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1.
Biochim Biophys Acta Mol Basis Dis ; : 165772, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32220628

RESUMO

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of rare monogenic neurodegenerative diseases predominantly affecting children. All NCLs are lethal and incurable and only one has an approved treatment available. To date, 13 NCL subtypes (CLN1-8, CLN10-14) have been identified, based on the particular disease-causing defective gene. The exact functions of NCL proteins and the pathological mechanisms underlying the diseases are still unclear. However, gene therapy has emerged as an attractive therapeutic strategy for this group of conditions. Here we provide a short review discussing updates on the current gene therapy studies for the NCLs.

2.
Nano Lett ; 20(3): 1747-1754, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32027140

RESUMO

Plasmonic nanostructures have a wide range of applications, including chemical and biological sensing. However, the development of techniques to fabricate submicrometer-sized plasmonic structures over large scales remains challenging. We demonstrate a high-throughput, cost-effective approach to fabricate Au nanoribbons via chemical lift-off lithography (CLL). Commercial HD-DVDs were used as large-area templates for CLL. Transparent glass slides were coated with Au/Ti films and functionalized with self-assembled alkanethiolate monolayers. Monolayers were patterned with lines via CLL. The lifted-off, exposed regions of underlying Au were selectively etched into large-area grating-like patterns (200 nm line width; 400 nm pitch; 60 nm height). After removal of the remaining monolayers, a thin In2O3 layer was deposited and the resulting gratings were used as plasmonic sensors. Distinct features in the extinction spectra varied in their responses to refractive index changes in the solution environment with a maximum bulk sensitivity of ∼510 nm/refractive index unit. Sensitivity to local refractive index changes in the near-field was also achieved, as evidenced by real-time tracking of lipid vesicle or protein adsorption. These findings show how CLL provides a simple and economical means to pattern large-area plasmonic nanostructures for applications in optoelectronics and sensing.

3.
Sci Rep ; 9(1): 17065, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745158

RESUMO

Porous carbon are excellent electrode materials for energy-storage devices. Here, we present a facile in-situ reduction method to improve the electrochemical performance of carbon materials by gold nanoparticles. The prepared porous carbon microspheres decorated with gold-nanoparticle had a 3D honeycomb-like structure with a high specific surface area of about 1635 m2 g-1, confirmed by scanning electron microscopy, transmission electron microscopy, and the Brunauer-Emmett-Teller method. The electrochemical performance of as-synthesized porous carbon microspheres was exemplified as electrode materials for supercapacitor with a high specific capacitance of 440 F g-1 at a current density of 0.5 A g-1, and excellent cycling stability with a capacitance retention of 100% after 2000 cycles at 10 A g-1 in 6 M KOH electrolyte. Our method opened a new direction for the gold-nanoparticle-decorated synthesis of porous carbon microspheres and could be further applied to synthesize porous carbon microspheres with various nanoparticle decorations for numerous applications as energy storage devices, enhanced absorption materials, and catalytical sites.

4.
Biochim Biophys Acta Mol Basis Dis ; : 165614, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31783156

RESUMO

The NCLs (neuronal ceroid lipofuscinosis) are forms of neurodegenerative disease that affect people of all ages and ethnicities but are most prevalent in children. Commonly known as Batten disease, this debilitating neurological disorder is comprised of 13 different subtypes that are categorized based on the particular gene that is mutated (CLN1-8, CLN10-14). The pathological mechanisms underlying the NCLs are not well understood due to our poor understanding of the functions of NCL proteins. Only one specific treatment (enzyme replacement therapy) is approved, which is for the treating the brain in CLN2 disease. Hence there remains a desperate need for further research into disease-modifying treatments. In this review, we present and evaluate the genes, proteins and studies performed in the social amoeba, nematode, fruit fly, zebrafish, mouse and large animals pertinent to NCL. In particular, we highlight the use of multicellular model organisms to study NCL protein function, pathology and pathomechanisms. Their use in testing novel therapeutic approaches is also presented. With this information, we highlight how future research in these systems may be able to provide new insight into NCL protein functions in human cells and aid in the development of new therapies.

