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1.
J Proteome Res ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231884

RESUMO

ARID3C is a protein located on human chromosome 9 and expressed at low levels in various organs, yet its biological function has not been elucidated. In this study, we investigated both the cellular localization and function of ARID3C. Employing a combination of LC-MS/MS and deep learning techniques, we identified NPM1 as a binding partner for ARID3C's nuclear shuttling. ARID3C was found to predominantly localize with the nucleus, where it functioned as a transcription factor for genes STAT3, STAT1, and JUNB, thereby facilitating monocyte-to-macrophage differentiation. The precise binding sites between ARID3C and NPM1 were predicted by AlphaFold2. Mutating this binding site prevented ARID3C from interacting with NPM1, resulting in its retention in the cytoplasm instead of translocation to the nucleus. Consequently, ARID3C lost its ability to bind to the promoters of target genes, leading to a loss of monocyte-to-macrophage differentiation. Collectively, our findings indicate that ARID3C forms a complex with NPM1 to translocate to the nucleus, acting as a transcription factor that promotes the expression of the genes involved in monocyte-to-macrophage differentiation.

2.
Ecol Evol ; 13(12): e10792, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38077507

RESUMO

Climatic fluctuations and geological events since the LGM are believed to have significantly impacted the population size, distribution, and mobility of many species that we observe today. In this paper, we determined the processes driving the phylogeographic structure of the Korean endemic white forsythia by combining the use of genome-wide SNPs and predicting paleoclimatic habitats during the LGM (21 kya), Early Holocene (10 kya), Mid-Holocene (6 kya), and Late Holocene (3 kya). Using a maximum of 1897 SNPs retrieved from 124 samples across nine wild populations, five environmental predictors, and the species' natural occurrence records, we aimed to infer the species' demographic history and reconstruct its possible paleodistributions with the use of approximate Bayesian computation and ecological niche models, respectively. Under this integrated framework, we found strong evidence for patterns of range shift and expansion, and population divergence events from the onset of the Holocene, resulting in the formation of its five distinct genetic units. The most highly supported model inferred that after the split of an ancestral population into the southern group and a larger central metapopulation lineage, the latter gave rise to the eastern and northern clusters, before finally dividing into two sub-central groups. While the use of molecular data allowed us to identify and refine the (phylo)genetic relationships of the species' lineages and populations, the use of ecological data helped us infer a past LGM refugium and the directions of post-glacial range dynamics. The time frames of these demographic events were shown to be congruent with climatic and geological events that affected the central Korean Peninsula during these periods. These findings gave us a better understanding of the consequences of past spatiotemporal factors that may have resulted in the current fragmented population distribution of this endangered plant.

3.
Sci Rep ; 13(1): 22303, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102231

RESUMO

In this study, numerical simulation was employed to predict the performance and internal flow characteristics of the inlet of an axial-flow pump by assigning an absolute flow angle to the inlet guide vane (IGV) trailing-edge flow. Further, the finite volume method based on the three-dimensional Reynolds-averaged Navier-Stokes equations was employed to discretize the governing equations. The shear stress transport model was used as the turbulence model, and an appropriate number of nodes were selected for the hexahedral grid system through a grid-dependency test. The performance curve and changes in the internal flow field were investigated based on the variation in the flow angle at the inlet of the axial-flow pump. These results can be used to establish an efficient operational plan by adjusting the IGV angle of IGV when installing a variable IGV for an axial-flow pump.

4.
Plants (Basel) ; 12(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37050109

RESUMO

Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.

5.
Nat Commun ; 14(1): 685, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755020

RESUMO

Constructing a mono-atom step-level ultra-flat material surface is challenging, especially for thin films, because it is prohibitively difficult for trillions of clusters to coherently merge. Even though a rough metal surface, as well as the scattering of carriers at grain boundaries, limits electron transport and obscures their intrinsic properties, the importance of the flat surface has not been emphasised sufficiently. In this study, we describe in detail the initial growth of copper thin films required for mono-atom step-level flat surfaces (MSFSs). Deposition using atomic sputtering epitaxy leads to the coherent merging of trillions of islands into a coplanar layer, eventually forming an MSFS, for which the key factor is suggested to be the individual deposition of single atoms. Theoretical calculations support that single sputtered atoms ensure the formation of highly aligned nanodroplets and help them to merge into a coplanar layer. The realisation of the ultra-flat surfaces is expected to greatly assist efforts to improve quantum behaviour by increasing the coherency of electrons.

