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1.
J Chem Inf Model ; 64(3): 638-652, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38294781

RESUMEN

A simple approach was developed to computationally construct a polymer dataset by combining simplified molecular-input line-entry system (SMILES) strings of a targeted polymer backbone and a variety of molecular fragments. This method was used to create 14 polymer datasets by combining seven polymer backbones and molecules from two large molecular datasets (MOSES and QM9). Polymer backbones that were studied include four polydimethylsiloxane (PDMS) based backbones, poly(ethylene oxide) (PEO), poly(allyl glycidyl ether) (PAGE), and polyphosphazene (PPZ). The generated polymer datasets can be used for various cheminformatics tasks, including high-throughput screening for gas permeability and selectivity. This study utilized machine learning (ML) models to screen the polymers for CO2/CH4 and CO2/N2 gas separation using membranes. Several polymers of interest were identified. The results highlight that employing an ML model fitted to polymer selectivities leads to higher accuracy in predicting polymer selectivity compared to using the ratio of predicted permeabilities.


Asunto(s)
Dióxido de Carbono , Polímeros , Polietilenglicoles , Quimioinformática , Ensayos Analíticos de Alto Rendimiento
2.
Planta ; 259(1): 12, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057597

RESUMEN

MAIN CONCLUSION: Transcriptional and metabolic regulation of lignin biosynthesis and lignification plays crucial roles in Avicennia marina pneumatophore development, facilitating its adaptation to coastal habitats. Avicennia marina is a pioneer mangrove species in coastal wetland. To cope with the periodic intertidal flooding and hypoxia environment, this species has developed a complex and extensive root system, with its most unique feature being a pneumatophore with a distinct above- and below-ground morphology and vascular structure. However, the characteristics of pneumatophore lignification remain unknown. Studies comparing the anatomy among above-ground pneumatophore, below-ground pneumatophore, and feeding root have suggested that vascular structure development in the pneumatophore is more like the development of a stem than of a root. Metabolome and transcriptome analysis illustrated that the accumulation of syringyl (S) and guaiacyl (G) units in the pneumatophore plays a critical role in lignification of the stem-like structure. Fourteen differentially accumulated metabolites (DAMs) and 10 differentially expressed genes involved in the lignin biosynthesis pathway were targeted. To identify genes significantly associated with lignification, we analyzed the correlation between 14 genes and 8 metabolites and further built a co-expression network between 10 transcription factors (TFs), including 5 for each of MYB and NAC, and 23 enzyme-coding genes involved in lignin biosynthesis. 4-Coumarate-CoA ligase, shikimate/quinate hydroxycinnamoyl transferase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and peroxidase were identified to be strongly correlated with these TFs. Finally, we examined 9 key candidate genes through quantitative real-time PCR to validate the reliability of transcriptome data. Together, our metabolome and transcriptome findings reveal that lignin biosynthesis and lignification regulate pneumatophore development in the mangrove species A. marina and facilitate its adaptation to coastal habitats.


Asunto(s)
Avicennia , Avicennia/genética , Avicennia/metabolismo , Lignina/metabolismo , Reproducibilidad de los Resultados , Perfilación de la Expresión Génica , Transcriptoma/genética , Metaboloma
3.
Environ Sci Technol ; 57(25): 9321-9331, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37315293

RESUMEN

Alkylphenols (APs) represent one of the highest exposure levels among endocrine disrupting chemicals (EDCs) in the South China Sea (SCS) due to their extensive use as plastic additives. The concerns about EDCs, including APs, have been reiterated since the surge in plastic waste from the COVID-19 response, but far less is known about the response of AP loadings in the SCS to emerging public policies and activities, including the COVID-19 pandemic. Here, we used cetaceans as bioindicators for monitoring two major APs, 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP), in nine stranded cetacean species (n = 110) in the SCS between 2004 and 2021. Prior to the COVID-19, APs loads showed decreasing temporal trends for finless porpoises and humpback dolphins, most likely due to China's restrictions on AP use or a shift in dominant prey species. Unexpectedly, AP loads continued to decline after the COVID-19 outbreak, probably due to a temporal-lag response of marine AP fluxes to the pandemic. The health risk assessments based on hormone biomarkers and toxicity thresholds suggest the potential adverse effects of APs on cetaceans, while recent declines in APs, though limited, may mitigate the detrimental impacts.


