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1.
Chemosphere ; 257: 127154, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32512328

RESUMO

Carcinogenic polycyclic aromatic hydrocarbons (cPAHs) in ambient PM2.5 and a specific molecular marker of biomass burning, levoglucosan, are used to investigate the influence on public health of biomass burning. In this work, we present an effective method for one-time analysis of cPAHs and levoglucosan by GC-MS without derivatization. The method was applied for the analysis of PM2.5 samples (64.3 ±â€¯17.6 µg m-3, n = 57) collected during a smoke haze period in Chiang Mai, Thailand. Levoglucosan was analyzed by using both the developed method (GC-MS) and a reference method (HPAEC-PAD) for comparison. Its average concentration obtained from GC-MS (0.31 ±â€¯0.21 µg m-3) was about 4 times less than the concentration obtained from the reference method (1.22 ±â€¯0.76 µg m-3). Therefore, a correcting factor (CF = 4) was used as a multiplying factor, to obtain a comparative value (1.23 ±â€¯0.86 µg m-3). The average concentration of cPAHs found in PM2.5 samples was 5.88 ±â€¯1.97 ng m-3 with the highest value of 10.86 ng m-3 indicating medium to high cancer risk due to PAHs exposure when referring to values of toxicity equivalence and inhalation cancer risk. Diagnostic ratios of BaA/(BaA + CHR) (0.48 ± 0.04) and IND/(IND + BPER) (0.58 ± 0.04) and strong correlations between PM2.5, levoglucosan and cPAHs concentrations implied that the major source of air pollution in the study period was biomass burning. PM2.5 concentration as a pollution indicator was labelled as BB-low, BB-medium, BB-high or BB-extreme; <50, 50-75, 75-100 and > 100 µg m-3, respectively. The levoglucosan and cPAHs concentration during BB-extreme pollution was 4.3 times and 2.34 times, respectively, that during BB-low pollution, and the correlation coefficient (r) between the concentrations of levoglucosan and cPAHs was as high as 0.987, indicating that the more intense the burning of biomass, the higher the carcinogenic risk in the urban air.


Assuntos
Poluentes Atmosféricos/toxicidade , Monitoramento Ambiental/métodos , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Biomassa , Carcinógenos/análise , Poluição Ambiental/análise , Cromatografia Gasosa-Espectrometria de Massas , Glucose/análogos & derivados , Humanos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Estações do Ano , Fumaça/análise , Tailândia
2.
Sci Total Environ ; 733: 138991, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32470716

RESUMO

Levoglucosan, an anhydrosaccharide, is commonly used as an organic tracer for biomass burning, but has also been identified from coal smoke particulate matter (PM) including lignites. Here we showed that stable carbon isotope analysis specifically of levoglucosan may be one possible way to determine the relative contributions from coal combustion versus biomass burning sources. PM samples were collected from low-temperature burning/smoldering of Miocene lignites from Poland and basket willow (Salix viminalis L.) representative of biomass. The calculated levoglucosan δ13C values of xylites varied from -23.6 to -21.6‰, while for detritic coal samples they ranged from -24.2 to -23.1‰, with means of -22.7 and -23.7‰, respectively. The calculated levoglucosan δ13C value of basket willow wood was -27.1‰. Values of willow wood mixtures with xylite varied from -25.8 to -23.4‰ (with an increasing proportion of xylite), while values of mixtures of willow and detritic coal ranged from -26.9 to -24.6‰ (with an increasing proportion of detritic coal). The δ13C values for the mixtures changed proportionally to the contents of individual components with R2 = 0.88 and 0.89 for willow with xylite and detritic coal, respectively. The hopanoid distributions characteristic for low-temperature lignite/peat burning, with a predominance of 22R-α,ß-homohopane, ßß-hopanes and hopenes, as well as low or very low values of the homohopane index, were observed in smoke PM from most lignite samples and absent in the basket willow sample. Thus, the relatively high content of hopanes (with the occurrence of 22R-α,ß-homohopane, ßß-hopanes and hopenes) in atmospheric PM samples can be treated as additional tracers of lignite combustion.


