de Astronomia para as orientadoras dos CCIs e PCAs, atividades relacionadas a visitas das crianças ao Observatório, proposta de construção de gnômons e relógios de Sol nos diversos Centros Comunitários de Limeira e divulgação do projeto na imprensa. O painel inclui discussões sobre a aprendizagem de crianças carentes, relatos que mostram a postura das orientadoras sobre a pertinência do ensino de Astronomia, relatos do monitor que fez o atendimento no Observatório e o que o número de crianças atendidas representou para as atividades da instituição desde o início de suas atividades e, em particular, em 2001. Os resultados são baseados na análise de relatos das orientadoras e do monitor do Observatório, registros de visitas e matérias da imprensa local. Conclui com uma avaliação do que tal projeto representou para as Instituições participantes. Para o Observatório, em particular, foi feita uma análise com relação às outras modalidades de atendimentos que envolvem alunos de escolas e público em geral. Também é abordada a questão do compromisso social do Observatório na educação do

Autoguía para el telescopio 2,15 mts de CASLEO

NASA Astrophysics Data System (ADS)

Aballay, J. A.; Casagrande, A. R.; Pereyra, P. F.; Marún, A. H.

Se está desarrollando un sistema de autoguía para el telescopio de 2,15 mts. El mismo se realizará aprovechando el Offset Guider. Al ocular móvil de éste se vinculará alguna cámara digital (ST4-ST7-CH250) para lograr la visión del objeto. El funcionamiento del equipo será el siguiente: primero, dadas las coordenadas del objeto a observar, se tomarán las coordenadas del telescopio para que, a través de una base de datos, se determine un campo de objetos que sirvan para la cámara de visión, luego, la PC obtendrá el offset entre la estrella de observación y la estrella seleccionada como guía, este valor será trasladado a los motores que posicionarán en forma automática el ocular. Una vez que la estrella es visualizada en la cámara (monitor de PC ) se correrá el programa que guiará el telescopio automáticamente.

Cellular and molecular basis of wound healing in diabetes

PubMed Central

Brem, Harold; Tomic-Canic, Marjana

2007-01-01

Diabetic foot ulcers (DFUs), a leading cause of amputations, affect 15% of people with diabetes. A series of multiple mechanisms, including decreased cell and growth factor response, lead to diminished peripheral blood flow and decreased local angiogenesis, all of which can contribute to lack of healing in persons with DFUs. In this issue of the JCI, Gallagher and colleagues demonstrate that in diabetic mice, hyperoxia enhances the mobilization of circulating endothelial progenitor cells (EPCs) from the bone marrow to the peripheral circulation (see the related article beginning on page 1249). Local injection of the chemokine stromal cell–derived factor–1α then recruits these EPCs to the cutaneous wound site, resulting in accelerated wound healing. Thus, Gallagher et al. have identified novel potential targets for therapeutic intervention in diabetic wound healing. PMID:17476353

Contributions of emotional prosody comprehension deficits to the formation of auditory verbal hallucinations in schizophrenia.

PubMed

Alba-Ferrara, Lucy; Fernyhough, Charles; Weis, Susanne; Mitchell, Rachel L C; Hausmann, Markus

2012-06-01

Deficits in emotional processing have been widely described in schizophrenia. Associations of positive symptoms with poor emotional prosody comprehension (EPC) have been reported at the phenomenological, behavioral, and neural levels. This review focuses on the relation between emotional processing deficits and auditory verbal hallucinations (AVH). We explore the possibility that the relation between AVH and EPC in schizophrenia might be mediated by the disruption of a common mechanism intrinsic to auditory processing, and that, moreover, prosodic feature processing deficits play a pivotal role in the formation of AVH. The review concludes with proposing a mechanism by which AVH are constituted and showing how different aspects of our neuropsychological model can explain the constellation of subjective experiences which occur in relation to AVH. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electron Spin Polarization Transfer to ortho-H2 by Interaction of para-H2 with Paramagnetic Species: A Key to a Novel para → ortho Conversion Mechanism.

PubMed

Terenzi, Camilla; Bouguet-Bonnet, Sabine; Canet, Daniel

2015-05-07

We report that at ambient temperature and with 100% enriched para-hydrogen (p-H2) dissolved in organic solvents, paramagnetic spin catalysis of para → ortho hydrogen conversion is accompanied at the onset by a negative ortho-hydrogen (o-H2) proton NMR signal. This novel finding indicates an electron spin polarization transfer, and we show here that this can only occur if the H2 molecule is dissociated upon its transient adsorption by the paramagnetic catalyst. Following desorption, o-H2 is created until the thermodynamic equilibrium is reached. A simple theory confirms that in the presence of a static magnetic field, the hyperfine coupling between unpaired electrons and nuclear spins is responsible for the observed polarization transfer. Owing to the negative electron gyromagnetic ratio, this explains the experimental results and ascertains an as yet unexplored mechanism for para → ortho conversion. Finally, we show that the recovery of o-H2 magnetization toward equilibrium can be simply modeled, leading to the para → ortho conversion rate.

