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1.
Langmuir ; 40(1): 938-949, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38134444

RESUMO

The superamphiphiles exhibit broad prospects for fabricating stimuli-responsive emulsions. Because the superamphiphiles are assembled via noncovalent interactions, they have the advantage of fast response and high efficiency. Recently, a series of switchable emulsions using CO2-responsive superamphiphiles have been developed, which extends the applications of CO2-responsive materials in widespread field. However, there is still a lack of fundamental understanding on the switching mechanism related to the assembled structure of superamphiphiles at the oil-water interface. We employed molecular dynamics (MD) simulations to investigate the reversible emulsification/demulsification process of a responsive emulsion system stabilized by a recently developed responsive superamphiphile (BTOA), which consists of oleic acid (OA) and cationic amine (named 1,3-bis(aminopropyl)tetramethyldisiloxane, BT). The simulation results present the morphologies in both the emulsion and demulsification states. It is found that the ionized OA- and the protonated BT+ together form an adsorption layer at the oil-water interface. The hydrophobic parts of BT+ are inserted into the adsorption layer, and the two amine groups contact the water phase. This adsorption layer reduces the interfacial tension and stabilizes the emulsion. After the bubbling of CO2, the surfactants were fully protonated to OA and BT2+. Because of the changes in the molecular polarity, OA and BT2+ entered the oil and water phases, respectively, resulting in demulsification. The structural and dynamical properties were analyzed to reveal the different intermolecular interactions that were responsible for the reversible reversibility of the emulsion. The observations are considered to be complementary to experimental studies and are expected to provide deeper insights into studies on developing responsive materials via supramolecular assemblies.

2.
Macromol Rapid Commun ; 45(7): e2300661, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38271638

RESUMO

Photocuring 3D printing of hydrogels, with sophisticated, delicate structures and biocompatibility, attracts significant attention by researchers and possesses promising application in the fields of tissue engineering and flexible devices. After years of development, photocuring 3D printing technologies and hydrogel inks make great progress. Herein, the techniques of photocuring 3D printing of hydrogels, including direct ink writing (DIW), stereolithography (SLA), digital light processing (DLP), continuous liquid interface production (CLIP), volumetric additive manufacturing (VAM), and two photon polymerization (TPP) are reviewed. Further, the raw materials for hydrogel inks (photocurable polymers, monomers, photoinitiators, and additives) and applications in tissue engineering and flexible devices are also reviewed. At last, the current challenges and future perspectives of photocuring 3D printing of hydrogels are discussed.


Assuntos
Hidrogéis , Engenharia Tecidual , Engenharia Tecidual/métodos , Hidrogéis/química , Polímeros , Impressão Tridimensional , Estereolitografia
3.
Macromol Rapid Commun ; 44(18): e2300214, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37306260

RESUMO

Poly(vinyl alcohol) (PVA)-based hydrogels have attracted great attention and been widely used in biological tissue engineering. With the development of modern medicine, precision medicine requires the customization of medical materials. However, lacking of photocurable functional groups or the performance of rapid phase transition makes PVA-based hydrogels difficult to be customizable molded through photocuring 3D printing technique. In this research, customizable PVA-based hydrogels with high performance through 3D photocurable printing and freezing-thawing (F-T) process are obtained. The ability of 3D-printable is endowed by the introduction of polyvinyl alcohol-styrylpyridine (PVA-SBQ), which can be photo-crosslinked quickly without photoinitiator. Meanwhile, the tunable mechanical properties are achieved by adjusting the mass ratio of PVA-SBQ to PVA, and PVA can offer the physical crosslinking points through freezing-thawing (F-T) process. The hydrogels with high resolution are prepared by digital light procession 3D printing with the mass ratio 1:1 of PVA-SBQ to PVA solution. Attributed to the absence of initiator, and no small molecule residues inside the hydrogels, the hydrogels have good biocompatibility and have the potential to be applicated in the field of biological tissue engineering.


Assuntos
Hidrogéis , Engenharia Tecidual , Hidrogéis/química , Álcool de Polivinil/química , Materiais Biocompatíveis/química
4.
Org Biomol Chem ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32458847

RESUMO

A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.

