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1.
Nano Lett ; 24(25): 7800-7808, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38870391

RESUMO

Metal nanoclusters feature a hierarchical structure, facilitating their ability to mimic enzyme-catalyzed reactions. However, the lack of true catalytic centers, compounded by tightly bound surface ligands hindering electron transfers to substrates, underscores the need for universal rational design methodologies to emulate the structure and mechanisms of natural enzymes. Motivated by the electron transfer in active centers with specific chemical structures, by integrating the peroxidase cofactor Fe-TCPP onto the surface of glutathione-stabilized gold nanoclusters (AuSG), we engineered AuSG-Fe-TCPP clusterzymes with a remarkable 39.6-fold enhancement in peroxidase-like activity compared to AuSG. Fe-TCPP not only mimics the active center structure, enhancing affinity to H2O2, but also facilitates the electron transfer process, enabling efficient H2O2 activation. By exemplifying the establishment of a detecting platform for trace H2O2 produced by ultrasonic cleaners, we substantiate that the bioinspired surface-ligand-engineered electron transfer can improve sensing performance with a wider linear range and lower detection limit.


Assuntos
Ouro , Peróxido de Hidrogênio , Nanopartículas Metálicas , Ouro/química , Peróxido de Hidrogênio/química , Transporte de Elétrons , Ligantes , Catálise , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Glutationa/química
2.
Opt Express ; 32(2): 2644-2657, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297788

RESUMO

Lu3Al5O12:Ce (LuAG:Ce) phosphor ceramics (PCs) with the excellent thermal stability and high saturation threshold are considered as the best green-fluorescent converters for high-power laser diodes (LDs) lighting. In this study, the effects of sintering additives and sintering processes on the transmittance and microstructure of LuAG:Ce PCs were systematically studied, and the luminescence performance of ceramics with different transmittance was compared. LuAG:Ce PCs with the transmittance of 80% (@800 nm, 1.5 mm) were obtained by using 0.1 wt.% MgO and 0.5 wt.% TEOS as sintering additives, combined with optimized vacuum pre-sintering and hot isostatic pressing. Compared to the non-HIP samples, the transmittance had increased by 11%. The microstructure of ceramics indicated that high transparency was closely related to the decrease in intergranular pores. Notably, the luminous efficiency of 253 lm/W and its saturation thresholds of > 46 W/mm2 were obtained simultaneously in green-emitting LDs devices. Moreover, under 3W laser irradiation, highly transparent ceramics had the low surface temperature of 66.4 °C, indicating the good heat dissipation performance. The observed high luminous efficiency and high saturation threshold of LuAG:Ce PCs were attributed to fewer pores and oxygen vacancies. Therefore, this work proves that highly transparent LuAG:Ce PCs are promising green-fluorescent converters for high-power LDs lighting.

3.
Neuroimmunomodulation ; 31(1): 126-141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843787

RESUMO

INTRODUCTION: Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear. METHODS: Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS. RESULTS: DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF. CONCLUSION: DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.


Assuntos
Fumarato de Dimetilo , AVC Isquêmico , Camundongos Endogâmicos C57BL , Animais , Fumarato de Dimetilo/farmacologia , Fumarato de Dimetilo/uso terapêutico , AVC Isquêmico/imunologia , AVC Isquêmico/tratamento farmacológico , Camundongos , Masculino , Humanos , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Modelos Animais de Doenças
4.
J Nanobiotechnology ; 22(1): 133, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539195

RESUMO

BACKGROUND: Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation. RESULTS: There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission. CONCLUSIONS: Overall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.