Assuntos
Poluentes Atmosféricos/análise , Carvão Mineral/análise , Biomassa , Monitoramento Ambiental , Glucose/análogos & derivados , Material Particulado/análise , Polônia , Temperatura
3.
Waste Manag ; 108: 70-77, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32335489

RESUMO

Levoglucosan is served as a significant versatile product to generate high value-added chemicals and pharmaceutical additives. Levoglucosan was predominately produced from pyrolysate of cellulose. However, the direct fast pyrolysis of waste biomass produces a small quantity of levoglucosan in comparison with the theoretical value of cellulose. This study explored Fenton pretreatment as a possible route to enhance levoglucosan yield during the fast pyrolysis of the waste corncob. The experimental results showed that different Fenton pretreated conditions and pyrolytic temperatures played vital roles in the formation of levoglucosan. The levoglucosan yield from fast pyrolysis at 500 °C of corncob pretreated by Fenton reaction of 14 mL/g H2O2 and 16 mM FeSO4 was about 95% higher than that of the untreated corncob. Additionally, Fenton pretreated corncob was capable of obtaining the levoglucosan at a low pyrolytic temperature (300 °C). It was mainly attributed to the effective disrupting of biomass structures and the selective degradation of lignin and hemicellulose during pretreatment. Furthermore, the powerful removal of alkali and alkaline earth metals during Fenton pretreatment was beneficial to increasing the levoglucosan yield. These findings demonstrate that Fenton pretreatment can provide a novel effective method to enhance levoglucosan yield during biomass fast pyrolysis.


Assuntos
Peróxido de Hidrogênio , Pirólise , Biomassa , Glucose/análogos & derivados , Lignina
4.
Nature ; 580(7804): 511-516, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32322067

RESUMO

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1-3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.


Assuntos
Encéfalo/fisiologia , Comportamento de Escolha/fisiologia , Açúcares da Dieta/metabolismo , Preferências Alimentares/fisiologia , Glucose/metabolismo , Intestinos/fisiologia , Animais , Encéfalo/citologia , Açúcares da Dieta/química , Glucose/análogos & derivados , Glucose/química , Masculino , Metilglucosídeos/química , Metilglucosídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Paladar/fisiologia , Tiazinas/metabolismo , Água/metabolismo
5.
Bioresour Technol ; 307: 123179, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32222688

RESUMO

This study aimed to evaluate the environmental impacts (i.e. global warming potential (GWP) and resource depletion (RD)) of the bio-based levoglucosan production process through fast pyrolysis of cotton straw via life cycle assessment (LCA). An LCA model consisting of feedstock transportation, biomass pretreatment, fast pyrolysis, bio-oil transportation, bio-oil recovery and levoglucosan extraction was developed. Results indicated that GWP and RD of bio-based levoglucosan production were approximately 2 and 32.5 times less than that of the petroleum-based counterpart. Sensitivity analysis showed that the GWP and RD of levoglucosan production were highly sensitive to plant size, hydrochloric acid usage, cooling energy, levoglucosan yield and bio-oil yield. The results of this research could provide a framework for robust decision making at an industrial level, which is useful for the commercial-scale production of levoglucosan.


Assuntos
Biocombustíveis , Pirólise , Biomassa , Glucose/análogos & derivados
6.
Environ Pollut ; 260: 114029, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32018200

RESUMO

Extreme droughts associated with changes in the climate have occurred every 5 years in the Amazon during the 21st century, with the most severe being in 2015. The increase in biomass burning (BB) events that occurred during the 2015 drought had several negative socioeconomic and environmental impacts, one of which was a decrease in the air quality. This study is an investigation into the air quality in the Manaus Metropolitan Region (MMR) (central Amazon, Brazil) during the dry (September to October) and wet (April to May) seasons of 2015 and 2016. A strong El Niño event began during the wet season of 2015 and ended during the wet season of 2016. Particulate matter samples were collected in the MMR during 2015 and 2016, and analyses of the satellite-estimated total carbon monoxide (CO) column and observed levoglucosan concentrations were carried out. Levoglucosan has been shown to be significantly correlated with regional fires and is a well-established chemical tracer for the atmospheric particulates emitted by BB, and CO can be treated as a gaseous-phase tracer for BB. The number of BB events increased significantly during the El Niño period when compared to the average number during 2003-2016. Consequently, the total CO column and levoglucosan concentration values in the MMR increased by 15% and 500%, respectively, when compared to the normal conditions. These results indicate that during the period that was analyzed, the impacts of BB were exacerbated during the strong El Niño event as compared to the non-El Niño period. In this study, we provided evidence that the air quality in the MMR will degrade in the future if droughts and BB occurrences continue to increase.


