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Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.
Assuntos
Exossomos , Células-Tronco Mesenquimais , Neoplasias da Glândula Tireoide , Animais , Radioisótopos do Iodo , Distribuição TecidualRESUMO
Yttrium-90 (90Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (99mTc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution. In order to monitor the real-time implantation of the microspheres into the tumor, the 90Y microspheres could be suspended in omnipaque contrast for allowing visualization of the correct distribution of the microspheres into the tumor. The radiochemical purity of mixing 90Y-microspheres in various concentrations of omnipaque was investigated. The radiochemical purity and feasibility of mixing 99mTc-MAA with various concentrations of a standard contrast agent were also investigated. Results showed the radiochemical feasibility of mixing 90Y-microspheres with omnipaque is radiochemically acceptable for allowing real-time visualization of radioembolization under fluoroscopy.
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Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Microesferas , Agregado de Albumina Marcado com Tecnécio Tc 99m , Iohexol , Estudos de Viabilidade , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Embolização Terapêutica/métodos , Compostos Radiofarmacêuticos , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
Introduction: Stroke is a major cause of death and disability worldwide, and it often results in depression, anxiety, stress, and cognitive impairment in survivors. There is a lack of community-based cognitive interventions for stroke survivors. This pilot single trial aimed to assess the feasibility, acceptability, and perceived effectiveness of a community-based cognitive intervention program called Train-Your-Brain (TYB) for stroke survivors and caregivers. The study focused on improvements in emotional and psychological well-being, as well as cognitive functioning. Methods: A quasi-experimental design was used in this study. A total of 48 participants were recruited and assessed using Depression, Anxiety, Stress Scale - 21 items (DASS-21), Montreal Cognitive Assessment (MoCA) and Symbol Digits Modality Test (SDMT) before and after the intervention. The TYB program consisted of nine sessions and was conducted via the Zoom software application. Participants provided feedback on the program, highlighting areas for improvement. Results: Twenty-seven stroke survivors and 21 caregivers completed the program. Participants expressed high satisfaction with the TYB program but recommended avoiding assessments in December and customizing the program for stroke survivors and caregivers. Stroke survivors showed significant improvements in depression and stress scores, while caregivers experienced no significant improvements after the program. While there was a slight improvement in stroke survivors' cognitive scores after the program, it was not statistically significant. Caregivers, however, experienced a significant decline in cognitive scores. Discussion: The TYB program provided group support and validation, resulting in improved mood and reduced stress among stroke survivors. Cultural collectivism played a significant role in fostering group cohesion. However, the program's limited focus on caregivers and timing of assessments during the December holidays may have affected the outcomes. The TYB program demonstrated feasibility and potential effectiveness in alleviating psychological distress and enhancing cognitive function among stroke survivors. Future research should explore long-term effects, larger sample sizes, and non-English-speaking populations to enhance generalizability. Tailored interventions for caregivers are necessary.
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Nuclear imaging is a powerful non-invasive imaging technique that is rapidly developing in medical theranostics. Nuclear imaging requires radiolabeling isotopes for non-invasive imaging through the radioactive decay emission of the radionuclide. Nuclear imaging probes, commonly known as radiotracers, are radioisotope-labeled small molecules. Nanomaterials have shown potential as nuclear imaging probes for theranostic applications. By modifying the surface of nanomaterials, multifunctional radio-labeled nanomaterials can be obtained for in vivo biodistribution and targeting in initial animal imaging studies. Various surface modification strategies have been developed, and targeting moieties have been attached to the nanomaterials to render biocompatibility and enable specific targeting. Through integration of complementary imaging probes to a single nanoparticulate, multimodal molecular imaging can be performed as images with high sensitivity, resolution, and specificity. In this review, nanomaterial nuclear imaging probes including inorganic nanomaterials such as quantum dots (QDs), organic nanomaterials such as liposomes, and exosomes are summarized. These new developments in nanomaterials are expected to introduce a paradigm shift in nuclear imaging, thereby creating new opportunities for theranostic medical imaging tools.
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Successful translation of laboratory-based surface-enhanced Raman scattering (SERS) platforms to clinical applications requires multiplex and ultratrace detection of small biomarker molecules from a complex biofluid. However, these biomarker molecules generally exhibit low Raman scattering cross sections and do not possess specific affinity to plasmonic nanoparticle surfaces, significantly increasing the challenge of detecting them at low concentrations. Herein, we demonstrate a "confine-and-capture" approach for multiplex detection of two families of urine metabolites correlated with miscarriage risks, 5ß-pregnane-3α,20α-diol-3α-glucuronide and tetrahydrocortisone. To enhance SERS signals by 1012-fold, we use specific nanoscale surface chemistry for targeted metabolite capture from a complex urine matrix prior to confining them on a superhydrophobic SERS platform. We then apply chemometrics, including principal component analysis and partial least-squares regression, to convert molecular fingerprint information into quantifiable readouts. The whole screening procedure requires only 30 min, including urine pretreatment, sample drying on the SERS platform, SERS measurements, and chemometric analyses. These readouts correlate well with the pregnancy outcomes in a case-control study of 40 patients presenting threatened miscarriage symptoms.