6 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

    Molecular pathologic interpretation of new retinoblastoma rosettes

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    Newly described retinoblastoma (RB) rosettes have various kinds of pathological significance. Some of their characteristics have been revealed in this immunohistochemistry study. Five paraffin-embedded eyeballs with RB and new rosettes were studied for neuron-specific enolase (NSE), p53, p16, BAX, c-Myc, glial fibrillary acidic protein, synaptophysin, and chromogranin. They were compared and interpreted using control specimens. NSE, P53, and P16 were significantly expressed in the cells of the new rosettes. The presence of new RB rosettes that mostly have histopathological high-risk factors and p53 positivity may be a strong marker of poor prognosis of RB

    Copper Complexes Relevant to the Catalytic Cycle of Copper Nitrite Reductase: Electrochemical Detection of NO(<i>g</i>) Evolution and Flipping of NO<sub>2</sub> Binding Mode upon Cu<sup>II</sup> → Cu<sup>I</sup> Reduction

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    Copper complexes of the deprotonated tridentate ligand, <i>N</i>-2-methylthiophenyl-2′-pyridinecarboxamide (HL1), were synthesized and characterized as part of our investigation into the reduction of copper­(II) <i>o</i>-nitrito complexes into the related copper nitric oxide complexes and subsequent evolution of NO­(<i>g</i>) such as occurs in the enzyme copper nitrite reductase. Our studies afforded the complexes [(L1)­Cu<sup>II</sup>Cl]<sub><i>n</i></sub> (<b>1</b>), [(L1)­Cu<sup>II</sup>(ONO)] (<b>2</b>), [(L1)­Cu<sup>II</sup>(H<sub>2</sub>O)]­(ClO<sub>4</sub>)·H<sub>2</sub>O (<b>3</b>·<b>H</b><sub><b>2</b></sub><b>O</b>), [(L1)­Cu<sup>II</sup>(CH<sub>3</sub>OH)]­(ClO<sub>4</sub>) (<b>4</b>), [(L1)­Cu<sup>II</sup>(CH<sub>3</sub>CO<sub>2</sub>)]·H<sub>2</sub>O (<b>5</b>·<b>H</b><sub><b>2</b></sub><b>O</b>), and [Co­(Cp)<sub>2</sub>]­[(L1)­Cu<sup>I</sup>(NO<sub>2</sub>)­(CH<sub>3</sub>CN)] (<b>6</b>). X-ray crystal structure determinations revealed distorted square-pyramidal coordination geometry around Cu<sup>II</sup> ion in <b>1</b>–<b>5</b>. Substitution of the H<sub>2</sub>O of <b>3</b> by nitrite quantitatively forms <b>2</b>, featuring the κ<sup>2</sup>-O,O binding mode of NO<sub>2</sub><sup>–</sup> to Cu<sup>II</sup>. Reduction of <b>2</b> generates two Cu<sup>I</sup> species, one with κ<sup>1</sup>-O and other with the κ<sup>1</sup>-N bonded NO<sub>2</sub><sup>–</sup> group. The Cu<sup>I</sup> analogue of <b>2</b>, compound <b>6</b>, was synthesized. The FTIR spectrum of <b>6</b> reveals the presence of κ<sup>1</sup>-N bonded NO<sub>2</sub><sup>–</sup>. Constant potential electrolysis corresponding to Cu<sup>II</sup> → Cu<sup>I</sup> reduction of a CH<sub>3</sub>CN solution of <b>2</b> followed by reaction with acids, CH<sub>3</sub>CO<sub>2</sub>H or HClO<sub>4</sub> generates <b>5</b> or <b>3</b>, and NO­(<i>g</i>), identified electrochemically. The isolated Cu<sup>I</sup> complex <b>6</b> independently evolves one equivalent of NO­(<i>g</i>) upon reaction with acids. Production of NO­(g) was confirmed by forming [Co­(TPP)­NO] in CH<sub>2</sub>Cl<sub>2</sub> (λ<sub>max</sub> in CH<sub>2</sub>Cl<sub>2</sub>: 414 and 536 nm, ν<sub>NO</sub> = 1693 cm<sup>–1</sup>)
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