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2.
Sci Total Environ ; 927: 172227, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582104

RESUMO

The sensory quality of drinking water, and particularly its taste and odor (T&O) is a key determinant of consumer acceptability, as consumers evaluate water by their senses. Some of the conventional treatment processes to control compounds which impart unpleasant T&O have limitations because of their low efficiency and/or high costs. Therefore, there is a great need to develop an effective process for removing T&O compounds without secondary concerns. The primary objective of this study was to assess for the first time the effectiveness of spirulina-based carbon materials in removing geosmin (GSM) and 2-methylisoborneol (2-MIB) from water, two commonly occurring natural T&O compounds. The efficiency of the materials to remove environmentally relevant concentrations of GSM and 2-MIB (ng L-1) from ultrapure and raw water was investigated using a sensitive headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC/MS) method. Moreover, the genotoxic and cytotoxic effects of the spirulina-based materials were assessed for the first time to evaluate their safety and their potential in the treatment of water for human consumption. Based on the results, spirulina-based materials were found to be promising for drinking water treatment applications, as they did not exert geno-cytotoxic effects on human cells, while presenting high efficiency in removing GSM and 2-MIB from water.


Assuntos
Água Potável , Odorantes , Spirulina , Paladar , Poluentes Químicos da Água , Purificação da Água , Água Potável/química , Odorantes/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Naftóis , Humanos , Canfanos , Adsorção , Microextração em Fase Sólida/métodos , Carbono , Cromatografia Gasosa-Espectrometria de Massas
3.
Wei Sheng Yan Jiu ; 53(2): 316-331, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38604970

RESUMO

OBJECTIVE: To establishe an analysis and identification method for 2-methylisoborneol(2-MIB) and geosmin(GSM) in water using purge and trap-gas chromatography-mass spectrometry. METHODS: The samples were enriched and analyzed using a purge and trap system, followed by the separation on a DB-624(30 m×0.25 mm, 1.4 µm) chromatographic column. Quantification was performed using gas chromatography-mass spectrometry with the selected ion monitoring and internal standard calibration. RESULTS: The calibration curves for 2-MIB and GSM showed an excellent linearity in the range of 1 to 100 ng/L with R~2 values greater than 0.999. The detection limit and quantification limit for both 2-MIB and GSM were 0.33 ng/L and 1.0 ng/L, respectively. Spike recovery experiments were further carried on the source water and drinking water at three concentration levels. It showed that the average recoveries were from 82.0% to 111.0% for 2-MIB while 84.0% to 110% for GSM. Additionally, the test precision of 2-MIB and GSM ranged from 1.9% to 7.3% and 1.9% to 5.0%(n=6), respectively. The analysis of multiple samples including the local source water, treated water and distribution network water confirmed the existence of 2-MIB and GSM. CONCLUSION: Compared to the national standard(GB/T 5750.8-2023), the proposed method enables fully automated sample introduction and analysis without the extra pre-treatment. It provides the advantages of simplicity, good repeatability and high accuracy.


Assuntos
Água Potável , Naftóis , Poluentes Químicos da Água , Água/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Água Potável/análise , Canfanos/análise , Poluentes Químicos da Água/análise , Odorantes/análise
4.
An Acad Bras Cienc ; 96(1): e20230145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451597

RESUMO

In the last few years, the presence of geosmin (GEO) in water bodies has caused serious problems related to water consumption by the population. Many studies focus on its occurrence and detection, but little is discussed about the technologies for treatment and removal of this contaminant. In this way, the present work aims to present a bibliographic search and a bibliometric analysis carried out in the Web of Science database and in VOSviewer software about geosmin remediation, in the last 10 years. 100 articles were found, of which only one, from 2021, was a review. It was possible to assess that the subject has gained greater notoriety in the last 7 years, since the year 2016 marked the increase of publications on the subject, as well as an increasing number of citations. Among the most published countries is the People's Republic of China, with 53% of publications. Bibliometric analysis showed that GEO is directly related to 2-methylisoborneol (2-MIB), since both occur simultaneously in water bodies. In addition, it was possible to identify that adsorptive processes are the most used in the removal of these contaminants, followed by advanced oxidative processes and biological processes, in that order.


