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Bacterial infections pose a seriously threat to the safety of the environment and human health. In particular, the emergence of drug-resistant pathogens as a result of antibiotic abuse and high trauma risk has rendered conventional therapeutic techniques insufficient for treating infections by these so-called "superbugs". Therefore, there is an urgent need to develop highly efficient and environmentally-friendly antimicrobial agents. Bismuth-based nanomaterials with unique structures and physicochemical characteristics have attracted considerable attention as promising antimicrobial candidates, with many demonstratingoutstanding antibacterial effects upon being triggered by broad-spectrum light. These nanomaterials have also exhibited satisfactory energy band gaps and electronic density distribution with improved photonic properties for extensive and comprehensive applications after being modified through various engineering methods. This review summarizes the latest research progress made on bismuth-based nanomaterials with different morphologies, structures and compositions as well as the different methods used for their synthesis to meet their rapidly increasing demand, especially for antibacterial applications. Moreover, the future prospects and challenges regarding the application of these nanomaterials are discussed. The aim of this review is to stimulate interest in the development and experimental transformation of novel bismuth-based nanomaterials to expand the arsenal of effective antimicrobials.
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Antiinfecciosos , Infecciones Bacterianas , Nanocompuestos , Humanos , Bismuto/química , Antibacterianos/químicaRESUMEN
Treatment of diabetic wounds is a significant clinical challenge due to the massive infections caused by bacteria. In this study, multifunctional glycol chitosan and polydopamine-coated BiO1-x I (GPBO) nanoparticles (NPs) with near-infrared (NIR) photothermal and photocatalytic abilities are prepared. When infection occurs, the local microenvironment becomes acidic, and the pH-switchable GPBO can target the bacteria of the wound site. The NIR-assisted GPBO treatment exhibits anti-bacterial effects with fast response, high efficiency, and long duration to Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. GPBO achieves excellent photothermal imaging and CT imaging of the mouse subcutaneous abscess model. With the assistance of NIR irradiation, the GPBO promotes the healing of the diabetic wound model with the effects of anti-bacteria, anti-inflammation, the M2 polarization promotion of macrophages, and angiogenesis. This is the first-time report of nano-sized BiO1-x I. The synthesis and selected application for the imaging and targeted therapy of diabetic wounds are presented. This study offers an example of the NP-assisted precise diagnosis and therapy of bacterial infection diseases.
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Quitosano , Diabetes Mellitus , Indoles , Nanopartículas , Polímeros , Ratones , Animales , Bismuto , Oxígeno/farmacología , Nanopartículas/uso terapéutico , Bacterias , Escherichia coliRESUMEN
The presence of TERTp mutation in isocitrate dehydrogenase-wildtype (IDHwt) histologically lower-grade glioma (LGA) has been linked to a poor prognosis. In this study, we aimed to develop and validate a radiomic nomogram based on multimodal MRI for predicting TERTp mutations in IDHwt LGA. One hundred and nine IDH wildtype glioma patients (TERTp-mutant, 78; TERTp-wildtype, 31) with clinical, radiomic, and molecular information were collected and randomly divided into training and validation set. Clinical model, fusion radiomic model, and combined radiomic nomogram were constructed for the discrimination. Radiomic features were screened with 3 algorithms (Wilcoxon rank sum test, elastic net, and the recursive feature elimination) and the clinical characteristics of combined radiomic nomogram were screened by the Akaike information criterion. Finally, receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis were utilized to assess these models. Fusion radiomic model with 4 radiomic features achieved an area under the curve value of 0.876 and 0.845 in the training and validation set. And, the combined radiomic nomogram achieved area under the curve value of 0.897 (training set) and 0.882 (validation set). Above that, calibration curve and Hosmer-Lemeshow test showed that the radiomic model and combined radiomic nomogram had good agreement between observations and predictions in the training set and the validation set. Finally, the decision curve analysis revealed that the 2 models had good clinical usefulness for the prediction of TERTp mutation status in IDHwt LGA. The combined radiomics nomogram performed great performance and high sensitivity in prediction of TERTp mutation status in IDHwt LGA, and has good clinical application.
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Neoplasias Encefálicas , Glioma , Telomerasa , Humanos , Nomogramas , Telomerasa/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Radiómica , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/patología , Imagen por Resonancia Magnética , Isocitrato Deshidrogenasa/genética , Mutación , Estudios RetrospectivosRESUMEN
Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.
