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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 758-760, 2024 Jun 10.
Artículo en Zh | MEDLINE | ID: mdl-38818565

RESUMEN

Char syndrome is a rare autosomal dominant genetic disorder characterized by patent ductus arteriosus, facial dysmorphism, and dysplasia of fingers/toes. It may also be associated with multiple papillae, dental dysplasia, and sleep disorders. TFAP2B has proven to be a pathogenic gene for neural crest derivation and development, and several variants of this gene have been identified. Bone morphogenetic protein signaling plays an important role in embryonic development by participating in limb growth and patterning, and regulation of neural crest cell development. TFAP2B is an upstream regulatory gene for bone morphogenetic proteins 2 and 4. Variants of the TFAP2B gene may lead to abnormal proliferation of neural crest cells by affecting the expression of bone morphogenetic proteins, resulting in multiple organ dysplasia syndrome. In addition, TFAP2B variants may only lead to patent ductus arteriosus instead of typical Char syndrome.


Asunto(s)
Conducto Arterioso Permeable , Humanos , Conducto Arterioso Permeable/genética , Factor de Transcripción AP-2/genética , Anomalías Múltiples/genética , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Cresta Neural/metabolismo , Cresta Neural/embriología , Cara/anomalías , Dedos/anomalías
2.
Ecotoxicology ; 30(8): 1632-1643, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33420883

RESUMEN

While expanded polystyrene (EPS) microplastics have been widely recognized as one of the most important components of plastic litter in the intertidal zones of the global ocean, our understanding of their environmental fate on island beaches is insufficient. In this study, we intended to reveal that the latest EPS microplastic pollution status on 5 island beaches in the Pearl River Estuary, China, by comprehensively assessing the abundance, distribution, size, surface texture and carrying capacity of heavy metals (Cd, As, Cr, Ni, Cu, Pb, Mn, Fe, Al). High level of EPS microplastic abundance ranged from 328 to 82,276 particles m-2 was found, with the highest abundance at Guishan Island and the lowest at Dong'ao Island. Spatial distribution of EPS microplastic abundance was significantly different among different islands. EPS microplastics in the size range of 1-2 mm were the most abundant. The content of heavy metals in EPS microplastics collected on the beaches was greater than that in the new EPS products. The average concentrations of heavy metals in EPS microplastics from 5 islands are Cd (0.27 ± 0.19 µg g-1), As (5.50 ± 3.84 µg g-1), Cr (14.9 ± 8.25 µg g-1), Cu (15.0 ± 7.66 µg g-1), Ni (17.2 ± 17.6 µg g-1), Pb (24.8 ± 7.39 µg g-1), Mn (730 ± 797 µg g-1), Fe (8340 ± 4760 µg g-1), and Al (9624 ± 6187 µg g-1), respectively. The correlation between heavy metals in EPS microplastics and sediments was better than that between heavy metals in EPS microplastics and seawater. The study results indicated that EPS microplastics could act as a carrier for the transport of heavy metals, which might pose a threat to biological and human health.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , China , Conservación de los Recursos Naturales , Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos , Humanos , Metales Pesados/análisis , Microplásticos , Plásticos , Poliestirenos/análisis , Ríos , Contaminantes Químicos del Agua/análisis
3.
J Gene Med ; 21(10): e3122, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31420900

RESUMEN

BACKGROUND: Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders. METHODS: The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction. RESULTS: We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM. CONCLUSIONS: A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.


Asunto(s)
Alelos , Sustitución de Aminoácidos , Anodoncia/diagnóstico , Anodoncia/genética , Deformidades Congénitas de las Extremidades/diagnóstico , Deformidades Congénitas de las Extremidades/genética , Mutación , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Adulto , Niño , Biología Computacional , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Linaje , Fenotipo , Polimorfismo de Nucleótido Simple , Radiografía , Síndrome
4.
Int J Mol Sci ; 15(11): 20339-54, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25383677

RESUMEN

Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn), were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs) containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand) in both folate-receptor (FR) overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.


