RESUMEN
Spherical molecularly imprinted polymers (MIPs) were prepared by emulsion polymerization. The isothermal adsorption and selective adsorption indicated that the MIPs obtained exhibit excellent specific recognition for the template (atrazine) and its analogues. The MIPs were encapsulated in a polypropylene microporous membrane to fabricate MIP adsorption packages for the direct extraction of triazines in uncentrifuged and unfiltered tea extracts. The extraction conditions affecting the extraction efficiency, including the type and volume of extraction solvent, the number of MIP adsorption packages, the surface area of the MIP adsorption packages, the mass of MIPs in the MIP adsorption packages, the extraction time, the eluting solvent, and the eluting volume, were optimized. Under the optimal extraction and high-performance liquid chromatography-tandem mass spectrometry conditions, the method exhibited excellent linearity in the range from 0.5 to 250 ng g-1, with R2 ≥ 0.9992. The detection limit of the method was 0.09-0.18 ng g-1. The intraday and interday relative standard deviations ranged from 3.1% to 7.5% and from 3.1% to 7.9%, respectively. The method was successfully used to detect triazines in five tea samples. At a spiking concentration of 2 ng g-1, satisfactory recoveries ranging from (81 ± 3)% to (104 ± 7)% were obtained. The membrane-protected solid-phase extraction method based on molecularly imprinted material is expected to be widely used to enrich triazines in complex samples. Graphical Abstract Schematic illustration of the MIPs combined with membrane-protected solid-phase extraction of triazines in tea sample.
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Impresión Molecular/métodos , Polímeros/química , Extracción en Fase Sólida/métodos , Té/química , Triazinas/análisis , Adsorción , Cromatografía Líquida de Alta Presión/métodos , Límite de Detección , Membranas Artificiales , Polimerizacion , Espectrometría de Masas en Tándem/métodosRESUMEN
Millions of people are infected each year by arboviruses (arthropod-borne viruses) such as chikungunya, dengue, and West Nile viruses, yet for reasons that are largely unknown, only a relatively small number of mosquito species are able to transmit arboviruses. Understanding the complex factors that determine vector competence could facilitate strategies for controlling arbovirus infections. Apoptosis is a potential antiviral defense response that has been shown to be important in other virus-host systems. However, apoptosis is rarely seen in arbovirus-infected mosquito cells, raising questions about its importance as an antiviral defense in mosquitoes. We tested the effect of stimulating apoptosis during arbovirus infection by infecting Aedes aegypti mosquitoes with a Sindbis virus (SINV) clone called MRE/Rpr, in which the MRE-16 strain of SINV was engineered to express the proapoptotic gene reaper from Drosophila. MRE/Rpr exhibited an impaired infection phenotype that included delayed midgut infection, delayed virus replication, and reduced virus accumulation in saliva. Nucleotide sequencing of the reaper insert in virus populations isolated from individual mosquitoes revealed evidence of rapid and strong selection against maintenance of Reaper expression in MRE/Rpr-infected mosquitoes. The impaired phenotype of MRE/Rpr, coupled with the observed negative selection against Reaper expression, indicates that apoptosis is a powerful defense against arbovirus infection in mosquitoes and suggests that arboviruses have evolved mechanisms to avoid stimulating apoptosis in mosquitoes that serve as vectors.
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Aedes/virología , Apoptosis/fisiología , Insectos Vectores/virología , Selección Genética , Virus Sindbis/fisiología , Aedes/genética , Animales , Insectos Vectores/genética , Saliva/virología , Replicación ViralRESUMEN
Conjugated microporous polymers (CMPs), in which rigid building blocks form robust networks, are usually synthesized as insoluble and unprocessable powders. We developed a methodology using electropolymerization for the synthesis of thin CMP films. The thickness of these films is synthetically controllable, ranging from nanometers to micrometers, and they are obtained on substrates or as freestanding films. The CMP films combine a number of striking physical properties, including high porosity, extended πâ conjugation, facilitated exciton delocalization, and high-rate electron transfer. We explored the CMP films as versatile platforms for highly sensitive and label-free chemo- and biosensing of electron-rich and electron-poor arenes, metal ions, dopamine, and hypochloroic acid, featuring rapid response, excellent selectivity, and robust reusability.
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Técnicas Biosensibles , Polímeros/química , PorosidadRESUMEN
Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.