Sudan azo dyes and Para Red degradation by prevalent bacteria of the human gastrointestinal tract☆

PubMed Central

Xu, Haiyan; Heinze, Thomas M.; Paine, Donald D.; Cerniglia, Carl E.; Chen, Huizhong

2018-01-01

Sudan azo dyes have genotoxic effects and ingestion of food products contaminated with Sudan I, II, III, IV, and Para Red could lead to exposure in the human gastrointestinal tract. In this study, we examined thirty-five prevalent species of human intestinal bacteria to evaluate their capacity to degrade Sudan dyes and Para Red. Among these tested bacterial strains, 23, 13, 33, 30, and 29 out of 35 species tested were able to reduce Sudan I, II, III, IV, and Para Red, respectively, to some extent. Bifidobacterium infantis, Clostridium indolis, Enterococcus faecalis, Lactobacillus rhamnosus, and Ruminococcus obeum were able to reduce completely all four tested Sudan dyes and Para Red. Escherichia coli and Peptostreptococcus magnus were the only two strains that were not able to reduce any of the tested Sudan dyes and Para Red to any significant extent. Metabolites of the reduction of the tested Sudan dyes and Para Red by E. faecalis were isolated and identified by HPLC and LC/ESI-MS analyses and compared with authentic standards. Thus it appears that the ability to reduce Sudan dyes and Para Red except Sudan II is common among bacteria in the human colon. PMID:19580882

Predictors of outcomes and refractoriness in status epilepticus: A prospective study.

PubMed

Atmaca, Murat Mert; Bebek, Nerses; Baykan, Betül; Gökyiğit, Ayşen; Gürses, Candan

2017-10-01

The objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). This is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. Logistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6-198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3-103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3-148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0-2, 3-4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both

A novel method to guide classification of para swimmers with limb deficiency.

PubMed

Hogarth, Luke; Payton, Carl; Van de Vliet, Peter; Connick, Mark; Burkett, Brendan

2018-05-30

The International Paralympic Committee has directed International Federations that govern Para sports to develop evidence-based classification systems. This study defined the impact of limb deficiency impairment on 100 m freestyle performance to guide an evidence-based classification system in Para Swimming, which will be implemented following the 2020 Tokyo Paralympic games. Impairment data and competitive race performances of 90 international swimmers with limb deficiency were collected. Ensemble partial least squares regression established the relationship between relative limb length measures and competitive 100 m freestyle performance. The model explained 80% of the variance in 100 m freestyle performance, and found hand length and forearm length to be the most important predictors of performance. Based on the results of this model, Para swimmers were clustered into four-, five-, six- and seven-class structures using nonparametric kernel density estimations. The validity of these classification structures, and effectiveness against the current classification system, were examined by establishing within-class variations in 100 m freestyle performance and differences between adjacent classes. The derived classification structures were found to be more effective than current classification based on these criteria. This study provides a novel method that can be used to improve the objectivity and transparency of decision-making in Para sport classification. Expert consensus from experienced coaches, Para swimmers, classifiers and sport science and medicine personnel will benefit the translation of these findings into a revised classification system that is accepted by the Para swimming community. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lake Champlain TMDL Modeling Quality Assurance Project Plan

EPA Pesticide Factsheets

This document presents the quality assurance project plan for providing support to US EPA Region 1 in revising the Lake Champlain Total Maximum Daily Load, under Contract Number EP-C-08-004, Task Order 80.

Action mechanism of tyrosinase on meta- and para-hydroxylated monophenols.

