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1.
Water Res ; 257: 121689, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38723350

RESUMO

With the global concerns on antibiotic resistance (AR) as a public health issue, it is pivotal to have data exchange platforms for studies on antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment. For this purpose, the NORMAN Association is hosting the NORMAN ARB&ARG database, which was developed within the European project ANSWER. The present article provides an overview on the database functionalities, the extraction and the contribution of data to the database. In this study, AR data from three studies from China and Nepal were extracted and imported into the NORMAN ARB&ARG in addition to the existing AR data from 11 studies (mainly European studies) on the database. This feasibility study demonstrates how the scientific community can share their data on AR to generate an international evidence base to inform AR mitigation strategies. The open and FAIR data are of high potential relevance for regulatory applications, including the development of emission limit values / environmental quality standards in relation to AR. The growth in sharing of data and analytical methods will foster collaboration on risk management of AR worldwide, and facilitate the harmonization in the effort for identification and surveillance of critical hotspots of AR. The NORMAN ARB&ARG database is publicly available at: https://www.norman-network.com/nds/bacteria/.

2.
Phytochemistry ; : 114104, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657884

RESUMO

Phytochemical investigation on aerial parts of Lysimachia atropurpurea L. (Myrsinaceae), guided by NMR methods, resulted in the isolation and characterization of three previously undescribed triterpenoid saponins named stralysaponins A-C along with five known compounds. Their structures were elucidated by 1D and 2D NMR spectroscopy and HR-ESI-MS. Stralysaponins A-C were categorized into 13ß-28-epoxyoleanane-type triterpenoid saponins, reaffirming their prevalent presence of this type in the Myrsinaceae family and the genus Lysimachia. The identified derivatives share a common four-unit branched sugar chain, with rhamnose as the terminal sugar linked at C-3 of the aglycone. The presence of triterpenoid saponins in L. atropurpurea is reported herein for the first time. This study enriched the chemical diversity of triterpenoid saponins of the genus Lysimachia. Additionally, it demonstrates the effectiveness of NMR-profiling in isolating previously undescribed triterpenoid saponins from Lysimachia spp.

3.
Molecules ; 29(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38675639

RESUMO

Milk is the most consumed liquid food in the world due to its high nutritional value and relatively low cost, characteristics that make it vulnerable to adulteration. One of the most common types of milk adulteration involves the undeclared addition of cow's milk to milk from other mammalian species, such as goats, sheep, buffalo or donkeys. The incidence of such adulteration not only causes a crisis in terms of commercial market and consumer uncertainty but also poses a risk to public health, as allergies can be triggered by proteins in undeclared cow's milk. In this study, a specific qualitative touchdown (TD) PCR method was developed to detect the undeclared addition of cow's milk in goat and sheep milk based on the discrimination of the peak areas of the melting curves after the modification of bovine-specific primers. The developed methodology has high specificity for the DNA templates of other species, such as buffalos and donkeys, and is able to identify the presence of cow's milk down to 1%. Repeatability was tested at low bovine concentrations of 5% and 1% and resulted in %RSD values of 1.53-2.04 for the goat-cow assay and 2.49-7.16 for the sheep-cow assay, respectively. The application of this method to commercial goat milk samples indicated a high percentage of noncompliance in terms of labeling (50%), while a comparison of the results to rapid immunochromatographic and ELISA kits validated the excellent sensitivity and applicability of the proposed PCR methodology that was able to trace more adulterated samples. The developed assays offer the advantage of multiple detection in a single run, resulting in a cost- and time-efficient method. Future studies will focus on the applicability of these assays in dairy products such as cheese and yogurt.


Assuntos
Contaminação de Alimentos , Cabras , Leite , Reação em Cadeia da Polimerase , Animais , Leite/química , Ovinos , Bovinos , Reação em Cadeia da Polimerase/métodos , Contaminação de Alimentos/análise , Búfalos
4.
Foods ; 13(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611440

RESUMO

Lactic acid bacteria (LAB) are widely applied for fermentation purposes in dairy and non-dairy food matrices with beneficial technological and health-promoting properties. This study describes the effect of two lactic acid bacteria, namely, Lactiplantibacillus paracasei SP5 and Pediococcus pentosaceus SP2, on the phenolic profiles, antioxidant activities, total phenolic content (TPC), carotenoid content, and sensorial profile of two different mixed fruit juices. After 48 h of fermentation, both LABs retained viability over 9 Log CFU/mL in both juices. The TPC, zeaxanthin + lutein, ß-carotene content, and antioxidant activity (AA) were elevated for both LABs and mixed juices after 48 h of fermentation compared to control samples. Regarding the phenolic profile, both juices exhibited a significant decrease in chlorogenic acid levels, while quinic acid and tyrosol concentrations showed notable increases.

