RESUMEN
Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.
Asunto(s)
Vacunas contra el Cáncer , Lípidos , Liposomas , Nanopartículas , ARN Mensajero , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Nanopartículas/química , Animales , Ratones , ARN Mensajero/genética , ARN Mensajero/inmunología , Lípidos/química , Humanos , Ácido Tióctico/química , Ácido Tióctico/farmacología , Polímeros/química , Guanidinas/química , Guanidinas/farmacología , Línea Celular TumoralRESUMEN
Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.
Asunto(s)
Vacunas contra el Cáncer , Liposomas , Nanopartículas , Neoplasias , Humanos , Presentación de Antígeno , Vacunas de ARNm , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismoRESUMEN
OBJECTIVES: Surface micro-area potential difference (MAPD) can achieve bacteriostatic performance independent of metal ion dissolution. To study the influence of MAPD on antibacterial properties and the cellular response, Ti-Ag alloys with different surface potentials were designed and prepared by changing the preparation and heat treatment processes. MATERIALS AND METHODS: Ti-Ag alloys (T4, T6, and S) were prepared by vacuum arc smelting, water quenching, and sintering. Cp-Ti was set as a control group in this work. The microstructures and surface potential distributions of the Ti-Ag alloys were analyzed by SEM and energy dispersive spectrometry. Plate counting and live/dead staining methods were used to evaluate the antibacterial properties of the alloys, and the mitochondrial function, ATP levels, and apoptosis were assessed in MC3T3-E1 cells to analyze the cellular response. RESULTS: Due to the formation of the Ti-Ag intermetallic phase in the Ti-Ag alloys, Ti-Ag (T4) without the Ti-Ag phase had the lowest MAPD, Ti-Ag (T6) with a fine Ti2Ag phase had a moderate MAPD, and Ti-Ag (S) with a Ti-Ag intermetallic phase had the highest MAPD. The primary results demonstrated that the Ti-Ag samples with different MAPDs exhibited different bacteriostatic effects, ROS expression levels, and apoptosis-related protein expression levels in cells. The alloy with a high MAPD exhibited a strong antibacterial effect. A moderate MAPD stimulated cellular antioxidant regulation (GSH/GSSG) and downregulated the expression of intracellular ROS. MAPD could also promote the transformation of the inactive mitochondria to biologically active mitochondria by increasing the ΔΨm and reducing apoptosis. CONCLUSION: The results here indicated that moderate MAPD not only had bacteriostatic effects but also promoted mitochondrial function and inhibited cell apoptosis, which provides a new strategy to improve the surface bioactivity of titanium alloys and a new idea for titanium alloy design. CLINICAL RELEVANCE: There are some limitations of the mechanism of MAPD. However, researchers will become increasingly aware of the advantages and disadvantages of MAPD and MAPD might provide an affordable solution of peri-implantitis.
Asunto(s)
Aleaciones , Titanio , Aleaciones/farmacología , Aleaciones/química , Titanio/farmacología , Titanio/química , Especies Reactivas de Oxígeno , Plata/farmacología , Plata/química , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
Liposomes and polymersomes, typical vesicular drug delivery systems (DDSs), have faced some limitations in cancer theranostics. Suprasomes, supramolecular vesicles assembled from amphiphiles linked by noncovalent interactions, show potential as new generation of vesicular DDSs. We construct suprasomes based on host-guest recognition, by which the desired functions can be integrated into carriers without tedious synthesis. Photothermally active host-guest complex is formed between a functional guest and pillar[5]arene, which further self-assembles into hollow suprasomes. A supramolecular nanomedicine is developed by encapsulating cisplatin in the suprasomes. The obtained cisplatin@Suprasomes achieve excellent anticancer efficacy and anti-metastasis combining chemotherapy and photothermal therapy, which ablate the tumors without relapse and metastasis. This work demonstrates the facile functionalization of suprasomes, holding promise as alternatives to liposomes and polymersomes.
