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1.
Am J Pathol ; 193(10): 1517-1527, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37356573

RESUMO

Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (Horizontal-Vertical Network) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). The tumor extraction model achieved an AUC of 0.9386 and 0.9062 in the internal and external test sets, respectively. The stratification model could predict the immunotherapy-sensitive subtypes (AUC range, 0.8685 to 0.9461), the genetic mutations (AUC range, 0.8283 to 0.9225), and the pathway activity (AUC range, 0.7568 to 0.8612) fairly accurately. In external validation, the prediction performance of Epstein-Barr virus and programmed cell death ligand 1 expression status achieved AUCs of 0.7906 and 0.6384, respectively. The segmentation model identified a relatively high proportion of inflammatory cells and connective cells in some immunotherapy-sensitive subtypes. The deep learning-based models potentially may serve as a valuable tool to screen for the beneficiaries of immunotherapy in gastric cancer patients.


Assuntos
Aprendizado Profundo , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Hematoxilina , Amarelo de Eosina-(YS) , Herpesvirus Humano 4 , Imunoterapia
2.
Apoptosis ; 28(9-10): 1285-1303, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37358747

RESUMO

Cerebral ischemia/reperfusion (I/R) injury can result in different levels of cerebral impairment, and in severe cases, death. Curcumin, an essential bioactive component of turmeric, has a rich history as a traditional medicine for various ailments in numerous countries. Experimental and clinical research has established that curcumin offers a protective effect against cerebral I/R injury. Curcumin exerts its protective effects by acting on specific mechanisms such as antioxidant, anti-inflammatory, inhibition of ferroptosis and pyroptosis, protection of mitochondrial function and structure, reduction of excessive autophagy, and improvement of endoplasmic reticulum (ER) stress, which ultimately help to preserve the blood-brain barrier (BBB) and reducing apoptosis. There is currently a shortage of drugs undergoing clinical trials for the treatment of cerebral I/R injury, highlighting the pressing need for research and development of novel treatments to address this injury. The primary objective of this study is to establish a theoretical basis for future clinical applications of curcumin by delineating the mechanisms and protective effects of curcumin against cerebral I/R injury. Adapted with permission from [1].


Assuntos
Isquemia Encefálica , Curcumina , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Apoptose , Traumatismo por Reperfusão/prevenção & controle , Isquemia Encefálica/tratamento farmacológico
3.
Small ; 14(22): e1703868, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29717805

RESUMO

Atomic force microscopy probes are proved to be powerful tools to measure and manipulate the individual cell, providing potential applications for the controlled drug/protein delivery. However, the measured insertion efficiency varies dramatically from 20 to 80%, in some cases, the nanotip can never penetrate the cell membrane no matter how much force is applied to it. Thus, the insertion mechanism of a living cell during the tip-cell interaction must be thoroughly investigated before this technology comes into practical applications. In this work, a multistructural cell model is established to study the tip-membrane interaction. The simulation results show that the stress of the cell membrane can be divided into two stages by the stress segmentation point S. After point S, the stress of the cell membrane increases slightly and most of the indentation force is allocated to the cytoskeleton. This phenomenon is called "stress segmentation effect of the cell membrane," which confirms the hypothesis based on the experimental studies. Moreover, according to the experimental and numerical studies, the hypothesis of the stress segmentation effect also explains the reason that modifying the cell membrane or using the manmade sharpened nanotip can increase the insertion efficiency.


