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1.
Ann Clin Microbiol Antimicrob ; 23(1): 13, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347529

RESUMO

BACKGROUND: Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. METHODS: Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. RESULTS: A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES-1 (10/47), blaVIM-2 (6/47), blaGES-14 (4/47), blaIMP-45 (2/47), blaKPC-2 (1/47), and blaNDM-14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4-O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018-2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). CONCLUSIONS: The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Idoso , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/tratamento farmacológico , Proteínas de Bactérias/genética , beta-Lactamases/genética , Sorogrupo , China/epidemiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genética
2.
Angew Chem Int Ed Engl ; 63(16): e202319907, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38391274

RESUMO

Encapsulating individual mammalian cells with biomimetic materials holds potential in ex vivo cell culture and engineering. However, current methodologies often present tradeoffs between homogeneity, stability, and cell compatibility. Here, inspired by bacteria that use proteins stably anchored on their outer membranes to nucleate biofilm growth, we develop a single-cell encapsulation strategy by using a DNA framework structure as a nucleator (DFN) to initiate the growth of DNA hydrogels under cell-friendly conditions. We find that among the tested structures, the tetrahedral DFN can evenly and stably reside on cell membranes, effectively initiating hybridization chain reactions which generate homogeneously dense yet flexible single-cell encapsulation for diverse cell lines. The encapsulation persists for up to 72 hours in a serum-containing cell culture environment, representing a ~70-fold improvement compared to encapsulations mediated by single-stranded DNA nucleators. The metabolism and proliferation of the encapsulated cells are suppressed, but can be restored to the original efficiencies upon release, suggesting the superior cell compatibility of the encapsulation. We also find that compared to naked cells, the encapsulated cells exhibit a lower autophagy level after undergoing mechanical stress, suggesting the protective effect of the DNA encapsulation. This method may provide a new tool for ex vivo cell engineering.


Assuntos
Materiais Biomiméticos , Hidrogéis , Animais , Hidrogéis/química , Linhagem Celular , DNA , Mamíferos
3.
Proc Natl Acad Sci U S A ; 117(50): 31639-31647, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33262279

RESUMO

Hierarchical nanomaterials have received increasing interest for many applications. Here, we report a facile programmable strategy based on an embedded segmental crystallinity design to prepare unprecedented supramolecular planar nanobrush-like structures composed of two distinct molecular packing motifs, by the self-assembly of one particular diblock copolymer poly(ethylene glycol)-block-poly(N-octylglycine) in a one-pot preparation. We demonstrate that the superstructures result from the temperature-controlled hierarchical self-assembly of preformed spherical micelles by optimizing the crystallization-solvophobicity balance. Particularly remarkable is that these micelles first assemble into linear arrays at elevated temperatures, which, upon cooling, subsequently template further lateral, crystallization-driven assembly in a living manner. Addition of the diblock copolymer chains to the growing nanostructure occurs via a loosely organized micellar intermediate state, which undergoes an unfolding transition to the final crystalline state in the nanobrush. This assembly mechanism is distinct from previous crystallization-driven approaches which occur via unimer addition, and is more akin to protein crystallization. Interestingly, nanobrush formation is conserved over a variety of preparation pathways. The precise control ability over the superstructure, combined with the excellent biocompatibility of polypeptoids, offers great potential for nanomaterials inaccessible previously for a broad range of advanced applications.

4.
Small ; 18(36): e2107640, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35119201

RESUMO

The cell microenvironment plays a crucial role in regulating cell behavior and fate in physiological and pathological processes. As the fundamental component of the cell microenvironment, extracellular matrix (ECM) typically possesses complex ordered structures and provides essential physical and chemical cues to the cells. Hydrogels have attracted much attention in recapitulating the ECM. Compared to natural and synthetic polymer hydrogels, DNA hydrogels have unique programmable capability, which endows the material precise structural customization and tunable properties. This review focuses on recent advances in programmable DNA hydrogels as artificial extracellular matrix, particularly the pure DNA hydrogels. It introduces the classification, design, and assembly of DNA hydrogels, and then summarizes the state-of-the-art achievements in cell encapsulation, cell culture, and tissue engineering with DNA hydrogels. Ultimately, the challenges and prospects for cellular applications of DNA hydrogels are delivered.


