Erythrocyte nanovesicles: Biogenesis, biological roles and therapeutic approach Erythrocyte nanovesicles

AbstractNanovesicles (NVs) represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs). Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis

Gender and Tahrir Square: contesting the state and imagining a new nation

This article argues that the concepts of ‘State’ and ‘Nation’ should be treated as separate from one another, hence, more than one image of the nation is possible at one given time. During the early days of the January 2011 Egyptian revolution, a contestation emerged between Mubarak’s state and the protesters in Tahrir Square over the image and notion of the Egyptian nation. Both the state and the protesters attempted to exclude one another from their respective discourse of the Egyptian nation. While reflecting back on a number of women’s voices who joined the early days of the Tahrir Square protests and using qualitative fieldwork interviews with Cairo-based feminist and political activists, this article points to the complexity of a newly forged image of Egyptian nationhood. In Tahrir Square, this image appeared to be largely framed within gendered criteria where notions of manhood and hyper visible gender equality were intrinsically linked to the broader objective of removing Mubarak and his regime. This raises the question of whether new gender paradigms of equality can continue to exist beyond Tahrir Square’s imagination of a ‘new’ nation

Influence of pravastatin chitosan nanoparticles on erythrocytes cholesterol and redox homeostasis: An in vitro study

AbstractThe objective of this study was to develop and characterize chitosan nanoparticles (CSNPs) to increase efficacy of pravastatin (PR) on erythrocytes redox status. CSNPs and PR loaded CSNPs (PRCSNPs) were prepared by ionic gelation method. The particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) were used to investigate physicochemical characters of the prepared nanoparticles. The present results revealed that CSNPs and PRCSNPs have nanosize about 90nm with spherical shape, positive zeta potential and prolonged PR release. Moreover, DSC and FTIR indicated no chemical interactions between PR and CS. In vitro studies revealed that, erythrocyte uptake of PR from PRCSNPs was higher than free PR solution. Incubation of erythrocytes in high cholesterol plasma, hypercholesterolemia (HC), increases membrane cholesterol, erythrocyte hemolysis, oxidized glutathione (GSH), protein carbonyl (PCC), and malondialdeyhe (MDA). However, HC significantly decreases PR uptake by erythrocytes, superoxide dismutase (SOD), glutathione peroxidase (GPx) catalase (CAT) activities, reduced GSH and nitrite levels compared to control. By contrast, treatment of HC with PR plus CS as free drug or nanostructure formula keeps the measured parameters at values near that of control. The effect of CSNPs and PRCSNPs on redox status of erythrocytes was more prominent than free drugs. In conclusion, PRCSNPs are promising drug carrier to deliver PR into erythrocytes, moreover, PRCSNPs possess promising characteristics with high biological safety for treatment of HC induced disruption of redox homeostasis

Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability

In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy

Multiwavelength Observations of 1ES 1959+650, One Year After the Strong Outburst of 2002

In April-May 2003, the blazar 1ES 1959+650 showed an increased level of X-ray activity. This prompted a multiwavelength observation campaign with the Whipple 10 m gamma-ray telescope, the Rossi X-ray Timing Explorer, the Bordeaux Optical Observatory, and the University of Michigan Radio Astrophysical Observatory. We present the multiwavelength data taken from May 2, 2003 to June 7, 2003 and compare the source characteristics with those measured during observations taken during the years 2000 and 2002. The X-ray observations gave a data set with high signal-to-noise light curves and energy spectra; however, the gamma-ray observations did not reveal a major TeV gamma-ray flare. Furthermore, we find that the radio and optical fluxes do not show statistically significant deviations from those measured during the 2002 flaring periods. While the X-ray flux and X-ray photon index appear correlated during subsequent observations, the apparent correlation evolved significantly between the years 2000, 2002, and 2003. We discuss the implications of this finding for the mechanism that causes the flaring activity.Comment: 17 pages, 6 figures, 2 table

