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1.
J Colloid Interface Sci ; 606(Pt 2): 1249-1260, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492463

RESUMO

In this study, an iron(III)-loaded magnetic chitosan/graphene oxide composite (Fe-MCG) was synthesized and applied for the adsorptive removal of sulfosalicylic acid (SSA) in aqueous solution. The results obtained from the application of various characterization techniques such as scanning electron microscopy (SEM), vibrating-sample magnetometry (VSM), and X-ray photoelectron spectroscopy (XPS) prove the successful formation of the composite with enhanced microstructure and superparamagnetic properties. The adsorption capacity of Fe-MCG towards SSA via batch mode reaches up to 135 mg/g at 293 K. The adsorption of SSA onto Fe-MCG is driven by monolayer adsorption with the chemical and physical adsorption processes both playing active roles. The Langmuir isotherm and pseudo-second-order kinetic models were observed to best describe the equilibrium adsorption and kinetic processes, respectively. The values obtained for the associated thermodynamic parameters confirm that the adsorptive process is spontaneous, exothermic and entropy-increasing. The efficacy and reusability of the spent Fe-MCG was studied using 0.01 mol/L NaOH solution. The kinetic process for the desorption of SSA from Fe-MCG is well described by the pseudo-second-order kinetic model. Based on the experimental results and XPS analysis, the underlying mechanisms for the uptake of SSA onto Fe-MCG involve electrostatic forces, complexation, π-π stacking, and hydrogen bonding. Overall, the excellent features of Fe-MCG enhance its potential as an adsorbent for the sequestration of SSA in environmental media.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Benzenossulfonatos , Grafite , Concentração de Íons de Hidrogênio , Ferro , Cinética , Fenômenos Magnéticos , Salicilatos , Termodinâmica
2.
J Colloid Interface Sci ; 606(Pt 1): 424-433, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34392036

RESUMO

Poor dispersion of metal oxide-biomass carbon composite limits its further improvement in electrochemical properties. The study reports synthesis of highly dispersed RuO2-biomass carbon nanocomposite (HD-RuO2-BC). Octyl ammonium salicylate ionic liquid was combined with Ru3+ ion to form Ru-based ionic liquid. Followed by addition of coconut meat, microwave treatment to form homogeneous solution, thermal reduction in N2 and oxidation in air in sequence. The resulting HD-RuO2-BC shows three-dimensional architecture and high Ru loading of 9.2%. RuO2 nanoparticles of 6.2 nm were uniformly dispersed in biomass carbon sheets. Excellent dispersion and small size of RuO2 nanoparticles achieve to a significant synergy between RuO2 and biomass carbon. HD-RuO2-BC electrode gives high capacitance of 907.7 F g-1 at 1 A g-1. The value is more than that of BC (150.6 F g-1) and RuO2 electrodes (584.7 F g-1), verifying that introduction of RuO2 achieves to an obviously enhanced capacitance. The symmetrical flexible supercapacitor exhibits excellent supercapacitor performances, including high capacitance (403.8 F g-1 at 1.0 A g-1), rate-capacity (223.1 F g-1 at 50 A g-1), cycling stability (98.2% capacity retention after 10,000 cycles at 50 A g-1) and energy density (378.7 Wh Kg-1at power density of 5199.2 W kg-1).


Assuntos
Compostos de Amônio , Líquidos Iônicos , Rutênio , Biomassa , Carbono , Cocos , Carne , Salicilatos , Solubilidade
3.
BMC Plant Biol ; 21(1): 413, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503442