Assuntos
Matriz Extracelular , Hidrogéis , DNA/química , Matriz Extracelular/química , Hidrogéis/química , Polímeros/análise , Engenharia Tecidual
5.
Molecules ; 26(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530499

RESUMO

"Smart" polymeric microcapsules with excellent permeability of membranes have drawn considerable attention in scientific and industrial research such as drug delivery carriers, microreactors, and artificial organelles. In this work, hybrid hollow polymeric microcapsules (HPs) containing redox-active gold-sulfide bond were prepared with bovine serum albumin, inorganic metal cluster (AuNCs), and poly(N-isopropylacrylamide) conjugates by using Pickering emulsion method. HPs were transferred from water-in-oil to water-in-water by adding PEGbis(N-succinimidylsuccinate). To achieve redox-responsive membrane, the Au-S bond units incorporated into the microcapsules' membranes, allowed us to explore the effects of a new stimuli, that is, the redox Au-S bond breaking on the microcapsules' membranes. The permeability of these hybrid hollow polymeric microcapsules could be sensitively tuned via adding environment-friendly hydrogen peroxide (H2O2), resulting from a fast fracture of Au-S bond. Meanwhile, AuNCs and conjugates could depart from the microcapsules, and enhance the permeability of the membrane. Based on the excellent permeability of the membrane, phosphatase was encapsuled into HPs and p-nitrophenyl phosphate as a substrate. After adding 1 × 10-2 and 1 × 10-4 M H2O2, the catalytic efficiency was nearly 4.06 and 2.22 times higher than that of HPs in the absence of H2O2, respectively. Hence, the unique redox-responsive HPs have potential applications in biocatalytic reaction, drug delivery, and materials as well as in bioscience.


Assuntos
Nitrofenóis/química , Compostos Organofosforados/química , Monoéster Fosfórico Hidrolases/metabolismo , Polímeros/síntese química , Resinas Acrílicas/química , Cápsulas , Catálise , Ouro/química , Peróxido de Hidrogênio/química , Oxirredução , Monoéster Fosfórico Hidrolases/química , Polímeros/química , Soroalbumina Bovina/química , Sulfetos/química , Propriedades de Superfície
6.
Langmuir ; 33(23): 5829-5834, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28557455

RESUMO

The interactions between a host, water-soluble corona[n]arene (S6-CAP), and a series of guests, bisquaternary ammonium derivatives (CnDAs), in water, were investigated. The host and guest can form 1:1 host-guest complex. Their binding constants decrease as the alkyl length of CnDAs increases, which can be tunable ranging from 103 to 106 M-1. The binding processes are mainly entropy-driven, while the enthalpy changes also play an important role in enhancing the host-guest interactions. In addition, a supra-amphiphile was fabricated with S6-CAP and a normal surfactant bearing bisquaternary ammonium (C4R). The S6-CAP·C4R complex forms micellar aggregates in water, and the system possesses better assembling activity and dilution stability than its building block C4R. This study enriches the families of supra-amphiphiles with a new architecture, and employing such a supra-amphiphile in biofunctional materials is highly anticipated.

7.
Biomacromolecules ; 18(10): 3367-3374, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28956910

RESUMO

Amphiphilic block copolymers containing polypeptides can self-assemble into a variety of nonspherical structures arising from strong interactions between peptide units. Here, we report the synthesis of a pH-responsive poly(ethyl glycol)-block-poly(l-glutamic acid)-block-poly(N-octylglycine) (PEG-b-PGA-b-PNOG) triblock copolymers by sequential ring-opening polymerization using amine-terminated poly(ethyl glycol) as the macroinitiator followed by selective deprotection of the benzyl protecting group. The obtained triblock copolymer can be directly dispersed in aqueous solution with hydrophilic PEG, pH-responsive PGA block, and hydrophobic PNOG. We present a systematic study of the influence of pH, molar fraction, and molecular weight on the self-assemblies. It was found that the PEG-b-PGA-b-PNOG triblock tends to form two-dimensional nanodisks and nanosheet-like assemblies. The nanodisk-to-nanosheet transition is highly dependent on the pH and molar fraction despite the different molecular weights. We demonstrate that the dominant driving force of the nanodisks and nanosheets is the hydrophobicity of the PNOG blocks. The obtained bioinspired 2D nanostructures are potential candidates for applications in nanoscience and biomedicine.