Asunto(s)
Liposomas , Neoplasias , Humanos , Medicina de Precisión , Cisplatino , Sistemas de Liberación de Medicamentos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on ß-cyclodextrin/camptothecin (CPT) host-guest molecular recognition and iron-carboxylate coordination. Iron ions stabilizing SNPs catalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD-L1 checkpoint blockade, SNPs enables enhanced immune therapy and a long-term tumor remission.
Asunto(s)
Nanopartículas , Neoplasias , Camptotecina/farmacología , Camptotecina/uso terapéutico , Línea Celular Tumoral , Humanos , Hierro/uso terapéutico , Nanomedicina , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Polímeros/uso terapéutico , beta-Ciclodextrinas/farmacología , beta-Ciclodextrinas/uso terapéuticoRESUMEN
Long-term storage of protein samples for transportation is a challenge in the field of mass spectrometric analysis because the low temperature condition is not easy to be maintained. Here we introduce a simple method to preserve proteins at room temperature for at least one month. In this method, the protein sample is run shortly into a polyacrylamide gel which is then excised after Coomassie staining. The protein gel band is then dehydrated by 100% acetonitrile three times and kept in 100% acetonitrile for storage at room temperature. By the TMT 10-plex based quantitative proteomic analyses, we have found that these proteins are stable in their levels and modifications (phosphorylation, oxidation, and ubiquitination) for 30 days. Further analysis has revealed this storage method also well preserves proteins even at 45 °C. We therefore recommend to use acetonitrile to dehydrate and store protein gel pieces as an effective alternative for sample shipping over days. Therefore, it might facilitate worldwide collaborations in the mass spectrometry-based proteomic research.
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Acetonitrilos/química , Resinas Acrílicas/química , Espectrometría de Masas/métodos , Preservación Biológica/métodos , Proteínas/análisis , Proteínas/química , Electroforesis en Gel de Poliacrilamida , Células HEK293 , Humanos , Oxidación-Reducción , Fosforilación , UbiquitinaciónRESUMEN
The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.
Asunto(s)
Materiales Biocompatibles Revestidos/química , Durapatita/química , Fémur/patología , Osteoporosis/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Prótesis e Implantes , Titanio/química , Vitamina K 2/análogos & derivados , Animales , Biomarcadores/metabolismo , Fenómenos Biomecánicos , Femenino , Osteoporosis/diagnóstico por imagen , Osteoporosis/patología , Osteoporosis/fisiopatología , Hormona Paratiroidea/farmacología , Implantación de Prótesis , Ratas Sprague-Dawley , Vitamina K 2/farmacología , Vitamina K 2/uso terapéutico , Microtomografía por Rayos XRESUMEN
The main bottlenecks for the widespread application of radical polymers in organic radical batteries are poor cycling stability, due to the dissolution of radical polymers into the electrolyte, and the low efficiency of multi-step synthesis strategies. Herein, a kind of electrolyte-resistant radical polymer bearing multi-pendant groups (poly(ethylene-alt-TEMPO maleate) (PETM)) is designed and synthesized through a one-step esterification reaction to graft 4-hydroxy-2,2,6,6-teramethylpiperidinyl-1-oxy into the commercially available poly(ethylene-alt-maleic anhydride). Interestingly, PETM is hardly soluble in the ethylene carbonate/dimethyl carbonate/ethyl methyl carbonate-based electrolyte, showing an extremely low solubility of 0.59 mg mL-1 , but is easily soluble in tetrahydrofuran and N-Methyl pyrrolidone. The derived binder-free PETM cathode exhibits nearly 100% utilization of the grafted nitroxide radicals (88 mA h g-1 ) and excellent rate capability with almost invariant capacitance from 10 C to 40 C. Significantly, the PETM cathodes retain 94% of the initial capacity after 1000 cycles, outperforming most reported radical polymer-based cathodes.
