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1.
Food Chem ; 450: 139269, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38613961

RESUMO

The purpose of this study was to determine the effect of pre-rigor salting on the quality characteristics of surimi gels prepared from snakehead fish muscle. Pre-rigor and post-rigor muscle were mixed with 0.3% or 3% NaCl (w/w) and made into surimi gels, respectively. Results showed that pre-rigor muscle had a higher content of ATP, longer sarcomere, higher pH and greater protein solubility. Metabolic profile suggested that pre-rigor muscle had higher content (a 28-fold increase) of antioxidants such as butyryl-l-carnitine. Transmission electron microscopy showed more damage of mitochondria in post-rigor muscle. Surimi paste from pre-rigor meat chopped with 3% NaCl generally showed greater radical scavenging ability and had higher content of free sulfhydryl. Surimi gel made from pre-rigor muscle salted with 3% NaCl showed a larger gel strength (3.18 kg*mm vs. 2.22 kg*mm) and better water-holding (86% vs. 80%) than that of post-rigor group. Based on these findings, we hypothesized that: In addition to other factors such as pH, degree of denaturation, etc., less protein oxidation in pre-rigor salted surimi also contributes to the improved gel properties.

2.
Angew Chem Int Ed Engl ; 63(12): e202319583, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38282100

RESUMO

Small molecules, including therapeutic drugs and tracer molecules, play a vital role in biological processing, disease treatment and diagnosis, and have inspired various nanobiotechnology approaches to realize their biological function, particularly in drug delivery. Desirable features of a delivery system for functional small molecules (FSMs) include high biocompatibility, high loading capacity, and simple manufacturing processes, without the need for chemical modification of the FSM itself. Herein, we report a simple and versatile approach, based on metal-phenolic-mediated assembly, for assembling FSMs into nanoparticles (i.e., FSM-MPN NPs) under aqueous and ambient conditions. We demonstrate loading of anticancer drugs, latency reversal agents, and fluorophores at up to ~80 % that is mostly facilitated by π and hydrophobic interactions between the FSM and nanoparticle components. Secondary nanoparticle engineering involving coating with a polyphenol-antibody thin film or sequential co-loading of multiple FSMs enables cancer cell targeting and combination delivery, respectively. Incorporating fluorophores into FSM-MPN NPs enables the visualization of biodistribution at different time points, revealing that most of these NPs are retained in the kidney and heart 24 h post intravenous administration. This work provides a viable pathway for the rational design of small molecule nanoparticle delivery platforms for diverse biological applications.


Assuntos
Nanopartículas , Distribuição Tecidual , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Fenóis , Polifenóis , Metais
3.
Angew Chem Int Ed Engl ; 63(4): e202315297, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37945544

RESUMO

Tailoring the hydrophobicity of supramolecular assembly building blocks enables the fabrication of well-defined functional materials. However, the selection of building blocks used in the assembly of metal-phenolic networks (MPNs), an emerging supramolecular assembly platform for particle engineering, has been essentially limited to hydrophilic molecules. Herein, we synthesized and applied biscatechol-functionalized hydrophobic polymers (poly(methyl acrylate) (PMA) and poly(butyl acrylate) (PBA)) as building blocks to engineer MPN particle systems (particles and capsules). Our method allowed control over the shell thickness (e.g., between 10 and 21 nm), stiffness (e.g., from 10 to 126 mN m-1 ), and permeability (e.g., 28-72 % capsules were permeable to 500 kDa fluorescein isothiocyanate-dextran) of the MPN capsules by selection of the hydrophobic polymer building blocks (PMA or PBA) and by controlling the polymer concentration in the MPN assembly solution (0.25-2.0 mM) without additional/engineered assembly processes. Molecular dynamics simulations provided insights into the structural states of the hydrophobic building blocks during assembly and mechanism of film formation. Furthermore, the hydrophobic MPNs facilitated the preparation of fluorescent-labeled and bioactive capsules through postfunctionalization and also particle-cell association engineering by controlling the hydrophobicity of the building blocks. Engineering MPN particle systems via building block hydrophobicity is expected to expand their use.