Assuntos
Comunicação Celular , Membrana Celular/metabolismo , Estresse Mecânico , Linhagem Celular , Membrana Celular/ultraestrutura , Fibroblastos/citologia , Análise de Elementos Finitos , Humanos , Microscopia de Força Atômica , Nanopartículas/química , Nanopartículas/ultraestrutura , Análise Numérica Assistida por Computador
4.
Q J Nucl Med Mol Imaging ; 60(3): 280-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25192307

RESUMO

BACKGROUND: The aim of this study was to evaluate the efficacy of radioiodine remnant ablation (RRA) for differentiated thyroid carcinoma (DTC) patients with an incomplete thyroidectomy. METHODS: The medical histories of postsurgical DTC patients who accepted RRA between 2010 and 2012 were retrospectively reviewed. Among them, 113 patients who had undergone a total or near-total thyroidectomy comprised the complete thyroidectomy group (CT group) and the remaining 40 patients who had undergone a lobectomy or sub-total thyroidectomy comprised the incomplete thyroidectomy group (ICT group). The difference in the patients' age, gender, histology, serum TSH level and 24hr radioactive iodine uptake (RIU) between the two groups was analyzed by χ2 Test or ANOVA. The efficacy of RRA in ICT group was evaluated by comparing its rate of complete ablation after the first RRA and its cumulative rate of complete ablation after the second RRA to the rate of complete ablation after the first RRA in CT group respectively by χ2 Test. RESULTS: Of all the clinical characteristics, only serum TSH level and 24hr RIU have significant difference between two groups (P<0.01 for both). The rate of complete ablation after the first RRA was 67.26% in CT group. The rate of complete ablation after the first RRA and the cumulative rate of complete ablation after the second RRA was 27.50% and 67.50% respectively in ICT group. The ablative rate of the first RRA between the two groups was compared by χ2 Test and the difference was significant (P<0.01). The ablative rate of the first RRA in CT group was compared with the cumulative rate of the second RRA in ICT group and the difference was not significant (P=0.978). CONCLUSIONS: Although the efficacy of RRA in DTC patients with an incomplete thyroidectomy is not as good as that of patients with a complete thyroidectomy after the first RRA, a higher ablative rate can still be achieved after the second or third RRA.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Tireoidectomia/métodos , Tireotropina/química , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/efeitos adversos , Tireotropina/sangue , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-37885200

RESUMO

In the 21st century, significant progress has been made in repairing damaged materials through material engineering. However, the creation of large-scale artificial materials still faces a major challenge in achieving proper vascularization. To address this issue, researchers have turned to biomaterials and three-dimensional (3D) bioprinting techniques, which allow for the combination of multiple biomaterials with improved mechanical and biological properties that mimic natural materials. Hydrogels, known for their ability to support living cells and biological components, have played a crucial role in this research. Among the recent developments, 3D bioprinting has emerged as a promising tool for constructing hybrid scaffolds. However, there are several challenges in the field of bioprinting, including the need for nanoscale biomimicry, the formulation of hydrogel blends, and the ongoing complexity of vascularizing biomaterials, which requires further research. On a positive note, 3D bioprinting offers a solution to the vascularization problem due to its precise spatial control, scalability, and reproducibility compared with traditional fabrication methods. This paper aims at examining the recent advancements in 3D bioprinting technology for creating blood vessels, vasculature, and vascularized materials. It provides a comprehensive overview of the progress made and discusses the limitations and challenges faced in current 3D bioprinting of vascularized tissues. In addition, the paper highlights the future research directions focusing on the development of 3D bioprinting techniques and bioinks for creating functional materials.

6.
Microsc Res Tech ; 87(4): 660-684, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38063315

RESUMO

Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that "force" represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM. RESEARCH HIGHLIGHTS: By examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.


Assuntos
Fenômenos Mecânicos , Humanos , Microscopia de Força Atômica , Estudos Prospectivos
7.
Traffic Inj Prev ; : 1-9, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141597

