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1.
Phytomedicine ; 129: 155656, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723529

ABSTRACT

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.


Subject(s)
Cell Proliferation , Deoxycytidine , Forkhead Box Protein M1 , Gemcitabine , Mice, Nude , Neoplastic Stem Cells , Pancreatic Neoplasms , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Forkhead Box Protein M1/metabolism , Humans , Animals , Pancreatic Neoplasms/drug therapy , Neoplastic Stem Cells/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Mice , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Drugs, Chinese Herbal/pharmacology , Complex Mixtures , Trametes
2.
Curr Microbiol ; 81(7): 183, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771359

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Monascus , Mycelium , Monascus/chemistry , Monascus/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mycelium/chemistry , Mycelium/radiation effects , Mycelium/drug effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Biological Products/pharmacology , Biological Products/chemistry , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/radiation effects , Complex Mixtures/pharmacology , Complex Mixtures/chemistry , Pigments, Biological/pharmacology , Photochemotherapy
3.
Mar Drugs ; 22(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38535453

ABSTRACT

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.


Subject(s)
Cosmetics , Seaweed , Antioxidants , Ethanol , Phenols , Complex Mixtures
4.
Ultrason Sonochem ; 104: 106842, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38460472

ABSTRACT

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.


Subject(s)
Meat , Muscle, Skeletal , Animals , Cattle , Muscle, Skeletal/chemistry , Meat/analysis , Lactic Acid/metabolism , Glycolysis/physiology , Complex Mixtures/analysis , Complex Mixtures/metabolism , Hydrogen-Ion Concentration
6.
J Magn Reson ; 361: 107653, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38471414

ABSTRACT

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.


Subject(s)
Isotopes , Protons , Magnetic Resonance Spectroscopy/methods , Complex Mixtures , Lipids
7.
Sci Rep ; 14(1): 6794, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38514663

ABSTRACT

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.


Subject(s)
Biological Products , Mycobacteriaceae , Mycobacterium tuberculosis , Mycobacterium tuberculosis/genetics , Molecular Dynamics Simulation , Molecular Docking Simulation , RNA, Ribosomal, 16S , Anti-Bacterial Agents/pharmacology , Mycobacterium smegmatis/genetics , Biological Products/pharmacology , Complex Mixtures , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry
8.
Talanta ; 272: 125746, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38447467

ABSTRACT

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.


Subject(s)
Endocrine Disruptors , Saccharomyces cerevisiae , Endocrine Disruptors/analysis , Estrogens/analysis , Biological Assay/methods , Complex Mixtures
9.
Lett Appl Microbiol ; 77(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38467396

ABSTRACT

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.


Subject(s)
Agave , Anti-Infective Agents , Ascomycota , Plants, Medicinal , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Anti-Bacterial Agents/pharmacology , Plants, Medicinal/microbiology , Gram-Negative Bacteria , Microbial Sensitivity Tests , Gram-Positive Bacteria , Fungi , Anti-Infective Agents/pharmacology , Anti-Infective Agents/metabolism , Endophytes , Complex Mixtures/metabolism , Complex Mixtures/pharmacology
10.
Nat Microbiol ; 9(4): 938-948, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38499812

ABSTRACT

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.


Subject(s)
Environmental Pollutants , Pesticides , Phylogeny , Pesticides/toxicity , Bacteria/genetics , Complex Mixtures
11.
Braz J Microbiol ; 55(2): 1679-1691, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38393617

ABSTRACT

Fungal plant pathogens are responsible for serious losses in many economically important crop species worldwide. Due to the use of fungicides and the fungi genome plasticity, multi-drug resistant strains are emerging as a new generation of pathogens, causing an expansive range of superficial and systemic plant infections, or new opportunistic fungal pathogens for humans. The group of antagonistic fungi Trichoderma spp. has been widely used to enhance plant growth and for the control of different pathogens affecting crops. Although Neurospora crassa is not a mycoparasitic fungus, its secretion of secondary metabolites with antimicrobial activity has been described. In this work, the effect of crude extract of the monoculture of Trichoderma asperellum T8a or the co-culture with N. crassa as an inhibitory treatment against the fungal pathogens Botrytis cinerea and Fusarium solani was evaluated. The findings demonstrate that the secondary metabolites contained in the T. asperellum crude extract have a clear fungistatic activity against B. cinerea and F. solani. Interestingly, this fungistatic activity highly increases when T. asperellum is co-cultivated with the non-pathogenic fungus N. crassa. Moreover, the co-culture crude extract also showed antifungal activity on post-harvest fruits, and no toxic effects on Murine fibroblast L929 (CCL-1) and murine macrophages RAW 264.7 (TIB-71) were observed. All these results together are solid evidence of the potential of the co-culture crude extract of T. asperellum and N. crassa, as an antifungal agent against phytopathogenic fungi, or post-harvest fruits during the transportation or commercialization time.