Asunto(s)
Cationes/química , Colesterol/análogos & derivados , Técnicas de Transferencia de Gen , Liposomas/química , Polietilenglicoles/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Colesterol/síntesis química , Colesterol/química , Colesterol/toxicidad , Fluorescencia , Receptor 1 de Folato/metabolismo , Ácido Fólico/química , Humanos , Ligandos , Espectrometría de Masas , Peso Molecular , Tamaño de la Partícula , Espectroscopía de Fotoelectrones , Polietilenglicoles/síntesis química , Polietilenglicoles/toxicidad , Espectroscopía de Protones por Resonancia Magnética , Electricidad Estática , Transfección , Temperatura de Transición
5.
Int J Mol Sci ; 15(2): 2761-72, 2014 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-24552875

RESUMEN

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Animales , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Femenino , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Trasplante Heterólogo , Verapamilo/química , Verapamilo/toxicidad , Vincristina/química , Vincristina/toxicidad
6.
Int J Mol Sci ; 15(3): 3373-88, 2014 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-24573250

RESUMEN

Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a double emulsification method. The processing parameters including the polymer types, organic phase, PVA types and amount were systemically investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock copolymers and lipids, had high entrapment efficiency (65%), submicron size (150 nm) and negatively charged surface (-23 mV). DSC analysis demonstrated the successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs was verified by TEM. Sal released slowly from the LPNPs without apparent burst release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising Sal vehicle for anti-cancer therapy and worthy of further investigation.


Asunto(s)
Antineoplásicos/química , Glucósidos/química , Lípidos/química , Nanopartículas/química , Fenoles/química , Polímeros/química , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Glucósidos/farmacología , Humanos , Microscopía Electrónica de Transmisión , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Fenoles/farmacología , Polietilenglicoles/química , Poliglactina 910/química , Solubilidad , Solventes/química , Agua/química
7.
Environ Pollut ; 318: 120920, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36565907

RESUMEN

The production and use of hexabromocyclododecanes (HBCDs) have been strictly limited due to their persistence, toxicity and bioaccumulation. However, the release of HBCDs from related products and wastes would continue for a long time, which may cause many environmental problems. In this study, we investigated the occurrence and distribution of HBCDs and microplastics (MPs) in aquatic organisms inhabiting different substrates. HBCDs were measurable in the seawater, sediment, expanded polystyrene (EPS) substrates and organism samples. Mostly, the concentrations of HBCDs in organisms inhabiting EPS buoys were significantly higher than those of the same species inhabiting other substrates. Meanwhile, the diastereomeric ratio (α/γ) of HBCDs in organisms inhabiting EPS buoys was closer to that in EPS buoys. The fugacity values of HBCDs in EPS buoys were much higher than those in other media, implying that HBCDs can be transferred from EPS buoys to other media. Additionally, MPs derived from EPS buoys would be mistaken as food and ingested by aquatic organisms. The transfer of HBCDs from EPS buoys to aquatic organisms can be achieved by aqueous and dietary exposures. In combination, the contribution of MP ingestion to HBCDs for aquatic organisms should be very limited. These results supported EPS buoys as an important source of HBCDs for the aquatic ecosystem. To effectively control HBCDs pollution, it is necessary to discontinue or reduce the use of EPS buoys.


Asunto(s)
Hidrocarburos Bromados , Contaminantes Químicos del Agua , Poliestirenos/análisis , Ecosistema , Plásticos , Monitoreo del Ambiente , Hidrocarburos Bromados/análisis , Organismos Acuáticos , Contaminantes Químicos del Agua/análisis
8.
Environ Pollut ; 322: 121158, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36716949