Assuntos
El Niño Oscilação Sul , Monitoramento Ambiental , Fogo , Glucose/análogos & derivados , Biomassa , Brasil , Monóxido de Carbono , Secas , Glucose/análise , Estações do Ano
7.
Nature ; 579(7799): 443-447, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32103179

RESUMO

In eukaryotic protein N-glycosylation, a series of glycosyltransferases catalyse the biosynthesis of a dolichylpyrophosphate-linked oligosaccharide before its transfer onto acceptor proteins1. The final seven steps occur in the lumen of the endoplasmic reticulum (ER) and require dolichylphosphate-activated mannose and glucose as donor substrates2. The responsible enzymes-ALG3, ALG9, ALG12, ALG6, ALG8 and ALG10-are glycosyltransferases of the C-superfamily (GT-Cs), which are loosely defined as containing membrane-spanning helices and processing an isoprenoid-linked carbohydrate donor substrate3,4. Here we present the cryo-electron microscopy structure of yeast ALG6 at 3.0 Å resolution, which reveals a previously undescribed transmembrane protein fold. Comparison with reported GT-C structures suggests that GT-C enzymes contain a modular architecture with a conserved module and a variable module, each with distinct functional roles. We used synthetic analogues of dolichylphosphate-linked and dolichylpyrophosphate-linked sugars and enzymatic glycan extension to generate donor and acceptor substrates using purified enzymes of the ALG pathway to recapitulate the activity of ALG6 in vitro. A second cryo-electron microscopy structure of ALG6 bound to an analogue of dolichylphosphate-glucose at 3.9 Å resolution revealed the active site of the enzyme. Functional analysis of ALG6 variants identified a catalytic aspartate residue that probably acts as a general base. This residue is conserved in the GT-C superfamily. Our results define the architecture of ER-luminal GT-C enzymes and provide a structural basis for understanding their catalytic mechanisms.


Assuntos
Microscopia Crioeletrônica , Retículo Endoplasmático/enzimologia , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Biocatálise , Domínio Catalítico , Sequência Conservada , Dolicol Monofosfato Manose/metabolismo , Fosfatos de Dolicol/metabolismo , Glucose/análogos & derivados , Glucose/metabolismo , Glicosiltransferases/deficiência , Técnicas In Vitro , Lipídeos , Proteínas de Membrana/deficiência , Modelos Moleculares , Mutação , Monossacarídeos de Poli-Isoprenil Fosfato/química , Monossacarídeos de Poli-Isoprenil Fosfato/metabolismo , Ligação Proteica , Saccharomyces cerevisiae/genética , Especificidade por Substrato
8.
J Chromatogr A ; 1610: 460557, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31570193

RESUMO

Biomass burning (BB) emissions are a significant source of particles to the atmosphere, especially in the Southern Hemisphere, where the occurrence of anthropogenic and natural wild fires is common. These emissions can threaten human health through increased exposure, whilst simultaneously representing a significant source of trace metals and nutrients to the ocean. One well known method to track BB emissions is through monitoring the atmospheric concentration of specific monosaccharide anhydrides (MAs), specifically levoglucosan and its isomers, mannosan and galactosan. Herein, a new method for the determination of levoglucosan and its isomers in marine and terrestrial aerosol samples is presented, which delivers both high selectivity and sensitivity, through the coupling of ion chromatography and triple quadrupole tandem mass spectrometry. Optimal chromatographic conditions, providing baseline separation for target anhydrosugars in under 8 min, were obtained using a Dionex CarboPacⓇ PA-1 column with an electrolytically generated KOH gradient. To improve the ionisation efficiency for MS detection, an organic make-up solvent was fed into the IC column effluent before the ESI source, and to further increase both sensitivity and selectivity, cationisation of levoglucosan was investigated by adding salts into the make-up solvent, namely, sodium, ammonium and lithium salts. Using positive lithium cationisation with 0.5 mM lithium chloride in methanol as the make-up solvent, delivered at a flow rate of 0.02 mL min-1, the levoglucosan response was improved by factors of 100 and 10, comparing to negative ionisation and positive sodium cationisation, respectively. Detection was carried out in SRM mode for quantitation and identification, achieving an instrumental LOD of 0.10, 0.12 and 0.5 µg L-1 for levoglucosan, mannosan and galactosan, respectively. Finally, the method was applied to the analysis of 41 marine and terrestrial aerosol samples from Australia, its surrounding coastal waters and areas within the remote Southern Ocean, covering a large range of BB marker concentrations.