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Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratas , Animales , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/etiología , Letrozol/farmacología , Letrozol/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches. METHODS: To obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single-cell RNA sequencing and T-cell/B-cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour-infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence in situ hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma. RESULTS: Promoting natural killer (NK) cell and CD8_GZMK T-cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2-like activity of tumour-associated macrophages (TAMs) could be an effective approach. Antigen-presenting cancer-associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen-presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro. CONCLUSION: Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.
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Cordoma , Neoplasias de Cabeza y Cuello , Neoplasias de la Base del Cráneo , Humanos , Animales , Ratones , Cordoma/genética , Cordoma/metabolismo , Cordoma/patología , Fibronectinas , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Neoplasias de la Base del Cráneo/genética , Neoplasias de la Base del Cráneo/metabolismo , Neoplasias de la Base del Cráneo/patología , Base del Cráneo/metabolismo , Base del Cráneo/patología , Microambiente TumoralRESUMEN
Recently, there has been an increasing concern about the privacy issue raised by identifiable information in machine learning. However, previous portrait matting methods were all based on identifiable images. To fill the gap, we present P3M-10k, which is the first large-scale anonymized benchmark for Privacy-Preserving Portrait Matting (P3M). P3M-10k consists of 10,421 high resolution face-blurred portrait images along with high-quality alpha mattes, which enables us to systematically evaluate both trimap-free and trimap-based matting methods and obtain some useful findings about model generalization ability under the privacy preserving training (PPT) setting. We also present a unified matting model dubbed P3M-Net that is compatible with both CNN and transformer backbones. To further mitigate the cross-domain performance gap issue under the PPT setting, we devise a simple yet effective Copy and Paste strategy (P3M-CP), which borrows facial information from public celebrity images and directs the network to reacquire the face context at both data and feature level. Extensive experiments on P3M-10k and public benchmarks demonstrate the superiority of P3M-Net over state-of-the-art methods and the effectiveness of P3M-CP in improving the cross-domain generalization ability, implying a great significance of P3M for future research and real-world applications. The dataset, code and models are available here (https://github.com/ViTAE-Transformer/P3M-Net).
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Despite great progress in the non-classical homogeneous nucleation and crystallization theory, the heterogeneous processes of atomic nucleation and crystallization remain poorly understood. Abundant theories and experiments have demonstrated the detailed dynamics of homogeneous nucleation; however, intensive dynamic investigations on heterogeneous nucleation are still rare. In this work, in situ transmission electron microscopy (TEM) at the atomic scale was carried out with temporal resolution for heterogeneous nucleation and crystallization. The results show a reversible amorphous to crystal phase transformation that is manipulated by the size threshold effect. Moreover, the two growth pathways of Bi particles can be mainly assigned to the atomic adsorption expansion in the amorphous state and effective fusion in the crystal contact process. These interesting findings, based on a real dynamic imaging system, strongly enrich and improve our understanding of the dynamic mechanisms in the non-classical heterogeneous nucleation and crystallization theory, providing insights into designing innovative materials with controlled microstructures and desired physicochemical properties.
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The development of highly efficient photonic nanomaterials with synergistic biological effects is critical and challenging task for public hygiene health well-being and has attracted extensive interest. In this study, a type of near-infrared (NIR) driven, virus-like heterojunction was first developed for synergistic biological application. The Ag-coated Bi2CO5 nanomaterial (BOCO@Ag) demonstrated good biocompatibility, low cytotoxicity, high antibacterial activity and excellent light utilization stability. The synthesized BOCO@Ag performed a potential high photothermal conversion (efficiency~46.81%) to generate high temperatures when irradiated with near-infrared light illumination. As expected, compared to single Ag+ disinfection, BOCO@Ag can exhibit better antibacterial performance when combined with photothermal energy and released Ag+ . These results suggest that BOCO@Ag can be a promising photo-activate antimicrobial candidate and provide security for humans health and the environment treatment.