Asunto(s)
Óxidos N-Cíclicos/química , Técnicas Electroquímicas/métodos , Electrólitos/química , Polímeros/química , Dioxolanos/química , Técnicas Electroquímicas/instrumentación , Electrodos , Formiatos/química , Furanos/química , Microscopía Electrónica de Rastreo , Polímeros/síntesis química , Pirrolidinonas/química , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Marcadores de SpinRESUMEN
PURPOSE: Ureteral stenting is associated with various morbidity and reduced quality of life. We systematically evaluated the efficacy and safety of solifenacin as monotherapy, or combined therapy with tamsulosin versus control or tamsulosin monotherapy in stent-related symptoms (SRSs). MATERIALS AND METHODS: Randomized controlled trials evaluating solifenacin or its combination with tamsulosin for the treatment of SRSs were identified via a comprehensive search of Pubmed, Embase, Ovid, The Cochrane Library and relevant sources up to February 2017. Ureteral stent symptom questionnaire (USSQ) and drug-related complications were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. RESULTS: There were 10 studies involving 1786 participants finally eligible in the quantitative analysis. Solifenacin monotherapy significantly reduced the total score of USSQ [MD -14.90; 95% CI (-25.19, -4.60); P = 0.005], as well as indexes of urinary symptoms, body pain, general health, sexual performance, and hematuria (P = 0.02, P = 0.009, P = 0.004, P = 0.02, P = 0.02, respectively), but the differences were insignificant when compared with tamsulosin except improved sexual performance (P = 0.004). Combined therapy of solifenacin and tamsulosin showed no beneficial effects in all indexes of USSQ over solifenacin monotherapy. Only slightly higher incidence of dry mouth (P = 0.02) was found with solifenacin versus control. CONCLUSIONS: The result demonstrates the safety and efficacy of solifenacin in reducing SRSs, but no significant advantage was found over tamsulosin. In addition, combination of solifenacin and tamsulosin did not show beneficial effects over solifenacin monotherapy. More high quality trials are warranted to further address this issue, however.
Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Antagonistas Muscarínicos/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Succinato de Solifenacina/uso terapéutico , Stents/efectos adversos , Sulfonamidas/uso terapéutico , Uréter/cirugía , Quimioterapia Combinada , Dolor en el Flanco/tratamiento farmacológico , Dolor en el Flanco/etiología , Estado de Salud , Hematuria/tratamiento farmacológico , Hematuria/etiología , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Complicaciones Posoperatorias/etiología , Calidad de Vida , Tamsulosina , Xerostomía/inducido químicamenteRESUMEN
The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic implant fixation, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings. This study aims to investigate effects of PTH + SIM on implant stabilization in osteopenic rats. Fourteen weeks after chronically fed a low protein diet, osteopenic rats randomly received implants. Subsequently, the animals were randomly divided into four groups: Control, SIM, PTH and PTH + SIM. Then all rats from groups PTH, SIM and PTH + SIM received PTH (40 µg/kg, three times a week), SIM (25 mg/kg, daily), or both for 12 weeks. The results of our study indicated that all treatments promoted bone healing around implant compared to Control, but PTH + SIM treatment showed significantly stronger effects than PTH or SIM alone in histological, micro-CT, and biomechanical tests. The results indicated additive effects of PTH and SIM on implant fixation in osteoporotic rats.
Asunto(s)
Artroplastia de Reemplazo de Cadera/instrumentación , Enfermedades Óseas Metabólicas/patología , Materiales Biocompatibles Revestidos/farmacología , Hormona Paratiroidea/farmacología , Simvastatina/farmacología , Titanio , Animales , Conservadores de la Densidad Ósea/farmacología , Regeneración Ósea/efectos de los fármacos , Proteínas en la Dieta/administración & dosificación , Femenino , Fémur/patología , Prótesis de Cadera , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Implantes Experimentales , Oseointegración/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Simvastatina/administración & dosificaciónRESUMEN
Ti-10Cu sintered alloy has shown very strong in vitro and in vivo antibacterial property and in vitro cell compatibility. In this paper, Ti-10Cu implant (Ti-Cu group) and commercial pure Ti implant (cp-Ti group) were implanted in rabbit femurs to investigate in vivo bone response to the Ti-10Cu alloy. X-ray photo, fluorescent microscopy, routine pathological examination and immunohistochemistry have been used to analyze bone growth, mineral apposition rate (MAR), bone implant contact (BIC), BMP-2 expression and TGF-ß1 expression. In both Ti-Cu and cp-Ti groups, new bone tissue was found at bone/implant interfaces 4 weeks postimplantation and completely filled the interfaces gap bone 12 weeks postimplantation. A significant MOD value in BMP-2 expression was observed at week 1 and week 4 in the Ti-Cu group with lower values of week 2 and 3 in both groups, which indicated strong positive activity. MOD value in TGF-ß1 expression decreased with the extension of implantation. However, no difference can be found in MAR, BIC and TGF-ß1 expression between the two groups at all intervals. It was deduced that Ti-Cu alloy exhibited as good bone response as cp-Ti. The good bone compatibility suggests that Ti-10Cu alloy might have potential application in orthopedic surgery and dental implant.