Assuntos
Atmosfera/química , Cromatografia/métodos , Glucose/análogos & derivados , Lítio/química , Espectrometria de Massas em Tandem/métodos , Anidridos/análise , Atmosfera/análise , Austrália , Cátions , Monitoramento Ambiental/métodos , Galactose/análogos & derivados , Galactose/análise , Glucose/análise , Isomerismo , Limite de Detecção , Manose/análogos & derivados , Manose/análise , Monossacarídeos/análise , Padrões de Referência
9.
Eur J Pharm Sci ; 141: 105091, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655208

RESUMO

In this paper, we studied the impact of saccharides having a similar backbone but differing in the degree of freedom, local molecular mobility, flexibility of the ring and intermolecular interactions on the glass-forming ability (GFA) of naproxen (NAP) in binary mixtures. For this purpose, a series of methyl and acetyl derivatives of glucose (GLS) and anhydroglucose (anhGLS), as well as neat anhGLS have been used to produce homogeneous solid dispersions (SDs) of varying molar concentration of examined active pharmaceutical ingredient (API). Systematic measurements with the use of Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS) enabled us to determine the phase transitions, homogeneity and molecular mobility of the investigated binary mixtures as well as the impact of excipient on the crystallization tendency of NAP. It turned out that acetylated glucose (acGLS), one of the most mobile and flexible saccharides of all examined herein materials, is the best excipient enhancing the GFA of studied API. Although, it should be noted that upon storage at room temperature, we observed the recrystallization of NAP from binary mixtures. Interestingly, API always crystallized to the initial polymorphic form, as shown by X-ray diffraction (XRD) investigations. Finally, since additional measurements with the use of Fourier Transform Infrared (FTIR) Spectroscopy clearly indicated that there are no significant differences in the intermolecular interactions in the systems composed of NAP and all examined saccharides, one can postulate that the mobility and ring flexibility of the matrix have, , the most important impact on the crystallization tendency of NAP upon cooling. Consequently, it seems that in some cases, more mobile/flexible matrices can be a much better choice to enhance the glass-forming ability of studied pharmaceutical.


Assuntos
Anti-Inflamatórios não Esteroides/química , Vidro/química , Glucose/análogos & derivados , Glucose/química , Naproxeno/química , Cristalização
10.
J Med Chem ; 63(2): 747-755, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31846326

RESUMO

Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.


Assuntos
Radioisótopos de Flúor/química , Galectina 3/antagonistas & inibidores , Glucose/farmacologia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Animais , Feminino , Glucose/análogos & derivados , Glucose/síntese química , Meia-Vida , Marcação por Isótopo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Long-Evans , Distribuição Tecidual
11.
Nephrol Ther ; 15(6): 439-447, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31585841

RESUMO

Many apheresis techniques can be performed in a blood-bank facility or a hemodialysis (HD) facility. However, it makes sense to perform apheresis in a hemodialysis facility as apheresis involves extra-corporeal circuits and because HD can be performed at the same time as apheresis (tandem procedure). Apheresis techniques comprise therapeutic plasma exchange, double-filtration plasmapheresis, and its derivative (rheopheresis and LDL-apheresis), and immunoadsorption (specific and semi-specific). We have setup an apheresis platform in our hospital that fulfills health recommendations. This process has involved financial investment and significant human resources, and has enabled us to network with different specialties (neurology, hematology, vascular medicine). We have setup protocols according to the type of pathology to be treated by apheresis, and to monitor clinical and biological data for each apheresis session. The main side effects of apheresis are a fall in blood pressure when a session is initiated, an increase in fluid overload, hypocalcemia, and the loss of some essential plasmatic factors. However, these side-effects are easily identified and can be properly managed in real time. Within two-years, we have performed 1845 apheresis sessions (134 patients). Of these, 66 received apheresis before and/or after kidney transplantation for ABO and/or HLA incompatibility (desensitization), for humoral rejection, or in the setting of relapsing focal-segmental glomerulosclerosis. Our patients' outcomes have been similar to those reported in the literature. The other 68 patients had various conditions. Because our program is now well-established, we are currently forming a specialist center to train physicians and nurses in the various apheresis techniques/procedures.