RESUMEN

In recent years, microplastics (MPs) as emerging carriers for environmental pollutants have attracted increasing worldwide attention. However, the adsorption of heavy metals on MPs, especially for biodegradable MPs, has been still poorly understood in estuarine environments. In this study, we investigated the aging of biodegradable and conventional MPs in the Pearl River Estuary after long-term exposure and their impacts on the adsorption of heavy metals from seawater. The results showed that the changes in surface characteristics were more prominent on biodegradable MPs than on conventional MPs after aging. Both biodegradable and conventional MPs could adsorb heavy metals, and their adsorption capacities fluctuated greatly on different MPs and different exposure times. The adsorption capacities of Cu, Pb, and As on biodegradable MPs were higher than those on conventional MPs, whereas Mn, Cr, and Co had lower adsorption on biodegradable MPs after 9-12 months by inductively coupled plasma-mass spectrometry (ICP-MS). The aging characteristics (CI, O/C, and Xc) of MPs accounted for a contribution of 51.0% on heavy metal adsorption, while the environmental factors (temperature, salinity, pH, and heavy metal concentration) only contributed to 13.2%. Therefore, the present study can provide important evidence on the environmental behaviors and ecological risks of biodegradable and conventional MPs in estuarine systems.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Microplásticos/química , Plásticos , Adsorción , Ríos , Estuarios , Contaminantes Químicos del Agua/análisis , Metales Pesados/análisis , China
9.
J Mater Chem B ; 11(37): 8933-8942, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37682063

RESUMEN

The inefficient treatment using protein-based nanovaccines is largely attributed to their inadequate immunogenicity. Herein, we developed a novel fluoropolymer (PF) via ring-opening polymerization and constructed a fluoropolymer-based nanovaccine for tumor immunotherapy. Due to the existence of fluoroalkyl chains, PF not only played a crucial role in tumor antigen delivery but also exhibited a remarkable adjuvant effect in enhancing the immunogenicity of nanovaccines. The nanovaccines formed by mixing PF with a model antigen ovalbumin (OVA) enhanced the uptake of antigen proteins by dendritic cells (DCs) and promoted the maturation and antigen presentation of DCs. Compared with free OVA, PF/OVA showed better efficacy in both pre-cancer prevention and tumor treatment. Furthermore, the proportion of CD4+ T and CD8+ T cells was significantly increased in lymph nodes and tumors of mice immunized with PF/OVA. Additionally, there was a great enhancement in the levels of key anti-tumor cytokines (TNF-α and IFN-γ) in the serum of the PF/OVA immunized mice. Our research has shown that fluoropolymer PF applied as a protein vector and adjuvant has great potential for the development of nanovaccines with robust immunogenicity.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Ratones , Animales , Polímeros de Fluorocarbono , Adyuvantes Inmunológicos , Inmunoterapia , Neoplasias/metabolismo , Antígenos de Neoplasias
10.
Comput Math Methods Med ; 2022: 4202823, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36193198

RESUMEN

Objective: Peri-implantitis (PI) is one of the main reasons for dental implant failure. Until now, the etiology and pathogenesis of PI remain unclear. Methods: In this study, we used differentially expressed genes (DEGs) analysis and gene function enrichment analysis to assess the expression profile of peri-implant bone tissue and gingiva in PI public data from the Gene Expression Omnibus (GEO) database. Then, we used gingival tissues from patients with PI and healthy individual to construct gene coexpression networks to reveal the biological functions of the genes in PI using RNA sequencing data. Afterward, key gene modules were selected to reveal the critical biological process or signaling pathway using Hallmark's gene enrichment and expression analysis of the related pathway members in PI. Results: DEGs were enriched in the formation of cellular responses to external stimuli in bone tissue. Cytokine production, lymphocyte activation, immune response-regulating signaling pathway, and blood vessel development were the top GO biology process or pathways of the DEGs in gingival tissue. Weighted gene coexpression network analysis (WGCNA) of RNA-seq data was used to assess the results of correlation analysis between modules and traits and correlation analysis between modules and functions. kMEpurple, kMEgreen, and kMEred modules were selected as the key gene modules. Signaling pathways and gene expression analysis were performed on selected modules, such as IL2/STAT5 signaling pathway, TNFα signaling pathway via NFκB, and angiogenesis were enriched in kMEpurple module. Hedgehog signaling pathway, Wnt ß-catenin signaling pathway, and IL2/STAT5 signaling pathway were enriched in kMEgreen module. Peroxisome, IL2/STAT5 signaling pathway, and epithelial-mesenchymal transformation process were enriched in kMEred module. All the enrichment results of key modules contained IL2/STAT5 signaling pathway. Conclusion. Differential gene and enrichment analysis based on public data showed differences in gene expression patterns and biological process between bone and gingival tissues in PI. This spatial-temporal heterogeneity is reflected in the formation of cellular responses to external stimuli, which was enriched in bone tissue, but cytokine production, lymphocyte activation, immune response regulating signaling pathway, and blood vessel development were enriched in gingival tissue. WGCNA and Hallmark gene sets enrichment analysis of the gingival tissue expression profile and showed that IL2-mediated activation of immune cells could be a critical mechanism in PI. As a new clinical treatment alternative, we suggest that IL2/STAT5 pathway blockers could be helpful in the treatment of PI.