5.
Anal Methods ; 16(17): 2684-2692, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38623768

RESUMO

This study presents the development and validation of a comprehensive high-resolution mass spectrometry (HRMS) methodology for the detection of 771 pesticides in olive oil, using liquid chromatography with electrospray ionization, operating in positive and negative mode, and gas chromatography with atmospheric-pressure chemical ionization in positive mode, both coupled to quadrupole-time-of-flight mass spectrometry (LC-(ESI)-/GC-(APCI)-QTOF MS). Special reference is made to the post-acquisition evaluation step, in which all LC/GC-HRMS analytical evidence (i.e. mass accuracy, retention time, isotopic pattern, MS/MS fragmentation) is taken into account in order to successfully identify the compounds. The sample preparation of the method involves a QuEChERS-based protocol, common for both techniques, differentiated only on the reconstitution step, making the method highly applicable in routine analysis. A smart evaluation of method's performance was carried out, with 65 representative analytes comprising the validation set. The method was validated in terms of linearity, accuracy, matrix effect and precision, while the limits of detection and quantification of the method were estimated. Finally, twenty Greek olive oil samples were analysed in both analytical platforms and the findings included the pesticides lambda-cyhalothrin, chlorpyrifos, phosphamidon, pirimiphos-methyl and esprocarb at low ng g-1 level.


Assuntos
Azeite de Oliva , Espectrometria de Massas por Ionização por Electrospray , Azeite de Oliva/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Líquida/métodos , Praguicidas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Resíduos de Praguicidas/análise , Limite de Detecção , Reprodutibilidade dos Testes , Contaminação de Alimentos/análise
6.
Environ Sci Technol ; 58(14): 6093-6104, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38545700

RESUMO

Second-generation anticoagulant rodenticides (SGARs) are widely used to control rodent populations, resulting in the serious secondary exposure of predators to these contaminants. In the United Kingdom (UK), professional use and purchase of SGARs were revised in the 2010s. Certain highly toxic SGARs have been authorized since then to be used outdoors around buildings as resistance-breaking chemicals under risk mitigation procedures. However, it is still uncertain whether and how these regulatory changes have influenced the secondary exposure of birds of prey to SGARs. Based on biomonitoring of the UK Common Buzzard (Buteo buteo) collected from 2001 to 2019, we assessed the temporal trend of exposure to SGARs and statistically determined potential turning points. The magnitude of difenacoum decreased over time with a seasonal fluctuation, while the magnitude and prevalence of more toxic brodifacoum, authorized to be used outdoors around buildings after the regulatory changes, increased. The summer of 2016 was statistically identified as a turning point for exposure to brodifacoum and summed SGARs that increased after this point. This time point coincided with the aforementioned regulatory changes. Our findings suggest a possible shift in SGAR use to brodifacoum from difenacoum over the decades, which may pose higher risks of impacts on wildlife.


Assuntos
Anticoagulantes , Rodenticidas , Animais , Anticoagulantes/análise , Rodenticidas/análise , Animais Selvagens , Aves , Reino Unido , Monitoramento Ambiental
7.
J Hazard Mater ; 469: 133955, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457976

RESUMO

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open-source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.


