Moxifloxacin Concentration and Proteomic Analysis of Aqueous Humor in Human Uveitis Associated with Oral Moxifloxacin Therapy

PURPOSE: The aim was to report the aqueous humor moxifloxacin concentration and proteome profile of an individual with bilateral uveitis-like syndrome with pigment dispersion. METHODS: Multiple reactions monitoring mass spectrometry quantified the aqueous concentration of moxifloxacin in the affected individual. Shotgun proteomic analysis performed via liquid chromatography tandem mass spectrometry (LC-MS/MS) defined the protein profile in the affected individual and unaffected control samples. RESULTS: Moxifloxacin was present at higher than expected levels in aqueous humor 18 days following oral administration. One-third of the proteins were identified by significantly lower spectral counts in the aqueous of the individual with moxifloxacin associated uveitis compared to the unaffected control. CONCLUSION: Moxifloxacin was detected in aqueous humor 18 days following the completion of oral administration. These results suggest that moxifloxacin toxicity may be responsible for the uveitis-like syndrome with pigment dispersion syndrome induced by moxifloxacin therapy

Crystal Structures of ABL-Related Gene (ABL2) in Complex with Imatinib, Tozasertib (VX-680), and a Type I Inhibitor of the Triazole Carbothioamide Class†

ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases and is deregulated in solid tumors. Oncogenic gene translocations occur in acute leukemia. So far no structural information for ABL2 has been reported. To elucidate structural determinants for inhibitor interaction, we determined the cocrystal structure of ABL2 with the oncology drug imatinib. Interestingly, imatinib not only interacted with the ATP binding site of the inactive kinase but was also bound to the regulatory myristate binding site. This structure may therefore serve as a tool for the development of allosteric ABL inhibitors. In addition, we determined the structures of ABL2 in complex with VX-680 and with an ATP-mimetic type I inhibitor, which revealed an interesting position of the DFG motif intermediate between active and inactive conformations, that may also serve as a template for future inhibitor design

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

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