5.
Can J Cardiol ; 35(8): 1039-1046, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376905

RESUMO

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with stenting requires consideration of patient characteristics, and decision makers require a comprehensive overview of the evidence. METHODS: We performed an umbrella review of systematic reviews (SRs) of randomized controlled trials of extended DAPT (> 12 months) compared with DAPT for 6 to 12 months after percutaneous coronary intervention with stenting. Outcomes of interest were death, myocardial infarction (MI), stroke, stent thrombosis, major adverse cardiac and cerebrovascular events, bleeding, and urgent revascularization. We aimed to assess the evidence of benefits and harms among clinically important subgroups (eg, elderly patients, those with diabetes, prior MI, acute coronary syndrome). We assessed the quality of the included reviews by use of A Measurement Tool to Assess Systematic Reviews (AMSTAR). RESULTS: Sixteen SRs involving 8 randomized controlled trials were included. Most scored 7 or more points on the AMSTAR checklist. There was no significant difference in outcomes with extended DAPT compared with 6 months of DAPT in most SRs, with the exception of an increased risk of major bleeding. Compared with 12 months, extended DAPT may reduce the risk of MI and stent thrombosis; however, the findings were not consistent across all reviews. There have been conflicting reports of an increased risk of death with extended DAPT. Few SRs assessed outcomes among patient subgroups. CONCLUSIONS: Extended DAPT may reduce the risk of MI and stent thrombosis but increase the risk of major bleeding and death. Whether the effects of extended DAPT are consistent across patient subgroups is unclear, and future SRs should address this knowledge gap.

6.
Food Res Int ; 119: 701-708, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30884706

RESUMO

Selenium (Se) and iodine (I) are essential elements for humans, and biofortification of vegetables with these elements is an effective way to amend their deficiencies in the diet. In this study, the distribution and transformation of Se and I species were investigated in radish seedlings that were simultaneously supplemented with these two elements; the fate and the bioaccessibility of Se and I species were dynamically surveyed in the oral, gastric and intestinal phases using a simulated in vitro digestion method. The radish seedlings were cultivated in hydroponic conditions with Se (IV), Se (VI), I- and IO3- (each 1 mg L-1). The results revealed that Se-methylselenocysteine (MeSeCys), selenocystine (SeCys2), selenomethionine (SeMet) and Se (VI) were present in radish, and MeSeCys was the dominant species in both gastric and intestinal extracts, comprising 32.7 ±â€¯1.5% and 39.6 ±â€¯1.1% of the total content, respectively. I- was also the dominant species, which accounted for 57.1 ±â€¯2.1%, 46.6 ±â€¯1.5% and 68.8 ±â€¯1.8% of the total digested content respectively in the oral, gastric and intestinal extracts. Meanwhile, IO3- was absent and organic I accounted for approximately 20%. The bioaccessibility of Se and I in the intestinal phase reached 95.5 ±â€¯2.5% and 85.8 ±â€¯0.9%, respectively; although after dialysis through membranes, the data reduced to 60.1 ±â€¯2.8% and 39.6 ±â€¯0.8%, respectively. Contents of MeSeCys and I- increased from the oral to intestinal phase and the bioaccessibility of both Se and I in radish was above 85%. So radish is suitable as a potential dietary source of Se and I with biofortification.

7.
Adv Healthc Mater ; 8(9): e1900039, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30838801

RESUMO

Nanomaterial-based immunotherapy stimulating T cell activation or tumor-associated macrophage (TAM) conversion holds great promise for promoting tumor suppression. Herein, a novel nanoplatform, iron oxide-embedded large-pore mesoporous organosilica nanospheres (IO-LPMONs), is prepared for the first time to simultaneously activate cytotoxic T cells and polarize macrophages for potent tumor immunotherapy. The IO-LPMONs have large mesopores (6.3 nm) and inorganic-organic hybrid shells, which contribute to a high payload (500 µg mg-1 ) of the antigen ovalbumin (OVA). The IO-LPMONs effectively deliver OVA to dendritic cells (DCs) and activate DCs. Subsequently, high activation of both CD4+ and CD8+ effector antigen-specific T cells is achieved for powerful antitumor effects. Moreover, the IO-LPMONs also act as an immune modulator to polarize TAMs from an immunosuppressive M2 to a tumor-killing M1 phenotype, which induces efficient apoptosis of tumor cells. The combined T cell activation and macrophage polarization strategy based on the IO-LPMONs elicits remarkable combined antitumor effects in vivo, showing great promise for tumor treatment.