PubMed

Fenoll, L G; Rodríguez-López, J N; Varón, R; García-Ruiz, P A; García-Cánovas, F; Tudela, J

2000-04-01

The relationship between the structure and activity of meta- and para-hydroxylated monophenols was studied during their tyrosinase-catalysed hydroxylation and the rate-limiting steps of the reaction mechanism were identified. The para-hydroxylated substrates permit us to study the effect of a substituent (R) in the carbon-1 position (C-1) of the benzene ring on the nucleophilic attack step, while the meta group permits a similar study of the effect on the electrophilic attack step. Substrates with a -OCH3 group on C-1, as p-hydroxyanisol (4HA) and m-hydroxyanisol (3HA), or with a -CH2OH group, as p-hydroxybenzylalcohol (4HBA) and m-hydroxybenzylalcohol (3HBA), were used because the effect of the substituent (R) size was assumed to be similar. However, the electron-donating effect of the -OCH3 group means that the carbon-4 position (C-4) is favoured for nucleophilic attack (para-hydroxylated substrates) or for electrophilic attack (meta-hydroxylated substrates). The electron-attracting effect of the -CH2OH group has the opposite effect, hindering nucleophilic (para) or electrophilic (meta) attack of C-4. The experimental data point to differences between the maximum steady-state rate (V(M)Max) of the different substrates, the value of this parameter depends on the nucleophilic and electrophilic attack. However, differences are greatest in the Michaelis constants (K(M)m), with the meta-hydroxylated substrates having very large values. The catalytic efficiency k(M)cat/K(M)m is much greater for thepara-hydroxylated substrates although it varies greatly between one substrate and the other. However, it varies much less in the meta-hydroxylated substrates since this parameter describes the power of the nucleophilic attack, which is weaker in the meta OH. The large increase in the K(M)m of the meta-hydroxylated substrates might suggest that the phenolic OH takes part in substrate binding. Since this is a weaker nucleophil than the para-hydroxylated substrates, the binding

Ro-vibrational Spectra of (para-H2 )N -CH4 in He Droplets.

PubMed

Hoshina, Hiromichi; Sliter, Russell; Ravi, Aakash; Kuma, Susumu; Momose, Takamasa; Vilesov, Andrey F

2016-11-18

In this work, we report on the infrared spectroscopic study of clusters of CH 4 molecules with up to N=80 para-hydrogen molecules assembled inside He droplets. Upon increase of the number of the added para-hydrogen molecules up to about N=12, both the rotational constant, B, and the origin frequency of the υ 3 band of CH 4 decrease gradually. In the range of 6 ≤N≤12, the spectra indicate some abrupt changes of B and υ 3 with both values being approximately constant at N≥12. The origin of this effect is discussed. Comparison of the spectra of methane molecules in para-hydrogen clusters to that in solid para-hydrogen is also presented. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identificación de Intervenciones para el Desarrollo Positivo de la Juventud

PubMed Central

Sardiñas, Lili M.; Padilla, Viviana; Aponte, Mari; Boscio, Ana Morales; Pedrogo, Coralee Pérez; Santiago, Betzaida; Morales, Ángela Pérez; Dávila, Paloma Torres; Cesáreo, Marizaida Sánchez

2017-01-01

Resumen En el mundo hay más personas en la etapa de la juventud que en cualquier otra etapa del desarrollo. La juventud en Puerto Rico enfrenta muchas situaciones que inciden en su desarrollo y preparación para la adultez. Por lo tanto, es imperante identificar intervenciones para el desarrollo positivo de la juventud que han demostrado ser basadas en la evidencia. Además, a partir de dicha identificación, desarrollar prácticas que ayuden a los jóvenes a desarrollarse para prevenir situaciones adversas, promover experiencias positivas y propiciar que los niños y jóvenes estén involucrados y comprometidos. Se identificaron 147 intervenciones a través de una revisión tradicional de la literatura científica estadounidense. Los resultados reflejan que las intervenciones atienden la reducción de factores de riesgo y el incremento de factores de protección. Sin embargo, ninguna intervención propicia que los niños y jóvenes estén involucrados y comprometidos con su desarrollo óptimo y con sus comunidades. No obstante, todas brindan herramientas que podrían ser de utilidad para fomentar dichas prácticas en el contexto de Puerto Rico. De las 147 intervenciones identificadas seis están diseñadas para la población puertorriqueña residente en la Isla. Con el propósito de hacer la información accesible a los profesionales y la comunidad se expandió la colección del Archivo de Programas y Prácticas Basadas en Evidencia para la Prevención. PMID:28919943

Development of quiet and durable porous Portland cement concrete paving materials

DOT National Transportation Integrated Search

2003-09-01

This report outlines the systematic research effort conducted in order to develop and characterize Enhanced Porosity Concrete (EPC) to mitigate the problem of tire-road interaction noise. The basic tenet of this research is that carefully introduced ...

ProUCL Version 4.0 Technical Guide

EPA Science Inventory

Statistical inference, including both estimation and hypotheses testing approaches, is routinely used to: estimate environmental parameters of interest, such as exposure point concentration (EPC) terms, not-to-exceed values, and background level threshold values (BTVs) for contam...

