Bone mesenchymal stem cell extracellular vesicles delivered miR let-7-5p alleviate endothelial glycocalyx degradation and leakage via targeting ABL2.

BACKGROUND: Endothelial glycocalyx (EG) is an active player and treatment target in inflammatory-related vascular leakage. The bone marrow mesenchymal stem cells (bMSCs) are promising potential treatments for leakage; however, the therapeutic effect and mechanism of bMSC on EG degradation needs to be elucidated. METHODS: EG degradation and leakage were evaluated in both lipopolysaccharide (LPS)-induced mice ear vascular leakage model and LPS-stimulated human umbilical vein endothelial cells (HUVECs) model treated with bMSCs. Extracellular vesicles (EVs) were extracted from bMSCs and the containing microRNA profile was analyzed. EV and miR let-7-5p were inhibited to determine their function in the therapeutic process. The ABL2 gene was knockdown in HUVECs to verify its role as a therapeutic target in EG degradation. RESULTS: bMSCs treatment could alleviate LPS-induced EG degradation and leakage in vivo and in vitro, whereas EVs/let-7-5p-deficient bMSCs were insufficient to reduce EG degradation. LPS down-regulated the expression of let-7-5p while upregulated endothelial expression of ABL2 in HUVECs and induced EG degradation and leakage. bMSC-EVs uptaken by HUVECs could deliver let-7-5p targeting endothelial ABL2, which suppressed the activation of downstream p38MAPK and IL-6, IL-1ß levels, and thus reversed LPS-induced EG degradation and leakage. CONCLUSION: bMCSs alleviate LPS-induced EG degradation and leakage through EV delivery of miR let-7-5p targeting endothelial ABL2.

Background Inflammation-related Endothelial vascular leakage (EVL) is associated with poor clinical prognosis. Endothelial glycocalyx (EG) is a novel therapeutic target for EVL. bMSCs (Bone Mesenchymal Stem Cells) are potential therapies for EVL, but the effect of bMSCs on EG has not been investigated.Significance bMSCs alleviating EG degradation and leakage was firstly clarified in our LPS-induced vascular leakage mice model. Histology and electrophysiology experiments validated that bMSCs achieve therapeutic effects through paracrine extracellular vesicles (EVs). EV-delivered MicroRNA sequencing revealed that miR let-7-5p down-regulated endothelial ABL2/p38MAPK-related inflammation activation. The bMSC-EV delivered let-7-5p was proved as an effective element in alleviating inflammation-related EG degradation and leakage, providing an executable approach for bMSCs to treat EVL. Video Abstract.

Research Trends and Hotspots of Medical Electrical Impedance Tomography Algorithms: A Bibliometric Analysis From 1987 to 2021.

Electrical impedance tomography (EIT) is a gradually maturing medical imaging technique that relies on computational algorithms for reconstructing and visualizing internal conductivity distributions within the human body. To provide a comprehensive and objective understanding of the current state and trends in the EIT algorithm research, we conducted bibliometric analysis on a 25-year EIT algorithm research dataset sourced from Web of Science Core Collections. We visualized publication characteristics, collaboration patterns, keywords, and co-cited references. The results indicate a steady increase in annual publications over recent decades. The United States, United Kingdom, China, and South Korea contributed 60% of the articles collaboratively. Keyword analysis unveiled three distinct stages in the evolution of EIT algorithm research: the establishment of fundamental algorithm frameworks, optimization for improved imaging performance, and the development of algorithms for clinical applications. Additionally, there has been a shift in research focus from traditional theories to the incorporation of new methods, such as artificial intelligence. Co-cited references suggest that integrating EIT with other established imaging techniques may emerge as a new trend in EIT algorithm research. In summary, EIT algorithms have been a consistent research focus, with current efforts centered on optimizing algorithms to enhance imaging performance. The emerging research trend involves utilizing more diverse and intersecting algorithms.

Emerging trends and hot spots on electrical impedance tomography extrapulmonary applications.

Objective: Electrical impedance tomography (EIT) develops rapidly in technology and applications. Nowadays EIT is used in multiple clinical and experimental scenarios including pulmonary, brain, and tissue monitoring, etc. The present study explores the research trends and hotspots on EIT extrapulmonary application research by bibliometrics analysis. Approach: Publications on EIT extrapulmonary applications between 1987 and 2021 were retrieved from the Web of Science Core Collection database. For precise screening, search strategy "electrical impedance tomography" plus "hemodynamic" or "brain" or "nerve" or "cancer" or "venous" or "vessel" or "tumor" or "veterinary" or "tissue" or "cell" or "wearable" or "application" and excluding "lung", "ventilation" "respiratory", "pulmonary", "algorithm", "current", "voltage" or "electrode" were used. CiteSpace and VOSviewer were used to analyze the publication features, collaboration, keywords co-occurrence, and co-cited reference. Main results: A total of 506 articles were finally identified. The global publication numbers on extrapulmonary applications gradually increased yearly in the past 30 years. The US, UK, and China contributed most three publications concerning EIT extrapulmonary applications. "tissues", "conductivity", "model" were research hotspots, and "cutaneous melanoma", "microstructure", "diagnosis" were recent topics (Portions of this research have previously been presented in poster form). Significance: Overall, EIT extrapulmonary applications bibliometrics analysis provides a unique insight into research focus, current trends, and future directions.

Protectin DX promotes epithelial injury repair and inhibits fibroproliferation partly via ALX/PI3K signalling pathway.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti-inflammatory and potent inflammation pro-resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)-induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor-ß1 (TGF-ß1 ) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

[Spectroscopy research on cholesterol in hypercholesterolemia serum].

The cholesterol with different concentration in hypercholesterolemia serum was studied by the method of spectroscopy technology. The absorption and fluorescence spectra of normal human serum and hypercholesterolemia serum were obtained respectively; the spectral characteristic of each sample and the difference between two kinds of samples were discussed too. The results indicate that the absorption and fluorescence spectra of hypercholesterolemia serum are different from those of normal human serum. The absorptivity and the fluorescence intensity of hypercholesterolemia serum are both higher than those of normal human serum. Besides, there are new absorptive peaks and new fluorescence peaks in the spectrogram. Thus, the abnormalism of cholesterol in serum can be judged by comparing the absorption and fluorescence spectra. The researches in the present paper provide an experimental foundation for the diagnosis of cholesterol in blood.

[Construction and identification of recombinant adenovirus vector containing thioredoxin reductase gene].

AIM: To construct recombinant adenovirus vector containing human thioredoxin reductase (TR) gene and to explore the correlation between antioxidant activity of TR and the degenerative neuropathy. METHODS: Full length TR cDNA was obtained from recombinant plasmid pGEM-TR via digestion with Apa I and Not I and was cloned into pShuttle vector and pShuttle-TR was recut with I-Ceu I and PI-Sce I. Fragment containing TR gene and CMV promoter was inserted into E1 and E3 deficient adeno-X virus DNA, and then the recombinant adenovirus vector was transfected into HEK 293 cells through lipofectamine and identified by PCR. The TR expression on and in cell lysate of CV1 cells infected with recombinant adenovirus was by immuno fluorescence assay and Western blot analysis. RESULTS: After replication of recombinant adenovirus Adeno-TR, the virus titer was about 4.4x10(11) pfu/L. The TR expression on CV1 cells was proved by fluorescent microscopy. Western blot analysis showed a band with relative molecular mass (M(r)) of 55,000. CONCLUSION: A recombinant adenovirus vector has been successfully constructed and TR is expressed on CV1 cells. This result lays the foundation for further study on function of TR and its correlation with degenerative neuropathy.