Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 442
Filtrar
1.
Chem Commun (Camb) ; 60(36): 4805-4809, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38602381

RESUMO

A rapid and eco-friendly route has been developed for the synthesis of SAPO-34 with short crystallization time (1-3 h), low silica content (as low as 6.2 wt%) and excellent methanol-to-olefin (MTO) catalytic performance by utilization of a recycled mother liquid at elevated crystallization temperature.

2.
ACS Appl Mater Interfaces ; 16(15): 18745-18753, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38573811

RESUMO

Zeolite-catalyzed dimethyl ether (DME) carbonylation provides a novel route to producing methyl acetate (MeOAc). Mordenite (MOR) has drawn significant interest because of its remarkable MeOAc selectivity in DME carbonylation, albeit with limited catalytic stability. Herein, novel MOR-based DME carbonylation catalysts, distinguished by long-term stability and high activity were successfully developed, based on an H2-promoted benign coke strategy. Both the H2 cofeeds and the presence of metal species with hydrogenation capability are demonstrated to be crucial for the regulation of coke depositions. The coke deposits can potentially cover the acid sites in the 12-MR main channels, thereby mitigating the occurrence of undesirable methanol-to-hydrocarbon side reactions. Meanwhile, the elimination of ultralarge coke species under the assistance of H2 and Cu species could ensure smooth mass transfer within the catalyst, contributing to its remarkable catalytic performance. The most highlighted DME carbonylation performance was achieved on coke-mediated CuZn-HMOR with a high MeOAc yield of 0.4-0.5 g·gcat-1·h-1 for over 520 h (over 50× enhancement versus HMOR), exhibiting promising industrial application potential. The current strategy is expected to inspire further research into zeolite-catalyzed reactions, which could be potentially improved by the presence of benign coke.

3.
Front Immunol ; 15: 1363517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562923

RESUMO

Background: Treatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs. Materials and methods: hUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server. Result: 3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs. Conclusion: Clinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as "division of labor" mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Camundongos , Animais , Ligantes , Infarto do Miocárdio/genética , Coração , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Células Estromais
4.
J Am Chem Soc ; 146(15): 10257-10262, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38578111

RESUMO

Sorption-based atmospheric water harvesting (AWH) is a promising solution for addressing water scarcity. Developing cost-effective and stable water adsorbents with high water uptake capacity and a low-temperature regeneration requirement is a crucially important procedure. In this Communication, we present a novel and stable aluminophosphate (AlPO) molecular sieve (MS) named DNL-11 with 16-ring channels synthesized by using an affordable and commercialized organic structure directing agent (OSDA), whose crystallographic structure is elucidated by three-dimensional electron diffraction (3D ED). DNL-11 exhibits a significant water uptake capacity (189 mg/g) at a very low vapor pressure (5% relative humidity at 30 °C). In addition, most of the adsorbed water can be effortlessly removed by purging N2 at 25 °C under ambient pressure conditions. This may expand the possibility of AWH under extreme drought conditions.

5.
Mol Ther ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582962

RESUMO

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

6.
Stem Cell Res Ther ; 15(1): 122, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679727

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. METHODS: In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. RESULTS: In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p < 0.05). MSC transplantation improved the function of 4-m walking test (4MWT) compared with the placebo group with a decrease of 2.05 s at 6 months of follow-up (p = 0.21). The measurement of grip strength revealed group difference with MSCs group demonstrating better performance, particularly at 6 months (p = 0.002). Inflammatory cytokines (TNF-α, IL-17) exhibited declines in MSCs group at 6 months compared to the placebo group (p = 0.034 and 0.033, respectively). There was no difference of incidence of AEs between the two groups. CONCLUSION: Intravenous transplantation of HUC-MSCs is a safe and effective therapeutic approach on aging frailty. The positive outcomes observed in improving quality of life, physical performance, and reducing chronic inflammation, suggest that HUC-MSC therapy may be a promising potential treatment option for aging frailty. TRIAL REGISTRATION: Clinicaltrial.gov; NCT04314011; https://clinicaltrials.gov/ct2/show/NCT04314011 .


