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1.
Aquat Toxicol ; 272: 106970, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38838503

RESUMEN

As well-known, microalgae have a pivotal role in aquatic environments, being the primary producer. In this study, we investigated the effects of Bisphenol A (BPA) analogues on cell ultrastructure, reactive oxygen species (ROS) production and photosynthetic pigment responses in the diatom Phaeodactylum tricornutum. Microalgae were exposed during both exponential and stationary growth phases to an environmental relevant concentration (300 ng/L) of three differing BPA analogues (BPAF, BPF, and BPS) and their mixture (100 ng/L of each compound). Bioaccumulation of such compounds in microalgae was also analysed. During the stationary growth phase, a significant increase in the percentage of cells with hydrogen peroxide production was recorded after exposure to both BPS and MIX. Conversely, no significant effects on total chlorophylls and carotenoids were observed. During exponential growth phase we observed that control cultures had chloroplasts with well-organized thylakoid membranes and a central pyrenoid. On the contrary, the culture cells treated with BPA analogues and MIX showed chloroplasts characterized by evident dilation of thylakoid membranes. The presence of degeneration areas in the cytoplasm was also recorded. During the stationary growth phase, control and culture cells were characterized by chloroplasts with a regular thylakoid system, whereas BPA analogues-exposed cells were characterized by a deep degradation of the cytoplasm but showed chloroplasts without evident alterations of the thylakoid system. Lipid bodies were visible in treated microalgae. Lastly, microalgae bioaccumulated mainly BPS and BPF, alone or in the MIX. Overall, results obtained revealed that BPA analogues can affect some important biochemical and ultrastructure features of microalgae, promoting ROS production. Lastly, the capability of microalgae to bioaccumulate bisphenols suggest a potential ecotoxicological risk for filter-feeders organisms.


Asunto(s)
Compuestos de Bencidrilo , Diatomeas , Microalgas , Fenoles , Especies Reactivas de Oxígeno , Contaminantes Químicos del Agua , Fenoles/toxicidad , Diatomeas/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Compuestos de Bencidrilo/toxicidad , Microalgas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Bioacumulación/efectos de los fármacos , Clorofila/metabolismo , Carotenoides/metabolismo , Fotosíntesis/efectos de los fármacos
2.
NanoImpact ; 35: 100514, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821169

RESUMEN

Nanoplastics are anticipated to be ubiquitous in various environmental compartments. However, challenges in analytical methods hinder our understanding of risks related to specific nanplastics characteristics such as size and chemical compositions, and interactions between nanoplastics and microorganisms. In this study, we applied fit-for-purpose analytical methods and techniques to understand how nanoplastic chemical composition influences their interaction with bacteria collected from activated sludge. When exposed to polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics for 5 days, the nanoplastics attached to the bacteria. Specifically, on day 1, there was a significant predominance of PS nanoplastics over PVC ones of similar size and shape, possibly due to differences in their chemical composition. After 5 days, there is a substantial decrease in nanoplastics attached to bacteria, suggesting bacterial defence mechanisms may reduce particles attachment over time. The overall bacterial community structure demonstrated a high degree of resilience. This resilience highlights the ability of microbial communities to maintain their structure despite nanoplastic stressors, as evidenced by consistent alpha diversity, PCoA, and PERMANOVA results. Understanding these mechanisms is crucial for assessing nanoplastic fate and thus environmental impacts.

3.
ACS Sens ; 9(3): 1482-1488, 2024 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-38416572

RESUMEN

A pH colorimetric sensor array (CSA) was prepared on a nitrocellulose membrane and used for accurate pH measurement in highly concentrated saline solutions. The CSAs consisted of sensing spots made of a suitable OrMoSil polymer prepared from organo-fluorinated-silane precursors and/or organosilane with tetraethyl orthosilicate hosting an acid-base indicator. Four CSAs were prepared: D, 1F, 2F, and 3F. In D, a nonfluorinated organosilane was present. From 1F to 3F, the concentration of the fluorinated organosilane increased and improved the pH measurement accuracy in highly saline concentrations. No recalibrations were required, and the analytical signal was stable in time. D, 1F, 2F, and 3F were deposited in triplicate, and they were prepared to work in the seawater pH interval (7.50-8.50). The use of fluorinated precursors led to a lower pH prediction error and tailored the interval of the CSA at more basic pH values so that the inflection points of the sigmoidal calibrations of D, 1F, 2F, and 3F moved from 6.97 to 7.98. The overall pH prediction error was 0.10 pH (1F), 0.02 pH (2F), and 0.04 pH units (3F). The CSAs were stable, reversible, reusable, and independent of salinity (S) between 20 and 40. The performances of the CSA were compared with those of a glass electrode, whose pHNIST values were converted in the pHSWS scale through a conversion equation. Being unaffected by the typical drawback of the glass electrode, the CSAs can be used directly in seawater real samples, and it validated the proposed conversion equation.