6.
Plants (Basel) ; 11(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36297700

RESUMO

Berberine and berbamine are bioactive compounds of benzylisoquinoline alkaloids (BIAs) present in Berberis species. The contents of berbamine are 20 times higher than berberine in leaf tissues in three closely related species: Berberis koreana, B. thunbergii and B. amurensis. This is the first report on the quantification of berberine compared to the berbamine in the Berberis species. Comparative transcriptome analyses were carried out with mRNAs from the leaf tissues of the three-species. The comparison of the transcriptomes of B. thunbergii and B. amurensis to those of B. koreana, B. thunbergii showed a consistently higher number of differentially expressed genes than B. amurensis in KEGG and DEG analyses. All genes encoding enzymes involved in berberine synthesis were identified and their expressions were variable among the three species. There was a single copy of CYP80A/berbamunine synthase in B. koreana. Methyltransferases and cytochrome P450 mono-oxidases (CYPs) are key enzymes for BIA biosynthesis. The current report contains the copy numbers and other genomic characteristics of the methyltransferases and CYPs in Berberis species. Thus, the contents of the current research are valuable for molecular characterization for the medicinal utilization of the Berberis species.

7.
Sci Rep ; 12(1): 15240, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085157

RESUMO

The stall in an axial fan is directly related to detrimental phenomena such as performance degradation, vibration, noise, and flow instability at low flow rates. As a kind of passive control method to handle the stall, two-dimensional plates so-named anti-stall fin (ASF) were suggested by ourselves and were attached inside the casing. In this study, the ASF's effect on the internal flow pattern was visually investigated in the flow passage, and its tendency was discussed with the performance curve. Subsequently, the ASF's functional limitations for various design parameters, which the ASF can derive aerodynamically, were presented as the primary focus of this study. Each one-factor analysis was performed, and the internal flow pattern was observed in parallel at the point where the ASF lost its function. For the radial length, axial length, number of fins, and positive-tangential angle, the ASF almost retained its function up to the limitation to prevent instability but radically lost its function at a certain flow rate. For the axial gap and negative-tangential angle, the ASF gradually lost its function. Mostly, this study was based on numerical analysis, and the performance was validated through experimental tests.


Assuntos
Febre Suína Africana , Osteopatia , Nadadeiras de Animais , Animais , Análise Fatorial , Artéria Radial , Suínos
8.
ACS Nano ; 16(10): 17033-17040, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36173357

RESUMO

High pressure or strain is an effective strategy for generating phase transformations in van der Waals (vdW) layered materials without introducing defects, but this approach remains difficult to perform consistently. We present a scalable and facile method for achieving phase transformation in vdW materials, wherein solid vdW materials are subject to internal thermal stress within a molten metal mantle as it undergoes cooling. This internal thermal stress is principally the product of differential thermal expansion between mantle and core and can be tuned by the mantle material and temperature conditions. We validated this approach by achieving phase transformation of red phosphorus to black phosphorus, and metallic 1T'- to semiconducting 2H-MoTe2 crystals. We further demonstrate quantum electronic phase transformation of suppressed charge density wave in TiSe2 by means of electron-phonon coupling using the same system.