RESUMO

BACKGROUND: In plants, basic leucine zipper transcription factors (TFs) play important roles in multiple biological processes such as anthesis, fruit growth & development and stress responses. However, systematic investigation and characterization of bZIP-TFs remain unclear in Chinese white pear. Chinese white pear is a fruit crop that has important nutritional and medicinal values. RESULTS: In this study, 62 bZIP genes were comprehensively identified from Chinese Pear, and 54 genes were distributed among 17 chromosomes. Frequent whole-genome duplication (WGD) and dispersed duplication (DSD) were the major driving forces underlying the bZIP gene family in Chinese white pear. bZIP-TFs are classified into 13 subfamilies according to the phylogenetic tree. Subsequently, purifying selection plays an important role in the evolution process of PbbZIPs. Synteny analysis of bZIP genes revealed that 196 orthologous gene pairs were identified between Pyrus bretschneideri, Fragaria vesca, Prunus mume, and Prunus persica. Moreover, cis-elements that respond to various stresses and hormones were found on the promoter regions of PbbZIP, which were induced by stimuli. Gene structure (intron/exon) and different compositions of motifs revealed that functional divergence among subfamilies. Expression pattern of PbbZIP genes differential expressed under hormonal treatment abscisic acid, salicylic acid, and methyl jasmonate  in pear fruits by real-time qRT-PCR. CONCLUSIONS: Collectively, a systematic analysis of gene structure, motif composition, subcellular localization, synteny analysis, and calculation of synonymous (Ks) and non-synonymous (Ka) was performed in Chinese white pear. Sixty-two bZIP-TFs in Chinese pear were identified, and their expression profiles were comprehensively analyzed under ABA, SA, and MeJa hormones, which respond to multiple abiotic stresses and fruit growth and development. PbbZIP gene occurred through Whole-genome duplication and dispersed duplication events. These results provide a basic framework for further elucidating the biological function characterizations under multiple developmental stages and abiotic stress responses.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Plantas/genética , Pyrus/genética , Estresse Fisiológico/genética , Ácido Abscísico/farmacologia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Cromossomos de Plantas , Éxons , Fragaria/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Estudo de Associação Genômica Ampla , Íntrons , Família Multigênica , Filogenia , Proteínas de Plantas/metabolismo , Pyrus/efeitos dos fármacos , Salicilatos/farmacologia , Ácido Salicílico/farmacologia , Sintenia
4.
J Anim Sci ; 99(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34551095

RESUMO

Two experiments were performed to evaluate the effects of bismuth subsalicylate (BSS) and calcium-ammonium nitrate (CAN) on in vitro ruminal fermentation, growth, apparent total tract digestibility of nutrients, liver mineral concentration, and carcass quality of beef cattle. In Exp. 1, four ruminally cannulated steers (520 ± 30 kg body weight [BW]) were used as donors to perform a batch culture and an in vitro organic matter digestibility (IVOMD) procedure. Treatments were arranged in a 2 × 2 factorial with factors being BSS (0 or 0.33% of substrate dry matter [DM]) and CAN (0 or 2.22% of substrate DM). In Exp. 2, 200 Angus-crossbred steers (385 ± 27 kg BW) were blocked by BW and allocated to 50 pens (4 steers/pen) in a randomized complete block design with a 2 × 2 + 1 factorial arrangement of treatments. Factors included BSS (0 or 0.33% of the diet DM) and nonprotein nitrogen (NPN) source (urea or encapsulated CAN [eCAN] included at 0.68% or 2.0% of the diet, respectively) with 0.28% ruminally available S (RAS). A low S diet was included as a positive control containing urea (0.68% of DM) and 0.14% RAS. For Exp. 1, data were analyzed using the MIXED procedure of SAS with the fixed effects of BSS, CAN, BSS × CAN, and the random effect of donor. For Exp. 2, the MIXED procedure of SAS was used for continuous variables and the GLIMMIX procedure for categorical data. For Exp. 1, no differences (P > 0.230) were observed for IVOMD. There was a tendency (P = 0.055) for an interaction regarding H2S production. Acetate:propionate increased (P = 0.003) with the addition of CAN. In Exp. 2, there was a NPN source effect (P = 0.032) where steers consuming urea had greater carcass-adjusted final shrunk BW than those consuming eCAN. Intake of DM (P < 0.001) and carcass-adjusted average daily gain (P = 0.024) were reduced by eCAN; however, it did not affect (P = 0.650) carcass-adjusted feed efficiency. Steers consuming urea had greater (P = 0.032) hot carcass weight, and a BSS × NPN interaction (P = 0.019) was observed on calculated yield grade. Apparent absorption of S decreased (P < 0.001) with the addition of BSS. Final liver Cu concentration was reduced (P = 0.042) by 58% in cattle fed BSS, indicating that BSS may decrease Cu absorption and storage in the liver. The results observed in this experiment indicate that BSS does not have negative effects on feedlot steer performance, whereas CAN may hinder performance of steers fed finishing diets.