Assuntos
Bibliometria , Naftóis , Humanos , Adsorção , Água
5.
Neurosci Lett ; 826: 137712, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447888

RESUMO

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.


Assuntos
Benzamidas , Glaucoma , Naftóis , Hipertensão Ocular , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Proteína X Associada a bcl-2 , Interleucina-6 , Camundongos Endogâmicos C57BL , Hipertensão Ocular/tratamento farmacológico , Glaucoma/tratamento farmacológico
6.
J Biotechnol ; 386: 1-9, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38479473

RESUMO

(-)-Geosmin has high demand in perfumes and cosmetic products for its earthy congenial aroma. The current production of (-)-geosmin is either by distillation of sun-baked soil or by inefficient chemical synthesis because of the presence of multiple chiral centers. Fermentation processes are not viable as the titers of the Streptomyces sp. based processes are low. This work presents an alternative route by the heterologous synthesis of (-)-geosmin in Saccharomyces cerevisiae. The enzyme involved is the bifunctional geosmin synthase that catalyzes the conversion of farnesyl diphosphate to germacradienol and germacradienol to geosmin. This study evaluated the activity of many orthologs of geosmin synthase when expressed heterologously in S. cerevisiae. When the well-characterized CAB41566 from Streptomyces coelicolor origin was tested, germacradienol and germacrene D were detected but no geosmin. Bioinformatic analysis based on high/low identities to N-terminal and C-terminal domains of CAB41566 was carried out to identify different orthologs of geosmin synthase proteins from different bacterial and fungal origins. ADO68918 of Stigmatella aurantiaca origin showed the best activity among the tested orthologs, not only in terms of geosmin production but also an order of magnitude higher total abundance of the products of geosmin synthase as compared to CAB41566. This study successfully demonstrated the production of (-)-geosmin in S. cerevisiae and offers an alternative, sustainable and environment-friendly approach to producing (-)-geosmin.


Assuntos
Streptomyces coelicolor , Streptomyces , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Streptomyces/metabolismo , Streptomyces coelicolor/metabolismo , Naftóis/química , Naftóis/metabolismo
7.
J Agric Food Chem ; 72(12): 6735-6743, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38533988

RESUMO

A requisite to improving the taste and odor attributes of farmed fish is the availability of accurate and practical analytical methods to quantify 2-methylisoborneol (MIB) and geosmin (GSM). Solid-phase microextraction (SPME) enables reliable measurement of nanogram per liter quantities of MIB and GSM in water. In contrast, direct headspace (HS)-SPME of biological matrices with variable proximate compositions can increase bias and uncertainty in off-flavor determinations. Analytical recovery plays a crucial role in the accurate determination of MIB and GSM in fish, and this study investigates strategies to maximize and account for this recovery factor. MIB and GSM values in off-flavor catfish and trout were measured using direct HS-SPME and distillation as sample preparation techniques. Trout samples prepared by distillation yielded 10-fold higher GSM recoveries than those from direct HS-SPME (31% versus 3%). A stable isotope dilution method (SIDM) was implemented by routinely spiking samples with known quantities of deuterium-labeled MIB and GSM, allowing for the correction of sample-to-sample recovery deviations. SIDM-determined GSM values generated recoveries of 106 and 95% for direct HS-SPME and distilled trout, respectively. Aspects of the strategies and techniques presented can be incorporated into existing analytical methods to improve the accuracy and sample throughput. Particularly, routine inclusion of SIDM in the evaluation of MIB and GSM can facilitate identification of reliable practices to control off-flavors in aquaculture.