9.
Molecules ; 27(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889464

RESUMO

The annual herb Euphorbia maculata L. produces anti-inflammatory and biologically active substances such as triterpenoids, tannins, and polyphenols, and it is used in traditional Chinese medicine. Of these bioactive compounds, terpenoids, also called isoprenoids, are major secondary metabolites in E. maculata. Full-length cDNA sequencing was carried out to characterize the transcripts of terpenoid biosynthesis reference genes and determine the copy numbers of their isoforms using PacBio SMRT sequencing technology. The Illumina short-read sequencing platform was also employed to identify differentially expressed genes (DEGs) in the secondary metabolite pathways from leaves, roots, and stems. PacBio generated 62 million polymerase reads, resulting in 81,433 high-quality reads. From these high-quality reads, we reconstructed a genome of 20,722 genes, in which 20,246 genes (97.8%) did not have paralogs. About 33% of the identified genes had two or more isoforms. DEG analysis revealed that the expression level differed among gene paralogs in the leaf, stem, and root. Whole sets of paralogs and isoforms were identified in the mevalonic acid (MVA), methylerythritol phosphate (MEP), and terpenoid biosynthesis pathways in the E. maculata L. The nucleotide information will be useful for identifying orthologous genes in other terpenoid-producing medicinal plants.


Assuntos
Euphorbia , DNA Complementar/genética , Euphorbia/genética , Euphorbia/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Terpenos/metabolismo , Transcriptoma/genética
10.
ACS Nano ; 16(6): 8851-8859, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35713417

RESUMO

Vertical van der Waals heterostructures (vdWhs), which are made by layer-by-layer stacking of two-dimensional (2D) materials, offer great opportunities for the development of extraordinary physics and devices such as topological superconductivity, robust quantum Hall phenomenon, electron-hole pair condensation, Coulomb drag, and tunneling devices. However, the size of vdWhs is still limited to the order of a few micrometers, which restricts the large-scale roll-to-roll processes for industrial applications. Herein, we report the sequential growth of a 14 in. vertical vdWhs on a rollable Al foil via chemical vapor deposition. By supplying chalcogen precursors to liquid transition-metal precursor-coated Al foils, we grew a wide range of individual 2D transition-metal dichalcogenide (TMD) films, including MoS2, VS2, ReS2, WS2, SnS2, WSe2, and vanadium-doped MoS2. Additionally, by repeating the growth process, we successfully achieved the layer-by-layer growth of ReS2/MoS2 and SnS2/ReS2/MoS2 vdWhs. The chemically inert Al native oxide layer inhibits the diffusion of chalcogen and metal atoms into Al foils, allowing for the growth of diverse TMDs and their vdWhs. The conductive Al substrate enables the effective use of vdWhs/Al as a hydrogen evolution reaction electrocatalyst with a transfer-free process. This work provides a robust route for the commercialization of 2D TMDs and their vdWhs at a low cost.

11.
PLoS One ; 17(5): e0267466, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511775

RESUMO

OBJECTIVES: The preventive effects of Korean red ginseng (KRG) on bone loss and microarchitectural deterioration have been extensively studied in animal models. However, few results have been reported for the effects of KRG on the trabecular microarchitecture as compared to changes resulting from physiological stimuli such as exercise load. We compared the effects of KRG and jump exercise on improvements in trabecular microarchitecture and strength of the distal femoral metaphysis in rats. METHODS AND MATERIALS: Eleven-week-old male Wistar rats were divided into sedentary (CON), KRG-administered (KRG), and jump-exercised (JUM) groups. Rats were orally administered KRG extract (200 mg/kg body weight/day) once a day for 6 weeks. The jump exercise protocol comprised 10 jumps/day, 5 days/week at a jump height of 40 cm. We used microcomputed tomography to assess the microarchitecture, volumetric bone mineral density (vBMD), and fracture load as predicted by finite element analysis at the right distal femoral metaphysis. The left femur was used for the quantitative bone histomorphometry measurements. RESULTS: Although KRG produced significantly higher trabecular bone volume (BV/TV) than CON, BV/TV was even higher in JUM than in KRG, and differences in vBMD and fracture load were only significant between JUM and CON. In terms of trabecular microarchitecture, KRG increased trabecular number and connectivity, whereas the JUM group showed increased trabecular thickness. Bone resorption showed significant decrease by JUM and KRG group. In contrast, bone formation showed significant increase by JUM group. CONCLUSIONS: These data show that KRG has weak but significant positive effects on bone mass and suggest that the effects on trabecular microarchitecture differ from those of jump exercise. The effects of combined KRG and jump exercise on trabecular bone mass and strength should be investigated.