4.
Angew Chem Int Ed Engl ; 62(45): e202312925, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37800651

RESUMO

Coordination assembly offers a versatile means to developing advanced materials for various applications. However, current strategies for assembling metal-organic networks into nanoparticles (NPs) often face challenges such as the use of toxic organic solvents, cytotoxicity because of synthetic organic ligands, and complex synthesis procedures. Herein, we directly assemble metal-organic networks into NPs using metal ions and polyphenols (i.e., metal-phenolic networks (MPNs)) in aqueous solutions without templating or seeding agents. We demonstrate the role of buffers (e.g., phosphate buffer) in governing NP formation and the engineering of the NP physicochemical properties (e.g., tunable sizes from 50 to 270 nm) by altering the assembly conditions. A library of MPN NPs is prepared using natural polyphenols and various metal ions. Diverse functional cargos, including anticancer drugs and proteins with different molecular weights and isoelectric points, are readily loaded within the NPs for various applications (e.g., biocatalysis, therapeutic delivery) by direct mixing, without surface modification, owing to the strong affinity of polyphenols to various guest molecules. This study provides insights into the assembly mechanism of metal-organic complexes into NPs and offers a simple strategy to engineer nanosized materials with desired properties for diverse biotechnological applications.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Fenóis , Polifenóis/química , Nanopartículas/química , Metais/química , Água
5.
Molecules ; 28(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630413

RESUMO

Irradiation can be used for the preservation of chickpea protein as it can destroy microorganisms, bacteria, virus, or insects that might be present. However, irradiation may provoke oxidative stress, and therefore modify the functionality and nutritional value of chickpea protein. In order to study the effects of irradiation on the physicochemical properties and digestion behaviour of chickpea protein, chickpea protein concentrate (CPC) was treated with electron beam irradiation (EBI) at doses of 5, 10, 15, and 20 kGy. After irradiation, protein solubility first increased at 10 kGy and 15 kGy, and then decreased at the higher dose of 20 kGy. This was supported by SDS-PAGE, where the intensity of major protein bands first increased and then decreased. Increased doses of EBI generally led to greater oxidative modification of proteins in CPC, indicated by reduced sulfhydryls and increased carbonyls. In addition, the protein structure was modified by EBI as shown by Fourier transform infrared spectroscopy analysis, where α-helix generally decreased, and ß-sheet increased. Although the protein digestibility was not significantly affected by EBI, the peptidomic analysis of the digests revealed significant differences among CPC irradiated with varying doses. A total of 337 peptides were identified from CPC irradiated with 0 kGy, 10 kGy, and 20 kGy, with 18 overlapping peptides and 60, 29, and 40 peptides specific to the groups of 0, 10, and 20 kGy respectively. Theoretical calculation showed that the distribution of peptide length, hydrophobicity, net charge, and C-terminal residues were affected by irradiation. The 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity showed a marginal decrease with an increasing dose of irradiation. In conclusion, EBI led to oxidative modification and structural changes in chickpea protein, which subsequently affected the physicochemical properties of peptides obtained from in-vitro digestion of CPC, despite similar digestibility.


Assuntos
Cicer , Elétrons , Eletroforese em Gel de Poliacrilamida , Valor Nutritivo , Estresse Oxidativo
6.
Molecules ; 28(14)2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37513304

RESUMO

In order to clarify the individual role of freezing and frozen storage on the quality of fish, fillets of large-mouth bass (Micropterus salmoides) were subjected to different freezing rates (freezing with -18 °C (A), -60 °C (B), and -60 °C with forced air circulation at 2 m/s (C), respectively) followed by frozen storage at -18 °C for 30 and 90 days. Another two groups were frozen at -60 °C, followed by storage at -40 °C (D) and -60 °C (E), respectively. Results showed that water-holding and TVBN were mainly affected by storage time. No significant changes were found in free thiol content among treatments. A greater freezing rate and lower storage temperature generally led to lower TBARS. GC × GC-TOFMS revealed a total of 66 volatile compounds, which were related to lipid oxidation. PLS-DA showed that fresh samples were separated from the frozen-thawed ones, and fillets in groups D and E were relatively close to fresh fillets in the composition of oxidation-related volatiles. In conclusion, freezing rate and storage temperature had a significant impact on lipid oxidation and protein denaturation in the fillets of large-mouth bass, while protein oxidation was more affected by freezing rate.