Asunto(s)
Colorimetría , Compuestos de Organosilicio , Concentración de Iones de Hidrógeno , Agua de Mar , Electrodos , Solución Salina
4.
Molecules ; 29(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38338386

RESUMEN

NiO-based nanomaterials have attracted considerable interest for different applications, which have stimulated the implementation of various synthetic approaches aimed at modulating their chemico-physical properties. In this regard, their bottom-up preparation starting from suitable precursors plays an important role, although a molecular-level insight into their reactivity remains an open issue to be properly tackled. In the present study, we focused on the fragmentation of Ni(II) diketonate-diamine adducts, of interest as vapor-phase precursors for Ni(II) oxide systems, by combining electrospray ionization mass spectrometry (ESI-MS) with multiple collisional experiments (ESI-MSn) and theoretical calculations. The outcomes of this investigation revealed common features in the fragmentation pattern of the target compounds: (i) in the first fragmentation, the three complexes yield analogous base-peak cations by losing a negatively charged diketonate moiety; in these cations, Ni-O and Ni-N interactions are stronger and the Ni positive charge is lower than in the parent neutral complexes; (ii) the tendency of ligand electronic charge to migrate towards Ni further increases in the subsequent fragmentation, leading to the formation of a tetracoordinated Ni environment featuring an interesting cation-π intramolecular interaction.

5.
RSC Adv ; 13(49): 34520-34523, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38024983

RESUMEN

Using a unified metal-free procedure, a selection of Thermally Activated Delayed Fluorescence (TADF) emitters has been synthesized and characterized. Different acceptor and donor moieties have been explored in order to develop red emitting dyes with reduction potentials suitable for the application in ECL using tri-propylamine as coreactant. The most promising compound shows terephthalonitrile as the acceptor and diphenylamines as donors, and it displayed an ECL efficiency that is double the one of the standard [Ru(bpy)3](PF6)2. Based on such findings, a novel water-soluble TADF emitter (Na4[4DPASO3TPN]) has been synthesized and characterized to enable electrochemiluminescence in an aqueous medium.

6.
Mar Environ Res ; 192: 106228, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37866198

RESUMEN

Bisphenol A is recognized as an endocrine disruptor that can affect several biological processes in marine species. Consequently, its use has been restricted and it has been replaced with other similar compounds named bisphenol A analogues (BPA analogues). BPA analogues are speculatively considered safer compounds than BPA and their usage is increasing with a consequent higher environmental release. In this study, specimens of the clam Ruditapes philippinarum were exposed to three main BPA analogues, namely BPAF, BPF, BPS and their mixture at an environmentally relevant concentration of 300 ng/L for 7 and 14 days. Effects on biomarkers indicative of cytotoxicity, oxidative stress and damage and neurotoxicity were evaluated. In addition, bioaccumulation of the compound tested was analysed in clam soft tissues. Results showed that BPA analogues at an environment concentration affected cellular parameters and antioxidant system causing also oxidative damage, suggesting that BPA analogues can be harmful compounds for clams.


Asunto(s)
Bivalvos , Estrés Oxidativo , Animales , Bioacumulación , Antioxidantes
7.
iScience ; 26(10): 107955, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37810222

RESUMEN

Mutations in MPV17 are a major contributor to mitochondrial DNA (mtDNA) depletion syndromes, a group of inherited genetic conditions due to mtDNA instability. To investigate the role of MPV17 in mtDNA maintenance, we generated and characterized a Drosophila melanogaster Mpv17 (dMpv17) KO model showing that the absence of dMpv17 caused profound mtDNA depletion in the fat body but not in other tissues, increased glycolytic flux and reduced lifespan in starvation. Accordingly, the expression of key genes of glycogenolysis and glycolysis was upregulated in dMpv17 KO flies. In addition, we demonstrated that dMpv17 formed a channel in planar lipid bilayers at physiological ionic conditions, and its electrophysiological hallmarks were affected by pathological mutations. Importantly, the reconstituted channel translocated uridine but not orotate across the membrane. Our results indicate that dMpv17 forms a channel involved in translocation of key metabolites and highlight the importance of dMpv17 in energy homeostasis and mitochondrial function.