Concentrating Solar Power Projects - Casablanca | Concentrating Solar Power

Science.gov Websites

(Badajoz) Owner(s): ACS - COBRA group (100%) Technology: Parabolic trough Turbine Capacity: Net: 50.0 MW Participants Developer(s): ACS - COBRA group Owner(s) (%): ACS - COBRA group (100%) EPC Contractor: Cobra

PROUCL 4.0 SOFTWARE

EPA Science Inventory

Statistical inference, including both estimation and hypotheses testing approaches, is routinely used to: estimate environmental parameters of interest, such as exposure point concentration (EPC) terms, not-to-exceed values, and background level threshold values (BTVs) for contam...

Electrical detection of ortho–para conversion in fullerene-encapsulated water

PubMed Central

Meier, Benno; Mamone, Salvatore; Concistrè, Maria; Alonso-Valdesueiro, Javier; Krachmalnicoff, Andrea; Whitby, Richard J.; Levitt, Malcolm H.

2015-01-01

Water exists in two spin isomers, ortho and para, that have different nuclear spin states. In bulk water, rapid proton exchange and hindered molecular rotation obscure the direct observation of two spin isomers. The supramolecular endofullerene H2O@C60 provides freely rotating, isolated water molecules even at cryogenic temperatures. Here we show that the bulk dielectric constant of this substance depends on the ortho/para ratio, and changes slowly in time after a sudden temperature jump, due to nuclear spin conversion. The attribution of the effect to ortho–para conversion is validated by comparison with nuclear magnetic resonance and quantum theory. The change in dielectric constant is consistent with an electric dipole moment of 0.51±0.05 Debye for an encapsulated water molecule, indicating the partial shielding of the water dipole by the encapsulating cage. The dependence of bulk dielectric constant on nuclear spin isomer composition appears to be a previously unreported physical phenomenon. PMID:26299447

Imaging of blood plasma coagulation at supported lipid membranes.

PubMed

Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia

2011-12-15

The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Cyanobacterial distributions along a physico-chemical gradient in the Northeastern Pacific Ocean.

PubMed

Sudek, Sebastian; Everroad, R Craig; Gehman, Alyssa-Lois M; Smith, Jason M; Poirier, Camille L; Chavez, Francisco P; Worden, Alexandra Z

2015-10-01

The cyanobacteria Prochlorococcus and Synechococcus are important marine primary producers. We explored their distributions and covariance along a physico-chemical gradient from coastal to open ocean waters in the Northeastern Pacific Ocean. An inter-annual pattern was delineated in the dynamic transition zone where upwelled and eastern boundary current waters mix, and two new Synechococcus clades, Eastern Pacific Clade (EPC) 1 and EPC2, were identified. By applying state-of-the-art phylogenetic analysis tools to bar-coded 16S amplicon datasets, we observed higher abundance of Prochlorococcus high-light I (HLI) and low-light I (LLI) in years when more oligotrophic water intruded farther inshore, while under stronger upwelling Synechococcus I and IV dominated. However, contributions of some cyanobacterial clades were proportionally relatively constant, e.g. Synechococcus EPC2. In addition to supporting observations that Prochlorococcus LLI thrive at higher irradiances than other LL taxa, the results suggest LLI tolerate lower temperatures than previously reported. The phylogenetic precision of our 16S rRNA gene analytical approach and depth of bar-coded sequencing also facilitated detection of clades at low abundance in unexpected places. These include Prochlorococcus at the coast and Cyanobium-related sequences offshore, although it remains unclear whether these came from resident or potentially advected cells. Our study enhances understanding of cyanobacterial distributions in an ecologically important eastern boundary system. © 2014 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

PubMed Central

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-01-01

Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

PubMed

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-03-01

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

PubMed

Qi, Weiwei; Yang, Chuan; Dai, Zhiyu; Che, Di; Feng, Juan; Mao, Yuling; Cheng, Rui; Wang, Zhongxiao; He, Xuemin; Zhou, Ti; Gu, Xiaoqiong; Yan, Li; Yang, Xia; Ma, Jian-Xing; Gao, Guoquan

2015-04-01

Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/β-catenin signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression

PubMed Central

Nahas, Ziad; Anderson, Berry S.; Borckardt, Jeff; Arana, Ashley B.; George, Mark S.; Reeves, Scott T.; Takacs, Istvan

2010-01-01

Background Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression. Methods We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications. Results All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms—Self-Report were 54.9% (± 37.7) and 60.1% (± 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection. Conclusions Bilateral EpCS over anterior and midlateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted. PMID:19819427

Mitochondria in the middle: exercise preconditioning protection of striated muscle

PubMed Central

Rodriguez, Dinah A.; Hord, Jeffrey M.

