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1.
Sci Rep ; 14(1): 19542, 2024 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174667

RESUMO

In this study, Fusarium equiseti was isolated from the weed plant Tridax procumbens in an agricultural field and a crude extract produced with 75% ethanol for use as active ingredient material in natural herbicides. The herbicidal effect of F. equiseti extract was tested on water hyacinth (Eichornia crassipes), an invasive aquatic weed, by leaf disk assay at concentrations of 0.05%, 0.1%, and 0.2% w/v crude extract. Dose-dependent visual toxicity symptoms were evident after three days, namely chlorosis, yellow leaves surrounded by dark brown edges. Photosynthetic pigments (chlorophyll a, b, and carotenoids) and membrane integrity (as electrolyte leakage and malondialdehyde content) were evaluated following the leaf disk test. 3 days after treatment, photosynthetic pigment contents showed dose-dependent decreases, while both measures of membrane integrity showed dose-dependent increases with increasing extract concentration. In addition, a cytogenetic assay was conducted on Allium cepa L. root, in which mitotic index reduction and depigmentation were evident as early as 24 h after herbicide application. Finally, anatomical analysis of treated E. crassipes leaves revealed degradation or damage of the ground tissue. All told, our results support the F. equiseti crude-based natural herbicide cloud as a sustainable alternative in agriculture.


Assuntos
Eichhornia , Fusarium , Herbicidas , Folhas de Planta , Herbicidas/farmacologia , Fusarium/efeitos dos fármacos , Folhas de Planta/química , Plantas Daninhas/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Raízes de Plantas/microbiologia , Misturas Complexas/farmacologia
2.
Environ Health Perspect ; 132(7): 75001, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968090

RESUMO

BACKGROUND: The National Institute of Environmental Health Sciences (NIEHS) continues to prioritize research to better understand the health effects resulting from exposure to mixtures of chemical and nonchemical stressors. Mixtures research activities over the last decade were informed by expert input during the development and deliberations of the 2011 NIEHS Workshop "Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects." NIEHS mixtures research efforts since then have focused on key themes including a) prioritizing mixtures for study, b) translating mixtures data from in vitro and in vivo studies, c) developing cross-disciplinary collaborations, d) informing component-based and whole-mixture assessment approaches, e) developing sufficient similarity methods to compare across complex mixtures, f) using systems-based approaches to evaluate mixtures, and g) focusing on management and integration of mixtures-related data. OBJECTIVES: We aimed to describe NIEHS driven research on mixtures and combined exposures over the last decade and present areas for future attention. RESULTS: Intramural and extramural mixtures research projects have incorporated a diverse array of chemicals (e.g., polycyclic aromatic hydrocarbons, botanicals, personal care products, wildfire emissions) and nonchemical stressors (e.g., socioeconomic factors, social adversity) and have focused on many diseases (e.g., breast cancer, atherosclerosis, immune disruption). We have made significant progress in certain areas, such as developing statistical methods for evaluating multiple chemical associations in epidemiology and building translational mixtures projects that include both in vitro and in vivo models. DISCUSSION: Moving forward, additional work is needed to improve mixtures data integration, elucidate interactions between chemical and nonchemical stressors, and resolve the geospatial and temporal nature of mixture exposures. Continued mixtures research will be critical to informing cumulative impact assessments and addressing complex challenges, such as environmental justice and climate change. https://doi.org/10.1289/EHP14340.


