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1.
Heliyon ; 10(15): e35027, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170476

RESUMEN

The importance of CSR in today's business environment cannot be ignored, especially more and more enterprises realize that when consumers perceive CSR, it will affect consumer behavior and then affect corporate efficiency and reputation. With the widespread application of social media, corporate social responsibility behaviors are easy to be participated and discussed by consumers on the Internet, forming electronic word-of-mouth. Therefore, this paper discusses the influence of electronic word-of-mouth between CSR and consumer satisfaction, taking China's largest Internet enterprise Tencent and its consumers and users as the research object. The overall purpose of this study is to explore the mediating role of electronic word-of-mouth in CSR and consumer satisfaction. This study uses Stimulus-Organism-Response (SOR) theory as the theoretical framework to explain the relationship between CSR initiatives, eWOM and consumer satisfaction. Using the quantitative method of questionnaire survey, taking China's enterprise Tencent as an example, a total of 490 valid questionnaires from Tencent WeChat users from four different levels of cities were received. The PLS-SEM model was used to deeply study the impact of CSR on consumer satisfaction and electronic word-of-mouth. The study found that philanthropic responsibility has a significant impact on consumer satisfaction, but environmental responsibility has no significant impact on satisfaction. At the same time, electronic word-of-mouth plays a key mediating role between the dimension of charitable responsibility and consumer satisfaction, but there is no mediating relationship between the dimension of environmental responsibility and consumer satisfaction. This study is beneficial to other enterprises in the formulation and planning of social responsibility, helps enterprises better understand consumer demands under different CSR dimensions, and provides a useful reference for the formulation of more accurate CSR strategies.

2.
ACS Appl Mater Interfaces ; 16(28): 35936-35948, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38958205

RESUMEN

Tissue-engineered heart valve (TEHV) has emerged as a prospective alternative to conventional valve prostheses. The decellularized heart valve (DHV) represents a promising TEHV scaffold that preserves the natural three-dimensional structure and retains essential biological activity. However, the limited mechanical strength, fast degradation, poor hemocompatibility, and lack of endothelialization of DHV restrict its clinical use, which is necessary for ensuring its long-term durability. Herein, we used oxidized chondroitin sulfate (ChS), one of the main components of the extracellular matrix with various biological activities, to cross-link DHV to overcome the above problems. In addition, the ChS-adipic dihydrazide was used to react with residual aldehyde groups, thus preventing potential calcification. The results indicated notable enhancements in mechanical properties and resilience against elastase and collagenase degradation in vitro as well as the ability to withstand extended periods of storage without compromising the structural integrity of valve scaffolds. Additionally, the newly cross-linked valves exhibited favorable hemocompatibility in vitro and in vivo, thereby demonstrating exceptional biocompatibility. Furthermore, the scaffolds exhibited traits of gradual degradation and resistance to calcification through a rat subcutaneous implantation model. In the rat abdominal aorta implantation model, the scaffolds demonstrated favorable endothelialization, commendable patency, and a diminished pro-inflammatory response. As a result, the newly constructed DHV scaffold offers a compelling alternative to traditional valve prostheses, which potentially advances the field of TEHV.


Asunto(s)
Sulfatos de Condroitina , Animales , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Ratas , Prótesis Valvulares Cardíacas , Ingeniería de Tejidos , Válvulas Cardíacas/efectos de los fármacos , Válvulas Cardíacas/química , Ratas Sprague-Dawley , Andamios del Tejido/química , Ensayo de Materiales , Humanos , Reactivos de Enlaces Cruzados/química , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Porcinos
3.
J Nanobiotechnology ; 22(1): 378, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943185

RESUMEN

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.