5.
Org Biomol Chem ; 17(9): 2356-2360, 2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30758386

RESUMO

Quinazolinones have broad applications in the biological, pharmaceutical and material fields. Studies on the synthesis of these compounds are therefore widely conducted. Herein, a novel and highly efficient copper-mediated tandem C(sp2)-H amination and annulation of benzamides and amidines for the synthesis of quinazolin-4(1H)-ones is proposed. This synthetic route can be useful for the construction of quinazolin-4(1H)-one frameworks.

6.
Biosci Biotechnol Biochem ; 81(10): 1899-1907, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28859546

RESUMO

The function of microRNA-34a (miR-34a) in transdifferentiation of glioma stem cells (GSCs) into vascular endothelial cells (VECs) was explored by focusing on Notch ligand Delta-like 1 (Dll1). MiR-34a mimics was transfected into CD133 + glioma cell U251. The angiogenesis feature of miR-34a transfected U251 cells was investigated and the expressions of CD31, CD34, Vwf, Notch 1, and Dll1 were quantified. Length of branching vessel-like structures in the miR-34a transfected U251 cells was significantly higher than control cells. The VEC feature of miR-34a overexpressed U251 cells was further confirmed by the expressions of CD31, CD34, and vWF. Transfection of miR-34a decreased the expression of Notch 1 and Dll1. Furthermore, the miR-34a overexpression-enhanced tube formation of GSCs was suppressed when the decreased expression of Dll1 was restored. The current study highlighted the potential of miR-34a as an inducer in GSCs' transdifferentiation into VECs by targeting Dll1.


Assuntos
Transdiferenciação Celular/genética , Células Endoteliais/patologia , Glioma/patologia , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Receptor Notch1/metabolismo , Transdução de Sinais/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Humanos , Regulação para Cima/genética
7.
PLoS One ; 19(6): e0305552, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885275

RESUMO

This study proposes a framework for the risk structure of group polarization in the online information of sudden public health incidents, as well as the causes and constraints of group polarization distributed in the ternary space. Then, combining the above two and based on the concept of phase change space, a simulation model of group polarization of online information in sudden public health incidents was constructed by reflecting the risk of group polarization with the number of network users who hold extreme views. The system dynamics simulation of the model is carried out by using the software Anylogic, and predict the evolution trend of the model from the perspective of simulation. The research results indicate that the model built in this study can effectively simulate the formation and dissemination of extreme opinions in the online public opinion of public health emergencies. The vital factors or constraints on the group polarization include emotional guidance, heat reduction, as well as and life pressure.


Assuntos
Emergências , Humanos , Medição de Risco/métodos , Simulação por Computador , Saúde Pública , Opinião Pública , Modelos Teóricos , Internet
8.
Int J Biol Macromol ; 261(Pt 1): 129699, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281517

RESUMO

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m2·g-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H2O2/K2S2O8 through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H2O2/K2S2O8, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H2O2/K2S2O8, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive 1O2 and ·OH. The significant contribution from 1O2 endowed CS-FC/H2O2/K2S2O8 with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.


Assuntos
Compostos Azo , Quitosana , Poluentes Ambientais , Compostos Ferrosos , Poluentes Químicos da Água , Metalocenos , Microesferas , Peróxido de Hidrogênio , Adsorção , Concentração de Íons de Hidrogênio , Cinética
9.
Artigo em Inglês | MEDLINE | ID: mdl-38593302

RESUMO

With the fast economic development and accelerating urbanization, more and more skyscrapers made entirely of concrete and glass are being constructed. To keep a comfortable indoor environment, massive energy for air conditioning or heating appliances is consumed. A huge amount of heat (>30%) is gained or released through glass windows. Using smart windows with the capability to modulate light is an effective way to reduce building energy consumption. Thermochromic hydrogel is one of the potential smart window materials due to its excellent thermal response, high radiation-blocking efficiency, cost-effectiveness, biocompatibility, and good uniformity. In this work, polyhydroxypropyl acrylate (PHPA) hydrogels with controllable lower critical solution temperature (LCST) were prepared by photopolymerization. The transition temperature and transition rate under "static transition" conditions were investigated. Unlike "static" conditions in which the transition temperature was not affected by the initial and final temperature and heating/cooling ramp, the transition temperature varied with the rate of temperature change under dynamic conditions. The "dynamic" transition temperature of the PHPA hydrogel gradually increased with the increase of the heating rate. It was the result of the movement of the molecular chains lagging behind the temperature change when the temperature change was too fast. The results of the solar irradiation experiment by filling PHPA hydrogels into double glazing windows showed that the indoor temperature was about 15 °C lower than that of ordinary glass windows, indicating that it can significantly reduce the energy consumption of air conditioning. In addition, a wide range of adjustable transition temperatures and fast optical response make PHPA hydrogels potentially applicable to smart windows.