2016-01-01

Abstract Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf‐1 and heat shock factor‐1 and up‐regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator‐1 (PGC‐1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia–reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ‐opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin‐1/PGC‐1 signalling) are central to the protective effects of exercise preconditioning. PMID:27060608

Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

2017-07-15

Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Concentrating Solar Power Projects - Andasol-2 | Concentrating Solar Power

Science.gov Websites

): ACS/Cobra Group Owner(s) (%): ACS/Cobra Group (100%) EPC Contractor: UTE CT Andasol-2: Cobra (80%) and (Model): UTE CT Andasol-2 (SKAL-ET) Mirror Manufacturer (Model): Flabeg (RP3) # of Heat Collector

J3Gen: A PRNG for Low-Cost Passive RFID

PubMed Central

Melià-Seguí, Joan; Garcia-Alfaro, Joaquin; Herrera-Joancomartí, Jordi

2013-01-01

Pseudorandom number generation (PRNG) is the main security tool in low-cost passive radio-frequency identification (RFID) technologies, such as EPC Gen2. We present a lightweight PRNG design for low-cost passive RFID tags, named J3Gen. J3Gen is based on a linear feedback shift register (LFSR) configured with multiple feedback polynomials. The polynomials are alternated during the generation of sequences via a physical source of randomness. J3Gen successfully handles the inherent linearity of LFSR based PRNGs and satisfies the statistical requirements imposed by the EPC Gen2 standard. A hardware implementation of J3Gen is presented and evaluated with regard to different design parameters, defining the key-equivalence security and nonlinearity of the design. The results of a SPICE simulation confirm the power-consumption suitability of the proposal. PMID:23519344

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratories (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors will be sending their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and then to the BCIL for performance evaluation. The technologies that will be tested are electro-chemical energy storage systems comprising of lead acid, lithium-ion or zinc-bromide. GS Battery and EPC Power have developed an energy storage systemmore » that utilizes zinc-bromide flow batteries to save fuel on a military microgrid. This report contains the testing results and some limited analysis of performance of the GS Battery, EPC Power HES RESCU.« less

Photodissociation dynamics of the ortho- and para-xylyl radicals

NASA Astrophysics Data System (ADS)

Pachner, Kai; Steglich, Mathias; Hemberger, Patrick; Fischer, Ingo

2017-08-01

The photodissociation dynamics of the C8H9 isomers ortho- and para-xylyl are investigated in a free jet. The xylyl radicals are generated by flash pyrolysis from 2-(2-methylphenyl)- and 2-(4-methylphenyl) ethyl nitrite and are excited into the D3 state. REMPI- spectra show vibronic structure and the origin of the transition is identified at 32 291 cm-1 for the para- and at 32 132 cm-1 for the ortho-isomer. Photofragment H-atom action spectra show bands at the same energy and thus confirm H-atom loss from xylyl radicals. To gain further insight into the photodissociation dynamics, velocity map images of the hydrogen atom photofragments are recorded. Their angular distribution is isotropic and the translational energy release is in agreement with a dissociation to products in their electronic ground state. Photodissociation of para-xylyl leads to the formation of para-xylylene (C8H8), while the data for ortho-xylyl agree much better with the isomer benzocyclobutene as the dominant molecular fragment rather than ortho-xylylene. In computations we identified a new pathway for the reaction ortho-xylyl → benzocyclobutene + H with a barrier of 3.39 eV (27 340 cm-1), which becomes accessible at the employed excitation energy. It proceeds via a combination of scissoring and rotational motion of the -CH2 and -CH3 groups. However, the observed rate constants measured by delaying the excitation and ionization laser with respect to each other are significantly faster than computed ones, indicating intrinsic non-RRKM behaviour. A comparably high value of around 30% of the excess energy is released as translation of the H-atom photofragment.

Photodissociation dynamics of the ortho- and para-xylyl radicals.