Assuntos
Exposição Ambiental , National Institute of Environmental Health Sciences (U.S.) , Humanos , Exposição Ambiental/estatística & dados numéricos , Estados Unidos , Poluentes Ambientais , Misturas Complexas/toxicidade
3.
Braz J Biol ; 84: e284085, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38958299

RESUMO

The current study evaluates the antibacterial activity of Camponotus compressus (Hymenoptera: Formicidae) body crude extracts. The increasing antibiotic resistance of bacteria has prompted the world to turn its attention towards insects in the search for new sources of antibacterial compounds. The body crude extract obtained with different solvents were tested against both Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Standard disc diffusion method was used to perform the activity. The extracts of C. compressus were investigated for their effectiveness against all resistant pathogenic bacteria. Staphylococcus aureus was found to be the most susceptible, exhibiting a high average growth inhibition, while Bacillus subtilis showed a lower average growth inhibition zone. Our findings regarding the inhibitory effect of C. compressus extracts show the presence of a broad-spectrum antibacterial compound. This will be helpful in the search for novel natural antibiotics against robust pathogenic bacterial strains.


Assuntos
Antibacterianos , Formigas , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Animais , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Formigas/efeitos dos fármacos , Misturas Complexas/farmacologia
4.
J Ethnopharmacol ; 334: 118578, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004194

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Trametes Robiniophila Murr, commonly known as Huaier, has been extensively documented in ethnopharmacology research in China. Huaier has a long history of clinical usage spanning over 1000 years in China. Traditional clinical application records demonstrate the wide utilization of Huaier for treating various cancers and enhancing the autoimmunity of tumor patients. AIM OF THE REVIEW: The present study provides a comprehensive review of the traditional uses, phytochemical constituents, pharmacological activities, anti-tumor mechanism, and potential applications of Huaier, thereby offering valuable insights for the further development and utilization of this natural product. MATERIALS AND METHODS: This study employed the keywords "Trametes Robiniophila Murr" and "Huaier" to retrieve relevant information on Huaier from various databases, including PubMed, Web of Science, Springer, Science Direct, ACS, Wiley, CNKI, Baidu Scholar, Google Scholar, and ancient materia medica. RESULTS: Trametes Robiniophila Murr (Huaier), a traditional Chinese medicine, has demonstrated significant efficacy in the clinical treatment of various tumors. The primary bioactive constituents of Huaier consist of fungal-derived compounds, including polysaccharides, proteins, ketones, alkaloids, and minerals. The research findings demonstrate that Huaier serves as a reliable adjunctive therapeutic agent by effectively inhibiting cancer cell proliferation, inducing apoptosis in cancer cells, suppressing tumor metastasis, regulating tumor stem cells and immune function. Therefore, it exerts a potent anti-tumor effect when used in conjunction with conventional anti-cancer therapies. CONCLUSIONS: The analysis of traditional uses, phytochemical composition, and pharmacological activity reveals that Huaier exhibits significant potential as a medicinal plant with diverse pharmacological effects. Owing to its numerous advantages, Huaier holds immense promise for application in the domains of tumor prevention and treatment, enhancing both survival time and quality of life among cancer patients.


Assuntos
Medicina Tradicional Chinesa , Neoplasias , Trametes , Trametes/química , Humanos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Medicina Tradicional Chinesa/métodos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Misturas Complexas
5.
J Proteome Res ; 23(7): 2315-2322, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38913967

RESUMO

Native top-down mass spectrometry (nTDMS) allows characterization of protein structure and noncovalent interactions with simultaneous sequence mapping and proteoform characterization. The majority of nTDMS studies utilize purified recombinant proteins, with significant challenges hindering application to endogenous systems. To perform native top-down proteomics (nTDP), where endogenous proteins from complex biological systems are analyzed by nTDMS, it is essential to separate proteins under nondenaturing conditions. However, it remains difficult to achieve high resolution with MS-compatible online chromatography while preserving protein tertiary structure and noncovalent interactions. Herein, we report the use of online mixed-bed ion exchange chromatography (IEC) to enable separation of endogenous proteins from complex mixtures under nondenaturing conditions, preserving noncovalent interactions for nTDP analysis. We have successfully detected large proteins (>146 kDa) and identified endogenous metal-binding and oligomeric protein complexes in human heart tissue lysate. The use of a mixed-bed stationary phase allowed retention and elution of proteins over a wide range of isoelectric points without altering the sample or mobile phase pH. Overall, our method provides a simple online IEC-MS platform that can effectively separate proteins from complex mixtures under nondenaturing conditions and preserve higher-order structure for nTDP applications.