Assuntos
Canfanos , Peixes-Gato , Naftóis , Animais , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas , Naftóis/química , Odorantes/análise
8.
Water Res ; 253: 121357, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401471

RESUMO

Freshwater benthic algae form complex mat matrices that can confer ecosystem benefits but also produce harmful cyanotoxins and nuisance taste-and-odor (T&O) compounds. Despite intensive study of the response of pelagic systems to anthropogenic change, the environmental factors controlling toxin presence in benthic mats remain uncertain. Here, we present a unique dataset from a rapidly urbanizing community (Kansas City, USA) that spans environmental, toxicological, taxonomic, and genomic indicators to identify the prevalence of three cyanotoxins (microcystin, anatoxin-a, and saxitoxin) and two T&O compounds (geosmin and 2-methylisoborneol). Thereafter, we construct a random forest model informed by game theory to assess underlying drivers. Microcystin (11.9 ± 11.6 µg/m2), a liver toxin linked to animal fatalities, and geosmin (0.67 ± 0.67 µg/m2), a costly-to-treat malodorous compound, were the most abundant compounds and were present in 100 % of samples, irrespective of land use or environmental conditions. Anatoxin-a (8.1 ± 11.6 µg/m2) and saxitoxin (0.18 ± 0.39 µg/m2), while not always detected, showed a systematic tradeoff in their relative importance with season, an observation not previously reported in the literature. Our model indicates that microcystin concentrations were greatest where microcystin-producing genes were present, whereas geosmin concentrations were high in the absence of geosmin-producing genes. Together, these results suggest that benthic mats produce microcystin in situ but that geosmin production may occur ex situ with its presence in mats attributable to adsorption by organic matter. Our study broadens the awareness of benthic cyanobacteria as a source of harmful and nuisance metabolites and highlights the importance of benthic monitoring for sustaining water quality standards in rivers.


Assuntos
Microcistinas , Naftóis , Saxitoxina , Tropanos , Animais , Humanos , Paladar , Odorantes/análise , Ecossistema , Toxinas de Cianobactérias , Rios/microbiologia
9.
Int J Hyg Environ Health ; 256: 114323, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237548

RESUMO

Whether adopting healthy lifestyles and maintaining moderate levels of essential metals could attenuate the reduction of heart rate variability (HRV) related to polycyclic aromatic hydrocarbons (PAHs) exposure are largely unknown. In this study, we measured urinary metals and PAHs as well as HRV, and constructed a healthy lifestyle score in 1267 coke oven workers. Linear regression models were used to explore the association of healthy lifestyle score and essential metals with HRV, and interaction analysis was performed to investigate the potential interaction between healthy lifestyle score, essential metals, and PAHs on HRV. Mean age of the participants was 41.9 years (84.5% male). Per one point higher healthy lifestyle score was associated with a 2.5% (95% CI, 1.0%-3.9%) higher standard deviation of all normal to normal intervals (SDNN), 2.1% (95% CI, 0.5%-3.6%) higher root mean square of successive differences in adjacent NN intervals (r-MSSD), 4.3% (95% CI, 0.4%-8.2%) higher low frequency, 4.4% (95% CI, 0.2%-8.5%) higher high frequency, and 4.4% (95% CI, 1.2%-7.6%) higher total power, respectively. Urinary level of chromium was positively associated with HRV indices, with the corresponding ß (95% CI) (%) was 5.17 (2.84, 7.50) for SDNN, 4.29 (1.74, 6.84) for r-MSSD, 12.26 (6.08, 18.45) for low frequency, 12.61 (5.87, 19.36) for high frequency, and 11.31 (6.19, 16.43) for total power. Additionally, a significant interaction was found between healthy lifestyle score and urinary total hydroxynaphthalene on SDNN (Pinteraction = 0.04), and higher level of urinary chromium could attenuate the adverse effect of total hydroxynaphthalene level on HRV (all Pinteraction <0.05). Findings of our study suggest adopting healthy lifestyle and maintaining a relatively high level of chromium might attenuate the reduction of HRV related to total hydroxynaphthalene exposure.


