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Alternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC–MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations ≥ 1 µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥ 0.4 µM) and ATX-I (≥ 2 µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins. [ABSTRACT FROM AUTHOR]

We analyzed the toxic effect of the ethanolic extract of Passiflora incarnata (EEP) and its nanoformulation (N-EEP) in the in vitro and in vivo models (zebrafish embryos and Swiss albino mice). The EEP composition was verified by phytochemical and GC–MS analysis. The synthesized N-EEP was characterized using UV–visible spectroscopy and scanning electron microscopy. In vitro results showed both EEP and N-EEP have a dose-dependent effect in L132 cells (normal embryonic lung cells). In zebrafish embryos, no developmental changes were observed for both EEP and N-EEP at 200 µg/ml. The acute and sub-acute toxicity of EEP and N-EEP was identified by oral administration in Swiss albino mice. A single-day oral dose of EEP and N-EEP at different concentrations was administered for acute toxicity, and changes in body weight, food, water intake, temperature, respiration rate, skin color changes, and eye color till 72 h was observed. In a sub-acute toxicity study, 28 days oral administration of different concentrations of EEP and N-EEP was done. Hematological analysis, serum hepatic biochemical parameter analysis, and histopathological analysis for the liver, kidney, spleen, intestine, and heart were performed. The results indicated that lower than 600 mg/kg of EEP and N-EEP can safely be used for the remediation of a spectrum of diseases. [ABSTRACT FROM AUTHOR]

The current research happens green mediated obtaining of MgO nanoparticles via Magnolia champaca (L) plant root for analysis of its significant bio-clinical implementations. The green-mediated obtained magnesium oxide nanoparticles are confirmed through using XRD, FTIR, SEM, TEM, and UV-visible spectroscopy analysis. The green-associated M. champaca synthesized MgO nanoparticles revealed an absorption wavelength of 470 nm which is respective to MgO NPs. FTIR spectrum of the plant obtained MgO NPs showed strong spectrum at 2357, 2178, and 2015cm−1 (methylene groups of proteins), 1611 cm−1 (amide or carboxylate salt), 1393 cm−1 (carboxylate salt as and adsorption of CO32– and CO2 in the surface of MgO-NPs.), 1059 cm−1 (Mg–OH stretching), 647, and 577 cm−1 (Mg-O). The shape morphology of plant-mediated MgO NPs was determined through SEM revealing irregular shape and a scale range of 100 nm. Total antioxidant activity, scavenging and DPPH activity of plant-mediated obtained MgO NPs, plant extract, and ascorbic acid are evaluated, and the obtained results show better antioxidant activity in MgO NPs. The higher zone of suppression has seemed on the plant-associated obtained MgO NPs (120 g/mL) towards B. subtilis MTCC 1133 (21 ± 0.22 mm) and P. aeruginosa MTCC 2582 (23 ± 0.30 mm). The plant-mediated obtained MgO NPs revealed higher antibacterial properties compared to the antibiotic drug which effectively lower the alterations for the formation of antibiotic resistance of bacterial samples. The plant-mediated and obtained MgO NPs was found to highest antioxidant properties when differentiate from ascorbic acid. Plant-mediated obtained MgO NPs give an effective method that might be safe and high-scale industrial formation showing the merits of eco-friendly and low economic and also useful for various biomedical implementations. [ABSTRACT FROM AUTHOR]

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 32 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker–Lonsdale drug release kinetics. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) have gained significant attention due to their unique mechanical, electrical, and thermal properties. These exciting properties of CNTs make them productive in various applications, from electronics to optics to therapeutics. However, concerns about the potential toxicity of carbon nanotubes have also been raised, prompting extensive research to understand their effects on human health and the environment. Several studies have investigated the toxicity of carbon nanotubes, and the results vary depending on factors such as size, shape, surface chemistry, and the route of exposure. This review highlights the toxicological aspects of CNTs with a special focus on the major consequences of CNT toxicity. The study unfolds the prospects on how the toxicity of CNTs causes adverse effects on the central nervous system, kidney, spleen, eye, cardiac, etc., and thus can influence numerous applications covering from clinical to environmental. Moreover, the report offers an imperative deliberation over the curing or remedies of CNT toxicity, which can provide collective insights for the researchers. Thus, this review report provides the developments, implications, and different approaches to CNT toxicity so that the readers can clearly understand the wide-ranging forecasts of CNT toxicity.

Abstract Auraptene (AUR) and umbelliprenin (UMB) are naturally occurring prenylated coumarins that have demonstrated promising anticancer effects across various human cancer cell lines. This meta-analysis aimed to systematically assess, compare, and quantify the anticancer efficacy of AUR and UMB by synthesizing evidence from in vitro studies. A comprehensive literature search identified 27 eligible studies investigating AUR or UMB against cancer cells. Mixed-effects models revealed significant negative associations between coumarin dose and viability for AUR (est. = − 2.27) and UMB (est. = − 3.990), underscoring their dose-dependent cytotoxicity. Meta-regression indicated slightly higher potency for UMB over AUR, potentially due to increased lipophilicity imparted by additional isoprenyl units. Machine learning approaches identified coumarin dose and cancer type as the most influential determinants of toxicity, while treatment duration and the specific coumarin displayed weaker effects. Moderate (AUR) to substantial (UMB) between-study heterogeneity was detected, although the findings proved robust. In summary, this meta-analysis establishes AUR and UMB as promising natural anticancer candidates with clear dose-toxicity relationships across diverse malignancies. The structural insights and quantifications of anticancer efficacy can inform forthcoming efforts assessing therapeutic potential in pre-clinical models and human trials.