Assuntos
Proteômica , Cromatografia por Troca Iônica/métodos , Humanos , Proteômica/métodos , Miocárdio/química , Espectrometria de Massas/métodos , Misturas Complexas/química , Proteínas/química , Proteínas/análise , Proteínas/isolamento & purificação
6.
Curr Microbiol ; 81(7): 183, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771359

RESUMO

The fungus Monascus is a well-known source of secondary metabolites with interesting pharmaceutical and nutraceutical applications. In particular, Monascus pigments possess a wide range of biological activities (e.g. antimicrobial, antioxidant, anti-inflammatory or antitumoral). To broaden the scope of their possible application, this study focused on testing Monascus pigment extracts as potential photosensitizing agents efficient in antimicrobial photodynamic therapy (aPDT) against bacteria. For this purpose, eight different extracts of secondary metabolites from the liquid- and solid-state fermentation of Monascus purpureus DBM 4360 and Monascus sp. DBM 4361 were tested against Gram-positive and Gram-negative model bacteria, Bacillus subtilis and Escherichia coli and further screened for ESKAPE pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. To the bacterial culture, increasing concentration of extracts was added and it was found that all extracts showed varying antimicrobial activity against Gram-positive bacteria in dark, which was further increased after irradiation. Gram-negative bacteria were tolerant to the extracts' exposure in the dark but sensitivity to almost all extracts that occurred after irradiation. The Monascus sp. DBM 4361 extracts seemed to be the best potential candidate for aPDT against Gram-positive bacteria, being efficient at low doses, i.e. the lowest total concentration of Monascus pigments exhibiting aPDT effect was 3.92 ± 1.36 mg/L for E. coli. Our results indicate that Monascus spp., forming monascuspiloin as the major yellow pigment and not-forming mycotoxin citrinin, is a promising source of antimicrobials and photoantimicrobials.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Monascus , Micélio , Monascus/química , Monascus/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Micélio/química , Micélio/efeitos da radiação , Micélio/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos da radiação , Misturas Complexas/farmacologia , Misturas Complexas/química , Pigmentos Biológicos/farmacologia , Fotoquimioterapia
7.
Phytomedicine ; 129: 155656, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723529

RESUMO

BACKGROUND: Gemcitabine is the first-line chemotherapy drug that can easily cause chemotherapy resistance. Huaier is a traditional Chinese medicine and shows an antitumor effect in pancreatic cancer, but whether it can enhance the gemcitabine chemotherapeutic response and the potential mechanism remain unknown. PURPOSE: This study was performed to explore the effect of Huaier in promoting the tumor-killing effect of gemcitabine and elucidate the possible mechanism in pancreatic cancer. METHODS: Cell Counting Kit-8 assays and colony formation assays were used to detect proliferation after different treatments. Protein coimmunoprecipitation was applied to demonstrate protein interactions. Nuclear protein extraction and immunofluorescence were used to confirm the intracellular localization of the proteins. Western blotting was performed to detect cell proliferation-related protein expression or cancer stem cell-associated protein expression. Sphere formation assays and flow cytometry were used to assess the stemness of pancreatic cancer cells. The in vivo xenograft model was used to confirm the inhibitory effect under physiological conditions, and immunohistochemistry was used to detect protein expression. RESULTS: Huaier suppressed the proliferation and stem cell-like properties of pancreatic cancer cells. We found that Huaier suppressed the expression of forkhead box protein M1 (FoxM1). In addition, Huaier inhibited FoxM1 function by blocking its nuclear translocation. Treatment with Huaier reversed the stemness induced by gemcitabine in a FoxM1-dependent manner. Furthermore, we verified the above results by an in vivo study, which reached the same conclusion as those in vitro. CONCLUSION: Overall, this study illustrates that Huaier augments the tumor-killing effect of gemcitabine through suppressing the stemness induced by gemcitabine in a FoxM1-dependent way. These results indicate that Huaier can be applied to overcome gemcitabine resistance.