Assuntos
Ração Animal , Rúmen , Ração Animal/análise , Animais , Bismuto , Cálcio , Bovinos , Dieta/veterinária , Digestão , Nitratos , Compostos Organometálicos , Salicilatos
5.
Int J Nanomedicine ; 16: 6441-6453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584410

RESUMO

Background: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis. Methods: AN-FTS was developed using a classic emulsification-solvent ultrasonication. The pharmacokinetics of DiD-loaded albumin nanoparticle were investigated in SD rats. The biodistribution and therapeutic efficacy of AN-FTS was assessed in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO). Results: AN-FTS showed a uniform spherical shape with the size of 100.6 ± 1.12 nm and PDI < 0.25. In vitro, AN-FTS displayed stronger inhibitory effects on the activation of renal fibroblasts cells NRK-49F than free FTS. In vivo, AN-FTS showed significantly higher peak concentration and area under the concentration-time curve. After intravenous administration to UUO-induced renal fibrosis mice, AN-FTS accumulated preferentially in the fibrotic kidney, and alleviated renal fibrosis and inflammation significantly more than the free drug. Mechanistically, the improved anti-fibrosis effect of AN-FTS was associated with greater inhibition in renal epithelial-to-mesenchymal transformation process via Ras/Raf1/p38 signaling pathway. Conclusion: The study reveals that AN-FTS is capable of delivering FTS to fibrotic kidney and showed superior therapeutic efficacy for renal fibrosis.


Assuntos
Nanopartículas , Transdução de Sinais , Albuminas , Animais , Farneseno Álcool/análogos & derivados , Fibrose , Camundongos , Proteínas Proto-Oncogênicas c-raf , Ratos , Ratos Sprague-Dawley , Salicilatos , Distribuição Tecidual
6.
J Med Food ; 24(8): 806-816, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382859

RESUMO

Even though nasopharyngeal carcinoma (NPC) is not common worldwide, it is a major public health burden in endemic areas. Distant metastasis often leads to a poor prognosis for NPC; therefore, new and effective anticancer strategies are needed. Ginkgolic acid (GA) is small-molecule compound existing in Ginkgo biloba that has various biologically relevant activities, including antitumor properties; however, its effects and mechanism of action in NPC are unknown. The effects of GA on NPC and such underlying mechanisms were investigated using 5-8F and CNE2 cells and NP69 human immortalized nasopharyngeal epithelial cells in this study. Moreover, the xenograft models were built to examine GA's effection in vivo. GA treatment decreased the survival and invasive capacity of 5-8F and CNE2 and induced their apoptosis, which varied with dose; this was accompanied by downregulation of B cell lymphoma (Bcl)2, upregulation of Bcl2-associated X protein, and activation of poly-ADP ribose polymerase, and caspase-9/-3. G0/G1 phase arrest was induced by GA in NPCs. It also reduced the expression of cyclin-dependent kinase 6 and its regulators cyclin D2 and cyclin D3. GA inhibited the activation of protein kinase B/nuclear factor signaling; this effect was potentiated with GA and 5-fluorouracil (5-FU), which also enhanced 5-FU-induced apoptosis. In summary, GA may be effective as an adjuvant to conventional chemotherapy drugs in preventing the progression of NPC.


