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1.
Chemosphere ; 286(Pt 3): 131851, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34391114

RESUMO

Food consumption has been recognized as the most significant contributor to human exposure to polyfluoroalkyl and perfluoroalkyl substances (PFASs) for the general population. In 2020, EFSA introduced for the first time safety limit of 4.4 ng/kg body weight (bw) for weekly intake for the sum of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) which are all perfluoralkyl acids (PFAAs) that belong to PFASs group. Fish and eggs have been found to contribute significantly, almost 50 % to PFOS and PFOA dietary intake of the Greek population. In the present study, estimation of human intake of these four PFASs from fish, eggs and drinking water consumption is attempted. Data from EFSA food consumption database for fish and eggs are used for assessment. Mean weekly intake estimated is above the tolerable weekly intake (TWI) recently proposed, mainly due to fish consumption. Exceedance of the proposed TWI emphasizes the need for continuous monitoring of levels of PFASs in food in parallel with efforts to lower these levels.


Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorcarbonetos , Ácidos Alcanossulfônicos/análise , Animais , Caprilatos/análise , Ovos , Fluorcarbonetos/análise , Grécia , Humanos , Ácidos Sulfônicos
2.
Chemosphere ; 287(Pt 2): 132242, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34826929

RESUMO

In this study, a multi-wavelength spectrophotometric method for simultaneous determination of peracetic acid (PAA) and coexistent hydrogen peroxide (H2O2) was presented. This method was based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) with the assistance of Fe2+/KI to produce a stable green radical (ABTS●+), which could be determined at four characteristic peaks (i.e., 415 nm, 650 nm, 732 nm, and 820 nm). The absorbances of ABTS●+ at four peaks were well linear (R2 > 0.999) with concentrations of both total peroxides (PAA + H2O2) and PAA in the range of 0-40 µM under optimized conditions. The sensitivities for determining total peroxides at 415 nm, 650 nm, 732 nm and 820 nm were determined to be 4.248 × 104 M-1 cm-1, 1.682 × 104 M-1 cm-1, 2.132 × 104 M-1 cm-1, and 1.928 × 104 M-1 cm-1, respectively. For determining PAA, the corresponding sensitivities were 4.622 × 104 M-1 cm-1, 1.895 × 104 M-1 cm-1, 2.394 × 104 M-1 cm-1 and 2.153 × 104 M-1 cm-1, respectively. The concentration of coexistent H2O2 was gained by deducting PAA concentration from total peroxides concentration. The ABTS method was accurate enough to determine PAA concentration in natural water samples. Moreover, the ABTS method was successfully used to determine the changes of PAA and coexistent H2O2 and to distinguish their role on naproxen degradation in heat-activated PAA process. Overall, the ABTS method could be used as an alternative method for the convenient, rapid and sensitive determination of PAA and the coexistent H2O2 in water samples.


Assuntos
Peróxido de Hidrogênio , Ácido Peracético , Benzotiazóis , Oxirredução , Estresse Oxidativo , Ácidos Sulfônicos
3.
Chemosphere ; 287(Pt 2): 132121, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34509758

RESUMO

Since the voluntary phaseout of perfluorooctanesulfonic acid (PFOS), smaller congeners, such as perfluorobutanesulfonic acid (PFBS) have served as industrial replacements and been detected in contaminated aquifers. This study sought to examine the effects of a maternal preconception PFBS exposure on the development of eggs and healthy offspring. Adult female zebrafish received a one-week waterborne exposure of 0.08, 0.14, and 0.25 mg/L PFBS. After which, females were bred with non-exposed males and embryos collected over 5 successful breeding events. PFBS concentrations were detected in levels ranging from 99 to 253 pg/embryo in the first collection but were below the limit of quantitation by fourth and fifth clutches. Therefore, data were subsequently binned into early collection embryos in which PFBS was detected and late collections, in which PFBS was below quantitation. In the early collection, embryo 24 h survival was significantly reduced. In the late collection, embryo development was impacted with unique patterns emerging between Nrf2a wildtype and mutant larvae. Additionally, the impact of nutrient loading into the embryos was assessed through measurement of fatty acid profiles, total cholesterol, and triglyceride content. There were no clear dose-dependent effects, but again unique patterns were observed between the genotypes. Preconception PFBS exposures were found to alter egg and embryo development, which is mediated by direct toxicant loading in the eggs, nutrient loading into eggs, and the function of Nrf2a. These findings provide insight into the reproductive and developmental effects of PFBS and identify maternal preconception as a novel critical window of exposure.


