Theranostics
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Sepsis is a common and life-threatening systemic disorder, often leading to acute injury of multiple organs. Here, we show that remote ischemic preconditioning (rIPC), elicited by brief episodes of ischemia and reperfusion in femoral arteries, provides protective effects against sepsis-induced acute kidney injury (AKI). Methods: Limb rIPC was conducted on mice in vivo 24 h before the onset of cecal ligation and puncture (CLP), and serum exosomes derived from rIPC mice were infused into CLP-challenged recipients. ⋯ Mechanistically, we discovered that miR-21 was transported from preischemic limbs to remote organs via serum exosomes. In kidneys, the enhanced exosomal miR-21 derived from cultured myotubes with H/R or the serum of mice treated with rIPC integrated into renal tubular epithelial cells and then targeted the downstream PDCD4/NF-κB and PTEN/AKT pathways, exerting anti-inflammatory and anti-apoptotic effects and consequently attenuating sepsis-induced renal injury both in vivo and in vitro. Conclusion: This study demonstrates a critical role for exosomal miR-21 in renoprotection conferred by limb rIPC against sepsis and suggests that rIPC and exosomes might serve as the possible therapeutic strategies for sepsis-induced kidney injury.
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Review
Recommendations for reporting on emerging optical imaging agents to promote clinical approval.
Intraoperative fluorescence imaging is particularly well-suited for surgical applications due to its inherently high sensitivity, resolution, and ability to provide images in real-time. To date, the intraoperative observation of fluorescence has largely been subjective. With the need to show objective evidence in order to demonstrate the benefit of this technique, quantitative data needs to be provided to overseeing regulatory bodies. ⋯ Qualitative analyses should consist of a bright field image, black-and-white fluorescence image, pseudo-colored fluorescence overlay image, and/or heat-map whereby fluorescence signal intensity differences are displayed on a color spectrum. Quantitative analyses should include 1) intraoperative data (consisting of images or video, raw numeric values and ratios); 2) specimen mapping, for correlation of fluorescence with the presence of disease (performed using fresh tissue); and 3) target validation (designed to determine fluorescence intensity relative to receptor density of a specific area). Including the aforementioned methods of both qualitative and quantitative analyses will ensure that trial results are comparable and could be collated in future studies to expedite FDA approval.
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Significantly reduced photon scattering and minimal tissue autofluorescence levels in the second biological transparency window (NIR-II; 1000-1700 nm) facilitate higher resolution in vivo biological imaging compared to tradition NIR fluorophores (~700-900 nm). However, the existing palette of NIR-II fluorescent agents including semiconducting inorganic nanomaterials and recently introduced small-molecule organic dyes face significant technical and regulatory hurdles prior to clinical translation. ⋯ This review focuses on the significant advantage of imaging past 1000 nm with NIR-I fluorophores from both a basic and clinical viewpoint. We further discuss optimizing NIR-I dyes around their NIR-II/shortwave infrared (SWIR) emission, NIR-II emission tail characteristics and prospects of NIR-II imaging with clinically available and commercially available dyes.
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Non-coding RNAs (ncRNAs) are considered major players in physiological and pathological processes based on their versatile regulatory roles in different diseases including cardiovascular disease. Circular RNAs (circRNAs), a newly discovered class of RNAs, constitute a substantial fraction of the mammalian transcriptome and are abundantly expressed in the cardiovascular system. However, the regulatory functions of these circRNAs in ischemic cardiac disease remain largely unknown. ⋯ Knockdown of circNCX1 in murine cardiomyocytes and heart tissues reduced the levels of CDIP1 and attenuated the apoptosis and I/R injury. Conclusions: Our findings reveal a novel regulatory pathway that comprises circNCX1, miR-133a-3p and CDIP1, that is involved in cardiomyocyte apoptosis. This pathway may serve as a potential therapeutic avenue for ischemic heart diseases.
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We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS:In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. ⋯ The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.