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Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1
摘要： PURPOSE. In this study, we aim to investigate whether mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) could regulate hyperglycemia-induced retinal inflammation by transferring microRNA-126 (miR-126). METHODS. MSC-Exos were isolated from the media of human umbilical cord-derived mesenchymal stem cells (hUCMSCs), and this isolation was followed by the transfer of miR-126. MSC-Exos or MSC-Exos overexpressing miR-126 were intravitreally injected into diabetic rats in vivo and were cocultured with high glucose-affected human retinal endothelial cells (HRECs) in vitro. Plasma samples were obtained from the vitreous of rats and from HREC cells after treatment for ELISA assay. Retinal sections were examined using immunohistochemistry. RT-PCR and Western blotting were conducted to assess the levels of high-mobility group box 1 (HMGB1), NLRP3 inflammasome, and NF-jB/P65 in retinas and HRECs. RESULTS. Our results showed that hyperglycemia greatly increased inflammation in diabetic rats or HRECs exposed to high glucose, increasing the levels of caspase-1, interleukin-1b (IL-1b) and IL-18. The administration of MSC-Exos could effectively reverse this reaction. Compared to control MSC-Exos, MSC-Exos overexpressing miR-126 more successfully suppressed the HMGB1 signaling pathway and suppressed inflammation in diabetic rats. The administration of miR-126-expressing MSC-Exos significantly reduced high glucose-induced HMGB1 expression and the activity of the NLRP3 inflammasome in HRECs. CONCLUSIONS. miR-126 expression in MSC-Exos reduces hyperglycemia-induced retinal inflammation by downregulating the HMGB1 signaling pathway.
关键词： HMGB1,exosome,NLRP3 inflammasome,miR-126,mesenchymal stem cell
更新于2025-09-19 17:15:36
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A simple, static preservation system for shipping retinal pigment epithelium cell sheets
摘要： The ability to move cells and tissues from bench to bedside is an essential aspect of regenerative medicine. In this study, we propose a simple, static shipping system to deliver tissue-engineered cell sheets. Notably, this system is electronic-device-free and simplified to minimize the number of packing and opening steps involved. Shipping conditions were optimized, and application and verification of the system were performed using human iPS-cells-derived or fetal retinal pigment epithelium (RPE) cell sheets. The temperature of the compartments within the insulated container was stable at various conditions, and filling up the cell vessel with medium effectively prevented turbulence-induced mechanical damage to the RPE cell sheets. Furthermore, no abnormal changes were observed in RPE morphology, transepithelial electrical resistance, or mRNA expression after transit by train and car. Taken together, our simple shipping system has the potential to minimize the costs and human error associated with bench to bedside tissue transfer. This specially designed regenerative tissue shipping system, validated for use in this field, can be used without any special training. This study provides a procedure for easily sharing engineered tissues with the goal of promoting collaboration between laboratories and hospitals and enhancing patient care.
关键词： shipping,induced pluripotent stem cells,product packaging,retinal pigment epithelium,human,regenerative medicine,temperature
更新于2025-09-19 17:15:36
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Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations
摘要： The transplantation of retinal cells has been studied in animals to establish proof of its potential benefit for the treatment of blinding diseases. Photoreceptor precursors have been grafted in animal models of Mendelian-inherited retinal degenerations, and retinal pigmented epithelial cells have been used to restore visual function in animal models of age-related macular degeneration (AMD) and recently in patients. Cell therapy over corrective gene therapy in inherited retinal degeneration can overcome the genetic heterogeneity by providing one treatment for all genetic forms of the diseases. In AMD, the existence of multiple risk alleles precludes a priori the use of corrective gene therapy. Mechanistically, the experiments of photoreceptor precursor transplantation reveal the importance of cytoplasmic material exchange between the grafted cells and the host cells for functional rescue, an unsuspected mechanism and novel concept. For transplantation of retinal pigmented epithelial cells, the mechanisms behind the therapeutic benefit are only partially understood, and clinical trials are ongoing. The fascinating studies that describe the development of methodologies to produce cells to be grafted and demonstrate the functional benefit for vision are reviewed.