Assuntos
Fluorcarbonetos , Peixe-Zebra , Animais , Desenvolvimento Embrionário , Feminino , Fluorcarbonetos/toxicidade , Humanos , Masculino , Exposição Materna , Ácidos Sulfônicos/toxicidade , Peixe-Zebra/genética
4.
Antiviral Res ; 195: 105183, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34626674

RESUMO

The likelihood of continued circulation of COVID-19 and its variants, and novel coronaviruses due to future zoonotic transmissions, combined with the current paucity of coronavirus antivirals, emphasize the need for improved screening in developing effective antivirals for the treatment of infection by SARS-CoV-2 (CoV2) and other coronaviruses. Here we report the development of a live-cell based assay for evaluating the intracellular function of the critical, highly-conserved CoV2 target, the Main 3C-like protease (Mpro). This assay is based on expression of native wild-type mature CoV2 Mpro, the function of which is quantitatively evaluated in living cells through cleavage of a biosensor leading to loss of fluorescence. Evaluation does not require cell harvesting, allowing for multiple measurements from the same cells facilitating quantification of Mpro inhibition, as well as recovery of function upon removal of inhibitory drugs. The pan-coronavirus Mpro inhibitor, GC376, was utilized in this assay and effective inhibition of intracellular CoV2 Mpro was found to be consistent with levels required to inhibit CoV2 infection of human lung cells. We demonstrate that GC376 is an effective inhibitor of intracellular CoV2 Mpro at low micromolar levels, while other predicted Mpro inhibitors, bepridil and alverine, are not. Results indicate this system can provide a highly effective high-throughput coronavirus Mpro screening system.


Assuntos
Técnicas Biossensoriais , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Pirrolidinas/farmacologia , SARS-CoV-2/enzimologia , Ácidos Sulfônicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Fluorescência , Células HEK293 , Humanos
5.
Virology ; 564: 33-38, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34619630

RESUMO

Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, ß-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E. In cell culture models, treatment of molnupiravir effectively inhibited viral replication and production of infectious viruses of the three seasonal coronaviruses. A time-of-drug-addition experiment indicates the specificity of molnupiravir in inhibiting viral components. Furthermore, combining molnupiravir with the protease inhibitor GC376 resulted in enhanced antiviral activity. Our findings highlight that the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.


Assuntos
Coronavirus Humano 229E/genética , Infecções por Coronavirus/tratamento farmacológico , Coronavirus Humano NL63/genética , Coronavirus Humano OC43/genética , Citidina/análogos & derivados , Hidroxilaminas/farmacologia , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Resfriado Comum/tratamento farmacológico , Coronavirus Humano 229E/efeitos dos fármacos , Coronavirus Humano 229E/fisiologia , Coronavirus Humano NL63/efeitos dos fármacos , Coronavirus Humano NL63/fisiologia , Coronavirus Humano OC43/efeitos dos fármacos , Coronavirus Humano OC43/fisiologia , Citidina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , Pirrolidinas/farmacologia , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Estações do Ano , Ácidos Sulfônicos/farmacologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
6.
Environ Sci Technol ; 55(20): 13749-13758, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34617730

