Human bone marrow mesenchymal stem cell-derived extracellular vesicles attenuate neuroinflammation evoked by focal brain injury in rats

Background Ischemic stroke is the major cause of long-term severe disability and death in aged population. Cell death in the infarcted region of the brain induces immune reaction leading to further progression of tissue damage. Immunomodulatory function of mesenchymal stem cells (MSCs) has been shown in multiple preclinical studies; however, it has not been successfully translated to a routine clinical practice due to logistical, economical, regulatory, and intellectual property obstacles. It has been recently demonstrated that therapeutic effect of intravenously administered MSCs can be recapitulated by extracellular vesicles (EVs) derived from them. However, in contrast to MSCs, EVs were not capable to decrease stroke-induced neuroinflammation. Therefore, the aim of the study was to investigate if intra-arterial delivery of MSC-derived EVs will have stronger impact on focal brain injury-induced neuroinflammation, which mimics ischemic stroke, and how it compares to MSCs. Methods The studies were performed in adult male Wistar rats with focal brain injury induced by injection of 1 mu l of 50 nmol ouabain into the right hemisphere. Two days after brain insult, 5 x 10(5) human bone marrow MSCs (hBM-MSCs) labeled with Molday ION or 1.3 x 10(9) EVs stained with PKH26 were intra-arterially injected into the right hemisphere under real-time MRI guidance. At days 1, 3, and 7 post-transplantation, the rats were decapitated, the brains were removed, and the presence of donor cells or EVs was analyzed. The cellular immune response in host brain was evaluated immunohistochemically, and humoral factors were measured by multiplex immunoassay. Results hBM-MSCs and EVs transplanted intra-arterially were observed in the rat ipsilateral hemisphere, near the ischemic region. Immunohistochemical analysis of brain tissue showed that injection of hBM-MSCs or EVs leads to the decrease of cell activation by ischemic injury, i.e., astrocytes, microglia, and infiltrating leucocytes, including T cytotoxic cells. Furthermore, we observed significant decrease of pro-inflammatory cytokines and chemokines after hBM-MSC or EV infusion comparing with non-treated rats with focal brain injury. Conclusions Intra-arterially injected EVs attenuated neuroinflammation evoked by focal brain injury, which mimics ischemic stroke, and this effect was comparable to intra-arterial hBM-MSC transplantation. Thus, intra-arterial injection of EVs might be an attractive therapeutic approach, which obviates MSC-related obstacles

Edge phonons in black phosphorus

Exfoliated black phosphorus has recently emerged as a new two-dimensional crystal that, due to its peculiar and anisotropic crystalline and electronic band structures, may have potentially important applications in electronics, optoelectronics and photonics. Despite the fact that the edges of layered crystals host a range of singular properties whose characterization and exploitation are of utmost importance for device development, the edges of black phosphorus remain poorly characterized. In this work, the atomic structure and the behavior of phonons near different black phosphorus edges are experimentally and theoretically studied using Raman spectroscopy and density functional theory calculations. Polarized Raman results show the appearance of new modes at the edges of the sample, and their spectra depend on the atomic structure of the edges (zigzag or armchair). Theoretical simulations confirm that the new modes are due to edge phonon states that are forbidden in the bulk, and originated from the lattice termination rearrangements.Comment: 15 pages, 4 figure

Plasma Cytokines/Chemokines as Predictive Biomarkers For Lymphedema in Breast Cancer Patients

Breast cancer-related lymphedema (BCRL) occurs in ~ 40% of patients after axillary lymph node dissection (ALND), radiation therapy (RT), or chemotherapy. First-line palliative treatment utilizes compression garments and specialized massage. Reparative microsurgeries have emerged as a second-line treatment, yet both compression and surgical therapy are most effective at early stages of LE development. Identifying patients at the highest risk for BCRL would allow earlier, more effective treatment. Perometric arm volume measurements, near-infrared fluorescent lymphatic imaging (NIRF-LI) data, and blood were collected between 2016 and 2021 for 40 study subjects undergoing treatment for breast cancer. Plasma samples were evaluated using MILLIPLEX human cytokine/chemokine panels at pre-ALND and at 12 months post-RT. A Mann-Whitne

Peripapillary Microvascular and Neural Changes in Diabetes Mellitus: An OCT-Angiography Study

Purpose: To evaluate peripapillary vessel density and morphology in patients with diabetes mellitus (DM) without clinical signs of diabetic retinopathy (DR) and with mild, nonproliferative DR and to correlate with peripapillary nerve fiber layer (NFL) thickness.Methods: One hundred seventeen eyes (34 healthy controls, 54 patients with DM without DR [noDR group] and 24 patients with mild DR [DR group]) were prospectively evaluated. All subjects underwent peripapillary and macular optical coherence tomography angiography (OCT-A). Peripapillary NFL thickness was also recorded. OCT-A slab of radial peripapillary plexus (RPC) and macular superficial capillary plexus (SCP) were analysed in order to calculate perfusion density (PD) and vessel density (VD). Further an image analysis of RPC slab was performed to identify number of branches (NoB) and total branches length (tBL).Results: In peripapillary area there was a significant decrease in VD (P = 0.003), NoB (P < 0.001), and tBL (P < 0.001) in noDR group versus controls; PD values were not different among groups (P = 0.126); there was a significant decrease in average NFL thickness in DR versus controls (P = 0.008) and in the inferior quadrant in noDR group versus controls (P = 0.03); there was a significant correlation between OCT-A and NFL thickness values (\u3c1 ranging from 0.19-0.57). In macular region PD and VD were decreased only in DR group (P < 0.05).Conclusions: There are early changes in the peripapillary vessel morphology and VD of the RPC in patients with DM without DR that correlate to NFL thinning. Earlier changes in superficial vessel density are documented in the peripapillary than in the macular region. These data may confirm a coexistence of an early neuronal and microvascular damage in patients with DM without clinical signs of DR

Why nature matters: A systematic review of intrinsic, instrumental, and relational values

\ua9 2023 The Author(s). Published by Oxford University Press on behalf of the American Institute of Biological Sciences. In this article, we present results from a literature review of intrinsic, instrumental, and relational values of nature conducted for the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, as part of the Methodological Assessment of the Diverse Values and Valuations of Nature. We identify the most frequently recurring meanings in the heterogeneous use of different value types and their association with worldviews and other key concepts. From frequent uses, we determine a core meaning for each value type, which is sufficiently inclusive to serve as an umbrella over different understandings in the literature and specific enough to help highlight its difference from the other types of values. Finally, we discuss convergences, overlapping areas, and fuzzy boundaries between different value types to facilitate dialogue, reduce misunderstandings, and improve the methods for valuation of nature\u27s contributions to people, including ecosystem services, to inform policy and direct future research

Dual-Labeling Strategies for Nuclear and Fluorescence Molecular Imaging: A Review and Analysis

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging