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1.
Stem Cells ; 41(2): 126-139, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573434

RESUMO

Human induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating organoids rely on Matrigel, whose batch-to-batch variability and xenogeneic source pose challenges to mechanistic research and translation to human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived organoids developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific functions than organoids formed on Matrigel. We show that RWVs produce highly functional liver organoids in part by eliminating the need for Matrigel, which has adverse effects on hepatic lineage differentiation. RWV liver organoids sustain durable function over long-term culture and express a range of mature functional genes at levels comparable to adult human liver, while retaining some fetal features. Our results indicate that RWVs provide a simple and high-throughput way to generate Matrigel-free liver organoids suitable for research and clinical applications.


Assuntos
Células-Tronco Pluripotentes Induzidas , Adulto , Humanos , Fígado , Organoides , Hepatócitos , Diferenciação Celular
2.
Int J Mol Sci ; 25(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38791280

RESUMO

Synchronous colorectal cancer (sCRC) is characterized by the occurrence of more than one tumor within six months of detecting the first tumor. Evidence suggests that sCRC might be more common in the serrated neoplasia pathway, marked by the CpG island methylator phenotype (CIMP), than in the chromosomal instability pathway (CIN). An increasing number of studies propose that CIMP could serve as a potential epigenetic predictor or prognostic biomarker of sCRC. Therapeutic drugs already used for treating CIMP-positive colorectal cancers (CRCs) are reviewed and drug selections for sCRC patients are discussed.


Assuntos
Neoplasias Colorretais , Ilhas de CpG , Metilação de DNA , Fenótipo , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Prognóstico , Biomarcadores Tumorais/genética , Epigênese Genética , Antineoplásicos/uso terapêutico
3.
Molecules ; 29(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611798

RESUMO

Efforts to develop high-performance electrocatalysts for the hydrogen evolution reaction (HER) are of utmost importance in ensuring sustainable hydrogen production. The controllable fabrication of inexpensive, durable, and high-efficient HER catalysts still remains a great challenge. Herein, we introduce a universal strategy aiming to achieve rapid synthesis of highly active hydrogen evolution catalysts using a controllable hydrogen insertion method and solvothermal process. Hydrogen vanadium bronze HxV2O5 was obtained through controlling the ethanol reaction rate in the oxidization process of hydrogen peroxide. Subsequently, the intermetallic PtCoVO supported on two-dimensional graphitic carbon nitride (g-C3N4) nanosheets was prepared by a solvothermal method at the oil/water interface. In terms of HER performance, PtCoVO/g-C3N4 demonstrates superior characteristics compared to PtCo/g-C3N4 and PtCoV/g-C3N4. This superiority can be attributed to the notable influence of oxygen vacancies in HxV2O5 on the electrical properties of the catalyst. By adjusting the relative proportions of metal atoms in the PtCoVO/g-C3N4 nanomaterials, the PtCoVO/g-C3N4 nanocomposites show significant HER overpotential of η10 = 92 mV, a Tafel slope of 65.21 mV dec-1, and outstanding stability (a continuous test lasting 48 h). The nanoarchitecture of a g-C3N4-supported PtCoVO nanoalloy catalyst exhibits exceptional resistance to nanoparticle migration and corrosion, owing to the strong interaction between the metal nanoparticles and the g-C3N4 support. Pt, Co, and V simultaneous doping has been shown by Density Functional Theory (DFT) calculations to enhance the density of states (DOS) at the Fermi level. This augmentation leads to a higher charge density and a reduction in the adsorption energy of intermediates.