Assuntos
Drogas Ilícitas , Poluentes Químicos da Água , Águas Residuárias , Fluxo de Trabalho , Psicotrópicos , China , Poluentes Químicos da Água/análise
8.
Chemosphere ; 352: 141425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340995

RESUMO

The presence of micropollutants in water bodies has become a growing concern due to their persistence, bioaccumulation and potential toxicological effects on aquatic life and humans. In this study, the performance of a column system consisting of zero-valent iron nanoparticles (nZVI) incorporated into a cationic resin and synthesized from green tea extract with the addition of persulfate for the elimination of selected pharmaceuticals and endocrine disruptors from wastewater is evaluated. Ibuprofen, naproxen, diclofenac and ketoprofen were the target pharmaceuticals from non-steroidal anti-inflammatory drugs group, while bisphenol A was the target endocrine disruptor. In this context, different real wastewater effluent matrices were investigated: anaerobic membrane bioreactor (AnMBR), upflow anaerobic sludge blanket reactor (UASB) after microfiltration, tertiary treated by conventional activated sludge system and saturated vertical constructed wetland followed by a sand filtration unit effluent (hybrid). The transformation products of diclofenac and bisphenol A were also identified. The experimental results indicated that the performance of the R-nFe/PS system towards the removal efficiency of the target compounds was enhanced in the order of effluents: tertiary > AnMBR ≈ hybrid > UASB. More than 70% removal was obtained for almost all target compounds when conventional tertiary effluent was used, while the maximum removal efficiency was about 50% in the case of filtered UASB. As far as we know, this is the first time that nZVI has been assessed in combination with persulfate for the removal of micropollutants in a continuous flow system receiving various types of real wastewater with different matrix characteristics.


Assuntos
Compostos Benzidrílicos , Fenóis , Águas Residuárias , Poluentes Químicos da Água , Humanos , Esgotos , Eliminação de Resíduos Líquidos/métodos , Diclofenaco , Ferro , Anaerobiose , Reatores Biológicos , Preparações Farmacêuticas
9.
Chemosphere ; 352: 141260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272137

RESUMO

The existence of the artificial sweetener acesulfame (ACE) in quantities of significance can negatively impact water quality, and its consumption has been associated with deleterious health effects. The present investigation explores the efficacy of heat-activated sodium persulfate (SPS) for eliminating ACE. The complete degradation of 0.50 mg L-1 of ACE was achieved within 45 min under a reaction temperature of 50 °C and 100 mg L-1 of SPS. The impact of thermal decomposition on ACE at a temperature of 60 °C was negligible. This study considers several factors, such as the SPS and ACE loading, the reaction temperature, the initial pH, and the water matrix of the reactor. The results indicate that the method's efficiency is positively correlated with higher initial concentrations of SPS, whereas it is inversely associated with the initial concentration of ACE. Furthermore, higher reaction temperatures and acidic initial pH levels promote the degradation of acesulfame. At the same time, certain constituents of the water matrix, such as humic acid, chlorides, and bicarbonates, can hinder the degradation process. Additionally, the data from LC-QToF-MS analysis of the samples were used to investigate transformation through suspect and non-target screening approaches. Overall, ACE's eight transformation products (TPs) were detected, and a potential ACE decomposition pathway was proposed. The concentration of TPs followed a volcano curve, decreasing in long treatment times. The ecotoxicity of ACE and its identified TPs was predicted using the ECOSAR software. The majority of TPs exhibited not harmful values.


Assuntos
Compostos de Sódio , Sulfatos , Poluentes Químicos da Água , Oxirredução , Poluentes Químicos da Água/análise , Temperatura Alta , Temperatura , Cinética , Edulcorantes/toxicidade , Edulcorantes/análise
10.
J Mol Biol ; 436(6): 168449, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244767

RESUMO

Inhibition of Insulin-Regulated Aminopeptidase is being actively explored for the treatment of several human diseases and several classes of inhibitors have been developed although no clinical applications have been reported yet. Here, we combine enzymological analysis with x-ray crystallography to investigate the mechanism employed by two of the most studied inhibitors of IRAP, an aryl sulfonamide and a 2-amino-4H-benzopyran named HFI-419. Although both compounds have been hypothesized to target the enzyme's active site by competitive mechanisms, we discovered that they instead target previously unidentified proximal allosteric sites and utilize non-competitive inhibition mechanisms. X-ray crystallographic analysis demonstrated that the aryl sulfonamide stabilizes the closed, more active, conformation of the enzyme whereas HFI-419 locks the enzyme in a semi-open, and likely less active, conformation. HFI-419 potency is substrate-dependent and fails to effectively block the degradation of the physiological substrate cyclic peptide oxytocin. Our findings demonstrate alternative mechanisms for inhibiting IRAP through allosteric sites and conformational restricting and suggest that the pharmacology of HFI-419 may be more complicated than initially considered. Such conformation-specific interactions between IRAP and small molecules can be exploited for the design of more effective second-generation allosteric inhibitors.