Assuntos
Nanoestruturas/química , Peptídeos/química , Polietilenoglicóis/química , Ácido Poliglutâmico/química , Concentração de Íons de Hidrogênio , Polimerização
8.
Angew Chem Int Ed Engl ; 56(20): 5546-5550, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28407350

RESUMO

Constructing polymeric toroids with a uniform, tunable size is challenging. Reported herein is the formation of uniform toroids from poly(γ-benzyl-l-glutamate)-graft-poly(ethylene glycol) (PBLG-g-PEG) graft copolymers by a two-step self-assembly process. In the first step, uniform rodlike micelles are prepared by dialyzing the polymer dissolved in tetrahydrofuran (THF)/N,N'-dimethylformamide (DMF) against water. With the addition of THF in the second step, the rodlike micelles curve and then close end-to-end to form uniform toroids, which resemble a cyclization reaction.

9.
Front Neurosci ; 18: 1368733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859924

RESUMO

Introduction: This research aims to address the challenges in model construction for the Extended Mind for the Design of the Human Environment. Specifically, we employ the ResNet-50, LSTM, and Object Tracking Algorithms approaches to achieve collaborative construction of high-quality virtual assets, image optimization, and intelligent agents, providing users with a virtual universe experience in the context of visual communication. Methods: Firstly, we utilize ResNet-50 as a convolutional neural network model for generating virtual assets, including objects, characters, and environments. By training and fine-tuning ResNet-50, we can generate virtual elements with high realism and rich diversity. Next, we use LSTM (Long Short-Term Memory) for image processing and analysis of the generated virtual assets. LSTM can capture contextual information in image sequences and extract/improve the details and appearance of the images. By applying LSTM, we further enhance the quality and realism of the generated virtual assets. Finally, we adopt Object Tracking Algorithms to track and analyze the movement and behavior of virtual entities within the virtual environment. Object Tracking Algorithms enable us to accurately track the positions and trajectories of objects, characters, and other elements, allowing for realistic interactions and dynamic responses. Results and discussion: By integrating the technologies of ResNet-50, LSTM, and Object Tracking Algorithms, we can generate realistic virtual assets, optimize image details, track and analyze virtual entities, and train intelligent agents, providing users with a more immersive and interactive visual communication-driven metaverse experience. These innovative solutions have important applications in the Extended Mind for the Design of the Human Environment, enabling the creation of more realistic and interactive virtual worlds.

10.
Biomed Pharmacother ; 173: 116398, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458011

RESUMO

Breast cancer has become the most prevalent malignancy worldwide; however, therapeutic efficacy is far from satisfactory. To alleviate the burden of this disease, it is imperative to discover novel mechanisms and treatment strategies. Protein phosphatase 2 A (PP2A) comprises a family of mammalian serine/threonine phosphatases that regulate many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathologies, and plays a pivotal role in the initiation and progression of tumours. The role of PP2A as a tumour suppressor has been extensively studied, and its regulation can serve as a target for anticancer therapy. Recent studies have shown that PP2A is a tumour promotor. PP2A-mediated anticancer therapy may involve two opposing mechanisms: activation and inhibition. In general, the contradictory roles of PP2A should not be overlooked, and more work is needed to determine the molecular mechanism by which PP2A affects in tumours. In this review, the literature on the role of PP2A in tumours, especially in breast cancer, was analysed. This review describes relevant targets of breast cancer, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may lead to effective therapeutic strategies or influence drug development in breast cancer.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo
11.
Crit Rev Oncol Hematol ; 196: 104309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423376