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Antibacterianos , Nanosferas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Desinfección , Humanos , Rayos Infrarrojos , PlataRESUMEN
The structural and physicochemical characteristics of oil bodies from hemp seeds were explored in this study. Oil bodies from several plant-based sources have been previously studied; however, this is the first time a characterisation of oil bodies from the seeds of industrial hemp is provided. The morphology of oil bodies in hemp seeds and after extraction was investigated using cryo-scanning electron microscopy (cryo-SEM), and the interfacial characteristics of isolated oil bodies were studied by confocal laser scanning microscopy (CLSM). Proteins associated with oil bodies were characterised using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The effect of pH and ionic strength on colloidal properties of the oil bodies was investigated. Oil bodies in hemp seeds appeared spherical and sporadically distributed in the cell, with diameters of 3 to 5 µm. CLSM images of isolated oil bodies revealed the uniform distribution of phospholipids and proteins at their interface. Polyunsaturated fatty acids were predominant in the lipid fraction and linoleic acid accounted for ≈61% of the total fatty acids. The SDS-PAGE analysis of washed and purified oil bodies revealed major bands at 15 kDa and 50-25 kDa, which could be linked to membrane-specific proteins of oil bodies or extraneous proteins. The colloidal stability of oil bodies in different pH environments indicated that the isoelectric point was between pH 4 and 4.5, where oil bodies experienced maximum aggregation. Changes in the ionic strength decreased the interfacial charge density of oil bodies (ζ-potential), but it did not affect their mean particle size. This suggested that the steric hindrance provided by membrane-specific proteins at the interface of the oil bodies could have prevented them from flocculation at low interfacial charge density. The results of this study provide new tertiary knowledge on the structure, composition, and colloidal properties of oil bodies extracted from hemp seeds, which could be used as natural emulsions or lipid-based delivery systems for food products.
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Synergetic therapy includes the combination of two or more conventional therapeutic approaches and can be used for tumor treatment by combining the advantages and avoiding the drawbacks of each type of treatment. In the present study, truncated tissue factor (tTF)-EG3287 fusion protein-encapsulated gold nanorod (GNR)-virus-inspired mesoporous silica core-shell nanoparticles (vinyl hybrid silica nanoparticles; VSNP) (GNR@VSNP-tTF-EG3287) were synthesized to achieve synergetic therapy by utilizing selective vascular thrombosis therapy (SVTT) and photothermal therapy (PTT). By integrating the targeted coagulation activity of tTF-EG3287 and the high tumor ablation effect of GNR@VSNP, local hyperthermia could induce a high percentage of apoptosis of vascular endothelial cells by using near-infrared light. This provided additional phospholipid sites for tTF-EG3287 and enhanced its procoagulant activity in vitro. In addition, the nanoparticles, which had unique topological viral structures, exhibited superior cellular uptake properties leading to significant antitumor efficacy. The in vivo antitumor results further demonstrated an interaction between SVTT and PTT, whereas the synergetic therapy (SVTT and PTT) achieved an enhanced effect, which was superior to the respective treatment efficacy of each modality or the additive effect of their individual efficacies. In summary, the synthesized GNR@VSNP-tTF-EG3287 exerted synergetic effects and enhanced the antitumor efficiency by avoiding multiple injections and suboptimal administration. These effects simultaneously affected both tumor blood supply and cancer cell proliferation. The data suggested that the integration of SVTT induced by tTF-EG3287 and PTT could provide potential strategies for synergetic tumor therapy.
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Antineoplásicos/uso terapéutico , Coagulantes/uso terapéutico , Nanotubos/química , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Coagulantes/química , Femenino , Oro/química , Oro/efectos de la radiación , Oro/toxicidad , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Rayos Infrarrojos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanotubos/efectos de la radiación , Nanotubos/toxicidad , Fragmentos de Péptidos/química , Fragmentos de Péptidos/uso terapéutico , Terapia Fototérmica , Porosidad , Conejos , Proteínas Recombinantes de Fusión/química , Dióxido de Silicio/química , Dióxido de Silicio/efectos de la radiación , Dióxido de Silicio/toxicidad , Tromboplastina/química , Tromboplastina/uso terapéutico , Trombosis/inducido químicamente , Factor A de Crecimiento Endotelial Vascular/química , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
X-ray computed tomography (CT) has been widely used in clinical practice, and contrast agents such as Iohexol are often used to enhance the contrast of CT imaging between normal and diseased tissue. However, such contrast agents can have some toxicity. Thus, new CT contrast agents are urgently needed. Owing to the high atomic number (Z = 83), low cost, good biological safety, and great X-ray attenuation property (5.74 cm2 kg-1 at 100 keV), bismuth has gained great interest from researchers in the field of nano-sized CT contrast agents. Here, we synthesized BiF3: Ln@PVP nanoparticles (NPs) with an average particle size of about 380 nm. After coating them with polyvinylpyrrolidone (PVP), the BiF3: Ln@PVP NPs possessed good stability and great biocompatibility. Meanwhile, compared with the clinical contrast agent Iohexol, BiF3: Ln@PVP NPs showed superior in vitro CT imaging contrast. Subsequently, after in situ injection with BiF3: Ln@PVP NPs, the CT value of the tumor site after the injection was significantly higher than that before the injection (the CT value of the pre-injection and post-injection was 48.9 HU and 194.58 HU, respectively). The morphology of the gastrointestinal (GI) tract can be clearly observed over time after oral administration of BiF3: Ln@PVP NPs. Finally, the BiF3: Ln@PVP NPs were completely discharged from the GI tract of mice within 48 h of oral administration with no obvious damage to the GI tract. In summary, our easily synthesized BiF3: Ln@PVP NPs can be used as a potential clinical contrast agent and may have broad application prospects in CT imaging.