Assuntos
Sítio Alostérico , Inibidores Enzimáticos , Insulina , Sulfonamidas , Humanos , Domínio Catalítico/efeitos dos fármacos , Cistinil Aminopeptidase/antagonistas & inibidores , Cistinil Aminopeptidase/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Insulina/metabolismo , Sulfonamidas/química , Sulfonamidas/farmacologia , Cristalografia por Raios X , Regulação Alostérica , Sítio Alostérico/efeitos dos fármacos , Células HEK293 , Células CHO , Animais , Cricetulus
11.
Sci Total Environ ; 914: 169747, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38159750

RESUMO

Ever since the outbreak of COVID-19 disease in Wuhan, China, different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. Wastewater-based epidemiology (WBE), an approach that has been successfully applied in numerous case studies worldwide, offers a cost-effective and rapid way for monitoring trends of SARS-Cov-2 in the community level without selection bias. Despite being a gold-standard procedure, WBE is a challenging approach due to the sample instability and the moderate efficiency of SARS-CoV-2 concentration in wastewater. In the present study, we introduce Spike-Seq, a custom amplicon-based approach for the S gene sequencing of SARS-CoV-2 in wastewater samples, which enables not only the accurate identification of the existing Spike-related genetic markers, but also the estimation of their frequency in the investigated samples. The implementation of Spike-Seq involves the combination of nested PCR-based assays that efficiently amplify the entire nucleotide sequence of the S gene and next-generation sequencing, which enables the variant detection and the estimation of their frequency. In the framework of the current work, Spike-Seq was performed to investigate the mutational profile of SARS-CoV-2 in samples from the Wastewater Treatment Plant (WWTP) of Athens, Greece, which originated from multiple timepoints, ranging from March 2021 until July 2022. Our findings demonstrate that Spike-Seq efficiently detected major genetic markers of B.1.1.7 (Alpha), B.1.617.2 (Delta) as well as B.1.1.529 (Omicron) variants in wastewater samples and provided their frequency levels, showing similar variant distributions with the published clinical data from the National Public Health organization. The presented approach can prove to be a useful tool for the detection of SARS-CoV-2 in challenging wastewater samples and the identification of the existing genetic variants of S gene.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Sequência de Bases , Marcadores Genéticos , Águas Residuárias , Sequenciamento de Nucleotídeos em Larga Escala , Mutação
12.
Anal Bioanal Chem ; 415(29-30): 7297-7313, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37946034

RESUMO

Chemicals infiltrate our daily experiences through multiple exposure pathways. Human biomonitoring (HBM) is routinely used to comprehensively understand these chemical interactions. Historically, HBM depended on targeted screening methods limited to a relatively small set of chemicals with triple quadrupole instruments typically. However, recent advances in high-resolution mass spectrometry (HRMS) have facilitated the use of broad-scope target, suspect, and non-target strategies, enhancing chemical exposome characterization within acceptable detection limits. Despite these advancements, establishing robust and efficient sample treatment protocols is still essential for trustworthy broad-range chemical analysis. This study sought to validate a methodology leveraging HRMS-based strategies for accurate profiling of exogenous chemicals and related metabolites in urine samples. We evaluated five extraction protocols, each encompassing various chemical classes, such as pharmaceuticals, plastic additives, personal care products, and pesticides, in terms of their extraction recoveries, linearity, matrix effect, sensitivity, and reproducibility. The most effective protocol was extensively validated and subsequently applied to 10 real human urine samples using wide-scope target analysis encompassing over 2000 chemicals. We successfully identified and semi-quantified a total of 36 chemicals using an ionization efficiency-based model, affirming the methodology's robust performance. Notably, our results dismissed the need for a deconjugation step, a typically labor-intensive and time-consuming process.