PubMed

Pachner, Kai; Steglich, Mathias; Hemberger, Patrick; Fischer, Ingo

2017-08-28

The photodissociation dynamics of the C 8 H 9 isomers ortho- and para-xylyl are investigated in a free jet. The xylyl radicals are generated by flash pyrolysis from 2-(2-methylphenyl)- and 2-(4-methylphenyl) ethyl nitrite and are excited into the D 3 state. REMPI- spectra show vibronic structure and the origin of the transition is identified at 32 291 cm -1 for the para- and at 32 132 cm -1 for the ortho-isomer. Photofragment H-atom action spectra show bands at the same energy and thus confirm H-atom loss from xylyl radicals. To gain further insight into the photodissociation dynamics, velocity map images of the hydrogen atom photofragments are recorded. Their angular distribution is isotropic and the translational energy release is in agreement with a dissociation to products in their electronic ground state. Photodissociation of para-xylyl leads to the formation of para-xylylene (C 8 H 8 ), while the data for ortho-xylyl agree much better with the isomer benzocyclobutene as the dominant molecular fragment rather than ortho-xylylene. In computations we identified a new pathway for the reaction ortho-xylyl → benzocyclobutene + H with a barrier of 3.39 eV (27 340 cm -1 ), which becomes accessible at the employed excitation energy. It proceeds via a combination of scissoring and rotational motion of the -CH 2 and -CH 3 groups. However, the observed rate constants measured by delaying the excitation and ionization laser with respect to each other are significantly faster than computed ones, indicating intrinsic non-RRKM behaviour. A comparably high value of around 30% of the excess energy is released as translation of the H-atom photofragment.

Rotational excitation of HCN by para- and ortho-H{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vera, Mario Hernández, E-mail: marhvera@gmail.com; InSTEC, Quinta de Los Molinos, Plaza, La Habana 10600; Kalugina, Yulia

Rotational excitation of the hydrogen cyanide (HCN) molecule by collisions with para-H{sub 2}( j = 0, 2) and ortho-H{sub 2}( j = 1) is investigated at low temperatures using a quantum time independent approach. Both molecules are treated as rigid rotors. The scattering calculations are based on a highly correlated ab initio 4-dimensional (4D) potential energy surface recently published. Rotationally inelastic cross sections among the 13 first rotational levels of HCN were obtained using a pure quantum close coupling approach for total energies up to 1200 cm{sup −1}. The corresponding thermal rate coefficients were computed for temperatures ranging from 5 to 100 K.more » The HCN rate coefficients are strongly dependent on the rotational level of the H{sub 2} molecule. In particular, the rate coefficients for collisions with para-H{sub 2}( j = 0) are significantly lower than those for collisions with ortho-H{sub 2}( j = 1) and para-H{sub 2}( j = 2). Propensity rules in favor of even Δj transitions were found for HCN in collisions with para-H{sub 2}( j = 0) whereas propensity rules in favor of odd Δj transitions were found for HCN in collisions with H{sub 2}( j ⩾ 1). The new rate coefficients were compared with previously published HCN-para-H{sub 2}( j = 0) rate coefficients. Significant differences were found due the inclusion of the H{sub 2} rotational structure in the scattering calculations. These new rate coefficients will be crucial to improve the estimation of the HCN abundance in the interstellar medium.« less

Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues.

PubMed

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-05-01

Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es ), electronic (σp ) and lipophilic (πp ) parameters of the para substituents. For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es ) are key determinants of this selectivity. © 2014 The British Pharmacological Society.

Quantitative structure–activity relationship analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-01-01

Background and Purpose Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure–activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es), electronic (σp) and lipophilic (πp) parameters of the para substituents. Experimental Approach For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key Results MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and Implications Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es) are key determinants of this selectivity. PMID:25438806

Summary of FY17 ParaChoice Accomplishments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levinson, Rebecca Sobel; West, Todd H.

As part of analysis support for FCTO, Sandia assesses the factors that influence the future of FCEVs and Hydrogen in the US vehicle fleet. Using ParaChoice, we model competition between FCEVs, conventional vehicles, and other alternative vehicle technologies in order to understand the drivers and sensitivities of adoption of FCEVs. ParaChoice leverages existing tools such as Autonomie (Moawad et al., 2016), AEO (U.S. Energy Information Administration, 2016), and the Macro System Model (Ruth et al., 2009) in order to synthesize a complete picture of the co-evolution of vehicle technology development, energy price evolution, and hydrogen production and pricing, with consumermore » demand for vehicles and fuel. We then assess impacts of FCEV market penetration and hydrogen use on green- house gas (GHG) emissions and petroleum consumption, providing context for the role of policy, technology development, infrastructure, and consumer behavior on the vehicle and fuel mix through parametric and sensitivity analyses.« less

Primer registro para Peru del genero Nielsonia Young, 1977 (Hemiptera: Cicadellidae: Cicadellinae: Cicadellini)

USDA-ARS?s Scientific Manuscript database

En este articulo se reporta por primera vez para el Peru una especies del genero Nielsonia Young, 1977, de material procedente del Departamento de Tumbes. El genero ha sido reportada anteriormente de Ecuador, como unico registro para Sudamerica, y America Central. El unico especimen hembra encontra...