Assuntos
Proliferação de Células , Desoxicitidina , Proteína Forkhead Box M1 , Gencitabina , Camundongos Nus , Células-Tronco Neoplásicas , Neoplasias Pancreáticas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Proteína Forkhead Box M1/metabolismo , Humanos , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto , Medicamentos de Ervas Chinesas/farmacologia , Misturas Complexas , Trametes
8.
Mar Drugs ; 22(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38535453

RESUMO

Brown seaweeds are attracting attention due to their richness in bioactive compounds, in particular, their phlorotannins. We present here a case study of two Fucales, Ascophyllum nodosum and Halidrys siliquosa, sustainably collected, to produce active polyphenols for the cosmetics sector. Phenolic contents of crude extracts, obtained by Accelerated Solvent Extraction (ASE), were more elevated in H. siliquosa at 100.05 mg/g dry weight (DW) than in A. nodosum (29.51 mg/g DW), considering 3 cycles with cell inversion. The temperature of extraction for a high phenolic content and high associated antioxidant activities close to positive controls was 150 °C for both algae and the use of only one cycle was enough. A semi-purification process using Solid-phase Extraction (SPE) was carried out on both ASE crude extracts (one per species). The majority of phlorotannins were found in the ethanolic SPE fraction for A. nodosum and the hydroethanolic one for H. siliquosa. The SPE process allowed us to obtain more concentrated fractions of active phenolic compounds (×1.8 and 2 in A. nodosum and H. siliquosa, respectively). Results are discussed in regard to the exploitation of seaweeds in Brittany and to the research of sustainable processes to produce active natural ingredients for cosmetics.


Assuntos
Cosméticos , Alga Marinha , Antioxidantes , Etanol , Fenóis , Misturas Complexas
9.
Ultrason Sonochem ; 104: 106842, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460472

RESUMO

The rate of pH decline post - mortem and its interaction with temperature influences the final tenderness of meat, and therefore, the manipulation of the rate of pH decline is a strategy of interest in order to obtain consistent high quality meat. Ultrasound is a potential early post - mortem carcass intervention, which may alter the rate of glycolysis based on its ability to alter enzyme activity. In this study, homogenates (prepared from early post-mortem Longissimus thoracis et lumborum muscle) were subjected to different ultrasound intensities (0 %/60 %/100 % amp) and treatment durations (15/ 30 min). The effect of these treatments on the inherent activity of the glycolytic enzymes was investigated using an in vitro glycolytic buffer model system. It was found that ultrasound treatment intensity and duration had a significant interactive effect on the rate of pH decline, and on reducing sugars and lactic acid concentrations, specifically following the 100 % amp ultrasound for 30 min treatment and between 30 and 240 min incubation. No significant differences in pH or metabolites content were observed between treatments after 1440 min of incubation. No effect of ultrasound intensity or treatment duration was observed on the degradation of glycogen. Under the reported conditions of this trial, it can be concluded that the application of ultrasound has limited potential to have an impact on the glycolytic pathways in bovine muscle.


Assuntos
Carne , Músculo Esquelético , Animais , Bovinos , Músculo Esquelético/química , Carne/análise , Ácido Láctico/metabolismo , Glicólise/fisiologia , Misturas Complexas/análise , Misturas Complexas/metabolismo , Concentração de Íons de Hidrogênio
10.
Sci Rep ; 14(1): 6794, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514663