8.
Food Funct ; 10(3): 1426-1432, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30762046

RESUMO

Consumption of arsenic (As)-contaminated vegetables is a major As exposure pathway for humans. However, little is known about plant As uptake characteristics and the bioaccessibility of As after ingestion of As-contaminated radish. The present study investigated As concentrations and species in As-contaminated radish and assessed the effects of steamed, griddled and boiled cooking on the bioaccessibility of As in radish using in vitro digestion. The results showed that the radish accumulated 46.3 ± 2.3, 79.2 ± 1.2 and 113.2 ± 3.7 µg As g-1 when treated with 0.5 mg L-1 As(iii) + 0.5 mg L-1 As(v), 1.0 mg L-1 As(iii) + 1.0 mg L-1 As(v) and 2.0 mg L-1 As(iii) + 2.0 mg L-1 As(v), respectively, in culture solution. In both gastric (G) and gastrointestinal (GI) fractions, the total As and species contents in radish decreased in the following order: raw > steamed > griddled > boiled. The bioaccessibility of total As was 97.5 ± 1.2%, 89.3 ± 1.3%, 84.8 ± 1.2% and 52.1 ± 1.1% in the GI phase when the radish was raw, steamed, griddled and boiled, respectively, and the bioaccessibility was not more than 60.1 ± 2.3% in the G phase. These data suggested that boiled cooking should be recommended for consumption of As-contaminated radish because it reduces total As and its species by approximately 50%. Additionally, organic As forms and factors influencing the bioaccessibility of As should be further studied to scientifically evaluate the health risks of As in radish.


Assuntos
Arsênico/farmacocinética , Contaminação de Alimentos , Raphanus/química , Disponibilidade Biológica , Culinária , Digestão , Humanos
9.
Chem Commun (Camb) ; 55(13): 1907-1910, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30675616

RESUMO

A method for Ni-catalyzed controlled decarbonylation of α-ketothioesters is described. Mono- and double-decarbonylations, which gave thioesters and thioethers, respectively, were selectively achieved by changing the ligand. A fundamental study of Ni-catalyzed decarbonylation of α-ketothioesters is presented.

10.
J Cell Physiol ; 234(4): 3526-3537, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30443946

RESUMO

In this study, we aimed to explore the association between miR-99a-5p and CDC25A in breast cancer and the regulatory mechanisms of miR-99a-5p on breast cancer. The expressions of messenger RNA and microRNAs in breast cancer tissues and adjacent tissues were analyzed by the Cancer Genome Atlas microarray analysis. Quantitative real-time polymerase chain reaction was conducted to find out the expression levels of miR-99a-5p and CDC25A. The expression levels of proteins (CDC25A, ki67, cyclin D1, p21, BAX, BCL-2, BCL-XL, MMP2, and MMP9) were determined by Western blot analysis. The relationship between miR-99a-5p and CDC25A was predicted and verified by bioinformatics analysis and dual luciferase assay. After transfection, cell proliferation, invasion, and apoptosis of breast cancer tissues were, respectively, observed by cell counting kit-8 assay, transwell assay, and flow cytometry (FCM). Furthermore, the relationship among miR-99a-5p, CDC25A, and cell-cycle progression was determined by FCM assay. The nude mouse transplantation tumor experiment was performed to verify the influence of miR-99a-5p on breast cancer cell in vivo. The expression of miR-99a-5p in breast cancer tissues and cells was significantly downregulated, whereas CDC25A expression was upregulated. MiR-99a-5p targeted CDC25A and suppressed its expression in breast cancer cells. Overexpression of miR-99a-5p and decreased expression of CDC25A could suppress breast cancer cell proliferation and invasion and facilitate apoptosis. Cell-cycle progression was significantly activated by downregulated miR-99a-5p and upregulated CDC25A. Moreover, miR-99a-5p overexpression repressed the expressions of CDC25A, marker ki67, and Cyclin D1 proteins, whereas it upregulated the expression of p21 protein. MicroRNA-99a-5p suppresses breast cancer progression and cell-cycle pathway through downregulating CDC25A.