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Qualidade de Vida , Cordão Umbilical , Humanos , Feminino , Masculino , Método Duplo-Cego , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Idoso , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Fragilidade/terapia , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Idoso de 80 Anos ou mais , Resultado do Tratamento
7.
Commun Biol ; 7(1): 505, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678117

RESUMO

Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP's structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.


Assuntos
Microscopia Crioeletrônica , Ácidos Graxos , alfa-Fetoproteínas , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/química , Glicosilação , Sítios de Ligação , Humanos , Ácidos Graxos/metabolismo , Metais/metabolismo , Metais/química , Modelos Moleculares , Conformação Proteica , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química
8.
Micromachines (Basel) ; 15(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38675282

RESUMO

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via laser beam power bed fusion (LB-PBF), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 °C for 1 h. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also influencing the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 h and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving LB-PBF and heat treatment.

9.
Polymers (Basel) ; 16(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611277

RESUMO

To investigate the relationship between structures and adsorption properties, four different morphologies of chitosan, with hydrogel (CSH), aerogel (CSA), powder (CSP), and electrospinning nanofiber (CSEN) characteristics, were employed as adsorbents for the removal of Acid Red 27. The structures and morphologies of the four chitosan adsorbents were characterized with SEM, XRD, ATR-FTIR, and BET methods. The adsorption behaviors and mechanisms of the four chitosan adsorbents were comparatively studied. All adsorption behaviors exhibited a good fit with the pseudo-second-order kinetic model (R2 > 0.99) and Langmuir isotherm model (R2 > 0.99). Comparing the adsorption rates and the maximum adsorption capacities, the order was CSH > CSA > CSP > CSEN. The maximum adsorption capacities of CSH, CSA, CSP, and CSEN were 2732.2 (4.523), 676.7 (1.119), 534.8 (0.885), and 215.5 (0.357) mg/g (mmol/g) at 20 °C, respectively. The crystallinities of CSH, CSA, CSP, and CSEN were calculated as 0.41%, 6.97%, 8.76%, and 39.77%, respectively. The crystallinity of the four chitosan adsorbents was the main factor impacting the adsorption rates and adsorption capacities, compared with the specific surface area. With the decrease in crystallinity, the adsorption rates and capacities of the four chitosan adsorbents increased gradually under the same experimental conditions. CSH with a low crystallinity and large specific surface area resulted in the highest adsorption rate and capacity.

10.
J Am Chem Soc ; 146(12): 8086-8097, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38479729

RESUMO

Achieving multiple high-value-added chemical production through novel reaction processes and shape-selective catalytic strategy is the key to realizing efficient low-carbon catalytic processes. In this work, a methanol-toluene coreaction system was developed, and combined control strategies of reaction pathway guidance and shape-selective catalysis were applied for the successful production of light olefins and para-xylene on single HZSM-5 catalyst bed. Cofeeding toluene additionally provides reactive and flowing aromatic hydrocarbon pool species that change the dominant reaction pathway in the complex network of the methanol reaction on HZSM-5 and promote the formation of ethylene. For the first time, the key reaction intermediates methylmethylenecyclodiene are directly captured and identified by experimental and theoretical techniques. This helps to propose the catalytic cycle for the dominant generation of ethylene and, more importantly, enriches the methanol-to-hydrocarbons (MTH) chemistry and hydrocarbon pool mechanism. Furthermore, 0.4HZSM-5@S-1-CLD, an optimized HZSM-5 catalyst modified by the silicalite-1 epitaxial growth followed by silanization approach, realizes highly selective production of light olefins (especially ethylene) and para-xylene, while excellent reactant activity is maintained. This highly efficient coreaction route gives an important leading significance in synthesizing the raw materials for the polyolefin and polyester industries. The establishment of the combined control strategies provides a model for the joint production of multiple target chemicals in complex catalytic processes.

