Inhibition of myocardial remodeling through miR-150/TET3 axis after AMI.

BACKGROUND: Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear. OBJECTIVES: We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway. METHODS: On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6Chigh monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6Chigh/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6Chigh/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6Chigh/low monocytes were further determined. RESULTS: We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn't reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6Clow monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/ß-actin vs. 0.99 ± 0.12/ß-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6Clow monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001). CONCLUSIONS: miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes.

Functionalized Periodic Mesoporous Silica Nanoparticles for Inhibiting the Progression of Atherosclerosis by Targeting Low-Density Lipoprotein Cholesterol.

Atherosclerotic disease is a substantial global burden, and existing treatments, such as statins, are recommended to lower low-density lipoprotein cholesterol (LDL-C) levels and inhibit the progression of atherosclerosis. However, side effects, including gastrointestinal unease, potential harm to the liver, and discomfort in the muscles, might be observed. In this study, we propose a novel method using periodic mesoporous silica nanoparticles (PMS) to create heparin-modified PMS (PMS-HP) with excellent biocompatibility, enabling selective removal of LDL-C from the blood. In vitro, through the introduction of PMS-HP into the plasma of mice, we observed that, compared to PMS alone, PMS-HP could selectively adsorb LDL-C while avoiding interference with valuable components such as plasma proteins and high-density lipoprotein cholesterol (HDL-C). Notably, further investigations revealed that the adsorption of LDL-C by PMS-HP could be well-fitted to quasi-first-order (R2 = 0.993) and quasi-second-order adsorption models (R2 = 0.998). Likewise, in vivo, intravenous injection of PMS-HP enabled targeted LDL-C adsorption (6.5 ± 0.73 vs. 8.6 ± 0.76 mM, p < 0.001) without affecting other plasma constituents, contributing to reducing intravascular plaque formation (3.66% ± 1.06% vs. 1.87% ± 0.79%, p < 0.05) on the aortic wall and inhibiting vascular remodeling (27.2% ± 6.55% vs. 38.3% ± 1.99%, p < 0.05). Compared to existing lipid adsorption techniques, PMS-HP exhibited superior biocompatibility and recyclability, rendering it valuable for both in vivo and in vitro applications.

Characterization of novel polydiacetylene gel dosimeter for radiotherapy.

Polymer gel dosimeters are instrumental for clinical and research applications in radiotherapy. These dosimeters possess the unique ability to record dose distribution in three dimensions. A Polymer gel dosimeter is composed of organic molecules in a gel matrix, which upon irradiation polymerize to form a conjugated polymer with optical absorbance proportional to the irradiated dose. Other required characteristics of a radiotherapy clinical dosimeter are soft-tissue equivalency, linear dose-response in a range of clinical treatments, and long term stability for the duration of the analysis. The dosimeter presented in this paper is based on diacetylene bearing fatty acid aggregates embedded in a soft-tissue equivalent gel matrix, Phytagel™, which upon irradiation polymerize to form a blue phase polydiacetylene with a strong optical absorption. Initial characterization showed that PDA-gel irradiated with 160 kV x-ray responded linearly to the irradiated dose, and the calculated diffusion coefficient is [Formula: see text] what is very low. It was also found that the percentage depth dose (PDD) curve of the PDA-gel in a 4 × 4 cm2 field, irradiated with 6 MV x-rays, was with good agreement with the literature. PDA-gel has the potential to detect absorbed dose in a range of clinical radiological irradiation regimes.

AN ESTIMATION OF THE EXPOSURE OF THE POPULATION OF ISRAEL TO NATURAL SOURCES OF IONIZING RADIATION.

The radiation dose to the population of Israel due to exposure to natural sources of ionizing radiation was assessed. The main contributor to the dose is radon that accounts for 60% of the exposure to natural sources. The dose due to radon inhalation was assessed by combining the results of a radon survey in single-family houses with the results of a survey in apartments in multi-storey buildings. The average annual dose due to radon inhalation was found to be 1.2 mSv. The dose rate due to exposure to cosmic radiation was assessed using a code that calculates the dose rate at different heights above sea level, taking into account the solar cycle. The annual dose was calculated based on the fraction of time spent indoors and the attenuation provided by buildings and was found to be 0.2 mSv. The annual dose due to external exposure to the terrestrial radionuclides was similarly assessed. The indoor dose rate was calculated using a model that takes into account the concentrations of the natural radionuclides in building materials, the density and the thickness of the walls. The dose rate outdoors was calculated based on the concentrations of the natural radionuclides in different geological units in Israel as measured in an aerial survey and measurements above ground. The annual dose was found to be 0.2 mSv. Doses due to internal exposure other than exposure to radon were also calculated and were found to be 0.4 mSv. The overall annual exposure of the population of Israel to natural sources of ionizing radiation is therefore 2 mSv and ranges between 1.7 and 2.7 mSv.

Nucleic acid fragmentation on the millisecond timescale using a conventional X-ray rotating anode source: application to protein-DNA footprinting.