RESUMO

The dispersion of perfluoroalkyl substances (PFAS) in surface and deep-water profiles (down to 5845 m deep) was evaluated through the Western Tropical Atlantic Ocean (TAO) between 15°N and 23°S. The sum concentrations for eight quantifiable PFAS (∑8PFAS) in surface waters ranged from 11 to 69 pg/L, which is lower than previously reported in the same area as well as in higher latitudes. Perfluoroalkyl carboxylic acids (PFCAs) were the predominant PFASs present in the Western TAO. The 16 surface samples showed variable PFAS distributions, with the predominance of perfluorooctanoic acid (PFOA) along the transect (67%; 11 ± 8 pg/L) and detection of perfluoroalkyl sulfonic acids (PFSAs) only in the Southern TAO. Perfluoroheptanoic acid (PFHpA) was often detected in the vertical profiles. PFAS distribution patterns (i.e., profiles and concentrations) varied with depth throughout the TAO latitudinal sectors (North, Equator, South Atlantic, and in the Brazilian coastal zone). Vertical profiles in coastal samples displayed decreasing PFAS concentrations with increasing depth, whereas offshore samples displayed higher PFAS detection frequencies in the intermediate water masses. Together with the surface currents and coastal upwelling, the origin of the water masses was an important factor in explaining PFAS concentrations and profiles in the TAO.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/análise , Oceano Atlântico , Ácidos Carboxílicos , Monitoramento Ambiental , Fluorcarbonetos/análise , Ácidos Sulfônicos/análise , Poluentes Químicos da Água/análise
7.
Enzyme Microb Technol ; 152: 109934, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34688090

RESUMO

The phenolic compound catechol has found various applications in the industry but is often discharged untreated in industrial effluents. Catechol is highly toxic and adversely affects the environment. This has increased extensive investigation into elucidating the effects of various synthetic elements or different biocatalysts on catechol, thereby leading the way to its bioremediation. Hence, an electrochemical-based study on catechol in the presence of the enzyme laccase could provide a basic understanding of the unique characteristics exhibited by catechol, thus facilitating a distinct perspective to its subsequent treatment and removal. The present study focuses on the electrochemical characterization of catechol based on the oxidation of laccase and the redox mediator 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Catechol exhibited distinct electrochemical behavior across various concentrations. The unique electroactive nature of ABTS assisted in the polymerization of catechol which was found to be concentration-dependent. Laccase produced a higher oxidation-reduction rate, thereby producing a much more stable condition for the polymerization of catechol. However, with the laccase-mediator system (LMS), the catechol polymerization rate was distinctly higher and more gradual with the enzyme utilizing the electroactive species produced by ABTS to increase the electron transfer and producing a combinatorial impact on the phenolic compound. This study could rightly serve as the building block in developing future technologies like wastewater treatment and biosensors for catechol bioremediation.


Assuntos
Lacase , Trametes , Benzotiazóis , Catecóis , Lacase/metabolismo , Oxirredução , Polimerização , Polyporaceae , Ácidos Sulfônicos , Trametes/metabolismo
8.
JCI Insight ; 6(20)2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34506304

RESUMO

Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial dysfunction and alterations in the Tie2/angiopoietin axis. Primary HUVECs treated with plasma from patients with severe COVID-19 upregulated the expression of thromboinflammatory genes, inhibited the expression of antithrombotic genes, and promoted coagulation on the endothelial surface. Pharmacologic activation of Tie2 with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells. Lung autopsies from patients with COVID-19 demonstrated a prothrombotic endothelial signature. Assessment of circulating endothelial markers in a cohort of 98 patients with mild, moderate, or severe COVID-19 revealed endothelial dysfunction indicative of a prothrombotic state. Angpt-2 concentrations rose with increasing disease severity, and the highest levels were associated with worse survival. These data highlight the disruption of Tie2/angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19. Our findings provide rationale for current trials of Tie2-activating therapy with AKB-9778 in COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptor TIE-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopoietina-2/metabolismo , Compostos de Anilina , Feminino , Expressão Gênica , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Receptor TIE-2/genética , SARS-CoV-2 , Transdução de Sinais , Ácidos Sulfônicos , Doenças Vasculares/metabolismo , Adulto Jovem
9.
Xenobiotica ; 51(10): 1110-1121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34477046

