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1.
Biochem Biophys Res Commun ; 710: 149857, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38583232

RESUMEN

Molecular mobility of intracellular water is a crucial parameter in the study of the mechanism of desiccation tolerance. As one of the parameters that reflecting molecular mobility, the viscosity of intracellular water has been found intimately related with the protection of the phospholipid membrane because it quantifies the diffusion ability of water and mass in the intracellular environment. In this work we measured the intracellular water relaxation time, which can be translated into water viscosity, by using a previously established NIR-dielectric method to monitor the drying process of baker's yeast and Jurkat cells with different desiccation tolerance. We found that intracellular saccharide can significantly decrease the intracellular water viscosity. Also, the intracellular water diffusion coefficient obtained from this method were found in good agreement with other reports.


Asunto(s)
Levadura Seca , Humanos , Agua/química , Espectroscopía Infrarroja Corta , Células Jurkat , Saccharomyces cerevisiae/química , Desecación
2.
Angew Chem Int Ed Engl ; : e202408667, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861650

RESUMEN

MXene usually exhibits weak pseudo-capacitance behavior in aqueous zinc-ion batteries, which cannot provide sufficient reversible capacity, resulting in the decline of overall capacity when used as the cathode materials. Taking inspiration from polymer electrolyte engineering, we have conceptualized an in-situ induced growth strategy based on MXene materials. Herein, 5.25 % MXene was introduced into the nucleation and growth process of vanadium oxide (HVO), providing the heterogeneous nucleation site and serving as an initiator to regulate the morphology and structural of vanadium oxide (T-HVO). The resulted materials can significantly improve the capacity and rate performance of zinc-ion batteries. The growth mechanism of T-HVO was demonstrated by both characterizations and DFT simulations, and the improved performance was systematically investigated through a series of in-situ experiments related to dynamic analysis steps. Finally, the evaluation and comparison of various defect introduction strategies revealed the efficient, safety, and high production output characteristics of the in-situ induced growth strategy. This work proposes the concept of in-situ induced growth strategy and discloses the induced chemical mechanism of MXene materials, which will aid the understanding, development, and application of cathode in aqueous zinc-ion batteries.

3.
Biochem Biophys Res Commun ; 652: 68-75, 2023 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-36812709

RESUMEN

Bone defects are common in orthopaedics and there is an urgent need to explore effective bone repair materials with osteoinductive activity. Peptide self-assembled nanomaterials have a fibrous structure like that of the extracellular matrix and are ideal bionic scaffold materials. In this study, a short peptide WP9QY (W9) with strong osteoinductive effect was tagged to a self-assembled peptide RADA16 molecule through solid phase synthesis to design a RADA16-W9 peptide gel scaffold. A rat cranial defect was used as a research model to explore the effect of this peptide material on the repair of bone defects in vivo. The structure characteristic of the functional self-assembling peptide nanofiber hydrogel scaffold RADA16-W9 was evaluated by atomic force microscopy (AFM). Then adipose stem cells (ASCs) were isolated from Sprague-Dawley (SD) rat and cultured. the cellular compatibility of scaffold was evaluated through Live/Dead assay. Furthermore, we explore the effects of hydrogels in vivo with the critical-sized mouse calvarial defect model. Micro-CT analysis showed that the RADA16-W9 group had higher levels of bone volume/total volume (BV/TV) (P < 0.05),Trabecular number(TB.N) (P < 0.05),bone mineral density (BMD)(P < 0.05) and trabecular thickness (Tb. Th) (P < 0.05) compared with the RADA16 and PBS groups. Hematoxylin and eosin (H&E) staining showed that RADA16-W9 group had the highest bone regeneration level. Histochemical staining showed significantly higher expression levels of osteogenic factors such as alkaline phosphatase (ALP) and osteocalcin (OCN) in the RADA16-W9 group than in the other two groups (P < 0.05). Reverse transcription polymerase chain reaction (RT-PCR) quantification showed higher mRNA expression levels of osteogenic-related genes ALP, Runt-related transcription factor 2(Runx2), OCN, Osteopontin (OPN) in the RADA16-W9 group than in the RADA16 and PBS groups (P < 0.05). The live/dead staining results showed that RADA16-W9 is not toxic to rASCs and has good biocompatibility. In vivo experiments show that it accelerates the process of bone reconstruction, significantly promoting bone regeneration and can be used to develop a molecular drug for bone defect repair.