The existing in vitro toxicological models lack translational potential, which makes difficult the application of gathered information to clinical usage. To tackle this issue, we built a model with four different types of primary liver cells: hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volumes of cell medium, hepatocyte proportions of total cells and additions of extracellular matrixes. We added rifampicin (RIF), ibuprofen (IBU) and 5-fluorouracil (5-FU) to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured in clinical diagnostics. When we exposed the selected model configuration to RIF, IBU and 5-FU, we observed similar glucose, triglyceride and albumin dynamics as in vivo (from clinical data). Therefore, we have built an in vitro liver model that resembles the liver microenvironment, and we have analysed it with clinical instrumentation to facilitate data translation. Furthermore, during these observations, we found that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function. [ABSTRACT FROM AUTHOR]

Zirconia nanoparticles are used in various industrial and biomedical applications such as dental implants, thermal barrier sprays, and fuel cells. The interaction of nanoparticles with the environment and humans is inevitable. Despite the enormous application potential of these nanoparticles, there are still some gaps in the literature regarding potential toxicological mechanisms and the genotoxicity of zirconia nanoparticles. The lung is one of the main exposure routes to nanomaterials; therefore, the present study was designed to determine the genotoxic and mutagenic effect of zirconia NPs in V-79 lung cells. Zirconia nanoparticles showed significant internalization in cells at 100 μg/mL and 150 μg/mL concentrations. Zirconia nanoparticles showed low cytotoxicity and were found to generate ROS in V-79 cells. In alkaline comet assay, zirconia nanoparticles (10 μg/mL, 50 μg/mL, and 100 μg/mL) exposed cells exhibited significant DNA strand breaks, while the neutral comet assay, which was used for double-strand break assessment, only revealed significant damage at 100 μg/mL. Chromosomal aberration induced by zirconia nanoparticles mainly resulted in the generation of gaps, few fragments, and breaks which signifies the low clastogenic activity of these nanoparticles in the V-79 cell line. In MN assay, zirconia nanoparticles resulted in no significant micronuclei induction at any given concentration. In the HPRT mutation assay, the particle shows a dose-dependent increase in the mutant frequency. It is evident from the result that zirconia nanoparticles cause dose-dependent cytotoxicity and genotoxicity, but still, more studies are needed to evaluate the clastogenic potential and the possible mechanism involved. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), a trichothecene mycotoxin, could lead to cytotoxicity in both animal bodies and plant seed cells. Ozone degradation technology has been applied to DON control. However, the safety and quality of the contaminated grain after DON degradation are largely obscured. In this work, we evaluated the cytotoxicity of ozone-treated DON through seed germination experiments and cytotoxicity tests. Cell experiments showed that the inhibition rate of HepG2 viability gradually increased within the concentrations of 1–10 mg/L of DON, alongside which an IC50 (half maximal inhibitory concentration) of 9.1 mg/L was determined. In contrast, degrading DON had no significant inhibitory effect on cell growth. Moreover, a 1–10 mg/L concentration of DON increased production of a large amount of reactive oxygen radicals in HepG2, with obvious fluorescence color development. However, fluorescence intensity decreased after DON degradation. Further, DON at a concentration of >1 mg/L significantly inhibited the germination of mung bean seeds, whereas no significant inhibition of their germination or growth were observed if DON degraded. Changes in total protein content, fatty acid value, and starch content were insignificant in wheat samples suffering ozone degradation, compared to the untreated group. Lastly, the ozone-treated wheat samples exhibited higher tenacity and whiteness. Together, our study indicated that the toxicity of DON-contaminated wheat was significantly reduced after ozone degradation. [ABSTRACT FROM AUTHOR]

Background: New fourth generation electronic nicotine delivery system (ENDS) devices contain high levels of nicotine salt (up to 60 mg/mL), whose cellular and molecular effects on immune cells are currently unknown. Here, we used a physiologically-relevant in vitro air-liquid interface (ALI) exposure model to assess the toxicity of distinct ENDS, a 3rd-generation electronic-cigarette (e-cig) and two 4th-generation ENDS devices (JUUL and Posh Plus). Methods: Murine macrophages (RAW 264.7) were exposed at the ALI to either air, Menthol or Crème Brûlée-flavored ENDS aerosols generated from those devices for 1-hour per day for 1 or 3 consecutive days. Cellular and molecular toxicity was evaluated 24 h post-exposure. Results: 1-day of Menthol-flavored JUUL aerosol exposure significantly decreased cell viability and significantly increased lactate dehydrogenase (LDH) levels compared to air controls. Further, JUUL Menthol elicited significantly increased reactive oxygen species (ROS) and nitric oxide (NO) production compared to air controls. Posh Crème Brûlée-flavored aerosols displayed significant cytotoxicity – decreased cell viability and increased LDH levels –after 1- and 3-day exposures, while the Crème Brûlée-flavored aerosol produced by the 3rd-generation e-cig device only displayed significant cytotoxicity after 3 days compared to air controls. Further, both Posh and third-generation e-cig Crème Brûlée flavored-aerosols elicited significantly increased ROS plus high levels of 8-isoprostane after 1 and 3 days compared to air controls, indicating increased oxidative stress. Posh and third-generation e-cig Crème Brûlée flavored-aerosols elicited reduction in NO levels after one day, but elicited increase in NO after 3 days. Genes in common dysregulated by both devices after 1 day included α7nAChR, Cyp1a1, Ahr, Mmp12, and iNos. Conclusion: Our results suggest that ENDS Menthol and Crème Brûlée-flavored aerosol exposures from both 3rd- and 4th-generation ENDS devices are cytotoxic to macrophages and cause oxidative stress. This can translate into macrophage dysfunction. Although 4th-generation disposable ENDS devices have no adjustable operational settings and are considered low-powered ENDS devices, their aerosols can induce cellular toxicity compared to air-exposed control cells. This study provides scientific evidence for regulation of nicotine salt-based disposable ENDS products.