Assuntos
NF-kappa B , Neoplasias Nasofaríngeas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , NF-kappa B/genética , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Salicilatos
7.
Anal Chim Acta ; 1176: 338754, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34399889

RESUMO

Homosalate (HMS) is an organic UV filter used in sunscreens and personal care products worldwide. It has been detected in various environmental matrices and in humans after application of HMS-containing products. However, sufficient data on the internal HMS exposure in humans is currently not available. Thus, we aimed at providing an analytical method for the sensitive determination of specific HMS metabolites in human urine. We describe the synthesis of analytical standards for the four oxidative HMS metabolites included in this method: 5-((2-hydroxybenzoyl)oxy)-3,3-dimethylcyclohexane-1-carboxylic acid (HMS-CA) and 3-hydroxy-3,5,5-trimethylcyclohexyl 2-hydroxybenzoate (3OH-HMS), as cis- and trans-isomers, respectively. After enzymatic hydrolysis, urine samples were analyzed using liquid chromatography-electrospray ionization-triple quadrupole-tandem mass spectrometry, including turbulent flow chromatography for online sample cleanup and analyte enrichment (online-SPE-LC-MS/MS). Quantification was performed by stable isotope dilution analysis, using deuterium-labeled HMS-CA as internal standards (cis and trans). Limits of quantification of 0.02-0.04 µg L-1 were sufficiently low to quantify the HMS metabolites for up to 96 h (trans-HMS-CA), 48 h (cis-HMS-CA and 3OH-trans-HMS), and 24 h (3OH-cis-HMS) after a pilot dermal application of a commercially available sunscreen in one human volunteer, showing clear elimination kinetics. Furthermore, in a German pilot population (n = 35), HMS metabolites were above the LOQ precisely in those three individuals who had applied sunscreen within the previous five days, thus corroborating the specificity of the identified metabolites as biomarkers of HMS exposure. The method is currently used in a human metabolism study and will be applied in future population-scale human biomonitoring studies.


Assuntos
Salicilatos , Espectrometria de Massas em Tandem , Cromatografia Líquida , Humanos , Protetores Solares
9.
J Chem Ecol ; 47(8-9): 799-809, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347233

RESUMO

Fall armyworm (Spodoptera frugiperda) is a major global pest of many crops, including maize (Zea mays). This insect is known to use host plant-derived volatile organic compounds to locate suitable hosts during both its adult and larval stages, yet the function of individual compounds remains mostly enigmatic. In this study, we use a combination of volatile profiling, electrophysiological assays, pair-wise choice behavioral assays, and chemical supplementation treatments to identify and assess specific compounds from maize that influence S. frugiperda host location. Our findings reveal that methyl salicylate and (E)-alpha-bergamotene are oviposition attractants for adult moths but do not impact larval behavior. While geranyl acetate can act as an oviposition attractant or repellent depending on the host volatile context and (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) is an oviposition deterrent. These compounds can also be attractive to the larvae when applied to specific maize inbreds. These data show that S. frugiperda uses different plant volatile cues for host location in its adult and larval stage and that the background volatile context that specific volatiles are perceived in, alters their impact as behavioral cues.


Assuntos
Herbivoria/efeitos dos fármacos , Oviposição/efeitos dos fármacos , Spodoptera/fisiologia , Compostos Orgânicos Voláteis/farmacologia , Zea mays/química , Animais , Compostos Bicíclicos com Pontes/isolamento & purificação , Compostos Bicíclicos com Pontes/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Larva/fisiologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Análise de Componente Principal , Salicilatos/isolamento & purificação , Salicilatos/farmacologia , Spodoptera/crescimento & desenvolvimento , Terpenos/isolamento & purificação , Terpenos/farmacologia , Compostos Orgânicos Voláteis/química , Zea mays/metabolismo
10.
J Food Sci ; 86(9): 4197-4208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34370293