Asunto(s)
Aleaciones/química , Antibacterianos/farmacología , Materiales Biocompatibles , Huesos/efectos de los fármacos , Cobre/química , Titanio/química , Animales , Femenino , Microscopía Fluorescente , ConejosRESUMEN
Titanium and titanium alloys have the advantages of a low density and a close elastic modulus to natural bone, which can reduce the stress-shielding effect and become one of the first choices for human hard tissue replacement and repair. However, implant site infection is still one of the main reasons for implantation failure. In this paper, 2.5 wt % Ag element was added to Ti-15Mo to obtain a low modulus, and a surface anodization was applied to improve the surface biocompatibility. The elastic modulus, micromorphology, surface elemental valence, corrosion resistance, antimicrobial properties, and cytocompatibility were investigated by mechanical tests, scanning electron microscopy, X-ray photoelectron spectroscopy, electrochemical tests, inductively coupled plasma spectroscopy, plate counting method, and cellular tests. The experimental results showed that the anodized Ti-15Mo-2.5Ag sample exhibited an elastic modulus of 79 GPa, a strong corrosion resistance, a strong antimicrobial ability of ≥99.99%, and good biocompatibility. It was demonstrated that the formation of Ag2O on the surface and Ag ion release improved the antimicrobial properties and that the structural synergism of silver ions with micro- and nanostructures played an important role in promoting the early spreading of cells and improving the cytocompatibility.
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Plata , Titanio , Titanio/química , Titanio/farmacología , Plata/química , Plata/farmacología , Nanoestructuras/química , Molibdeno/química , Molibdeno/farmacología , Aleaciones/química , Aleaciones/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Ensayo de Materiales , Animales , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Propiedades de Superficie , Ratones , CorrosiónRESUMEN
Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma". PEEPylated liposomes exhibit lower immunogenicity and generate negligible anti-PEEP antibodies (IgM and IgG) after repeated treatments. In vivo studies confirm that PEEPylated liposomes loaded with oxaliplatin (PEEPlipo@OxPt) show better pharmacokinetics compared to PEGlipo@OxPt, and they exhibit potent antitumor performances, which can be further promoted with checkpoint blockade immunotherapy. In addition, PEEPylated lipid nanoparticle is also used to develop an mRNA vaccine with the ability to evoke a potent antigen-specific T cell response and achieve excellent antitumor efficacy. PEEP shows promising potentials in the development of next-generation nanomedicines and vaccines with higher safety and efficacy.
Asunto(s)
Neoplasias , Polietilenglicoles , Humanos , Polietilenglicoles/farmacocinética , Liposomas , Neoplasias/tratamiento farmacológico , Inmunoterapia , Vacunación , EtilenosRESUMEN
Fluorescent nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics hold remarkable potential for image-guided phototherapy. The molecular packing is the key point for optimizing the performance of AIE luminogens (AIEgens) in the aggregated or solid state. However, so far, the packing mode of AIEgens in NPs is still vague, causing some challenges for understanding the relationship between the photophysical property and packing mode, as well as further optimizing the performance of NPs for biomedical applications. In this contribution, by simply controlling the length of alkoxy chains in the donor-acceptor conjugated OPTPA, a packing balance between the twisted molecular structure and effective π-conjugation is actualized. Subsequently, the possibility of amorphous-crystalline transition of AIEgens in the polymer-encapsulated NPs is presented for the first time, and the comprehensive performance of NPs is further optimized. Both in vitro and in vivo experiments indicate that crystalline AIEgen-based NPs are remarkably effective in trimodal imaging-guided synergistic phototherapy.