RESUMO

Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of drug-resistant strains of Mycobacterium tuberculosis has prompted an urgent need for innovative therapeutic solutions. One promising way to discover new tuberculosis drugs is by utilizing natural products from the vast biochemical space. Multidisciplinary methods can used to harness the bioactivity of these natural products. This study aimed to evaluate the antimycobacterial efficacy of functional crude extracts from bacteria isolated from gold mine tailings in South Africa. Bacterial strains were identified using 16S rRNA sequencing. The crude extracts obtained from the bacteria were tested against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. Untargeted HPLC-qTOF and molecular networking were used to identify the functional constituents present in extracts that exhibited inhibitory activity. A virtual screening workflow (VSW) was used to filter compounds that were strong binders to Mycobacterium tuberculosis Pks13 and PknG. The ligands returned from the VSW were subjected to optimization using density functional theory (DFT) at M06-2X/6-311++ (d,p) level of theory and basis set implemented in Gaussian16 Rev.C01. The optimized ligands were re-docked against Mycobacterium tuberculosis Pks13 and PknG. Molecular dynamics simulation and molecular mechanics generalized born surface area were used to evaluate the stability of the protein-ligand complexes formed by the identified hits. The hit that showed promising binding characteristics was virtually modified through multiple synthetic routes using reaction-driven enumeration. Three bacterial isolates showed significant activity against the two strains of Mycobacterium, while only two, Bacillus subtilis and Bacillus licheniformis, exhibited activity against both Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. The tentatively identified compounds from the bacterial crude extracts belonged to various classes of natural compounds associated with antimicrobial activity. Two compounds, cyclo-(L-Pro-4-OH-L-Leu) and vazabitide A, showed strong binding against PknG and Pks13, with pre-MD MM-GBSA values of - 42.8 kcal/mol and - 47.6 kcal/mol, respectively. The DFT-optimized compounds exhibited the same docking scores as the ligands optimized using the OPSL-4 force field. After modifying vazabitide A, its affinity to the Pks13 binding site increased to - 85.8 kcal/mol, as revealed by the post-MD MM-GBSA analysis. This study highlights the potential of bacteria isolates from gold mine tailings as a source of new scaffolds for designing and optimizing anti-Mycobacterium agents. These agents synthesized in-silico can be further tested in-vitro to evaluate their efficacy.


Assuntos
Produtos Biológicos , Mycobacteriaceae , Mycobacterium tuberculosis , Mycobacterium tuberculosis/genética , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , RNA Ribossômico 16S , Antibacterianos/farmacologia , Mycobacterium smegmatis/genética , Produtos Biológicos/farmacologia , Misturas Complexas , Antituberculosos/farmacologia , Antituberculosos/química
11.
Nat Microbiol ; 9(4): 938-948, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499812

RESUMO

Our understanding of how microbes respond to micropollutants, such as pesticides, is almost wholly based on single-species responses to individual chemicals. However, in natural environments, microbes experience multiple pollutants simultaneously. Here we perform a matrix of multi-stressor experiments by assaying the growth of model and non-model strains of bacteria in all 255 combinations of 8 chemical stressors (antibiotics, herbicides, fungicides and pesticides). We found that bacterial strains responded in different ways to stressor mixtures, which could not be predicted simply from their phylogenetic relatedness. Increasingly complex chemical mixtures were both more likely to negatively impact bacterial growth in monoculture and more likely to reveal net interactive effects. A mixed co-culture of strains proved more resilient to increasingly complex mixtures and revealed fewer interactions in the growth response. These results show predictability in microbial population responses to chemical stressors and could increase the utility of next-generation eco-toxicological assays.


Assuntos
Poluentes Ambientais , Praguicidas , Filogenia , Praguicidas/toxicidade , Bactérias/genética , Misturas Complexas
12.
Talanta ; 272: 125746, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447467