RESUMO

Although ginkgo nuts are very nutritious and loaded with numerous bioactive compounds, the nuts contain significant levels of unwanted compounds (ginkolic acids) which are toxic to consumption. To reduce or eliminate these toxic compounds without impacting the nutritional value and the bioactivity of the final product, an appropriate processing technology is needed. Thus, the effect of preheating (90 and 120°C) prior to drying (freeze drying: FD, hot air drying: HAD, and HAD in tandem with FD: HAD-FD) was evaluated on ginkgolic acids, pyridoxine analogues, phenolic compounds, and antioxidant properties of ginkgo nuts. Our results pointed out a significant decrease (below 50%) of ginkgolic acids in ginkgo nuts samples processed at 90°C compared to the control. The major compounds found after treatments were respectively, kaempferol (36.66-354.38 µg/g), quercetin (9.04-183.71 µg/g), and caffeic acid (19.66-106.88 µg/g). Principal component analysis (PCA) revealed that preheating at 90°C prior to HAD-FD would be a proper and reasonable approach for preserving the bioactive compounds and antioxidant capacity of ginkgo nuts (EC50 ranged from 2.25 to 4.60 mg/mL) while significantly reducing their content in toxic compounds.


Assuntos
Antioxidantes , Manipulação de Alimentos , Ginkgo biloba , Nozes , Piridoxina , Antioxidantes/química , Manipulação de Alimentos/métodos , Manipulação de Alimentos/normas , Alimentos em Conserva , Temperatura Alta , Nozes/química , Extratos Vegetais/química , Folhas de Planta/química , Salicilatos/análise
11.
FASEB J ; 35(8): e21759, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34245608

RESUMO

Life-style change and anti-inflammatory interventions have only transient effects in obesity. It is not clear how benefits obtained by these treatments can be maintained longer term, especially during sustained high caloric intake. Constitutive ablation of the activin receptor ALK7 in adipose tissue enhances catecholamine signaling and lipolysis in adipocytes, and protects mice from diet-induced obesity. Here, we investigated the consequences of conditional ALK7 ablation in adipocytes of adult mice with pre-existing obesity. Although ALK7 deletion had little effect on its own, it synergized strongly with a transient switch to low-fat diet (life-style change) or anti-inflammatory treatment (Na-salicylate), resulting in enhanced lipolysis, increased energy expenditure, and reduced adipose tissue mass and body weight gain, even under sustained high caloric intake. By themselves, diet-switch and salicylate had only a temporary effect on weight gain. Mechanistically, combination of ALK7 ablation with either treatment strongly enhanced the levels of ß3-AR, the main adrenergic receptor for catecholamine stimulation of lipolysis, and C/EBPα, an upstream regulator of ß3-AR expression. These results suggest that inhibition of ALK7 can be combined with simple interventions to produce longer-lasting benefits in obesity.


Assuntos
Receptores de Ativinas Tipo I/deficiência , Adipócitos/metabolismo , Ingestão de Alimentos , Lipólise , Obesidade/metabolismo , Receptores de Ativinas Tipo I/metabolismo , Adipócitos/patologia , Animais , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/patologia , Salicilatos/farmacologia
12.
BMC Infect Dis ; 21(1): 642, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218802

RESUMO

BACKGROUND: Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population. SETTINGS AND DESIGN: An open-label, randomised, parallel, superiority clinical trial. METHODS: We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment. RESULTS: Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454-4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394-3.774]. We didn't report serious adverse effects. CONCLUSIONS: Levofloxacin concomitant therapy wasn't superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population. TRIAL REGISTRATION: We registered this study as a standard randomized clinical trial ( Clinicaltrial.gov , identifier- NCT04348786 , date:29-January-2020).


Assuntos
Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Levofloxacino/uso terapêutico , Adulto , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Quimioterapia Combinada , Esomeprazol/uso terapêutico , Fezes/microbiologia , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Estudos Prospectivos , Salicilatos/uso terapêutico , Síria , Tinidazol/uso terapêutico , Resultado do Tratamento , Adulto Jovem
13.
Mar Pollut Bull ; 170: 112657, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217052