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High-efficiency nanotheranostic agents with multimodal imaging guidance have attracted considerable interest in the field of cancer therapy. Herein, novel silver-decorated bismuth-based heterostructured polyvinyl pyrrolidone nanoparticles (NPs) with good biocompatibility (Bi-Ag@PVP NPs) were synthesized for accurate theranostic treatment, which can integrate computed tomography (CT)/photoacoustic (PA) imaging and photodynamic therapy/photothermal therapy (PDT/PTT) into one platform. The Bi-Ag@PVP NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs. Moreover, after irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can efficiently induce the generation of reactive oxygen species (ROS), thereby synergizing PDT/PTT to exert an efficient tumor ablation effect both in vitro and in vivo. Furthermore, Bi-Ag@PVP NPs can also be employed to perform enhanced CT/PA imaging because of their high X-ray absorption attenuation and enhanced photothermal conversion. Thus, they can be utilized as a highly effective CT/PA imaging-guided nanotheranostic agent. In addition, an excellent antibacterial effect was achieved. After irradiation under an 808 nm laser, the Bi-Ag@PVP NPs can destroy the integrity of Escherichia coli, thereby inhibiting E. coli growth, which can minimize the risk of infection during cancer therapy. In conclusion, our study provides a novel nanotheranostic platform that can achieve CT/PA-guided PDT/PTT synergistic therapy and have potential antibacterial properties. Thus, this work provides an effective strategy for further broad clinical application prospects.
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Photothermal/photodynamic therapy (PTT/PDT) and synergistic therapeutic strategies are often sought after, owing to their low side effects and minimal invasiveness compared to chemotherapy and surgical treatments. However, in spite of the development of the most PTT/PDT materials with good tumor-inhibitory effect, there are some disadvantages of photosensitizers and photothermal agents, such as low stability and low photonic efficiency, which greatly limit their further application. Therefore, in this study, a novel bismuth-based hetero-core-shell semiconductor nanomaterial BiNS-Fe@Fe with good photonic stability and synergistic theranostic functions was designed. On the one hand, BiNS-Fe@Fe with a high atomic number exhibits good X-ray absorption, enhanced magnetic resonance (MR) T2-weighted imaging, and strong photoacoustic imaging (PAI) signals. In addition, the hetero-core-shell provides a strong barrier to decline the recombination of electron-hole pairs, inducing the generation of a large amount of reactive oxygen species (ROS) when irradiated with visible-NIR light. Meanwhile, a Fenton reaction can further increase ROS generation in the tumor microenvironment. Furthermore, an outstanding chemodynamic therapeutic potential was determined for this material. In particular, a high photothermal conversion efficiency (η = 37.9%) is of significance and could be achieved by manipulating surface decoration with Fe, which results in tumor ablation. In summary, BiNS-Fe@Fe could achieve remarkable utilization of ROS, high photothermal conversion law, and good chemodynamic activity, which highlight the multimodal theranostic potential strategies of tumors, providing a potential viewpoint for theranostic applications of tumors.