Nucleic acid fragmentation (footprinting) by *OH radicals is used often as a tool to probe nucleic acid structure and nucleic acid-protein interactions. This method has proven valuable because it provides structural information with single base pair resolution. Recent developments in the field introduced the 'synchrotron X-ray footprinting' method, which uses a high-flux X-ray source to produce single base pair fragmentation of nucleic acid in tens of milliseconds. We developed a complementary method that utilizes X-rays generated from a conventional rotating anode machine in which nucleic acid footprints can be generated by X-ray exposures as short as 100-300 ms. Our theoretical and experimental studies indicate that efficient cleavage of nucleic acids by X-rays depends upon sample preparation, energy of the X-ray source and the beam intensity. In addition, using this experimental set up, we demonstrated the feasibility of conducting X-ray footprinting to produce protein-DNA protection portraits at sub-second timescales.

Monte Carlo simulation of dose distributions from a synchrotron-produced microplanar beam array using the EGS4 code system.

Microbeam therapy is established as a general concept for brain tumour treatment. A synchrotron based x-ray source was chosen for experimental research into microbeam therapy, and therefore new simulations were essential for investigating the therapy parameters with a proper description of the synchrotron radiation characteristics. To design therapy parameters for tumour treatments, the newly upgraded LSCAT (Low energy SCATtering) package of the EGS4 Monte Carlo simulation code was adapted to develop an accurate self-written user code for calculating microbeam radiation dose profiles with a precision of 1 microm. LSCAT is highly suited to this purpose due to its ability to simulate low-energy x-ray transport with detailed photon interactions (including bound electron incoherent scattering functions, and linear polarized coherent scattering). The properties of the synchrotron x-ray microbeam, including its polarization, source spectrum and beam penumbra, were simulated by the new user codes. Two concentric spheres, an inner sphere, defined as a brain, and a surrounding sphere, defined as a skull, represented the phantom. The microbeam simulation was tested using a 3 x 3 cm array beam for small treatment areas and a 6 x 6 cm array for larger ones, with different therapy parameters, such as beam width and spacing. The results showed that the microbeam array retained an adequate peak-to-valley ratio, of five times at least, at tissue depths suitable for radiation therapy. Dose measurements taken at 1 microm resolution with an 'edge-on' MOSFET validated the basics of the user code for microplanar radiation therapy.

Computed tomography of x-ray index of refraction using the diffraction enhanced imaging method.

Diffraction enhanced imaging (DEI) is a new, synchrotron-based, x-ray radiography method that uses monochromatic, fan-shaped beams, with an analyser crystal positioned between the subject and the detector. The analyser allows the detection of only those x-rays transmitted by the subject that fall into the acceptance angle (central part of the rocking curve) of the monochromator/analyser system. As shown by Chapman et al, in addition to the x-ray attenuation, the method provides information on the out-of-plane angular deviation of x-rays. New images result in which the image contrast depends on the x-ray index of refraction and on the yield of small-angle scattering, respectively. We implemented DEI in the tomography mode at the National Synchrotron Light Source using 22 keV x-rays, and imaged a cylindrical acrylic phantom that included oil-filled, slanted channels. The resulting 'refraction CT image' shows the pure image of the out-of-plane gradient of the x-ray index of refraction. No image artefacts were present, indicating that the CT projection data were a consistent set. The 'refraction CT image' signal is linear with the gradient of the refractive index, and its value is equal to that expected. The method, at the energy used or higher, has the potential for use in clinical radiography and in industry.

Applications of a self-collimating BGO detector system to radiological emergency response.

The capability of a recently developed BGO detector system featuring a "self-collimating" structure to locate a point source was established by Monte Carlo simulations and by laboratory scale experiments. The detector system's capability to determine the direction of a nuclear plume resulting from a PWR1 or PWR2 type accident in stable atmospheric conditions by airborne monitoring of the 2.4 MeV photons emitted by 88Kr was established by Monte Carlo simulations.

Wall-less ion-counting nanodosimetry applied to protons.

A wall-less ion-counting nanodosemeter, conceived for precise ionisation-cluster measurements in an accelerator environment, is described. The technique provides an accurate means for counting single radiation-induced ions, in dilute gas models of condensed matter. The sensitive volume dimensions, a few tissue-equivalent nm in diameter by a few tens of nm, are tunable by a proper choice of the gas pressure and electric fields; nanometric sub-sections can be electronically selected. Detailed ion-cluster distributions are presented for protons of 7.15, 13.6 and 19.3 MeV, in biologically relevant DNA-like sensitive volumes of low-pressure propane. Experimental results are compared to model simulations.

Radon concentrations in different types of dwellings in Israel.