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Antibacterianos , Regeneración Ósea , Quitosano , Cobre , Fusobacterium nucleatum , Nanopartículas , Periodontitis , Quitosano/química , Quitosano/farmacología , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Periodontitis/terapia , Periodontitis/patología , Animales , Antibacterianos/farmacología , Antibacterianos/química , Regeneración Ósea/efectos de los fármacos , Ratas , Cobre/química , Cobre/farmacología , Fusobacterium nucleatum/efectos de los fármacos , Nanopartículas/química , Ratas Sprague-Dawley , Masculino , Sulfatos/química , Sulfatos/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Covalent organic frameworks (COFs) have emerged as a kind of crystalline polymeric materials with high compositional and geometric tunability. Most COFs are currently designed and synthesized as mesoporous (2-50 nm) and microporous (1-2 nm) materials, while the development of ultramicroporous (<1 nm) COFs remains a daunting challenge. Here, we develop a pore partition strategy into COF chemistry, which allows for the segmentation of a mesopore into multiple uniform ultramicroporous domains. The pore partition is implemented by inserting an additional rigid building block with suitable symmetries and dimensions into a prebuilt parent framework, leading to the partitioning of one mesopore into six ultramicropores. The resulting framework features a wedge-shaped pore with a diameter down to 6.5 Å, which constitutes the smallest pore among COFs. The wedgy and ultramicroporous one-dimensional channels enable the COF to be highly efficient for the separation of five hexane isomers based on the sieving effect. The obtained average research octane number (RON) values of those isomer blends reach up to 99, which is among the highest records for zeolites and other porous materials. Therefore, this strategy constitutes an important step in the pore functional exploitation of COFs to implement pre-designed compositions, components, and functions.
Asunto(s)
Estructuras Metalorgánicas , Zeolitas , Polímeros , Isomerismo , PorosidadRESUMEN
Recently, photodynamic therapy (PDT) has been considered as a new strategy for atherosclerosis treatment. Targeted delivery of photosensitizer could significantly reduce its toxicity and enhance its phototherapeutic efficiency. CD68 is an antibody that can be conjugated to nano-drug delivery systems to actively target plaque sites, owing to its specific binding to CD68 receptors that are highly expressed on the surfaces of macrophage-derived foam cells. Liposomes are very popular nanocarriers due to their ability to encapsulate a wide range of therapeutic compounds including drugs, microRNAs and photosensitizers, and their ability to be surface-modified with targeting moieties leading to the development of nanocarriers with an improved targeted ability. Hence, we designed a Ce6-loaded liposomes using the film dispersion method, followed by the conjugation of CD68 antibody on the liposomal surface through a covalent crosslinking reaction, forming CD68-modified Ce6-loaded liposomes (CD68-Ce6-mediated liposomes). Flow cytometry results indicated that Ce6-containing liposomes were more effective in promoting intracellular uptake after laser irradiation. Furthermore, CD68-modified liposomes significantly strengthened the cellular recognization and thus internalization. Different cell lines have been incubated with the liposomes, and the results showed that CD68-Ce6-mediated liposomes had no significant cytotoxicity to coronary artery endothelial cells (HCAEC) under selected conditions. Interestingly, they promoted autophagy in foam cells through the increase in LC3-â , LC3-â ¡ expression and the decrease in p62 expression, and restrained the migration of mouse aortic vascular smooth muscle cells (MOVAS) in vitro. Moreover, the enhancement of atherosclerotic plaque stability and the reduction in the cholesterol content by CD68-Ce6-mediated liposomes were dependent on transient reactive oxygen species (ROS) generated under laser irradiation. In summary, we demonstrated that CD68-Ce6-mediated liposomes, as a photosensitizer nano-drug delivery system, have an inhibitory effect on MOVAS migration and a promotion of cholesterol efflux in foam cells, and thereby, represent promising nanocarriers for atherosclerosis photodynamic therapy.