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Antineoplásicos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Apoptosis/efectos de los fármacos , Bismuto/química , Células Hep G2 , Humanos , Rayos Infrarrojos , Hierro/química , Hierro/efectos de la radiación , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Ratones , Imagen Multimodal , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Terapia Fototérmica , Especies Reactivas de Oxígeno/metabolismoRESUMEN
It is interesting yet challenging to design theranostic nanoplatforms for the accurate diagnosis and therapy of diseases; these nanoplatforms consist of single contrast-enhanced imaging or therapeutic agents, and they possess their own unique shortcomings that limit their widespread bio-medical applications. Therefore, designing a potential theranostic agent is an emerging approach for the synergistic diagnosis and therapeutics in bio-medical applications. Herein, a lanthanide-loaded (NaLnF4) heterostructure BiOCl ultrathin nanosheet (BiNS@NaLnF4) as a theranostic agent was synthesized facilely by a solvothermal protocol. BiNS@NaLnF4 was employed as a multi-modal contrast agent for computed tomography (CT) and magnetic resonance imaging (MRI), showing a high-performance X-ray absorption contrast effect, an outstanding T1-weighted imaging function result, good cytocompatibility and favorable in vivo effective imaging for CT. Notably, BiNS@NaLnF4 was applied to achieve a satisfactory photon-thermal conversion efficiency (35.3%). Moreover, the special heterostructure barrier achieved increased utilization of electrons/holes, enhancing the generation of reactive oxygen species (ROS) under visible-light irradiation to further expand the therapeutic effect. Dramatically, visible light emission with the up-conversion law was employed to stimulate ROS after irradiation with a 980 nm laser. Simultaneously, the as-prepared BiNS@NaLnF4 can be applied in photothermal/photodynamic therapy (PTT/PDT) investigation for tumor ablation. In summary, the results reveal that BiNS@NaLnF4 is a potential multi-modal theranostic candidate, providing new insights for synergistic theranostics of tumors.
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Fotoquimioterapia , Nanomedicina Teranóstica , Medios de Contraste , Imagen por Resonancia Magnética , Medicina de Precisión , Tomografía Computarizada por Rayos XRESUMEN
Osteoclasts are multinucleated terminal cells that originate from a hematopoietic monocyte/macrophage lineage. Excessive osteoclast formation in vivo can lead to bone metabolic diseases such as postmenopausal osteoporosis, multiple myeloma, rheumatoid arthritis, and lytic bone metastases of cancer cells. Au nanoparticles (AuNPs) are inorganic nanoparticles with outstanding biocompatibility. We assessed their effect on osteoclastogenesis and found that pre-osteoclast fusion induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF) was suppressed by AuNPs. Cell migration and actin ring formation were also significantly inhibited. Finally, AuNPs reduced osteoclast bone absorption function. Interestingly, we observed altered fusogenic gene expression in treated pre-osteoclasts. Our results suggest that AuNPs have potential as a therapeutic agent for osteoclast-related bone metabolism diseases.
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Nanopartículas del Metal , Osteoclastos , Diferenciación Celular , Oro/farmacología , Osteogénesis/genéticaRESUMEN
Osteoporosis, a common and serious bone disorder affecting aged people and postmenopausal women, is characterized by osteoclast overactivity. One therapeutic strategy is suppressing the bone resorption function of hyperactive osteoclasts, but there is no effective drug in clinical practice so far. Herein, it is demonstrated that fullerenols suppress the bone resorption of osteoclasts by inhibiting ruffled borders (RBs) formation. The RBs formation, which is supported by well-aligned actin bundles (B-actins), is a critical event for osteoclast bone resorption. To facilitate this function, osteoclast RBs dynamics is regulated by variable microenvironments to bundle F-actins, protrude cell membrane, and so on. B-actin perturbation by fullerenols is determined here, offering an opportunity to regulate osteoclast function by destroying RBs. In vivo, the therapeutic effect of fullerenols on overactive osteoclasts is confirmed in a mouse model of lipopolysaccharide-induced bone erosion. Collectively, the findings suggest that fullerenols adhere to F-actin surfaces and inhibit RBs formation in osteoclasts, mainly through hampering Ca2+ from bundling F-actins, and this is likely due to the stereo-hindrance effect caused by adherent fullerenols.