RESUMO

Mercury (Hg) concentrations based on dietary sources have shown to predict differences in fish; however, they are usually applied at an individual scale and are rarely directed at a known trophic transfer. We combined gut content analysis and stable isotope analysis (δ15N and δ13C) to provide a quantitative estimate of Hg and selenium (Se) biomagnification in the striped marlin (Kajikia audax) and blue marlin (Makaira nigricans) food web from the southwestern Gulf of California. Hg and Se concentrations (mean ± SD; µg g-1, dw) were different among K. audax (Hg = 3.6 ± 2.1, Se = 5.5 ± 5.4) and M. nigricans (Hg = 19.0 ± 29.6, Se = 8.8 ± 10.5). Such variations of element concentrations could be linked to predation with different Hg and Se contents. Diet data presented as prey weight (%W) indicated a higher proportion of large prey fish for the blue marlin than the striped marlin. δ15N and δ13C indicated pelagic food sources with epipelagic preferences for the blue marlin and mesopelagic for the striped marlin. The relationship between Hg concentrations and δ15N was positive along the food web of both marlin species, indicating biomagnification of Hg. However, Se biomagnification was not clearly evidenced, and Se:Hg ratios decreased with δ15N, attributed to increasing Hg concentrations with increased trophic level.


Assuntos
Mercúrio , Selênio , Poluentes Químicos da Água , Animais , Carbono , Isótopos de Carbono/análise , Combinação de Medicamentos , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Glicerol , Mercúrio/análise , Isótopos de Nitrogênio/análise , Salicilatos , Selênio/análise , Poluentes Químicos da Água/análise
14.
J Chem Inf Model ; 61(8): 4045-4057, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34292735

RESUMO

The release of anticoagulant drugs such as warfarin from human serum albumin (HSA) has been important not only mechanistically but also clinically for patients who take multiple drugs simultaneously. In this study, the role of some commonly used drugs, including s-ibuprofen, ascorbic acid, and salicylic acid, was investigated in the release of warfarin bound to HSA in silico. The effects of the aforementioned drugs on the HSA-warfarin complex were investigated with molecular dynamics (MD) simulations using two approaches; in the first perspective, molecular docking was used to model the interaction of each drug with the HSA-warfarin complex, and in the second approach, drugs were positioned randomly and distant from the binary complex (HSA-warfarin) in a physiologically relevant concentration. The results obtained from both approaches indicated that s-ibuprofen and ascorbic acid both displayed allosteric effects on the release of warfarin from HSA. Although ascorbic acid aided in warfarin release, leading to destabilization of HSA, ibuprofen demonstrated a stabilizing effect on releasing the anticoagulant drug through several noncovalent interactions, including hydrophobic, electrostatic, and hydrogen-bonding interactions with the protein. The calculated binding free energy and energy contribution of involved residues using the molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) method, along with root mean square deviation (RMSD) values, protein gyration, and free energy surface (FES) mapping of the protein, provided valuable details on the nature of the interactions of each drug on the release of warfarin from HSA. These results can provide important information on the mechanisms of anticoagulant release that has not been revealed in molecular details previously.


Assuntos
Ibuprofeno , Varfarina , Anticoagulantes/farmacologia , Sítios de Ligação , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Salicilatos , Albumina Sérica/metabolismo , Albumina Sérica Humana
15.
Eur J Med Chem ; 224: 113691, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274830

RESUMO

The Staphylococcus aureus can switch to a transient genotype-invariant dormancy, known as a persister, to survive treatment with high doses of antibiotics. This transient persister is an important reason underlying its resistance. There is an urgent need to find new antibacterial agents capable of eradicating methicillin-resistant S. aureus (MRSA) persisters. In this study, 37 new derivatives of cajaninstilbene acid (CSA) were designed and synthesized, and their biological activity against MRSA persisters was evaluated. Most of the newly synthesized derivatives exhibit more potent antimicrobial properties against S. aureus and MRSA than CSA itself, and 23 of the 37 derivatives show a tendency to eradicate MRSA persisters. A representative compound (A6) was demonstrated to target bacterial cell membranes. It eradicated the adherent biofilm of MRSA in a concentration dependent manner, and showed a synergistic antibacterial effect with piperacilin. In a model mouse abscess caused by MRSA persisters, A6 effectively reduced the bacterial load in vivo. These results indicate that A6 is a potential candidate for treatment of MRSA persister infections.


Assuntos
Antibacterianos/síntese química , Biofilmes/efeitos dos fármacos , Salicilatos/química , Estilbenos/química , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Modelos Animais de Doenças , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos , Testes de Sensibilidade Microbiana , Células RAW 264.7 , Salicilatos/farmacologia , Salicilatos/uso terapêutico , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Staphylococcus aureus/fisiologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Relação Estrutura-Atividade
16.
Acta Crystallogr C Struct Chem ; 77(Pt 6): 262-270, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34089249

RESUMO

The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one, C15H23NO4) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, C7H5BrO3), 4-bromo- (4-BrSalA, C7H5BrO3) and 3,5-dibromosalicylic acid (3,5-Br2SalA, C7H4Br2O3)] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P21) reported previously. The 5-BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4-BrSalA and 3,5-Br2SalA cocrystals retain the highly preserved 21 stacks of the molecular pairs, but these pack with a varying degree of slippage with respect to neighbouring stacks, altering the close contacts between them, and represent two potential alternative homostructural arrangements for the parent compound. Structure redeterminations of the bromosalicylic acids 5-BrSalA, 4-BrSalA and 3,5-Br2SalA at 100 K show that the packing efficiency of the cocrystals need not be higher than the parent coformers, based on specific-volume calculations, attributable to the strong O-H...O=C hydrogen bonds of 2.54 Šin the cocrystals.


Assuntos
Antimaláricos/química , Salicilatos/química , Antimaláricos/farmacologia , Cristalografia por Raios X , Ligação de Hidrogênio , Salicilatos/farmacologia , Solubilidade
17.
Drug Deliv ; 28(1): 1312-1320, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34176371

RESUMO

The cochlea's inaccessibility and complex nature provide significant challenges to delivering drugs and other agents uniformly, safely and efficiently, along the entire cochlear spiral. Large drug concentration gradients are formed along the cochlea when drugs are administered to the middle ear. This undermines the major goal of attaining therapeutic drug concentration windows along the whole cochlea. Here, utilizing a well-known physiological effect of salicylate, we demonstrate a proof of concept in which drug distribution along the entire cochlea is enhanced by applying round window membrane low-frequency micro vibrations with a probe that only partially covers the round window. We provide evidence of enhanced drug influx into the cochlea and cochlear apical drug distribution without breaching cochlear boundaries. It is further suggested that ossicular functionality is not required for the effective drug distribution we report. The novel method presented here of local drug delivery to the cochlea could be implemented when ossicular functionality is absent or impeded and can be incorporated in clinically approved auditory protheses for patients who suffer with conductive, sensorineural or mixed hearing loss.


Assuntos
Anti-Inflamatórios/farmacocinética , Cóclea/metabolismo , Janela da Cóclea/metabolismo , Salicilatos/farmacocinética , Vibração , Animais , Anti-Inflamatórios/administração & dosagem , Cobaias , Salicilatos/administração & dosagem
18.
Sci Rep ; 11(1): 12038, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103581

RESUMO

We investigated the larvicidal potential of 10 plant essential oils (EOs) against the Asian tiger mosquito Aedes albopictus. Among the EOs, larvicidal activity against Ae. albopictus was strongest in those derived from massoia (Massoia aromatica) and nutmeg (Myristica fragrans). Larvicidal activities of massoia and nutmeg EOs against Ae. albopictus were 95.0% and 85.0% at 50 µg/mL, respectively. A total of 4 and 14 compounds were identified from massoia and nutmeg, respectively, and two massoia lactones, C10 and C12, were isolated from massoia EO. Among the identified compounds, benzyl salicylate, terpinolene, C12 massoia lactone, sabinene, benzyl benzoate, methyl eugenol, and C10 massoia lactone exhibited the strong larvicidal activity. Cellulose nanocrystal (CNC)-stabilized Pickering emulsions of massoia and nutmeg EOs were developed to overcome the insolubility of EOs in water. CNC/massoia and CNC/nutmeg emulsions were stable for at least 10 days, and larvicidal activities of CNC/massoia PE and CNC/nutmeg were higher than those of crude massoia and nutmeg EOs. This study presents a CNC-stabilized PE, a suitable formulation for EOs, as a potential larvicide against Ae. albopictus.