Asunto(s)
Implantes Dentales , Periimplantitis , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Proteínas Hedgehog/genética , Humanos , Interleucina-2/genética , Periimplantitis/genética , Factor de Transcripción STAT5/genética , Transducción de Señal/genética , Factor de Necrosis Tumoral alfa
11.
Sci Total Environ ; 841: 156749, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35718172

RESUMEN

Microplastic contamination is an emerging global threat for various marine organisms. Marine invertebrates such as bivalve mollusks are more susceptible to the widespread presence of microplastics due to their limited abilities to escape from pollution exposure and they can readily ingest environmental pollutants like microplastics through their filter-feeding behaviors. In this study, microplastic contamination in bivalves related to species, spatial, and temporal variability were conducted. Results showed that the frequency of microplastic occurrence varied from 86.7 % to 93.3 % in six species of bivalves, and the average abundance of microplastics ranged from 3.5 to 8.6 items per individual or from 0.2 to 3.1 items per gram tissues wet weight. No significant difference was observed in microplastic abundances of bivalves collected from different research regions and sampling seasons. However, the sediment-dwelling bivalves had higher microplastics abundances than the water-dwelling bivalves. Microplastic features with various shapes, colors, sizes, and polymer types detected in bivalves were similar with those in seawater and sediment environments that they are living in. The potential risk assessment of microplastics in bivalves basing on polymer hazard index (PHI) was in the risk levels of II-III, implying that microplastic contamination in bivalves may pose health risk to human via seafood consumption.


Asunto(s)
Bivalvos , Contaminantes Químicos del Agua , Animales , Organismos Acuáticos , Bahías , Monitoreo del Ambiente/métodos , Humanos , Microplásticos , Plásticos , Contaminantes Químicos del Agua/análisis
12.
Sci Total Environ ; 827: 154281, 2022 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-35247408

RESUMEN

Microplastics are ubiquitous in the aquatic environment. However, the occurrence of microplastics in farmed fish is under-researched. Herein, microplastic abundance in the stomach and intestine of marine-cultured hybrid groupers (Epinephelus fuscoguttatus × Epinephelus lanceolatus) in the Pearl River Estuary (PRE) was examined. Microplastics were detected in all fish samples, with an average abundance of 35.36 n/individual or 0.62 n/g. The fish intestine contained more microplastics (23.91 n/individual, i.e., 1.10 n/g) than the stomach (12.80 n/individual, i.e., 0.37 n/g). In addition, the ingested microplastics were predominantly fibre-shaped (70.1%), and nearly 70% were smaller than 1 mm in diameter. Potential factors affecting the ingestion of microplastics by farmed hybrid groupers include fish diet and the availability of microplastics in their feeding habitat.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Animales , China , Monitoreo del Ambiente , Estuarios , Peces , Plásticos , Ríos , Contaminantes Químicos del Agua/análisis
13.
Sci Total Environ ; 822: 153604, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35114230