RESUMO

Razuprotafib, a sulphamic acid-containing phosphatase inhibitor, is shown in vivo to undergo enzymatic oxidation and methylation to form a major metabolite in monkey and human excreta with an m/z- value of 633.LC-MS/MS analysis of samples derived from incubations of razuprotafib with human liver microsomes and recombinant CYP2C8 enzyme has elucidated the metabolic pathway for formation of the thiol precursor to the S-methyl metabolite MS633 (m/z- 633).Under in vitro conditions, the major pathway of razuprotafib metabolism involves extensive oxidation of the thiophene and phenyl rings.A single oxidation takes place at one of the phenyl groups. Multiple oxidations occur at the thiophene moiety: initial oxidation results in the formation of a thiolactone followed by a second oxidation giving rise to an S-oxide of the thiolactone, which is further metabolised to the ring-opened form and ultimate formation of a thiol (m/z- 619).An additional mono-oxidation pathway involves epoxidation of the thiophene followed by hydrolysis to a diol.The thiol and diol metabolites are trapped by the addition of a nucleophilic trapping agent, 3-methoxyphenacyl bromide (MPB), giving adducts with m/z- 767.The thiol is a likely precursor to the major in vivo razuprotafib metabolite, MS633.


Assuntos
Microssomos Hepáticos , Espectrometria de Massas em Tandem , Fosfatase Ácida/metabolismo , Compostos de Anilina , Cromatografia Líquida , Citocromo P-450 CYP2C8/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Oxirredução , Estresse Oxidativo , Ácidos Sulfônicos
10.
Environ Sci Technol ; 55(18): 12291-12301, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34495656

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (Kd) for each compound were calculated using regression analysis of the dose-dependent changes in HSA melting temperature. Estimated Kd values for HSA binding of octanoic acid, decanoic acid, hexadecenoic acid, ibuprofen, and warfarin agreed with established values. The binding affinities for 24 PFAS that included perfluoroalkyl carboxylic acids (C4-C12), perfluoroalkyl sulfonic acids (C4-C8), mono- and polyether perfluoroalkyl ether acids, and polyfluoroalkyl fluorotelomer substances were determined. These results demonstrate the utility of this differential scanning fluorimetry assay as a rapid high-throughput approach for determining the relative protein-binding properties and identification of chemical structures involved in binding for large numbers of structurally diverse PFAS.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Ácidos Carboxílicos , Fluorometria , Humanos , Albumina Sérica Humana , Ácidos Sulfônicos
11.
Molecules ; 26(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34500664

RESUMO

This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2'-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3ß-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of -87.91, -78.11, and -68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.


Assuntos
COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Protease de Coronavírus/farmacologia , Gengibre/química , Extratos Vegetais/farmacologia , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/ultraestrutura , Inibidores de Protease de Coronavírus/química , Inibidores de Protease de Coronavírus/isolamento & purificação , Inibidores de Protease de Coronavírus/uso terapêutico , Cristalografia por Raios X , Ensaios Enzimáticos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Pirrolidinas/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Relação Estrutura-Atividade , Ácidos Sulfônicos/farmacologia
12.
ACS Appl Mater Interfaces ; 13(36): 43696-43707, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34470205