10.
ACS Appl Mater Interfaces ; 16(23): 29600-29609, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38832656

RESUMO

Hydrogel tubes made of sodium alginate (SA) have potential applications in drug delivery, soft robots, biomimetic blood vessels, tissue stents, and other fields. However, the continuous preparation of hollow SA hydrogel tubes with good stability and size control remains a huge challenge for chemists, material scientists, and medical practitioners. Inspired by the plant apical growth strategy, a new method named soft cap-guided growth was proposed to produce SA hydrogel tubes. Due to the introduction of inert low gravity substances, such as air and heptane, into the extrusion needle in front of calcium chloride solution to form a soft cap, the SA hydrogel tubes with controllable sizes were fabricated rapidly and continuously without using a template through a negative gravitropism mechanism. The SA hydrogel tubes had good tensile strength, high burst pressure, and good cell compatibility. In addition, hydrogel tubes with complex patterns were conveniently created by controlling the motion path of a soft cap, such as a rotating SA bath or magnetic force. Our research provided a simple innovative technique to steer the growth of hydrogel tubes, which made it possible to mass produce hydrogel tubes with controllable sizes and programmable patterns.


Assuntos
Alginatos , Hidrogéis , Alginatos/química , Hidrogéis/química , Resistência à Tração
11.
Carbohydr Polym ; 312: 120770, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37059526

RESUMO

Treating wastewater containing malachite green (MG) using porous materials with both adsorption and degradation functions have become a major challenge in achieving the carbon neutrality goal. Herein by incorporating the ferrocene (Fc) group as a Fenton active center, a novel composite porous material (DFc-CS-PEI) was prepared using chitosan (CS) and polyethyleneimine (PEI) as skeletons and oxidized dextran as a crosslinker. DFc-CS-PEI not only possesses satisfactory adsorption performance to MG but also excellent degradability in the presence of a minor amount of H2O2 (3.5 mmol/L) without any additional assistance, due to high specific surface area and active Fc group. The maximum adsorption capacity is ca. 177.73 ± 3.11 mg/g, outperforming most CS-based adsorbents. The removal efficiency of MG is significantly enhanced from 20 % to 90 % as DFc-CS-PEI and H2O2 coexist, due to ·OH-dominated Fenton reaction, and remained in a wide pH range (2.0-7.0). Cl- exhibits notable suppression on the degradation of MG because of quenching effects. Note that DFc-CS-PEI has a very small iron leaching (0.2 ± 0.015 mg/L), and can be rapidly recycled by simple water-washing, without any harmful chemicals and potential second pollution. Such versatility, high stability, and green recyclability make the as-prepared DFc-CS-PEI a promising porous material for the treatment of organic wastewater.

12.
ACS Appl Mater Interfaces ; 14(26): 30332-30342, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35730674

RESUMO

Liquid conductor-based flexible sensors with high mechanical deformability and reliable electrical reversibility have aroused great interest in electronic skin, soft robotics, environmental monitoring, and other fields. Herein, we develop a novel strategy to fabricate liquid conductor-based flexible sensors by combining ionic liquid-based magnetofluids (IL-MFs), magnetic printing, and photopolymerization techniques. The as-prepared sensors exhibit excellent electromechanical properties, such as a wide detection range, low hysteresis, fast response time, good durability, etc. Moreover, the gauge factors (GFs) of the sensor could be easily adjusted by changing the modulators with different line widths or patterns, and the strain sensors can also be designed for anisotropic monitoring. Apart from serving as strain sensors, the magnetofluid-based flexible sensors can be used to detect external pressure, human activities, and changes in temperature, illumination, and magnetic field as well. This work provides a facile strategy to fabricate liquid conductor-based multifunctional sensors. Such a magnetofluid-based sensor has a great promising future.