11.
J Colloid Interface Sci ; 664: 626-639, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490038

RESUMO

Dealuminated Beta zeolite has a large amount of silanol defects on its interface, which provides an ideal place for embedding metal species and creating metal active sites in a confined microenvironment. The confined metal sites as well as their surroundings are closely related to the reactant activation and transient state achievement. Hence, unraveling the confined metal sites is of great significance for the catalytic reaction process. Herein, niobium species were incorporated into the silanol defects over dealuminated Beta zeolite with a facile dry impregnation method, co-grinding the niobium precursor with dealuminated Beta zeolite support. The successful incorporation of niobium into the silanol defects for 30Nb-Beta zeolite was verified by DRIFT, 1H MAS NMR, UV-Vis and UV-Raman characterizations. XAS characterization and DFT calculations further disclosed that the confined Nb species existed as (SiO)2Nb(OH)(=O), containing two Si-O-Nb bonds, one Nb=O bond as well as one Nb-OH bond. The synthesized 30Nb-Beta zeolite catalyst displayed a superior cyclohexene conversion of 51.1%, cyclohexene oxide selectivity of 83.1% as well as TOF value of 188.2 h-1 ascribed to the inherent electrophilicity of Nb(V) for confined (SiO)2Nb(OH)(=O) species as well as the low oxygen transfer energy barrier for NbV-OOH species. Furthermore, the prepared 30Nb-Beta zeolite can be effectively employed to other cyclic alkene epoxidation reactions.

12.
Aging (Albany NY) ; 16(6): 5651-5675, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38517374

RESUMO

Heart failure (HF) is a serious global health issue that demands innovative treatment approaches. In this study, we collected samples from 4 HF patients before and after MSC therapy and performed scRNA-seq. After the MSC therapy, the proportion of CD14+ monocytes decreased significantly in both the treatment response and non-response groups, with a more pronounced decrease in the treatment response group. The therapy-response and non-response group were clearly separated in the UMAP plot, while the CD14+ monocytes in the therapy-response group before and after MSC therapy were very similar, but there were significant differences in the non-response group. By further performing NMF analysis, we identified 11 subsets of CD14+ monocytes. More importantly, we identified a therapy-related CD14+ monocyte subpopulation. The predictive model based on CD14+ monocytes constructed by machine learning algorithms showed good performance. Moreover, genes such as FOS were highly enriched in the therapy-related CD14+ monocytes. The SCENIC analysis revealed potential regulatory factors for this treatment-responsive CD14+ monocytes, and FOS/JUN were identified as potential core indicators/regulators. Finally, HF patients were divided into three groups by NMF analysis, and the therapy-responsive CD14+ monocyte characteristics were differentially activated among the three groups. Together, this study identifies treatment-responsive CD14+ monocytes as a crucial biomarker for assessing the suitability of MSC therapy and determining which HF patients could benefit from it. This provides new clues for further investigating the therapeutic mechanisms of MSC therapy, offering beneficial insights for personalized treatment and improving prognosis in HF patients.


Assuntos
Insuficiência Cardíaca , Transplante de Células-Tronco Mesenquimais , Humanos , Biomarcadores , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Monócitos , RNA-Seq
13.
ACS Biomater Sci Eng ; 10(4): 2451-2462, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38429076

RESUMO

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.


Assuntos
Grafite , Hidrogéis , Infarto do Miocárdio , Ratos , Camundongos , Animais , Hidrogéis/farmacologia , Conexina 43 , Ratos Sprague-Dawley , Infarto do Miocárdio/cirurgia , Condutividade Elétrica , Impressão Tridimensional
14.
J Am Chem Soc ; 146(7): 4958-4972, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38334752

RESUMO

Temperature is a critical parameter in chemical conversion, significantly affecting the reaction kinetics and thermodynamics. Measuring temperature inside catalyst particles of industrial interest (∼micrometers to millimeters), which is crucial for understanding the evolution of chemical dynamics at catalytic active sites during reaction and advancing catalyst designs, however, remains a big challenge. Here, we propose an approach combining two-photon confocal microscopy and state-of-the-art upconversion luminescence (UL) imaging to measure the spatiotemporal-resolved temperature within individual catalyst particles in the industrially significant methanol-to-hydrocarbons reaction. Specifically, catalyst particles containing zeolites and functional nanothermometers were fabricated using microfluidic chips. Our experimental results directly demonstrate that the zeolite density and particle size can alter the temperature distribution within a single catalyst particle. Importantly, the observed temperature heterogeneity plays a decisive role in the activation of the reaction intermediate and the utilization of active sites. We expect that this work opens a venue for unveiling the reaction mechanism and kinetics within industrial catalyst particles by considering temperature heterogeneity.