[Display omitted] • In-depth analysis of glass/carbon-fiber composites thermochemical behavior. • Thermogravimetry mass spectrometry mimicking composite pyrolytic recycling. • Online mass spectrometric product monitoring at Auger pilot plant scale-up. • Morphological investigation revealed residual occluded coke on the fibers. • Toxicological assessment found low hazardous potential of the recovered fibers. The increasing demand for lightweight materials with exceptional stability and durability has resulted in a significant rise in fiber-reinforced plastic (FRP) production. These materials find applications in various fields. However, the exceptional properties and diverse compositional range of FRPs pose challenges to conventional recycling strategies. Pyrolysis has emerged as a highly promising approach for separating the fibers from the polymer matrix. In this study, we employed thermal analysis coupled with high-resolution mass spectrometry to investigate the pyrolysis process. Representative FRP showed a starting decomposition temperature of 300 °C and bisphenol A, styrene, alkenes, and phenols could be identified. The identified parameters were used to operate a pilot plant with a capacity of up to 50 kg/h FRP, and reactor products were directly analyzed with soft photoionization mass spectrometry. The findings demonstrated good agreement between the pilot plant results and laboratory experiments, particularly for smaller compounds (m / z <2 0 0). The non-condensable fraction showed a range of 17 to 22 MJ/m3 as lower heating value. Analysis of the recovered fibers (diameter between 6.20 and 8.05 μm) revealed residual coke, but no toxic fibers were detected, according to the World Health Organization's definition. Yet, the organic coating of the fibers contained small amounts of potentially harmful PAHs. A toxicological assessment using a multicellular in vitro model confirmed the low hazardous potential of the recovered fibers. The findings contribute to developing sustainable and environmentally friendly recycling strategies for FRP while addressing important aspects related to the safety and toxicological implications of the resulting chemicals and fibers. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air–liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes. [ABSTRACT FROM AUTHOR]

This study outlines the synthesis of biogenic copper oxide nanoparticles (CuONPs) using an extract derived from Cassia fistula Linn (Cf) leaves through a green synthesis approach. Characterization of the synthesized CfBio-CuONPs was carried out using UV- VIS, FTIR, DLS, XRD, and TEM studies. The CfBio-CuONPs exhibited a prominent peak at 272 nm in UV–VIS spectroscopy, and XRD measurements confirmed their crystalline nature. The FTIR spectrum of CfBio-CuONPs revealed the presence of functional groups such as O–H and aromatic groups. TEM analysis confirmed that the CfBio-CuONPs were predominantly spherical with diameters ranging from 15 to 25 nm. Subsequently, the antibacterial potential of CfBio-CuONPs was evaluated against four pathogenic bacteria, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Bacillus subtilis. Among these, B. subtilis exhibited the highest zone of inhibition (26.93 ± 2.01 mm), followed by E. coli (24.25 ± 1.04 mm), P. aeruginosa (23.98 ± 0.97 mm), and S. epidermidis (22.97 ± 1.20 mm). CfBio-CuONPs demonstrated maximum antioxidant activity (78 ± 1.54%) at a dose-dependent concentration of 2000 µg/ml. Furthermore, in vitro toxicity assessment using the toxtrak test indicated that CfBio-CuONPs exhibited a significantly stronger toxic effect value/PI against E. coli (93.52%) compared to P. aeruginosa (92.65%), B. subtilis (91.25%), and S. epidermidis (82.89%). These results underscore the notable toxicity of CfBio-CuONPs against E. coli, surpassing that against other bacteria and conventional antibiotics. This study highlights the potential utility of CfBio-CuONPs for eradicating pathogenic microorganisms and suggests potential implications for ecotoxicology. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is a fish pathogen which is widely associated with diseases related to freshwater fishes. Vibrio parahemolyticus is a major globally emerging marine pathogen. Seven novel compounds were extracted from the ethyl acetate extract of Bacillus licheniformis, a novel marine bacterium isolated from marine actinomycetes. The compounds were identified using Gas Chromatography-Mass Spectroscopy (GC–MS). Only one bioactive compound having potent antibacterial activity was virtually screened to understand its drug-like property according to Lipinski's rule. The core proteins, 3L6E and 3RYL from the pathogens, A. hydrophila and V. parahemolyticus were targeted for drug discovery. In the present in-silico approach, Phenol,2,4-Bis(1,1-Dimethylethyl) a potent bioactive compound present in Bacillus licheniformis was used to prevent the infection due to the two pathogens. Further, using this bioactive compound, molecular docking was done to block their specific target proteins. This bioactive compound satisfied all the five rules of Lipinski. Molecular docking result revealed the best binding efficacy of Phenol,2,4-Bis(1,1-Dimethylethyl) against 3L6E and 3RYL with − 4.24 kcal/mol and − 4.82 kcal/mol, respectively. Molecular dynamics (MD) simulations were also executed to determine the binding modes as well as the stability of the protein–ligand docking complexes in the dynamic structure. The in vitro toxicity analysis of this potent bioactive compound against Artemia salina was carried out, revealing the non-toxic nature of B. licheniformis ethyl acetate extract. Thus, the bioactive compound of B. licheniformis was found to be a potent antibacterial agent against A. hydrophila and V. parahemolyticus. [ABSTRACT FROM AUTHOR]