Assuntos
Grafite , Osteogênese , Pontos Quânticos , Humanos , Ratos , Animais , Ligamento Periodontal , Dinâmica Mitocondrial , Células-Tronco , Diferenciação Celular , Hidrogéis/farmacologia , Células Cultivadas
5.
PLoS One ; 19(4): e0301051, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662690

RESUMO

To investigate the interplay among technological innovation, industrial structure, production methodologies, economic growth, and environmental consequences within the paradigm of a green economy and to put forth strategies for sustainable development, this study scrutinizes the limitations inherent in conventional deep learning networks. Firstly, this study analyzes the limitations and optimization strategies of multi-layer perceptron (MLP) networks under the background of the green economy. Secondly, the MLP network model is optimized, and the dynamic analysis of the impact of technological innovation on the digital economy is discussed. Finally, the effectiveness of the optimization model is verified by experiments. Moreover, a sustainable development strategy based on dynamic analysis is also proposed. The experimental results reveal that, in comparison to traditional Linear Regression (LR), Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), and Naive Bayes (NB) models, the optimized model in this study demonstrates improved performance across various metrics. With a sample size of 500, the optimized model achieves a prediction accuracy of 97.2% for forecasting future trends, representing an average increase of 14.6%. Precision reaches 95.4%, reflecting an average enhancement of 19.2%, while sensitivity attains 84.1%, with an average improvement of 11.8%. The mean absolute error is only 1.16, exhibiting a 1.4 reduction compared to traditional models and confirming the effectiveness of the optimized model in prediction. In the examination of changes in industrial structure using 2020 data to forecast the output value of traditional and green industries in 2030, it is observed that the output value of traditional industries is anticipated to decrease, with an average decline of 11.4 billion yuan. Conversely, propelled by the development of the digital economy, the output value of green industries is expected to increase, with an average growth of 23.4 billion yuan. This shift in industrial structure aligns with the principles and trends of the green economy, further promoting sustainable development. In the study of innovative production methods, the green industry has achieved an increase in output and significantly enhanced production efficiency, showing an average growth of 2.135 million tons compared to the average in 2020. Consequently, this study highlights the dynamic impact of technological innovation on the digital economy and its crucial role within the context of a green economy. It holds certain reference significance for research on the dynamic effects of the digital economy under technological innovation.


Assuntos
Desenvolvimento Econômico , Invenções , Desenvolvimento Sustentável , Desenvolvimento Sustentável/tendências , Invenções/tendências , Desenvolvimento Econômico/tendências , Redes Neurais de Computação , Máquina de Vetores de Suporte , Teorema de Bayes , Humanos
6.
J Colloid Interface Sci ; 667: 64-72, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38615624

RESUMO

Na3V2(PO4)3 (NVP) has attracted considerable attention as a promising cathode material for sodium-ion batteries (SIBs). But its insufficient electronic conductivity, limited capacities, and fragile structure hinder its extended application, particularly in scenarios involving rapid charging and prolonged cycling. A hybrid cathode material has been developed to integrate both amorphous and crystalline phases, with the objective of improving the rate performance and Na storage capacity by leveraging bi-phase coordination. Consequently, the combination of amorphous and crystalline phases enhanced the kinetics of Na-ion diffusion, resulting in a 1-2 orders of magnitude enhancement in diffusion dynamics. Furthermore, the existence of amorphous states has been demonstrated to elevate the active Na2 site content, resulting in an increased reversible capacity. This assertion is substantiated by evidence derived from solid-state nuclear magnetic resonance (ss-NMR) and electrochemical characteristics. The innovative bi-phase collaborative material provides a specific capacity of 114 mAh/g at 0.2 C, exceptional rate performance of 82 mAh/g at 10 C, and remarkable long-term cycle stability, retaining 95 mAh/g at 5 C even after 300 cycles. In conclusion, the homogeneous hybridization of amorphous and crystalline phases presents itself as a promising and effective strategy for improving Na-ion storage capacity of cathodes in SIBs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38623809

RESUMO

Significance: Acute wounds such as severe burns and chronic wounds like diabetic ulcers present a significant threat to human health. Wound dressings made from natural polymers offer inherent properties that effectively enhance wound healing outcomes and reduce healing time. Recent Advances: Numerous innovative hydrogels are being developed and translated to the clinic to successfully treat various wound types. This underscores the substantial potential of hydrogels in the future wound care market. Economically, annual sales of wound care products are projected to reach $15-22 billion by 2024. Critical Issues: While chitosan-, cellulose-, and collagen-based hydrogel dressings are currently commercially available, scaling-up and manufacturing hydrogels for commercial products remain a challenging process. In addition, ensuring the sterility and stability of the chemical or biological components comprising the hydrogel is a critical consideration. Future Directions: In light of the persistent increase in wound fatalities and the resulting economic and social impacts, as well as the importance of educating the public about dietary health and disease, there should be increased investment in new wound care dressings, particularly hydrogels derived from natural products. With numerous researchers dedicated to advancing preclinical hydrogels, the future holds promise for more innovative and more personalized hydrogel wound dressings.