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Aterosclerosis , Nanopartículas , Fotoquimioterapia , Placa Aterosclerótica , Porfirinas , Ratones , Animales , Fármacos Fotosensibilizantes , Liposomas , Placa Aterosclerótica/tratamiento farmacológico , Células Endoteliales , Fotoquimioterapia/métodos , Aterosclerosis/tratamiento farmacológico , Porfirinas/farmacología , Porfirinas/química , Línea Celular Tumoral , Nanopartículas/químicaRESUMEN
Many tissues have a three-dimensional (3D) anisotropic structure compatible with their physiological functions. Engineering an in vitro 3D tissue having the natural structure and functions is a hotspot in tissue engineering with application for tissue regeneration, drug screening, and disease modeling. Despite various designs that have successfully guided the cellular alignment, only a few of them could precisely control the orientation of each layer in a multilayered construct or achieve adequate cell contact between layers. This study proposed a design of a multilayered 3D cell/scaffold model, that is, the cell-loaded aligned nanofiber film/hydrogel (ANF/Gel) model. The characterizations of the 3D cell-loaded ANF/Gel model in terms of design, construction, morphology, and cell behavior were systematically studied. The ANF was produced by efficiently aligned electrospinning using a self-designed, fast-and-easy collector, which was designed based on the parallel electrodes and modified with a larger gap area up to about 100 cm2. The nanofibers generated by this simple device presented numerous features like high orientation, uniformity in fiber diameter, and thinness. The ANF/Gel-based cell/scaffold model was formed by encapsulating cell-loaded multilayered poly(lactic-co-glycolic acid)-ANFs in hydrogel. Cells within the ANF/Gel model showed high viability and displayed aligned orientation and elongation in accordance with the nanofiber orientation in each film, forming a multilayered tissue having a layer spacing of 60 µm. This study provides a multilayered 3D cell/scaffold model for the in vitro construction of anisotropic engineered tissues, exhibiting potential applications in cardiac tissue engineering.
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Nanofibras , Ingeniería de Tejidos , Hidrogeles/química , Nanofibras/química , Poliésteres/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases, comprising seven members SIRT1-SIRT7. Sirtuins have been extensively studied in regulating ageing and age-related diseases. Sirtuins are also pivotal modulators in oxidative stress and inflammation, as they can regulate the expression and activation of downstream transcriptional factors (such as Forkhead box protein O3 (FOXO3a), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB)) as well as antioxidant enzymes, through epigenetic modification and post-translational modification. Most importantly, studies have shown that aberrant sirtuins are involved in the pathogenesis of infectious and inflammatory oral diseases, and oral cancer. In this review, we provide a comprehensive overview of the regulatory patterns of sirtuins at multiple levels, and the essential roles of sirtuins in regulating inflammation, oxidative stress, and bone metabolism. We summarize the involvement of sirtuins in several oral diseases such as periodontitis, apical periodontitis, pulpitis, oral candidiasis, oral herpesvirus infections, dental fluorosis, and oral cancer. At last, we discuss the potential utilization of sirtuins as therapeutic targets in oral diseases.
RESUMEN
The signal-to-noise ratio of a sensor system is determined by the affinity of its active component for the analyte on one hand and its inertness with respect to unrelated stimuli (noise) on the other hand. Nonspecific interactions between the environment and biosensor components (typically constructed from glass, silica, or transition metal oxides) result in nonspecific adsorption onto the latter and constitute a major source of noise. We have previously introduced a polymeric interface for preventing nonspecific adsorption while allowing for high-affinity, specific interactions. It is based on the coassembly of biotinylated and nonbiotinylated poly(l-lysine)-graft-poly(ethylene glycol) from aqueous solutions to negatively charged surfaces, such as Nb(2)O(5). In this study, we investigated by atomic force microscopy the nanoscale organization of this interface for each individual step involved in the preparation of a bioactive interface: polymer adsorption, loading with streptavidin, and binding of biotinylated vesicles.