8.
Dalton Trans ; 52(31): 10677-10688, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37337724

RESUMEN

NiO-based films and nanostructured materials have received increasing attention for a variety of technological applications. Among the possible strategies for their fabrication, atomic layer deposition (ALD) and chemical vapor deposition (CVD), featuring manifold advantages of technological interest, represent appealing molecule-to-material routes for which a rational precursor design is a critical step. In this context, the present study is focused on the coordination sphere engineering of three heteroleptic Ni(II) ß-diketonate-diamine adducts of general formula [NiL2TMEDA] [L = 1,1,1-trifluoro-2,4-pentanedionate (tfa), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedionate (fod) or 2,2,6,6-tetramethyl-3,5-heptanedionate (thd), and TMEDA = N,N,N',N'-tetramethylethylenediamine]. Controlled variations in the diketonate structure are pursued to investigate the influence of steric hindrance and fluorination degree on the chemico-physical characteristics of the compounds. A multi-technique investigation supported by density functional calculations highlights that all complexes are air-insensitive and monomeric and that their thermal properties and fragmentation patterns are directly dependent on functional groups in the diketonate ligands. Preliminary thermal CVD experiments demonstrate the precursors' suitability for the obtainment of NiO films endowed with flat and homogeneous surfaces, paving the way to future implementation for CVD end-uses.

9.
Inorg Chem ; 62(4): 1383-1393, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36638827

RESUMEN

Herein, we report a new method to synthesize molecular gold nanoclusters (AuNCs) stabilized by phosphine (PR3) and di-N-heterocyclic carbene (di-NHC) ligands. The interaction of di-NHC gold(I) complexes, with the general formula [(di-NHC)Au2Cl2] with well-known [Au11(PPh3)8Cl2]Cl clusters provides three new classes of AuNCs through a controllable reaction sequence. The synthesis involves an initial ligand metathesis reaction to produce [Au11(di-NHC)(PPh3)6Cl2]+ (type 1 clusters), followed by a thermally induced rearrangement/metal complex addition with the formation of Au13 clusters [Au13(di-NHC)2(PPh3)4Cl4]+ (type 2 clusters). Finally, an additional metathesis process yields [Au13(di-NHC)3(PPh3)3Cl3]2+ (type 3 clusters). The electronic and steric properties of the employed di-NHC ligand affect the product distribution, leading to the isolation and full characterization of different clusters as the main product. A type 3 cluster has been also structurally characterized and was preliminarily found to be strongly emissive in solution.

10.
Mass Spectrom Rev ; 42(4): 1424-1461, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35474466

RESUMEN

Gestational diabetes (GDM) is one of the most common complications occurring during pregnancy. Diagnosis is performed by oral glucose tolerance test, but harmonized testing methods and thresholds are still lacking worldwide. Short-term and long-term effects include obesity, type 2 diabetes, and increased risk of cardiovascular disease. The identification and validation of sensitidve, selective, and robust biomarkers for early diagnosis during the first trimester of pregnancy are required, as well as for the prediction of possible adverse outcomes after birth. Mass spectrometry (MS)-based omics technologies are nowadays the method of choice to characterize various pathologies at a molecular level. Proteomics and metabolomics of GDM were widely investigated in the last 10 years, and various proteins and metabolites were proposed as possible biomarkers. Metallomics of GDM was also reported, but studies are limited in number. The present review focuses on the description of the different analytical methods and MS-based instrumental platforms applied to GDM-related omics studies. Preparation procedures for various biological specimens are described and results are briefly summarized. Generally, only preliminary findings are reported by current studies and further efforts are required to determine definitive GDM biomarkers.


Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Embarazo , Femenino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Biomarcadores , Prueba de Tolerancia a la Glucosa , Espectrometría de Masas
11.
J Hazard Mater ; 441: 129921, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36103767

RESUMEN

Glyphosate will be banned from Europe by the end of 2022, but its widespread use in the last decades and its persistence in the environment require the development of novel remediation processes. In this work, a bacterial consortium was designed de novo with the aim to remove glyphosate from polluted water, supported by the oxygen produced by a microalgal species. To this goal, bioinformatics tools were employed to identify the bacterial strains from contaminated sources (Pseudomonas stutzeri; Comamonas odontotermitis; Sinomonas atrocyanea) able to express enzymes for glyphosate degradation, while the microalga Chlorella protothecoides was chosen for its known performances in wastewater treatment. To follow a bioaugmentation approach, the designed consortium was cultivated in continuous photobioreactors at increasing glyphosate concentrations, from 5 to 50 mg L-1, to boost its acclimation to the presence of the herbicide and its capacity to remove it from water. C. protothecoides tolerance to glyphosate was verified through batch experiments. Remarkably, steady state conditions were reached and the consortium was able to live as a community in the reactor. The consortium activity was validated in both synthetic and real wastewater, where glyphosate concentration was reduced by about 53% and 79%, respectively, without the detection of aminomethylphosphonic acid formation.


Asunto(s)
Chlorella , Herbicidas , Microalgas , Bacterias/metabolismo , Biodegradación Ambiental , Chlorella/metabolismo , Glicina/análogos & derivados , Herbicidas/metabolismo , Microalgas/metabolismo , Oxígeno/metabolismo , Fotobiorreactores/microbiología , Aguas Residuales , Agua , Glifosato
12.
Crit Rev Anal Chem ; 53(8): 1807-1827, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35201944

RESUMEN

One of the most valuable practices for analyzing not-so-analytical-friendly analytes in complex, heterogenous matrices is derivatization. Availability of numerous derivatizing reagents (DRs) makes the modification of analyte more exploitable in terms of an analytical perspective. A wide array of derivatization techniques like pre or post-column, in-situ, enzymatic, ultrasound-assisted, microwave-assisted, photochemical derivatization has added much-needed methodological strength in analyzing intricate analytical matrices (food, water, and soil). In recent years, analytical chemistry has achieved greater heights through the development of new sensitive methods with simple conventional instruments like High-Performance Liquid Chromatography (HPLC) devoid of Mass detectors. The prompt availability of these straightforward instruments also makes it a favorable option for routine analysis in food, environmental, bioanalytical chemistry. Analyzing food, environmental or bioanalytical specimen has some of the most problematic aspects, like the low concentration of the analytes accompanied by not too suitable analytical properties. Even though conventional HPLC lacks the required sensitivity but merger with derivatization can lead to a remarkable increase in sensitivity. In recent years there has been a lot of application of diverse derivatizations to increase the sensitivity and selectivity of the analyte for available instruments, resulting in notable findings. Therefore, this review describes the application of derivatization principles in the analysis of analytes in food and additional matrices using conventional HPLC instruments such as HPLC-UV, HPLC-DAD, and HPLC-FD. In this article, we will briefly review the different modes and multiple types of derivatizing reagents with their mechanisms and importance for encouraging the use of established HPLC instruments.


Asunto(s)
Agua , Cromatografía Líquida de Alta Presión/métodos , Indicadores y Reactivos , Agua/química
13.
Analyst ; 147(22): 5138-5148, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36227218

RESUMEN

Thermal modification of wood is a well-known industrial process performed to increase the durability and dimensional stability or to change the colour of natural wood. The treatment influences many other properties of wood including the emission of volatile organic compounds (VOCs). VOC release ultimately affects the quality of indoor air and the capability of having low VOC emission is often included as a key parameter for the attribution of quality labels. In the present work, wood from six tree species was subjected to different types of treatment and VOC profiling was carried out on both treated and untreated samples by means of PTR-ToF-MS. Different types of thermal treatment were tested, involving either overpressure or vacuum and the effect of different temperature profiles was evaluated. Hardwood and softwood showed different release profiles under all tested conditions: the headspace of softwood was richer in several VOCs, such as terpenes, phenols and C6-C9 aldehydes and carboxylic acids. Upon thermal treatment, terpene emissions decreased, whereas several other VOCs, such as formic acid, formaldehyde, furfural and acetic acid, were released in higher amounts. With its high sensitivity and throughput, PTR-ToF-MS appears to be a very powerful analytical tool, useful in supporting the selection of wood materials for different end uses.