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Nanopartículas , Vendajes , Colorantes Fluorescentes , Estructura Molecular , Fototerapia , PolímerosRESUMEN
Pear is a major fruit tree crop distributed worldwide, yet its breeding is a very time-consuming process. To facilitate molecular breeding and gene identification, here we have performed genome-wide association studies (GWAS) on eleven fruit traits. We identify 37 loci associated with eight fruit quality traits and five loci associated with three fruit phenological traits. Scans for selective sweeps indicate that traits including fruit stone cell content, organic acid and sugar contents might have been under continuous selection during breeding improvement. One candidate gene, PbrSTONE, identified in GWAS, has been functionally verified to be involved in the regulation of stone cell formation, one of the most important fruit quality traits in pear. Our study provides insights into the complex fruit related biology and identifies genes controlling important traits in pear through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in perennial trees.
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Frutas/genética , Estudio de Asociación del Genoma Completo , Pyrus/genética , Sitios de Carácter Cuantitativo/genética , Arabidopsis/genética , Genes de Plantas , Variación Genética , Genética de Población , Lignina/metabolismo , Filogenia , Plantas Modificadas Genéticamente , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The sensitivity of the commonly used immunochromatographic fecal occult blood test (iFOBT) is critical in the routine screening of digestive tract cancers. OBJECTIVE: To determine whether the performance of the iFOBT might be improved by optimizing detergents and buffers in stool solution. METHODS: We tested different buffers and detergents in stool solution. The specificity of the new solution condition was confirmed by dot immunoblotting. A total of 1122 clinical stool specimens were collected to evaluate the clinical application of this refined stool solution. RESULTS: The different salts exerted minor effects; also, sodium dodecyl sulfate (SDS) prevented the test from working as designed. However, 1% Triton X-100 improved the sensitivity significantly, as confirmed by dot immunoblot testing. With 1% Triton X-100 in the stool solution, the rate of positive iFOBT results in patients with digestive tract cancers increased, from 40.4% to 49.4%. CONCLUSION: Use of 1% Triton X-100 improves the sensitivity of the iFOBT and thus, this substance should be routinely included in iFOBT for screening of digestive tract cancers.
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Cromatografía de Afinidad/métodos , Sangre Oculta , Hemoglobinas/análisis , Humanos , Immunoblotting , Octoxinol , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Circulating EBV-DNA is an accurate biomarker of tumor load in extranodal natural killer (NK)/T cell lymphoma (ENKTL); however, its role in patients treated with P-GEMOX has not been evaluated. In this study, we examined plasma EBV-DNA of 99 patients at different time points by real-time quantitative polymerase chain reaction. Multivariate analysis revealed that ECOG PS score, response rate, and post-treatment EBV-DNA level were independent predictors of progression-free survival (PFS) and overall survival (OS). Positive post-treatment plasma EBV-DNA was associated with poor OS in ENKTL patients. The 3-year OS for patients with positive pre-, interim-, post-treatment EBV-DNA was significantly lower than that for patients with negative EBV-DNA; the values were 70.2% vs. 93.9% (p = .022), 53.8% vs. 99.1% (p < .001), and 40.6% vs. 91.8% (p < .001), respectively. We conclude that monitoring dynamic changes in plasma EBV-DNA in ENKTL patients treated with P-GEMOX could predict important outcomes such as OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Desoxicitidina/análogos & derivados , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/etiología , Polietilenglicoles/administración & dosificación , Carga Viral , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , ADN Viral , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Femenino , Humanos , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/mortalidad , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Adulto JovenRESUMEN