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Complejos Multiproteicos/síntesis química , Complejos Multiproteicos/metabolismo , Niobio/metabolismo , Óxidos/metabolismo , Adsorción , Técnicas Biosensibles/métodos , Biotinilación , Microscopía de Fuerza Atómica , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Polilisina/química , Polilisina/metabolismo , Polímeros/química , Unión Proteica , Proteínas/química , Relación Señal-Ruido , Estreptavidina , Propiedades de SuperficieRESUMEN
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biodegradable polyester, has been a good candidate of biomaterial employed in tissue engineering. However, the PHBV film is hydrophobic and has no recognition sites for cell attachment. In this study, PHBV films are activated by ammonia plasma treatment to produce amino groups on the surface, followed by sequential reactions with a heterobifunctional cross-linker containing a segment of poly(ethylene glycol) (PEG) and further with RGD-containing peptides. XPS analyses of modified surfaces after each reaction step reveal that the RGD-containing peptides have been covalently grafted onto PHBV films. The result of cell viability assay indicates that the RGD-modified PHBV films exhibit a distinctly improved cellular compatibility. Moreover, according to the results of serum adsorption tests by optical waveguide lightmode spectroscopy (OWLS) and fibrinogen adsorption tests by enzyme-linked immunosorbent assay (ELISA) on unmodified and modified PHBV surfaces, the introduced PEG chains can significantly decrease the nonspecific adsorption of proteins from serum and fibrinogen from plasma, thus decreasing the risk of thrombus formation and improving the blood compatibility of implanted materials.
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Materiales Biocompatibles/síntesis química , Oligopéptidos/química , Poliésteres/química , Polietilenglicoles/química , Adsorción , Materiales Biocompatibles/farmacocinética , Proteínas Sanguíneas/metabolismo , Reactivos de Enlaces Cruzados , Humanos , Unión Proteica/efectos de los fármacos , Trombosis/inducido químicamenteRESUMEN
The effective therapy for lung infectious diseases became more and more difficult since the severe antibiotic resistance of pathogenic microorganisms, it is urgent to develop new antimicrobial agents. Luteolin has been reported to play a crucial part in host immune responses. However, the clinical use of luteolin is impeded due to its hydrophobicity and low oral bioavailability. In this study, we formulated luteolin-loaded Methoxy poly(ethylene glycol)-poly(lactide) micelles (luteolin/MPEG-PLA), to improve the bioavailability of luteolin in lung infectious diseases. The results showed that luteolin/MPEG-PLA treatment could reduce the adhesion of Klebsiella pneumoniae (K. pneumoniae) to lung epithelial cells and enhance the germicidal ability of macrophages against K. pneumoniae compared to untreated group. Meanwhile, luteolin/MPEG-PLA showed stronger adhesion resistance of epithelial cells and germicidal ability of macrophages compared with free luteolin. In vivo study, luteolin/MPEG-PLA administration significantly promoted the clearance of bacteria and reduced inflammatory infiltration of lung tissue in K. pneumoniae induced lung infectious mice model. Further studies showed that treatment with luteolin/MPEG-PLA reduced the mRNA expression of LPS-induced inflammatory cytokines and chemokines in macrophages significantly. In general, luteolin/MPEG-PLA can enhance the anti-bacterial ability of lung epithelial cells and macrophages, and has a stronger therapeutic effect than free luteolin in bacterial-induced lung infection. Luteolin/MPEG-PLA may be an excellent potential drug for bacterial-induced lung infectious diseases treatment.
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Luteolina , Micelas , Animales , Antiinflamatorios , Bacterias , Portadores de Fármacos , Pulmón , Luteolina/farmacología , Ratones , Poliésteres , PolietilenglicolesRESUMEN
Periodontitis is a prevalent chronic disease that results in loss of periodontal ligament and bone resorption. Triggered by pathogens and prolonged inflammation, periodontitis is modulated by the immune system, especially pro-inflammatory cells, such as T helper (Th) 17 cells. Originated from CD4+ Th cells, Th17 cells play a central role for they drive and regulate periodontal inflammation. Cytokines secreted by Th17 cells are also major players in the pathogenesis of periodontitis. Given the importance of Th17 cells, modulators of Th17 cells are of great clinical potential and worth of discussion. This review aims to provide an overview of the current understanding of the effect of Th17 cells on periodontitis, as well as a brief discussion of current and potential therapies targeting Th17 cells. Lastly, we highlight this article by summarizing the causal relationship between A20 (encoded by TNFAIP3), an anti-inflammatory molecule, and Th17 cell differentiation.