4.
Phys Chem Chem Phys ; 25(32): 21661-21672, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37551545

RESUMO

Since electrocatalytic oxygen evolution (OER) is a four-electron transfer reaction with very slow kinetics, there is great competition to develop cheap, durable and efficient catalysts for oxygen evolution. A molecular model is designed for density functional theory (DFT) simulation calculations to guide the experiment, and this hypothesis is fully supported by the experimental data. Herein, regulating the composition and morphology of the bimetallic VCo and MoCo sulfide and monometallic sulfide nanoparticles (NPs) at the oil-water interface was achieved via a one-step hydrothermal method for efficient and durable OER electrocatalysts. Compared to CoS and MoCoS, the VCoS NPs show superior OER performance. By adjusting the atomic composition ratio of the VCoS nanoparticles, the VCoS NPs (1 : 2 : 1.5 mole ratio) showed a significant OER overpotential η = 255 mV (10 mA cm-2), and their outstanding stability was demonstrated after 48 h of continuous testing. The CoS and MoCoS NPs were also tested for comparison. Density functional theory (DFT) calculations showed that appropriate V doping (VCoS) can heighten the density of states (DOS) of the Fermi level, which generates more charge density and reduces the intermediate adsorption energy. This study not only provides efficient and powerful integrated catalysts, but also details a DFT calculation model guided by experiments to regulate the oxygen insertion technology, thus leading to the design of ideal materials and enabling more far-reaching applications in electrocatalysis.

5.
Nature ; 469(7330): 428-31, 2011 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-21248852

RESUMO

General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels (pLGICs) such as inhibitory GABA(A) (γ-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus (GLIC), whose X-ray structure was recently solved, is also sensitive to clinical concentrations of general anaesthetics. Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC. These reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer. Both molecules establish van der Waals interactions with the protein; propofol binds at the entrance of the cavity whereas the smaller, more flexible, desflurane binds deeper inside. Mutations of some amino acids lining the binding site profoundly alter the ionic response of GLIC to protons, and affect its general-anaesthetic pharmacology. Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects. These data provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs.


Assuntos
Anestésicos Gerais/química , Anestésicos Gerais/metabolismo , Cianobactérias/química , Isoflurano/análogos & derivados , Canais Iônicos de Abertura Ativada por Ligante/química , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Propofol/química , Sítios de Ligação/genética , Cristalografia por Raios X , Desflurano , Fenômenos Eletrofisiológicos , Isoflurano/química , Isoflurano/metabolismo , Canais Iônicos de Abertura Ativada por Ligante/genética , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Propofol/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Prótons
6.
Proc Natl Acad Sci U S A ; 108(29): 12143-8, 2011 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-21730130

RESUMO

Pentameric ligand-gated ion channels (pLGICs), which mediate chemo-electric signal transduction in animals, have been recently found in bacteria. Despite clear sequence and 3D structure homology, the phylogenetic distance between prokaryotic and eukaryotic homologs suggests significant structural divergences, especially at the interface between the extracellular (ECD) and the transmembrane (TMD) domains. To challenge this possibility, we constructed a chimera in which the ECD of the bacterial protein GLIC is fused to the TMD of the human α1 glycine receptor (α1GlyR). Electrophysiology in Xenopus oocytes shows that it functions as a proton-gated ion channel, thereby locating the proton activation site(s) of GLIC in its ECD. Patch-clamp experiments in BHK cells show that the ion channel displays an anionic selectivity with a unitary conductance identical to that of the α1GlyR. In addition, pharmacological investigations result in transmembrane allosteric modulation similar to the one observed on α1GlyR. Indeed, the clinically active drugs propofol, four volatile general anesthetics, alcohols, and ivermectin all potentiate the chimera while they inhibit GLIC. Collectively, this work shows the compatibility between GLIC and α1GlyR domains and points to conservation of the ion channel and transmembrane allosteric regulatory sites in the chimera. This provides evidence that GLIC and α1GlyR share a highly homologous 3D structure. GLIC is thus a relevant model of eukaryotic pLGICs, at least from the anionic type. In addition, the chimera is a good candidate for mass production in Escherichia coli, opening the way for investigations of "druggable" eukaryotic allosteric sites by X-ray crystallography.