Phytotoxic induction by imidacloprid and its nano form on the cucumber plant and the adverse impact on the tissue culture of HepG2 cell line were demonstrated. Nano-form of imidacloprid was loaded on chitosan nanoparticles (NPs). Significant increase in the plant morphological parameters was noticed after the last periods. The nano-form exhibited significant increases in the fruits yield greater than the traditional form. Also, the quality recognized the same pattern. All treatments of the nano-form: dose, 1/2 dose and 2-times dose showed an increase in the leave pigments greater than the traditional form. The bio-safety procedure on HepG2 cell lines showed a slight difference between the traditional and nano-form (1.22-folds). However, lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) level showed significant increases in the treated cells, respect to their controls. Nano-formulation practices have advantages on the vegetable crops to increase their characteristics. Further toxicological studies must be required before field particles. [ABSTRACT FROM AUTHOR]

Background: Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects in vivo leading to carcinogenesis. Methods: In vitro toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite. The analysis of the in vitro data allowed us to assess the major fibre parameters responsible for alterations in the key characteristics of carcinogens for each investigated fibre and the intensity of their effect. Results: Crystal habit and density of the fibres affect exposure but are not major parameters contributing to the KCs. For chrysotile, besides length, we found that fibre parameters that greatly contribute to the KCs are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are the fibre length, iron content and related parameters like the ferrous iron content, iron nuclearity, transition metals content and zeta potential. Conclusions: The results of our study can be a starting point for developing personalized cancer screening and prevention strategies as long as the nature of the fibre of the exposed patient is known. We can speculate on a future personalized prevention therapy targeting the fibres with surface-engineered nanocarriers with active complexes that are selective for the surface charge of the fibres. For chrysotile, a complex with deferasirox that can chelate Fe2+ and deferoxamine that preferentially chelates Fe3+ is proposed with the anchorage to the silica chrysotile surface driven by aspartic acid. For crocidolite, deferiprone chelating both Fe3+ and Fe2+ combined with lysine to attract the silica crocidolite surface is proposed.

Introduction: Swietenia macrophylla King (family Meliaceae) is a timber species with medicinal value. The seed is used as traditional medicine, however there are reports of liver injury, suspected to be associated with S. macrophylla seed consumption. The aim of this study is to assess the toxicity of S. macrophylla seed prepared in different solvent of extraction using a cell-based assay. Methods: Two methods were employed in the preparation of the seed extracts. In the first method, the dried seed was extracted with ethanol, methanol, or 50% ethanol. In the second method, the dried seed was extracted sequentially with solvents following ascending polarity. HepG2 cells were used as an in vitro liver model. The cells were treated with various concentrations of seed extracts and the cell viability was assessed by the 3, (4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Swietenia macrophylla seed was cytotoxic towards HepG2 cells with the chloroform extract being the most cytotoxic, followed by the ethyl acetate and hexane extracts. The ethanol, methanol, and 50% ethanol extracts were also cytotoxic but to a lesser extent than the three non-polar extracts. The water extract does not negatively affect cell viability. Conclusion: The findings reveal the cytotoxic effect of S. macrophylla seed is dependent on solvent extraction. [ABSTRACT FROM AUTHOR]

Polydimethylsiloxane (PDMS) is a substitute for vitreous humour in vitreoretinal surgery and is usually produced from octamethylcyclotetrasiloxane (D4). In Indonesia, both commercial PDMS and D4 are limited and expensive. Dichlorodimethylsilane (DCMS) can be an alternative to produce PDMS. DCMS is cheaper and easier to obtain than D4. However, more extra effort is needed in order to produce PDMS from DCMS. Therefore, this study aimed to produce PDMS from DCMS by varying the ratio of DCMS precursor to dichloromethane (DCM) solvent at ratios of 1:1 and 1:4 through the hydrolysis–condensation method under neutral conditions. The PDMS produced had medium- (2.06 Pa·s) and high viscosity (3.59 Pa·s), with densities ranging from 0.96 to 0.99 g/mL. The refractive index was 1.4034–1.4036 and surface tension was 21 × 10−3 N/m, while they were able to transmit ~100% visible light, which were similar values to the commercial PDMS characteristics. PDMS samples were characterized using IR and NMR spectroscopy, which confirmed they were of PDMS type. The most optimum DCMS:DCM ratio was 1:1 due to the medium-viscosity PDMS type that could be produced. The in vitro HET–CAM toxicity test showed that samples were non-irritant, similar to PDMS produced from D4. PDMS from DCMS was non-toxic and ready to be used as a vitreous humuor substitution. [ABSTRACT FROM AUTHOR]