Asunto(s)
Válvulas Cardíacas , Hidrogeles , Ratas Sprague-Dawley , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Animales , Andamios del Tejido/química , Anisotropía , Ratas , Hidrogeles/química , Materiales Biocompatibles/química , Prótesis Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , Masculino
4.
Foods ; 13(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38928840

RESUMEN

Pigmented rice grains are important resources for health and nutritional perspectives. Thus, a thorough dissection of the variation of nutrients and bioactive metabolites in different colored rice is of global interest. This study applied LC-MS-based widely targeted metabolite profiling and unraveled the variability of metabolites and nutraceuticals in long grain/non-glutinous black (BR), red (RR), green (GR), and white rice (WR) grains. We identified and classified 1292 metabolites, including five flavonoid compounds specific to BR. The metabolite profiles of the four rice grains showed significant variation, with 275-543 differentially accumulated metabolites identified. Flavonoid (flavone, flavonol, and anthocyanin) and cofactor biosynthesis were the most differentially regulated pathways among the four rice types. Most bioactive flavonoids, anthocyanidins (glycosylated cyanidins and peonidins), phenolic acids, and lignans had the highest relative content in BR, followed by RR. Most alkaloids, amino acids and derivatives, lipids, and vitamins (B6, B3, B1, nicotinamide, and isonicotinic acid) had higher relative contents in GR than others. Procyanidins (B1, B2, and B3) had the highest relative content in RR. In addition, we identified 25 potential discriminatory biomarkers, including fagomine, which could be used to authenticate GR. Our results show that BR and RR are important materials for medicinal use, while GR is an excellent source of nutrients (amino acids and vitamins) and bioactive alkaloids. Moreover, they provide data resources for the science-based use of different colored rice varieties in diverse industries.

5.
Redox Biol ; 73: 103215, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38810422

RESUMEN

The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) is known to be involved in the pathogenesis of cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role in calcific aortic valve disease remains to be elucidated. In this study, we identified FOXO1 significantly down-regulated in the aortic valve interstitial cells (VICs) of calcified aortic valves by investigating clinical specimens and GEO database analysis. FOXO1 silencing or inhibition promoted VICs osteogenic differentiation in vitro and aortic valve calcification in Apoe-/- mice, respectively. We identified that FOXO1 facilitated the ubiquitination and degradation of RUNX2, which process was mainly mediated by SMAD-specific E3 ubiquitin ligase 2 (SMURF2). Our discoveries unveil a heretofore unacknowledged mechanism involving the FOXO1/SMURF2/RUNX2 axis in CAVD, thereby proposing the potential therapeutic utility of FOXO1 or SMURF2 as viable strategies to impede the progression of CAVD.


Asunto(s)
Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Proteína Forkhead Box O1 , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Animales , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Ratones , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Calcinosis/metabolismo , Calcinosis/patología , Calcinosis/genética , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/genética , Masculino , Osteogénesis/genética , Modelos Animales de Enfermedad , Diferenciación Celular
6.
Nat Commun ; 15(1): 4573, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811581

RESUMEN

The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.


Asunto(s)
Cromosomas de las Plantas , Genoma de Planta , Haplotipos , Oryza , Sitios de Carácter Cuantitativo , Oryza/genética , Sitios de Carácter Cuantitativo/genética , Cromosomas de las Plantas/genética , Fitomejoramiento/métodos , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Mapeo Cromosómico , Estrés Fisiológico/genética , Genes de Plantas
7.
Physiol Plant ; 176(2): e14301, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38629128

RESUMEN

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.


Asunto(s)
Genes de Plantas , Oryza , Fitomejoramiento , Tolerancia a la Sal , Oryza/anatomía & histología , Oryza/genética , Oryza/crecimiento & desarrollo , Tolerancia a la Sal/genética , Cromosomas de las Plantas/genética , Alelos , Fitomejoramiento/métodos , Sitios de Carácter Cuantitativo/genética , Genotipo , Transcriptoma , Genoma de Planta/genética , Regiones Promotoras Genéticas , Regulación de la Expresión Génica de las Plantas , Germinación , Brotes de la Planta , Raíces de Plantas , Técnicas de Genotipaje , Polimorfismo Genético , Fenotipo
8.
Adv Healthc Mater ; 13(16): e2303737, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38560921