Assuntos
Remoção de Componentes Sanguíneos , Unidades Hospitalares de Hemodiálise/organização & administração , Remoção de Componentes Sanguíneos/efeitos adversos , Remoção de Componentes Sanguíneos/instrumentação , Remoção de Componentes Sanguíneos/métodos , Remoção de Componentes Sanguíneos/estatística & dados numéricos , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Grupos Diagnósticos Relacionados , Glucose/administração & dosagem , Glucose/efeitos adversos , Glucose/análogos & derivados , Necessidades e Demandas de Serviços de Saúde , Hospitais Universitários/organização & administração , Humanos , Hipocalcemia/etiologia , Hipotensão/etiologia , Transplante de Rim , Equipe de Assistência ao Paciente , Utilização de Procedimentos e Técnicas , Diálise Renal , Estudos Retrospectivos
12.
Molecules ; 24(16)2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430978

RESUMO

: The management of pain in patients affected by diabetic neuropathy still represents an unmet therapeutic need. Recent data highlighted the pain-relieving efficacy of glucosinolates deriving from Brassicaceae. The purpose of this study was to evaluate the anti-hyperalgesic efficacy of Eruca sativa defatted seed meal, along with its main glucosinolate, glucoerucin (GER), on diabetic neuropathic pain induced in mice by streptozotocin (STZ). The mechanism of action was also investigated. Hypersensitivity was assessed by paw pressure and cold plate tests after the acute administration of the compounds. Once bio-activated by myrosinase, both E. sativa defatted meal (1 g kg-1 p.o.) and GER (100 µmol kg-1 p.o., equimolar to meal content) showed a dose-dependent pain-relieving effect in STZ-diabetic mice, but the meal was more effective than the glucosinolate. The co-administration with H2S scavengers abolished the pain relief mediated by both E. sativa meal and GER. Their effect was also prevented by selectively blocking Kv7 potassium channels. Repeated treatments with E. sativa meal did not induce tolerance to the anti-hypersensitive effect. In conclusion, E. sativa meal can be suggested as a new nutraceutical tool for pain relief in patients with diabetic neuropathy.


Assuntos
Brassicaceae/química , Neuropatias Diabéticas/complicações , Glucose/análogos & derivados , Imidoésteres/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Glucose/farmacologia , Glucosinolatos/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sementes/química , Estreptozocina/farmacologia
13.
Scand J Rheumatol ; 48(5): 383-392, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31354003

RESUMO

Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA.


Assuntos
Artrite Experimental/tratamento farmacológico , Desoxicitidina/análogos & derivados , Glucose/análogos & derivados , Membrana Sinovial/patologia , Triterpenos/farmacologia , Animais , Artrite Experimental/diagnóstico , Artrite Experimental/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Desoxicitidina/metabolismo , Medicamentos de Ervas Chinesas , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Citometria de Fluxo , Glucose/farmacologia , Fenótipo , Radiografia , Ratos , Ratos Wistar , Membrana Sinovial/metabolismo
14.
Chemosphere ; 233: 852-861, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340411

RESUMO

A common strategy to improve indoor air quality in households burning coal and biomass is the introduction of advanced combustion solid fuel stoves, which can use existing fuels yet emit fewer pollutants. Chemical composition of PM is affected by numerous combustion parameters, but is often not considered in energy transitions, despite varying toxicity among chemical components. We analyzed PM2.5 emissions from combustion of solid fuels (coal, wood, and straw; whole and pelletized) in a variety of stoves (cookstoves and heating stoves; traditional and semi-gasifier, including forced versus natural draft and fixed versus reciprocating grate). To assess the effects of fuel and stove type on PM2.5 composition, we measured elemental carbon (EC), organic carbon (OC), water-soluble OC, water-soluble inorganic ions (e.g. SO42-, Cl-, K+), and organic molecular markers. PM2.5 emissions from traditional stoves were mostly carbonaceous: 76-90% organic matter (OM), 5-6% EC, and less than 2% inorganic ions. In contrast, semi-gasifier stoves emitted more inorganic PM2.5: on average, ions comprised 65%, 9% was OM, and 4% was EC. Within the semi-gasifier cookstoves, forced-draft cookstove emissions had lower OM (1-3%) and higher ion concentrations (84-88%) than the natural-draft cookstove (5-14% OM, 30-83% ions). Levoglucosan was detected in PM2.5 from combustion of wood in the traditional cookstove and biomass pellets in the natural-draft semi-gasifier cookstove, but not from wood pellets in the forced-draft semi-gasifier cookstove. Across a range of different fuels and stoves, stove type influenced emitted PM composition more than fuel type, underscoring the impact of combustion conditions on PM chemical composition.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Carbono/análise , Carvão Mineral/análise , Glucose/análogos & derivados , Material Particulado/análise , Biomassa , Culinária , Glucose/análise , Utensílios Domésticos , Produtos Domésticos , Madeira/química
15.
J Pharm Biomed Anal ; 175: 112762, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31336286