15.
J Am Chem Soc ; 145(44): 24191-24201, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37877469

RESUMO

The pure-silica zeolite plays a crucially important role in the gas separation of alkane/alkene, the low-k dielectric material, and the robust matrix for confining metal species during catalysis. However, the environmentally friendly synthesis of pure-silica zeolites is still challenging since (1) the toxic fluoride or dealuminum seeds are inevitably utilized through the hydrothermal synthesis and (2) it will also take a longer crystallization time. Herein, we present an efficient method called the OSDA-mismatch approach for the fluoride- and seed-free synthesis of pure-silica zeolites using Si-SOD (enriched 4-rings) as the sole silica source. This approach allows for the rapid and green synthesis of 15 pure-silica zeolites (CHA, *BEA, EUO, SFF, STF, -SVR, *-SVY, DOH, MTN, NON, *MRE, MEL, MFI, MTW, and *STO). Furthermore, distinct crystallization mechanisms of two significant pure-silica CHA- and *BEA-type zeolites (denoted as Si-CHA and Si-BEA) are investigated in detail by advanced characterization techniques such as FIB, 3D ED, 4D-STEM, HRTEM, Raman, and 29Si MAS NMR. More importantly, Si-CHA displays promising propane/propylene separation performance even better than the one synthesized in the presence of toxic HF. In addition, the incorporation of Zn species within Si-BEA fabricated by this approach also renders superior performance on propane dehydrogenation.

16.
J Cell Physiol ; 238(12): 2827-2840, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37801347

RESUMO

Growth differentiation factor 11 (GDF11) is a putative systemic rejuvenation factor. In this study, we characterized the mechanism by which GDF11 reversed aging of mesenchymal stem cells (MSCs). In culture, aged MSCs proliferate slower and are positive for senescence markers senescence-associated ß-galactosidase and P16ink4a . They have shortened telomeres, decreased GDF11 expression, and reduced osteogenic potential. GDF11 can block MSC aging in vitro and reverse age-dependent bone loss in vivo. The antiaging effect of GDF11 is via activation of the Smad2/3-PI3K-AKT-mTOR pathway. Unexpectedly, GDF11 also upregulated a DNA demethylase Tet2, which served as a key mediator for GDF11 to autoregulate itself via demethylation of the GDF11 promoter. Mutation of Tet2 facilitates MSC aging by blocking GDF11 expression. Mutagenesis of Tet2-regulated CpG sites also blocks GDF11 expression, leading to MSC aging. Together, a novel mutual regulatory relationship between GDF11 and an epigenetic factor Tet2 unveiled their antiaging roles.


Assuntos
Senescência Celular , Células-Tronco Mesenquimais , Senescência Celular/genética , Fatores de Diferenciação de Crescimento/genética , Fatores de Diferenciação de Crescimento/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Humanos
17.
Stem Cell Res Ther ; 14(1): 278, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37775801