Assuntos
Aedes/efeitos dos fármacos , Aedes/metabolismo , Celulose/química , Inseticidas/química , Nanopartículas/química , Óleos Voláteis/química , Animais , Benzoatos/química , Cromatografia Gasosa , Monoterpenos Cicloexânicos/química , Emulsões , Eugenol/análogos & derivados , Eugenol/química , Lactonas/química , Larva , Myristica , Óleos Vegetais/química , Salicilatos/química , Solubilidade
19.
J Nanobiotechnology ; 19(1): 177, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118951

RESUMO

BACKGROUND: Ras activation is a frequent event in hepatocellular carcinoma (HCC). Combining a RAS inhibitor with traditional clinical therapeutics might be hampered by a variety of side effects, thus hindering further clinical translation. Herein, we report on integrating an IR820 nanocapsule-augmented sonodynamic therapy (SDT) with the RAS inhibitor farnesyl-thiosalicylic acid (FTS). Using cellular and tumor models, we demonstrate that combined nanocapsule-augmented SDT with FTS induces an anti-tumor effect, which not only inhibits tumor progression, and enables fluorescence imaging. To dissect the mechanism of a combined tumoricidal therapeutic strategy, we investigated the scRNA-seq transcriptional profiles of an HCC xenograft following treatment. RESULTS: Integrative single-cell analysis identified several clusters that defined many corresponding differentially expressed genes, which provided a global view of cellular heterogeneity in HCC after combined SDT/FTS treatment. We conclude that the combination treatment suppressed HCC, and did so by inhibiting endothelial cells and a modulated immunity. Moreover, hepatic stellate secretes hepatocyte growth factor, which plays a key role in treating SDT combined FTS. By contrast, enrichment analysis estimated the functional roles of differentially expressed genes. The Gene Ontology terms "cadherin binding" and "cell adhesion molecule binding" and KEGG pathway "pathway in cancer" were significantly enriched by differentially expressed genes after combined SDT/FTS therapy. CONCLUSIONS: Thus, some undefined mechanisms were revealed by scRNA-seq analysis. This report provides a novel proof-of-concept for combinatorial HCC-targeted therapeutics that is based on a non-invasive anti-tumor therapeutic strategy and a RAS inhibitor.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Diatermia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Análise de Sequência de RNA , Proteínas ras/antagonistas & inibidores , Animais , Carcinoma Hepatocelular/radioterapia , Linhagem Celular Tumoral , Terapia Combinada , Modelos Animais de Doenças , Células Endoteliais , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/radioterapia , Camundongos Endogâmicos BALB C , Camundongos Nus , Salicilatos
20.
Food Chem ; 360: 130120, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34034050

RESUMO

Methyl salicylate (MeSA) is a plant metabolite that induces plant defence resistance and an odorous volatile compound presenting green nuances. This volatile compound was shown to be present in wine samples, sometimes at concentrations above its olfactory detection threshold. MeSA is localized in grapes, particularly in the skins and stems, and is extracted during red wine vinification. It was detected at the highest concentrations in wines of several grape varieties, made from grapes affected by cryptogamic diseases, namely downy mildew caused by Plasmopara viticola, and black rot caused by Guignardia bidwellii. It has also been detected in wines from vines affected by Esca, a Grapevine Trunk Disease. MeSA can also be considered to be a chemical marker in grapes and wine indicative of the level of development of several vine cryptogamic diseases.


Assuntos
Salicilatos/análise , Vitis/química , Vinho/análise , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/metabolismo , Cromatografia Líquida de Alta Pressão , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Doenças das Plantas/microbiologia , Salicilatos/isolamento & purificação , Extração em Fase Sólida , Paladar/fisiologia , Vitis/metabolismo
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