Micro/nano plastics (M/NPs) are emerging pollutants that have extensively infiltrated various aspects of human life, posing a significant threat to the natural ecological systems. M/NPs can enter the digestive system through the oral cavity and accumulate in various organs. The current research on M/NPs primarily relies on model organisms, and there remains a dearth of direct evidence concerning the impact of M/NPs on human health. Commonly utilized specific two dimensional (2D) cultured cell lines exhibit substantial disparities in physiological functions when compared to multicellular tissues in vivo. The conduct of animal experiments is a time-consuming process, constrained by ethical considerations, and also confronted with interspecies variations. A significant breakthrough in biology is the development of organoids derived from stem cells. Intestinal organoids can mimic the complex structure and functionality of tissue, and can generate cell-cell and cell-matrix interactions that closely resemble physiological responses in the body. As a result, they provide a more accurate reflection of toxic effects and mechanisms, and hold great potential for applications in the environmental toxicology assessment. However, the current research on the toxic mechanisms of M/NPs using intestinal organoids is still in its early stages. The focus of this review is on the application of intestinal organoids in toxicology studies of M/NPs, assessing the correlation between M/NPs and diseases, as well as elucidating the molecular mechanisms underlying toxic effects. Ultimately, we present the challenges and potential solutions for utilizing intestinal organoids as models to evaluate M/NPs-induced toxicity, aiming to provide valuable insights for future research.

PHYTOTOXIC effects of propamocarb-HCl pesticide and its Nano form on cucumber plant and their adverse impact on tissue culture of HepG2 line were studied. Nano form was loaded on chitosan nanoparticles (NPs). Significant increase in plant morphological parameters was noticed after the last periods of transplanting. Also, it exhibited significant increases in fruits yield greater than the traditional form. The quality recognized the same pattern. All treatments: Doses, ½ doses, and double doses showed an increase in leave pigments in the case of nano-form treatments greater than the traditional form. Biosafety profile on HepG2 cell lines showed a slight difference with 1.22 folds between the traditional and nano-form. While, lactate dehydrogenase (LDH) and malondialdehyde (MDA) showed a significant increase, compared to their control. Such a finding provides the advantage of nano-formation on vegetable crops, but it must be coupled with further toxicological studies. [ABSTRACT FROM AUTHOR]

Recently, carbon nanotubes (CNTs) have become a possible new choice in variable disciplines such as gene therapy, bioengineering, cancer treatment and nanotechnology applications in devices, and optics. This is because multi-walled carbon nanotubes (MWCNTs) are more durable and possess high electrical and thermal conductivity along with some of the significant unique physico-chemical characteristics. As the manufacturing and usage of CNTs rises, the likelihood of exposure to CNTs, whether directly or indirectly, is higher in the general population. As a result, it becomes crucial to examine the problems related to the toxicity of CNTs and identify the most effective solutions to address such concerns. Available data demonstrates unequivocally that nanotubes may, in some circumstances, pass membrane barriers and enter the organ which may lead to adverse consequences such as inflammatory and fibrotic responses. So, the first step in assessing the biosafety and biocompatibility of CNTs in living organisms is to quantify their abundance. This review article discusses the toxicity mechanisms of MWCNTs in vitro and in vivo in different bio-systems (specifically liver) and their interaction mechanism. In addition, it highlights the latest advances in carbon nanotubes in the healthcare and pharmaceutical sector from multiple perspectives. [ABSTRACT FROM AUTHOR]

Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections. Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer, which heat treatment (curing) modifies. Although toxicity was found related to aggregation status - loose aggregates significantly more toxic than tight aggregates - the precise mechanism linking aggregation and toxicity was not well understood. This study directly measured drug release rate from various AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state, drug release, and in vitro toxicity. UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features: a ∼25 nm blue-shift of the main absorption peak (λmax) in aqueous buffer and a decrease in the OD346/OD322 ratio upon thermal curing, reflecting tighter aggregation. In vitro release testing (IVRT) data showed, by applying and fitting first-order release kinetic models for one or two pools, that curing impacts two significant changes: a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated, more thermodynamically stable drug pool. The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data. The in vitro toxicity assay indicated a decreased toxicity with curing, as shown by the significantly increased concentration, causing half-maximal potassium release (TC50). The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation. This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release (directly measured rate constants), providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.