Subject(s)
Botrytis , Coculture Techniques , Fruit , Fusarium , Trichoderma , Fusarium/drug effects , Fusarium/growth & development , Fruit/microbiology , Fruit/chemistry , Botrytis/drug effects , Botrytis/growth & development , Trichoderma/metabolism , Trichoderma/genetics , Animals , Mice , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Plant Diseases/microbiology , Plant Diseases/prevention & control , Neurospora crassa/drug effects , Neurospora crassa/metabolism , RAW 264.7 Cells , Complex Mixtures/pharmacology , Complex Mixtures/chemistry
12.
J Sep Sci ; 47(4): e2300811, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38403440

ABSTRACT

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.


Subject(s)
Fallopia japonica , Molecular Imprinting , Nanotubes, Carbon , Vitis , Resveratrol , Molecularly Imprinted Polymers , Arachis , Polymers , Adsorption , Complex Mixtures , Magnetic Phenomena , Solid Phase Extraction
13.
J Sep Sci ; 47(4): e2300770, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38403448

ABSTRACT

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.


Subject(s)
Acetates , Biphenyl Compounds , Countercurrent Distribution , Matricaria , Picrates , Countercurrent Distribution/methods , Plant Extracts/chemistry , Antioxidants/analysis , Liquid Chromatography-Mass Spectrometry , Reproducibility of Results , Complex Mixtures , Chromatography, High Pressure Liquid/methods
14.
J Environ Manage ; 354: 120401, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38382437

ABSTRACT

Aluminum (Al)-based drinking water treatment residue (DWTR) has often been attempted to be recycled as dominant ingredient to produce sintered ceramsite for water treatment. This study aimed to determine the long-term performance of DWTR-based ceramsite in treating domestic wastewater based on a 385-d biofilter test and by using physicochemical, metagenomic, and metatranscriptomic analyses. The results showed that the ceramsite-packed biofilter exhibited high and stable capability in removing phosphorus (P) and chemical oxygen demand (COD), with removal efficiencies of 92.6 ± 3.97% and 81.1 ± 14.0% for total P and COD, respectively; moreover, 88-100% of ammonium-nitrogen (N) was normally converted, and the total N removal efficiency reached 80-86% under proper aeration. Further analysis suggested that the forms of the removed P in the ceramsite were mainly NH4F- and NaOH-extractable. Microbial communities in the ceramsite biofilter exhibited relatively high activity. Typically, various organic matter degradation-related genes (e.g., hemicellulose and starch degradations) were enriched, and a complete N-cycling pathway was established, which is beneficial for enriching microbes involved in ammonium-N conversion, especially Candidatus Brocadia, Candidatus Jettenia, Nitrosomonas, and Nitrospira. In addition, the structures of the ceramsite had high stability (e.g., compressive strength and major compositions). The ceramsites showed limited metal and metalloid pollution risks and even accumulated copper from the wastewater. These results demonstrate the high feasibility of applying ceramsite prepared from Al-based DWTR for water treatment.


Subject(s)
Ammonium Compounds , Complex Mixtures , Drinking Water , Water Purification , Wastewater , Water Purification/methods , Nitrogen , Aluminum
15.
Chemosphere ; 353: 141431, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38401859

ABSTRACT

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.


Subject(s)
Herbicides , Neuroblastoma , Pesticides , Humans , Pesticides/toxicity , Herbicides/toxicity , Drug Interactions , Complex Mixtures/toxicity
16.
Microb Pathog ; 189: 106573, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38354989

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Medicine, Chinese Traditional , Animals , Humans , Cell Membrane Permeability , Biofilms , Candida albicans , Anti-Infective Agents/pharmacology , Complex Mixtures/pharmacology , Permeability , Microbial Sensitivity Tests , Mammals
17.
Environ Pollut ; 346: 123594, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38378077

ABSTRACT

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.


Subject(s)
Chlorophenols , Complex Mixtures , Microbiota , Wastewater , Denitrification , Titanium/chemistry , Electrodes , Nitrogen , Bioreactors , Oxidation-Reduction
18.
Environ Geochem Health ; 46(3): 78, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38367092

ABSTRACT

Industrial by-products are stored in large quantities in the open, leading to wasted resources and environmental pollution, and the natural environment is similarly faced with phosphate depletion and serious water and soil pollution. This study uses these by-products to produce a new sludge/biomass ash ceramsite that will be used to adsorb nitrogen and phosphorus from wastewater, and solidify heavy metals in the soil while releasing Olsen P. The sludge/biomass ash ceramsites are made using sewage sludge and biomass ash in a certain ratio calcined at high temperatures and modified for the adsorption of nitrogen and phosphorus from wastewater. Sludge/biomass ash ceramsites before and after phosphorus adsorption, biochar and biomass ash were compared to analyze their heavy metal adsorption capacity and potential as phosphate fertilizer. After phosphorus adsorption, the sludge/biomass ash ceramsites released effective phosphorus steadily and rapidly in the soil, with a greater initial release than biochar and biomass ash, and the ceramsites were in a granular form that could be easily recycled. Biochar and biomass residue, due to their surface functional groups, are better at solidifying heavy metals than sludge/biomass ash ceramsites. Biochar, biomass ash and sludge/biomass ash ceramsites significantly reduced the concentrations of Cd, Cu, Pb and Zn in the soil. Correlation analysis demonstrated that there was a synergistic relationship between the increase in soil Olsen P content and the change in pH, with the increase in soil Olsen P content and the increase in pH contributing to heavy metal solidification.