RESUMO

High-performance thin-layer chromatography hyphenated with planar multiplex bioassays and high-resolution tandem mass spectrometry contributes to the non-target detection or even identification of active compounds in complex mixtures such as food, feed, cosmetics, commodities, and environmental samples. It can be used to discover previously unknown harmful or active substances in complex samples and to tentatively assign molecular formulas. This method is already faster than the commonly used in vitro assays along with liquid chromatographic separations, but overnight cell cultivation still prevents a planar bioassay from being performed within one day. There is also still potential for optimization in terms of sustainability. To achieve this, the planar bioassay protocols for the detection of androgen-like and estrogen-like compounds were harmonized. The successful minimization of the cell culture volume enabled accelerated cell cultivation, which allowed the bioassay to be performed within one day. This was considered a milestone achieved, as up to 23 samples per plate can now be analyzed from the start of cultivation to the biological endpoint on the same day. Doubling the substrate amount and increasing the pH of the silica gel layer led to a more sensitive and selective bioassay due to the enhanced fluorescence of the formed end-product. The faster and more sustainable bioassay protocol was applied to complex samples such as sunscreen and red wine to detect estrogen-like compounds. The developed method was validated by comparison with a standard method.


Assuntos
Disruptores Endócrinos , Saccharomyces cerevisiae , Disruptores Endócrinos/análise , Estrogênios/análise , Bioensaio/métodos , Misturas Complexas
13.
Lett Appl Microbiol ; 77(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38467396

RESUMO

Endophytic microorganisms associated with medicinal plants are of particular interest as they are a potential source of new bioactive chemicals effective against novel emerging and drug-resistant pathogens. Agave americana is a tropical medicinal plant with antibacterial, antifungal, and anticancer properties. We studied the biodiversity of fungal endophytes of A. americana and their antimicrobial production potential. Isolated endophytic fungi were classified into 32 morphotypes (15 from stem and 17 from leaf) based on their cultural and morphological characteristics. Among the fungal crude extracts tested, 82% of isolates from the leaves and 80% of the isolates from the stem showed antibacterial activity against the bacterial strains (Escherichia coli ATTC 25902, Staphylococcus aureus ATTC 14775, and Bacillus subtilis NRRL 5109) tested. Extracts from four fungal isolates from leaves showed antifungal activity against at least one of the fungal strains (Candida albicans ATTC 10231 and Aspergillus fumigatus NRRL 5109) tested. Crude extracts of seven fungal isolates showed a zone of inhibition of more than 11 mm at 10 mgml-1 against both Gram-positive and Gram-negative bacteria tested. Penicillium, Colletotrichum, Curvularia, Pleosporales, Dothideomycetes, and Pleurotus are the main endophytes responsible for bioactive potential. These results indicate that A. americana harbors endophytes capable of producing antimicrobial metabolites.


Assuntos
Agave , Anti-Infecciosos , Ascomicetos , Plantas Medicinais , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Antibacterianos/farmacologia , Plantas Medicinais/microbiologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Bactérias Gram-Positivas , Fungos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Endófitos , Misturas Complexas/metabolismo , Misturas Complexas/farmacologia
15.
J Magn Reson ; 361: 107653, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471414

RESUMO

Nuclear magnetic resonance (NMR) based 13C tracing has broad applications across medical and environmental research. As many biological and environmental samples are heterogeneous, they experience considerable spectral overlap and relatively low signal. Here a 1D 1H-12C/13C is introduced that uses "in-phase/opposite-phase" encoding to simultaneously detect and discriminate both protons attached to 12C and 13C at full 1H sensitivity in every scan. Unlike traditional approaches that focus on the 12C/13C satellite ratios in a 1H spectrum, this approach creates separate sub-spectra for the 12C and 13C bound protons. These spectra can be used for both quantitative and qualitative analysis of complex samples with significant spectral overlap. Due to the presence of the 13C dipole, faster relaxation of the 1H-13C pairs results in slight underestimation compared to the 1H-12C pairs. However, this is easily compensated for, by collecting an additional reference spectrum, from which the absolute percentage of 13C can be calculated by difference. When combined with the result, 12C and 13C percent enrichment in both 1H-12C and 1H-13C fractions are obtained. As the approach uses isotope filtered 1H NMR for detection, it retains nearly the same sensitivity as a standard 1H spectrum. Here, a proof-of-concept is performed using simple mixtures of 12C and 13C glucose, followed by suspended algal cells with varying 12C /13C ratios representing a complex mixture. The results consistently return 12C/13C ratios that deviate less than 1 % on average from the expected. Finally, the sequence was used to monitor and quantify 13C% enrichment in Daphnia magna neonates which were fed a 13C diet over 1 week. The approach helped reveal how the organisms utilized the 12C lipids they are born with vs. the 13C lipids they assimilate from their diet during growth. Given the experiments simplicity, versatility, and sensitivity, we anticipate it should find broad application in a wide range of tracer studies, such as fluxomics, with applications spanning various disciplines.