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Periodontitis/inmunología , Células Th17/inmunología , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/inmunología , Animales , HumanosRESUMEN
The clinical efficacy of Oxaliplatin (L-OHP) is potentially limited by dose-dependent neurotoxicity and high partitioning to erythrocytes in vivo. Long-circulating liposomes could improve the pharmacokinetic profile of L-OHP and thus enhance its therapeutic efficacy and reduce its toxicity. The purpose of this study was to prepare L-OHP long-circulating liposomes (L-OHP PEG lip) by reverse-phase evaporation method (REV) and investigate their pharmacokinetic behavior based on total platinum in rat plasma using atomic absorption spectrometry (AAS). A simple and a sensitive AAS method was developed and validated to determine the total platinum originated from L-OHP liposomes in plasma. Furthermore, long-circulating liposomes were fully characterized in vitro and showed great stability when stored at 4°C for one month. The results showed that the total platinum in plasma of L-OHP long-circulating liposomes displayed a biexponential pharmacokinetic profile with five folds higher bioavailability and longer distribution half-life compared to L-OHP solution. Thus, long-circulating liposomes prolonged L-OHP circulation time and may present a potential candidate for its tumor delivery. Conclusively, the developed AAS method could serve as a reference to investigate the pharmacokinetic behavior of total platinum in biological matrices for other L-OHP delivery systems.
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Oxaliplatino/sangre , Oxaliplatino/farmacocinética , Animales , Rastreo Diferencial de Calorimetría , Liberación de Fármacos , Inyecciones Intravenosas , Cinética , Liposomas , Concentración Osmolar , Oxaliplatino/administración & dosificación , Tamaño de la Partícula , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrofotometría Atómica , TemperaturaRESUMEN
BACKGROUND: Therapy for glioblastoma (GBM) has always been very challenging, not only because of the presence of the blood-brain barrier (BBB) but also due to susceptibility to drug resistance. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) has revolutionized gene editing technology and is capable of treating a variety of genetic diseases, including human tumors, but there is a lack of safe and effective targeting delivery systems in vivo, especially in the central nervous system (CNS). METHODS: Lipid-polymer hybrid nanoparticles (LPHNs-cRGD) were constructed for efficient and targeting delivery of CRISPR/Cas9 plasmids targeting O6-methylguanine-DNA methyltransferase (MGMT), a drug-resistance gene to temozolomide (TMZ). Focused ultrasound (FUS)-microbubbles (MBs) were used to non-invasively and locally open the BBB to further facilitate gene delivery into glioblastoma in vivo. The gene editing efficiency and drug sensitivity changes were evaluated both in vitro and in vivo. RESULTS: The gene-loaded LPHNs-cRGD were successfully synthesized and could protect pCas9/MGMT from enzyme degradation. LPHNs-cRGD could target GBM cells and mediate the transfection of pCas9/MGMT to downregulate the expression of MGMT, resulting in an increased sensitivity of GBM cells to TMZ. MBs-LPHNs-cRGD complexes could safely and locally increase the permeability of the BBB with FUS irradiation in vivo and facilitated the accumulation of nanoparticles at the tumor region in orthotopic tumor-bearing mice. Furthermore, the FUS-assisted MBs-LPHNspCas9/MGMT-cRGD enhanced the therapeutic effects of TMZ in glioblastoma, inhibited tumor growth, and prolonged survival of tumor-bearing mice, with a high level of biosafety. CONCLUSION: In this work, we constructed LPHNs-cRGD for targeting delivery of the CRISPR/Cas9 system, in combination with FUS-MBs to open the BBB. The MBs-LPHNs-cRGD delivery system could be a potential alternative for efficient targeting gene delivery for the treatment of glioblastoma.
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Neoplasias Encefálicas/terapia , Resistencia a Antineoplásicos , Terapia Genética , Glioblastoma/terapia , Ultrasonido Enfocado de Alta Intensidad de Ablación , Lípidos/química , Nanopartículas/química , Polímeros/química , Animales , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Desoxirribonucleasa I/metabolismo , Glioblastoma/tratamiento farmacológico , Humanos , Ratones Endogámicos NOD , Ratones SCID , Microburbujas , Nanopartículas/ultraestructura , Péptidos Cíclicos/química , Plásmidos/genética , Temozolomida/farmacología , Temozolomida/uso terapéutico , Distribución Tisular , TransfecciónRESUMEN
The development of diversified biomaterials in tissue engineering has been promoted by growing research into carbon-based nanomaterials. Usually, ideal scaffold materials should possess properties similar to the extracellular matrix of natural myocardial tissue. In this study, dopamine-reduced graphene oxide (GO), was prepared and doped into gelatin methacrylate (GelMA) hydrogels, resulting in novel conductive and mechanical properties for controlling cell growth. Cardiomyocytes (CMs) cultured on PDA-rGO-incorporated hydrogels (GelMA-PDA-rGO) had greater cytocompatibility than those cultured on GelMA hydrogels, as evidenced by higher cell survival rates and up-regulation of cardiac-relevant proteins. Finally, electrical stimulation was applied to facilitate the maturation of CMs which was seeded on different hydrogels. The findings revealed that electrical stimulation of conductive hybrid hydrogel scaffolds improved the orientational order parameter of sarcomeres (OOP). In addition, propagation of intercellular pacing signals, which improves the expression of gap junction proteins was noticed, likewise calcium handling capacity was present in conductive hybrid hydrogels compared to those in pure GelMA group. This study has shown that the combination of GelMA-PDA-rGO based conductive hydrogels and electrical stimulation possessed synergistic effects for engineering a more functional and mature myocardium layer as well as further application in drug screening and disease modeling in vitro.