Assuntos
Coque , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Masculino , Adulto , Feminino , Hidrocarbonetos Policíclicos Aromáticos/urina , Frequência Cardíaca , Coque/análise , Naftóis/análise , Naftóis/farmacologia , Metais/urina , Cromo/análise , Cromo/farmacologia , Estilo de Vida Saudável , Exposição Ocupacional/análise
10.
J Hazard Mater ; 466: 133539, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38271873

RESUMO

2-Methylisoborneol (2-MIB) and geosmin are compounds released by algae that significantly degrade reservoir water quality, posing a threat to both the safety of drinking water and the quality of aquatic products sourced from these environments. However, few studies have explored how enhanced thermal stratification affects the occurrence and regulation of odorants in large drinking water reservoirs. Through systematic monitoring and investigation of Xin'anjiang Reservoir, we found that enhanced thermal stratification promotes filamentous cyanobacteria, particularly Leptolyngbya sp., as the primary contributor to 2-MIB production within the 1-10 m layer of the water column. The highest 2-MIB concentration, 92.5 ng/L, was recorded in the riverine region, which was 2.54 and 14.52 times higher than that in the transitional and central parts of the reservoir, respectively. Temperature indirectly impacted algal growth and odorant production by modulating TN/TP ratios. Geosmin concentration responded rapidly to relatively low TN/TP ratios (< 25). Our findings suggest that phosphorus control in estuaries should be enhanced during thermal stratification period. In summary, our study provides valuable insights to inform pragmatic water intake strategies and the distribution and release of odorants caused by thermal stratification. This is particularly relevant in the context of future global warming and extremely high temperatures during the warm season.


Assuntos
Cianobactérias , Água Potável , Naftóis , Fitoplâncton , Odorantes , Paladar , Cianobactérias/metabolismo , China
11.
Langmuir ; 40(3): 1869-1877, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38194363

RESUMO

Characterization studies of 1-butyl-3-methyl-imidazolium bis(2-ethylhexyl) sulfosuccinate vesicles at different pH values have been carried out by using liquid surface tension, transmission electron microscopy, and dynamic light scattering. The results show that there are no vesicle changes in its size and negative Z potential at pH 3, 6, and 10. Furthermore, indomethacin and 1-naphthol, both pH-dependent, electroactive, and fluorescence probes, were used to further characterize the bilayer employing electrochemical and emission techniques. The partition of indomethacin and 1-naphthol between the water and bilayer pseudophases only occurs for the neutral species and does not happen for the anionic species because the highly negative Z bilayer potential prevents incorporation due to negative repulsion. For the neutral species, the partition constant values were evaluated by square wave voltammetry and emission spectroscopy. Finally, for the indomethacin incorporated into the vesicle bilayer at pH 3, the release profile was monitored over time at pH 6. It was found that a change in the pH values causes the complete release of indomethacin after 25 min, which led us to think that the vesicles presented in this work can be used as a pH-sensitive nanocarrier for neutral pH-sensitive drugs.


Assuntos
Indometacina , Naftóis , Succinatos , Espectrometria de Fluorescência , Concentração de Íons de Hidrogênio
12.
Appl Microbiol Biotechnol ; 108(1): 133, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38229332

RESUMO

Transcription factor Cmr1 (Colletotrichum melanin regulation 1) and its homologs in several plant fungal pathogens are the regulators of the 1,8-dihydroxynaphthalene (DHN)-melanin biosynthesis pathway and have evolved functional diversification in morphology and pathogenicity. The fungal genus Alternaria comprises the group of "black fungi" that are rich in DHN-melanin in the primary cell wall and septa of the conidia. Some Alternaria species cause many economically important plant diseases worldwide. However, the evolution and function of Cmr1 homologs in Alternaria remain poorly understood. Here, we identified a total of forty-two Cmr1 homologs from forty-two Alternaria spp. and all contained one additional diverse fungal specific transcription factor motif. Phylogenetic analysis indicated the division of these homologs into five major clades and three branches. Dated phylogeny showed the A and D clades diverged latest and earliest, respectively. Molecular evolutionary analyses revealed that three amino acid sites of Cmr1 homologs in Alternaria were the targets of positive selection. Asmr1, the homolog of Cmr1 in the potato early blight pathogen, Alternaria solani was amplified and displayed the sequence conservation at the amino acid level in different A. solani isolates. Asmr1 was further confirmed to have the transcriptional activation activity and was upregulated during the early stage of potato infection. Deletion of asmr1 led to the decreased melanin content and pathogenicity, deformed conidial morphology, and responses to cell wall and fungicide stresses in A. solani. These results suggest positive selection and functional divergence have played a role in the evolution of Cmr1 homologs in Alternaria. KEY POINTS: • Cmr1 homologs were under positive selection in Alternaria species • Asmr1 is a functional transcription factor, involved in spore development, melanin biosynthesis, pathogenicity, and responses to cell wall and fungicide stresses in A. solani • Cmr1 might be used as a potential taxonomic marker of the genus Alternaria.