RESUMEN

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV is cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA. Notably, DHV cross-linked with middle- and high-molecular-weight OHA could drive the macrophage polarization toward the M2 phenotype in vitro. Moreover, DHV cross-linked with middle-molecular-weight OHA scaffolds are further modified with RGD-PHSRN peptide (RPF-OHA/DHV) to block the residual aldehyde groups of the unreacted OHA. The results show that RPF-OHA/DHV not only exhibits anti-calcification properties, but also facilitates endothelial cell adhesion and proliferation in vitro. Furthermore, RPF-OHA/DHV shows excellent performance under an in vivo hemodynamic environment with favorable recellularization and immune regulation without calcification. The optimistic results demonstrate that OHA with different molecular weights has different cross-linking effects on DHV and that RPF-OHA/DHV scaffold with enhanced immune regulation, anti-calcification, and recellularization properties for clinical transformation.


Asunto(s)
Ácido Hialurónico , Ingeniería de Tejidos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Animales , Ingeniería de Tejidos/métodos , Humanos , Válvulas Cardíacas , Andamios del Tejido/química , Inmunomodulación/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Ratones , Calcinosis , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacología , Prótesis Valvulares Cardíacas , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Adhesión Celular/efectos de los fármacos
9.
Plant J ; 119(1): 478-489, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38659310

RESUMEN

The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno , Tolerancia a la Sal , Triticum , Triticum/genética , Triticum/fisiología , Triticum/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología
10.
Acta Biomater ; 178: 181-195, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447808

RESUMEN

Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98.3% in the high shear stress group (45 dyn/cm2). Furthermore, we found that Piezo1 served as a crucial mechanosensor for the differentiation and maturation of VELs. Mechanistically, the activation of Piezo1 by shear stress resulted in the influx of calcium ions, which in turn initiated the Akt signaling pathway and promoted the differentiation of hiPSCs into mature VELs. Moreover, VELs cultured on decellularized heart valves (DHVs) exhibited a notable propensity for proliferation, robust adhesion properties, and antithrombotic characteristics, which were dependent on the activation of the Piezo1 channel. Overall, our study demonstrated that proper shear stress activated the Piezo1 channel to facilitate the differentiation and maturation of hiPSC-VELs via the Akt pathway, providing a potential cell source for regenerative medicine, drug screening, pathogenesis, and disease modeling. STATEMENT OF SIGNIFICANCE: This is the first research that systematically analyzes the effect of shear stress on valvular endothelial-like cells (VELs) derived from human induced pluripotent stem cells (hiPSCs). Mechanistically, unidirectional shear stress activates Piezo1, resulting in an elevation of calcium levels, which triggers the Akt signaling pathway and then facilitates the differentiation of functional maturation VELs. After exposure to shear stress, the VELs exhibited enhanced proliferation, robust adhesion capabilities, and antithrombotic characteristics while being cultured on decellularized heart valves. Thus, it is of interest to develop hiPSCs-VELs using shear stress and the Piezo1 channel provides insights into the functional maturation of valvular endothelial cells, thereby serving as a catalyst for potential applications in the development of therapeutic and tissue-engineered heart valves in the future.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Células Endoteliales , Calcio/metabolismo , Fibrinolíticos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diferenciación Celular/fisiología , Endotelio
11.
Circulation ; 149(18): 1435-1456, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38357822

RESUMEN

BACKGROUND: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated. METHODS: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation. RESULTS: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144+ cells and 30% CD144- cells were obtained. On the basis of single-cell RNA sequencing data, the CD144+ cells and CD144- cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144+ cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144- cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144+ cells and CD144- cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-ß, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition. CONCLUSIONS: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.