Evaluation of Minimum Asphalt Concrete Thickness Criteria

DTIC Science & Technology

2008-10-01

9 Figure 6. Dry density versus moisture content for CH material... density measurements. ............................ 24 Figure 18. EPC installation in a crushed gravel base course layer...Construction Materials Materials Characterization Laboratory Testing Field Testing Test Section Construction Hydrometer, Modified Proctor , Specific

Differential regulation of ParaHox genes by retinoic acid in the invertebrate chordate amphioxus (Branchiostoma floridae).

PubMed

Osborne, Peter W; Benoit, Gérard; Laudet, Vincent; Schubert, Michael; Ferrier, David E K

2009-03-01

The ParaHox cluster is the evolutionary sister to the Hox cluster. Like the Hox cluster, the ParaHox cluster displays spatial and temporal regulation of the component genes along the anterior/posterior axis in a manner that correlates with the gene positions within the cluster (a feature called collinearity). The ParaHox cluster is however a simpler system to study because it is composed of only three genes. We provide a detailed analysis of the amphioxus ParaHox cluster and, for the first time in a single species, examine the regulation of the cluster in response to a single developmental signalling molecule, retinoic acid (RA). Embryos treated with either RA or RA antagonist display altered ParaHox gene expression: AmphiGsx expression shifts in the neural tube, and the endodermal boundary between AmphiXlox and AmphiCdx shifts its anterior/posterior position. We identified several putative retinoic acid response elements and in vitro assays suggest some may participate in RA regulation of the ParaHox genes. By comparison to vertebrate ParaHox gene regulation we explore the evolutionary implications. This work highlights how insights into the regulation and evolution of more complex vertebrate arrangements can be obtained through studies of a simpler, unduplicated amphioxus gene cluster.

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

PubMed Central

Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

2016-01-01

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

Guía para la evaluación del riesgo de los polinizadores

EPA Pesticide Factsheets

La Guía para la evaluación del riesgo de los polinizadores de la EPA es parte de una estrategia de la evaluación de los riesgos que presentan los pesticidas para las abejas a fin de mejorar la protección de los polinizadores.

Para-Nonylphenol Induces Apoptosis of U937 Human Monocyte Leukemia Cells in vitro.

PubMed

Santa, Kazuki; Ohsawa, Tomonori; Sakimoto, Takehiko

2016-01-01

Human autoimmune diseases are caused by a variety of factors, such as environmental chemicals, including para-nonylphenol. Macrophages play many critical roles in the regulation of immunity and the progression of autoimmune diseases. However, little information is available regarding the effects of para-nonylphenol on cellular signaling pathways and the death of these cells in vitro. Here, we show that very high concentrations of para-nonylphenol (50-100 μM) induce apoptosis in U937 human monocyte leukemia cells in a dose-dependent manner. Cell viability was judged using the trypan blue exclusion method. FACS analysis for DNA fragmentation was conducted, cellular signaling pathways were evaluated using western blot analysis, and caspase activity was measured by using substrates. U937 cells were differentiated by PMA. Treatment with > 50 μM para-nonylphenol induced apoptosis in U937 monocyte cells and MCF- 7 and MDA-MB231 human breast cancer cells. We found cytochrome c release from the mitochondria to the cytoplasm, DNA fragmentation, and decreased expression of anti-apoptotic protein Bcl-XL. Caspase 3 and 9 were induced, but caspase 1 and 3-inhibitor treatment suppressed apoptosis. Para-nonylphenol decreased the levels of activated AKT and increased the levels of activated JNK/SAPK at 15 min after treatment. Furthermore, with PMA treatment, U937 cells were differentiated into a macrophage-like phenotype and showed attenuated cell death against para-nonylphenol. As this assay system is simple and rapid, it may represent a useful artificial tool to clarify the signaling pathways of apoptotic cell death in human monocytes in vitro. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sobre la terapia génica para enfermedades de la retina.

PubMed

Fischer, M Dominik

2017-07-11

Las mutaciones en un gran número de genes provocan degeneración de la retina y ceguera sin que exista actualmente cura alguna. En las últimas décadas, la terapia génica para enfermedades de la retina ha evolucionado y se ha convertido en un nuevo y prometedor paradigma terapéutico para estas enfermedades poco comunes. Este artículo refleja las ideas y los conceptos que parten de la ciencia básica hacia la aplicabilidad de la terapia génica en el ámbito clínico. Se describen los avances y las reflexiones actuales sobre la eficacia de los ensayos clínicos en la actualidad y se discuten los posibles obstáculos y soluciones de cara al futuro de la terapia génica para enfermedades de la retina. © 2017 S. Karger AG, Basel.