RESUMO

Graphene is a two-dimensional semiconducting material whose application for diagnostics has been a real game-changer in terms of sensitivity and response time, variables of paramount importance to stop the COVID-19 spreading. Nevertheless, strategies for the modification of docking recognition and antifouling elements to obtain covalent-like stability without the disruption of the graphene band structure are still needed. In this work, we conducted surface engineering of graphene through heterofunctional supramolecular-covalent scaffolds based on vinylsulfonated-polyamines (PA-VS). In these scaffolds, one side binds graphene through multivalent π-π interactions with pyrene groups, and the other side presents vinylsulfonated pending groups that can be used for covalent binding. The construction of PA-VS scaffolds was demonstrated by spectroscopic ellipsometry, Raman spectroscopy, and contact angle measurements. The covalent binding of -SH, -NH2, or -OH groups was confirmed, and it evidenced great chemical versatility. After field-effect studies, we found that the PA-VS-based scaffolds do not disrupt the semiconducting properties of graphene. Moreover, the scaffolds were covalently modified with poly(ethylene glycol) (PEG), which improved the resistance to nonspecific proteins by almost 7-fold compared to the widely used PEG-monopyrene approach. The attachment of recognition elements to PA-VS was optimized for concanavalin A (ConA), a model lectin with a high affinity to glycans. Lastly, the platform was implemented for the rapid, sensitive, and regenerable recognition of SARS-CoV-2 spike protein and human ferritin in lab-made samples. Those two are the target molecules of major importance for the rapid detection and monitoring of COVID-19-positive patients. For that purpose, monoclonal antibodies (mAbs) were bound to the scaffolds, resulting in a surface coverage of 436 ± 30 ng/cm2. KD affinity constants of 48.4 and 2.54 nM were obtained by surface plasmon resonance (SPR) spectroscopy for SARS-CoV-2 spike protein and human ferritin binding on these supramolecular scaffolds, respectively.


Assuntos
Biomarcadores/análise , COVID-19/diagnóstico , Grafite/química , Imunoensaio/métodos , Glicoproteína da Espícula de Coronavírus/análise , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Etilenos/química , Ferritinas/imunologia , Ferritinas/metabolismo , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Poliaminas/química , Polietilenoglicóis/química , Pirenos/química , Teoria Quântica , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Semicondutores , Glicoproteína da Espícula de Coronavírus/imunologia , Ácidos Sulfônicos/química , Ressonância de Plasmônio de Superfície
13.
Molecules ; 26(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500747

RESUMO

The chemical composition of essential oils (EOs) from dried and fresh flowers of Lavandula angustifolia L. (lavender), named LA 2019 and LA 2020, respectively, grown in central Italy was analyzed and compared by GC and GC-MS. For both samples, 61 compounds were identified, corresponding to 97.9% and 98.1% of the total essential oils. Explorative data analysis, performed to compare the statistical composition of the samples, resulted in a high level of global similarity (around 93%). The compositions of both samples were characterized by 10 major compounds, with a predominance of Linalool (35.3-36.0%), Borneol (15.6-19.4%) and 1,8-Cineole (11.0-9.0%). The in vitro antibacterial activity assay by disk diffusion tests against Bacillus subtilis PY79 and Escherichia coli DH5α showed inhibition of growth in both indicator strains. In addition, plate counts revealed a bactericidal effect on E. coli, which was particularly noticeable when using oil from the fresh lavender flowers at the highest concentrations. An in vitro antifungal assay showed that the EOs inhibited the growth of Sclerotium rolfsii, a phytopathogenic fungus that causes post-harvest diseases in many fruits and vegetables. The antioxidant activity was also assessed using the ABTS free radical scavenging assay, which showed a different antioxidant activity in both EOs. In addition, the potential application of EOs as a green method to control biodeterioration phenomena on an artistic wood painting (XIX century) was evaluated.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Flores/química , Lavandula/química , Óleos Voláteis/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Basidiomycota/efeitos dos fármacos , Benzotiazóis/antagonistas & inibidores , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Relação Estrutura-Atividade , Ácidos Sulfônicos/antagonistas & inibidores
14.
Carbohydr Polym ; 270: 118356, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364601

RESUMO

A cellulose-g-poly-(acrylamide-co-sulfonic acid) polymeric bio-adsorbent (CASA) was prepared by grafting copolymerization, and used to adsorb Cr(III) from leather wastewater. The SEM, XRD, FTIR, and XPS results showed that CASA contains many spherical particles and functional groups such as NH2, CO, and HSO3. The adsorption experiments revealed that CASA presented excellent adsorption performance for Cr(III) (274.69 mg/g of max adsorption capacity) from high-salinity wastewater, which was much better than other reported adsorbents with different structures. Meanwhile, adsorption equilibrium could be reached within 10 min due to the introduction of abundant sulfonic acid groups on its surface. In addition, the adsorption process followed the Langmuir adsorption isotherm, and the experimental data conformed to the pseudo-second-order kinetics model. Moreover, the main adsorption mechanisms include chelation, electrostatic interactions, and cation exchange, which provide an important theoretical basis for the removal of toxic inorganic pollutants from leather wastewater.