Asunto(s)
COVID-19 , Delfines , Disruptores Endocrinos , Marsopas , Contaminantes Químicos del Agua , Animales , Humanos , Biomarcadores Ambientales , Pandemias , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , COVID-19/epidemiología , China/epidemiología , Marsopas/fisiología , Delfines/fisiología , Plásticos
4.
Environ Sci Technol ; 57(15): 6284-6295, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37013483

RESUMEN

Since the wide occurrence of endocrine disrupting chemicals (EDCs) in water is associated with various adverse effects in aquatic organisms, it is urgent to identify key bioconcentratable EDCs. Currently, bioconcentration is generally ignored during the identification of key EDCs. Thus, a methodology for effect-based identification of bioconcentratable EDCs was established in Microcosm, validated in the field, and applied to typical surface water in Taihu Lake. In Microcosm, an inverted U-shaped relationship between logBCFs and logKows was observed for typical EDCs, with medium hydrophobic EDCs (3 ≤ logKow ≤ 7) exhibiting the greatest bioconcentration potentials. On this basis, enrichment methods for bioconcentratable EDCs were established using POM and LDPE, which better fitted the bioconcentration characteristics and enabled the enrichment of 71 ± 8% and 69 ± 6% bioconcentratable compounds. The enrichment methods were validated in the field, where LDPE exhibited a more significant correlation with the bioconcentration characteristics than POM, with mean correlation coefficients of 0.36 and 0.15, respectively, which was selected for further application. By application of the new methodology in Taihu Lake, 7 EDCs were prioritized from 79 identified EDCs as key bioconcentratable EDCs on consideration of their great abundance, bioconcentration potentials, and anti-androgenic potencies. The established methodology could support the evaluation and identification of bioconcentratable contaminants.


Asunto(s)
Disruptores Endocrinos , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Disruptores Endocrinos/análisis , Agua , Polietileno , Monitoreo del Ambiente/métodos
5.
J Environ Manage ; 336: 117632, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36921474

RESUMEN

Although the fates of microplastics (0.1-5 mm) in marine environments and freshwater are increasingly studied, little is known about their vector effect in wastewater treatment plants (WWTPs). Previous studies have evaluated the accumulation of antibiotic resistance genes (ARGs) on microplastics, but there is no direct evidence for the selection and horizontal transfer of ARGs on different microplastics in WWTPs. Here, we show biofilm formation as well as bacterial community and ARGs in these biofilms grown on four kinds of microplastics via incubation in the aerobic and anaerobic tanks of a WWTP. Microplastics showed differential capacities for bacteria and ARGs enrichment, differing from those of the culture environment. Furthermore, ARGs in microplastic biofilms were horizontally transferred at frequencies higher than those in water samples in both tanks. Therefore, microplastics in WWTPs can act as substrates for horizontal transfer of ARGs, potentially causing a great harm to the ecological environment and adversely affecting human health.


Asunto(s)
Antibacterianos , Microplásticos , Humanos , Antibacterianos/farmacología , Plásticos , Genes Bacterianos , Aguas Residuales , Farmacorresistencia Microbiana/genética , Bacterias/genética
6.
J Clin Periodontol ; 49(10): 1067-1078, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35713233

RESUMEN

AIM: Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. MATERIALS AND METHODS: Ligature-induced PD (LIP) was induced in male C57/B6J mice, and sub-gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4 ) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4 , CCl4 +LIP, and CCl4 +LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α-smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT-PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. RESULTS: Mice in the CCl4 +LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red-positive and α-SMA-positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4 -induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro-genic genes and the protein levels of transforming growth factor ß were much higher in the CCl4 +LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro-inflammatory nuclear factor-kappa B pathway in the livers of CCl4 -injected mice. Moreover, PD altered both oral and liver microbiota in CCl4 -injected mice. CONCLUSIONS: PD aggravates CCl4 -induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver.