RESUMO

BACKGROUND: Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) exhibit the potential to repair the injured heart after myocardial infarction (MI) by promoting neovascularization and cardiomyocyte survival. However, because of the low cellular retention and poor engraftment efficacy, cell therapy of MI is partly mediated by exosomes secreted from the transplanted cells. In this study, we investigated whether exosomes secreted from hiPSC-ECs could become a promising acellular approach to repair the infarcted heart after MI and elucidated the underlying protective mechanism. METHODS: The hiPSC-ECs were differentiated, and exosomes were isolated in vitro. Then, hiPSC-EC exosomes were delivered by intramyocardial injection in a murine MI model in vivo. Echocardiography, combined with hemodynamic measurement, histological examination, Ca2+ transient and cell shortening assessment, and Western blot, was used to determine the protective effects of hiPSC-EC exosomes on the infarcted heart. Furthermore, microRNA sequencing, luciferase activity assay, and microRNA gain-loss function experiments were performed to investigate the enriched microRNA and its role in exosome-mediated effects. RESULTS: In vitro, the hiPSC-EC exosomes enhanced intracellular Ca2+ transients, increased ATP content, and improved cell survival to protect cardiomyocytes from oxygen-glucose deprivation injury. Congruously, hiPSC-EC exosome administration in vivo improved the myocardial contractile function and attenuated the harmful left ventricular remodeling after MI without increasing the frequency of arrhythmias. Mechanistically, the hiPSC-EC exosomes notably rescued the protein expression and function of the sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA-2a) and ryanodine receptor 2 (RyR-2) to maintain intracellular Ca2+ homeostasis and increase cardiomyocyte contraction after MI. The microRNA sequencing showed that miR-100-5p was the most abundant microRNA in exosomes. miR-100-5p could target protein phosphatase 1ß (PP-1ß) to enhance phospholamban (PLB) phosphorylation at Ser16 and subsequent SERCA activity, which contributes to the hiPSC-EC exosome-exerted cytoprotective effects on maintaining intracellular Ca2+ homeostasis and promoting cardiomyocyte survival. CONCLUSION: The hiPSC-EC exosomes maintain cardiomyocyte Ca2+ homeostasis to improve myocardial recovery after MI, which may provide an acellular therapeutic option for myocardial injury.


Assuntos
Exossomos , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Infarto do Miocárdio , Humanos , Camundongos , Animais , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , Infarto do Miocárdio/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo
19.
Regen Ther ; 24: 282-287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37559872

RESUMO

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), a kind of adult stem cell, were studied for clinical applications in regenerative medicine. To date, the safety evaluations of intravenous infusion of allogeneic hUC-MSCs were focused on fever, infection, malignancy, and death. However, the characteristics of dynamical changes in vital signs during hUC-MSCs infusion are largely unknown. In this study, twenty participants with allogeneic hUC-MSCs transplanted (MSC group) and twenty sex- and age-matched individuals with cardiovascular disease who treated with the equal volume of 0.9% normal saline were recruited (NS group). Heart rate, respiratory rate, oxygen saturation, systolic and diastolic blood pressure, and temperature were monitored at intervals of 15 min during infusion. Adverse events were recorded during infusion and within seven days after infusion. No adverse events were observed during and after infusion in both groups. Compared with the baseline, the mean systolic blood pressure (SBP) levels were significantly decreased at 15 min, 30 min, 45 min and 60 min in the MSC group (all P < 0.05) during infusion. In addition, SBP changed significantly from baseline during hUC-MSCs infusion when compared with that of NS group (P < 0.05). Repeated measures analysis of variance confirmed difference over time on the SBP levels (P < 0.05). Our results showed that the process of allogeneic hUC-MSCs intravenous infusion was safe and the vital signs were stable, whereas a slight decrease in SBP was observed.

20.
Natl Sci Rev ; 10(9): nwad120, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37565191

RESUMO

The successful development and application in industry of methanol-to-olefins (MTO) process brought about an innovative and efficient route for olefin production via non-petrochemical resources and also attracted attention of C1 chemistry and zeolite catalysis. Molecular sieve catalysts with diversified microenvironments embedding unique channel/cavity structure and acid properties, exhibit demonstrable features and advantages in the shape-selective catalysis of MTO. Especially, shape-selective catalysis over 8-MR and cavity-type zeolites with acidic supercage environment and narrow pore opening manifested special host-guest interaction between the zeolite catalyst and guest reactants, intermediates and products. This caused great differences in product distribution, catalyst deactivation and molecular diffusion, revealing the cavity-controlled methanol conversion over 8-MR and cavity-type zeolite catalyst. Furthermore, the dynamic and complicated cross-talk behaviors of catalyst material (coke)-reaction-diffusion over these types of zeolites determines the catalytic performance of the methanol conversion. In this review, we shed light on the cavity-controlled principle in the MTO reaction including cavity-controlled active intermediates formation, cavity-controlled reaction routes with the involvement of these intermediates in the complex reaction network, cavity-controlled catalyst deactivation and cavity-controlled diffusion. All these were exhibited by the MTO reaction performances and product selectivity over 8-MR and cavity-type zeolite catalysts. Advanced strategies inspired by the cavity-controlled principle were developed, providing great promise for the optimization and precise control of MTO process.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA