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This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 µL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro-computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.
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Cartílago Articular , Osteoartritis , Sinovitis , Ratas , Animales , Microtomografía por Rayos X , Activación de Macrófagos , Adyuvante de Freund/efectos adversos , Adyuvante de Freund/metabolismo , Liposomas/efectos adversos , Liposomas/metabolismo , Cartílago Articular/metabolismo , Articulación Temporomandibular/metabolismo , Sinovitis/metabolismo , Remodelación Ósea , Osteoartritis/metabolismoRESUMEN
The distribution of Ly6C/G-positive cells in response to an infection of the mouse respiratory tract with influenza A virus was followed noninvasively over time by immuno-positron emission tomography. We converted nanobodies that recognize Ly6C and Ly6G, markers of neutrophils and other myeloid cells, as well as an influenza hemagglutinin-specific nanobody, into 89Zr-labeled PEGylated positron emission tomography (PET) imaging agents. The PET images showed strong accumulation of these imaging agents in the lungs of infected mice. Immunohistochemistry of influenza virus-infected mice and control mice, injected with a biotinylated and PEGylated version of the Ly6C/G-specific nanobody, showed the presence of abundant Ly6C/G-positive myeloid cells and positivity for Ly6C/G on bronchial epithelium in influenza virus-infected mice. This is consistent with focal inflammation in the lungs, a finding that correlated well with the immuno-PET results. No such signals were detected in control mice. Having shown by PET the accumulation of the Ly6C/G-specific nanobody in infected lungs, we synthesized conjugates of Ly6C/G-specific nanobodies with dexamethasone to enable targeted delivery of this immunosuppressive corticosteroid to sites of inflammation. Such conjugates reduced the weight loss that accompanies infection, while the equivalent amount of free dexamethasone was without effect. Nanobody-drug conjugates thus enable delivery of drugs to particular cell types at the appropriate anatomic site(s). By avoiding systemic exposure to free dexamethasone, this strategy minimizes its undesirable side effects because of the much lower effective dose of the nanobody-dexamethasone conjugate. The ability to selectively target inflammatory cells may find application in the treatment of other infections or other immune-mediated diseases.
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Gripe Humana , Anticuerpos de Dominio Único , Corticoesteroides , Animales , Antiinflamatorios , Dexametasona/farmacología , Hemaglutininas , Humanos , Inflamación/tratamiento farmacológico , Ratones , PolietilenglicolesRESUMEN
An optical fiber sensing probe using a composite sensitive film of polyacrylonitrile (PAN) nanofiber membrane and gold nanomembrane is presented for the detection of a carcinoembryonic antigen (CEA), a biomarker associated with colorectal cancer and other diseases. The probe is based on a tilted fiber Bragg grating (TFBG) with a surface plasmon resonance (SPR) gold nanomembrane and a functionalized polyacrylonitrile (PAN) PAN nanofiber coating that selectively binds to CEA molecules. The performance of the probe is evaluated by measuring the spectral shift of the TFBG resonances as a function of CEA concentration in buffer. The probe exhibits a sensitivity of 0.46â dB/(µg/ml), a low limit of detection of 505.4â ng/mL in buffer, and a good selectivity and reproducibility. The proposed probe offers a simple, cost-effective, and a novel method for CEA detection that can be potentially applied for clinical diagnosis and monitoring of CEA-related diseases.
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Resinas Acrílicas , Antígeno Carcinoembrionario , Oro , Nanofibras , Fibras Ópticas , Resonancia por Plasmón de Superficie , Antígeno Carcinoembrionario/análisis , Oro/química , Nanofibras/química , Resonancia por Plasmón de Superficie/instrumentación , Resonancia por Plasmón de Superficie/métodos , Resinas Acrílicas/química , Humanos , Técnicas Biosensibles/instrumentación , Membranas Artificiales , Nanopartículas del Metal/química , Reproducibilidad de los Resultados , Tecnología de Fibra Óptica/instrumentaciónRESUMEN
Morphology-transformational self-assembly of peptides allows for manipulation of the performance of nanostructures and thereby advancing the development of biomaterials. Acceleration of the morphological transformation process under a biological microenvironment is important to efficiently implement the tailored functions in living systems. Herein, we report redox-regulated in situ seed-induced assembly of peptides via design of two co-assembled bola-amphiphiles serving as a redox-resistant seed and a redox-responsive assembly monomer, respectively. Both of the peptides are able to independently assemble into nanoribbons, while the seed monomer exhibits stronger assembling propensity. The redox-responsive monomer undergoes morphological transformation from well-defined nanoribbons to nanoparticles. Kinetics studies validate the role of the assembled inert monomer as the seeds in accelerating the assembly of the redox-responsive monomer. Alternative addition of oxidants and reductants into the co-assembled monomers promotes the redox-regulated assembly of the peptides facilitated by the in situ-formed seeds. The reduction-induced assembly of the peptide could also be accelerated by in situ-formed seeds in cancer cells with a high level of reductants. Our findings demonstrate that through precisely manipulating the assembling propensity of co-assembled monomers, the in situ seed-induced assembly of peptides could be achieved. Combining the rapid assembly kinetics of the seed-induced assembly with the common presence of redox agents in a biological microenvironment, this strategy potentially offers a new method for developing biomedical materials in living systems.