8.
Bioresour Technol ; 397: 130481, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395233

RESUMO

Brown algae are rich in biostimulants that not only stimulate the overall development and growth of plants but also have great beneficial effects on the whole soil-plant system. However, alginate, the major component of brown algae, is comparatively difficult to degrade. The cost of preparing alginate oligosaccharides (AOSs) is still too high to produce seaweed fertilizer. In this work, the marine bacterium Vibrio sp. B1Z05 is found to be capable of efficient alginate depolymerization and harbors an extended pathway for alginate metabolism. The B1Z05 extracellular cell-free supernatant exhibited great potential for AOS production at low cost, which, together with cellulase, can efficiently hydrolyze seaweed. The brown algal hydrolysis rates were significantly greater than those of the commercial alginate lyase product CE201, and the obtained seaweed extracts were rich in phytohormones. This work provides a low-cost but efficient strategy for the sustainable production of desirable AOSs and seaweed fertilizer.


Assuntos
Celulase , Phaeophyceae , Alga Marinha , Celulase/metabolismo , Hidrólise , Fertilizantes , Polissacarídeo-Liases/metabolismo , Alga Marinha/metabolismo , Alginatos/metabolismo , Oligossacarídeos/metabolismo
9.
Heliyon ; 10(15): e35742, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170321

RESUMO

Application of deep learning (DL) and machine learning (ML) is rapidly increasing in the medical field. DL is gaining significance for medical image analysis, particularly, in oral and maxillofacial surgeries. Owing to the ability to accurately identify and categorize both diseased and normal soft- and hard-tissue structures, DL has high application potential in the diagnosis and treatment of tumors and in orthognathic surgeries. Moreover, DL and ML can be used to develop prediction models that can aid surgeons to assess prognosis by analyzing the patient's medical history, imaging data, and surgical records, develop more effective treatment strategies, select appropriate surgical modalities, and evaluate the risk of postoperative complications. Such prediction models can play a crucial role in the selection of treatment strategies for oral and maxillofacial surgeries. Their practical application can improve the utilization of medical staff, increase the treatment accuracy and efficiency, reduce surgical risks, and provide an enhanced treatment experience to patients. However, DL and ML face limitations, such as data drift, unstable model results, and vulnerable social trust. With the advancement of social concepts and technologies, the use of these models in oral and maxillofacial surgery is anticipated to become more comprehensive and extensive.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(3): 273-278, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38512038

RESUMO

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.


Assuntos
Doenças Transmissíveis , Antígenos HLA-E , Humanos , Células Matadoras Naturais , Citocinas
11.
Adv Sci (Weinh) ; 11(19): e2307409, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477567

RESUMO

Uncontrollable massive bleeding caused by trauma will cause the patient to lose a large amount of blood and drop body temperature quickly, resulting in hemorrhagic shock. This study aims to develop a hemostatic product for hemorrhage management. In this study, waste pomelo peel as raw material is chosen. It underwent processes of carbonization, purification, and freeze-drying. The obtained carbonized pomelo peel (CPP) is hydrophilic and exhibits a porous structure (nearly 80% porosity). The water/blood absorption ratio is significantly faster than the commercial Gelfoam and has a similar water/blood absorption capacity. In addition, the CPP showed a water-triggered shape-recoverable ability. Moreover, the CPP shows ideal cytocompatibility and blood compatibility in vitro and favorable tissue compatibility after long terms of subcutaneous implantation. Furthermore, CPP can absorb red blood cells and fibrin. It also can absorb platelets and activate platelets, and it is capable of achieving rapid hemostasis on the rat tail amputation and hepatectomized hemorrhage model. In addition, the CPP not only can quickly stop bleeding in the rat liver-perforation and rabbit heart uncontrolled hemorrhage models, but also promotes rat liver and rabbit heart tissue regeneration in situ. These results suggest the CPP has shown great potential for managing uncontrolled hemorrhage.