Low molecular weight proteins, known as chemokines, facilitate the migration and localization of immune cells to the site of infection and injury. One of the first chemokines identified, CXCL8 functions as a key neutrophil activator, recruiting neutrophils to sites of inflammation. Several viral infections, including zoonotic coronaviruses and poxviruses, have been reported to induce the expression of CXCL8. Dromedary camels are known to harbor several potentially zoonotic pathogens, but critical immune molecules such as chemokines remain unidentified. We report here the identification of CXCL8 from the dromedary camel - the first chemokine identified from camelids. The complete dromedary CXCL8 cDNA sequence as well as the corresponding gene sequence from dromedary and two New World camelids - alpaca and llama were cloned. CXCL8 mRNA expression was relatively higher in PBMC, spleen, lung, intestine, and liver. Poly(I:C) and lipopolysaccharide stimulated CXCL8 expression in vitro , while interferon treatment inhibited it. In vitro infection with potentially zoonotic camelpox virus induced the expression of CXCL8 in camel kidney cells. Toxicological studies on camelids have been limited, and no biomarkers have been identified. Hence, we also evaluated CXCL8 mRNA expression as a potential biomarker to assess heavy metal toxicity in camel kidney cells in vitro. CXCL8 expression was increased after in vitro exposure to heavy metal compounds of cobalt and cadmium, suggesting potential utility as a biomarker for renal toxicity in camels. The results of our study demonstrate that camel CXCL8 plays a significant role in immunomodulatory and induced toxicity responses in dromedary camels. • Dromedary CXCL8 - the first chemokine identified from camelids. • Camelpox virus infection induces the expression of CXCL8 in vitro. • Poly(I:C) and LPS stimulates CXCL8 expression in vitro , while IFN inhibits it. • CXCL8 expression induced in camel kidney cells exposed to heavy metals in vitro. • CXCL8 show potential utility as biomarker for in vitro toxicity in camels. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air–liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Microplastics (MPs) represent a worldwide emerging relevant concern toward human and environmental health due to their intentional or unintentional release. Human exposure to MPs by inhalation is predicted to be among the most hazardous. MPs include both engineered, or primary MPs, and secondary MPs, materials obtained by fragmentation from any plastic good. The major part of the environmental MPs is constituted by the second ones that are irregular in size, shape and composition. These features make the study of the biological impact of heterogenous MPs of extremely high relevance to better estimate the real toxicological hazards of these materials on human and environmental organisms. The smallest fractions of plastic granules, relying on the micron‐sized scale, can be considered as the most abundant component of the environmental MPs, and for this reason, they are typically used to perform toxicity tests using in vitro systems representative of an inhalation exposure scenario. In the present work, MPs obtained from industrial treatment of waste plastics (wMPs < 50 μm) were investigated, and after the physico‐chemical characterization, the cytotoxic, inflammatory and genotoxic responses, as well as the modality of wMPs interactions with alveolar lung cells, were determined. Obtained results indicated that, at high concentrations (100 μg/ml) and prolonged exposure time (48 h), wMPs affect biological responses by inducing inflammation and genotoxicity, as a result of the cell–wMP interactions, also including the uptake of the smaller particles. The toxicity of waste microplastics (wMPs < 50 μm), recovered from industrially recycled plastic granules, was evaluated by using an in vitro model of the lung (A549 cell line), in order to understand the biological outcomes induced by the inhalation of microplastics. Data showed that a prolonged (48 h) exposure to wMPs (100 μg/ml) induced cell viability reduction, inflammation and genotoxicity, as results of lung cell and wMPs interactions. [ABSTRACT FROM AUTHOR]

Curcumin; the major polyphenolic compound, isolated from Curcuma longa L.; loaded polyvinylpyrrolidone K90 fibers were prepared using electrospinning method. Effectiveness was tested on human colorectal adenocarcinoma cells with the presence of the endocrine disrupter Bisphenol A. Curcumin-loaded fibers were shown to have good physicochemical properties where excellent morphology of the electrospin fibers were formed. With the presence of 8 nM Bisphenol A, 17.37 mM fibers were found to inhibit proliferation in the cells in a dose-dependent manner. Fibers induced a significant increase in malondialdehyde by Thiobarbituric Acid Reactive Substances Assay compared to the control and this effect was supported by the presence of Bisphenol A. Western blot results indicate Super Oxide Dismutase-1 levels were increased by fiber, while Bisphenol A coincubated group resulted in a decrease. Fibers increased the expression of Estrogen Receptor 2, while Estrogen Receptor 1 expression did not change. Estrogen Receptor 2 expression was increased by coincubation with Bisphenol A; indicating a possible role of Estrogen Receptor 2 in the protective effects of fiber. This study presents that fiber had enhanced bioavailability and solubility with increased anticancer effect in human colon adenocarcinoma cells in presence of Bisphenol A; where involved mechanisms are antioxidant system and estrogen receptor expression. [ABSTRACT FROM AUTHOR]

Polydimethylsiloxane (PDMS) is a substitute for vitreous humour in vitreoretinal surgery and is usually produced from octamethylcyclotetrasiloxane (D4). In Indonesia, both commercial PDMS and D4 are limited and expensive. Dichlorodimethylsilane (DCMS) can be an alternative to produce PDMS. DCMS is cheaper and easier to obtain than D4. However, more extra effort is needed in order to produce PDMS from DCMS. Therefore, this study aimed to produce PDMS from DCMS by varying the ratio of DCMS precursor to dichloromethane (DCM) solvent at ratios of 1:1 and 1:4 through the hydrolysis–condensation method under neutral conditions. The PDMS produced had medium- (2.06 Pa·s) and high viscosity (3.59 Pa·s), with densities ranging from 0.96 to 0.99 g/mL. The refractive index was 1.4034–1.4036 and surface tension was 21 × 10−3 N/m, while they were able to transmit ~100% visible light, which were similar values to the commercial PDMS characteristics. PDMS samples were characterized using IR and NMR spectroscopy, which confirmed they were of PDMS type. The most optimum DCMS:DCM ratio was 1:1 due to the medium-viscosity PDMS type that could be produced. The in vitro HET–CAM toxicity test showed that samples were non-irritant, similar to PDMS produced from D4. PDMS from DCMS was non-toxic and ready to be used as a vitreous humuor substitution.