Assuntos
Fungicidas Industriais , Naftóis , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Alternaria/genética , Alternaria/metabolismo , Melaninas/metabolismo , Fungicidas Industriais/metabolismo , Filogenia
13.
Sci Rep ; 14(1): 1419, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228813

RESUMO

Onoceroids are a rare family of triterpenes. One representative onoceroid is ambrein, which is the main component of ambergris used as a traditional medicine. We have previously identified the onoceroid synthase, BmeTC, in Bacillus megaterium and succeeded in creating ambrein synthase by introducing mutations into BmeTC. Owing to the structural similarity of ambrein to vitamin D, a molecule with diverse biological activities, we hypothesized that some of the activities of ambergris may be induced by the binding of ambrein to the vitamin D receptor (VDR). We demonstrated the VDR binding ability of ambrein. By comparing the structure-activity relationships of triterpenes with both the VDR affinity and osteoclastic differentiation-promoting activity, we observed that the activity of ambrein was not induced via the VDR. Therefore, some of the activities of ambergris, but not all, can be attributed to its VDR interaction. Additionally, six unnatural onoceroids were synthesized using the BmeTC reactions, and these compounds exhibited higher VDR affinity than that of ambrein. Enzymatic syntheses of onoceroid libraries will be valuable in creating a variety of bioactive compounds beyond ambergris.


Assuntos
Âmbar-Gris , Triterpenos , Âmbar-Gris/química , Receptores de Calcitriol , Triterpenos/farmacologia , Naftóis/química , Vitamina D
14.
Environ Sci Pollut Res Int ; 31(8): 12431-12445, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38231335

RESUMO

Numerous utilities encounter issues with taste and odor that alter the public's impression of the safety of drinking water. The creation of certain components in water naturally due to global climate change is another source of taste and odor components, in addition to industrial emissions. Geosmin and 2-methylisoborneol (2-MIB), both of which are generated by blue-green algae and actinomycetes, are two substances that contribute to the musty and earthy smells in drinking water sources. Unfortunately, current conventional treatment plants only partially remove 2-MIB and geosmin. Therefore, to protect the environment and public health, more up-to-date or optimized treatment methods should be applied to outdated treatment facilities. Best treatment practices, evaluation standards, and decision-making approaches, however, are still shrouded in mystery. The goal of this study was to identify the most effective treatment options for 2-MIB and geosmin. By using the analytical hierarchy process (AHP), a total of 22 assessment criteria were found and prioritized. A thorough literature search led to the identification of potential treatment options, and their effectiveness was evaluated. These options and priority rankings were decided upon using AHP in the decision-making process. Advanced oxidation techniques came out on top in the final priority ranking, followed by membrane filtering, adsorption, oxidation, hybrid processes, and traditional treatment methods. The applied analytical decision techniques may also be used to choose the optimal treatment options, even though the results are particular to 2-MIB and geosmin.


Assuntos
Água Potável , Poluentes Químicos da Água , Purificação da Água , Purificação da Água/métodos , Processo de Hierarquia Analítica , Naftóis , Odorantes/análise , Tomada de Decisões
15.
Anal Chem ; 96(5): 1932-1940, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38241704