Assuntos
Isótopos , Prótons , Espectroscopia de Ressonância Magnética/métodos , Misturas Complexas , Lipídeos
16.
Chemosphere ; 353: 141431, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401859

RESUMO

Assessing a complex mixture of pesticides at the impacted sites has been challenging for risk assessors for 50 years. The default assumption is that at low concentrations, pesticides interact additively with one another; thus, the risk posed by each component of a complex mixture could be simply added up. The EPA interaction-based hazard index (HIInteraction) modifies this assumption using a binary weight-of-evidence (BINWOE). However, data gaps often preclude HIInteraction use at most sites. This study evaluated these assumptions using the BINWOE to estimate the hazard index (HI) of select pesticide mixtures. The lack of in vivo binary interaction data led us to use a cell line, SH-SY5Y, to obtain the data necessary for the BINWOE approach. In the risk assessment, we considered the most active exposure scenario inhaling a mixture of volatile pesticides from contaminated soil and groundwater. The potential interactions between pesticides in 15 binary mixtures were investigated using the MTT assay in SH-SY5Y cells. Our findings showed that 60% of the binary mixtures elicited synergism (in at least one concentration), 27% displayed antagonism, and 13% showed additive effects in SH-SY5Y cells. Combining human safety data with in vitro interaction data indicated that adults and toddlers were at the highest risk when considering industrial and commercial land use, respectively, compared to other subpopulations. Incorporating interaction data into the risk assessment either increased the risk by up to 20% or decreased the risk by 2%, depending on the mixture. Our results demonstrate the predominant synergistic interactions, even at low concentrations, altered risk characterization at the complex operating site. Most concerning, organochlorine pesticides with the same mechanism of action did not follow dose additivity when evaluated by SH-SY5Y cell lines. Based on our observations, we caution that current HI methods based on additivity assumptions may underestimate the risk of organochlorine mixtures.


Assuntos
Herbicidas , Neuroblastoma , Praguicidas , Humanos , Praguicidas/toxicidade , Herbicidas/toxicidade , Interações Medicamentosas , Misturas Complexas/toxicidade
17.
Microb Pathog ; 189: 106573, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354989

RESUMO

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.


Assuntos
Anti-Infecciosos , Medicina Tradicional Chinesa , Animais , Humanos , Permeabilidade da Membrana Celular , Biofilmes , Candida albicans , Anti-Infecciosos/farmacologia , Misturas Complexas/farmacologia , Permeabilidade , Testes de Sensibilidade Microbiana , Mamíferos
18.
Environ Pollut ; 346: 123594, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38378077