Assuntos
Proteínas de Bactérias/metabolismo , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína/fisiologia , Receptores de Glicina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Álcoois , Sequência de Aminoácidos , Anestésicos Gerais , Animais , Proteínas de Bactérias/genética , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Cricetinae , DNA Complementar/genética , Eletrofisiologia , Ivermectina , Canais Iônicos de Abertura Ativada por Ligante/genética , Dados de Sequência Molecular , Oócitos/metabolismo , Técnicas de Patch-Clamp , Propofol , Estrutura Terciária de Proteína/genética , Receptores de Glicina/genética , Proteínas Recombinantes de Fusão/genética , Análise de Sequência de DNA , Xenopus
7.
Foods ; 12(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36766206

RESUMO

Plant fiber/plastic composites (PPCs) have been widely used in food contact materials (FCMs) for many benefits, such as their claimed better environmental footprint compared to conventional plastics. However, their safety is still not fully understood and must be comprehensively evaluated. Non-volatiles extracted from six PPCs with different plant fibers and polymer matrices were characterized by employing ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in combination with various spectral libraries and manual elucidation, taking into account spectral similarity and characteristic product ions. A total of 115 compounds were tentatively identified, 50 of which were oligomers or their derivatives from the sample with polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) as the polymer matrix, and some of them were Cramer rules class III substances based on the threshold of toxicological concern (TTC). Seven reaction products between PLA and PBAT monomers, as well as four derivatives of melamine, were elucidated and well detailed for the first time. In addition, bisphenol S was detected in all samples even though its origin remains to be further explored. Isoprothiolane, as an insecticide and fungicide used to control a range of rice pests, was identified in the sample with rice husk as fillers, experimentally confirming the presence of agrochemicals in samples containing plant fibers.

8.
Biomedicines ; 11(2)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36830778

RESUMO

Disorders/differences of sex development (DSDs) are a group of rare and phenotypically variable diseases. The underlying genetic causes of most cases of 46XY DSDs remains unknown. Despite the advent of genetic testing, current investigations of the causes of DSDs allow genetic-mechanism identification in about 20-35% of cases. This study aimed primarily to establish a rapid and high-throughput genetic test for undervirilized males with and without additional dysmorphic features. Routine chromosomal and endocrinological investigations were performed as part of DSD evaluation. We applied whole-exome sequencing (WES) complemented with multiplex ligation-dependent probe amplification to seek explainable genetic causes. Integrated computing programs were used to call and predict the functions of genetic variants. We recruited 20 patients and identified the genetic etiologies for 14 (70%) patients. A total of seven of the patients who presented isolated DSD phenotypes were found to have causative variants in the AR, MAP3K1, and FLNA genes. Moreover, the other seven patients presented additional phenotypes beyond undervirilized genitalia. Among them, two patients were compatible with CHARGE syndrome, one with Robinow syndrome, and another three with hypogonadotropic hypogonadism. One patient, who carried a heterozygous FLNA mutation, also harbored a heterozygous PTPN11 mutation and thus presented some phenotypes of Noonan syndrome. We identified several genetic variants (12 nonsense mutations and one microdeletion) that account for syndromic and nonsyndromic DSDs in the Taiwanese population. The identification of these causative genes extended our current understanding of sex development and related congenital disorders.

9.
Front Microbiol ; 14: 1137369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065141

RESUMO

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood. Methods: We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman's rank correlation coefficient test. Results: Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated. Conclusion: Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

10.
J Hazard Mater ; 424(Pt B): 127417, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34673397

RESUMO

Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology.