Assuntos
Bass , Animais , Congelamento , Temperatura , Lipídeos , Boca , Armazenamento de Alimentos/métodos
7.
Angew Chem Int Ed Engl ; 62(18): e202302448, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36872291

RESUMO

Flexible metal-organic materials are of growing interest owing to their ability to undergo reversible structural transformations under external stimuli. Here, we report flexible metal-phenolic networks (MPNs) featuring stimuli-responsive behavior to diverse solute guests. The competitive coordination of metal ions to phenolic ligands of multiple coordination sites and solute guests (e.g., glucose) primarily determines the responsive behavior of the MPNs, as revealed experimentally and computationally. Glucose molecules can be embedded into the dynamic MPNs upon mixing, leading to the reconfiguration of the metal-organic networks and thus changes in their physicochemical properties for targeting applications. This study expands the library of stimuli-responsive flexible metal-organic materials and the understanding of intermolecular interactions between metal-organic materials and solute guests, which is essential for the rational design of responsive materials for various applications.

8.
J Am Chem Soc ; 144(27): 12510-12519, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35775928

RESUMO

Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid synthesis and study of diverse polypeptide-based materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide-polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (Ka of ∼2 × 104 M-1) and polyproline (Ka of ∼2 × 106 M-1) exhibited stronger interactions with polyphenols than other amino acids (Ka of ∼2 × 103 M-1). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine-tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline-tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.


Assuntos
Peptídeos , Polifenóis , Cápsulas/química , Sistemas de Liberação de Medicamentos , Simulação de Acoplamento Molecular , Peptídeos/química , Taninos/química
9.
Angew Chem Int Ed Engl ; 61(34): e202208037, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35726006

RESUMO

Coordination states of metal-organic materials are known to dictate their physicochemical properties and applications in various fields. However, understanding and controlling coordination sites in metal-organic systems is challenging. Herein, we report the synthesis of site-selective coordinated metal-phenolic networks (MPNs) using flavonoids as coordination modulators. The site-selective coordination was systematically investigated experimentally and computationally using ligands with one, two, and multiple different coordination sites. Tuning the multimodal Fe coordination with catechol, carbonyl, and hydroxyl groups within the MPNs enabled the facile engineering of diverse physicochemical properties including size, selective permeability (20-2000 kDa), and pH-dependent degradability. This study expands our understanding of metal-phenolic chemistry and provides new routes for the rational design of structurally tailorable coordination-based materials.


Assuntos
Metais , Fenóis , Ligantes , Metais/química , Fenóis/química
10.
Adv Sci (Weinh) ; 9(6): e2104331, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34997692

RESUMO

Fluorinated motifs are promising for the engineering of repellent coatings, however, a fundamental understanding of how to effectively bind these motifs to various substrates is required to improve their stability in different use scenarios. Herein, the binding of fluorinated polyhedral oligomeric silsesquioxanes (POSS) using a cyanoacrylate glue (binder) is computationally and experimentally evaluated. The composite POSS-binder coatings display ultralow surface energy (≈10 mJ m-2 ), while still having large surface adhesions to substrates (300-400 nN), highlighting that super-repellent coatings (contact angles >150°) can be readily generated with this composite approach. Importantly, the coatings show super-repellency to both corrosive liquids (e.g., 98 wt% H2 SO4 ) and ultralow surface tension liquids (e.g., alcohols), with ultralow roll-off angles (<5°), and tunable resistance to liquid penetration. Additionally, these coatings demonstrate the potential in effective cargo loading and robust self-cleaning properties, where experimental datasets are correlated with both relevant theoretical predictions and systematic all-atom molecular dynamics simulations of the repellent coatings. This work not only holds promise for chemical shielding, heat transfer, and liquid manipulations but offers a facile yet robust pathway for engineering advanced coatings by effectively combining components for their mutually desired properties.

11.
Environ Pollut ; 263(Pt B): 114388, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32222665

RESUMO

In China, ambient fine particulate matter (PM2.5) causes a large health burden and raises specific concerns for policymakers. However, assessments of the health effects associated with air pollution from industrial land layouts remain inadequate. This study established a comprehensive assessment framework to quantify the health and economic impacts of PM2.5 exposure at different industrial geographical locations. This framework aims to optimize the spatial distribution of industrial emissions to achieve the lowest public health costs in Changsha, a representative industrial city in China. Health effects were estimated by applying the integrated exposure-response model and a long-range pollution dispersion model (CALPUFF). The value of statistical life (VSL) was used to monetize health outcomes. It was found that implementing an optimal industrial land layout can yield considerable social and financial benefits. Compared with the current industrial space layout, in 2030, the averted contribution by Changsha's industrial sector to PM2.5-related mortality and corresponding economic losses will be 60.8% and 0.69 billion US dollars (USD), respectively. The results of optimization analyses highlighted that population density and emission location are significant factors affecting the health burden. This method can identify the optimal geographical allocation of industrial land with minimal expected health and economic burden. These results will also provide policymakers with a measurable assessment of health risks related to industrial spatial planning and the associated health costs to enhance the effectiveness of efforts to improve air quality.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Material Particulado/análise , Saúde Pública
12.
Int J Nanomedicine ; 14: 9721-9730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849464