Asunto(s)
Cirrosis Hepática , Microbiota , Periodontitis , Actinas , Alanina Transaminasa , Animales , Compuestos Azo , Tetracloruro de Carbono/efectos adversos , Hidroxiprolina/metabolismo , Cirrosis Hepática/inducido químicamente , Masculino , Azul de Metileno , Ratones , Periodontitis/complicaciones , ARN Ribosómico 16S , Factor de Crecimiento Transformador beta/metabolismo
7.
Biofouling ; 38(8): 824-836, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36314065

RESUMEN

The motion paths of Balanus reticulatus cyprids were similar on all the titanium alloys surfaces. On the parallel grinding surfaces, the temporary attachment duration and the settlement ratio of the cyprids were influenced by the roughness and the composition of the surfaces and correlated positively. The surface roughness could also change the contact area and the numbers of the attachment points of the cyprids in the similar pattern. Consequently, the roughness and the composition of the surfaces regulated the cyprid settlement by the temporary attachment duration. The cross grinding increased the temporary attachment duration but drastically decreased the settlement ratio to 0 compared to the parallel grinding, possibly due to the voids and the drastic decrease of the contact area and the numbers of the attachment points of the cyprids on the cross grinding surface, respectively. The cross grinding therefore significantly reduced the cyprid settlement compared to the parallel grinding.


Asunto(s)
Thoracica , Animales , Titanio , Aleaciones , Larva , Conducta Animal , Biopelículas
8.
Int J Geriatr Psychiatry ; 36(4): 467-478, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33105039

RESUMEN

OBJECTIVE: Poor oral health is common in dementia, but findings of epidemiological studies have been inconsistent. This meta-analysis examined oral health in patients with dementia diagnosed according to standardized diagnostic criteria. METHODS: Six international databases (PubMed, EMBASE, PsycINFO, Medline, Cochrane Library, and Web of Science) were searched from their commencement date until 8 November 2018. Oral health was measured by the Remaining Teeth (RT) and Decayed, Missing, and Filled Teeth (DMFT) Index. The mean differences (MD) and 95% confidence intervals (CI) of DMFT Index total and component scores were calculated using a random-effect model. RESULTS: Twenty-four studies were included for analyses. The pooled DMFT Index was 23.48 (95% CI: 22.34, 24.62), while the pooled score for each component was 2.38 (95% CI: 1.56, 3.20) in decayed teeth (DT), 18.39 (95% CI: 15.92, 20.87) in missing teeth (MT), 2.29 (95% CI: 0.62, 3.95) in filled teeth (FT), and 11.59 (95% CI: 9.14, 14.05) in RT. Compared to controls, people with dementia had significantly a higher DMFT Index total score (MD = 3.80, 95% CI: 2.21, 5.39, p < 0.00,001), and significantly lower number of RT (MD = -3.15, 95% CI: -4.23, -2.06, p < 0.00,001). Subgroup analyses revealed that higher DMFT Index score was significantly associated with year of survey (>2010), study design (case-control study), percentage of females (≤54.3), and the Mini Mental State Examination score (≤18.2). Higher MT score was significantly associated with study design (cross-sectional study), and lower FT score was significantly associated with year of survey (>2010). CONCLUSIONS: Oral health was significantly poorer in people with dementia compared with controls. Regular screening and effective treatment should be implemented for this population.


Asunto(s)
Demencia , Salud Bucal , Estudios de Casos y Controles , Estudios Transversales , Demencia/epidemiología , Femenino , Humanos , Estudios Observacionales como Asunto , Resultado del Tratamiento
9.
JAMA ; 325(1): 50-58, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33300950

RESUMEN

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.