Assuntos
Hidrolases , Polietilenotereftalatos , Fluorescência , Plásticos , Biologia Sintética
11.
J Colloid Interface Sci ; 582(Pt A): 112-123, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32814219

RESUMO

Multifunctional cotton fabrics have attracted significant attention as next-generation wearable materials. Herein, we report a facile method for the fabrication of flexible and wearable cotton fabrics with ultra-high electromagnetic interference (EMI) shielding, antibacterial, and superhydrophobic properties. Cotton fabrics were first coated chemically with silver nanoparticles using polydopamine as adhesive and then with hydrophobic polydimethylsiloxane or polyimide. The introduction of polydopamine significantly increased the bond between silver nanoparticles and cotton fibers, thereby preventing silver nanoparticles from falling off the surface. The composite fabrics exhibited a high conductivity of ~1000 S/cm, and their EMI shielding effectiveness increased up to ~110 dB. The composite fabrics exhibited excellent self-cleaning performance and acid-alkali corrosion resistance because of their superhydrophobicity. Notably, the fabric composites showed a significant antibacterial action against Staphylococcus aureus and Escherichia coli.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Fibra de Algodão , Interações Hidrofóbicas e Hidrofílicas , Micro-Ondas , Polímeros , Prata/farmacologia
12.
Anesth Analg ; 110(1): 59-63, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19933531

RESUMO

A prokaryotic member of the gamma-aminobutyric acid type A receptor superfamily (GLIC) was recently cloned from the cyanobacterium Gloeobacter violaceus, its function characterized, and its 3-dimensional x-ray diffraction crystal structure determined. We report its modulation by 9 anesthetics using 2-electrode voltage clamping in Xenopus laevis oocytes. Desflurane, halothane, isoflurane, sevoflurane, and propofol inhibited currents through GLIC at and below concentrations used clinically. Hill numbers averaged 0.3, indicating negative cooperativity or multiple sites or mechanisms of action. A 2-site model fit the data for desflurane and halothane better than a 1-site model. Xenon and etomidate modulated GLIC at or above clinical concentrations, with no cooperativity. Ethanol and nitrous oxide did not modulate GLIC at surgical anesthetic concentrations. These investigations lay the groundwork for further structural and functional studies of anesthetic actions on GLIC.


Assuntos
Anestésicos/farmacologia , Cianobactérias/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Algoritmos , Anestésicos Inalatórios/farmacologia , Animais , Depressores do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Etanol/farmacologia , Feminino , Oócitos/metabolismo , Técnicas de Patch-Clamp , Prótons , Receptores de GABA-A/efeitos dos fármacos , Receptores Nicotínicos/efeitos dos fármacos , Xenopus laevis
13.
J Int Med Res ; 48(3): 300060519871863, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31847632

RESUMO

OBJECTIVES: The objective was to investigate the effects of microRNA-421 against myocardial ischemia/reperfusion injury in C57BL/6 mice. METHODS: Male C57BL/6 mice (n = 27) were randomly divided into three groups: normal control (NC) group (sham-treated); I/R model group, which underwent the I30min/R24h model (ischemia for 30 minutes followed by reperfusion for 24 hours); and the miRNA group, which were injected with miR-421. Pathology was assessed by hematoxylin and eosin staining and myocardial infarct size was measured by triphenyltetrazolium chloride staining. The apoptosis rate was measured by TUNEL assay, and relative expression of toll-like receptor-4 (TLR4), Janus kinase 2 (JAK2), and signal transducer and activator of translation 3 (STAT3) was evaluated by immunohistochemistry. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and high mobility group protein B1 (HMGB1) serum concentrations were measured by ELISA. RESULTS: Compared with the NC group, in the model group, the myocardial infarction was large; inflammatory cell infiltration was severe; apoptosis was enhanced; expression of TLR4, JAK2, and STAT3 was increased; and serum concentrations of IL-6, TNF-α, IL-10, and HMGB1 were significantly increased. In the miRNA group, the ischemia/reperfusion injury was significantly improved. CONCLUSIONS: Overexpression of miRNA-421 could reduce ischemia/reperfusion inflammatory response, perhaps via inactivation of TLR4, JAK2, and STAT3.


