Endoglin Regulates Cyclooxygenase-2 Expression and Activity

Jerkic, Mirjana[et alt.] 9 p.-8 fig.The endoglin heterozygous (Eng+/−) mouse, which serves as a model of hereditary hemorrhagic telangiectasia (HHT), was shown to express reduced levels of endothelial NO synthase (eNOS) with impaired activity. Because of intricate changes in vasomotor function in the Eng+/− mice and the potential interactions between the NO- and prostaglandin-producing pathways, we assessed the expression and function of cyclooxygenase (COX) isoforms. A specific upregulation of COX-2 in the vascular endothelium and increased urinary excretion of prostaglandin E2 were observed in the Eng+/− mice. Specific COX-2 inhibition with parecoxib transiently increased arterial pressure in Eng+/− but not in Eng+/+ mice. Transfection of endoglin in L6E9 myoblasts, shown previously to stimulate eNOS expression, led to downregulation of COX-2 with no change in COX-1. In addition, COX-2 promoter activity and protein levels were inversely correlated with endoglin levels, in doxycyclin-inducible endothelial cells. Chronic NO synthesis inhibition with Nω-nitro-l-arginine methyl ester induced a marked increase in COX-2 only in the normal Eng+/+ mice. Nω-nitro-l-arginine methyl ester also increased COX-2 expression and promoter activity in doxycyclin-inducible endoglin expressing endothelial cells, but not in control cells. The level of COX-2 expression following transforming growth factor-β1 treatment was less in endoglin than in mock transfected L6E9 myoblasts and was higher in human endothelial cells silenced for endoglin expression. Our results indicate that endoglin is involved in the regulation of COX-2 activity. Furthermore, reduced endoglin levels and associated impaired NO production may be responsible, at least in part, for augmented COX-2 expression and activity in the Eng+/− miceThis work was supported by grants from Ministerio de Educacion y Ciencia (SAF2001/1701 to J.M.L.-N. and SAF2004–01390 to C.B.), Fondo de Investigación Sanitaria (PI020200 to C.B.), HHT Foundation International to C.B., and by the Heart and Stroke Foundation of Canada (T5016) to M.L. M.J. was supported by a Fellowship from Instituto Reina Sofía de Investigación Nefrológica. C.P.H.V. was supported by NIH grant #P2015555 from the National Center for Research ResourcesPeer reviewe

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system

Stratus Ocean Reference Station (20˚S, 85˚W), mooring recovery and deployment cruise, R/V Ron Brown cruise 04-11, December 5 - December 24, 2004

The Ocean Reference Station at 20° S, 85° W under the stratus clouds west of northern Chile and Peru is being maintained to provide ongoing, climate-quality records of surface meteorology, of air-sea fluxes of heat, freshwater, and momentum, and of upper ocean temperature, salinity, and velocity variability. The Stratus Ocean Reference Station (ORS Stratus) is supported by the National Oceanic and Atmospheric Administration’s (NOAA) Climate Observation Program. It is recovered and redeployed annually, with cruises that have come between October and December. During the December 2004 cruise of NOAA's R/V Ronald H. Brown to the ORS Stratus site, the primary activities where the recovery of the WHOI surface mooring that had been deployed in November 2003, the deployment of a new WHOI surface mooring at that site, the in-situ calibration of the buoy meteorological sensors by comparison with instrumentation put on board by staff of the NOAA Environmental Technology Laboratory (ETL), and observations of the stratus clouds and lower atmosphere by NOAA ETL and Jason Tomlinson from Texas A&M. The ORS Stratus buoys are equipped with two Improved Meteorological systems, which provide surface wind speed and direction, air temperature, relative humidity, barometric pressure, incoming shortwave radiation, incoming longwave radiation, precipitation rate, and sea surface temperature. The IMET data are made available in near real time using satellite telemetry. The mooring line carries instruments to measure ocean salinity, temperature, and currents. The ETL instrumentation used during the 2004 cruise included cloud radar, radiosonde balloons, and sensors for mean and turbulent surface meteorology. The atmospheric observations also benefited from the C-Band radar mounted on the R/V Ronald H. Brown. In addition to this work, buoy work was done in support of the Chilean Navy Hydrographic and Oceanographic Service (SHOA). A tsunami warning mooring was reinstalled at 75°W, 20°S for SHOA, after the previous buoy installed last year failed. SHOA personnel were onboard to direct the deployment and to gain experience. Four students from the University of Concepcion collected hydrographic data and water samples. One other Chilean student from the University of Chile was involved in the atmospheric sampling program, with a particular focus on the near coast jet. Finally, the cruise hosted a teacher participating in NOAA's Teacher at Sea Program, Mary Esther Cook, who used her experience to develop lessons for her class back in Arkansas.Funding was provided by the National Oceanic and Atmospheric Administration under Contract Number NA17RJ1225

Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation

Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. Methods We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. Results We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. Conclusions This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

Nature of Cardiac Rehabilitation Around the Globe

BackgroundCardiac rehabilitation (CR) is a clinically-effective but complex model of care. The purpose of this study was to characterize the nature of CR programs around the world, in relation to guideline recommendations, and compare this by World Health Organization (WHO) region.MethodsIn this cross-sectional study, a piloted survey was administered online to CR programs globally. Cardiac associations and local champions facilitated program identification. Quality (benchmark of ≥ 75% of programs in a given country meeting each of 20 indicators) was ranked. Results were compared by WHO region using generalized linear mixed models.Findings111/203 (54.7%) countries in the world offer CR; data were collected in 93 (83.8%; N = 1082 surveys, 32.1% program response rate). The most commonly-accepted indications were: myocardial infarction (n = 832, 97.4%), percutaneous coronary intervention (n = 820, 96.1%; 0.10), and coronary artery bypass surgery (n = 817, 95.8%). Most programs were led by physicians (n = 680; 69.1%). The most common CR providers (mean = 5.9 ± 2.8/program) were: nurses (n = 816, 88.1%; low in Africa, p

Cardiac Rehabilitation Availability and Density around the Globe

BackgroundDespite the epidemic of cardiovascular disease and the benefits of cardiac rehabilitation (CR), availability is known to be insufficient, although this is not quantified. This study ascertained CR availability, volumes and its drivers, and density.MethodsA survey was administered to CR programs globally. Cardiac associations and local champions facilitated program identification. Factors associated with volumes were assessed using generalized linear mixed models, and compared by World Health Organization region. Density (i.e. annual ischemic heart disease [IHD] incidence estimate from Global Burden of Disease study divided by national CR capacity) was computed.FindingsCR was available in 111/203 (54.7%) countries; data were collected in 93 (83.8% country response; N?=?1082 surveys, 32.1% program response rate). Availability by region ranged from 80.7% of countries in Europe, to 17.0% in Africa (p

TGF-_1 induce la expresion y secrecion de uroquinasa en queratinocitos transformados de piel de raton Implicaciones en la progresion maligna

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Expression of JNK kinases in THP-1 cells treated with Ru(II) complexes

C-Jun N-terminalne kinaze (JNK) spadaju u mitogen-aktivirane protein kinaze (MAPK) i imaju važnu ulogu u kontroli niza ćelijskih procesa uključujući proliferaciju, kancerogenezu i apoptozu. Kompleksi rutenijuma pokazali su izuzetan potencijal kao mogući citostatici. Upravo iz ovih razloga ispitivan je mehanizam delovanja kompleksa Ru(II) sa N-alkilfenotiazinima (hlorpromazinom, trifluoperazinom i tioridazinom) na signalne parametre (t-JNK, p-JNK i β-aktin) u THP-1 ćelijama humane leukemije. U ćelijama tretiranim kompleksom sa fluoperazinom u koncentraciji od 10 μM (IC50 je 10,5 μM) ekspresija t-JNK povećana je za 47,45%, dok je ekspresija p-JNK dvostruko veća u poređenju sa netretiranim ćelijama, što sugeriše da su t-JNK i p-JNK uključeni u apoptozu ovih ćelija.The c-Jun N-terminal kinase (JNK) belongs to the family of mitogen-activated protein kinases (MAPKs) that play an important role in the control of a number of celular processes, including proliferation, cancerogenesis and apoptosis. Ruthenium complexes have shown remarkable potential as possible cytostatics. Precisely for these reasons, the mechanism of action of Ru(II) complexes with N-alkylphenothiazines (chlorpromazine, trifluoperazine, and thioridazine) on signalling parameters (t-JNK, p-JNK and β-actin) in THP-1 human leucemic cells was investigated. In cells treated with fluoperazine complex at a concentration of 10 μM (IC50 is 10.5 μM), an increased expression of t-JNK by 47.45% was found while the expression of p-JNK was twice higher compared to untreated cells, suggesting that t-JNK and p-JNK are involved in the apoptosis of these cells.Book of abstract