RESUMO

OBJECTIVES: To conduct an in-depth study on the spatial distribution of traffic conflicts in the continuous merging areas of cross-river bridges and ensure public transportation safety. METHODS: First, we utilized drone aerial photography to collect videos of vehicle movements. Using the YOLOv7 object detection algorithm and the Strong SORT multi-object tracking algorithm, we extracted high-precision vehicle trajectory time-series data. Next, based on the motion characteristics of traffic entities, we proposed using Deceleration Rate (DR) to describe rear-end conflicts and Lane Change Speed (LCS) to describe lane-changing conflicts. Additionally, we employed the K-means clustering method to determine the threshold values for minor, moderate, and severe levels of rear-end and lane-changing conflicts. Finally, based on the obtained trajectory data, the values of traffic conflicts are calculated and their severity is classified. A heat map of the spatial distribution of vehicle conflicts in continuous merging zones is then created to study the spatial distribution patterns of traffic conflicts. RESULTS: The threshold values for minor, moderate, and severe levels of rear-end conflicts are determined to be 3.06 m/s2, 5.36 m/s2, and 8.04 m/s2, respectively. For lane-changing conflicts, the thresholds are 1.13 m/s, 2.07 m/s, and 3.45 m/s. The spatial distribution of traffic conflicts exhibits a "first increase, then decrease, and then increase again" trend. CONCLUSIONS: The study identifies the critical areas of traffic conflicts in the continuous merging zones of cross-river bridges. The research results provide a novel approach for acquiring traffic data in these areas and offer a reliable quantitative method for assessing safety risks on these road segments. This provides a theoretical basis for proposing targeted traffic safety management strategies.

8.
Microsc Res Tech ; 87(8): 1678-1692, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38500314

RESUMO

The magnitude of vascular residual stress, an inherent characteristic exclusive to the vasculature, exhibits a strong correlation with vascular compliance, tensile resistance, vascular rigidity, and vascular remodeling subsequent to vascular transplantation. Vascular residual stress can be quantified by evaluating the magnitude of the opening angle within the vascular ring. For decellularized vessels, the vascular ring's opening angle diminishes, consequently reducing residual stress. The decellularization process induces a laxity in the vascular fiber structure within decellularized vessels. To investigate the interrelation between the magnitude of residual stress and the microstructure as well as mechanical properties of elastin and collagen within blood vessels, this study employed fresh blood vessels, stress-relieved vessels, and sections of decellularized blood vessels. Structural scanning and force map experiments on the surface of the sections were conducted using atomic force microscopy (AFM). The findings revealed well-organized arrangements of elastin and collagen within fresh vessels, wherein the regularity of collagen and elastin exhibited variability as residual stress declined. Furthermore, both stress-relieved and decellularized vessel sections exhibited a reduction in the mean Young's modulus to varying extents in comparison to fresh vessels. The validity of our experimental results was further corroborated through finite element simulations. Hence, residual stress assumes a crucial role in upholding the structural stability of blood vessels, and the intricate association between residual stress and the microstructural and micromechanical properties of blood vessels holds significant implications for comprehending the impact of vascular diseases on vascular structure and advancing the development of biomimetic artificial blood vessels that replicate residual stress. RESEARCH HIGHLIGHTS: In this inquiry, we scrutinized the interconnection amid vascular residual stress and the microscale and nanoscale aspects of vascular structure and mechanical function, employing AFM. We ascertained that residual stress assumes a pivotal role in upholding vascular microstructure and mechanical attributes. The experimental outcomes were subsequently validated through finite element simulation.


Assuntos
Vasos Sanguíneos , Colágeno , Elastina , Microscopia de Força Atômica , Estresse Mecânico , Microscopia de Força Atômica/métodos , Elastina/análise , Animais , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/ultraestrutura , Módulo de Elasticidade , Fenômenos Biomecânicos
9.
Front Immunol ; 15: 1388176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840908