RESUMO

OBJECTIVE: To assess the efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy for early-stage triple-negative breast cancer (TNBC) patients with different clinical characteristics. METHODS: Randomized clinical trials for PD-1/PD-L1 inhibitors and chemotherapy combination were included. Pooled analysis of odds ratio (OR) for pathological complete response (pCR) and hazard ratio (HR) for event-free survival (EFS) was conducted overall and for predefined subgroups. RESULTS: The combination of immunotherapy and chemotherapy significantly improved pCR rate in early TNBC patients (OR, 1.77), and the incidence of events was significantly reduced by 37%. Lymph node metastasis was associated with more benefits on pCR (OR[N0], 1.29; OR[N+], 2.57; P = 0.01), while earlier T stage was related to more benefits on EFS (HR[T1-T2], 0.48; HR[T3-T4], 0.85; P = 0.05). CONCLUSION: The addition of PD-1/PD-L1 inhibitors to chemotherapy offers improved pCR and EFS in early TNBC patients. T and N stages may have implications for the efficacy.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias de Mama Triplo Negativas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Receptor de Morte Celular Programada 1 , Prognóstico
12.
Medicine (Baltimore) ; 103(18): e37928, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701264

RESUMO

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health. CASE PRESENTATION: This report examines a 39-year-old male with type 2 diabetes who developed depressive symptoms after starting liraglutide for glycemic control and weight reduction. Symptoms included poor mood, irritability, decreased interest and energy, progressing to sadness, low self-esteem, and physical discomfort. A clinical diagnosis of a depressive episode was made, coinciding with the initiation of liraglutide. INTERVENTION AND OUTCOME: The patient depressive symptoms significantly improved within a week after discontinuing liraglutide and starting antidepressant therapy. This suggests a possible link between liraglutide and depression, despite considering other factors like diabetes-related stress. DISCUSSION: The report explores potential mechanisms, such as GLP-1RA effects on glucose fluctuations and dopamine modulation, which might contribute to depressive symptoms. The influence on the brain reward system and the reduction in cravings for addictive substances after GLP-1RA use is also discussed as a factor in mood regulation. CONCLUSION: This case highlights the necessity of being vigilant about potential psychiatric side effects, particularly depression, associated with GLP-1RAs. The rarity of such reports calls for more research to investigate and understand these implications further.


Assuntos
Depressão , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Liraglutida , Humanos , Liraglutida/uso terapêutico , Liraglutida/efeitos adversos , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Adulto , Depressão/tratamento farmacológico , Depressão/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico
13.
Enzyme Microb Technol ; 179: 110465, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38852283

RESUMO

Enzymatic production of D-mannose attracts increasing attention because of the health effects and commercial values of D-mannose. Several kinds of epimerases or isomerases have been used for enzymatic production of D-mannose from D-glucose or D-fructose. D-Mannose epimerase (MEase), belonging to N-acyl-D-glucosamine 2-epimerase superfamily enzymes, catalyzes the C-2 epimerization between D-glucose and D-mannose. In this study, a novel MEase was identified from Cytophagaceae bacterium SJW1-29. Sequence and structure alignments indicate that it is highly conserved with the reported R. slithyformis MEase with the known crystal structure. It was a metal-independent enzyme, with an optimal pH of 8.0 and an optimal temperature of 40 °C. The specific activities on D-glucose and D-mannose were 2.90 and 2.96 U/mg, respectively. The Km, kcat, and kcat/Km on D-glucose were measured to be 194.9 mM, 2.72 s-1, and 0.014 mM-1 s-1, respectively. The purified enzyme produced 23.15 g/L of D-mannose from 100 g/L of D-glucose at pH 8.0 and 40 °C for 8 h, with a conversion rate of 23.15 %.

14.
Ambio ; 53(7): 1077-1091, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38366296

RESUMO

The Chinese government has pursued comprehensive ecological conservation and restoration by establishing an ecological barrier system. However, the majority of international research tends to focus on the connectivity between habitats, overlooking the functions that ecological barriers play in ecological conservation and restoration. The existing literature lacks a systematic exploration of the theory and practice of ecological barriers. This study employed the literature analysis tool CiteSpace to present the theoretical and developmental trends in ecological barriers from various perspectives, including research fields, historical evolution, research hotspots, and major research nations. By analyzing the differences in the understanding of ecological barriers between China and other countries, examining the ecological barriers construction history in China, and exploring the types and functions of ecological barriers, this study summarizes the framework of China's ecological barriers construction system as "features-functions-problems." Constructing an ecological barrier system can help achieve ecological conservation and restoration goals in China.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Conservação dos Recursos Naturais/métodos , China , Ecologia , Recuperação e Remediação Ambiental/métodos
15.
J Med Chem ; 67(1): 165-179, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38117948