Conformational Explosion: Understanding the Complexity of the Para-Dialkylbenzene Potential Energy Surfaces

NASA Astrophysics Data System (ADS)

Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

2017-06-01

This talk focuses on the single-conformation spectroscopy of small-chain para-dialkylbenzenes. This work builds on previous studies from our group on long-chain n-alkylbenzenes that identified the first folded structure in octylbenzene. The dialkylbenzenes are representative of a class of molecules that are common components of coal and aviation fuel and are known to be present in vehicle exhaust. We bring the molecules para-diethylbenzene, para-dipropylbenzene and para-dibutylbenzene into the gas phase and cool the molecules in a supersonic expansion. The jet-cooled molecules are then interrogated using laser-induced fluorescence excitation, fluorescence dip IR spectroscopy (FDIRS) and dispersed fluorescence. The LIF spectra in the S_{0}-S_{1} origin region show dramatic increases in the number of resolved transitions with increasing length of alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an 'egg carton' shape to the potential energy surface. We use a combination of electronic frequency shift and alkyl CH stretch infrared spectra to generate a consistent set of conformational assignments.

Nonrelativistic para-Lorentzian mechanics

NASA Astrophysics Data System (ADS)

Vargas, J. G.

1981-04-01

After reviewing the foundations of special relativity and the room left for rival theories, a set of nonrelativistic para-Lorentzian transformations is derived uniquely, based on (a) a weaker first principle, (b) the requirement that the transformations sought do not give rise to the clock “paradox” (in a refined version), and (c) the compliance of the transformations with the classical experiments of Michelson-Morley, Kennedy-Thorndike, and Ives-Stilwell. The corresponding dynamics is developed. Most of the experimental support of special relativity is reconsidered in the light of the new theory. It is concluded that the relativity of simultaneity has so far not been tested.

TELEMEDICINA: UN DESAFÍO PARA AMÉRICA LATINA

PubMed Central

Litewka, Sergio

2011-01-01

La telemedicina es una tendencia creciente en la prestación de los servicios médicos. Aunque la eficacia de esta práctica no ha estado bien establecida, es probable que los países en desarrollo compartirán este nuevo paradigma con los desarrollados. Los defensores de la telemedicina en América Latina sostienen que será una herramienta útil para reducir las disparidades y mejorar la accesibilidad de atención de salud. Aunque América Latina quizá se convierta en un lugar para la investigación e investigación de estos procedimientos, no está claro cómo la telemedicina podría contribuir a mejorar la accesibilidad para las poblaciones desfavorecidas, o coexistir con sistemas de atención de salud públicos crónicamente enfermos. Telemedicine is a growing trend in the provision of medical services. Although the effectiveness of this practice has not been well established, it is likely that developing countries will share this new paradigm with developed ones. Supporters of telemedicine in Latin America maintain that it will be a useful tool for reducing disparities and improving health care accessibility. Although Latin America might become a place for research and investigation of these procedures, it is not clear how telemedicine could contribute to improving accessibility for disadvantaged populations, or coexist with chronically ill-funded public healthcare systems. PMID:21625326

TELEMEDICINA: UN DESAFÍO PARA AMÉRICA LATINA.

PubMed

Litewka, Sergio

2005-01-01

La telemedicina es una tendencia creciente en la prestación de los servicios médicos. Aunque la eficacia de esta práctica no ha estado bien establecida, es probable que los países en desarrollo compartirán este nuevo paradigma con los desarrollados. Los defensores de la telemedicina en América Latina sostienen que será una herramienta útil para reducir las disparidades y mejorar la accesibilidad de atención de salud. Aunque América Latina quizá se convierta en un lugar para la investigación e investigación de estos procedimientos, no está claro cómo la telemedicina podría contribuir a mejorar la accesibilidad para las poblaciones desfavorecidas, o coexistir con sistemas de atención de salud públicos crónicamente enfermos.Telemedicine is a growing trend in the provision of medical services. Although the effectiveness of this practice has not been well established, it is likely that developing countries will share this new paradigm with developed ones. Supporters of telemedicine in Latin America maintain that it will be a useful tool for reducing disparities and improving health care accessibility. Although Latin America might become a place for research and investigation of these procedures, it is not clear how telemedicine could contribute to improving accessibility for disadvantaged populations, or coexist with chronically ill-funded public healthcare systems.