Asunto(s)
Diferenciación Celular , Válvulas Cardíacas , Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Válvulas Cardíacas/citología , Válvulas Cardíacas/metabolismo , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/citología , Transducción de Señal
13.
J Genet Genomics ; 50(11): 861-871, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37734712

RESUMEN

Brassinosteroids (BRs) are vital plant steroid hormones involved in numerous aspects of plant life including growth, development, and responses to various stresses. However, the underlying mechanisms of how BR regulates abiotic stress responses in wheat (Triticum aestivum L.) remain to be elucidated. Here, we find that BR signal core transcription factor BRASSINAZOLE-RESISTANT1 (TaBZR1) is significantly up-regulated by salt treatment. Overexpression of Tabzr1-1D (a gain-of-function TaBZR1 mutant protein) improves wheat salt tolerance. Furthermore, we show that TaBZR1 binds directly to the G-box motif in the promoter of ABA biosynthesis gene TaNCED3 to activate its expression and promotes ABA accumulation. Moreover, TaBZR1 associates with the promoters of ROS-scavenging genes TaGPX2 and TaGPX3 to activate their expression. Taken together, our results elucidate that TaBZR1 improves salt-stress tolerance by activating some genes involved in the biosynthesis of ABA and ROS scavenging in wheat, which gives us a new strategy to improve the salt tolerance of wheat.


Asunto(s)
Factores de Transcripción , Triticum , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triticum/genética , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Plantas Modificadas Genéticamente/genética , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo
14.
ASAIO J ; 69(9): 885-893, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37506117

RESUMEN

Tissue-engineered heart valve (TEHV) is a promising alternative to current heart valve substitute. Decellularized porcine aortic heart valves (DAVs) are the most common scaffolds of TEHV. Hard to endothelialization is one of the disadvantages of DAVs. Therefore, we aimed to immobilize endothelial progenitor cell (EPC)-aptamer onto DAVs for accelerating endothelialization. In this study, three groups of scaffolds were constructed: DAVs, aptamer-immobilized DAVs (aptamer-DAVs), and glutaraldehyde crosslinked DAVs (GA-DAVs). The results of flow cytometry revealed that EPC-aptamer was specific to EPCs and was immobilized onto DAVs. Cells adhesion experiments demonstrated that EPCs adhered more tightly onto aptamer-DAVs group than other two groups of scaffolds. And cell proliferation assay indicated that EPCs seeded onto aptamer-DAVs group grew faster than DAVs group and GA-DAVs group. Moreover, dynamic capture experiment in flow conditions revealed that the number of EPCs captured by aptamer-DAVs group was more than other two groups. In conclusion, aptamer-DAVs could specifically promote adhesion and proliferation of EPCs and had ability to capture EPCs in simulated flow condition. This could promote re-endothelialization of scaffolds.


Asunto(s)
Bioprótesis , Células Progenitoras Endoteliales , Prótesis Valvulares Cardíacas , Porcinos , Animales , Válvulas Cardíacas , Adhesión Celular , Ingeniería de Tejidos/métodos
15.
BMC Genomics ; 24(1): 419, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37491214