Assuntos
Proteína HMGB1 , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Animais , Proteína HMGB1/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão/genética , Receptor 4 Toll-Like/genética
14.
JCI Insight ; 5(20)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32910808

RESUMO

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix-integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic livers. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lacked FAK in liver epithelial cells developed more severe liver injury and worse fibrosis as compared with controls. Increased fibrosis in liver epithelial FAK-deficient mice was linked to the activation of several profibrotic pathways, including the hedgehog/smoothened pathway. FAK-deficient hepatocytes produced increased Indian hedgehog in a manner dependent on matrix stiffness. Furthermore, expression of the hedgehog receptor, smoothened, was increased in macrophages and biliary cells of hepatocyte-specific FAK-deficient fibrotic livers. These results indicate that liver epithelial FAK has important regulatory roles in the response to liver injury and progression of fibrosis.


Assuntos
Células Epiteliais/metabolismo , Quinase 1 de Adesão Focal/genética , Cirrose Hepática/genética , Receptor Smoothened/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais/patologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Proteínas Hedgehog/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/lesões , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Camundongos Knockout , Transdução de Sinais/genética
15.
Phytomedicine ; 77: 153272, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32702592

RESUMO

BACKGROUND: Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. PURPOSE: To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. METHODS: Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. RESULTS: TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. CONCLUSION: TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.


Assuntos
Alcaloides/farmacologia , Alstonia/química , Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Células A549 , Alcaloides/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antivirais/química , Citocinas/metabolismo , Cães , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/tratamento farmacológico , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Replicação Viral/efeitos dos fármacos
16.
Anesth Analg ; 108(5): 1538-45, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19372333

RESUMO

INTRODUCTION: Elevated concentrations of isovaleric (IVA), methylmalonic (MMA), and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses. First, that these metabolites would have anesthetic-sparing effects, possibly being anesthetics by themselves. Second, that these compounds would modulate glycine and gamma-aminobutyric acid (GABA(A)) receptor function, increasing chloride currents through these channels as potent clinical inhaled anesthetics do. Third, that these compounds would affect physical properties of lipids. METHODS: Anesthetic EC(50)s were measured in Xenopus laevis tadpoles. Glycine and GABA(A) receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. Pressure-area isotherms of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were measured with and without added organic acids. RESULTS: IVA acid was an anesthetic in tadpoles, whereas MMA and propionic acid decreased isoflurane's EC(50) by half. All three organic acids concentration-dependently increased current through alpha(1) glycine receptors. There were minimal effects on alpha(1)beta(2)gamma(2s) GABA(A) receptors. The organic acids increased total lateral pressure (surface pressure) of DPPC monolayers, including at mean molecular areas typical of bilayers. CONCLUSION: IVA, MMA, and propionic acid have anesthetic effects in tadpoles, positively modulate glycine receptor function and affect physical properties of DPPC monolayers.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/metabolismo , Anestésicos Inalatórios/farmacologia , Membrana Celular/efeitos dos fármacos , Isoflurano/farmacologia , Ácido Metilmalônico/farmacologia , Ácidos Pentanoicos/farmacologia , Propionatos/farmacologia , Receptores de Glicina/efeitos dos fármacos , Animais , Membrana Celular/metabolismo , Cloretos/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hemiterpenos , Larva/efeitos dos fármacos , Larva/metabolismo , Potenciais da Membrana , Mutação , Pressão , Receptores de GABA-A/metabolismo , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Propriedades de Superfície , Xenopus laevis
17.
Int J Biol Macromol ; 137: 215-223, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31255620