RESUMEN

The prevalence of microplastics in the marine environment has attracted extensive attention. So far, no information is known regarding the temporal and spatial variations of microplastics in Zhongsha Atoll. This study, for the first time, comprehensively investigated the occurrence and distribution of microplastics in the surface seawater in Zhongsha Atoll based on two ocean cruises. The abundances of microplastics measured in the surface seawater of Zhongsha Atoll were in the ranges of not detected (ND) to 67 items/m3, and ND to 160 items/m3 in 2019 and 2020, respectively. All microplastics detected in Zhongsha Atoll were fibers, most of which were transparent and less than 2 mm. Polyethylene terephthalate was the dominating composition of microplastics. These results suggested that sewage, surface runoff, atmospheric deposition by neighboring land, and fishing activities may be the primary pollution sources. This study provides critical information on microplastic pollution in Zhongsha Atoll for the first time, calling for more research in the management of marine plastic debris in the future.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Plásticos , Agua de Mar , Contaminantes Químicos del Agua/análisis
14.
Nanomedicine ; 7(6): 665-73, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21419870

RESUMEN

Unresolved problems associated with ligand-targeting of liposomal nanoparticles (NPs) to solid tumors include variable target receptor expression due to genetic heterogeneity and insufficient target specificity, leading to systemic toxicities. This study addresses these issues by developing a novel ligand-targeting strategy for liposomal NPs using RR-11a, a synthetic enzyme inhibitor of Legumain, an asparaginyl endopeptidase. Cell-surface expression of Legumain is driven by hypoxic stress, a hallmark of solid tumors. Legumain-targeted RR-11a-coupled NPs revealed high ligand-receptor affinity, enhanced solid-tumor penetration and uptake by tumor cells. Treatment of tumor-bearing mice with RR-11a-coupled NPs encapsulating doxorubicin resulted in improved tumor selectivity and drug sensitivity, leading to complete inhibition of tumor growth. These antitumor effects were achieved while eliminating systemic drug toxicity. Therefore, synthetic enzyme inhibitors, such as RR-11a, represent a new class of compounds that can be used for highly specific ligand-targeting of NPs to solid tumors. FROM THE CLINICAL EDITOR: This study addresses the problems associated with ligand-targeting of liposomal nanoparticles to solid tumors with variable target receptor expression. A novel and efficacious targeting strategy has been developed towards a synthetic enzyme inhibitor of Legumain. The authors demonstrate successful tumor growth inhibiting effect while eliminating systemic drug toxicity in an animal model using this strategy.


Asunto(s)
Antineoplásicos/administración & dosificación , Cisteína Endopeptidasas/metabolismo , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Liposomas/química , Nanopartículas/química , Inhibidores de Proteasas/metabolismo , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisteína Endopeptidasas/genética , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica , Ligandos , Ratones , Ratones Endogámicos BALB C , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Inhibidores de Proteasas/química
15.
Biomed Mater ; 16(5)2021 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-34340221

RESUMEN

CaCO3particles, due to their unique properties such as biodegradation, pH-sensitivity, and porous surface, have been widely used as carrier materials for delivering drugs, genes, vaccines, and other bioactive molecules. In these applications, CaCO3particles are often administered intravenously. In this sense, the interaction between CaCO3particles and blood components plays a key role in their delivery efficacy and biosafety, though the hemocompatibility of CaCO3particles has not been evaluated until now. Deficiency in the biosafety information has delayed the clinical use of CaCO3particles in delivery systems. In this work, we investigated the biosafety of CaCO3particles, focusing on theirin vitroandin vivoeffects on key blood components (red blood cells, platelets, etc) and coagulation functions. We foundin vitrothat high concentrations of CaCO3particles can cause the aggregation and hemolysis of red blood cells, with platelet activation and coagulation prolongation.In vivo, we found that intravenously injected CaCO3particles at 50 mg kg-1significantly disturbed the red blood cells, and platelet-related blood routine indexes, but did not induce visible abnormalities in the tissue structures of the key organs. Overall, these effects may be due to the enormous adsorption capability of the porous surface of CaCO3particles. 0.1 mg ml-1of the CaCO3particles exhibit excellent compatibility for their practical applications. These results would be expected to greatly promote thein vivoapplications and clinical use of CaCO3particles in biomedicine.