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Fulerenos/química , Osteoclastos/efectos de los fármacos , Actinas/metabolismo , Animales , Calcio/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Fulerenos/farmacología , Humanos , Ratones , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Dispersión del Ángulo PequeñoRESUMEN
Endocytosis is an important pathway to regulate the metabolism of low-density lipoprotein (LDL) in cells. At the same time, engineering nanoparticles (ENPs) enter the cell through endocytosis in biomedical applications. Therefore, a crucial question is whether the nanoparticles involved in endocytosis could impact the natural metabolism of LDL in cells. In this study, we fabricated a series of gold nanoparticles (AuNPs) (13.00 ± 0.69 nm) with varied surface charge densities. The internalized AuNPs with high-surface negative-charge densities (HSNCD) significantly reduced LDL uptake in HepG-2, HeLa, and SMMC-7721 cells compared with those cells in control group. Notably, the significant reduction of LDL uptake in cells correlates with the reduction of LDL receptors (LDL-R) on the cell surface, but there is no change in protein and mRNA of LDL-Rs. The cyclic utilization of LDL-R in cells is a crucial pathway to maintain the homoeostasis of LDL uptake. The release of LDL-Rs from LDL/LDL-R complexes in endosomes depended on reduction of the pH in the lumen. AuNPs with HSNCD hampered vacuolar-type Hâº-ATPase V1 (ATPaseV1) and ATPaseV0 binding on the endosome membrane, blocking protons to enter the endosome by the pump. Hence, fewer freed LDL-Rs were transported into recycling endosomes (REs) to be returned to cell surface for reuse, reducing the LDL uptake of cells by receptor-mediated endocytosis. The restrained LDL-Rs in the LDL/LDL-R complex were degraded in lysosomes.
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Oro/metabolismo , Lipoproteínas LDL/metabolismo , Nanopartículas/metabolismo , Transporte Biológico , Endocitosis , Endosomas/metabolismo , Oro/química , Células Hep G2 , Humanos , Lisosomas/metabolismo , Nanopartículas/química , Nanopartículas/ultraestructura , Receptores de LDL/metabolismo , Electricidad Estática , Propiedades de SuperficieRESUMEN
Designing nanosized multi-modality contrast agents for high-resolution imaging is challenging since most agents are only useful for single-mode imaging. In this work, we successfully synthesized biocompatible polyethylene glycol (PEG-) and l-glutamine (GLN-) modified Ba4Yb3F17:Lu3+,Gd3+ nanoparticles (LNPs@PEG@GLN) that can be employed as a multi-modality contrast agent. Fluorescence dye-modified LNPs@PEG@GLN nanoparticles can be used for computed tomography (CT), magnetic resonance imaging (MRI), and fluorescence imaging (FI). They display high X-ray absorption, outstanding T2-weighted imaging capability, and good fluorescence uptake. Furthermore, LNPs@PEG@GLN enhances contrast efficiencies for different imaging modalities in vivo. Interestingly, LNPs@PEG@GLN is a promising agent for CT angiography. These nanoparticles could be a promising contrast agent for multi-modality imaging and diagnosing vascular diseases.
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BACKGROUND: Tumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis. RESULTS: In this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young's modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility. CONCLUSIONS: With intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.
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Actinas/metabolismo , Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Fulerenos/química , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Citoesqueleto de Actina/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Módulo de Elasticidad , Femenino , Fulerenos/farmacología , Fulerenos/uso terapéutico , Humanos , Integrinas/metabolismo , Neoplasias Pulmonares/secundario , Ratones DesnudosRESUMEN
The widespread application of TiO2 nanoparticles (NPs) as additives in foods such as gum, candy and puddings has dramatically increased the human ingestion and accumulation of these nanomaterials. Although the toxicity of TiO2 NPs has been extensively studied, their impact on gut microbiota in vivo still needs further research. In this study, TiO2 NPs with two main crystalline phases anatase and rutile were orally administrated to mice for 28 days. The dynamic influences of anatase and rutile on gut microbiota structures were investigated at doses equivalent to those consumed by people who love to eat candies. The results showed that titanium accumulated in the spleen, lung, and kidney but had no significant effects on organ histology. Gavage of rutile NPs but not anatase NPs resulted in longer intestinal villi and irregular arrangement of villus epithelial cells. Treatment with TiO2 NPs did not decrease gut microbiota diversity but shifted their structures in a time-dependent manner. Rutile NPs had a more pronounced influence on the gut microbiota than anatase NPs. The most influenced phylum was Proteobacteria, which was significantly increased by rutile but not by anatase. At the genus level, Prevotella was significantly decreased by both the TiO2 NPs, Rhodococcus was enriched by rutile NPs, and Bacteroides was increased by anatase NPs. Overall, these results suggested that chronic overconsumption of TiO2 NP-containing foods is likely to deteriorate the gastrointestinal tract and change the structures of microbiota. The crystalline phases may play an important role in mediating the intestinal impact of TiO2 NPs.