11.
EBioMedicine ; 39: 422-435, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30555043

RESUMO

BACKGROUND: Progression of Alzheimer's disease is thought initially to depend on rising amyloidß and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidß, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. METHODS: CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. FINDINGS: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. INTERPRETATION: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidß levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition. FUNDING: GlaxoSmithKline; BBSRC; UCL; ARUK; MRC.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Cognição/fisiologia , Hipocampo/fisiologia , Microglia/fisiologia , Presenilina-1/genética , Animais , Comportamento Animal , Modelos Animais de Doenças , Hemizigoto , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Transmissão Sináptica
12.
Nano Lett ; 18(9): 5590-5595, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30060654

RESUMO

Nanoribbon- and nanowire-based field-effect transistors (FETs) have attracted significant attention due to their high surface-to-volume ratios, which make them effective as chemical and biological sensors. However, the conventional nanofabrication of these devices is challenging and costly, posing a major barrier to widespread use. We report a high-throughput approach for producing arrays of ultrathin (∼3 nm) In2O3 nanoribbon FETs at the wafer scale. Uniform films of semiconducting In2O3 were prepared on Si/SiO2 surfaces via a sol-gel process prior to depositing Au/Ti metal layers. Commercially available high-definition digital versatile discs were employed as low-cost, large-area templates to prepare polymeric stamps for chemical lift-off lithography, which selectively removed molecules from self-assembled monolayers functionalizing the outermost Au surfaces. Nanoscale chemical patterns, consisting of one-dimensional lines (200 nm wide and 400 nm pitch) extending over centimeter length scales, were etched into the metal layers using the remaining monolayer regions as resists. Subsequent etch processes transferred the patterns into the underlying In2O3 films before the removal of the protective organic and metal coatings, revealing large-area nanoribbon arrays. We employed nanoribbons in semiconducting FET channels, achieving current on-to-off ratios over 107 and carrier mobilities up to 13.7 cm2 V-1 s-1. Nanofabricated structures, such as In2O3 nanoribbons and others, will be useful in nanoelectronics and biosensors. The technique demonstrated here will enable these applications and expand low-cost, large-area patterning strategies to enable a variety of materials and design geometries in nanoelectronics.


Assuntos
Índio/química , Nanotecnologia/métodos , Nanotubos de Carbono/química , Semicondutores , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Ouro/química , Nanotecnologia/economia , Nanotecnologia/instrumentação , Nanotubos de Carbono/ultraestrutura , Dióxido de Silício/química , Titânio/química
13.
ACS Appl Mater Interfaces ; 10(20): 16992-17003, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29722264

RESUMO

Non-small cell lung cancer (NSCLC) is difficult to cure because of the high recurrence rate and the side effects of current treatments. It is urgent to develop a new treatment that is safer and more effective than current treatments against NSCLC. Herein, we constructed anti-epidermal growth factor receptor (EGFR) peptide-conjugated PEGylated triangular gold nanoplates (TGN-PEG-P75) as a targeting photothermal therapy (PTT) agent to treat NSCLC under the guidance of computed tomography (CT) and photoacoustic (PA) imaging. The surface of TGNs is successfully conjugated with a novel peptide P75 that has the specific affinity to epidermal growth factor receptor (EGFR). It is found that the EGFR is overexpressed in NSCLC cells. The TGN-PEG-P75 has uniform edge length (77.9 ± 7.0 nm) and neutrally charged surface. The cell uptake experiments demonstrate remarkable affinity of the TGN-PEG-P75 to high EGFR expression cells than low EGFR expression cells (5.1-fold). Thanks to the strong near-infrared absorbance, high photothermal conversion efficiency, and the increased accumulation in tumor cells via the interaction of P75 and EGFR, TGN-PEG-P75 exhibits 3.8-fold superior therapeutic efficacy on HCC827 cells than TGN-PEG. The in vivo CT/PA dual-modal imaging of the TGN-PEG-P75 is helpful in selecting the optimal treatment time and providing real-time visual guidance of PTT. Furthermore, treatments on HCC827 tumor-bearing mouse model demonstrate that the growth of NSCLC cells can be effectively inhibited by the TGN-PEG-P75 through PTT, indicating the great promise of the nanoplatform for treating NSCLC in vivo.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Receptores ErbB , Ouro , Camundongos , Peptídeos , Técnicas Fotoacústicas , Fototerapia
14.
Sci Total Environ ; 633: 836-847, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29602121

