Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

<p>Abstract</p> <p>Objective</p> <p>To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction.</p> <p>Methods</p> <p>Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls.</p> <p>Results</p> <p>The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.</p> <p>Conclusion</p> <p>There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue.</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here:</p> <p><url>http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998</url>.</p

Hydrogen isotope separation using graphene-based membranes in liquid water

Hydrogen isotope separation has been effectively achieved using gaseous H2/D2 filtered through graphene/Nafion composite membranes. Nevertheless, deuteron nearly does not exist in the form of gaseous D2 in nature but in liquid water. Thus, it is a more feasible way to separate and enrich deuterium from water. Herein we have successfully transferred monolayer graphene to a rigid and porous polymer substrate PITEM (polyimide tracked film), which could avoid the swelling problem of the Nafion substrate, as well as keep the integrity of graphene. Meanwhile, defects in large area of CVD graphene could be successfully repaired by interfacial polymerization resulting in high separation factor. Moreover, a new model was proposed for the proton transport mechanism through monolayer graphene based on the kinetic isotope effect (KIE). In this model, graphene plays the significant role in the H/D separation process by completely breaking the O-H/O-D bond, which can maximize the KIE leading to prompted H/D separation performance. This work suggests a promising application of using monolayer graphene in industry and proposes a pronounced understanding of proton transport in grapheneComment: 10 pages, 4 figures (6pages, 6figures for SI

Delivery Efficiency of miR-21i-CPP-SWCNT and Its Inhibitory Effect on Fibrosis of the Renal Mesangial Cells

MicroRNA 21 (miR-21) was proved to cause renal fibrosis and the inhibition of miR-21 would improve the poor prognosis in renal cell carcinoma diseases. The complementary oligonucleotide of mature miR-21 was considered to be an effective intracellular miR-21 inhibitor (miR-21i). The directly effective delivery of miR-21i into fibrotic cell is a facile method for treatment of renal fibrosis. Herein, the miR-21i-CPP-SWCNT delivery system, synthesized via single-walled carbon nanotube (SWCNT) and cell-penetrating peptide (CPP), was taken as a novel fibrosis-targeting therapeutic carrier. The miR-21i and CPP firstly bind together via electrostatic forces, and subsequently miR-21i-CPP binds to the surface of SWCNTs via hydrophobic forces. CPP could endow the delivery system with targeting property, while SWCNT would enhance its penetrating ability. The exogenous miR-21i released from the designed miR-21i-CPP-SWCNTs had successfully inhibited the expression of fibrosis-related proteins in renal mesangial cells (RMCs). We found that the expression of TGF-β1 proteins was more sensitive to miR-21i-CPP-SWCNT than the expression of α-SMA proteins

In vivo coherent Raman imaging of the melanomagenesis-associated pigment pheomelanin

Melanoma is the most deadly form of skin cancer with a yearly global incidence over 232,000 patients. Individuals with fair skin and red hair exhibit the highest risk for developing melanoma, with evidence suggesting the red/blond pigment known as pheomelanin may elevate melanoma risk through both UV radiation-dependent and -independent mechanisms. Although the ability to identify, characterize, and monitor pheomelanin within skin is vital for improving our understanding of the underlying biology of these lesions, no tools exist for real-time, in vivo detection of the pigment. Here we show that the distribution of pheomelanin in cells and tissues can be visually characterized non-destructively and noninvasively in vivo with coherent anti-Stokes Raman scattering (CARS) microscopy, a label-free vibrational imaging technique. We validated our CARS imaging strategy in vitro to in vivo with synthetic pheomelanin, isolated melanocytes, and the Mc1re/e, red-haired mouse model. Nests of pheomelanotic melanocytes were observed in the red-haired animals, but not in the genetically matched Mc1re/e; Tyrc/c (“albino-red-haired”) mice. Importantly, samples from human amelanotic melanomas subjected to CARS imaging exhibited strong pheomelanotic signals. This is the first time, to our knowledge, that pheomelanin has been visualized and spatially localized in melanocytes, skin, and human amelanotic melanomas

Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data

This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure:activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances. Both diindolylmethane (DIM) and resveratrol are specifically-acting dietary anti-androgens. The EARs for several anti-androgens were therefore expressed relative to the EAR of DIM, and how this ‘dietary comparator ratio’ (DCR) approach may be used to make safety decisions was assessed using an exposure-led case study for an anti-androgenic botanical ingredient. This highlights a pragmatic approach which allows novel chemical exposures to be put into context against dietary exposures to natural anti-androgenic substances. The DCR approach may have utility for other modes of action where appropriate comparators can be identified

Multimodality microscopy and micro-Raman spectroscopy for in vivo skin characterization and diagnosis

Accurate and early diagnosis of skin diseases will improve clinical outcomes. Visual inspection alone has limited diagnostic accuracy, while biopsy followed by histopathology examination is invasive and time-consuming. The objective is to design and develop a multimodal optical instrument that provides biochemical and morphological information on human skin in vivo. Raman spectroscopy (RS) is capable of providing biochemical information of tissues. Reflectance confocal microscopy (RCM), which generates micron-level resolution images with capability of optical sectioning, can provide refractive-index-based morphological information of the skin. Multiphoton microscopy (MPM) could simultaneously provide biochemistry-based morphological information from two-photon fluorescence (TPF) and second-harmonic-generation (SHG) images. The thesis hypothesis is that a multimodality instrument combining RS, RCM, and MPM could be developed and provide complementary information in real-time for in vivo skin evaluation and aiding non-invasive diagnosis. A confocal Raman spectroscopy system was initially developed and tested in a study on in vivo mouse skin. Spectral biomarkers (899 and 1325-1330 cm-¹) were found to differentiate tumor-bearing skin from normal skin. A RCM system was then integrated with the spectroscopy system to guide spectral measurements. Noninvasive morphological and biochemical analysis was performed on ex vivo and in vivo human skin. The system was further enhanced by adding an MPM module that can image cellular structures with TPF signals from keratin, NADH, and melanin, as well as image elastic and colla ii gen fibers via TPF and SHG signals, respectively. The finalized system was utilized to noninvasively measure a cherry angioma lesion and its surrounding structures on the skin of a volunteer. Confocal Raman spectra from various regions-of-interest acquired under the guidance of MPM and RCM imaging showed different spectral patterns for blood vessels, keratinocytes, and dermal fibers. The system was also successfully used to perform imaging directed two-photon absorption based photothermolysis on ex vivo mouse skin. All the results showed positive evidence, well supporting the overall hypothesis. The developed multimodality system, capable of acquiring co-registered RCM, TPF and SHG images simultaneously at video-rate, and performing image-guided region-of-interest Raman spectral measurements of human skin in vivo, is a powerful tool for non-invasive skin evaluation and diagnosis.Medicine, Faculty ofGraduat

SIMULATION-BASED PERFORMANCE COMPARISONS OF GEOCAST ROUTING PROTOCOLS

Intelligent Transportation System (ITS)  is the main research domain for making road transport safer and more comfortable. For the sake of increasing the benefits of ITS, projects about Inter-Vehicle Communication (IVC)  system have been proposed to make communications among vehicles possible, to exchange traffic information and avoid accidents. In order to create communication network among vehicles or between vehicles and infrastructure,  Vehicular Ad hoc Networks (VANETs) has been proposed. Many applications in VANETs need to send messages to vehicles within a specific geographic region. This behavior is called geocast and this specific geographic region is called the Zone of Relevance (ZOR). Some routing protocols which are related to Geocast have been proposed in literature for VANETs. So it is significant to evaluate and compare the performance of these known Geocast routing protocols. In this thesis, categories of the routing protocols, as well as communication forwarding schemes are introduced. The routing protocols in VANETs are also summarized and compared. In order to evaluate the performance of these protocols, the evaluation methods are proposed and then a Geocast routing simulator is designed and used to simulate the Geocast network environment and several Geocast routing protocols