Assuntos
Acrilamida/química , Celulose/química , Cromo/isolamento & purificação , Ácidos Sulfônicos/química , Águas Residuárias/química , Purificação da Água/métodos , Adsorção , Cátions , Cromo/química , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletroquímica de Varredura/métodos , Poli G/química , Polímeros/química , Salinidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Eletricidade Estática , Água/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
15.
Biochem Biophys Res Commun ; 573: 69-75, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34388457

RESUMO

Breast cancer (BRCA) is one of the most threatening cancer types, especially among the female population. 70% of breast cancer are estrogen receptor α (ERα) positive and endocrine therapy is effective to decrease breast cancer risk. Autophagy, a highly conserved cellular recycling process, has been regarded to serve a protective role in BRCA. Autophagy-related gene 13 (Atg13) is participated in autophagy and is critical to autophagy initiation. Briefly, we observed that ERα, a well-known transcription factor that can promote breast cancer cell proliferation, expressed higher in breast cancer tissues. Moreover, ERα had a significant positive correlation with Atg13 and may be able to regulate the transcription of Atg13 via binding the promoter region of Atg13. Surprisingly, Oxabicycloheptene sulfonate (OBHS), the drug that we reported as a selective estrogen receptor modulator (SERM) before, may have the ability to decrease the expression of ERα and suppress the autophagy. In conclusion. We found that ERα could be involved in autophagy by binding the promoter of Atg13, and compound OBHS may be able to affect the viability of breast cancer cells by decreasing the expression of ERα and Atg13.


Assuntos
Antineoplásicos/farmacologia , Proteínas Relacionadas à Autofagia/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Ácidos Sulfônicos/farmacologia , Proteínas Relacionadas à Autofagia/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Receptor alfa de Estrogênio/metabolismo , Células HEK293 , Humanos
16.
J Med Chem ; 64(16): 12322-12358, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34378914

RESUMO

Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 µM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.


Assuntos
Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Sulfonas/farmacologia , Ácidos Sulfônicos/farmacologia , Tripanossomicidas/farmacologia , Compostos de Vinila/farmacologia , Animais , Cisteína Endopeptidases/química , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/metabolismo , Inibidores de Cisteína Proteinase/toxicidade , Ensaios Enzimáticos , Feminino , Células HeLa , Humanos , Cinética , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Testes de Sensibilidade Parasitária , Ligação Proteica , Relação Estrutura-Atividade , Sulfonas/síntese química , Sulfonas/metabolismo , Sulfonas/toxicidade , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/metabolismo , Ácidos Sulfônicos/toxicidade , Tripanossomicidas/síntese química , Tripanossomicidas/metabolismo , Tripanossomicidas/toxicidade , Trypanosoma brucei brucei/efeitos dos fármacos , Compostos de Vinila/síntese química , Compostos de Vinila/metabolismo , Compostos de Vinila/toxicidade
17.
Environ Health ; 20(1): 97, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454526

RESUMO

BACKGROUND: Environmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA. METHODS: We measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014-15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length. RESULTS: Regression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (ß (95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (- 0.14(- 0.28, - 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding. CONCLUSION: Our findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.