RESUMO

Cytoplasmic vacuolation-associated cell death, known as methuosis, offers a promising nonapoptotic approach for cancer treatment. In this study, we outline the synthesis and evaluation of potent methuosis-inducing compounds. These compounds selectively induce cell death, characterized by extensive cytoplasmic vacuolation in HeLa and MDA-MB-231 cells. Notably, compound L22 exhibited a remarkable interaction with PIKfyve kinase, boasting a Kd value of 0.47 nM, surpassing the positive controls D-13 and MOMIPP in potency. Furthermore, it is important to highlight that cell death induced by compound L22 is unequivocally attributed to methuosis as it differs from apoptosis, necrosis, or autophagy. Importantly, when administered orally, L22 effectively inhibited tumor growth in a HeLa xenograft model without any apparent signs of toxicity. These results underscore the potential of L22 as a valuable tool for in-depth investigations into the mechanisms of methuosis and as a promising lead compound to guide structural optimization.


Assuntos
Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular , Apoptose , Fosfatos de Fosfatidilinositol/farmacologia
16.
Int J Surg ; 110(6): 3269-3284, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506734

RESUMO

BACKGROUND: Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. METHODS: Inspired by the local application of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. RESULTS: The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. CONCLUSION: Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.


Assuntos
Regeneração Óssea , Alicerces Teciduais , Animais , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Ratos , Impressão Tridimensional , Osteogênese/efeitos dos fármacos , Porosidade , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Coelhos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/administração & dosagem , Masculino , Modelos Animais de Doenças , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Flavonoides/química
17.
Adv Mater ; 35(45): e2302323, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37463346

RESUMO

Extracellular vesicles (EVs) are natural carriers for intercellular transfer of bioactive molecules, which are harnessed for wide biomedical applications. However, a facile yet general approach to engineering interspecies EV-cell communications is still lacking. Here, the use of DNA to encode the heterogeneous interfaces of EVs and cells in a manner free of covalent or genetic modifications is reported, which enables orthogonal EV-cell interkingdom interactions in complex environments. Cholesterol-modified DNA strands and tetrahedral DNA frameworks are employed with complementary sequences to serve as artificial ligands and receptors docking on EVs and living cells, respectively, which can mediate specific yet efficient cellular internalization of EVs via Watson-Crick base pairing. It is shown that based on this system, human cells can adopt EVs derived from the mouse, watermelon, and Escherichia coli. By implementing several EV-cell circuits, it shows that this DNA-programmed system allows orthogonal EV-cell communications in complex environments. This study further demonstrates efficient delivery of EVs with bioactive contents derived from feeder cells toward monkey female germline stem cells (FGSCs), which enables self-renewal and stemness maintenance of the FGSCs without feeder cells. This system may provide a universal platform to customize intercellular exchanges of materials and signals across species and kingdoms.


Assuntos
Vesículas Extracelulares , Nicho de Células-Tronco , Humanos , Animais , Camundongos , Comunicação Celular , DNA , Engenharia
18.
Anal Chim Acta ; 1281: 341910, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38783745

RESUMO

BACKGROUND: Melanoma is a highly aggressive tumor and a significant cause of skin cancer-related death. Timely diagnosis and treatment require identification of specific biomarkers in exosomes secreted by melanoma cells. In this study, label-free surface-enhanced Raman spectroscopy (SERS) method with size-matched selectivity was used to detect membrane proteins in exosomes released from a stimulated environment of fibroblasts (L929) co-cultured with melanoma cells (B16-F10). To promote normal secretion of exosomes, micro-plasma treatment was used to gently induce the co-cultured cells and slightly increase the stress level around the cells for subsequent detection using the SERS method. RESULTS AND DISCUSSION: Firstly, changes in reactive oxygen species/reactive nitrogen species (ROS/RNS) concentrations in the cellular microenvironment and the viability and proliferation of healthy cells are assessed. Results showed that micro-plasma treatment increased extracellular ROS/RNS levels while modestly reducing cell proliferation without significantly affecting cell survival. Secondly, the particle size of secreted exosomes isolated from the culture medium of L929, B16-F10, and co-cultured cells with different micro-plasma treatment time did not increase significantly under single-cell conditions at short treatment time but might be changed under co-culture condition or longer treatment time. Third, for SERS signals related to membrane protein biomarkers, exosome markers CD9, CD63, and CD81 can be assigned to significant Raman shifts in the range of 943-1030 and 1304-1561 cm-1, while the characteristics SERS peaks of L929 and B16-F10 cells are most likely located at 1394/1404, 1271 and 1592 cm-1 respectively. SIGNIFICANCE AND NOVELTY: Therefore, this micro-plasma-induced co-culture model provides a promising preclinical approach to understand the diagnostic potential of exosomes secreted by cutaneous melanoma/fibroblasts. Furthermore, the label-free SERS method with size-matched selectivity provides a novel approach to screen biomarkers in exosomes secreted by melanoma cells, aiming to reduce the use of labeling reagents and the processing time traditionally required.