Subject(s)
Complex Mixtures , Metals, Heavy , Soil Pollutants , Sewage/chemistry , Wastewater , Biomass , Metals, Heavy/analysis , Charcoal/chemistry , Soil/chemistry , Phosphorus/analysis , Phosphates/analysis , Nitrogen/analysis , Soil Pollutants/analysis
19.
Asian Pac J Cancer Prev ; 25(1): 123-137, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38285776

ABSTRACT

BACKGROUND: Acute Myeloid Leukaemia (AML) is considered to be an extremely heterogeneous malignancy of bone marrow and blood. The first line of therapy for AML is prolonged chemotherapy. Due to the presence of molecular heterogeneity in AML as confirmed by next-generation sequencing, researchers are planning to develop newer strategies of therapy. OBJECTIVE: In the present study we have explored the anti-cancer potentiality of the hydro-ethanolic extract (50% and 70%) of the whole flower of Nymphaea caerulea against the Acute Myeloid Leukaemia cell line, THP-1 with control of normal human kidney epithelial cell line (HEK 293). The present study is a novel contribution to the existing scientific knowledge as at present no study as an anti-leukaemic agent is available on N. caerulea (blue lotus) extract and exploring its action mechanism on in-vitro cell line model. METHODS: Some targeted cytokine and apoptotic genes genes to deduce the anti-cancer mechanism of action of the crude extract (hydro-ethanolic extract (50% and 70%) of the whole flower) were selected as Interferon (IFN) γ, Interleukins - IL-6, IL-8, IL- 10, IL-1ß, Transforming Growth Factor (TGF ß1), Tumor Necrosis Factor (TNF α), Caspase 3(CAS 3), Caspase 9 (CAS 9), CD95 (Fas), Tumor Necrosis Factor Receptor 1 (TNFRSF1A) to observe relative fold changes of the expression using Real-Time PCR with housekeeping gene ß-actin. Cellular cytopathic effect (CPE), cell viability assay by methylene blue assay, and cell cytotoxicity of the crude extract against the THP-1 cell line were also studied along with it's bio-active compositional analysis of the extract was explored using ultra-performance liquid chromatography followed by mass spectra. RESULTS: The N. caerulea flower extract is capable of inducing apoptosis in AML and it can balance cytokine alterations in such diseases. CONCLUSIONS: Nymphaea caerulea flower extract appears to be a good anti-leukemia agent.


Subject(s)
Leukemia, Myeloid, Acute , Nymphaea , Humans , THP-1 Cells , Nymphaea/chemistry , HEK293 Cells , Cytokines , Leukemia, Myeloid, Acute/genetics , Tumor Necrosis Factor-alpha/genetics , Interleukin-6/genetics , Flowers , Complex Mixtures , Cell Line, Tumor
20.
Environ Sci Pollut Res Int ; 31(10): 15078-15090, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38286931

ABSTRACT

Green and low-carbon materialization for dredged sediment (DS) is limited due to its low pozzolanic activity. In this study, a novel DS-based non-sintered lightweight aggregate (LWA) is developed by steel slag (SS) and fly ash (FA) activation. Process optimization is performed by the response surfaces, and the basic properties and characterization of the optimal product are investigated. Results indicated that the optimized design ceramic aggregate (ODCA) was prepared as follows: raw pellets comprising of 59.2% DS, 5% SS, 35.8% FA, 5% MK, 5% H2O2, and 2‰ foam stabilizer were activated by alkali activator (1.5 weight ratio of 14 M NaOH to water glass) and then cured at 80 °C and 95% humidity for 24 h. The basic and environmental performances of ODCA were in accordance with standards, whose bulk density was as low as 665.8 kg/m3, the high cylinder compressive strength was 6.143 MPa, and leaching concentrations of heavy metals were controllable. The regulation mechanism of LWA performances could be summarized as follows. SS and FA additives played the role for the mechanical strength enhancement and passivation of heavy metals, which promoted the formation of sillimanite, chabazite, and C-S-H / C-S-A-H gels in ODCA. The bulk density of ODCA was greatly reduced by H2O2 addition, where ODCA had an open-pore structure with a median pore size of 4969.75 nm. Note that C-S-H/C-S-A-H were the key hydration products to give ODCA light density and high mechanical strength, simultaneously.


Subject(s)
Coal Ash , Complex Mixtures , Metals, Heavy , Coal Ash/chemistry , Industrial Waste/analysis , Steel , Hydrogen Peroxide , Metals, Heavy/chemistry
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