Assuntos
Monitoramento Ambiental , Humanos , Monitoramento Ambiental/métodos , Cromatografia Líquida/métodos , Reprodutibilidade dos Testes , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas/métodos
13.
Heliyon ; 9(11): e21311, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37954321

RESUMO

The determination of volatile compounds is essential for the chemical characterisation of honey's aroma and its correlation to its sensory profile and botanical origin. The present study describes the development, optimization and validation of a new, simple and reliable method for the determination of volatile compounds in honey using headspace solid-phase microextraction combined with gas chromatography/mass spectrometry (HS-SPME-GC-MS). The optimization of the SPME conditions showed that the ratio of honey: water (2:1) and the incubation temperature (60 °C) are the most critical parameters. Gas chromatography was performed with medium polar Varian CP-Select 624 column and the experimental Retention Index for a number of compounds was determined as an additional identification feature for suspect analysis. The simultaneous use of four internal standards chlorobenzene, benzophenone, 2-pentanol and 4-methyl-2-pentanone and matrix matched calibration enhanced method accuracy achieving recoveries 73-114 % and repeatability ranging between 3.9 and 19 % relative standard deviations. Furthermore, the superiority of the HS-SPME to static head space technique was verified exhibiting four-to nine-fold higher sensitivity. Target and suspect screening were applied to 30 Greek honey samples and 53 volatile compounds belonging to different chemical classes, such as alkanes, aldehydes, ketones, alcohols, and esters were identified with quantified concentrations ranging between 3.1 µg kg-1 (Limonene) up to 20 mg kg-1 (Benzeneacetaldehyde). Among the new findings is the detection of Myrtenol in Greek pine honey and 2,3-butanediol in Greek oak honey. The developed analytical protocol can be a valuable tool in order to chemically characterize honey based on the volatile content.

14.
Metabolites ; 13(11)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37999243

RESUMO

Preterm delivery (PTD) is a notable pregnancy complication, affecting one out of every ten births. This study set out to investigate whether analyzing the metabolic composition of amniotic fluid (AF) collected from pregnant women during the second trimester of pregnancy could offer valuable insights into prematurity. The research employed 1H-NMR metabolomics to examine AF samples obtained from 17 women who gave birth prematurely (between 29+0 and 36+5 weeks of gestation) and 43 women who delivered at full term. The application of multivariate analysis revealed metabolites (dimethylglycine, glucose, myo-inositol, and succinate) that can serve as possible biomarkers for the prognosis and early diagnosis of preterm delivery. Additionally, pathway analysis unveiled the most critical metabolic pathways relevant to our research hypothesis. In summary, these findings suggest that the metabolic composition of AF in the second trimester can be a potential indicator for identifying biomarkers associated with the risk of PTD.

15.
Environ Int ; 181: 108288, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37918065

RESUMO

A collaborative trial involving 16 participants from nine European countries was conducted within the NORMAN network in efforts to harmonise suspect and non-target screening of environmental contaminants in whole fish samples of bream (Abramis brama). Participants were provided with freeze-dried, homogenised fish samples from a contaminated and a reference site, extracts (spiked and non-spiked) and reference sample preparation protocols for liquid chromatography (LC) and gas chromatography (GC) coupled to high resolution mass spectrometry (HRMS). Participants extracted fish samples using their in-house sample preparation method and/or the protocol provided. Participants correctly identified 9-69 % of spiked compounds using LC-HRMS and 20-60 % of spiked compounds using GC-HRMS. From the contaminated site, suspect screening with participants' own suspect lists led to putative identification of on average ∼145 and ∼20 unique features per participant using LC-HRMS and GC-HRMS, respectively, while non-target screening identified on average ∼42 and ∼56 unique features per participant using LC-HRMS and GC-HRMS, respectively. Within the same sub-group of sample preparation method, only a few features were identified by at least two participants in suspect screening (16 features using LC-HRMS, 0 features using GC-HRMS) and non-target screening (0 features using LC-HRMS, 2 features using GC-HRMS). The compounds identified had log octanol/water partition coefficient (KOW) values from -9.9 to 16 and mass-to-charge ratios (m/z) of 68 to 761 (LC-HRMS and GC-HRMS). A significant linear trend was found between log KOW and m/z for the GC-HRMS data. Overall, these findings indicate that differences in screening results are mainly due to the data analysis workflows used by different participants. Further work is needed to harmonise the results obtained when applying suspect and non-target screening approaches to environmental biota samples.