RESUMO

BACKGROUND: Most of the oral drugs have the properties of weak intestinal absorption and low bioavailability, which leads to little treatment to diseases. By nanotechnology, these drugs can be efficiently delivered to pass biological barriers and promote the cell uptake ability for the enhancement of the oral bioavailability. METHODS: The present work chose the prepared curcumin-loaded galactosylated albumin nanoparticles (Gal-BSA NPs) as the nano-drug samples to study the intestinal capacity and the oral bioavailability. RESULTS: The cell uptake assay showed that the Gal-BSA NPs could promote the internalization of more curcumin into the Caco-2 cells. Moreover, the cell uptake mechanism of Gal-BSA-Cur NPs depended on the clathrin-mediated endocytosis transport. The intestinal permeation assay using one Ussing chamber exhibited that the absorptive amounts of curcumin in Gal-BSA-Cur NPs group were 1.5-fold of pure curcumin group. Meanwhile, the permeation mechanism of Gal-BSA-Cur NPs across the intestine mainly depended on the passive transport. The pharmacokinetics study in vivo suggested that the oral bioavailability of Gal-BSA-Cur NPs was improved by 1.4-fold compared with pure curcumin. CONCLUSION: All results demonstrated that Gal-BSA NPs could improve the intestinal absorption capacity and oral bioavailability of curcumin through the double absorption mechanisms of the clathrin-mediated endocytosis and the passive transport.


Assuntos
Curcumina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Curcumina/administração & dosagem , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Endocitose/efeitos dos fármacos , Galactose/química , Humanos , Masculino , Nanopartículas/química , Ratos Sprague-Dawley , Soroalbumina Bovina/química
13.
Talanta ; 202: 392-401, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171200

RESUMO

A novel restricted access molecularly imprinted polymers (RAMIPs) fiber was developed for solid-phase microextraction (SPME) of hesperetin and its metabolites in livers of live rats in vivo. Hesperetin as the template, N-isopropylacrylamide as the functional monomer, ethylene glycol dimethyl acrylate as the crosslinker, 2,2-azobisisobutyonnitrile as initiator and bovine serum albumin as the restricted access material were applied in the preparation process. Scanning electron microscopy and Fourier transform infrared spectroscopy were applied to characterize the polymers. The adsorption experiments indicated that RAMIPs-SPME fibers performed high selective recognition property to hesperetin. The selectivity experiment indicated that the adsorption capacity and selectivity of RAMIPs-SPME fibers to hesperetin was higher than that of quercetin, luteolin and baicalein. Macromolecules elimination test showed RAMIPs-SPME fibers could eliminate 94.80%-98.96% of macromolecules, which indicated that RAMIPs-SPME fibers can be used to extract analytes directly from complex biological samples. Furthermore, RAMIPs-SPME sampling combined to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to capture and identify hesperetin and its metabolites in rat livers in vivo. Finally, hesperetin-7-O-glucuronide, hesperetin-3'-O-glucuronide, eriodictyol and homoeriodictyol were identified as the metabolites of hesperetin. In comparison with the MIPs fibers, commercial PDMS and DVB fibers, RAMIPs-SPME fibers possessed better exclusion effect to macromolecules and higher selectivity to hesperetin and its metabolites. The results demonstrated that the prepared RAMIPs-SPME fiber were proven to be effective tool for the selective adsorption and enrichment of hesperetin and its metabolites from the complex biological fluids.


Assuntos
Hesperidina/análise , Impressão Molecular , Polímeros/química , Microextração em Fase Sólida , Hesperidina/metabolismo
14.
Int J Nanomedicine ; 13: 8309-8323, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584302