Asunto(s)
Hidrogeles , Péptidos , Ratones , Ratas , Animales , Hidrogeles/química , Ratas Sprague-Dawley , Péptidos/química , Osteogénesis , Regeneración Ósea , Andamios del Tejido/química , Diferenciación Celular
4.
Chem Rec ; 23(12): e202300203, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37639150

RESUMEN

In recent years, water pollution has posed a serious threat to aquatic organisms and humans. Advanced oxidation processes (AOPs) based on activated peroxymonosulfate (PMS) show high oxidation, good selectivity, wide pH range and no secondary pollution in the removal of organic pollutants in water. Carbon-based materials are emerging green catalysts that can effectively activate persulfates to generate radical and non-radical active species to degrade organic pollutants. Compared with transition metal catalysts, carbon-based materials are widely used in SR-AOPs because of their low cost, non-toxicity, acid and alkali resistance, large specific surface area, and scalable surface charge, which can be used for selective control of specific water pollutants. This paper mainly presents several carbon-based materials used to activate PMS, including raw carbon materials and modified carbon materials (heteroatom-doped and metal-doped), analyzes and summarizes the mechanism of activating PMS by carbon-based catalysts, and discusses the influencing factors (temperature, pH, PMS concentration, catalyst concentration, inorganic anions, inorganic cations and dissolved oxygen) in the activation process. Finally, the future challenges and prospects of carbon-based materials in water pollution control are also presented.

5.
Molecules ; 29(1)2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38202736

RESUMEN

How to efficiently activate peroxymonosulfate (PMS) in a complex water matrix to degrade organic pollutants still needs greater efforts, and cobalt-based bimetallic nanomaterials are desirable catalysts. In this paper, sea urchin-like NiCo2O4 nanomaterials were successfully prepared and comprehensively characterized for their structural, morphological and chemical properties via techniques, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), among others. The sea urchin-like NiCo2O4 nanomaterials exhibited remarkable catalytic performance in activating PMS to degrade phenol. Within the NiCo2O4/PMS system, the removal rate of phenol (50 mg L-1, 250 mL) reached 100% after 45 min, with a reaction rate constant k of 0.091 min-1, which was 1.4-times higher than that of the monometallic compound Co3O4/PMS system. The outstanding catalytic activity of sea urchin-like NiCo2O4 primarily arises from the synergistic effect between Ni and Co ions. Additionally, a comprehensive analysis of key parameters influencing the catalytic activity of the sea urchin-like NiCo2O4/PMS system, including reaction temperature, initial pH of solution, initial concentration, catalyst and PMS dosages and coexisting anions (HCO3-, Cl-, NO3- and humic acid), was conducted. Cycling experiments show that the material has good chemical stability. Electron paramagnetic resonance (EPR) and quenching experiments verified that both radical activation (SO4•-, •OH, O2•-) and nonradical activation (1O2) are present in the NiCo2O4/PMS system. Finally, the possible degradation pathways in the NiCo2O4/PMS system were proposed based on gas chromatography-mass spectrometry (GC-MS). Favorably, sea urchin-like NiCo2O4-activated PMS is a promising technology for environmental treatment and the remediation of phenol-induced water pollution problems.

6.
Crit Rev Eukaryot Gene Expr ; 32(1): 25-33, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35377978

RESUMEN

INTRODUCTION: FOXD2-AS1 is known to promote the development of several cancers. However, its role in pancreatic adenocarcinoma (PAAD) is unclear. METHODS: Expression of FOXD2-AS1 and miR-30a-3p in PAAD patients was analyzed with RT-qPCR. A follow-up study was performed to analyze the prognostic value of FOXD2-AS1 for PAAD. Overexpression assays were performed to analyze the crosstalk between FOXD2-AS1 and miR-30a-3p. Cell invasion and migration were analyzed by transwell assays. RESULTS: Analysis of the TCGA dataset revealed that FOXD2-AS1 was upregulated in PAAD tissues compared to the non-cancer tissues (1.89 vs. 0.2 TPM), indicating potential involvement of FOXD2-AS1 in PAAD. Our own data also showed FOXD2-AS1 was overexpressed in PAAD. Moreover, high FOXD2-AS1 levels predicted poor survival. It is predicted that miR-30a-3p can bind FOXD2-AS1, while their overexpression did not affect each other's expression. Correlation analysis revealed a significant correlation between FOXD2-AS1 and COX-2. In addition, FOXD2-AS1 overexpression increased COX-2 level, while miR-30a-3p played an opposite role. FOXD2-AS1 and COX-2 overexpression increased PAAD cell invasion and migration. MiR-30a-3p played an opposite role and inhibited the effects of FOXD2-AS1 and COX-2 overexpression. CONCLUSION: FOXD2-AS1 may promote PAAD cell invasion and migration by sponging miR-30a-3p to upregulate COX-2.