Asunto(s)
Capecitabina/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Capecitabina/efectos adversos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Síndrome Mano-Pie/etiología , Humanos , Quimioterapia de Mantención , Mastectomía , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Observación , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugía
10.
Water Sci Technol ; 83(9): 2192-2206, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33989186

RESUMEN

Modifying environmentally harmful waste polystyrene foam as an efficient recyclable adsorbent for organic dyes is important. Amidation modified polystyrene (PS-SD) was prepared by the Friedel-Crafts reaction and N,N'-dicyclohexylcarbodiimide (DCC) dehydration condensation reaction of waste polystyrene foam. PS-SD had highly efficient removal performance for organic dyes in large volume water sample solutions, and equilibrium was achieved in 0.5 h. The maximum adsorption capacities for Methylene blue (MB) and Congo red (CR) were 881.62 and 1,880.91 mg/g, respectively, at room temperature according to the Langmuir adsorption isotherm (R2 > 0.99). The kinetic data of the two dyes followed pseudo-second-order kinetics. The removal percentage remained high (>85%) after eight filtration-regeneration cycles. Experimental results showed that PS-SD was an excellent adsorbent for water treatment with high recyclability and long life.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Colorantes , Cinética , Azul de Metileno , Poliestirenos
11.
Environ Sci Technol ; 54(13): 8115-8122, 2020 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-32531169

RESUMEN

Edible bivalves are one of the major types of seafood and may be subject to antibiotic and microplastics (MPs) coexposure under realistic scenarios. However, the effect of MPs on the bioaccumulation of antibiotics in edible bivalves and subsequent health risks for consumers remain poorly understood. Therefore, the bioaccumulation of two frequently detected veterinary antibiotics, oxytetracycline (OTC) and florfenicol (FLO), with or without the copresence of MPs was investigated in the blood clam. Health risks associated with the consumption of contaminated clams were also assessed. Furthermore, the activity of GST and expression of key detoxification genes were analyzed as well. The bioaccumulation of OTC and FLO in clams was found to be aggravated by MPs. Because the estimated target hazard quotients (THQs) were far less than the critical value, direct toxic effects of consuming contaminated clams are negligible. However, the dietary exposure doses of the human gut microbiota (DEGM) to the antibiotics tested were greater than or similar to corresponding minimum selective concentrations (MSC), indicating a potential antibiotic resistance risk. Moreover, the GST activity and expression of detoxification genes were significantly suppressed by MPs, suggesting that the disruption of detoxification represents one possible explanation for the aggravated bioaccumulation observed here.


Asunto(s)
Bivalvos , Contaminantes Químicos del Agua , Animales , Antibacterianos/toxicidad , Bioacumulación , Humanos , Microplásticos , Plásticos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
12.
Anal Bioanal Chem ; 411(23): 6021-6029, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31289898

RESUMEN

Cytobiological methods for cell nucleus-related studies start with the extraction processes of intranuclear components with many cell lysis buffers, following with the structural characterizations and quantitative analysis of the extracted components. In this study, we tried to evaluate the availability and reliability of these extraction-based analytical methods from their spectral features. We implemented an in situ surface-enhanced Raman scattering spectroscopy (SERS) strategy with the help of the nucleus-targeting nanoprobes to investigate the molecular information of nucleus, in comparison with these ex situ methods. This study provides valuable references for choosing an appropriate detection method according to different detection purposes, and also points out the risks of many developing cell-related analytical methods that combine the traditional cytobiological techniques from exogenous interferences during sample preprocesses. Graphical abstract.