RESUMEN

BACKGROUND: Calcific aortic valve disease (CAVD) is a common valve disease with an increasing incidence, but no effective drugs as of yet. With the development of sequencing technology, non-coding RNAs have been found to play roles in many diseases as well as CAVD, but no circRNA/lncRNA-miRNA-mRNA interaction axis has been established. Moreover, valve interstitial cells (VICs) and valvular endothelial cells (VECs) play important roles in CAVD, and CAVD differed between leaflet phenotypes and genders. This work aims to explore the mechanism of circRNA/lncRNA-miRNA-mRNA network in CAVD, and perform subgroup analysis on the important characteristics of CAVD, such as key cells, leaflet phenotypes and genders. RESULTS: We identified 158 differentially expressed circRNAs (DEcircRNAs), 397 DElncRNAs, 45 DEmiRNAs and 167 DEmRNAs, and constructed a hsa-circ-0073813/hsa-circ-0027587-hsa-miR-525-5p-SPP1/HMOX1/CD28 network in CAVD after qRT-PCR verification. Additionally, 17 differentially expressed genes (DEGs) in VICs, 9 DEGs in VECs, 7 DEGs between different leaflet phenotypes and 24 DEGs between different genders were identified. Enrichment analysis suggested the potentially important pathways in inflammation and fibro-calcification during the pathogenesis of CAVD, and immune cell patterns in CAVD suggest that M0 macrophages and memory B cells memory were significantly increased, and many genes in immune cells were also differently expressed. CONCLUSIONS: The circRNA/lncRNA-miRNA-mRNA interaction axis constructed in this work and the DEGs identified between different characteristics of CAVD provide a direction for a deeper understanding of CAVD and provide possible diagnostic markers and treatment targets for CAVD in the future.


Asunto(s)
Estenosis de la Válvula Aórtica , MicroARNs , ARN Largo no Codificante , Femenino , Masculino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Circular/metabolismo , Células Endoteliales , Células Cultivadas , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , MicroARNs/genética , MicroARNs/metabolismo
16.
Plant Physiol ; 193(2): 1580-1596, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37335918

RESUMEN

Brassinosteroids play an essential role in promoting skotomorphogenesis, yet the underlying mechanisms remain unknown. Here we report that a plant-specific BLISTER (BLI) protein functions as a positive regulator of both BR signaling and skotomorphogenesis in Arabidopsis (Arabidopsis thaliana). We found that the glycogen synthase kinase 3 (GSK3)-like kinase BRASSINOSTEROID INSENSITIVE2 interacts with and phosphorylates BLI at 4 phosphorylation sites (Ser70, Ser146, Thr256, and Ser267) for degradation; in turn, BR inhibits degradation of BLI. Specifically, BLI cooperates with the BRASSINAZOLE RESISTANT1 (BZR1) transcription factor to facilitate the transcriptional activation of BR-responsive genes. Genetic analyses indicated that BLI is essentially required for BZR1-mediated hypocotyl elongation in the dark. Intriguingly, we reveal that BLI and BZR1 orchestrate the transcriptional expression of gibberellin (GA) biosynthetic genes to promote the production of bioactive GAs. Our results demonstrate that BLI acts as an essential regulator of Arabidopsis skotomorphogenesis by promoting BR signaling and GA biosynthesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Fosforilación , Glucógeno Sintasa Quinasa 3/genética , Brasinoesteroides/metabolismo , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo
17.
Clin Immunol ; 252: 109647, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37211291

RESUMEN

BACKGROUND: IRF4 is the pioneer factor for effector T cell maturation. Here we investigated the function of IRF4 in maintaining OX40-related T cell responses following alloantigen activation in a mouse heart transplantation model. METHODS: Irf4flox/flox mice were bred with Ox40cre/+ mice to generate Irf4flox/floxOx40cre/+ mice. Wild type C57BL/6, Irf4flox/floxOx40cre/+ mice were transplanted with BALB/c heart allografts, with or without BALB/c skin-sensitization. CD4+ TEa T cells co-transfer experiments and flow cytometric analysis were conducted to investigate the amount of CD4+ T cells and the percentage of the T effector subset. RESULTS: Irf4flox/floxOx40cre/+ and Irf4flox/floxOx40cre/+ TEa mice were constructed successfully. IRF4 ablation in activated OX40-mediated alloantigen specific CD4+ TEa T cells reduced effector T cell differentiation (CD44hiCD62Llo, Ki67, IFN-γ), which caused long-term allograft survival (> 100 d) in the chronic rejection model. In the donor skin-sensitized heart transplantation model, the formation and function of alloantigen-specific memory CD4+ TEa cells were also impaired in Irf4flox/floxOx40cre/+ mice. Additionally, deletion of IRF4 after T cell activation in Irf4flox/floxOx40cre/+ mice reduced T cell reactivation in vitro. CONCLUSIONS: IRF4 ablation after OX40-related T cell activation could reduce effector and memory T cell formation and inhibit their function in response to alloantigen stimulation. These findings could have significant implications in targeting activated T cells to induce transplant tolerance.