Assuntos
Técnicas de Cocultura , Exossomos , Fibroblastos , Análise Espectral Raman , Exossomos/metabolismo , Exossomos/química , Fibroblastos/metabolismo , Fibroblastos/citologia , Camundongos , Animais , Análise Espectral Raman/métodos , Gases em Plasma/química , Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Melanoma/metabolismo , Melanoma/patologia , Sobrevivência Celular
19.
RSC Adv ; 12(46): 29777-29784, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36321098

RESUMO

Biomaterials have drawn considerable attention in recent years because of environmental concerns. In this paper, several different poly(lactide)-b-poly(butadiene)-b-poly(lactide) (PLA-b-PB-b-PLA) triblock copolymers were synthesized by the bulk ring-opening polymerization of lactide initiated by flexible macro-initiator hydroxyl-terminated polybutadiene (HTPB) by adjusting the ratio of HTPB to lactide and the optical isomer of lactide. Afterwards, a chain-extension reaction with hexamethylene diisocyanate (HDI) was carried out to prepare (PLA-b-PB-b-PLA) n multi-block copolymers with enhanced molecular weight. The structures and properties of these block copolymers were then characterized by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), atomic force microscope (AFM) and Fourier-transform infrared (FTIR). Toughening effect of the (PLA-b-PB-b-PLA) n multiblock copolymers on biodegradable poly(l-lactide) (PLLA) film was investigated and the blended film with higher (poly(d-lactide)-b-poly(butadiene)-b-poly(d-lactide)) n (PDLA-b-PB-b-PDLA) n loading (15 wt%) exhibited better toughness nearly without loss of the tensile strength. The mechanical properties of the (PLA-b-PB-b-PLA) n /PLLA blended film were proved to be influenced by the different isomers of PLA and rubbery PB chains.

20.
J Hazard Mater ; 437: 129393, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35728318

RESUMO

Fe0-Fe3O4 nanoparticles and cerium dioxide hollow spheres as efficient heterogeneous electro-Fenton reagents were rationally designed to be embedded in porous carbon derived from skimmed cotton for the electrocatalytic degradation of ceftriaxone sodium. Skimmed cotton porous carbon material has a hollow tubular structure, and cerium dioxide is dispersed on the surface of the carbon material in a hollow sphere structure of uniform size. Fe0-Fe3O4 nanoparticles were wrapped in irregular particle shapes on the surface of cerium dioxide hollow spheres, and the remaining part was laid flat on the surface of porous carbon material. The as-synthesized Fe0-Fe3O4/CeO2/C showed excellent degradation efficiency of 95.59 % for ceftriaxone sodium within 120 mins and obtained a COD removal rate of 95.21 % at 240 mins. The zero-valent iron as a reducing agent effectively accelerated the Fe3+/Fe2+ cycle, allowing the composites to exhibit higher catalytic activity and further reducing the possibility of secondary contamination. Moreover, the existence of cerium dioxide further promoted the redox cycle of Ce4+/Ce3+ and accelerated the electron transfer in the interface of the catalyst. The synergistic effect of iron and cerium greatly facilitated the production of hydroxyl radicals and increased the yield of hydroxyl radicals in the reaction system.


Assuntos
Ceftriaxona , Poluentes Químicos da Água , Carbono/química , Catálise , Eletrodos , Peróxido de Hidrogênio/química , Ferro/química , Oxirredução , Poluentes Químicos da Água/química
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