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Hidrogeles , Miocitos Cardíacos , Animales , Animales Recién Nacidos , Estimulación Eléctrica , Gelatina , Grafito , Indoles , Polímeros , Ratas , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
The miR let-7b-5p (a kind of microRNAs) has many pathophysiological regulation effects, including human hepatocellular carcinoma (HCC) pathogenesis. This study investigated whether nanoparticle-mediated miR let-7b-5p could jointly enhance the therapeutic effect of sorafenib on HCC by inhibiting the proliferation of HCC cells, inducing apoptosis, and reversing drug resistance. We evaluated the level of miR let-7b-5p in sorafenib-resistant HepG2 cells (HepG2R) and HepG2 HCC cells by qRT-PCR and analyzed the biological effects of hepatocellular carcinoma treated with sorafenib with miR let-7b-5p, and further studied the toxicity of nanoparticles (Ab-miR-NPs) that deliver miR let-7b-5p mimics and target GPC3 on the surface of hepatocellular carcinoma cells. Results showed that, in HepG2 cells, the expression level of miR let-7b-5p was significantly higher than that in HepG2R cells. Targeted nanoparticle Ab-miR-NPs mediated the delivery of miR let-7b-5p to the HCC cytoplasm and released miRNA after being broken down, down-regulating the expression of IGF1R and inhibiting AKT/mTOR and Ras/Raf signal transmission. Ab-miR-NPs not only enhanced the proliferation of sorafenib in cultured HepG2R cells and induced cell apoptosis efficiency, but they also improved the anti-tumor activity in the mouse models. These results indicated that GPC3 antibody-modified PLGA-PLL (polylactic acid-glycolic acetic copolymer grafted hyper-branched polylysine) loaded miR let-7b-5p polymer nanoparticles combined with sorafenib may be a new treatment strategy for HCC resistant to sorafenib.
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Carcinoma Hepatocelular , Glipicanos/administración & dosificación , Neoplasias Hepáticas , MicroARNs , Nanopartículas , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos , Glipicanos/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Ratones , MicroARNs/genética , Polímeros , SorafenibRESUMEN
PURPOSE: Management of maxillary hypoplasia in patients with cleft lip and palate (CLP) remains a significant clinical challenge. The objective of this retrospective study is to evaluate the accuracy of virtual surgical planning (VSP) with different maxillary advancement techniques. METHODS: Ninety adult patients with cleft-related maxillary hypoplasia between April 2010 and April 2016 were enrolled in our study. Various surgical techniques including conventional orthognathic surgery, total maxillary distraction osteogenesis, and anterior maxillary segmental distraction were used according to the characteristics of patients. All the cases were aided with VSP and three-dimensional (3D)-printed surgical splints. The virtual surgical plan was compared with the postoperative surgical results by analyzing the positions of several landmarks and planes relative to reference planes. RESULTS: Both the profile and occlusion were improved significantly in all the cases. VSP was successfully transferred to actual surgery with the help of 3D-printed surgical splints in different surgical techniques. CONCLUSION: Management of cleft-related maxillary hypoplasia requires both comprehensive surgical planning and accurate execution. VSP serves as a viable alternative to conventional model surgery with high accuracy in patients with adult CLP.