RESUMO

The tumor microenvironment is closely linked to the initiation, promotion, and progression of solid tumors. Among its constitutions, immunologic cells emerge as critical players, facilitating immune evasion and tumor progression. Apart from their indirect impact on anti-tumor immunity, immunocytes directly influence neoplastic cells, either bolstering or impeding tumor advancement. However, current therapeutic modalities aimed at alleviating immunosuppression from regulatory cells on effector immune cell populations may not consistently yield satisfactory results in various solid tumors, such as breast carcinoma, colorectal cancer, etc. Therefore, this review outlines and summarizes the direct, dualistic effects of immunocytes such as T cells, innate lymphoid cells, B cells, eosinophils, and tumor-associated macrophages on tumor cells within the tumor microenvironment. The review also delves into the underlying mechanisms involved and presents the outcomes of clinical trials based on these direct effects, aiming to propose innovative and efficacious therapeutic strategies for addressing solid tumors.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/patologia , Animais , Imunidade Inata , Comunicação Celular/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Evasão Tumoral , Imunoterapia/métodos
10.
Materials (Basel) ; 17(20)2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39459677

RESUMO

This study compared the physical properties and mechanical strength development of PCBAs with water, sealed, standard, and open ambient air curing over 28 days to find a suitable curing method for the production of phosphogypsum-based cold-bonded aggregates. The types and relative amounts of hydration products, microstructural morphology and pore structure parameters were characterized utilizing XRD, TGA, FTIR, SEM and nitrogen adsorption methods. According to the results, water curing leads to rapid increases in single aggregate strength, reaching 5.26 MPa at 7 d. The standard curing condition improved the 28 d mechanical strength of the aggregates by 19.3% over others by promoting the generation of hydration products and the transformation of the C-S-H gel to a higher degree of polymerization and by optimizing the pore structure. Further, PCBAs achieved an excellent solidification of phosphorus impurities under all four curing conditions. This work provides significant guidance for selecting an optimized PCBA curing method for industrial production.

11.
Biomed Mater ; 19(3)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38593822

RESUMO

This study utilized the freeze-drying method to create a chitosan (CS) and polyvinyl alcohol (PVA) sponge. To enhance its antibacterial properties, curcumin and nano silver (Cur@Ag) were added for synergistic antibacterial. After adding curcumin and nano silver, the mechanical properties of the composite sponge dressing (CS-PVA-Cur@Ag) were improved. The porosity of the composite sponge dressing was closed to 80%, which was helpful for drug release, and it had good water absorption and water retention rate. The nano silver diameter was 50-80 nm, which was optimal for killing bacteria. Antibacterial tests usedEscherichia coliandStaphylococcus aureusdemonstrated that little nano silver was required to eliminate bacteria. Finally, in the rat full-thickness skin wound model, the composite sponge dressing can promote wound healing in a short time. In summary, CS-PVA-Cur@Ag wound dressing could protect from bacterial infection and accelerate wound healing. Thus, it had high potential application value for wound dressing.


Assuntos
Quitosana , Curcumina , Prata , Ratos , Animais , Álcool de Polivinil , Antibacterianos , Bactérias , Água
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 29(6): 1212-6, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23469559

RESUMO

Chitosan is a natural biopolymer and is made up of D-glucosamine subunits linked by beta-(1,4) glycosidic bond. In recent years, the application of chitosan has attracted more and more attention because of its good biological function in cell biology. The properties of chitosan-based biomaterial are attributed to the physical properties and chemical composition of chitosan. The author of this paper summarized recent related studies and progresses of the influence of physical properties of chitosan on cell activity and cell mechanics property at home and abroad. The findings show that most studies mainly focused on the influence of chitosan and cell activity, while few were on cell mechanics property. The related studies of the influence of chitosan on cell will contribute to the explanation for the mechanism of the interaction between chitosan and cell, and provide the theoretical support for the further study.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quitosana/farmacologia , Alicerces Teciduais/química , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fenômenos Químicos , Quitosana/química , Humanos , Engenharia Tecidual
13.
Colloids Surf B Biointerfaces ; 218: 112784, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36030725