RESUMO

BACKGROUND: The main objective of this study was to develop novel BSA nanoparticles (BSA NPs) for improving the bioavailability of curcumin as an anticancer drug, and those BSA NPs were galactosylated for forming the curcumin-loaded galactosylated BSA nanoparticles (Gal-BSA-Cur NPs), thus enhancing their ability to target asialoglycoprotein receptor (ASGPR) overexpressed on hepatocellular carcinoma (HCC) cells. MATERIALS AND METHODS: Gal-BSA-Cur NPs were prepared by the desolvation method and showed a spherical shape and well distribution with the average particle size of 116.24 nm. RESULTS: In vitro drug release assay exhibited that Gal-BSA-Cur NPs had higher release rates and improved the curcumin solubility. Cell uptake studies confirmed that Gal-BSA-Cur NPs could selectively recognize receptors on the surface of HCC (HepG2) cells and improve internalization ability of drug compared with BSA NPs-loaded curcumin (BSA-Cur NPs), which might be due to high affinity to galactose. Further, the effects of Gal-BSA-Cur NPs were evaluated by cytotoxicity assay, crystal violet assay, cell apoptosis assay, and wound healing assay, respectively, which revealed that Gal-BSA-Cur NPs could inhibit HepG2 cells proliferation, induce cell apoptosis, and inhibit cell migration. CONCLUSION: Immunofluorescence staining has proved that the effects of Gal-BSA-Cur NPs related to the suppression of the nuclear factor κB-p65 (NF-κB-p65) expression in HepG2 cell nucleus. Therefore, these results indicate that novel Gal-BSA-Cur NPs are potential candidates for targeted curcumin delivery to HCC cells.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Movimento Celular , Curcumina/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Galactose/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Soroalbumina Bovina/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ligação Competitiva , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/síntese química , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Endocitose , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Fator de Transcrição RelA/metabolismo
15.
Talanta ; 184: 307-315, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29674047

RESUMO

In present study, novel magnetic molecularly imprinted polymers for hesperetin were successfully prepared by surface molecular imprinting method using functionalized Fe3O4 particles as the magnetic cores. Hesperetin as the template, N-Isopropylacrylamide as the functional monomer, ethylene glycol dimethyl acrylate as the crosslinker, 2,2-azobisisobutyonnitrile as initiator and acetonitrile-methanol (3:1, v/v) as the porogen were applied in the preparation process. Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscope, x-ray diffraction and vibrating sample magnetometry were applied to characterize the magnetic molecularly imprinted polymers. The adsorption experiments indicated that the magnetic molecularly imprinted polymers performed high selective recognition property to hesperetin. The selectivity experiment indicated that the adsorption capacity and selectivity of polymers to hesperetin was higher than that of luteolin, baicalein and ombuin. Furthermore, the magnetic molecularly imprinted polymers were employed as adsorbents for extraction and enrichment of hesperetin from the dried pericarp of Citrus reticulata Blanco. The recoveries of hesperetin in the dried pericarp of Citrus reticulata Blanco ranged from 90.5% to 96.9%. The linear range of 0.15-110.72 µg/mL was obtained with correlation coefficient of greater than 0.9991. The limit of detection and quantification of the proposed method was 0.06 µg/mL and 0.15 µg/mL, respectively. Based on three replicate measurements, intra-day RSD was 0.71% and inter-day RSD was 2.31%. These results demonstrated that the prepared magnetic molecularly imprinted polymers were proven to be an effective material for the selective adsorption and enrichment of hesperetin from natural medicines, fruits and et al.


Assuntos
Citrus/química , Frutas/química , Hesperidina/análise , Nanopartículas de Magnetita/química , Impressão Molecular , Polímeros/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
16.
Environ Int ; 116: 92-100, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29660613

RESUMO

Both climate change and intensive human activities are thought to have contributed to the impairment of atmospheric visibility in Beijing. But the detailed processes involved and relative roles of human activities and climate change have not been quantified. Optical extinction of aerosols, the inverse of meteorological visibility is especially sensitive to fine particles <1.0 µm. These submicron particles are considered more hazardous than larger ones in terms of cardiovascular and respiratory diseases. Here we used the aerosol optical extinction (inverse of visibility) as the indicator of submicron particles pollution to estimate its inter-annual variability from 1980 to 2015. Our results indicated that optical extinction experienced two different periods: a weakly increasing stage (1980-2005) and a rapidly increasing stage (2005-2015). We attributed the variations of optical extinction to the joint effects of human activities and climate change. Over the past 36 years, human activities played a leading role in the increase of optical extinction, with a positive contribution of 0.077 km-1/10 y. While under the effects of climate change, optical extinction firstly decreased by 0.035 km-1/10 y until 2005 and then increased by 0.087 km-1/10 y. Detailed analysis revealed that the abrupt change (around 2005) of optical extinction resulted from the trend reversals of climate change. We found since 2005 the decreasing trend by 0.58 m·s-1/10 y in wind speed, the growing trend at 8.69%/10 y in relative humidity and the declining trend by 2.72 hPa/10 y in atmospheric pressure have caused the rapid increase of optical extinction. In brief, the higher load of fine particles <1.0 µm in Beijing in recent decades could be associated with both human activities and climate change. Particularly after 2005, the adverse climate change aggravated the situation of submicron particles pollution.