Accumulating evidence suggests that improvements in osteogenesis and angiogenesis play an important role in repairing osteoporotic bone defects. Cinnamomum cassia (C. cassia), a traditional Chinese medicinal herb, is reported to show anabolic effects on osteoblasts. However, whether C. cassia could actually repair bone defects in osteoporotic conditions remains unknown. The purpose of this study was to evaluate the effect of combined treatment with Cinnamaldehyde (main oil isolated from the C. cassia) and ß-tricalcium phosphate (ß-TCP) on bone formation and angiogenesis in critical size calvarial defects in ovariectomized (OVX) rats. Using a previously established OVX model, 5 mm critical size calvarial defect was established in OVX rats. All OVX rats were then randomly divided into OVX group (OVX rats + empty defect), TCP group (OVX rats + ß-TCP), and CTCP group (Cinnamaldehyde 75 mg/kg/day for 12 weeks + ß-TCP). Twelve weeks after treatment, according to Micro-CT and HE staining, combination of Cinnamaldehyde and ß-TCP had an additive effect on bone regeneration compared with other groups (p < 0.05). Based on dynamic fluorochrome-labelling analysis, Cinnamaldehyde+ß-TCP continuously promoted new bone mineralization compared with other groups at each time point (p < 0.05). Microfil perfusion suggested that CTCP group showed more neovascularization compared with other groups (p < 0.05). Immunohistochemical assay supported the findings that Cinnamaldehyde+ß-TCP enhanced expression of OCN, VEGF and CD31. The present study demonstrated that combined treatment with Cinnamaldehyde and ß-TCP promoted bone formation and angiogenesis in osteoporotic bone defects, which provides a promising new strategy for repairing bone defects in osteoporotic conditions.
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Acroleína/análogos & derivados , Inductores de la Angiogénesis/administración & dosificación , Fosfatos de Calcio/administración & dosificación , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Ovariectomía/efectos adversos , Acroleína/administración & dosificación , Animales , Materiales Biocompatibles/administración & dosificación , Quimioterapia Combinada , Femenino , Osteogénesis/fisiología , Osteoporosis/diagnóstico por imagen , Osteoporosis/metabolismo , Ovariectomía/tendencias , Ratas , Ratas Sprague-Dawley , Cráneo/diagnóstico por imagen , Cráneo/efectos de los fármacos , Cráneo/metabolismoRESUMEN
Potassium detection is critical in monitoring imbalances in electrolytes and physiological status. The development of rapid and robust potassium sensors is desirable in clinical chemistry and point-of-care applications. In this study, composite supramolecular hydrogels are investigated: polyethylene glycol methacrylate and acrylamide copolymer (P(PEGMA-co-AM)) are functionalized with 18-crown-6 ether by employing surface initiated polymerization. Real-time potassium ion monitoring is realized by combining these compounds with quartz crystal microbalance. The device demonstrates a rapid response time of ≈30 s and a concentration detection range from 0.5 to 7.0 × 10-3 m. These hydrogels also exhibit high reusability and K+ ion selectivity relative to other cations in biofluids such as Na+ , NH4+ , Mg2+ , and Ca2+ . These results provide a new approach for sensing alkali metal ions using P(PEGMA-co-AM) hydrogels.
Asunto(s)
Éteres Corona/química , Hidrogeles/química , Metacrilatos/química , Polietilenglicoles/química , Potasio/química , Tecnicas de Microbalanza del Cristal de CuarzoRESUMEN
This study investigates the anti-bacterial property of Ti-Cu sintered alloys against Porphyromonas gingivalis. The anti-anaerobic property of Ti-Cu sintered alloys against P. gingivalis was investigated by antibacterial activity test, DNA measurement, DAPI staining and morphology observation. The antibacterial rates of the Ti-5Cu against P. gingivalis after 18 and 24 h incubation were 36.04 and 54.39%, and those of Ti-10Cu were 68.69 and 75.39%, which were lower than their anti-aerobic abilities. The concentration of P. gingivalis DNA gradually decreased with the increasing Cu content, which was nearly 50% after 24 h incubation on Ti-10Cu. SEM results showed that the shape of P. gingivalis changed and the bacteria broke apart with the addition of Cu and the extension of the culture time. Ti-Cu sintered alloys could not only kill anaerobic bacteria but also reduce the activity of the survived bacteria. The anti-anaerobic mechanism was thought to be in associated with the Cu ion released from Ti-Cu alloy.