RESUMO

Soil contamination by trace elements such as arsenic (As) can pose considerable threats to human health, and need to be carefully identified through site investigation before the soil remediation and development works. However, due to the high costs of soil sampling and testing, decisions on risk management or mitigation strategies are often based on limited data at the site, with substantial uncertainty in the spatial distributions of potentially toxic elements. This study incorporates the restricted maximum likelihood method with three-dimensional spatial autocovariance structure, to investigate the spatial variability features of As-containing soils of geogenic origin. A recent case study in Hong Kong is presented, where >550 samples were retrieved and tested for distributions of As concentrations. The proposed approach is applied to characterize their spatial correlation patterns, to predict the As concentrations at unsampled locations, and to quantify the uncertainty of such estimates. The validity of the approach is illustrated by utilizing the multi-stage site investigation data, through which the advantages of the approach over traditional geostatistical methods are revealed and discussed. The new approach also quantifies the effectiveness of soil sampling on reduction of uncertainty levels across the site. This can become a useful indicator for risk management or mitigation strategies, as it is often necessary to balance between the available resources for soil sampling at the site and the needs for proper characterization of contaminant distributions.

15.
Glob Chang Biol ; 24(2): 786-795, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29140600

RESUMO

Forested catchments provide critically important water resources. Due to dramatic global forest change over the past decades, the importance of including forest or vegetation change in the assessment of water resources under climate change has been highly recognized by Intergovernmental Panel on Climate Change (IPCC); however, this importance has not yet been examined quantitatively across the globe. Here, we used four remote sensing-based indices to represent changes in vegetation cover in forest-dominated regions, and then applied them to widely used models: the Fuh model and the Choudhury-Yang model to assess relative contributions of vegetation and climate change to annual runoff variations from 2000 to 2011 in forested landscape (forest coverage >30%) across the globe. Our simulations show that the global average variation in annual runoff due to change in vegetation cover is 30.7% ± 22.5% with the rest attributed to climate change. Large annual runoff variation in response to vegetation change is found in tropical and boreal forests due to greater forest losses. Our simulations also demonstrate both offsetting and additive effects of vegetation cover and climate in determining water resource change. We conclude that vegetation cover change must be included in any global models for assessing global water resource change under climate change in forest-dominant areas.


Assuntos
Mudança Climática , Conservação dos Recursos Naturais , Florestas , Recursos Hídricos , Taiga
16.
ACS Nano ; 12(1): 662-670, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29271636

RESUMO

Adjuvant treatments following breast-conserving surgery (BCS) are essential to reduce the risk of local recurrences in patients with breast cancer. However, current adjuvant treatments are based on ionizing radiation, which brings radiation-induced damage and amplifies the risk of death. Here we explore the feasibility of using non-ionizing light to induce photothermal therapy as an adjuvant treatment to BCS. In an orthotopic breast cancer mice model, we demonstrate that adjuvant photothermal therapy (aPTT) decreases the incidence of local recurrences after BCS with no expense of cosmetic outcome. In comparison with conventional photothermal therapy, the technique used in aPTT provides more uniformly distributed light energy and less risk of skin burns and local recurrences. Overall, this work represents a departure from the traditional concept of using PTT as an alternative to surgery and reveals the potential of using PTT as an alternative to adjuvant radiation therapy, which is valuable especially for patients susceptible to radiation damage.