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Nanoestructuras , Nanotubos de Carbono , Sustancias Reductoras , Péptidos/química , Nanoestructuras/química , Materiales Biocompatibles , Oxidación-ReducciónRESUMEN
Drought stress exerts a significant impact on the growth, development, and yield of fruit trees. Cerasus humilis is an endemic drought-resistant fruit tree in northern China. To elucidate the underlying mechanism of drought resistance in C. humilis, comprehensive physiological measurements and transcriptome analysis were conducted on the leaves of C. humilis subjected to 15- or 22-days of drought stress. We identified multiple GO terms and KEGG pathways associated with the drought stress response by performing GO and KEGG analysis on DEGs. Furthermore, through the prediction of transcription factors (TFs) and analysis of their expression levels, we observed differential expression patterns among most members of stress-responsive TF families as the duration of drought stress increased. WGCNA analysis was performed on the transcriptome to identify gene cluster modules that exhibited a strong correlation with the durations of drought. Subsequently, these modules underwent GO and KEGG enrichment analyses. The study revealed that the TF-mediated lignin biosynthesis pathway, along with the plant hormone signal transduction pathway, played a prominent role in responding to drought stress of C. humilis. Gene profiling analysis, qRT-PCR, and determination of phytohormone and lignin contents further supported this hypothesis. The hierarchical gene regulatory network was finally constructed based on DEGs from the aforementioned key enriched pathways to predict the gene regulatory mechanisms in response to stress for C. humilis. The findings from this study provide valuable insights into how C. humilis copes with drought stress while analyzing crucial gene pathways associated with its resistance from a TF perspective. This research is significant for the genetic breeding of economic forests.
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Sequías , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Fisiológico/genética , Transcriptoma/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Redes Reguladoras de Genes , Lignina/metabolismo , Lignina/genética , Lignina/biosíntesis , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transducción de Señal/genética , Resistencia a la SequíaRESUMEN
BACKGROUND: The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized. RESULTS: In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection. CONCLUSION: Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.
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Nanopartículas , Poliestirenos , Animales , Ratones , Poliestirenos/toxicidad , Especies Reactivas de Oxígeno , Necroptosis , Plásticos , Hepatocitos , Macrófagos , Mitocondrias , Nanopartículas/toxicidad , HígadoRESUMEN
Microorganism-mediated self-assembling of living formulations holds great promise for disease therapy. Here, we constructed a prebiotic-probiotic living capsule (PPLC) by coculturing probiotics (EcN) with Gluconacetobacter xylinus (G. xylinus) in a prebiotic-containing fermentation broth. Through shaking the culture, G. xylinus secretes cellulose fibrils that can spontaneously encapsulate EcN to form microcapsules under shear forces. Additionally, the prebiotic present in the fermentation broth is incorporated into the bacterial cellulose network through van der Waals forces and hydrogen bonding. Afterward, the microcapsules were transferred to a selective LB medium, which facilitated the colonization of dense probiotic colonies within them. The in vivo study demonstrated that PPLC-containing dense colonies of EcN can antagonize intestinal pathogens and restore microbiota homeostasis by showing excellent therapeutic performance in treating enteritis mice. The in situ self-assembly of probiotics and prebiotics-based living materials provides a promising platform for the treatment of inflammatory bowel disease.
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Enfermedades Inflamatorias del Intestino , Prebióticos , Animales , Ratones , Cápsulas , Técnicas de Cocultivo , CelulosaRESUMEN
BACKGROUND: Immediate rehabilitation is a considerable therapeutic challenge but is necessary for edentulous patients with oronasal fistulas, especially those with inadequate residual bone and a history of radiotherapy. CASE PRESENTATION: We report a rare case of a 63-year-old patient who was missing the majority of his maxillary teeth and who had a defect due to palatal mucoepidermoid carcinoma resection. The patient also received radiotherapy twice within one year postoperatively. An implant-supported prosthesis with an obturator was fabricated immediately. CONCLUSION: This technique improved patients' oral function, enhanced the aesthetic effect, and increased their confidence.