RESUMO

As a triterpene saponin, pedunculoside is one of the most abundant, representative and active components in plants of genus Ilex (Aquifoliaceae). Pedunculoside has been used to treat myocardial ischemia, ameliorate hyperlipidemia and prevent liver injury. In this paper, a systemic in vitro liver microsomes / S9 and intestinal bacteria incubation, and in vivo animal experiment were performed, using LC-Q-TOF/MS analysis and a three-step data processing protocol. As a result, Bifidobacterium adolescentis and Bifidobacterium breve were identified to potentially metabolize pedunculoside among the intestinal bacteria tested. A total of 11 metabolites were found and tentatively identified, with 6 in both microsomal and bacterial incubation systems, and 9 after rats orally administered with pedunculoside. The metabolites detected involving both phase I and phase II metabolism, mainly through deglycosylation (hydrolyzation), dehydrogenation, hydroxylation and conjugation, and some of them underwent more than one-step metabolic reactions. Most of the metabolites have not been reported before. In vitro, liver microsome and intestinal bacteria prefer to metabolize pedunculoside in totally different ways; while in vivo, intestinal tract is the most important site for the metabolism and excretion of pedunculoside, where both intestinal bacteria and the host metabolic enzymes participate in its metabolism and disposition. The importance of intestinal bacteria should be highlighted. This study would contribute to a better understanding of pedunculoside metabolism, which can provide scientific evidence for its pharmacodynamic mechanism research and prove its clinical application.


Assuntos
Biotransformação/fisiologia , Glucose/análogos & derivados , Metaboloma/fisiologia , Triterpenos/química , Triterpenos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/metabolismo , Fezes/química , Glucose/química , Glucose/metabolismo , Hidroxilação/fisiologia , Ilex/metabolismo , Intestinos/fisiologia , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas/química , Saponinas/metabolismo , Espectrometria de Massas em Tandem/métodos
16.
Planta Med ; 85(9-10): 729-737, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167298

RESUMO

Rotundic acid and pedunculoside are the most abundant constituents in Ilicis Rotundae Cortex, and possess lipid-lowering activity. In this study, we evaluated the pharmacokinetic interactions of rotundic acid with pedunculoside and other ingredients from Ilicis Rotundae Cortex with rotundic acid and pedunculoside, and preliminarily investigated the effects of gut microbiota on their pharmacokinetics using a pseudo-germ-free rat model. After a single oral administration of each monomer, a monomer mixture, and Ilicis Rotundae Cortex extract to the conventional and pseudo-germ-free rats, rotundic acid and pedunculoside were quantified in plasma by an UPLC/Q-TOF-MS/MS method. The systemic exposure (maximum plasma concentration and area under concentration-time curve) of two analytes in conventional rats were increased in an approximately dose-dependent manner. Oral administration of rotundic acid and pedunculoside in the forms of a monomer mixture and Ilicis Rotundae Cortex extract to the conventional rats significantly decreased the systemic exposure compared with the monomer groups, which demonstrated the existence of significant pharmacokinetic interactions. The pseudo-germ-free rats were prepared by nonabsorbable antibiotic treatment, and the systemic exposure of two analytes were significantly decreased and most of the "time to reach the maximum" values were delayed in comparison to conventional rats, therefore gut microbiota might serve as an efficient absorption promoter. These results provide a scientific basis for the clinical application of the two bioactive constituents and Ilicis Rotundae Cortex.


Assuntos
Microbioma Gastrointestinal/fisiologia , Glucose/análogos & derivados , Triterpenos/farmacocinética , Administração Oral , Animais , Calibragem , Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/administração & dosagem , Glucose/farmacocinética , Interações Ervas-Drogas , Masculino , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Triterpenos/administração & dosagem
17.
Cancer Sci ; 110(8): 2408-2420, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215094

RESUMO

Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model). The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression. Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion. ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression. The lines were subjected to comprehensive genomic analyses. In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines. Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues. Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium. Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. G6PD overexpression in response to TCA exposure was observed. Both NF-κB (p65) and O-GlcNAc were expressed more highly in ESCC-DRtca2M than in the other cell lines. Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells. Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines. While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression. Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former. The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy. While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.