Asunto(s)
Núcleo Celular/química , ADN/análisis , Nanopartículas del Metal/química , Proteínas Nucleares/análisis , Espectrometría Raman/métodos , Fluoresceína-5-Isotiocianato/química , Colorantes Fluorescentes/química , Oro/química , Células Hep G2 , Humanos , Nanopartículas del Metal/ultraestructura , Péptidos/química , Polietilenglicoles/química
13.
Bioorg Chem ; 91: 103114, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31336307

RESUMEN

The endoglycosidase (EndoS and its glycosynthase mutants D233A, D233Q) gene was fused with cellulose binding domain (CBD) using pET-35b vector and the fusion enzymes were successfully expressed in Escherichia coli. Then a simplified approach for one-step immobilization and purification of EndoS enzymes using cellulose as matrices were developed and excellent loading efficiency (81-90%) was achieved in optimal condition. The cellulose immobilized CBD-EndoS and the glycosynthase mutants presented high catalytic activity and were successfully applied in a two-step antibody Fc N-glycan remodeling, generating a therapeutic antibody with homogeneous glycoform in high efficiency. The cellulose immobilized CBD-EndoS and its mutants (D233A and D233Q) displayed excellent storage stability when stored at 4 degrees for one month. Reusability studies demonstrated that the cellulose immobilized CBD-EndoS and its mutants could be recycled for five times without obvious activity loss.


Asunto(s)
Celulosa/genética , Ingeniería Genética , Glicósido Hidrolasas/metabolismo , Fragmentos Fc de Inmunoglobulinas/metabolismo , Polisacáridos/metabolismo , Celulosa/aislamiento & purificación , Celulosa/metabolismo , Enzimas Inmovilizadas/genética , Enzimas Inmovilizadas/aislamiento & purificación , Enzimas Inmovilizadas/metabolismo , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/aislamiento & purificación , Fragmentos Fc de Inmunoglobulinas/genética , Modelos Moleculares , Conformación Molecular , Mutación , Polisacáridos/genética
14.
Oral Dis ; 25(1): 97-107, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30169911

RESUMEN

OBJECTIVES: Our aim was to identify and prevalidate a set of salivary proteins that can distinguish oral squamous cell carcinomas (OSCC) patients from healthy individuals and patients with oral potentially malignant disorders (OPMD). SUBJECTS AND METHODS: Proteomes of 60 saliva samples from healthy individuals, OPMD patients, and OSCC patients were assayed using the isobaric tags for relative and absolute quantitation (iTRAQ) method. Enzyme-linked immunosorbent assay (ELISA) was used to prevalidate the candidate biomarkers in an independent sample set (n = 90). RESULTS: In total, 246 differentially expressed proteins were identified by comparing each two groups, and 21 proteins were differentially expressed when OSCC was compared with both OPMD and Control. Three proteins, namely, solute carrier family 3 member 2 (SLC3A2), S100 calcium-binding protein A2 (S100A2), and interleukin-1 receptor antagonist protein (IL1RN), were selected as candidate biomarkers. Comparing the OSCC group with the healthy group, the area under curve (AUC) of the three combined biomarkers was 0.89, with a sensitivity of 83.33% and a specificity of 83.33%. Comparing the OSCC group with the OPMD group, the AUC value was 0.87, with a sensitivity of 93.33% and a specificity of 70.00%. CONCLUSION: Our study indicates that salivary proteomics is promising for the discovery of OSCC biomarkers.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de la Boca/diagnóstico , Saliva/química , Adulto , Anciano , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteómica , Sensibilidad y Especificidad
15.
Small ; 14(42): e1801905, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30346089

RESUMEN

Accumulating studies have investigated the efficacy of receptor-mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low-density lipoprotein receptor (LDLR) is designed to generate a novel drug-loaded system, designated as OMCN-PEG-Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood-brain barrier and exerts therapeutic efficacy through both near-infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma-killing temperature in a glioma-bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug-loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR-overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near-infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug-loaded system as a promising drug delivery vehicle for clinical application in glioma therapy.