RESUMO

Selective labeling of the protein of interest (POI) in genetically unmodified live cells is crucial for understanding protein functions and kinetics in their natural habitat. In particular, spatiotemporally controlled installation of the labels on a POI under light control without affecting their original activity is in high demand but is a tremendous challenge. Here, we describe a novel ligand-directed photoclick strategy for spatiotemporally controlled labeling of endogenous proteins in live cells. It was realized with a designer labeling reagent skillfully integrating the photochemistries of 2-nitrophenylpropyloxycarbonyl and 3-hydroxymethyl-2-naphthol with an affinity ligand. Highly electrophilic ortho-naphthoquinone methide was photochemically released and underwent a proximity coupling reaction with nucleophilic amino acid residues on the POI in live cells. With fluorescein as a marker, this photoclick strategy enables time-resolved labeling of carbonic anhydrase subtypes localized either on the cell membrane or in the cytoplasm and a discriminable visualization of their metabolic kinetics. Given the versatility underlined by facilely tethering other functional entities (e.g., biotin, a peptide short chain) via acylation or (in cell) Huisgen cycloaddition, this affinity-driven photoclick chemistry opens up enormous opportunities for discovering dynamic functions and mechanistic interrogation of endogenous proteins in live cells.


Assuntos
Naftóis , Proteínas , Ligantes , Proteínas/química , Naftóis/química , Fluoresceína
16.
J Biomol Struct Dyn ; 42(4): 1655-1669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37194452

RESUMO

Many natural products have been shown to possess antiplasmodial activities, but their protein targets are unknown. This work employed molecular docking and molecular dynamics simulations to explore the inhibitory activity of some antiplasmodial natural products against wild-type and mutant strains of Plasmodium falciparum dihydrofolate reductase (PfDHFR). From the molecular docking study, 6 ligands preferentially bind at the active site of the DHFR domain with binding energies ranging from -6.4 to -9.5 kcal/mol. Interactions of compounds with MET55 and PHE58 were mostly observed in the molecular docking study. From the molecular dynamics study, the binding of 2 of the ligands-nitidine and oplodiol-was observed to be stable against all tested strains of PfDHFR. The average binding free energy of oplodiol in complex with the various PfDHFR strains was -93.701 kJ/mol whereas that of nitidine was -106.206 kJ/mol. The impressive in silico activities of the 2 compounds suggest they could be considered for development as potential antifolate agents.Communicated by Ramaswamy H. Sarma.


Assuntos
Antimaláricos , Benzofenantridinas , Produtos Biológicos , Naftóis , Plasmodium falciparum/metabolismo , Antimaláricos/farmacologia , Antimaláricos/química , Simulação de Acoplamento Molecular , Tetra-Hidrofolato Desidrogenase/química
17.
J Pharmacol Exp Ther ; 388(2): 506-517, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-37442618

RESUMO

The ocular surface comprises the wet mucosal epithelia of the cornea and conjunctiva, the associated glands, and the overlying tear film. Epitheliopathy is the common pathologic outcome when the ocular surface is subjected to oxidative stress. Whether different stresses act via the same or different mechanisms is not known. Dynasore and dyngo-4a, small molecules developed to inhibit the GTPase activity of classic dynamins DNM1, DNM2, and DNM3, but not mdivi-1, a specific inhibitor of DNM1L, protect corneal epithelial cells exposed to the oxidant tert-butyl hydroperoxide (tBHP). Here we report that, while dyngo-4a is the more potent inhibitor of endocytosis, dynasore is the better cytoprotectant. Dynasore also protects corneal epithelial cells against exposure to high salt in an in vitro model of dysfunctional tears in dry eye. We now validate this finding in vivo, demonstrating that dynasore protects against epitheliopathy in a mouse model of dry eye. Knockdown of classic dynamin DNM2 was also cytoprotective against tBHP exposure, suggesting that dynasore's effect is at least partially on target. Like tBHP and high salt, exposure of corneal epithelial cells to nitrogen mustard upregulated the unfolded protein response and inflammatory markers, but dynasore did not protect against nitrogen mustard exposure. In contrast, mdivi-1 was cytoprotective. Interestingly, mdivi-1 did not inhibit the nitrogen mustard-induced expression of inflammatory cytokines. We conclude that exposure to tBHP or nitrogen mustard, two different oxidative stress agents, cause corneal epitheliopathy via different pathologic pathways. SIGNIFICANCE STATEMENT: Results presented in this paper, for the first time, implicate the dynamin DNM2 in ocular surface epitheliopathy. The findings suggest that dynasore could serve as a new topical treatment for dry eye epitheliopathy and that mdivi-1 could serve as a medical countermeasure for epitheliopathy due to nitrogen mustard exposure, with potentially increased efficacy when combined with anti-inflammatory agents and/or UPR modulators.