Assuntos
Osso Esponjoso , Panax , Animais , Densidade Óssea/fisiologia , Osso Esponjoso/diagnóstico por imagem , Masculino , Ratos , Ratos Wistar , Microtomografia por Raio-X
12.
Nature ; 603(7901): 434-438, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35296844

RESUMO

Oxidation can deteriorate the properties of copper that are critical for its use, particularly in the semiconductor industry and electro-optics applications1-7. This has prompted numerous studies exploring copper oxidation and possible passivation strategies8. In situ observations have, for example, shown that oxidation involves stepped surfaces: Cu2O growth occurs on flat surfaces as a result of Cu adatoms detaching from steps and diffusing across terraces9-11. But even though this mechanism explains why single-crystalline copper is more resistant to oxidation than polycrystalline copper, the fact that flat copper surfaces can be free of oxidation has not been explored further. Here we report the fabrication of copper thin films that are semi-permanently oxidation resistant because they consist of flat surfaces with only occasional mono-atomic steps. First-principles calculations confirm that mono-atomic step edges are as impervious to oxygen as flat surfaces and that surface adsorption of O atoms is suppressed once an oxygen face-centred cubic (fcc) surface site coverage of 50% has been reached. These combined effects explain the exceptional oxidation resistance of ultraflat Cu surfaces.

13.
Adv Mater ; 34(10): e2106551, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34962658

RESUMO

Magnetic order has been proposed to arise from a variety of defects, including vacancies, antisites, and grain boundaries, which are relevant in numerous electronics and spintronics applications. Nevertheless, its magnetism remains controversial due to the lack of structural analysis. The escalation of ferromagnetism in vanadium-doped WSe2 monolayer is herein demonstrated by tailoring complex configurations of Se vacancies (SeVac ) via post heat-treatment. Structural analysis of atomic defects is systematically performed using transmission electron microscopy (TEM), enabled by the monolayer nature. Temperature-dependent magnetoresistance hysteresis ensures enhanced magnetic order after high-temperature heat-treatment, consistent with magnetic domain analysis from magnetic force microscopy (MFM). The vanadium-Se vacancy pairing is a key to promoting ferromagnetism via spin-flip by electron transfer, predicted from density-functional-theory (DFT) calculations. The approach toward nanodefect engineering paves a way to overcome weak magnetic order in diluted magnetic semiconductors (DMSs) for renovating semiconductor spintronics.

14.
J Bone Metab ; 28(4): 253-265, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34905673

RESUMO

Mechanical loading is generally considered to have a positive impact on the skeleton; however, not all types of mechanical loading have the same beneficial effect. Many researchers have investigated which types of mechanical loading are more effective for improving bone mass and strength. Among the various mechanical loads, high-impact loading, such as jumping, appears to be more beneficial for bones than low-impact loadings such as walking, running, or swimming. Therefore, the different forms of mechanical loading exerted by running, swimming, and jumping exercises may have different effects on bone adaptations. However, little is known about the relationships between the types of mechanical loading and their effects on trabecular bone structure. The purpose of this article is to review the recent reports on the effects of treadmill running, jumping, and swimming on the trabecular bone microarchitecture in small animals. The effects of loading on trabecular bone architecture appear to differ among these different exercises, as several reports have shown that jumping increases the trabecular bone mass by thickening the trabeculae, whereas treadmill running and swimming add to the trabecular bone mass by increasing the trabecular number, rather than the thickness. This suggests that different types of exercise promote gains in trabecular bone mass through different architectural patterns in small animals.