RESUMO

In response to the demand for advanced purification of industrial secondary effluent, a new method has been developed for treating chlorophenol wastewater using the novel ceramsite-based Ti/SnO2-Sb particle electrodes (Ti/SnO2-Sb/CB) enhanced electrocatalytic denitrification biofilter (EDNBF-P) to achieve removal of chlorophenols (CPs), denitrification, and reduction of effluent toxicity. The results showed that significantly improved CPs and TN removal efficiency at low COD/N compared to conventional denitrification biofilter, with CPs removal rates increasing by 0.33%-59.27% and TN removal rates increasing by 12.53%-38.92%. Under the conditions of HRT = 2h, 3V voltage, charging times = 12h, and 25 °C, the concentrations of the CPs in the effluent of EDNBF-P were all below 1 mg/L, the TN concentration was below 15 mg/L, while the effluent toxicity reached the low toxicity level. Additionally, the Ti/SnO2-Sb/CB particle electrodes effectively alleviated the accumulation of NO2--N caused by applied voltage. The Silanimonas, Pseudomonas and Rhodobacter was identified as the core microorganism for denitrification and toxicity reduction. This study validated that EDNBF-P could achieve synergistic treatment of CPs and TN through electrocatalysis and microbial degradation, providing a methodological support for achieving advanced purification of chlorophenol wastewater with low COD/N in industrial applications.


Assuntos
Clorofenóis , Misturas Complexas , Microbiota , Águas Residuárias , Desnitrificação , Titânio/química , Eletrodos , Nitrogênio , Reatores Biológicos , Oxirredução
19.
J Sep Sci ; 47(4): e2300811, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403440

RESUMO

In this work, surface molecularly imprinted polymers based on magnetic multi-walled carbon nanotubes were prepared for the specific recognition and adsorption of resveratrol. The functionalization of magnetic multi-walled carbon nanotubes and the synthesis process of surface molecularly imprinted polymers were optimized. Characterizations were performed to demonstrate the successful synthesis of the imprinted materials. The imprinted materials showed satisfactory adsorption capacity of resveratrol (45.73 ± 1.72 mg/g) and excellent selectivity (imprinting factor 2.89 ± 0.15). In addition, the imprinted materials were used as adsorbents in molecularly imprinted solid-phase extraction for the purification of resveratrol from crude extracts of some food and medicinal resources, achieving recoveries of 93.69%-95.53% with high purities of 88.37%-92.33%. Moreover, the purified products exhibited extremely strong free radical scavenging activity compared with crude extracts. Overall, this work provided a promising approach for the highly selective purification of resveratrol from natural resources, which would contribute to the application of this valuable compound in the food/nutraceutical fields.


Assuntos
Fallopia japonica , Impressão Molecular , Nanotubos de Carbono , Vitis , Resveratrol , Polímeros Molecularmente Impressos , Arachis , Polímeros , Adsorção , Misturas Complexas , Fenômenos Magnéticos , Extração em Fase Sólida
20.
J Sep Sci ; 47(4): e2300770, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403448

RESUMO

German chamomile is one of the most effective herbal elements used in anti-allergic products and as an antioxidant. Herein, the antioxidant activity of different extract fractions of German chamomile was initially evaluated using an off-line 2,2-diphenyl-1-picrylhydrazyl spectrophotometric assay. The ethyl acetate extract demonstrated the highest efficacy in scavenging free radicals. Based on this, a rapid screening and separation method using ultra-high-performance liquid chromatography combined with the 2,2-diphenyl-1-picrylhydrazyl assay was implemented to identify antioxidants in the ethyl acetate fraction of German chamomile flowers. Ten potential radical scavengers were tentatively screened from German chamomile using a target-guided isolating approach with off-line two-dimensional high-speed countercurrent chromatography and the structures of the compounds were analyzed and identified. Ultimately, 10 radical scavengers were obtained from the ethyl acetate extract with a purity quotient exceeding 90%. The results demonstrated the effectiveness and reproducibility of this method for isolating potential antioxidants from complex mixtures in a targeted manner. This strategy can be applied to the target-guided isolation of complex mixtures of natural products with broad K-values and similar structures.


Assuntos
Acetatos , Compostos de Bifenilo , Distribuição Contracorrente , Matricaria , Picratos , Distribuição Contracorrente/métodos , Extratos Vegetais/química , Antioxidantes/análise , Espectrometria de Massa com Cromatografia Líquida , Reprodutibilidade dos Testes , Misturas Complexas , Cromatografia Líquida de Alta Pressão/métodos
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