Asunto(s)
Trasplante de Corazón , Células T de Memoria , Animales , Ratones , Memoria Inmunológica , Isoantígenos , Células T de Memoria/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
18.
New Phytol ; 239(3): 920-935, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37209253

RESUMEN

Drought stress causes substantial losses in crop production per year worldwide, threatening global food security. Identification of the genetic components underlying drought tolerance in plants is of great importance. In this study, we report that loss-of-function of the chromatin-remodeling factor PICKLE (PKL), which is involved in repression of transcription, enhances drought tolerance of Arabidopsis. At first, we find that PKL interacts with ABI5 to regulate seed germination, but PKL regulates drought tolerance independently of ABI5. Then, we find that PKL is necessary for repressing the drought-tolerant gene AFL1, which is responsible for the drought-tolerant phenotype of pkl mutant. Genetic complementation tests demonstrate that the Chromo domain and ATPase domain but not the PHD domain are required for the function of PKL in regulating drought tolerance. Interestingly, we find that the DNA-binding domain (DBD) is essential for the protein stability of PKL. Furthermore, we demonstrate that the SUMO E3 ligase MMS21 interacts with and enhances the protein stability of PKL. Genetic interaction analysis shows that MMS21 and PKL additively regulate plant drought tolerance. Collectively, our findings uncover a MMS21-PKL-AFL1 module in regulating plant drought tolerance and offer insights into a novel strategy to improve crop drought tolerance.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Resistencia a la Sequía , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Sequías , Regulación de la Expresión Génica de las Plantas
19.
BMC Biol ; 21(1): 20, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36726089

RESUMEN

BACKGROUND: DNA mutations of diverse types provide the raw material required for phenotypic variation and evolution. In the case of crop species, previous research aimed to elucidate the changing patterns of repetitive sequences, single-nucleotide polymorphisms (SNPs), and small InDels during domestication to explain morphological evolution and adaptation to different environments. Additionally, structural variations (SVs) encompassing larger stretches of DNA are more likely to alter gene expression levels leading to phenotypic variation affecting plant phenotypes and stress resistance. Previous studies on SVs in rice were hampered by reliance on short-read sequencing limiting the quantity and quality of SV identification, while SV data are currently only available for cultivated rice, with wild rice largely uncharacterized. Here, we generated two genome assemblies for O. rufipogon using long-read sequencing and provide insights on the evolutionary pattern and effect of SVs on morphological traits during rice domestication. RESULTS: In this study, we identified 318,589 SVs in cultivated and wild rice populations through a comprehensive analysis of 13 high-quality rice genomes and found that wild rice genomes contain 49% of unique SVs and an average of 1.76% of genes were lost during rice domestication. These SVs were further genotyped for 649 rice accessions, their evolutionary pattern during rice domestication and potential association with the diversity of important agronomic traits were examined. Genome-wide association studies between these SVs and nine agronomic traits identified 413 candidate causal variants, which together affect 361 genes. An 824-bp deletion in japonica rice, which encodes a serine carboxypeptidase family protein, is shown to be associated with grain length. CONCLUSIONS: We provide relatively accurate and complete SV datasets for cultivated and wild rice accessions, especially in TE-rich regions, by comparing long-read sequencing data for 13 representative varieties. The integrated rice SV map and the identified candidate genes and variants represent valuable resources for future genomic research and breeding in rice.


Asunto(s)
Domesticación , Oryza , Genoma de Planta , Oryza/genética , Estudio de Asociación del Genoma Completo , Variación Genética , Fitomejoramiento , Fenotipo
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