Assuntos
Monitoramento Ambiental , Peixes , Animais , Humanos , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos
16.
Molecules ; 28(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37836613

RESUMO

Significant efforts have been spent in the modern era towards implementing environmentally friendly procedures like composting to mitigate the negative effects of intensive agricultural practices. In this context, a novel fertilizer was produced via the hydrolysis of an onion-derived compost, and has been previously comprehensively chemically characterized. In order to characterize its efficacy, the product was applied to tomato plants at five time points to monitor plant health and growth. Control samples were also used at each time point to eliminate confounding parameters due to the plant's normal growth process. After harvesting, the plant leaves were extracted using aq. MeOH (70:30, v/v) and analyzed via UPLC-QToF-MS, using a C18 column in both ionization modes (±ESI). The data-independent (DIA/bbCID) acquisition mode was employed, and the data were analyzed by MS-DIAL. Statistical analysis, including multivariate and trend analysis for longitudinal monitoring, were employed to highlight the differentiated features among the controls and treated plants as well as the time-point sequence. Metabolites related to plant growth belonging to several chemical classes were identified, proving the efficacy of the fertilizer product. Furthermore, the efficiency of the analytical and statistical workflows utilized was demonstrated.


Assuntos
Fertilizantes , Solanum lycopersicum , Fertilizantes/análise , Fluxo de Trabalho , Espectrometria de Massas/métodos , Agricultura , Cromatografia Líquida de Alta Pressão
17.
Molecules ; 28(19)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37836742

RESUMO

Inflammatory mediators constitute a recently coined term in the field of metal-based complexes with antiplatelet activities. Our strategy targets Platelet-Activating Factor (PAF) and its receptor, which is the most potent lipid mediator of inflammation. Thus, the antiplatelet (anti-PAF) potency of any substance could be exerted by inhibiting the PAF-induced aggregation in washed rabbit platelets (WRPs), which internationally is a well-accepted methodology. Herein, a series of mononuclear (mer-[Cr(pqx)Cl3(H2O]) (1), [Co(pqx)Cl2(DMF)] (2) (DMF = N,N'-dimethyl formamide), [Cu(pqx)Cl2(DMSO)] (3) (DMSO = dimethyl sulfoxide), [Zn(pqx)Cl2] (4)) and dinuclear complexes ([Mn(pqx)(H2O)2Cl2]2 (5), [Fe(pqx)Cl2]2 (6) and [Ni(pqx)Cl2]2 (7)) incorporating the 2-(2'-pyridyl)quinoxaline ligand (pqx), were biologically evaluated as inhibitors of the PAF- and thrombin-induced aggregation in washed rabbit platelets (WRPs). The molecular structure of the five-co-ordinate analog (3) has been elucidated by single-crystal X-ray diffraction revealing a trigonal bipyramidal geometry. All complexes are potent inhibitors of the PAF-induced aggregation in WRPs in the micromolar range. Complex (6) displayed a remarkable in vitro dual inhibition against PAF and thrombin, with IC50 values of 1.79 µM and 0.46 µM, respectively. Within the series, complex (5) was less effective (IC50 = 39 µM) while complex (1) was almost 12-fold more potent against PAF, as opposed to thrombin-induced aggregation. The biological behavior of complexes 1, 6 and 7 on PAF's basic metabolic enzymatic pathways reveals that they affect key biosynthetic and catabolic enzymes of PAF underlying the anti-inflammatory properties of the relevant complexes. The in vitro cytotoxic activities of all complexes in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) are described via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results reveal that complex 3 is the most potent within the series.


Assuntos
Antineoplásicos , Complexos de Coordenação , Elementos de Transição , Animais , Humanos , Coelhos , Agregação Plaquetária , Fator de Ativação de Plaquetas/farmacologia , Fator de Ativação de Plaquetas/metabolismo , Plaquetas/metabolismo , Trombina/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/metabolismo , Ligantes , Mediadores da Inflamação/metabolismo , Dimetil Sulfóxido/farmacologia , Quinoxalinas/farmacologia , Células HEK293 , Células HeLa , Antineoplásicos/farmacologia , Elementos de Transição/metabolismo
18.
ACS Omega ; 8(37): 33639-33650, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37744818