Asunto(s)
Compuestos Orgánicos Volátiles , Madera , Formaldehído , Aldehídos
14.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36232826

RESUMEN

A small library of new angelicin derivatives was designed and synthesized with the aim of bypassing the side effects of trimethylangelicin (TMA), a promising agent for the treatment of cystic fibrosis. To prevent photoreactions with DNA, hindered substituents were inserted at the 4 and/or 6 positions. Unlike the parent TMA, none of the new derivatives exhibited significant cytotoxicity or mutagenic effects. Among the synthesized compounds, the 4-phenylderivative 12 and the 6-phenylderivative 25 exerted a promising F508del CFTR rescue ability. On these compounds, preliminary in vivo pharmacokinetic (PK) studies were carried out, evidencing a favorable PK profile per se or after incorporation into lipid formulations. Therefore, the selected compounds are good candidates for future extensive investigation to evaluate and develop novel CFTR correctors based on the angelicin structure.


Asunto(s)
Fibrosis Quística , Furocumarinas , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , ADN/uso terapéutico , Furocumarinas/química , Furocumarinas/farmacología , Furocumarinas/uso terapéutico , Humanos , Lípidos/uso terapéutico , Mutación
15.
Pharmaceutics ; 14(9)2022 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-36145554

RESUMEN

4,6,4'-trimethylangelicin (TMA) is a promising pharmacological option for the treatment of cystic fibrosis (CF) due to its triple-acting behavior toward the function of the CF transmembrane conductance regulator. It is a poorly water-soluble drug, and thus it is a candidate for developing a self-emulsifying formulation (SEDDS). This study aimed to develop a SEDDS to improve the oral bioavailability of TMA. Excipients were selected on the basis of solubility studies. Polyoxyl-35 castor oil (Cremophor® EL) was proposed as surfactant, diethylene glycol-monoethyl ether (Transcutol® HP) as cosolvent, and a mixture of long-chainmono-,di-, and triglycerides (Maisine® CC) or medium-chain triglycerides (LabrafacTM lipophile) as oil phases. Different mixtures were prepared and characterized by measuring the emulsification time, drop size, and polydispersity index to identify the most promising formulation. Two formulations containing 50% surfactant (w/w), 40% cosolvent (w/w), and 10% oil (w/w) (Maisine® CC or LabrafacTM lipophile) were selected. The results showed that both formulations were able to self-emulsify, producing nanoemulsions with a drop size range of 20-25 nm, and in vivo pharmacokinetic studies demonstrated that they were able to significantly increase the oral bioavailability of TMA. In conclusion, SEEDS are useful tools to ameliorate the pharmacokinetic profile of TMA and could represent a strategy to improve the therapeutic management of CF.

16.
Mar Drugs ; 20(9)2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36135761

RESUMEN

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Phaeophyceae , Algas Marinas , Animales , Proteína C-Reactiva/metabolismo , Suplementos Dietéticos , Diglicéridos/metabolismo , Ácido Graso Sintasas , Inflamación/metabolismo , Interleucina-6/metabolismo , Metabolismo de los Lípidos , Hígado , Ratones , Ratones Endogámicos C57BL , Modelos Teóricos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Perilipina-2/metabolismo , Peroxidasa/metabolismo , Phaeophyceae/metabolismo , ARN Mensajero/metabolismo , Ratas , Algas Marinas/química , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Esteroles/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
17.
J Agric Food Chem ; 70(36): 11412-11418, 2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36039915

RESUMEN

The Rio defect is a coffee off-flavor associated to unpleasant medicinal, phenolic, and iodine-like notes. 2,4,6-Trichloroanisole (TCA) is the main marker of this alteration. A new approach for TCA detection in green coffee beans was evaluated using chemical ionization time-of-flight mass spectrometry and employing a Vocus ion source and ion-molecule reactor (IMR). The sample set consisted of 22 green Coffea arabica from different geographical origins, four of which presented the Rio defect according to an expert cup-tasting panel. Vocus CI-MS was able to perform TCA detection in 3 s, with a sensitivity comparable to that of a sensory panel and showed remarkably good correlation (R2 ≥ 0.9997) with SPME-GC-MS measurements carried out on coffee headspace and hydro-alcoholic extracts. The results demonstrate how the introduction of new quick and sensitive analytical tools could help provide a more comprehensive picture of the Rio coffee off-flavor.