Detection of the BL Lac Object H1426+428 at TeV Gamma Ray Energies

A very high energy (VHE) gamma-ray signal has been detected at the 5.4 sigma level from H1426+428, an x-ray selected BL Lacertae object at a redshift of 0.129. The object was monitored from 1995 - 1998 with the Whipple 10m imaging atmospheric Cherenkov telescope as part of a general blazar survey; the results of these observations, although not statistically significant, were consistently positive. X-ray observations of H1426+428 during 1999 with the BeppoSAX instrument revealed that the peak of its synchrotron spectrum occurs at > 100 keV, leading to the prediction of observable TeV emission from this object. H1426+428 was monitored extensively at the Whipple Observatory during the 1999, 2000, and 2001 observing seasons. The strongest TeV signals were detected in 2000 and 2001. During 2001, an integral flux of 2.04 +/- 0.35 x10e-11 cm-2 s-1 above 280 GeV was recorded from H1426+428. The detection of H1426+428 supports the idea that, as also seen in Markarian 501 and 1ES2344+514, BL Lacertae objects with extremely high synchrotron peak frequencies produce gamma rays in the TeV range.Comment: 35 pages, 7 figures, accepted by ApJ Two upper limits in Table 3 (upper limits for 1995 and 1997) are different from the ApJ versio

Multiwavelength Observations of the Blazar Mrk 421 in December 2002 and January 2003

We report on a multiwavelength campaign on the TeV gamma-ray blazar Markarian (Mrk) 421 performed during December 2002 and January 2003. These target of opportunity observations were initiated by the detection of X-ray and TeV gamma-ray flares with the All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer (RXTE) and the 10 m Whipple gamma-ray telescope.The campaign included observational coverage in the radio (University of Michigan Radio Astronomy Observatory), optical (Boltwood, La Palma KVA 0.6m, WIYN 0.9m), X-ray (RXTE pointed telescopes), and TeV gamma-ray (Whipple and HEGRA) bands. At TeV energies, the observations revealed several flares at intermediate flux levels, peaking between 1 and 1.5 times the flux from the Crab Nebula. While the time averaged spectrum can be fitted with a single power law of photon index Gamma =2.8, we find some evidence for spectral variability. Confirming earlier results, the campaign reveals a rather loose correlation between the X-ray and TeV gamma-ray fluxes. In one case, a very strong X-ray flare is not accompanied by a comparable TeV gamma-ray flare. Although the source flux was variable in the optical and radio bands, the sparse sampling of the optical and radio light curves does not allow us to study the correlation properties in detail. We present a simple analysis of the data with a synchrotron-self Compton model, emphasizing that models with very high Doppler factors and low magnetic fields can describe the data.Comment: Accepted for publication in the Astrophysical Journa

Longevity-Related Gene Transcriptomic Signature in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) (grade IV astrocytoma) has been assumed to be the most fatal type of glioma with low survival and high recurrence rates, even after prompt surgical removal and aggressive courses of treatment. Transcriptional reprogramming to stem cell-like state could explain some of the deregulated molecular signatures in GBM disease. The present study aimed to quantify the expression profiling of longevity-related transcriptional factors SOX2, OCT3/4, and NANOG to evaluate their diagnostic and performance values in high-grade gliomas. Forty-four specimens were obtained from glioblastoma patients (10 females and 34 males). Quantitative real-time polymerase chain reaction was applied for relative gene expression quantification. In silico network analysis was executed. NANOG and OCT3/4 mRNA expression levels were significantly downregulated while that of SOX2 was upregulated in cancer compared to noncancer tissues. Receiver operating characteristic curve analysis showed high diagnostic performance of NANOG and OCT3/4 than SOX2. However, the aberrant expressions of the genes studied were not associated with the prognostic variables in the current population. In conclusion, the current study highlighted the aberrant expression of certain longevity-associated transcription factors in glioblastoma multiforme which may direct the attention towards new strategies in the treatment of such lethal disease

VERITAS: the Very Energetic Radiation Imaging Telescope Array System

The Very Energetic Radiation Imaging Telescope Array System (VERITAS) represents an important step forward in the study of extreme astrophysical processes in the universe. It combines the power of the atmospheric Cherenkov imaging technique using a large optical reflector with the power of stereoscopic observatories using arrays of separated telescopes looking at the same shower. The seven identical telescopes in VERITAS, each of aperture 10 m, will be deployed in a filled hexagonal pattern of side 80 m; each telescope will have a camera consisting of 499 pixels with a field of view of 3.5 deg VERITAS will substantially increase the catalog of very high energy (E > 100GeV) gamma-ray sources and greatly improve measurements of established sources.Comment: 44 pages, 16 figure