Assuntos
Poluição do Ar , Mudança Climática , Atividades Humanas , Pequim , Humanos , Smog
17.
Eur J Med Chem ; 126: 810-822, 2017 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-27951489

RESUMO

Based on our recent investigations on chalcone derivatives as AChE inhibitors, a series of ferulic acid (FA) tertiary amine derivatives similar to chalcone compounds were designed and synthesized. The results of bioactivity evaluation revealed that most of new synthesized compounds had comparable or more potent AChE inhibitory activity than the control drug Rivastigmine. The alteration of carbon chain linking tertiary amine groups and ferulic acid scaffold markedly influenced the inhibition activity against AChE. Among them the inhibitory activity of compound 6d (IC50: 0.71 ± 0.09 µmol/L) and 6e (IC50: 1.11 ± 0.17 µmol/L) was equal to 15-fold and 9-fold than that of Rivastigmine against AChE (IC50: 10.54 ± 0.86 µmol/L), respectively. Moreover, compound 6d shows the highest selectivity for AChE over butyrylcholinesterase(BuChE) (ratio: 18.3). The kinetic study suggested that compound 6d revealed a mixed-type inhibition against AChE. The result of molecular docking showed that compound 6d combines to AChE with three amino acid sites(Trp84, Tyr334 and Trp279), while combines to BuChE with two amino acid sites (Tyr67 and Gly66) in enzyme domains, respectively. Compound 6d might act as a potential agent for the treatment of Alzheimer's diseases (AD).


Assuntos
Acetilcolinesterase/metabolismo , Amidas/química , Aminas/química , Butirilcolinesterase/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Acetilcolinesterase/química , Butirilcolinesterase/química , Domínio Catalítico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Ácidos Cumáricos/metabolismo , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
18.
Sci Rep ; 6: 28611, 2016 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-27334428

RESUMO

EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer cell lines. Gefitinib suppressed EGFR signaling and inhibited phosphorylation of ERK and Akt. Metformin amplified this inhibitory effect and enhanced gefitinib-induced activation of AMPK signaling pathway. In vivo intravesical treatment of metformin and gefitinib on syngeneic orthotopic mice confirmed the significant inhibitory effect on bladder tumor growth. These two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metformina/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinazolinas/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Gefitinibe , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo
19.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 34(2): 162-5, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27337925

RESUMO

OBJECTIVE: This study aimed at using cone beam computed tomography (CBCT) to study the influence ofprolonged unilateral posterior teeth loss on bilateral condylar morphology. METHODS: The CBCT images of 30 patients withprolonged unilateral posterior teeth loss and 30 healthy people as controls were corrected. Mimics 15.0 software was used tomeasure volume, area, distance, and bone density of condyle. The results were statistically analyzed. RESULTS: The volumeand bone density of condylar head and the entire condyle on missing teeth side were less than the contralateral side (P<0.05).The area and bone density of condylar transverse plane were greater than the contralateral side (P<0.05). CONCLUSION: After prolonged unilateral posterior teeth loss, adaptive reconstruction occurs in the bilateral condyles, and condyle of missing teethside is smaller than the contralateral side.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Côndilo Mandibular/cirurgia , Perda de Dente , Densidade Óssea , Estudos de Casos e Controles , Humanos , Côndilo Mandibular/patologia , Software
20.
Am J Cancer Res ; 6(2): 498-508, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27186419

RESUMO

Quercetin, a natural existing polyphenol compound, has shown anticancer capacity for liver, breast, nasopharyngeal and prostate carcinoma but has not been clinically approved yet. This might be due to lack of clear mechanistic picture. Bladder cancer is one of the most common cancers of the urinary tract in the world. In China, bladder cancer has the highest rate of incidence out of all malignancies of the urinary system. The anticancer application of quercetin on bladder cancer has not been investigated either. This study was aimed to examine the mechanisms of quercetin on inhibition of bladder cancer. First, two human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. Second, AMPK pathway including 4E-BP1 and S6K were examined by western blot. Quercetin induces apoptosis and inhibits migration. We are the first to show that quercetin displays potent inhibition on bladder cancer cells via activation of AMPK pathway.

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