15.
J Appl Clin Med Phys ; 22(10): 270-277, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34529348

RESUMO

In this study, breast phantoms were fabricated by emulating glandular and adipose tissues separately using a three-dimensional (3D) printer. In addition, direct and quantitative glandular dose evaluations were performed. A quantitative method was developed to evaluate the glandular and adipose tissues separately when performing glandular dose evaluations. The variables used for glandular dose evaluation were breast thickness, glandular tissue ratio, and additional filter materials. The values obtained using a Monte Carlo simulation and those measured using a glass dosimeter were compared and analyzed. The analysis showed that as the glandular tissue ratio increased, the dose decreased by approximately 10%, which is not a significant variation. The comparison revealed that the simulated values of the glandular dose were approximately 15% higher than the measured values. The use of silver and rhodium filters resulted in a mean simulated dose of 1.00 mGy and 0.72 mGy, respectively, while the corresponding mean measured values were 0.89 mGy ± 0.03 mGy and 0.62 mGy ± 0.02 mGy. The mean glandular dose can be reliably evaluated by comparing the simulated and measured values.


Assuntos
Mama , Mamografia , Mama/diagnóstico por imagem , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação
16.
Adv Sci (Weinh) ; 8(16): e2003709, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34085785

RESUMO

Among transition metal dichalcogenides (TMdCs) as alternatives for Pt-based catalysts, metallic-TMdCs catalysts have highly reactive basal-plane but are unstable. Meanwhile, chemically stable semiconducting-TMdCs show limiting catalytic activity due to their inactive basal-plane. Here, metallic vanadium sulfide (VSn ) nanodispersed in a semiconducting MoS2 film (V-MoS2 ) is proposed as an efficient catalyst. During synthesis, vanadium atoms are substituted into hexagonal monolayer MoS2 to form randomly distributed VSn units. The V-MoS2 film on a Cu electrode exhibits Pt-scalable catalytic performance; current density of 1000 mA cm-2 at 0.6 V and overpotential of -0.08 V at a current density of 10 mA cm-2 with excellent cycle stability for hydrogen-evolution-reaction (HER). The high intrinsic HER performance of V-MoS2 is explained by the efficient electron transfer from the Cu electrode to chalcogen vacancies near vanadium sites with optimal Gibbs free energy (-0.02 eV). This study provides insight into ways to engineer TMdCs at the atomic-level to boost intrinsic catalytic activity for hydrogen evolution.

17.
Biochim Biophys Acta Proteins Proteom ; 1869(9): 140672, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34000451

RESUMO

Krüppel-like factor 2 (Klf2) is a DNA-binding transcription factor that regulates embryonic stem cell-specific gene expression. Transcription cofactors such as p300 acetyltransferase and Erk kinases interact with Klf2, providing an additional layer of transcription regulation in embryonic stem cells. To carry out a thorough survey of the Klf2 interactome in embryonic stem cells and identify novel transcription cofactors, we designed a modified immunoprecipitation-mass spectrometry (IP-MS) method. In this method, recombinant Klf2, expressed and purified from Sf9 insect cells instead of ectopically expressed in cells, was used as bait. Using this modified IP-MS method, we discovered nine Klf2-interacting proteins, including the previously reported Crebbp and p300. These proteins showed at least an 8-fold increase in signal intensity in Klf2 pull-downs compared with controls, with P-values <0.010. Among the identified Klf2-binding proteins confirmed using our IP-MS workflow was Snd1, which we found to interact directly with Klf2 and function as a transcriptional coactivator of Klf2 to drive the Oct4 gene expression. Collectively, our IP-MS protocol may offer a useful tool for identifying novel transcription cofactors in stem cells.