RESUMO

Poly(butylene succinate-co-cyclohexane dimethanol succinate) (P(BS-co-CHDMS)) and poly(butylene succinate-co-butanediol cyclohexanedicarboxylic acid) (P(BS-co-BCHDA)) were catalytically degraded by Candida antarctica lipase Novozyme 435 (N435) in CHCl3 and THF. The results indicated that the degradation rate was P(BS-co-CHDMS) > P(BS-co-BCHDA) > poly(butylene succinate) (PBS). The degradation rate of copolyesters was higher in CHCl3 than in THF, the highest degradation rate of 67% being obtained for P(BS-co-CHDMS). Hence, the CHCl3 solvent is more suitable for the enzyme-catalytic degradation of copolyesters, since the lipase can easier recognize the butylene succinate (BS-), (butanediol cyclohexanedicarboxylic acid) (BCA-), and (cyclohexane dimethanol succinate-type) (CMS-type) ester bonds in this solvent. Moreover, it can recognize the CMS-type ester bonds with a higher specificity than the (butanediol cyclohexanedicarboxylic acid type) (BCA-type) ester bonds. Molecular simulation results indicated that the structure of the lipase was stable in CHCl3 and THF. However, CHCl3 proved to be more suitable for a stable activity of the enzyme. The active pocket contains acyl-binding hydrophilic residues which are recognized by the substrate. The increase in the content of saturated cycles can increase the hydrophobicity of the substrate and thus, the amount of substrate bond to enzyme active site is increased, which facilitates the enzymatic degradation of copolyesters.


Assuntos
Lipase/química , Poliésteres/química , Solventes/química , Sítios de Ligação , Catálise , Domínio Catalítico , Enzimas Imobilizadas , Proteínas Fúngicas , Hidrólise , Simulação de Dinâmica Molecular , Estrutura Molecular , Polímeros
18.
Polymers (Basel) ; 11(3)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30960399

RESUMO

In this study, first, a green and efficient NaOH/urea aqueous solution system was used to dissolve cellulose. Second, the resulting solution was mixed with sodium montmorillonite. Third, a cellulose/montmorillonite aerogel with a three-dimensional porous structure was prepared via a sol-gel process, solvent exchange and freeze-drying. The viscoelastic analysis results showed that the addition of montmorillonite accelerated the sol-gel process in the cellulose solution. During this process, montmorillonite adhered to the cellulose substrate surface via hydrogen bonding and then became embedded in the pore structure of the cellulose aerogel. As a result, the pore diameter of the aerogel decreased and the specific surface area of the aerogel increased. Furthermore, the addition of montmorillonite increased the compressive modulus and density of the cellulose aerogel and reduced volume shrinkage during the preparation process. In addition, the oil/water adsorption capacities of cellulose aerogels and cellulose/montmorillon aerogels were investigated.

20.
Int J Biol Macromol ; 140: 1175-1182, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465799

RESUMO

Traditional superhydrophobic cotton fabrics (SCFs) for oil/water separation were usually fabricated by surface coating with inorganic nanoparticles combined with nonrenewable and nonbiodegradable or even toxic fossil-based chemicals, which would lead to secondary environmental pollution after their lifetime. In this study, we report robust, nanoparticle-free, fluorine-free SFC, which was prepared by acid etching followed by surface coating with epoxidized soybean oil resin (CESO) and subsequent modification with stearic acid (STA). No toxic compound and no nanoparticle were included within the SCF and all the raw materials including cotton fabric, CESO and STA are biodegradable and derived from biological resources. The SCF showed excellent mechanical stability and chemical/environmental resistances. The superhydrophobicity of the SFC survived from mechanical abrasion, tape peeling, ultrasonication, solvent erosion and low/high temperature exposure. The SCF also exhibited good acid/alkali resistance with contact angle over 150° toward different pH water droplets. Moreover, the SCF could efficiently separate oil/water mixtures with efficiency above 97.9% and the superhydrophobicity remained after reusing for at least 10 times. The fully biological-derived SCF with excellent mechanical and chemical resistances exhibit great potential for separation of oil/water mixtures.


Assuntos
Fibra de Algodão , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Óleo de Soja/química , Água/química , Ácidos Decanoicos/química , Ácidos Dicarboxílicos/química , Temperatura , Molhabilidade
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