Asunto(s)
Materiales Biocompatibles , Carbonato de Calcio , Hemólisis/efectos de los fármacos , Ensayo de Materiales , Nanopartículas , Animales , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/química , Coagulación Sanguínea/efectos de los fármacos , Pruebas de Coagulación Sanguínea , Plaquetas/efectos de los fármacos , Carbonato de Calcio/efectos adversos , Carbonato de Calcio/química , Eritrocitos/efectos de los fármacos , Humanos , Nanopartículas/efectos adversos , Nanopartículas/química , Activación Plaquetaria/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
16.
Chemosphere ; 246: 125708, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31911330

RESUMEN

Considering the magnitude of pollution caused by marine plastics, the present study assessed their abundance, distribution, surface morphology and polymer type in ten sandy beaches spread across three states (Maharashtra, Karnataka and Goa) along the west coast of India (WCI). The total abundance of plastics (∼1-100 mm) in the studied beaches ranged from 4.1 to 23.4% (19±1-346 ± 2 items/m2). Location-wise, the abundances of both micro (43.6 ± 1.1-346 ± 2 items/m2) and macroplastics (21.6±3-195 ± 6 items/m2) were relatively higher in beaches along the Maharashtra coast. Surface morphology-wise, fragments were predominantly abundant in both micro (76±2-346 ± 2 items/m2) and macroplastics (50.6 ± 1.5-195 ± 6 items/m2) followed by pellets (43.3 ± 2.5-245.6 ± 2 items/m2). Fourier-transform infrared spectroscopy (FT-IR) analysis of plastics revealed a dominance of polyethylene (PE) followed by polypropylene (PP). IR spectra of the collected plastics at absorption band at 1750-1700 cm-1 reflect minimal surface oxidation. White-colored plastics were observed most frequently, followed by pale-yellow, dark-brown, green, blue, transparent and red. A short-term (72 h) experimental study to assess the toxicity of PE microbeads (∼1 mm) in a commercially important shrimp species, Litopenaeus vannamei revealed toxicological changes. An elevated level of lipid peroxidation (LPX)-the tagged biochemical marker, was recorded only at the maximum dose (0.15 mg/L) of PE microbeads. A moderate increase in the levels of enzymatic antioxidants (catalase and glutathione S-transferase) was also recorded at the same dose. Comprehensive information on marine plastics, including ecotoxicity provided in this study, would help in evolving strategies in minimizing plastic pollution along the WCI.


Asunto(s)
Monitoreo del Ambiente , Plásticos/análisis , Contaminantes Químicos del Agua/análisis , Contaminación Ambiental/análisis , Contaminación Ambiental/estadística & datos numéricos , India , Microplásticos , Polietileno/análisis , Polímeros , Polipropilenos , Espectroscopía Infrarroja por Transformada de Fourier , Residuos/análisis
17.
Mar Pollut Bull ; 158: 111383, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32753173

RESUMEN

The estuaries of populated catchments have been documented as hotspots of plastic pollution. In this study, microplastics (0.355-5.0 mm) and large plastic debris (>5.0 mm) of surface water collected from the Inner Lingding Bay of the Pearl River Estuary (PRE) were quantified and categorized according to their size, shape, colour and composition. Both microplastics and large plastic debris were detected at all sampling sites with mean abundances of 2.376 ± 0.700 n/m3 and 0.110 ± 0.039 n/m3, respectively. Microplastics constitute 95.4% of the total abundance by number. The average microplastic concentration in the inner PRE was almost 3.5 times higher than that in the central PRE, indicating a positive correlation between plastic concentration and proximity to the river mouth. This result reveals the important role of rivers in transporting plastic debris from land to the oceans.


