28 research outputs found

    Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

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    Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

    Absolute cerebral blood volume and blood flow measurements based on synchrotron radiation quantitative computed tomography

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    Synchrotron radiation computed tomography opens new fields by using monochromatic x-ray beams. This technique allows one to measure in vivo absolute contrast-agent concentrations with high accuracy and precision, and absolute cerebral blood volume or flow can be derived from these measurements using tracer kinetic methods. The authors injected an intravenous bolus of an iodinated contrast agent in healthy rats, and acquired computed tomography images to follow the temporal evolution of the contrast material in the blood circulation. The first image acquired before iodine infusion was subtracted from the others to obtain computed tomography slices expressed in absolute iodine concentrations. Cerebral blood volume and cerebral blood flow maps were obtained after correction for partial volume effects. Mean cerebral blood volume and flow values (n 7) were 2.1 ± 0.38 mL/100 g and 129 ± 18 mL · 100 g−1 · min−1 in the parietal cortex; and 1.92 ± 0.32 mL/100 g and 125 ± 17 mL · 100 g−1 · min−1 in the caudate putamen, respectively. Synchrotron radiation computed tomography has the potential to assess these two brainperfusion parameters. Key Words: Synchrotron radiation— Computed tomography—Cerebral blood volume—Cerebral blood flow—Iodinated contrast agent—Partial volume effects

    In vivo measurement of gadolinium concentration in a rat glioma model by monochromatic quantitative computed tomography: comparison between gadopentetate dimeglumine and gadobutrol

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    Rationale and Objectives: Monochromatic quantitative computed tomography allows a nondestructive and quantitative measurement of gadolinium (Gd) concentration. This technique was used in the C6 rat glioma model to compare gadopentetate dimeglumine and gadobutrol. Methods: Rats bearing late-stage gliomas received 2.5 mmol/kg (392.5 mg Gd/kg) of gadopentetate dimeglumine (n 5) and gadobutrol (n 6) intravenously before the imaging session performed at the European Synchrotron Radiation Facility. Results: Monochromatic quantitative computed tomography enabled in vivo follow-up of Gd concentration as a function of time in specified regions of interest. Surprisingly, after gadobutrol injection, Gd concentrations in the center and periphery of the tumor were higher than those after gadopentetate injection, although identical in normal and contralateral area of the brain. Conclusion: The in vivo assessment of absolute Gd concentrations revealed differences in gadobutrol and gadopentetate dimeglumine behaviors in tumoral tissues despite injections in the same conditions. These differences might be attributed to different characteristics of the contrast agents

    Sensitivity variation of doped Fricke gel irradiated with monochromatic synchrotron X-rays between 33.5 and 80 keV

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    An experimental binary radiotherapy proposes the concomitant use of a high-Z compound and synchrotron X rays for enhancing radiation dose selectively in tumours by a photoelectric effect. This study aimed at measuring the resulting dose enhancement in irradiated material. A doped Fricke gel dosemeter model was manufactured with 10 mg ml1 of iodine (Telebrix) or barium (Micropaque). Samples were irradiated with a monochromatic synchrotron beam at 33.5, 50, 65 and 80 keV. The ensuing enhancement of the sensitivity of the dosemeter was derived from the nuclear magnetic resonance relaxation rates measured at different X-ray doses. Our results demonstrate (1) the preservation of a linear relationship between relaxation rates and X-ray doses for dosemeters doped with high-Z atoms and (2) a clear energy-dependent sensitivity enhancement for barium-doped Fricke gels. This enhancement was neither reproducible with iodinated compounds nor clearly related to the expected dose enhancement factor. However 1% barium sulphate in the gel could significantly improve the gel\u27s response when it was irradiated by low-energy X rays

    Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways

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    Combination of cis-platinum with ionizing radiation is one of the most promising anticancer treatments that appears to be more efficient than radiotherapy alone. Unlike conventional X-ray emitters, accelerators of high energy particles like synchrotrons display powerful and monochromatizable radiation that makes the induction of an Auger electron cascade in cis-platinum molecules [also called photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we examined the molecular consequences of one of the first attempts of synchrotron PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble-France). PATPlat was found to result in an extra number of slowly repairable DNA double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and activation of proto-oncogenic c-Abl tyrosine kinase
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