Asunto(s)
Adenocarcinoma , MicroARNs , Neoplasias Pancreáticas , ARN Largo no Codificante , Adenocarcinoma/genética , Línea Celular Tumoral , Proliferación Celular/genética , Ciclooxigenasa 2/genética , Estudios de Seguimiento , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Páncreas/metabolismo , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/genética
7.
BMC Med Educ ; 21(1): 242, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33902559

RESUMEN

BACKGROUND: Shortages of qualified health workers have been a global concern, especially in developing countries. China also faces this dilemma, which hinders the development of public health services. Senior high school students are a group who are considering their college majors and careers after graduation. They are also a potential and basic talent reserve for the health sector. This survey focused on senior high school students' intention to learn clinical medicine and explored potential influencing factors. METHODS: An anonymous questionnaire containing 20 items was distributed to 5344 senior high school students. The questions covered the following topics: students' intention to learn clinical medicine, personal and family information, understanding of medical education, cognition of doctors' working conditions, and doctor-patient relationships. Logistic regression and the chi-square test were used to compare students with and without a clear intention to learn clinical medicine to explore influencing factors. RESULTS: Only 5.6% of senior high school students had a clear intention to learn medicine (CILCM). Personal and family information had distinct impacts. Interest and anatomy course were also associated with students' choice. There was a positive correlation between understanding of medical education and students' intention Meanwhile, students' cognition of doctors, career prospects, and social status had significant impacts. The more optimistic students were about doctors' working conditions and doctor-patient relationships, the more likely they were to have a CILCM. CONCLUSION: To some extent, this survey reflects the shortage of medical talent in China and provides possible clues for solving this problem. In addition, these findings may provide a perspective for understanding the development of health services in developing countries.


Asunto(s)
Facultades de Medicina , Estudiantes de Medicina , Selección de Profesión , China , Humanos , Intención , Encuestas y Cuestionarios
8.
Future Oncol ; 16(5): 117-127, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31789058

RESUMEN

Aim: Several studies reported the association of platelet-to-lymphocyte ratio (PLR) and prognosis in nasopharyngeal carcinoma (NPC), but the results remain controversial. Therefore, we investigated the prognostic value of PLR in NPC through meta-analysis. Materials & methods: A comprehensive literature search of PubMed, Embase and Web of Science was performed. Results: A total of 9 studies comprising of 3459 patients with NPC were included. The data demonstrated that an increased PLR predicted poor overall survival, progression-free survival and distant metastasis-free survival. There was no significant association between PLR and sex, age, T stage, N stage, tumor node metastasis (TNM) stage or intensity-modulated radiotherapy. Conclusion: This meta-analysis revealed that PLR might be a potential predicative biomarker of poor prognosis in patients with NPC.


Asunto(s)
Plaquetas/metabolismo , Linfocitos/metabolismo , Carcinoma Nasofaríngeo/sangre , Pronóstico , Biomarcadores de Tumor/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/epidemiología , Carcinoma Nasofaríngeo/patología , Estadificación de Neoplasias , Neutrófilos/metabolismo , Neutrófilos/patología
9.
Entropy (Basel) ; 22(12)2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33297386

RESUMEN

With the rapid development of computer technology, the research on complex networks has attracted more and more attention. At present, the research directions of cloud computing, big data, internet of vehicles, and distributed systems with very high attention are all based on complex networks. Community structure detection is a very important and meaningful research hotspot in complex networks. It is a difficult task to quickly and accurately divide the community structure and run it on large-scale networks. In this paper, we put forward a new community detection approach based on internode attraction, named IACD. This algorithm starts from the perspective of the important nodes of the complex network and refers to the gravitational relationship between two objects in physics to represent the forces between nodes in the network dataset, and then perform community detection. Through experiments on a large number of real-world datasets and synthetic networks, it is shown that the IACD algorithm can quickly and accurately divide the community structure, and it is superior to some classic algorithms and recently proposed algorithms.