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Labio Leporino/cirugía , Fisura del Paladar/cirugía , Maxilar/anomalías , Osteogénesis por Distracción/métodos , Osteotomía Le Fort/métodos , Adulto , Femenino , Humanos , Masculino , Maxilar/cirugía , Micrognatismo/cirugía , Procedimientos Quirúrgicos Ortognáticos/métodos , Planificación de Atención al Paciente , Resultado del Tratamiento , Interfaz Usuario-Computador , Adulto JovenRESUMEN
The field of cardiac tissue engineering has made significant strides in therapeutic and pharmaceutical applications, highlighted by the development of smart biomaterials. Scaffolds with appropriate properties mimicking the nature of a heart matrix will be highly beneficial for cardiac tissue engineering. In this study, high-aspect-ratio water-dispersed gold nanowires (AuNWs) were synthesized and incorporated into gelatin methacrylate (GelMA) hydrogels, demonstrating enhanced electrical conductivity and mechanical properties of the biomaterial scaffolds. Cardiac cells cultured on GelMA-AuNW hybrid hydrogels exhibited better biological activities such as cell viability and maturation state compared to those cultured on GelMA hydrogels. Moreover, cardiomyocytes showed synchronous beating activity and a faster spontaneous beating rate on GelMA-AuNW hybrid hydrogels. Our strategy of integrating high-aspect-ratio water-dispersed gold nanowires within gelatin methacrylate hydrogels provides a favorable biomaterial scaffold to construct functional cardiac tissue for further applications in cardiac tissue engineering and drug screening.
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Gelatina/química , Oro/química , Hidrogeles/química , Metacrilatos/química , Miocitos Cardíacos/metabolismo , Nanocables/química , Andamios del Tejido/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Calcio/metabolismo , Técnicas de Cultivo de Célula , Proliferación Celular , Supervivencia Celular , Conductividad Eléctrica , Gelatina/metabolismo , Ventrículos Cardíacos , Humanos , Hidrogeles/metabolismo , Fenómenos Mecánicos , Miocitos Cardíacos/citología , Procesos Fotoquímicos , Fármacos Fotosensibilizantes/química , Ratas Sprague-Dawley , Ingeniería de Tejidos , AguaRESUMEN
Having advantageous biocompatibility and osteoconductive properties known to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs), hydroxyapatite (HA) is a commonly used material for bone tissue engineering. What remains unclear, however, is whether HA holds a similar potential for stimulating the osteogenic differentiation of MSCs to that of a more frequently used osteogenic-inducing medium (OIM). To that end, we used PHBV electrospun nanofibrous scaffolds to directly compare the osteogenic capacities of HA with OIM over MSCs. Through the observation of cellular morphology, the staining of osteogenic markers, and the quantitative measuring of osteogenic-related genes, as well as microRNA analyses, we not only found that HA was as capable as OIM for differentiating MSCs down an osteogenic lineage; albeit, at a significantly slower rate, but also that numerous microRNAs are involved in the osteogenic differentiation of MSCs through multiple pathways involving the inhibition of cellular proliferation and stemness, chondrogenesis and adipogenesis, and the active promotion of osteogenesis. Taken together, we have shown for the first time that PHBV electrospun nanofibrous scaffolds combined with HA have a similar osteogenic-inducing potential as OIM and may therefore be used as a viable replacement for OIM for alternative in vivo-mimicking bone tissue engineering applications.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Durapatita/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Nanofibras/química , Osteogénesis/efectos de los fármacos , Poliésteres/química , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Durapatita/química , Matriz Extracelular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/metabolismo , Poliésteres/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Ingeniería de Tejidos , Andamios del Tejido/químicaRESUMEN
OBJECTIVE: To assess the outcome of orthodontic treatment for adolescents with congenital missing teeth using the PAR (Peer Assessment Ration) index. METHODS: The PAR index was adopted to evaluate and compare the teeth arrangement, molar occlusion, overjet, overbite and centerline condition of 20 adolescents with congenital missing teeth before and after orthodontic treatments. RESULTS: The initial PAR scores and weighted PAR total scores decreased significantly after Orthodontic treatments (P < 0.01), except for the centerline. The PAR total scores decreased by 14.25 +/- 7.91 (80.90% +/- 11.09%). The weighted PAR total scores decreased by 15.45 +/- 8.16 (75.34% +/- 18.41%). CONCLUSION: PAR index can well reflect the improvement of occlusion characters by orthodontic treatment for adolescents with congenital missing teeth. But further improvement is needed for clinical application.