• 10 µg/L CPT reduced rainbow trout sperm motility to the % 50 level. • 5 µg/L MCZ reduced rainbow trout sperm motility to the % 50 level. • 200 µg/L AZX reduced rainbow trout sperm motility to the % 50 level. • The changes in fatty acids caused by the fungicides were shown for the first time. • This study is the first to measure changes in TAC and DPPH by the fungicides. An in vitro study using rainbow trout spermatozoa was designed to evaluate the toxic effects of different concentrations of captan (CPT), mancozeb (MCZ), and azoxystrobin (AZX) fungicides on motility parameters, lipid peroxidation, SOD activity, total antioxidant capacity (TAC), and DPPH inhibition. Moreover, changes in fatty acids profiles caused by the fungicides were determined for the first time. The results revealed that motility parameters, SOD activities, TAC values, and DPPH inhibitions decreased significantly while lipid peroxidation increased after ≥2 µg/L of CPT, ≥1 µg/L of MCZ, and ≥5 µg/L of AZX incubations for 2 h at 4 °C. Additionally, 10 µg/L CPT, 5 µg/L MCZ, and 200 µg/L AZX reduced motility to the 50 % level. Our results clearly demonstrated significant changes in the fatty acids profiles of spermatozoa exposed to these concentrations of the fungicides. The highest lipid peroxidation and the lowest monounsaturated and polyunsaturated saturated fatty acids (MUFA and PUFA, respectively) were detected in AZX. Even though the susceptibility of spermatozoa to oxidative damage is generally attributed to PUFA contents, the results of this study have represented that MUFA content could play a part in this tendency. Moreover, the lower concentration of MCZ reduced motility to the % 50 level while it deteriorated the fatty acids profile less than did AZX. Overall, the present study demonstrated that the detrimental effects of the fungicides on mitochondrial respiration and related enzymes have more priority than oxidative stress in terms of their toxicities on spermatozoa. It has also been suggested that fish spermatozoa are a good model for determining changes in the fatty acid profiles by fungicides, probably, by other pesticides and environmental contaminants as well. [ABSTRACT FROM AUTHOR]

Drugs can be toxic to the fetus depending on the amount that permeates across the maternal–fetal barrier. One way to limit the amount which penetrates this barrier is to increase the molecular size of the drug. In this study, we have achieved this by encapsulating our model antibiotic (vancomycin hydrochloride, a known nephrotoxic agent) in liposomes. PEGylated and non-PEGylated liposomes encapsulating vancomycin hydrochloride were prepared using two different methods: thin-film hydration followed by the freeze–thaw method and the reverse-phase evaporation method. These liposomes were characterized by their hydrodynamic size and zeta potential measurements, CryoTEM microscopy, loading and encapsulation efficiency studies, in vitro release measurements and in vitro cytotoxicity assays using NRK-52 E rat kidney cells. We also determined the in vitro permeability of these liposomes across the human placental cell and dog kidney cell barriers. Vancomycin hydrochloride-loaded PEGylated liposomes (VHCL-lipo) of a size less than 200 nm were prepared. The VHCL-lipo were found to have the faster release of vancomycin hydrochloride and resulted in greater viability of NRK-52E cells. In vitro, the VHCL-lipo permeated the human placental cell and dog kidney cell barriers to a lesser extent than the free vancomycin hydrochloride. The data suggest a reduction in nephrotoxicity and permeability of vancomycin hydrochloride after encapsulation in PEGylated liposomes. [ABSTRACT FROM AUTHOR]

Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of “unregulated” or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies.Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.

High-energy industrial processes have been associated with particle release into workplace air that can adversely affect workers' health. The present study assessed the toxicity of incidental fine (PGFP) and nanoparticles (PGNP) emitted from atmospheric plasma (APS) and high-velocity oxy-fuel (HVOF) thermal spraying. Lactate dehydrogenase (LDH) release, 2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) metabolisation, intracellular reactive oxygen species (ROS) levels, cell cycle changes, histone H2AX phosphorylation (γ-H2AX) and DNA damage were evaluated in human alveolar epithelial cells at 24 h after exposure. Overall, HVOF particles were the most cytotoxic to human alveolar cells, with cell viability half-maximal inhibitory concentration (IC50) values of 20.18 µg/cm2 and 1.79 µg/cm2 for PGFP and PGNP, respectively. Only the highest tested concentration of APS-PGFP caused a slight decrease in cell viability. Particle uptake, cell cycle arrest at S + G2/M and γ-H2AX augmentation were observed after exposure to all tested particles. However, higher levels of γ-H2AX were found in cells exposed to APS-derived particles (~16%), while cells exposed to HVOF particles exhibited increased levels of oxidative damage (~17% tail intensity) and ROS (~184%). Accordingly, APS and HVOF particles seem to exert their genotoxic effects by different mechanisms, highlighting that the health risks of these process-generated particles at industrial settings should not be underestimated. [ABSTRACT FROM AUTHOR]

Information about the potential oral health effects of vaping from electronic cigarettes (e-cigs) is still sparse and inconsistent. The purpose of this study was to compare the safety and cytotoxicity of e-cig liquid aerosols versus traditional cigarette (t-cig) smoke on human epithelial oral cells. T-cig smoke and e-cig aerosols were generated by a newly developed automated smoking instrument in order to simulate realistic user puffing behaviors. Air–liquid interface transwell cell cultures were exposed to standardized puff topography (puff duration: 2 s, puff volume: 35 mL, puff frequency: 1 puff every 60 s) of reference t-cigs or commercially available e-cigs at different air dilutions. Cell viability, morphology, and death rate were evaluated with MTT and TUNEL assays. The inflammatory cytokine gene expression of inflammatory genes was assessed by quantitative RT-PCR. E-cigs and t-cigs indicated similar adverse effects by enhancing cytotoxicity and cell death in a dose-dependent manner. E-cig aerosol and t-cig smoke treatment expressed upregulation of inflammatory cytokines up to 3.0-fold (p < 0.05). These results indicate that e-cig smoking may contribute to oral tissue–cell damage and tissue inflammation. Our approach allows the production of e-cig aerosol and t-cig smoke in order to identify harmful effects in oral tissues in vitro. [ABSTRACT FROM AUTHOR]