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Prótesis Dental de Soporte Implantado , Prótesis de Recubrimiento , Boca Edéntula , Humanos , Persona de Mediana Edad , Masculino , Boca Edéntula/rehabilitación , Neoplasias Palatinas/cirugía , Neoplasias Palatinas/rehabilitación , Obturadores Palatinos , Diseño de DentaduraRESUMEN
Targeted liposomes, as a promising carrier, have received tremendous attention in COVID-19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time-consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one-step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death-ligand 1 (PD-L1)-targeting aptamer modified indocyanine green (ICG)-liposome (Apt-ICG@Lip) is successfully constructed via the MMD. ICG and the PD-L1-targeting aptamer are used as model drug and targeting moiety, respectively. The Apt-ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD-L1-expressing tumor models) show that Apt-ICG@Lip can realize PD-L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.
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COVID-19 , Liposomas , Humanos , Antígeno B7-H1 , Microfluídica , Vacunas contra la COVID-19 , Reproducibilidad de los Resultados , Verde de Indocianina , Línea Celular TumoralRESUMEN
Nanozymes are nanomaterials with biocatalytic properties under physiological conditions and are one class of artificial enzymes to overcome the high cost and low stability of natural enzymes. However, surface ligands on nanomaterials will decrease the catalytic activity of the nanozymes by blocking the active sites. To address this limitation, ligand-free PtAg nanoclusters (NCs) are synthesized and applied as nanozymes for various enzyme-mimicking reactions. By taking advantage of the mutual interaction of zeolitic imidazolate frameworks (ZIF-8) and Pt precursors, a good dispersion of PtAg bimetal NCs with a diameter of 1.78 ± 0.1 nm is achieved with ZIF-8 as a template. The incorporation of PtAgNCs in the voids of ZIF-8 is confirmed with structural analysis using the atomic pair-distribution function and powder X-ray diffraction. Importantly, the PtAgNCs present good catalytic activity for various enzyme-mimicking reactions, including peroxidase-/catalase- and oxidase-like reactions. Further, this work compares the catalytic activity between PtAg NCs and PtAg nanoparticles with different compositions and finds that these two nanozymes present a converse dependency of Ag-loading on their activity. This study contributes to the field of nanozymes and presents a potential option to prepare ligand-free bimetal biocatalysts with sizes in the nanocluster regime.
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Nanopartículas del Metal , Imitación Molecular , Peroxidasa/química , Peroxidasa/metabolismo , Nanopartículas del Metal/química , Platino (Metal)/química , Plata/química , Aleaciones/químicaRESUMEN
The host restriction factor APOBEC3G (A3G) inhibits an extensive variety of viruses, including retroviruses, DNA viruses, and RNA viruses. Our study shows that A3G inhibits enterovirus 71 (EV71) and coxsackievirus A16 (CA16) via competitively binding the 5' untranslated region (UTR) with the host protein poly(C)-binding protein 1 (PCBP1), which is required for the replication of multiple EVs. However, whether A3G inhibits other EVs in addition to EV71 and CA16 has not been investigated. Here, we demonstrate that A3G could inhibit the replication of EVD68, which requires PCBP1 for its replication, but not CA6, which does not require PCBP1 for replication. Further investigation revealed that the nucleic-acid-binding activity of A3G is required for EVD68 restriction, similar to the mechanism presented for EV71 restriction. Mechanistically, A3G competitively binds to the cloverleaf (1 to 123 nucleotides [nt]) and the stem-loop IV (234 to 446 nt) domains of the EVD68 5' UTR with PCBP1, thereby inhibiting the 5' UTR activity of EVD68; by contrast, A3G does not interact with CA6 5' UTR, resulting in no effect on CA6 replication. Moreover, the nonstructural protein 2C, encoded by EVD68, overcomes A3G suppression by inducing A3G degradation via the autophagy-lysosome pathway. Our findings revealed that A3G might have broad-spectrum antiviral activity against multiple EVs through this general mechanism, and they might provide important information for the development of an anti-EV strategy. IMPORTANCE As the two major pathogens causing hand, foot, and mouth disease (HFMD), enterovirus 71 (EV71) and coxsackievirus A16 (CA16) attract a lot of attention for the study of their pathogenesis, their involvement with cellular proteins, and so on. However, other EVs such as CA6 and EVD68 constantly occur sporadically or have spread worldwide in recent years. Therefore, more information related to these EVs is needed in order to develop a broad-spectrum anti-EV inhibitor. In this study, we first reveal that the protein poly(C)-binding protein 1 (PCBP1), involved in PV- and EV71 virus replication, is also required for the replication of EVD68, but not for the replication of CA6. Next, we found that the host-restriction factor A3G specifically inhibits the replication of EVD68, but not the replication of CA6, by competitively binding to the 5' UTR of EVD68 along with PCBP1. Our findings broaden knowledge related to EV replication and the interplay between EVs and host factors.