Assuntos
Neoplasias da Mama/cirurgia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/prevenção & controle , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Mastectomia Segmentar/métodos , Camundongos Nus , Fototerapia/métodos , Resultado do Tratamento
17.
J Colloid Interface Sci ; 513: 214-221, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29153715

RESUMO

Herein, a mesoporous organosilica nanoparticle (MON) based nanodrug highly loaded with cisplatin (CDDP) and doxorubicin (DOX) (denoted as MONs/CDDP/DOX) has been successfully prepared for the first time. The MONs are characterized with core-contained double hollow shells, thioether and ethane groups separately incorporated frameworks, uniform diameter (420 nm), large surface area (592 m2/g), and ordered pore size (2.5 nm). The safety evaluation of the MONs based on cell viability, haemolytic activity, histological change, and serum biochemical index demonstrates that they have excellent biological compatibility. The efficient uptake of the MONs by human breast cancer MCF-7 cells is further confirmed via confocal laser scanning imaging and flow cytometry. Importantly, the contents of CDDP and DOX in the MONs/CDDP/DOX nanodrug are as high as 120 mg/g and 85 mg/g, respectively. Therefore, the MONs/CDDP/DOX shows a significant improved killing effect against human breast cancer MCF-7 cells compared with sole DOX or CDDP loaded MONs, demonstating the promise of the nanodrug for cancer treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Etano/química , Nanopartículas/química , Compostos de Organossilício/química , Sulfetos/química , Protocolos de Quimioterapia Combinada Antineoplásica/química , Materiais Biocompatíveis/química , Sobrevivência Celular , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Células Tumorais Cultivadas
18.
ACS Appl Mater Interfaces ; 9(36): 30543-30552, 2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28809111

RESUMO

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.


Assuntos
Nanopartículas , Neoplasias da Mama , Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Microambiente Tumoral
19.
BMJ Open ; 7(4): e015421, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28377396

RESUMO

INTRODUCTION: Although dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting, the optimal duration is unknown. Recent evidence indicates there may be benefits in extending the duration beyond 12 months but such decisions may increase the risk of bleeding. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review assessing the optimal duration of DAPT. METHODS AND ANALYSIS: We will perform a comprehensive search of the published and grey literature for systematic reviews involving randomised controlled trials (RCTs) assessing the optimal duration of DAPT following PCI with stenting. The intervention of interest is extended DAPT (beyond 12 months) compared with short-term DAPT (6-12 months). Studies will be selected for inclusion by two reviewers, and the quality will be assessed. The primary outcomes of interest are all-cause mortality and cardiovascular mortality. Secondary outcomes will be bleeding (major, minor and gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Outcomes will be assessed while on DAPT and after withdrawal of DAPT. Data will be summarised with respect to the number of included RCTs, number of participants, effect estimates and heterogeneity. Data will be reported separately based on patient demographics, procedural parameters (eg, stent types, lesion complexity and concurrent disease) and clinical presentation (eg, acute coronary syndromes, infarct type). ETHICS AND DISSEMINATION: Our umbrella review aims to provide a comprehensive overview of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration and reimbursement of DAPT following PCI with stenting. Results will be disseminated through a peer-reviewed publication and conference presentations. Ethics approval is not required for this study. TRIAL REGISTRATION NUMBER: CRD42016047735.


Assuntos
Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Cuidados Pós-Operatórios/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Humanos
20.
PLoS One ; 12(4): e0174208, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28399174

RESUMO

Eucalyptus species are widely planted for reforestation in subtropical China. However, the effects of Eucalyptus plantations on the regional water use remain poorly understood. In an age sequence of 2-, 4- and 6-year-old Eucalyptus plantations, the tree water use and soil evaporation were examined by linking model estimations and field observations. Results showed that annual evapotranspiration of each age sequence Eucalyptus plantations was 876.7, 944.1 and 1000.7 mm, respectively, accounting for 49.81%, 53.64% and 56.86% of the annual rainfall. In addition, annual soil evaporations of 2-, 4- and 6-year-old were 318.6, 336.1, and 248.7 mm of the respective Eucalyptus plantations. Our results demonstrated that Eucalyptus plantations would potentially reduce water availability due to high evapotranspiration in subtropical regions. Sustainable management strategies should be implemented to reduce water consumption in Eucalyptus plantations in the context of future climate change scenarios such as drought and warming.


Assuntos
Eucalyptus/metabolismo , Agricultura Florestal , Modelos Teóricos , Transpiração Vegetal/fisiologia , Água/química , China , Clima , Florestas , Chuva/química , Solo/química , Temperatura Ambiente , Volatilização
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