关键词： retinitis pigmentosa,photoreceptors,retinal pigmented epithelium,age-related macular degeneration,cytoplasmic material transfer,induced-pluripotent stem cells
更新于2025-09-19 17:15:36
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The maximum a posteriori probability rule for atom column detection from HAADF STEM images
摘要： Recently, the maximum a posteriori (MAP) probability rule has been proposed as an objective and quantitative method to detect atom columns and even single atoms from high-resolution high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) images. The method combines statistical parameter estimation and model-order selection using a Bayesian framework and has been shown to be especially useful for the analysis of the structure of beam-sensitive nanomaterials. In order to avoid beam damage, images of such materials are usually acquired using a limited incoming electron dose resulting in a low contrast-to-noise ratio (CNR) which makes visual inspection unreliable. This creates a need for an objective and quantitative approach. The present paper describes the methodology of the MAP probability rule, gives its step-by-step derivation and discusses its algorithmic implementation for atom column detection. In addition, simulation results are presented showing that the performance of the MAP probability rule to detect the correct number of atomic columns from HAADF STEM images is superior to that of other model-order selection criteria, including the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC). Moreover, the MAP probability rule is used as a tool to evaluate the relation between STEM image quality measures and atom detectability resulting in the introduction of the so-called integrated CNR (ICNR) as a new image quality measure that better correlates with atom detectability than conventional measures such as signal-to-noise ratio (SNR) and CNR.
关键词： Atom detection,Scanning transmission electron microscopy (STEM),Atom detectability,Model selection
更新于2025-09-19 17:15:36
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Probing primary mesenchymal stem cells differentiation status by micro-Raman spectroscopy
摘要： We have employed micro-Raman spectroscopy to get insight into intrinsic biomolecular profile of individual mesenchymal stem cell isolated from periodontal ligament. Furthermore, these cells were stimulated towards adipogenic, chondrogenic, and osteogenic lineages and their status of differentiation was assessed using micro-Raman spectroscopy. In both cases, glass coverslips were used as substrates, due to their wide availability and cost effectiveness. In all sample groups, the same type of behavior was observed, manifested as changes in Raman spectra: the increase of relative intensity of protein/lipid bands and decrease of nucleic acid bands. Comprehensive statistical analysis in the form of principal component analysis was performed, which revealed noticeable grouping of cells with the similar features. Despite the inhomogeneity of primary stem cells and their differentiated lineages, we demonstrated that micro-Raman spectroscopy is sufficient for distinguishing cells' status, which can be valuable for medical and clinical application.
关键词： differentiation,stem cells,Raman spectroscopy
更新于2025-09-19 17:15:36
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Photoactivable elimination of tumorigenic human induced pluripotent stem cells using a lectin-doxorubicin prodrug conjugate
摘要： Human pluripotent stem cells (hPSCs) are attractive resources for regenerative medicine but medical applications are hindered by their tumorigenic potential. Previously, we identified a hPSC-specific lectin probe, rBC2LCN, through comprehensive glycome analysis using high-density lectin microarrays. Here, we developed a lectin-doxorubicin (DOX) prodrug conjugate with controllable photolysis activation for the elimination of tumorigenic human induced pluripotent stem cells. rBC2LCN was fused with a biotin-binding protein, Tamavidin (BC2Tama), and the fusion protein was expressed in Escherichia coli and purified using affinity chromatography. BC2Tama was then conjugated with doxorubicin-photocleavable biotin (DOXPCB). The BC2Tama-DOXPCB conjugates were observed to bind to the hPSCs followed by internalization. Upon ultraviolet light exposure, doxorubicin was released inside the cells, which allowed specific killing of the hPSCs. Thus, BC2Tama-DOXPCB should be useful for the targeted elimination of hPSCs contained in hPSC-derived cell therapy products. This is the first report of the generation of lectin-prodrug conjugates. BC2Tama should be applicable for the targeted delivery of various types of biotinylated compounds into hPSCs.
关键词： prodrugs,pluripotent stem cells,tumorigenicity,lectin
更新于2025-09-19 17:15:36
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Dopaminergic induction of human dental pulp stem cells by photobiomodulation: comparison of 660nm laser light and polychromatic light in the nir
摘要： Human dental pulp stem cells (hDPSCs) are able to differentiate into dopaminergic neurons and help the maintenance of partially degenerated neurons, which makes them as an alternative cell source for treatment of Parkinsons' disease (PD) patients. Here, the effect of photobiomodulation with polychromatic light source in the near infrared (NIR) range (600–1200 nm) or low level 660 nm diode laser light on hDPSCs during dopaminergic induction was investigated. Real time RT-qPCR analysis indicated that expressions of brain derived neurotrophic factor (BDNF), glial cell line derived neurotropic factor (GNDF), matrix associated protein 2 (MAP2), nuclear receptor related 1 protein (NURR1) and dopamine transporter (DAT) were increased, especially in the first 7 days of dopaminergic induction when 660 nm laser light was applied with a total energy density of 1.6 J/cm2. The activity of polychromatic light on hDPSCs depended on the differentiation media and protein type. BDNF, GDNF, NURR-1 and MAP2 expressions were increased in the presence of pre-induction factors, and decreased when the post-induction factors were added into the culture medium. In contrast with all these promising results, the dopaminergically induced hDPSCs did not show any functional characteristics of dopaminergic neurons and died after they were transferred to a new laminin coated culture plates. In conclusion, the expression of dopaminergic neuron protective protein mRNAs in hDPSCs was increased by photobiomodulation in defined conditions. However, the cells were not able to differentiate into functional dopaminergic neurons either in control or in photobiomodulated groups that are prone to cell death and exhibit immature dopaminergic neuron characteristics.