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Regiones no Traducidas 5'/fisiología , Desaminasa APOBEC-3G/metabolismo , Proteínas de Unión al ADN/metabolismo , Enterovirus Humano D/fisiología , Proteínas de Unión al ARN/metabolismo , Replicación Viral , Desaminasa APOBEC-3G/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN/genética , Enterovirus Humano A/fisiología , Células HEK293 , Humanos , Conformación de Ácido Nucleico , ARN Viral/química , ARN Viral/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/genética , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismoRESUMEN
BACKGROUND: Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet. METHODS: The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays. RESULTS: hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods. CONCLUSIONS: These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.
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Células Madre Mesenquimatosas , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Ratones , Animales , Adenoviridae , Pulpa Dental , Sincalida , Viroterapia Oncolítica/métodos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The relationship between anemia and depression remains controversial. OBJECTIVE: To explore the association between anemia/hemoglobin and depression. METHODS: The data for our cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Weighted multivariate logistic regression was performed to examine the association between anemia/hemoglobin and depression. Inverse variance weighted (IVW), weighted-median, and MR-Egger were used in MR analyses to assess the causal relationship between anemia/hemoglobin and depression. Heterogeneity and directional pleiotropy were assessed using the Cochrane Q test and Egger-intercept test, respectively. Sensitivity analysis was conducted by the leave-one-out approach. All analyses were carried out using IBM SPSS 24.0 and R version 4.2.2. RESULTS: A total of 29,391 NHANES participants were included in this study. After adjusting for all covariates, the association between anemia/hemoglobin and depression was not significant (P < 0.05). IVW estimates revealed that broad anemia had no significant effect on the risk of depression (OR = 1.00, 95% CI = 0.99-1.01, P = 0.432). Findings of weighted median and MR-Egger were consistent with those from IVW (weighted median: OR = 1.00, 95% CI = 0.99-1.02; P = 0.547; MR-Egger: OR = 1.01, 95% CI = 0.98-1.03, P = 0.605). The results of three MR Analyses methods also showed no causal association between hemoglobin and depression. CONCLUSIONS: Our findings do not support a causal association between anemia and depression. The association between hemoglobin concentration and depression was not statistically significant either.
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Anemia , Análisis de la Aleatorización Mendeliana , Humanos , Encuestas Nutricionales , Estudios Transversales , Anemia/epidemiología , NonoxinolRESUMEN
OBJECTIVES: Periodontitis is closely associated with kidney disease and reactive oxygen species (ROS) involvement. Mitochondria are the primary source of both endogenous ROS and renal energy. We investigated whether resveratrol (RSV) prevents renal injury and mitochondrial dysfunction in periodontitis rats. METHODS: Thirty male Wistar rats were divided into control, experimental periodontitis (Ep) and Ep-RSV groups. To induce periodontitis, a steel ligature was placed on the cervix of the bilateral first maxillary molars. RSV (50 mg/kg/day) to the Ep-RSV group and vehicle to the Ep and control groups were gavaged. After 8 weeks, alveolar bone loss, pocket depth, gingival blood index and tooth mobility were assessed. Oxidative stress parameters, mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial ROS, adenosine triphosphate (ATP), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were analysed in renal. Renal function and histology were also evaluated. RESULTS: Compared with the control group, the Ep group showed renal structural destruction, elevated oxidative stress levels, mitochondrial structure destruction, MMP loss, mitochondrial ROS accumulation, ATP reduction, and decreased SIRT1 and PGC-1α levels. RSV prevented these destruction (p < 0.05). However, there was no significant impairment in renal function (p > 0.05). CONCLUSIONS: Periodontitis induces mitochondrial dysfunction in renal tissues. Resveratrol exerts a preventive effect on periodontitis-induced kidney injury by preventing mitochondrial dysfunction.