Asunto(s)
Carbono/química , Doxiciclina/química , Glioma/tratamiento farmacológico , Nanopartículas/química , Péptidos/química , Polietilenglicoles/química , Animales , Doxiciclina/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Humanos
16.
Nanotechnology ; 29(34): 345101, 2018 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-29786605

RESUMEN

In this research, a novel method was used to successfully stably coat Pluronic P123 on mesoporous silica nanoparticles (MSNs). Co-constructing a drug delivery system (DDS) with P123 and MSNs has not been previously reported. In this DDS, the coating of P123 was realized through a hydrophobic interaction with octadecyl chain-modified MSNs. The experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segments could keep the nanoassemblies stable. For comparison, nanoassemblies consisting of P123 and octadecyl chain-modified MSNs with or without a disulfide bond were prepared, which were denoted as PSMSNs and PMSNs, respectively. The disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decreasing the toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with the PMSNs, PSMSNs displayed a redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, the cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in the tumor was enhanced after coating the MSNs by virtue of the 'EPR' effect of nanoparticles compared with the solution form.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Poloxámero/química , Dióxido de Silicio/química , Adsorción , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Humanos , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Nitrógeno/química , Oxidación-Reducción , Porosidad , Distribución Tisular/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
17.
Nanotechnology ; 28(29): 295102, 2017 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-28656906

RESUMEN

For releasing both drug and heat to selected sites, a combination of chemotherapy and photothermal therapy in one system is a more effective way to destroy cancer cells than monotherapy. Graphene oxide (GO) with high drug-loading efficiency and near-infrared (NIR) absorbance has great potential in drug delivery and photothermal therapy, but it is difficult to load drugs with high solubility. Herein, we develop a versatile drug delivery nanoplatform based on GO for integrated chemotherapy and photothermal therapy by a facile method of simultaneous reduction and surface functionalization of GO with poly(dopamine) (PDA). Due to the excellent adhesion of PDA, both low and high solubility drugs can be encapsulated in the PDA-functionalized GO nanocomposite (rGO-PDA). The fabricated nanocomposite exhibits good biocompatibility, excellent photothermal performance, high drug loading capacity, an outstanding sustained release property, and efficient endocytosis. Moreover, NIR laser irradiation facilitates the release of loaded drugs from rGO-PDA. These features make the rGO-PDA nanocomposite achieve excellent in vivo synergistic antitumor therapeutic efficacy.


Asunto(s)
Portadores de Fármacos , Grafito , Hipertermia Inducida/métodos , Indoles , Nanocompuestos , Neoplasias/terapia , Fototerapia/métodos , Polímeros , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Grafito/química , Grafito/farmacología , Células HeLa , Humanos , Indoles/química , Indoles/farmacología , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Neoplasias/metabolismo , Neoplasias/patología , Polímeros/química , Polímeros/farmacología
18.
J Mater Sci Mater Med ; 28(3): 50, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28197822

RESUMEN

Fast and stable repair of segmental bone defects remains a challenge for clinical orthopedic surgery. In recent years, porous tantalum has been widely applied in clinical orthopedics for low modulus of elasticity, with three-dimensional microstructures similar to cancellous bone and excellent biocompatibility. To further improve bone the repairing ability of porous tantalum, the cyclo(-RGDfK-) peptide was coated on the surface of porous tantalum scaffolds. A model of 15 mm segmental defect was made at the midshaft of right radius in New Zealand White rabbits. In the experimental group, defects were implanted (press-fit) using porous tantalum scaffolds modified with cyclo(-RGDfK-) peptide. Control animals were implanted with non-modified porous tantalum scaffolds or xenogeneic cancellous bone scaffolds, respectively. No implant was provided for the blank group. Bone repair was assessed by X-ray and histological observations at 4, 8, and 16 weeks post-operation, with biomechanical tests and micro-computed tomography performed at 16 weeks post-surgery. The results showed that bone formation was increased at the interface and inside the inner pores of modified porous tantalum scaffolds than those of non-modified porous tantalum scaffolds; biomechanical properties in the modified porous tantalum group were superior to those of the non-modified porous tantalum and xenogeneic cancellous bone groups, while new bone volume fractions using micro-computed tomography analysis were similar between the modified porous tantalum and xenogeneic cancellous bone groups. Our findings suggested that modified porous tantalum scaffolds had enhanced repairing ability in segmental bone defect in rabbit radius, and may serve as a potential material for repairing large bone defects.