Asunto(s)
Plásticos , Contaminantes Químicos del Agua/análisis , China , Monitoreo del Ambiente , Estuarios , Microplásticos , Océanos y Mares , Ríos
18.
ACS Biomater Sci Eng ; 6(1): 664-672, 2020 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33463219

RESUMEN

Local resection or ablation remains an important approach to treat drug-resistant central neurological disease. Conventional surgical approaches are designed to resect the diseased tissues. The emergence of photothermal therapy (PTT) offers a minimally invasive alternative. However, their poor penetration and potential off-target effect limit their clinical application. Here, polydopamine nanoparticles (PDA-NPs) were prepared and characterized. Studies were performed to evaluate whether PDA-NPs combined with near-infrared (NIR) light can be used to ablate deep brain structures in vitro and in vivo. PDA-NPs were prepared with a mean diameter of ∼150 nm. The particles show excellent photothermal conversion efficiency. PDA-NPs did not show remarkable cytotoxicity against neuronal-like SH-SY5Y cell lines. However, it can cause significant cell death when combined with NIR irradiation. Transcranial NIR irradiation after PDA-NPs administration induced enhanced local hyperthermia as compared with NIR alone. Local temperature exceeded 60 °C after 6 min of irradiation plus PDA while it can only reach 48 °C with NIR alone. PTT with PDA (10 mg/mL, 3 µL) and NIR (1.5 W/cm2) can ablate deep brain structures precisely with an ablation volume of ∼6.5 mm3. Histological analysis confirmed necrosis and apoptosis in the targeted area. These results demonstrate the potential of NP-assisted PTT for the treatment against nontumorous central neurological diseases.


Asunto(s)
Nanopartículas , Fototerapia , Encéfalo/cirugía , Indoles , Polímeros
19.
Chemosphere ; 246: 125771, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31918091

RESUMEN

Chemical pollution in the plastic debris is an increasing global concern as most pollutants might transfer from the environment to living organisms via plastic debris. In this study, biocides in the plastic debris floating on the surface water of the Pearl River system were investigated. The abundances of large plastic debris and microplastics in the surface water were 0.07 ± 0.13 and 0.94 ± 1.87 items/m3, respectively. Totally, 15 and 16 out of 19 biocides were detected in the large plastic debris and microplastics, with the concentration of each biocide in the ranges of 22.6-2460 ng/g and 16.9-2890 ng/g, respectively. Meanwhile, the concentration ranges of the detected biocides were 0.01-215 ng/L in surface water. Triclosan, triclocarban, methylparaben, and N,N-diethyl-3-methylbenzamide (DEET) were the frequently detected compounds in the plastic samples and surface water. The partition coefficients (Kd) of biocides between the plastic debris and surface water showed a weak positive correlation with Kow values. Biocides were also detected on the natural floats (tree leaves and branches) at concentrations of 13.7-786 ng/g. The annual mass load of biocides in plastic debris at each site was up to 265 g/y, thereby suggesting that plastic debris might be an important carrier for the emerging contaminants, such as biocides.


Asunto(s)
Desinfectantes/análisis , Monitoreo del Ambiente , Plásticos/análisis , Contaminantes Químicos del Agua/análisis , Carbanilidas , China , Parabenos , Ríos/química , Triclosán/análisis , Residuos/análisis
20.
Environ Pollut ; 258: 113734, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31884260

RESUMEN

Microplastics are widespread across the global oceans, yet the potential risks of the ubiquitous environmental contaminant to marine organisms has been less known. Accumulation of microplastics and associated contaminants in marine fish, may pose adverse impacts to human health via seafood consumption. This study evaluated microplastic contamination in 24 fish species collected from Beibu Gulf, one of the world's largest fishing grounds in South China Sea. Microplastics were detected in 12 fish species at an abundance of 0.027-1.000 items individual-1 and found in fish stomach, intestines and gills with the count percentage of 57.7%, 34.6% and 7.7%, respectively. Transparent fibers were observed as the predominant microplastics, which might be ingested accidently by fish or transferred through other animals at lower trophic levels. Majority of microplastics were identified as polyester (44%) and nylon (38%), whereas polypropylene (6%), polyethylene (6%), and acrylics (6%) were also found. Relatively, higher microplastic abundances were found in demersal fish compared to the pelagic species. Overall, the abundance of microplastics was documented as relatively low in the commercial fish collected from the open water of Beibu Gulf, South China Sea.


Asunto(s)
Peces , Tracto Gastrointestinal , Branquias , Microplásticos/análisis , Contaminantes Químicos del Agua/análisis , Animales , China , Monitoreo del Ambiente , Océanos y Mares
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