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Periodontitis , Sirtuina 1 , Femenino , Ratas , Masculino , Animales , Resveratrol/farmacología , Resveratrol/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/farmacología , Ratas Wistar , Estrés Oxidativo , Periodontitis/complicaciones , Periodontitis/prevención & control , Periodontitis/metabolismo , Riñón/metabolismo , Mitocondrias , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacologíaRESUMEN
OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease that is associated with aging and is influenced by both genetic and environmental factors. Several studies and clinical trials have demonstrated that resveratrol (Res) and salidroside (Sal) are not only biologically safe but also influence AD biomarker trajectories. However, their clinical applications have been quite limited due to poor specificity, low solubility, and insufficient blood-brain barrier (BBB) penetration. Therefore, we developed a nano-drug delivery system in which Res and Sal were encapsulated in liposomes, which were surface-modified with ApoE (ApoE-Res/Sal-Lips) to compensate for these deficiencies. METHOD: In this study, ApoE-Res/Sal-Lips were prepared using a standard thin-film hydration method for liposomes. Then, cellular uptake of the loaded liposomes was assessed in vitro using fluorescent staining assays. A BBB model was constructed to investigate the capacity of the liposomes to cross the BBB in vitro, and the ability of liposomes to target the brain was observed by in vivo imaging. In addition, the neuroprotective effects of the different liposome formulations in APP/PS-1 mice were evaluated by measuring the changes in levels of oxidative, anti-inflammatory, and anti-apoptotic factors in the mice brains. RESULTS: In vitro, ApoE-Res/Sal-Lips increased the uptake of Res and Sal by bEnd.3 and N2a cells, enhanced BBB penetration, and improved transport efficiency. In vivo, the ApoE-Res/Sal-Lips were found to alleviate AD pathological symptoms, reduce learning and memory impairments, and improve brain function. CONCLUSION: ApoE-Res/Sal-Lips provide a new method for the treatment of AD.
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Enfermedad de Alzheimer , Glucósidos , Enfermedades Neurodegenerativas , Fenoles , Ratones , Animales , Liposomas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Resveratrol/farmacología , Barrera Hematoencefálica , Apolipoproteínas E/farmacología , Apolipoproteínas E/uso terapéuticoRESUMEN
Reinforcement of polymer nanocomposites can be achieved by the selection of the appropriate fabrication method, surface modification, and orientation of the filler. Herein, we present a nonsolvent-induced phase separation method with ternary solvents to prepare thermoplastic polyurethane (TPU) composite films with excellent mechanical properties using 3-Glycidyloxypropyltrimethoxysilane-modified cellulose nanocrystals (GLCNCs). ATR-IR and SEM analyses of the GLCNCs confirmed that GL was successfully coated on the surface of the nanocrystals. The incorporation of GLCNCs in TPU resulted in the enhancement of the tensile strain and toughness of pure TPU owing to the enhanced interfacial interactions between them. The GLCNC-TPU composite film had tensile strain and toughness values of 1740.42% and 90.01 MJ/m3, respectively. Additionally, GLCNC-TPU exhibited a good elastic recovery rate. CNCs were readily aligned along the fiber axis after the spinning and drawing of the composites into fibers, which further improved the mechanical properties of the composites. The stress, strain, and toughness of the GLCNC-TPU composite fiber increased by 72.60%, 10.25%, and 103.61%, respectively, compared to those of the pure TPU film. This study demonstrates a facile and effective strategy for fabricating mechanically enhanced TPU composites.
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Nanopartículas , Poliuretanos , Poliuretanos/química , Silanos , Celulosa/química , Polímeros/química , Nanopartículas/químicaRESUMEN
Thermal insulating composites are indispensable in electronic applications; however, their poor thermal conductivity and flexibility have become bottlenecks for improving device operations. Hexagonal boron nitride (BN) has excellent thermal conductivity and insulating properties and is an ideal filler for preparing thermally insulating polymer composites. In this study, we report a method to fabricate BN/polyurethane (PU) composites using an improved nonsolvent-induced phase separation method with binary solvents to improve the thermal performance and flexibility of PU. The stress and strain of BN60/PU are 7.52 ± 0.87 MPa and 707.34 ± 38.34%, respectively. As prepared, BN60/PU composites with unordered BN exhibited high thermal conductivity and a volume resistivity of 0.653 W/(m·K) and 23.9 × 1012 Ω·cm, which are 218.71 and 39.77% higher than that of pure PU, respectively. Moreover, these composite films demonstrated a thermal diffusion ability and maintained good integrity after 1000 bending cycles, demonstrating good mechanical and thermal reliability for practical use. Our findings provide a practical route for the production of flexible materials for efficient thermal management.