RESUMO

Mechanical properties play key roles in the immune system, especially the activation, transformation and subsequent effector responses of immune cells. As transmembrane adhesion receptors, integrins mediate the adhesion events of both cells and cell-extracellular matrix (ECM). Integrin affinity would influence the crosslinking of cytoskeleton, leading to the change of elastic properties of cells. In this study, the cells were treated with F-actin destabilizing agent Cytochalasin-D (Cyt-D), fixed by Glutaraldehyde, and cultivated in hypotonic solution respectively. We used Atomic force microscopy (AFM) to quantitatively measure the elasticity of Jurkat cells and adhesion properties between integrins and vascular cell adhesion molecule-1 (VCAM-1), and immunofluorescence to study the alteration of cytoskeleton. Glutaraldehyde had a positive effect on the adhesion force and Young's modulus. However, these mechanical properties decreased in a hypotonic environment, confirming the findings of cellular physiological structure. There was no significant difference in the bond strength and elasticity of Jurkat cells treated with Cytochalasin-D, probably because of lower importance of actin in suspension cells. All the treatments in this study pose a negative effect on the adhesion probability between integrins and VCAM-1, which demonstrates the effect of structural alteration of the cytoskeleton on the conformation of integrin. Clear consistency between adhesion force of integrin/VCAM-1 bond and Young's modulus of Jurkat cells was shown. Our results further demonstrated the relationship between cytoskeleton and integrin-ligand by mechanical characteristics.


Assuntos
Integrinas , Molécula 1 de Adesão de Célula Vascular , Actinas , Adesão Celular , Citocalasinas/farmacologia , Glutaral , Humanos , Soluções Hipotônicas/farmacologia , Integrinas/metabolismo , Células Jurkat , Ligantes , Microscopia de Força Atômica/métodos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/farmacologia
14.
Biosens Bioelectron ; 201: 113932, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35065388

RESUMO

Electrochemiluminescence (ECL) is a process in which luminescence is produced by oxidizing or reducing luminophores to transfer radiant charges between electrochemically generated free radicals. Although about 7000 electrochemiluminescence articles have been published in the past 20 years (2000-2021), only a few review articles have summarized the development and application of ECL. In order to better understand the development status, research hotspots and future development trends of ECL technology, it is very necessary to conduct a comprehensive retrospective analysis. This review is based on the bibliometric analysis method of CiteSpace software to quantitatively analyze, visually review and comment on the articles published in the field of ECL in the past 20 years. Quantitatively analyze the authors, the institutional and other basic information to understand the basic development status of ECL, and then visually analyze the high-frequency keywords, burst keywords, keyword clusters, etc., to understand each the evolution of the main research hotspots and development directions of the period, and finally a detailed review and analysis of the selected highly cited articles. We particularly emphasized the development needs of electrochemiluminescence technology in improving the performance of ECL sensors, developing materials with excellent ECL performance, innovating and cooperating with other devices, and developing high-speed and high-throughput ECL sensors. We hope to provide new ideas for promoting the industrial development and clinical application of electrochemiluminescence technology.


Assuntos
Técnicas Biossensoriais , Bibliometria , Publicações , Estudos Retrospectivos , Tecnologia
15.
Food Res Int ; 140: 110043, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648269

RESUMO

A higher level of food safety is required due to the fast-growing human population along with the increased awareness of healthy lifestyles. Currently, a large percentage of food is spoiled during storage and processing due to enzymes and microbial activity, causing huge economic losses to both producers and consumers. Atomic force microscopy (AFM), as a powerful scanning probe microscopy, has been successfully and widely used in food preservation research. This technique allows a non-invasive examination of food products, providing high-resolution images of surface structure and individual polymers as well as the physical properties and adhesion of single molecules. In this paper, detailed applications of AFM in food preservation are reviewed. AFM has been used to provide comprehensive information in food preservation by evaluating the spoilage with its related structure modification. By utilizing AFM imaging and force measurement function, the main mechanisms involved in the loss of food quality and preservation technologies development can be further elucidated. It is also capable of exploring the activities of enzymes and microbes in influencing the quality of food products during storage. AFM provides comprehensive solutions to overcome spoilage issues with its versatile functions and high-throughput outcomes. Further research and development of this novel technique in order to solve integrated problems in food preservation are necessary.