RESUMO

Heterostructured photocatalytic materials in the form of photonic crystals have been attracting attention for their unique light harvesting ability that can be ideally combined with judicious compositional modifications toward the development of visible light-activated (VLA) photonic catalysts, though practical environmental applications, such as the degradation of pharmaceutical emerging contaminants, have been rarely reported. Herein, heterostructured MoS2-TiO2 inverse opal films are introduced as highly active immobilized photocatalysts for the VLA degradation of tetracycline and ciprofloxacin broad-spectrum antibiotics as well as salicylic acid. A single-step co-assembly method was implemented for the challenging incorporation of MoS2 nanosheets into the nanocrystalline inverse opal walls. Compositional tuning and photonic band gap engineering of the MoS2-TiO2 photonic films showed that integration of low amounts of MoS2 nanosheets in the inverse opal framework maintains intact the periodic macropore structure and enhances the available surface area, resulting in efficient VLA antibiotic degradation far beyond the performance of benchmark TiO2 films. The combination of broadband MoS2 visible light absorption and photonic-assisted light trapping together with the enhanced charge separation that enables the generation of reactive oxygen species via firm interfacial coupling between MoS2 nanosheets and TiO2 nanoparticles is concluded as a competent approach for pharmaceutical abatement in water bodies.

19.
Int J Mol Sci ; 24(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37762269

RESUMO

(1) Carfilzomib (Cfz) is an antineoplastic agent indicated for the treatment of multiple myeloma. However, its beneficial action is attenuated by the occurrence of cardiotoxicity and nephrotoxicity as the most common adverse effects. Presently, there is well-established knowledge on the pathomechanisms related to these side effects; however, the research on the metabolic alterations provoked by the drug is limited. (2) An in vivo simulation of Cfz-induced toxicity was developed in (i) Cfz-treated and (ii) control mice. An RP-HRMS-based protocol and an advanced statistical treatment were used to investigate the impact of Cfz on the non-polar metabolome. (3) The differential analysis classified the Cfz-treated and control mice and resulted in a significant number of identified biomarkers with AUC > 0.9. The drug impaired the biosynthesis and degradation of aromatic amino acids (AAA) and led to alterations of uremic toxins in the renal and urine levels. Furthermore, the renal degradation of tryptophan was affected, inducing its degradation via the kynurenine pathway. (4) The renal levels of metabolites showed impaired excretion and degradation of AAAs. Cfz was, finally, correlated with the biosynthesis of renal dopamine, explaining the biochemical causes of water and ion retention and the increase in systolic pressure.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metabolômica , Animais , Camundongos , Oligopeptídeos/farmacologia , Aminoácidos Aromáticos , Metaboloma
20.
Sci Total Environ ; 900: 166136, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37567285

RESUMO

Due to governments' actions to contain the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the activity of common circulating respiratory viruses was significantly disrupted after the COVID-19 pandemic and thorough surveillance of respiratory pathogens was considered essential worldwide. Wastewater-based epidemiology has proven to be a valuable tool, that provides complementary information on disease outbreaks and is increasingly used to study the infection dynamics of other viruses, apart from SARS-CoV-2. The aims of the present study were the detection of four commonly circulating respiratory viruses: SARS-CoV-2, influenza A, B and Human Respiratory Syncytial Virus (RSV), the evaluation of the COVID-19 pandemic impact on their seasonality and the determination of the possible common trends in the viral load of these viruses in the wastewater of the Attica region. A standardized and validated concentration and extraction protocol was used, generic for all four viruses, followed by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) assays. The study proved that there was a prolonged period when all four viruses circulated in the population and an early outbreak of seasonal influenza and RSV in 2022-2023, compared to data from the pre-COVID-19 period. SARS-CoV-2, influenza A and RSV concentrations showed peak levels during December, followed by a slight decline in influenza A concentrations, followed by steady increase of influenza B concentrations in January 2023. SARS-CoV-2 was the dominant virus throughout the whole study period. This is the first study in Greece that investigated the most common circulating viruses simultaneously and in one of the largest timelines, providing crucial information about their infection dynamics during a period when an outbreak of respiratory diseases was declared by the National Public Health Organization. Presented results highlight the establishment of environmental surveillance as a non-invasive and complementary virus outbreak monitoring tool and the importance of influenza A, B and RSV integration into a wastewater-based surveillance system to help in disease management.


Assuntos
COVID-19 , Influenza Humana , Humanos , COVID-19/epidemiologia , Vigilância Epidemiológica Baseada em Águas Residuárias , SARS-CoV-2 , Águas Residuárias , Pandemias
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