Assuntos
Imunoprecipitação/métodos , Fatores de Transcrição Kruppel-Like/metabolismo , Espectrometria de Massas/métodos , Animais , Linhagem Celular , Proteínas de Ligação a DNA , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/fisiologia , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Ligação Proteica , Fatores de Transcrição
18.
J Tissue Eng ; 12: 20417314211008626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959246

RESUMO

Exosomes derived from mesenchymal stem cells (MSCs) have been studied as vital components of regenerative medicine. Typically, various isolation methods of exosomes from cell culture medium have been developed to increase the isolation yield of exosomes. Moreover, the exosome-depletion process of serum has been considered to result in clinically active and highly purified exosomes from the cell culture medium. Our aim was to compare isolation methods, ultracentrifuge (UC)-based conventional method, and tangential flow filtration (TFF) system-based method for separation with high yield, and the bioactivity of the exosome according to the purity of MSC-derived exosome was determined by the ratio of Fetal bovine serum (FBS)-derived exosome to MSC-derived exosome depending on exosome depletion processes of FBS. The TFF-based isolation yield of exosome derived from human umbilical cord MSC (UCMSC) increased two orders (92.5 times) compared to UC-based isolation method. Moreover, by optimizing the process of depleting FBS-derived exosome, the purity of UCMSC-derived exosome, evaluated using the expression level of MSC exosome surface marker (CD73), was about 15.6 times enhanced and the concentration of low-density lipoprotein-cholesterol (LDL-c), known as impurities resulting from FBS, proved to be negligibly detected. The wound healing and angiogenic effects of highly purified UCMSC-derived exosomes were improved about 23.1% and 71.4%, respectively, with human coronary artery endothelial cells (HCAEC). It suggests that the defined MSC exosome with high yield and purity could increase regenerative activity.

19.
Nanomaterials (Basel) ; 11(5)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923237

RESUMO

Non-volatile memory (NVM) devices based on three-terminal thin-film transistors (TFTs) have gained extensive interest in memory applications due to their high retained characteristics, good scalability, and high charge storage capacity. Herein, we report a low-temperature (<100 °C) processed top-gate TFT-type NVM device using indium gallium zinc oxide (IGZO) semiconductor with monolayer gold nanoparticles (AuNPs) as a floating gate layer to obtain reliable memory operations. The proposed NVM device exhibits a high memory window (ΔVth) of 13.7 V when it sweeps from -20 V to +20 V back and forth. Additionally, the material characteristics of the monolayer AuNPs (floating gate layer) and IGZO film (semiconductor layer) are confirmed using transmission electronic microscopy (TEM), atomic force microscopy (AFM), and x-ray photoelectron spectroscopy (XPS) techniques. The memory operations in terms of endurance and retention are obtained, revealing highly stable endurance properties of the device up to 100 P/E cycles by applying pulses (±20 V, duration of 100 ms) and reliable retention time up to 104 s. The proposed NVM device, owing to the properties of large memory window, stable endurance, and high retention time, enables an excellent approach in futuristic non-volatile memory technology.

20.
ACS Nano ; 15(4): 7575-7585, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33724774

RESUMO

Kidney tissue engineering and regeneration approaches offer great potential for chronic kidney disease treatment, but kidney tissue complexity imposes an additional challenge in applying regenerative medicine for renal tissue regeneration. In this study, a porous pneumatic microextrusion (PME) composite scaffold consisting of poly(lactic-co-glycolic acid) (PLGA, P), magnesium hydroxide (MH, M), and decellularized porcine kidney extracellular matrix (kECM, E) is functionalized with bioactive compounds, polydeoxyribonucleotide (PDRN), and tumour necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-primed mesenchymal stem-cell-derived extracellular vesicles (TI-EVs) to improve the regeneration and maintenance of a functional kidney tissue. The combination of PDRN and TI-EVs showed a significant synergistic effect in regenerative processes including cellular proliferation, angiogenesis, fibrosis, and inflammation. In addition, the PME/PDRN/TI-EV scaffold induced an effective glomerular regeneration and restoration of kidney function compared to the existing PME scaffold in a partial nephrectomy mouse model. Therefore, such an integrated bioactive scaffold that combines biochemical cues from PDRN and TI-EVs and biophysical cues from a porous PLGA scaffold containing MH and kECM can be used as an advanced tissue engineering platform for kidney tissue regeneration.


Assuntos
Vesículas Extracelulares , Rim , Animais , Camundongos , Polidesoxirribonucleotídeos , Regeneração , Suínos , Engenharia Tecidual , Alicerces Teciduais
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