Assuntos
Conservação de Alimentos , Nanotecnologia , Alimentos , Humanos , Fenômenos Mecânicos , Microscopia de Força Atômica
16.
Brain Res Bull ; 175: 234-243, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34333049

RESUMO

INTRODUCTION: The contribution of neuroinflammation in cognitive impairment is increasingly recognized. Non-steroidal anti-inflammatory drugs had been proven that it could improve cognitive impairment in large dose but with more side effect, which limited the application. The main objective of this study was to investigate whether the combined use of nicotine and celecoxib could obtain synergistic neuroprotective effect in ischemic rats. METHODS: Twenty adult Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four groups with different interventions: nicotine (1.5 mg/kg/d), celecoxib (15 mg/kg/d), nicotine (1.5 mg/kg/d) +celecoxib (15 mg/kg/d), or saline after surgery. The other five SD rats also underwent same surgery by injecting saline instead of endothelin-1, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. Micro PET/CT with 2-[18F]-A-85380 were performed for α4ß2-nAChRs detection in vivo. Western blot, real-time PCR and immunohistochemical staining were adopted to detect the expression of α4ß2-nAChRs and inflammatory factors which included TNF-α, IL-1ß, IL-6 in brain tissue. Microglial activation in the brain was monitored by immunofluorescence with IBA1 staining. RESULTS: The MWM test showed rats given with nicotine or celecoxib alone showed much better memory than rats with saline, no difference was observed between nicotine and celecoxib. The rat memory was recovered most significant when the nicotine and celecoxib were combined (p < 0.05). Micro-PET/CT showed much more tracer uptake in the left thalamus and whole brain in rats given with nicotine, or nicotine + celecoxib (nico + cele group) than saline treated rats, whereas the rats given celecoxib did not. Compared with saline treated rats, we found the proteins of α4nAChR and ß2nAChR in rats given nicotine or nico + cele increased significantly, and mRNA/proteins of TNF-α, IL-1ß and IL-6 decreased at the same time. The α 4nAChR and ß 2nAChR proteins in rats given celecoxib is the same as saline treated rats, whereas the inflammatory factors decreased obviously compared with saline treated rats. Microglial activation was confirmed in saline treated rats, which was inhibited in rats give nicotine, celecoxib or both. CONCLUSIONS: The study revealed the combined use of nicotine and celecoxib may improve the cognitive function in ischemic rats, with a better effect than either alone. Both nicotine and celecoxib can inhibit inflammation, but through different mechanisms: nicotine can activate α4ß2-nAChRs while celecoxib is cyclooxygenase-2 inhibitor. Our findings suggest the combined application of two drugs with different anti-inflammation mechanism could attenuate cognitive impairment more effectively in ischemic rats, which may hold therapeutic potential in the clinical practice.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Doenças Neuroinflamatórias/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Animais , Química Encefálica/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/biossíntese , Cognição/efeitos dos fármacos , Citocinas/biossíntese , Sinergismo Farmacológico , Quimioterapia Combinada , Endotelina-1/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas dos Microfilamentos/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/metabolismo , Microtomografia por Raio-X
17.
Regen Biomater ; 8(2): rbaa058, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33738112

RESUMO

Decellularization method based on trypsin-digestion is widely used to construct small diameter vascular grafts. However, this method will reduce the opening angle of the blood vessel and result in the reduction of residual stress. Residual stress reduced has an adverse effect on the compliance and permeability of small diameter vascular grafts. To improve the situation, acellular blood vessels were treated with glutaraldehyde and photooxidation crosslinking respectively, and the changes of opening angle, circumferential residual strain of native blood vessels, decellularized arteries and crosslinked blood vessels were measured by means of histological examination, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this study. The opening angle of decellularized arteries significantly restored after photooxidation crosslinking (P = 0.0216), while that of glutaraldehyde crosslinking blood vessels reduced. The elastic fibers inside the blood vessels became densely rearranged after photooxidation crosslinking. The results of finite element simulation showed that the residual stress increased with the increase of opening angle. In this study, we found at the first time that photooxidation crosslinking method could significantly increase the residual stress of decellularized vessels, which provides biomechanical support for the development of new biomaterials of vascular grafts.