Asunto(s)
Coffea , Anisoles , Coffea/química , Cromatografía de Gases y Espectrometría de Masas , Semillas/química
18.
Biology (Basel) ; 11(5)2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35625421

RESUMEN

The effect of liver steatosis on drug metabolism has been investigated in both preclinical and clinical settings, but the findings of these studies are still controversial. We here evaluated the pharmacokinetic profile of the main sofosbuvir metabolite GS-331007 in healthy animals and rats with non-alcoholic fatty liver disease (NAFLD) after the oral administration of a single 400 mg/kg dose of sofosbuvir. The plasma concentration of GS-331007 was evaluated by HPLC-MS. The expression of the two enzymes uridine monophosphate-cytidine monophosphate kinase 1 (UMP-CMPK1), and nucleoside diphosphate kinase (ND-PK), responsible for the formation of the active metabolite GS-331007-TP, were measured by qRT-PCR and Western Blot. We demonstrated that in rats with steatosis, the area under the plasma concentration-vs-time curve (AUC) and the peak plasma concentration (Cmax) of GS-331007 increased significantly whereas the expression of UMP-CMPK was significantly lower than that of healthy animals. The reduction of UMP-CMPK expression suggests an impairment of sofosbuvir activation to GS-331007-TP, giving a possible explanation for the reduction of sofosbuvir efficacy in patients affected by genotype 3 Hepatitis C virus (HCV), which is often associated with liver steatosis. Furthermore, since GS-331007 plasma concentration is altered by steatosis, it can be suggested that the plasma concentration of this metabolite may not be a reliable indicator for exposure-response analysis in patients with NAFLD.

19.
Int J Mol Sci ; 23(9)2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35563418

RESUMEN

Limits of Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry (MS) in the study of small molecules are due to matrix-related interfering species in the low m/z range. Single-walled carbon nanohorns (SWCNH) were here evaluated as a specific surface for the rapid analysis of amino acids and lipids by Surface-Assisted Laser Desorption Ionization (SALDI). The method was optimized for detecting twenty amino acids, mainly present as cationized species, with the [M+K]+ response generally 2-time larger than the [M+Na]+ one. The [M+Na]+/[M+K]+ signals ratio was tentatively correlated with the molecular weight, dipole moment and binding affinity, to describe the amino acids' coordination ability. The SWCNH-based surface was also tested for analyzing triglycerides in olive oil samples, showing promising results in determining the percentage composition of fatty acids without any sample treatment. Results indicated that SWCNH is a promising substrate for the SALDI-MS analysis of low molecular weight compounds with different polarities, enlarging the analytical platforms for MALDI applications.


Asunto(s)
Carbono , Rayos Láser , Aminoácidos , Carbono/química , Peso Molecular , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
20.
Life (Basel) ; 11(12)2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34947832

RESUMEN

One of the main concerns in industrialized countries is represented by per- and poly-fluoroalkyl substances (PFAS), persistent contaminants hardly to be dealt with by conventional wastewater treatment processes. Phyco-remediation was proposed as a green alternative method to treat wastewater. Synechocystis sp. PCC6803 is a unicellular photosynthetic organism candidate for bioremediation approaches based on synthetic biology, as it is able to survive in a wide range of polluted waters. In this work, we assessed the possibility of applying Synechocystis in PFAS-enriched waters, which was never reported in the previous literature. Respirometry was applied to evaluate short-term toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which did not affect growth up to 0.5 and 4 mg L-1, respectively. Continuous and batch systems were used to assess the long-term effects, and no toxicity was highlighted for both compounds at quite high concentration (1 mg L-1). A partial removal was observed for PFOS and PFOA, (88% and 37%, with removal rates of about 0.15 and 0.36 mg L-1 d-1, respectively). Measurements in fractionated biomass suggested a role for Synechocystis in the sequestration of PFAS: PFOS is mainly internalized in the cell, while PFOA is somehow transformed by still unknown pathways. A preliminary bioinformatic search gave hints on transporters and enzymes possibly involved in such sequestration/transformation processes, opening the route to metabolic engineering in the perspective application of this cyanobacterium as a new phyco-remediation tool, based on synthetic biology.

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