13.
J Bacteriol ; 193(17): 4557-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21725015

RESUMO

Strain HQM9, an aerobic, rod-shaped marine bacterium from red algae, can produce agarases and liquefy solid plating media efficiently when agar is used as a coagulant. Here we report the draft genome sequence and the initial findings from a preliminary analysis of strain HQM9, which should be a novel species of Flavobacteriaceae.


Assuntos
Flavobacteriaceae/classificação , Flavobacteriaceae/genética , Genoma Bacteriano , Água do Mar/microbiologia , Biodegradação Ambiental , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , RNA de Transferência/genética , Análise de Sequência
14.
J Neuroinflammation ; 8: 154, 2011 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-22053982

RESUMO

BACKGROUND: Increasing evidence suggests that microglial activation may participate in the aetiology and pathogenesis of Parkinson's disease (PD). CD200-CD200R signalling has been shown to be critical for restraining microglial activation. We have previously shown that expression of CD200R in monocyte-derived macrophages, induced by various stimuli, is impaired in PD patients, implying an intrinsic abnormality of CD200-CD200R signalling in PD brain. Thus, further in vivo evidence is needed to elucidate the role of malfunction of CD200-CD200R signalling in the pathogenesis of PD. METHODS: 6-hydroxydopamine (6-OHDA)-lesioned rats were used as an animal model of PD. CD200R-blocking antibody (BAb) was injected into striatum to block the engagement of CD200 and CD200R. The animals were divided into three groups, which were treated with 6-OHDA/Veh (PBS), 6-OHDA/CAb (isotype control antibody) or 6-OHDA/BAb, respectively. Rotational tests and immunohistochemistry were employed to evaluate motor deficits and dopaminergic neurodegeneration in animals from each group. HPLC analysis was used to measure monoamine levels in striatum. Morphological analysis and quantification of CD11b- (or MHC II-) immunoreactive cells were performed to investigate microglial activation and possible neuroinflammation in the substantia nigra (SN). Finally, ELISA was employed to assay protein levels of proinflammatory cytokines. RESULTS: Compared with 6-OHDA/CAb or 6-OHDA/Veh groups, rats treated with 6-OHDA/BAb showed a significant increase in counts of contralateral rotation and a significant decrease in TH-immunoreactive (TH-ir) neurons in SN. A marked decrease in monoamine levels was also detected in 6-OHDA/BAb-treated rats, in comparison to 6-OHDA/Veh-treated ones. Furthermore, remarkably increased activation of microglia as well as up-regulation of proinflammatory cytokines was found concomitant with dopaminergic neurodegeneration in 6-OHDA/BAb-treated rats. CONCLUSIONS: This study shows that deficits in the CD200-CD200R system exacerbate microglial activation and dopaminergic neurodegeneration in a 6-OHDA-induced rat model of PD. Our results suggest that dysfunction of CD200-CD200R signalling may be involved in the aetiopathogenesis of PD.


Assuntos
Antígenos CD/metabolismo , Neurônios Dopaminérgicos/patologia , Microglia/metabolismo , Degeneração Neural/patologia , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Receptores Imunológicos/metabolismo , Animais , Anticorpos Bloqueadores/administração & dosagem , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Dopamina/metabolismo , Humanos , Masculino , Microglia/citologia , Microglia/efeitos dos fármacos , Degeneração Neural/induzido quimicamente , Degeneração Neural/fisiopatologia , Oxidopamina/farmacologia , Transtornos Parkinsonianos/induzido quimicamente , Ratos , Ratos Sprague-Dawley
15.
Artigo em Inglês | MEDLINE | ID: mdl-34245965