Assuntos
Ácidos e Sais Biliares/metabolismo , Vias Biossintéticas/fisiologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Hexosaminas/metabolismo , Via de Pentose Fosfato/fisiologia , Acetilglucosamina/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Glucose/análogos & derivados , Glucose/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia
18.
Chemistry ; 25(39): 9272-9279, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31099933

RESUMO

There is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C-terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C-6. Our strategy uses levoglucosan as inexpensive starting material and facilitates an approach to complex carbohydrate analogues with multiple C-F bonds. The challenge of our synthetic route centered around an efficient preparation of crucial 1,6-anhydro-2,4-dideoxy-difluoroglucopyranose and focused on achieving a difficult glycosylation of the trifluoroallopyranose donor. The results clearly highlight challenges related to the preparation of polyhalogenated complex organic molecules and pave the way to access novel medically relevant tools.


Assuntos
Carboidratos/química , Glucose/química , Dissacarídeos/química , Fluoretação , Glucose/análogos & derivados , Glicoconjugados/química , Piranos/química , Estereoisomerismo
19.
Bioorg Med Chem ; 27(10): 2122-2126, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30935790

RESUMO

We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the fluorophore moiety to a fluorescein analogue, 2-Me TokyoGreen, which is less negatively charged. TokyoGreen-conjugated glucosamines TGG1 and TGG2 were successfully taken up into cells via GLUT. We further derivatized TGG1 and TGG2, and among the synthesized compounds, 2-Me-4-OMe TGG showed weak fluorescence under the acidic conditions of the extracellular environment inside tumors and in gastric cancers, and strong fluorescence at the intracellular physiological pH, under the control of a photoinduced electron transfer (PeT) process. This fluorogenic platform should be useful for developing a range of activatable fluorescent substrates targeting GLUTs, as well as derivatives that would be fluorescently activated by various intracellular enzymes, such as esterases, ß-galactosidase and bioreductases.


Assuntos
Corantes Fluorescentes/química , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Animais , Linhagem Celular , Fluoresceína/química , Glucosamina/análogos & derivados , Glucosamina/metabolismo , Glucose/análogos & derivados , Glucose/metabolismo , Camundongos , Microscopia de Fluorescência
20.
J Dairy Sci ; 102(6): 4925-4934, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928267

RESUMO

Streptococcus thermophilus, one of the most important industrial lactic acid bacteria, is widely used as a starter culture in the dairy industry. Streptococcus thermophilus S-3 isolated from Chinese traditional dairy products has shown great potential for the production of larger amounts of exopolysaccharides (EPS), which significantly affect the organoleptic properties of fermented milk products. To understand the relationship between the genotype and phenotype of S. thermophilus S-3 in terms of EPS biosynthesis, its genome of strain S-3 was sequenced and the genes related to carbohydrate utilization, nucleotide sugars synthesis, and EPS biosynthesis were investigated. The genomic analysis revealed that S. thermophilus S-3 can use sucrose, mannose, glucose, galactose, and lactose. Phenotypic analysis showed that S-3 prefers fermenting lactose to fermenting glucose or galactose. The genetic analysis of nucleotide sugars and EPS biosynthesis revealed that S-3 can synthesize uridine diphosphate (UDP)-glucose, deoxythymidine diphosphate-glucose, deoxythymidine diphosphate-rhamnose, UDP-galactose, UDP-N-acetylgalactosamine, and UDP-N-acetylglucosamine. A high yield of EPS from S-3 cultivated with lactose rather than glucose as the carbon source was correlated with high transcriptional levels of the genes associated with metabolism of these nucleotide sugars and EPS biosynthesis. Our results provide a better understanding of EPS biosynthesis in S. thermophilus and can facilitate enhanced EPS production by lactic acid bacteria fermentation via genetic and metabolic engineering approaches.


Assuntos
Polissacarídeos Bacterianos/biossíntese , Streptococcus thermophilus/metabolismo , Animais , Fermentação , Galactose/metabolismo , Genoma Bacteriano , Genótipo , Glucose/análogos & derivados , Lactose/metabolismo , Fenótipo , Streptococcus thermophilus/genética , Nucleotídeos de Timina
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