10.
Opt Express ; 26(16): 20708-20717, 2018 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-30119376

RESUMEN

Extracting precise target characteristics from microwave image is needed and calls for high-resolution microwave imaging radar systems. In this paper, a Ka-band ultra-wideband microwave photonic (MWP) imaging radar is developed and experimentally demonstrated. In the transmitter, continuous ultra-wideband linear frequency modulation (LFM) wave is generated based on optical frequency sextupling technique. In the receiver, a combination of optical frequency mixer with fiber delay lines and electric analog-to-digital converter (ADC) is capable of receiving target echoes and imaging targets with different distances. The maximum instantaneous bandwidth of the transmitted waveform is measured to be 10.02 GHz and corresponding range resolution is calibrated to be 1.68 cm. Out-field tests with demonstrator working at synthetic aperture radar (SAR) or inverse synthetic aperture radar (ISAR) mode are carried out. Different targets such as an unmanned aerial vehicle (UAV), airliner and Leifeng pagoda are imaged. Based on corresponding high-resolution microwave images, quantitative information of the targets can be identified, which shows the great potential of the radar demonstrator for various remote sensing applications.

11.
Nanotechnology ; 28(14): 145705, 2017 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-28206983

RESUMEN

We report the successful formation of an immutable array of α-PbO2 phase TiO2 nanotubes by compression of a TiO2 nanotube array in an anatase phase. During compression to 31.3 GPa, the TiO2 nanotubes started to directly transform from an anatase phase to a baddeleyite phase at 14.5 GPa and completed the transition at 30.1 GPa. Under decompression, the baddeleyite phase transformed to an α-PbO2 phase at 4.6 GPa, which was quenchable to ambient pressure. Notably the tubular array microstructure was retained after the application of ultra high pressure and undergoing a series of phase transformations. Measurements indicated that the nanotubes in the array possessed higher compressibility than in the bulk form. The highly aligned array structure is believed to reinforce the nanotubes themselves, giving exceptional stability. This, as well as the wall thickness, may also account for their different phase transition pathway.

12.
Phys Chem Chem Phys ; 19(39): 26758-26764, 2017 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-28948241

RESUMEN

We report on the intriguing structural and electrical transport properties of compressed InN. Pronounced anomalies of the resistivity, Hall coefficient, electron concentration, and mobility are observed at ∼11.5 GPa, accompanied by a wurtzite-rocksalt structural transition confirmed using high-pressure XRD measurements and first-principles calculations. The pressure-tuned electrical properties of wurtzite and rocksalt InN are also studied, respectively. Particularly, compression pressure significantly decreases the electron concentration of rocksalt InN by two orders of magnitude and increases the mobility by ten fold. The obvious variations in electrical parameters can be rationalized by our band structure simulations, which reveal a direct-indirect energy crossover at 10 GPa, followed by the rapidly increasing patterns of the energy gap with a pressure coefficient of 33 meV GPa-1. Moreover the electron effective mass and energy gap are found to well satisfy with the k·p model. Definite correlation between the structural change and the electrical transport properties should shed a new light on building InN-based applications in the future.

13.
Sensors (Basel) ; 17(10)2017 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-29065538

RESUMEN

In this paper, capacitive-type humidity sensors were prepared by sequentially drop-coating the aqueous suspensions of zinc oxide (ZnO) nanopowders and polyvinyl pyrrolidone-reduced graphene oxide (PVP-RGO) nanocomposites onto interdigitated electrodes. Significant improvements in both sensitivity and linearity were achieved for the ZnO/PVP-RGO sensors compared with the PVP-RGO/ZnO, PVP-RGO, and ZnO counterparts. Moreover, the produced ZnO/PVP-RGO sensors exhibited rather small hysteresis, fast response-recovery time, and long-term stability. Based on morphological and structural analyses, it can be inferred that the excellent humidity sensing properties of the ZnO/PVP-RGO sensors may be attributed to the high surface-to-volume ratio of the multilayer structure and the supporting roles of the PVP-RGO nanocomposites. The results in this work hence provide adequate guidelines for designing high-performance humidity sensors that make use of the multilayer structure of semiconductor oxide materials and PVP-RGO nanocomposites.

14.
Phys Chem Chem Phys ; 18(6): 5012-8, 2016 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-26812067

RESUMEN

In this work, we report the pressure-dependent electrical transport and structural properties of SnSe. In our experiments an electronic transition from a semiconducting to semimetallic state was observed at 12.6 GPa, followed by an orthorhombic to monoclinic structural transition. Hall effect measurements indicate that both the carrier concentration and mobility vary abnormally accompanied by the semimetallic electronic transition. First-principles band structure calculations confirm the semiconducting-semimetallic transition, and reveal that the semimetallic character of SnSe can be attributed to the enhanced coupling of Sn-5s, Sn-5p, and Se-3p orbitals under compression that results in the broadening of energy bands and subsequently the closure of the band gap. The pressure modulated variations of electrical transport and structural properties may provide an approach to improving the thermoelectric properties of SnSe.