RESUMO

Although many studies have shown that lncRNA, a non-coding RNA with a length of more than 200 bases, is involved in various biological functions, including the immune process, stress process, and cell development process. However, the function of lncRNA in abalone, especially in immunity, has been rarely studied. H. discus hannai and H. diversicolor are two main aquaculture abalone, and their growth is easily affected by the main pathogen Vibrio parahaemolyticus. Through rigorous screening procedures for transcripts in this study, we found that lncRNAs were 34,240, 23,022 in Haliotis diversicolor and H. discus hannai injected with V. parahaemolyticus, respectively. We also identified the unique and common lncRNAs and mRNAs of two abalone species for the first time; the shared lncRNAs and mRNAs in Haliotis diversicolor and H. discus hannai were 2352 and 13,165, respectively. Then gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed target genes of common and unique lncRNAs has shown that common lncRNAs could be widely involved in the biological processes of stress and cell development in both abalone species. In contrast, unique lncRNAs are linked to the Toll-like receptor, NF-kappaB signaling pathway of H. diversicolor, and pattern recognition receptors and lectins immune-related pathways of H. discus hannai. The co-expression network shows that some immune-related genes, such as INFK1, INFK2, CASP2, CASP8, IRAK1, lectin C, were closely related to lncRNAs. Further, we identified the targeted relationship between some immune-related genes and lncRNAs by qRT-PCR, through which we showed that the expression trend between targeted genes, such as INFK1 and Lnc7057, lectin C and Lnc6943, Lnc5637, and PLCG1 and Lnc1692, were consistent. In general, our results showed that lncRNA expression was induced in the two species of abalone after being infected with V. parahaemolyticus, and lncRNA was involved in the immune response of abalone by targeting coding genes.


Assuntos
Gastrópodes , RNA Longo não Codificante , Vibrio parahaemolyticus , Animais , Gastrópodes/genética , Ontologia Genética , Imunidade , RNA Longo não Codificante/genética
16.
Can J Neurol Sci ; 37(2): 229-34, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20437934

RESUMO

OBJECTIVE: Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture. METHODS: We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the AnnexinV-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA. RESULTS: We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly. CONCLUSIONS: Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.


Assuntos
Acetilcolina/metabolismo , Acetilcisteína/análogos & derivados , Apoptose/efeitos dos fármacos , Inibidores de Cisteína Proteinase/farmacologia , Acetilcisteína/farmacologia , Animais , Anexina A5/metabolismo , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina C/metabolismo
17.
ACS Appl Mater Interfaces ; 12(12): 14272-14279, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32129592

RESUMO

To date, ionogel sensors have aroused the extensive interest as an alternative to hydrogel sensors, as they are promising materials to solve the problems of easy drying and easy freezing. However, the weak mechanical properties of ionogels have seriously hindered their large-scale application. Herein, a robust physically linked double-network ionogel (DN ionogel) was fabricated via interpenetrating a poly(hydroxyethyl acrylate) network into an agarose network in 1-ethyl-3-methylimidazolium chloride. The DN ionogel possessed good mechanical properties, high transparency, extreme temperature tolerance, and excellent self-adhesion. The superior electromechanical properties render the DN ionogel as a perfect candidate to be utilized as a strain sensor to monitor various human activities. In addition, the DN ionogel exhibited reasonably high sensitivity to temperature. Therefore, it is believed that this high performance strain-temperature bimodal sensor offers a promising prospect in flexible intelligent electronics.

18.
Neurochem Res ; 34(3): 528-35, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18758955

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive impairment of memory and cognition. Previous data have shown that beta-amyloid (Abeta) cascade plays a central role in AD pathophysiology and thus drugs regulate amyloid precursor protein (APP) metabolism may have therapeutic potential. Here the effects of PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, on APP processing were investigated. Using SH-SY5Y(APP695) cells, it showed that PMS777 treatment caused significant decreased secretion of sAPPalpha into the conditioned media without affecting cellular holoAPP synthesis. When PC12 cells were incubated with PMS777, the same effect was observed. The data also indicated that 10 muM PMS777 incubation decreased the release of Abeta42 into the cell media as compared with vehicle group in SH-SY5Y(APP695) cells. Pretreatment of cells with M-receptor scopolamine antagonized the decreased secretion of sAPPalpha induced by PMS777, but N-receptor alpha-bungarotoxin pretreatment did not have such an effect. These results indicated that PMS777 could modulate APP processing in vitro and that decreasing Abeta generation might demonstrate its therapeutic potential in AD.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Inibidores da Colinesterase/farmacologia , Furanos/farmacologia , Fator de Ativação de Plaquetas/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Bungarotoxinas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Antagonistas Muscarínicos/farmacologia , Ratos , Escopolamina/farmacologia
19.
Mol Brain ; 11(1): 75, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30563578