Assuntos
Síndromes do Olho Seco , Hidrazonas , Mecloretamina , Naftóis , Quinazolinonas , Camundongos , Animais , Mecloretamina/toxicidade , Mecloretamina/metabolismo , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/tratamento farmacológico , Córnea , Lágrimas , Dinaminas
18.
Ecotoxicol Environ Saf ; 269: 115775, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070413

RESUMO

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 µg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.


Assuntos
Carpas , Doenças dos Peixes , MicroRNAs , Naftóis , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Carpas/genética , Carpas/metabolismo , RNA Mensageiro , Sistema Enzimático do Citocromo P-450/genética , Água Doce , Glucuronosiltransferase/genética , Difosfato de Uridina , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo
19.
Water Res ; 249: 121015, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103440

RESUMO

A new concept is presented for eliminating off-flavor from cold-water RAS-grown fish, while feeding, and as a part of the normal grow-out period. The technology is based on disconnecting the nitrification biofilter, and instead passing the water through an electrolysis system, which both oxidizes the ammonia and disinfects the water, while also removing the off-flavor compounds from the water, which thereby results in the purging of the fish. The purging period was expected to last up to 2 weeks and the fish are fed throughout it. Laboratory and pilot plant experiments were performed to prove the new concept. Lab experiments included quantification of the removal of MIB and geosmin by electrooxidation and stripping, together and separately, in the presence and absence of organic matter. A pilot plant experiment was performed using Rainbow trout to determine the rate at which the off-flavor compounds were removed from the water and the fish flesh (both skin and muscle were tested). The results show that the treatment process eliminated off-flavors in the water after ∼7 days and that the fish were below taste and odor threshold for geosmin and MIB after a maximum of 11 days. Detachment from the biofilter and the fact that the water was vigorously disinfected during the electrooxidation step guaranteed that no further off-flavor compounds would be generated during the operation. Aquacultural-management assessment indicates that RAS farms can increase both their annual production and their income by more than 10%, by implementing the suggested concept as part of the grow-out period.


Assuntos
Canfanos , Água , Animais , Naftóis , Peixes , Odorantes/prevenção & controle
20.
Environ Sci Pollut Res Int ; 31(3): 4196-4208, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100023

RESUMO

Contamination by odor substances such as geosmin (GSM) and 2-methylisoborneol (2-MIB) was examined in the cultured water from aquaculture farming in the region of the Hongze Lake in 2022, and some factors influencing residual levels of them in the water were analyzed. Geographically, high concentrations of GSM were located mainly in the north and northeast culture areas of the lake, while those of 2-MIB were found in the northeast and southwest. Analysis of the water in the enclosure culture revealed significant differences in the concentrations of GSM and 2-MIB among the cultured species. The mean concentrations of GSM in culture water were ranked in the order: crab > the four major Chinese carps > silver and bighead carp, and silver and bighead carp > crab > the four major Chinese carps for 2-MIB. The concentration of GSM was significantly higher at 38.99 ± 18.93 ng/L in crab culture water compared to other fish culture water. Significant differences were observed in GSM concentrations between crab enclosure culture and pond culture, while 2-MIB levels were comparable. These findings suggest that cultural management practices significantly affect the generation of odor substances. The taste and odor (T&O) assessment revealed that the residual levels of GSM and 2-MIB in most samples were below the odor threshold concentrations (OTCs), although high levels of GSM and 2-MIB in all water bodies were at 30.9% and 27.5%, respectively. Compared with the corresponding data from other places and the regulation guidelines of Japan, USA, and China, the region in the Hongze Lake is generally classified as a slightly T&O area, capable of supporting the aquaculture production scale.


Assuntos
Canfanos , Lagos , Poluentes Químicos da Água , Animais , Lagos/análise , Prata/análise , Água/análise , Naftóis , Aquicultura , Odorantes/análise , Poluentes Químicos da Água/análise
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