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An Advanced In Situ Magnetic Resonance Photo and Ultrasound Theranostics Nanocomposite Platform: Bridging your Blood-Brain Hurdle and also Increasing the Reductions of Glioblastoma Employing Iron-Platinum Nanoparticles throughout Nanobubbles.
A better understanding of B1 receptor inflammatory signaling may lead to the development of therapeutics that target B1 receptors to treat neurogenic hypertension. Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine. Late treatment with tissue plasminogen activator (tPA) leads to reperfusion injury and poor outcome in ischemic stroke. We have recently shown the beneficial effects of local brain hypothermia after late thrombolysis. Herein, we investigated whether transient whole-body hypothermia was neuroprotective and could prevent the side effects of late tPA therapy at 5.5 h after embolic stroke. After induction of stroke, male rats were randomly assigned into four groups Control, Hypothermia, tPA and Hypothermia+tPA. Hypothermia started at 5 h after embolic stroke and continued for 1 h. Thirty min after hypothermia, tPA was administrated. Infarct volume, brain edema, blood-brain barrier (BBB) and matrix metalloproteinase-9 (MMP-9) were assessed 48 h and neurological functions were assessed 24 and 48 hour post-stroke. Compared with the control or tPA groups, whole-body hypothermia decreased infarct volume (P  less then  0.01), BBB disruption (P  less then  0.05) and MMP-9 level (P  less then  0.05). check details However, compared with hypothermia alone a combination of hypothermia and tPA was more effective in reducing infarct volume. While hypothermia alone did not show any effect, its combination with tPA reduced brain edema (P  less then  0.05). Hypothermia alone or when combined with tPA decreased MMP-9 compared with control or tPA groups (P  less then  0.01). Although delayed tPA therapy exacerbated BBB integrity, general cooling hampered its leakage after late thrombolysis (P  less then  0.05). Moreover, only combination therapy significantly improved sensorimotor function as well as forelimb muscle strength at 24 or 48 h after stroke (P  less then  0.01). Transient whole-body hypothermia in combination with delayed thrombolysis therapy shows more neuroprotection and extends therapeutic time window of tPA up to 5.5 h. AIMS Dendritic cells (DCs) actively participate in the pathogenesis of multiple sclerosis (MS), an autoimmune disease. Astragaloside IV (ASI), an active monomer isolated from the Chinese medicine Astragalus membranaceus, has a wide range of pharmacological effects. We aimed to elucidate the effects of ASI on the development of DCs in the early stage of MS/EAE. MAIN METHODS The mice were administered with ASI (20 mg/kg) daily 3 days in advance of EAE induction and continuously until day 7 post-immunization. The effect of ASI on CD11c+ DC cells from bone marrow (BMDCs) or the spleen of EAE mice at day 7 post-immunization were investigated respectively by flow cytometry, elisa, western blot, real-time PCR and immunofluorescence. KEY FINDINGS ASI administration in the early stage of EAE was demonstrated to delay the onset and alleviate the severity of the disease. ASI inhibited the maturation and the antigen presentation of DCs in spleen of EAE mice and LPS-stimulated BMDCs, as evidenced by decreased expressions of CD11c, CD86, CD40 and MHC II. Accordingly, DCs treated by ASI secreted less IL-6 and IL-12, and prevented the differentiation of CD4+ T cells into Th1 and Th17 cells, which was probably through inhibiting the activation of NFκB and MAPKs signaling pathways. SIGNIFICANCE Our results implicated the alleviative effect of early ASI administration on EAE might be mediated by suppressing the maturation and function of DCs. The novel findings may add to our knowledge of ASI in the potentially clinical treatment of MS. MR Imaging the spinal cord of non-human primates (NHP), such as squirrel monkey, is important since the injuries in NHP resemble those that afflict human spinal cords. Our previous studies have reported a multi-parametric MRI protocol, including functional MRI, diffusion tensor imaging, quantitative magnetization transfer and chemical exchange saturation transfer, which allows non-invasive detection and monitoring of injury-associated structural, functional and molecular changes over time. High signal-to-noise ratio (SNR) is critical for obtaining high-resolution images and robust estimates of MRI parameters. In this work, we describe our construction and use of a single channel coil designed to maximize the SNR for imaging the squirrel monkey cervical spinal cord in a 21 cm bore magnet at 9.4 T. We first numerically optimized the coil dimension of a single loop coil and then evaluated the benefits of a quadrature design. We then built an optimized coil based on the simulation results and compared its SNR performance with a non-optimized single coil in both phantoms and in vivo. Porcine models of ophthalmological diseases are often used in pre-clinical translational studies due to pigs' similarities to humans. In particular, the iodoacetic acid (IAA) model of photoreceptor degeneration seems to mimic well the endstage phenotype of human pathologies as retinitis pigmentosa and age-related macular degeneration, with high potential for prosthesis/retinal devices testing. IAA is capable of inducing photoreceptor death by blockage of glycolysis, and its effects on the retina have been described. Nonetheless, up to date, literature lacks of a comprehensive morpho-functional characterization of the entire visual system of this model. This gap is particularly critical for prosthesis testing as inner retinal structures and optic pathways must be preserved to elicit cortical responses and restore vision. In this study, we investigated the functional and anatomical features of the visual system of IAA-treated pigs and compared them to control animals. IAA was administered intravenously at 12 mg/kg; control animals received saline solution (NaCl 0.
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