18.
Biotechnol J ; 15(8): e1900559, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32240578

RESUMO

Immunotherapy has remarkable success outcomes against hematological malignancies with high rates of complete remission. To date, many studies have been conducted to increase its effectiveness in other types of cancer. However, it still yields unsatisfying results in solid tumor therapy. This limitation is partly attributed to the lack of understanding of how immunotherapy works in cancer from other perspectives. The traditional studies focus on the biological and chemical perspectives to determine which molecular substrates are involved in the immune system that can eradicate cancer cells. In the last decades, accumulating evidence has shown that physical properties also play important roles in the immune system to combat cancer, which is studied in mechanoimmunology. Mechanoimmunology analysis requires special tools; and herein, atomic force microscopy (AFM) appears as a versatile tool to determine and quantify the mechanical properties of a sample in nanometer precisions. Owing to its multifunctional capabilities, AFM can be used to explore immune system function from the physical perspective. This review paper explains the mechanoimmunology of how immune systems work through AFM, which includes mechanosignaling, mechanosensing, and mechanotransduction, with the aim to deepen the understanding of the mechanistic role of immunotherapy for further development in cancer treatment.


Assuntos
Imunoterapia , Microscopia de Força Atômica , Neoplasias , Animais , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Mecanotransdução Celular , Neoplasias/terapia
19.
J Mater Chem B ; 8(43): 9825-9835, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33000844

RESUMO

Bacterial biofilms caused by antibiotic resistance are a severe cause of infection threatening human health nowadays. The primary causes of this emerging threat are poor penetration of conventional antibiotics and the growing number of varied strains of resistant bacteria. Recently, bulk phytochemical oils have been widely explored for their potential as antibacterial agents. However, due to their poor solubility, low stability, and highly volatile properties, essential oils are not effective for in vitro and in vivo antibacterial applications and require further preparation. In this review, we discuss the recent progress and strategies to overcome the drawbacks of bulk phytochemical oils using nano-delivery, as well as the current challenges and future outlook of these nano-delivery systems against bacterial resistance.


Assuntos
Antibacterianos/administração & dosagem , Portadores de Fármacos/química , Nanoestruturas/química , Óleos Voláteis/administração & dosagem , Compostos Fitoquímicos/administração & dosagem , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Modelos Moleculares , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/farmacologia , Percepção de Quorum/efeitos dos fármacos
20.
Biomater Sci ; 7(9): 3581-3593, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265011

RESUMO

Nanomedicine has shown remarkable progress in preclinical studies of tumor treatment. Over the past decade, scientists have developed various nanocarriers (NCs) for delivering drugs into the tumor area. However, the average amount of accumulated drugs in tumor sites is far from satisfactory. This limitation is strongly related to the corona formation during blood circulation. To overcome this issue, NCs should be designed to become highly stealthy by modifying their surface charge. However, at the same time, stealthy effects not only prevent protein formation but also alleviate the cellular uptake of NCs. Therefore, it is necessary to develop NCs with switchable properties, which are stealthy in the circulation system and sticky when arriving at tumor sites. In this review, we discuss the recent strategies to develop passive and active charge-switchable NCs, known as chameleon-like drug delivery systems, which can reversibly transform their surface from stealthy to sticky and have various designs.


Assuntos
Antineoplásicos/administração & dosagem , Nanocápsulas/química , Animais , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Nanomedicina/métodos , Tamanho da Partícula , Permeabilidade , Polímeros/química , Propriedades de Superfície
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