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Electrónica , Poliuretanos , Reproducibilidad de los Resultados , Conductividad TérmicaRESUMEN
Dental caries, particularly secondary caries, which is the main contributor to dental repair failure, has been the subject of extensive research due to its biofilm-mediated, sugar-driven, multifactorial, and dynamic characteristics. The clinical utility of restorations is improved by cleaning bacteria nearby and remineralizing marginal crevices. In this study, a novel multifunctional dental resin composite (DRC) composed of Sr-N-co-doped titanium dioxide (Sr-N-TiO2) nanoparticles and nano-hydroxyapatite (n-HA) reinforcing fillers with improved antibacterial and mineralization properties is proposed. The experimental results showed that the anatase-phase Sr-N-TiO2 nanoparticles were synthesized successfully. After this, the curing depth (CD) of the DRC was measured from 4.36 ± 0.18 mm to 5.10 ± 0.19 mm, which met the clinical treatment needs. The maximum antibacterial rate against Streptococcus mutans (S. mutans) was 98.96%, showing significant inhibition effects (p < 0.0001), which was experimentally verified to be derived from reactive oxygen species (ROS). Meanwhile, the resin exhibited excellent self-remineralization behavior in an SBF solution, and the molar ratio of Ca/P was close to that of HA. Moreover, the relative growth rate (RGR) of mouse fibroblast L929 indicated a high biocompatibility, with the cytotoxicity level being 0 or I. Therefore, our research provides a suitable approach for improving the antibacterial and mineralization properties of DRCs.
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Caries Dental , Nanopartículas , Animales , Ratones , Durapatita/farmacología , Resinas Compuestas/farmacología , Antibacterianos/farmacología , Ensayo de MaterialesRESUMEN
PURPOSE: To explore the outcomes of bone augmentation in the aesthetic zone of the anterior teeth using computer-aided design and a 3D-printed template. METHODS: Ten patients with severe bone defects in the aesthetic zone of anterior teeth were included in the study; CT data were collected before surgery. The design of the osteotomy line in the bone defect area was determined under computer simulation. The position parameters and osteotomy line of the free bone were determined via virtual surgery. A 3D-printed template was prepared to guide the accurate placement of the bone graft. Reexamination was conducted to evaluate the position of the bone graft immediately after the operation and the resorbed capacity of the bone graft before implant restoration. RESULTS: The position of the bone graft was consistent with the preoperative design. The amount of bone graft resorbed was within the acceptable range three months after the operation, and the effect of implant restoration was satisfactory. CLINICAL SIGNIFICANCE: Use of computer-aided design and a 3D-printed template can be an effective approach for accurate bone augmentation in the aesthetic zone of the anterior teeth.
Asunto(s)
Diseño Asistido por Computadora , Estética Dental , Impresión Tridimensional , Humanos , Simulación por Computador , OsteotomíaRESUMEN
AIM: The present study aimed to develop a method for measuring 3D maxillary tooth movement during orthodontic treatment and to verify the accuracy of the method. MATERIALS AND METHODS: A 3D model analysis method was established to measure tooth movement by combining the effects of CBCT and intraoral scans. Transformation matrices were used to abstract the motion features of the teeth and translate them into translations and rotations. To test the validity and reliability of the method for clinical application, the inclination of the central incisor was measured using a 3D model analysis method and cephalometric analysis. Measurement error, correlation, and agreement between the two methods were analyzed using the Dahlberg formula, intraclass correlation coefficient, and Bland-Altman analysis, respectively. The performance of the 3D model analysis method was evaluated by monitoring the canine movement of a patient who underwent a premolar extraction. RESULTS: The measurement error was 0.58 degrees for the 3D model analysis and 2.02 degrees for the cephalometric analysis. There was no significant difference in the central incisor inclination measurements between the cephalometric and the 3D model analyses methods. A high correlation (0.974) and narrow limits of agreement (-3.55 degrees, 4.16 degrees) were obtained between the two methods. Minute movements and additional details of orthodontic tooth movements could be observed using the 3D model analysis method. CONCLUSION: The 3D model analysis method was reliable and reproducible for clinical application in monitoring the 3D maxillary tooth movement during orthodontic treatment. The trueness should be further evaluated. (Int J Comput Dent 2023;26(1): 49-0; doi: 10.3290/j.ijcd.b3818301).