Asunto(s)
Sustitutos de Huesos/química , Oligopéptidos/química , Radio (Anatomía)/cirugía , Tantalio/química , Andamios del Tejido/química , Animales , Fenómenos Biomecánicos , Elasticidad , Masculino , Ortopedia , Porosidad , Presión , Conejos , Radio (Anatomía)/fisiología , Estrés Mecánico , Tomografía Computarizada por Rayos X , Microtomografía por Rayos X
19.
Biomed Environ Sci ; 30(10): 701-707, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29122090

RESUMEN

OBJECTIVE: To analyze the prevalence and years lived with disability (YLD) from dental caries among children and adolescents and the time trends over the past two decades in Sichuan province, the largest province in west China. METHODS: Based on the Global Burden of Disease Study 2015 (GBD2015), which systematically assessed the epidemiological characteristics of major diseases and their transitions by country and region from 1990 to 2015, we extracted the estimated results for China. We then used the Bayesian meta-regression method to estimate the sex- and age-specific prevalences and YLDs from dental caries among children and adolescents under 15 years old in Sichuan province and compared them with global and national indicators for the same period. RESULTS: In 2015, there were almost 6 million cases of dental caries in children and adolescents (aged < 15 years) in Sichuan province, accounting for 6% of the total cases in China. For children under 5 years, the prevalence of deciduous caries was 55.9%, and the YLDs value was 10.8 per 100,000, while it was 24.3% and 5.1 per 100,000 respectively among 5- to 14-year-olds; for those aged 5 to 14 years, the prevalence of permanent caries was 21.5%, and the YLDs value was 11.5 per 100,000. From 1990 to 2015, the prevalence of dental caries for children under 5 years increased substantially, by 16.2%, and the YLDs increased by 8.7%. Among those aged 5 to 14 years, the prevalence increased and the YLDs decreased. CONCLUSION: Dental caries remains a huge health burden in Western China. In contrast to the global and national data, the trend has increased rapidly over the past 25 years in this region. This work provides suggestions for the prevention and control for oral health in China with the policy of two-child.


Asunto(s)
Caries Dental/epidemiología , Caries Dental/patología , Adolescente , Niño , Preescolar , China/epidemiología , Personas con Discapacidad , Femenino , Humanos , Masculino , Prevalencia
20.
Zhongguo Zhong Yao Za Zhi ; 42(1): 113-118, 2017 Jan.
Artículo en Zh | MEDLINE | ID: mdl-28945034

RESUMEN

To prepare the intrauterine slow release silicone rubber bar made of Panax notoginseng and Rubia cordifolia, and finish its preliminary evaluation of in vitro releasing properties. The open mill method was used for plasticating of silicone rubber. The process parameters of the silicone rubber and drugs mixing were optimized by orthogonal test. The parameters of silicone rubber vulcanization was optimized by single factor test. The preliminary evaluation of in vitro release performance of the silicone rubber bar was conducted with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1, purpurin and rubimaillin as the indexes. The results showed that optimum technologic parameters for silicone rubber and drugs mixing:the roller spacing 2 mm; speed ratio 1∶1.2; front roller temperature 55-60 ℃; rear roll temperature 50-55 ℃; and mixing time 20 min. The optimum parameters for silicone rubber vulcanization:temperature 90 ℃, and time 60 min. The studies on release process in vitro revealed that the release process of silicone rubber bar was in line with the Higuchi equations. After 90 days, the cumulative release of ginsenoside Rg1, ginsenoside Rb1 and notoginsenoside R1 was 46.7%, and the cumulative release of purpurin and rubimaillin was 51.9%. The preparation method can be applied to the preparation of silicone rubber bar, with slow release characteristics.


Asunto(s)
Liberación de Fármacos , Medicamentos Herbarios Chinos/química , Ginsenósidos/química , Panax notoginseng/química , Rubia/química , Elastómeros de Silicona/química
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