Assuntos
Ácidos Graxos/sangue , Bombeiros , Retardadores de Chama/análise , Fluorcarbonetos/sangue , Organofosfatos/urina , Ácidos Sulfônicos/sangue , Telômero , Adulto , Monitoramento Biológico , Estudos de Coortes , Feminino , Humanos , Leucócitos/metabolismo , Pessoa de Meia-Idade , Exposição Ocupacional/análise , São Francisco
18.
Xenobiotica ; 51(10): 1132-1145, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34420473

RESUMO

The disposition of radioactivity following subcutaneous 14C-razuprotafib, a Tie2 activator, was explored in multiple species.The absorption and clearance of razuprotafib and total radioactivity in human plasma are rapid and pharmacokinetics support razuprotafib as primary circulating component. Radioactivity is distributed greater to human plasma than whole blood (B:P = 0.36).In pigmented rats, radioactivity distributes to whole-body tissues rapidly and, within 24 h, is localised to elimination pathway end organs and injection site.Overall recovery of radioactivity across species is >93%, with the majority recovered within 24-48 h, and >80% in faeces.The CYP2C8 enzyme contributes significantly to razuprotafib metabolism.A hydrolysis product of razuprotafib (m/z- 380) is the main component in rat plasma at 2 h (49% peak area radioactivity), while razuprotafib (m/z- 585) is the main component in plasma for dog (58%), monkey (99.3%), and human (100%).Razuprotafib is present in dog, monkey, and human faeces, with the greatest percentage of radioactivity as metabolites. The major metabolite (>25%) in monkey and human, m/z- 633, is an S-methylated oxidised derivative of razuprotafib and is localised in faeces.Overall disposition of 14C-razuprotafib in human is best modelled by monkey over lower order species.


Assuntos
Fosfatase Ácida , Compostos de Anilina , Animais , Cães , Fezes , Humanos , Cinética , Ratos , Ácidos Sulfônicos , Distribuição Tecidual
19.
Food Res Int ; 147: 110525, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399503

RESUMO

Microenvironmental factors may influence the antioxidant efficacy of food-derived peptides. This study evaluated the in vitro antioxidant properties of peptides released during the ripening (9 to 24 months of processing) of Spanish dry-cured ham (Biceps femoris muscle) assisted by spectral-chromatographic methodologies. Results indicated that 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical-cation (ABTS●+) quenching capacity of peptide extracts significantly increased (P < 0.05) until 24 months whereas peroxyl radical (ROO●) scavenging activity increased slowly and remained with non-significant change (P > 0.05) between 15 and 24 months. However, both ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH●) scavenging ability significantly decreased (P < 0.05) at 24 months. Additionally, morphological traits of peptide extracts suggested that a prolonged ripening enabled the formation/reconstruction of intra-/inter-molecular interactions in dispersion medium. Meta-analysis of chromatographic and spectral fingerprinting proved that the non-conjugated/π-conjugated oligomers mediated by aromatic moieties probably differentiated DPPH● and ABTS●+ antioxidant performance of peptides, showing a potentially altered solvent polarization process.


Assuntos
Antioxidantes , Carne de Porco , Peptídeos , Extratos Vegetais , Ácidos Sulfônicos
20.
Biomolecules ; 11(8)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34439780

RESUMO

The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v/v. After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.


Assuntos
Bebidas Alcoólicas/análise , Tecnologia de Alimentos/métodos , Mel/análise , Iridoides/química , Fenóis/química , Saccharomyces/metabolismo , Antocianinas/biossíntese , Antocianinas/química , Antocianinas/classificação , Antocianinas/isolamento & purificação , Antioxidantes/química , Antioxidantes/classificação , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Ácido Elágico/química , Ácido Elágico/isolamento & purificação , Ácido Elágico/metabolismo , Fermentação , Flavonóis/química , Flavonóis/classificação , Flavonóis/isolamento & purificação , Flavonóis/metabolismo , Frutas/química , Sucos de Frutas e Vegetais/análise , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Ácido Gálico/metabolismo , Humanos , Iridoides/classificação , Iridoides/isolamento & purificação , Iridoides/metabolismo , Fenóis/classificação , Fenóis/isolamento & purificação , Fenóis/metabolismo , Picratos/antagonistas & inibidores , Prunus avium/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/isolamento & purificação , Ácido Quínico/metabolismo , Ácidos Sulfônicos/antagonistas & inibidores
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