RESUMO

Accumulating evidence indicates that microglia activation is associated with an increased risk for developing Parkinson's disease (PD). With the progressive and selective degeneration of dopaminergic (DA) neurons, proinflammatory cytokines are elevated in the substantia nigra (SN) of PD patients. Thus, anti-inflammation has become one of the therapeutic strategies of PD. Eriocalyxin B (EriB), a diterpenoid isolated from Isodoneriocalyx, was previously reported to have anti-inflammatory effects. MPTP mouse model and MPP+ cell model were prepared to detect the role of EriB in regulating microglia activation and neuron protection. Midbrain tissue and primary cultured microglia and neuron were used to examine microglia activation and neuron damage by immunofluorescence, real-time PCR, western-blot and Elisa assay. Open field activity test was to evaluate the changes of behavioral activity in MPTP-induced PD mouse model. EriB was efficacious in protecting DA neurons by inhibiting microglia activation in PD mice model. Treatment with EriB led to amelioration of disordered sports of PD mice model, which correlated with reduced microglia-associated inflammation and damaged DA neurons. EriB treatment abolished MPP+ induced microglia activation damages to DA neurons in a microglia and DA neurons co-culture system. The underlying mechanism of EriB-induced protective effects involved inhibition of microglia associated proinflammatory cytokines production through the phenotypic shift of microglial cells as well as activator of transcription and nuclear factor-κB (NF-κB) signaling pathways. These findings demonstrate that EriB exerts potent anti-inflammatory effects through selective modulation of microglia activation by targeting NF-κB signaling pathways, thus exerting the protective effect against on MPP+-induced DA neurons injury. This study may provide insights into the promising therapeutic role of EriB for PD.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Diterpenos/farmacologia , Neurônios Dopaminérgicos/patologia , Microglia/patologia , NF-kappa B/metabolismo , Transdução de Sinais , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Diterpenos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Fenótipo , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
20.
Neurochem Int ; 50(1): 39-50, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16971022

RESUMO

Increasing evidence suggests the involvement of immune/inflammatory system in Parkinson's disease (PD). Many immune/inflammatory factors may synergistically participate in PD. In this study, we demonstrated that immunoglobulin G from the serum of 4/11 PD patients (PDIgG, 60microg/ml) and recombinant human C5a (0.1nM) synergistically induced selective dopaminergic neurodegeneration in rat mesencephalic neuron-glia cultures, while that PDIgG alone or C5a alone was minimally toxic or nontoxic. IgG from 17 disease controls and from 7 normal controls did not significantly induce dopaminergic neurotoxicity in the cultures even in the presence of C5a. Using mesencephalic neuron-enriched cultures, we found that the synergistic dopaminergic neurotoxicity was mediated by glia. The results from microglia-supplemented neuronal cultures, astroglia-supplemented neuronal cultures and neuron-astroglia cocultures indicated that microglia, not astroglia, played a pivotal role in the neurotoxicity. Through immunocytochemistry analysis and assay of proinflammatory factors, we observed that each of the four PDIgGs (60microg/ml) and C5a (0.1nM) synergistically induced microglia activation and production of superoxide and nitric oxide (NO) in neuron-glia cultures. Further investigations indicated that superoxide and NO were both responsible for the synergistic neurotoxicity. Finally, using F(ab')(2) fragments of PDIgG, we demonstrated that microglial Fc receptors may play an important role in the neurotoxicity. Our work provides new evidence for the involvement of the immune/inflammatory system in PD and helpful clues for studying the combined effect of antibody and complement on microglia.


Assuntos
Complemento C5a/metabolismo , Dopamina/metabolismo , Imunoglobulina G/metabolismo , Microglia/metabolismo , Doença de Parkinson/metabolismo , Animais , Células Cultivadas , Neurônios/metabolismo , Ratos
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