Assuntos
Celulose , Modelos Animais de Doenças , Hemorragia , Animais , Coelhos , Ratos , Celulose/química , Citrus/química , Hemostáticos/farmacologia , Masculino , Hemostasia/efeitos dos fármacos , Ratos Sprague-Dawley , Géis , Ferimentos e Lesões/complicações
12.
Bioact Mater ; 41: 371-384, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39157691

RESUMO

Improving the comprehensive performance of low alloyed Mg is a significant challenge for biomedical applications. This paper developed a high-performance Mg-Zn alloy with uniform ultrafine grains and nano-precipitates through a straightforward, high-temperature reciprocating equal channel angle extrusion (ECAP) process and researched the microstructure, mechanical property, degradation behaviour, and biocompatibility of the developed alloy. Results showed that the lean Mg-2Zn alloy successfully refined grain to about 1 µm and produced plenty of nano-particles with uniform distribution, providing high comprehensive mechanical properties (YS: 235 MPa, UTS: 267 MPa, EL: 15.6 %). Additionally, Zn-riched nano-particles in the matrix could decrease the Zn aggregation at the corrosion layer-matrix interface and form a dense oxide film, achieving a low degradation rate (0.13 mm/year in vivo). Finally, this work realizes the low alloy content, low cost, and good properties of one biodegradable Mg alloy, which will benefit the promotion of future clinical applications.

13.
Int Immunopharmacol ; 133: 112074, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615383

RESUMO

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.


Assuntos
Antígeno B7-H1 , Neoplasias Encefálicas , Glioma , Microglia , Receptor de Morte Celular Programada 1 , Animais , Humanos , Masculino , Camundongos , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Glioma/metabolismo , Glioma/patologia , Glioma/imunologia , Microglia/metabolismo , Microglia/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral/imunologia
14.
Acta Biomater ; 180: 183-196, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38604465

RESUMO

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Magnésio , Nanocompostos , Stents , Animais , Coelhos , Magnésio/química , Magnésio/farmacologia , Nanocompostos/química , Corrosão , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Incrustação Biológica/prevenção & controle , Dioxanos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Polímeros/química , Polímeros/farmacologia , Ligas/química , Ligas/farmacologia
15.
Adv Mater ; : e2406594, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940263

RESUMO

Sulfurized polyacrylonitrile (SPAN) recently emerges as a promising cathode for high-energy lithium (Li) metal batteries owing to its high capacity, extended cycle life, and liberty from costly transition metals. As the high capacities of both Li metal and SPAN lead to relatively small electrode weights, the weight and specific energy density of Li/SPAN batteries are particularly sensitive to electrolyte weight, highlighting the importance of minimizing electrolyte density. Besides, the large volume changes of Li metal anode and SPAN cathode require inorganic-rich interphases that can guarantee intactness and protectivity throughout long cycles. This work addresses these crucial aspects with an electrolyte design where lightweight dibutyl ether (DBE) is used as a diluent for concentrated lithium bis(fluorosulfonyl)imide (LiFSI)-triethyl phosphate (TEP) solution. The designed electrolyte (d = 1.04 g mL-1) is 40%-50% lighter than conventional localized high-concentration electrolytes (LHCEs), leading to 12%-20% extra energy density at the cell level. Besides, the use of DBE introduces substantial solvent-diluent affinity, resulting in a unique solvation structure with strengthened capability to form favorable anion-derived inorganic-rich interphases, minimize electrolyte consumption, and improve cell cyclability. The electrolyte also exhibits low volatility and offers good protection to both Li metal anode and SPAN cathode under thermal abuse.

16.
Signal Transduct Target Ther ; 9(1): 127, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38782919

RESUMO

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.


Assuntos
RNA Helicases DEAD-box , Insuficiência Cardíaca , Miócitos Cardíacos , Animais , Humanos , Camundongos , Apoptose/genética , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/metabolismo , Homeostase/genética , Camundongos Knockout , Camundongos Transgênicos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Dinâmica Mitocondrial/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo
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