关键词： Dopaminergic neuron,Photobiomodulation,Parkinson's disease,Polychromatic light,Human dental pulp stem cells,Laser
更新于2025-09-19 17:13:59
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Improved 3D Stem Mapping Method and Elliptic Hypothesis-Based DBH Estimation from Terrestrial Laser Scanning Data
摘要： The detailed structure information under the forest canopy is important for forestry surveying. As a high-precision environmental sensing and measurement method, terrestrial laser scanning (TLS) is widely used in high-precision forestry surveying. In TLS-based forestry surveys, stem-mapping, which is focused on detecting and extracting trunks, is one of the core data processing tasks and the basis for the subsequent calculation of tree attributes; one of the most basic attributes is the diameter at breast height (DBH). This article explores and improves the methods for stem mapping and DBH estimation from TLS data. Firstly, an improved 3D stem mapping algorithm considering the growth direction in random sample consistency (RANSAC) cylinder fitting is proposed to extract and fit the individual tree point cloud section. It constructs the hierarchical optimum cylinder of the trunk and introduces the growth direction into the establishment of the backbone buffer in the next layer. Experimental results show that it can effectively remove most of the branches and reduce the interference of the branches to the discrimination of trunks and improve the integrity of stem extraction by about 36%. Secondly, a robust least squares ellipse fitting method based on the elliptic hypothesis is proposed for DBH estimation. Experimental results show that the DBH estimation accuracy of the proposed estimation method is improved compared with other methods. The mean root mean squared error (RMSE) of the proposed estimation method is 1.14 cm, compared with other methods with a mean RMSE of 1.70, 2.03, and 2.14 cm. The mean relative accuracy of the proposed estimation method is 95.2%, compared with other methods with a mean relative accuracy of 92.9%, 91.9%, and 90.9%.
关键词： diameter at breast height (DBH),terrestrial laser scanning (TLS),robust least square elliptic fitting,3D stem-mapping
更新于2025-09-19 17:13:59
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[IEEE 2019 IEEE 8th International Conference on Advanced Optoelectronics and Lasers (CAOL) - Sozopol, Bulgaria (2019.9.6-2019.9.8)] 2019 IEEE 8th International Conference on Advanced Optoelectronics and Lasers (CAOL) - Mechanisms of Immunocorrective Action of Complex Treatment Using Photodynamic, Cell and Tissue Therapy in Patients with Purulent Wounds of The Lower Extremities
摘要： It was shown that the combined use of photodynamic therapy of different wavelengths (red ? = 660 nm, green = 530 nm, blue ? = 440 nm), hematopoietic stem cells and platelet growth factor is an effective treatment for purulent-septic complications, which can be considered as a new technology for correcting afferent and efferent immunoreactivity in patients with chronic purulent wounds that are not susceptible to antibiotic therapy.
关键词： purulent wounds,photodynamic therapy,hematopoietic stem cells,platelet growth factor
更新于2025-09-19 17:13:59
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Striated 2D Lattice with Sub‐nm 1D Etch Channels by Controlled Thermally Induced Phase Transformations of PdSe <sub/>2</sub>
摘要： 2D crystals are typically uniform and periodic in-plane with stacked sheet-like structure in the out-of-plane direction. Breaking the in-plane 2D symmetry by creating unique lattice structures offers anisotropic electronic and optical responses that have potential in nanoelectronics. However, creating nanoscale-modulated anisotropic 2D lattices is challenging and is mostly done using top-down lithographic methods with ≈10 nm resolution. A phase transformation mechanism for creating 2D striated lattice systems is revealed, where controlled thermal annealing induces Se loss in few-layered PdSe2 and leads to 1D sub-nm etched channels in Pd2Se3 bilayers. These striated 2D crystals cannot be described by a typical unit cells of 1–2 ? for crystals, but rather long range nanoscale periodicity in each three directions. The 1D channels give rise to localized conduction states, which have no bulk layered counterpart or monolayer form. These results show how the known family of 2D crystals can be extended beyond those that exist as bulk layered van der Waals crystals by exploiting phase transformations by elemental depletion in binary systems.
关键词： Se vacancies,Pd2Se3,2D crystals,PdSe2,STEM,1D channels
更新于2025-09-19 17:13:59