The average radon concentration in Israeli dwellings was assessed by combining the results of a 2006 radon survey in single-family houses with the results of a 2011 radon survey in apartments of multistorey buildings. Both surveys were based on long-term measurements using CR-39 detectors. The survey in multistorey buildings was intended to assess the influence of recent practices in the local building industry on the radon concentrations. These practices include the use of building materials with higher concentrations of the natural radionuclides in the last 20 y than before, as well as the improvement in sealing techniques over that period. Another practice in place since the early 1990 s is the building of a shielded area in every apartment that is known as an RSS (residential secure space). The RSS is a room built from massive concrete walls, floor and ceiling that can be hermetically sealed and is intended to protect its residents from a missile attack. The influence of the above-mentioned features on radon concentrations was estimated by dividing the participating apartments into two groups: apartments in buildings >20 y, built using building materials with low concentrations of the natural radionuclides, regular sealing and without an RSS and apartments in buildings newer than 10 y, built using building materials with higher concentrations of the natural radionuclides, improved sealing and including an RSS. It was found that the average radon concentration in apartments in new buildings was significantly higher than in old buildings and the average radon concentration in single-family houses was significantly higher than in apartments in multistorey buildings. Doses due to indoor radon were estimated on the basis of the updated information included in the 2009 International Commission on Radiological Protection statement on radon.

SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for Radiotherapy.

PURPOSE: The new beam and delivery system consists of an electron accelerator and a system of magnets (one or more). Introducing a transverse magnetic field in and near the tumor, causes the electrons to spiral in this region, thereby producing an effective peak in the depth dose distribution, within the tumor volume. Although the basic idea is not new, we suggest here for the first time, a viable as well as a workable, magnetic field configuration, which in addition to focusing the beam does not interfere with its propagation to the target. METHODS: The electron accelerator: can be a linear accelerator or any other type electron accelerator, capable of producing different electron energies for different depths and dose absorption accumulation. The Field size can be as small as a pencil beam and as big as any of the other standard field sizes that are used in radiotherapy. The scatter filter can be used or removed. The dose rate accumulation can be as higher as possible.The magnets are able to produce magnetic fields. The order, direction, width, place, shape and number of the magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the electron beam. Prototypes were successfully tested by means of computer simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA package, for electron beam MC simulation. RESULTS: Our results suggest that by using an electron beam at different energies, combined with magnetic fields, we could modify the delivered dose. This is caused by manipulating the electron motion via the Lorentz force. The applied magnetic field, will focus the electron beam at a given depth and deposit the energy in a given volume and depth, where otherwise the electron energy will have spread deeper. The direction and magnitude of the magnetic fields will prevent the scattering of the electron beam and its absorption in remote volumes. In practice, we get a pseudo Bragg peak depth dose distribution, applying a relatively low cost system. The therapeutic efficiency induced by the system is of similar efficiency as the ion beam therapy techniques. CONCLUSIONS: Our novel concept demonstrates treatment that is almost similar to proton therapy and in some parameters even better performance.Unlike the current high-energy electron therapy, our system's beam deposit almost all of its energy on its target, with a low amount of radiation deposited in tissues from the surface of the skin to the front of tumor, and almost no "exit dose" beyond the tumor. This property will enables to hit tumors with higher, potentially more effective radiation doses, while being considerably less expensive.

Solid-state NMR studies of interstitial phosphorus atoms in rhodium carbonyl clusters.

Pure samples and as-prepared mixtures of Rh9 and Rh10 carbonyl clusters with interstitial P atoms have been studied quantitatively by 31P MAS and 1H-31P CP/MAS NMR. Information on the 31P chemical shift tensor of the Rh9 and Rh10 clusters has been derived from spinning sideband simulations. The chemical shift anisotropy is slightly larger in the Rh10 clusters (340-400 ppm) than in the Rh9 clusters (230-300 ppm), while the asymmetry parameters are similar (eta = 0.1-0.4). The results contribute to the understanding of the relationship between the shielding anisotropy and the structure of the cluster cavity.

Response of avian embryonic brain to spatially segmented x-ray microbeams.

Duck embryo was studied as a model for assessing the effects of microbeam radiation therapy (MRT) on the human infant brain. Because of the high risk of radiation-induced disruption of the developmental process in the immature brain, conventional wide-beam radiotherapy of brain tumors is seldom carried out in infants under the age of three. Other types of treatment for pediatric brain tumors are frequently ineffective. Recent findings from studies in Grenoble on the brain of suckling rats indicate that MRT could be of benefit for the treatment of early childhood tumors. In our studies, duck embryos were irradiated at 3-4 days prior to hatching. Irradiation was carried out using a single exposure of synchrotron-generated X-rays, either in the form of parallel microplanar beams (microbeams), or as non-segmented broad beam. The individual microplanar beams had a width of 27 microm and height of 11 mm, and a center-to-center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40, 80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the broad beam. The biological end point employed in the study was ataxia. This neurological symptom of radiation damage to the brain developed within 75 days of hatching. Histopathological analysis of brain tissue did not reveal any radiation induced lesions for microbeam doses of 40-160 Gy (in-slice), although some incidences of ataxia were observed in that dose group. However, severe brain lesions did occur in animals in the 450 Gy microbeam dose groups, and mild lesions in the 18 Gy broad beam dose group. These results indicate that embryonic duck brain has an appreciably higher tolerance to the microbeam modality, as compared to the broad beam modality. When the microbeam dose was normalized to the full volume of the irradiated tissue. i.e., the dose averaged over microbeams and the space between the microbeams, brain tolerance was estimated to be about three times higher to microbeam irradiation as compared with broad beam irradiation.