15.
Phys Chem Chem Phys ; 17(39): 26277-82, 2015 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-26380933

RESUMEN

Herein, we report on the intriguing electrical transport properties of compressed AlAs. The relative permittivity and the resistances of both the grain and bulk boundaries vary abnormally at ∼10.9 GPa, accompanied by the cubic-hexagonal structural transition of AlAs. With further compression, the boundary effect becomes undistinguished, and subsequently, the electrical transport mechanism converts from boundary- to bulk-dominated, which gives rise to a significant reduction in the total resistance of AlAs. After being quenched to ambient pressure, resistances recover to the initial values followed by the re-emergence of the boundary effect. Eg decreases with pressure and its pressure dependence changes at ∼14.0 GPa, which rationalizes the anomalous variation of the electrical transport properties. The experimental results indicate that the boundary effect can be modulated by compression and increases the resistance difference between the two states. This opens up a new possible basis for optimizing the performance of AlAs-based applications, including multilevel phase-change memories.

16.
Front Oncol ; 14: 1254705, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601757

RESUMEN

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

17.
Sci Rep ; 14(1): 15962, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987626

RESUMEN

The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Células Madre Neoplásicas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/efectos de los fármacos , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
18.
mSphere ; 9(6): e0018224, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38738873

RESUMEN

The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria. IMPORTANCE: Colistin is last-resort antibiotic used to treat serious clinical infections caused by MDR bacterial pathogens. The recent emergence of transferable plasmid-mediated COL resistance gene mcr-1 has raised the specter of a rapid worldwide spread of COL resistance. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. Our research showed that berberine combined with EDTA effectively reversed COL resistance both in vivo and in vitro through multiple modes of action. The discovery of berberine in combination with EDTA as a new and safe COL adjuvant provides a therapeutic regimen for combating Gram-negative bacteria infections. Our findings provide a potential therapeutic option using existing antibiotics in combination with antibiotic adjuvants and address the prevalent infections caused by MDR Gram-negative pathogens worldwide.


Asunto(s)
Antibacterianos , Berberina , Colistina , Ácido Edético , Escherichia coli , Salmonella , Colistina/farmacología , Berberina/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Antibacterianos/farmacología , Animales , Ratones , Ácido Edético/farmacología , Salmonella/efectos de los fármacos , Salmonella/genética , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Proteínas de Escherichia coli/genética , Simulación del Acoplamiento Molecular , Farmacorresistencia Bacteriana/genética , Quimioterapia Combinada , Ratones Endogámicos BALB C , Sinergismo Farmacológico
19.
Redox Biol ; 72: 103129, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38574433

RESUMEN

AIMS: Doxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity. METHODS AND RESULTS: Doxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart. Overexpression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function. CONCLUSION: Semaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.


Asunto(s)
Cardiotoxicidad , Doxorrubicina , Péptidos Similares al Glucagón , Proteínas de la Membrana , Animales , Ratones , Cardiotoxicidad/etiología , Cardiotoxicidad/metabolismo , Doxorrubicina/efectos adversos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Péptidos Similares al Glucagón/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Humanos
20.
Artículo en Inglés | MEDLINE | ID: mdl-36752406

RESUMEN

Cell delivery using magnetic microswimmers is a promising tool for targeted therapy. However, it remains challenging to rapidly and uniformly manufacture cell-loaded microswimmers that can be assembled into cell-supporting structures at diseased sites. Here, rapid and uniform manufacturable 2D magnetic achiral microswimmers with pores were fabricated to deliver bone marrow mesenchymal stem cells (BMSCs) to regenerate articular-damaged cartilage. Under actuation with magnetic fields, the BMSC-loaded microswimmers take advantage of the achiral structure to exhibit rolling or swimming motions to travel on smooth and rough surfaces, up inclined planes, or in the bulk fluid. Cell viability, proliferation, and differentiation tests performed days after cell seeding verified the microswimmers' biocompatibility. Long-distance targeting and in situ assemblies into 3D cell-supporting structures with BMSC-loaded microswimmers were demonstrated using a knee model and U-shaped wells. Overall, combining the advantages of preparing an achiral 2D structured microswimmer with magnetically driven motility results in a platform for cell transport and constructing 3D cell cultures that can improve cell delivery at lesion sites for biomedical applications.

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