Deuteration is a chemical modification strategy that has recently gained traction in drug development. The replacement of one or more hydrogen atom(s) in a drug molecule with its heavier stable isotope deuterium can enhance its metabolic stability and pharmacokinetic properties. However, it remains uninterrogated if rational deuteration at bioactivation "hot-spots" could attenuate its associated toxicological consequences. Here, our preliminary screening with benzofuran antiarrhythmic agents first revealed that dronedarone and its major metabolite N-desbutyldronedarone elicited a greater loss of viability and cytotoxicity in human hepatoma G2 (HepG2) cells as compared with amiodarone and its corresponding metabolite N-desethylamiodarone. A comparison of dronedarone and its in-house synthesized deuterated analogue (termed poyendarone) demonstrated that deuteration could attenuate its in vitro toxicity in HepG2 cells by modulating the extent of mitochondrial dysfunction, reducing the dissipation of mitochondrial membrane potential, and evoking a distinct apoptotic kinetic signature. Furthermore, although pretreatment with the CYP3A inducer rifampicin or the substitution of glucose with galactose in the growth media significantly augmented the loss of cell viability elicited by dronedarone and poyendarone, a lower loss of cell viability was consistently observed in poyendarone across all concentrations. Taken together, our preliminary investigations suggested that the rational deuteration of dronedarone at its benzofuran ring reduces aberrant cytochrome P450 3A4/5-mediated bioactivation, which attenuated its mitochondrial toxicity in human hepatic HepG2 cells. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) have become ubiquitous environmental contaminants that have been associated with adverse pregnancy outcomes in women and experimental research models. Adverse developmental and reproductive outcomes have been investigated for relatively few PFAS, and such studies are not scalable to address the thousands of unique chemical structures. As the placenta has been reported as a PFAS target tissue, the human placental trophoblast JEG-3 cell line was employed in a high-throughput toxicity screen (HTTS) to evaluate the effects of 42 unique PFAS on viability, proliferation, and mitochondrial membrane potential (MMP). HTTS concentration-response curve fitting determined EC50 values for 79% of tested compounds for at least one of the three endpoints. Trophoblast migratory potential was evaluated for a subset of six prioritized PFAS using a scratch wound assay. Migration, measured as the percent of wound closure after 72 h, was most severely inhibited by exposure to 100 µM perfluorooctanoic acid (PFOA; 72% closure), perfluorooctanesulfonic acid (PFOS; 57% closure), or ammonium perfluoro-2-methyl-3-oxahexanoate (GenX; 79% closure). PFOA and GenX were subsequently evaluated for disrupted expression of 46 genes reported to be vital to trophoblast health. Disrupted regulation of oxidative stress was suggested by altered expression of GPEX1 (300 µM GenX and 3 µM GenX), GPER1 (300 µM GenX), and SOD1 and altered cellular response to xenobiotic stress was indicated by upregulation of the placental efflux transporter, ABCG2 (300 µM GenX, 3 µM GenX, and 100 µM PFOA). These findings suggest the placenta is potentially a direct target of PFAS exposure and indicate that trophoblast cell gene expression and function are disrupted at PFAS levels well below the calculated cytotoxicity threshold (EC50). Future work is needed to determine the mechanism(s) of action of PFAS towards placental trophoblasts.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 3 2 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.

The uncertainty of potential risks associated with micro- and nanoplastics (MNPs) are of growing public concern. However, the diversity of MNPs in the environment makes a systematic analysis of potential health effects challenging. New tools and approaches are necessary to investigate biological effects of MNPs. With this quick scoping review, we aim to analyse the suitability of in vitro models for assessing the interaction of MNPs with intestinal cells. Our analysis revealed that currently the majority of in vitro tests are based on the three cell lines Caco-2, HT-29, and HCT-116. They have particularly been used to assess endpoints related to basal cytotoxicity, the internalisation of MNPs and effects on the intestinal barrier. When co-cultured with various cell lines, they also allow to investigate additional effects such as inflammation, metabolic actions and the relevance of the intestinal mucus. However, methodological gaps remain regarding the assessment of a potential accumulation of MNPs, leaching of additives/impurities and in resulting long-term effects as well as cell-type specific toxicities. In addition, only few in vitro studies investigated effects of MNPs on the microbiome. Stem cell-based assays using, for example, the emerging organoid technology are promising for analysing MNP effects on tissue-like structures, while avoiding the particular characteristics of the currently used cancer derived cell lines. The various cell lines and culture techniques can be combined in testing strategies, to better elucidate potential biological interaction of MNPs with biological systems. We suggest to implement a tiered testing strategy, in which monocultures can serve as a tool for high-throughput testing of MNPs. In the next steps co-cultures can be used to assess the potential of a systemic uptake of MNPs and organ-on-a-chip models will provide more reliable insights into relevant doses triggering biological effects. Finally, organoids can help to discover new and more complex reactions initiated by MNPs.

Varroa destructor is the most important ectoparasitic mite of honey bees that has a negative impact on bee health and honey production. The control programs are mainly based on the use of synthetic acaricides that are often administered indiscriminately. All this has led to drug resistance that now represent a great concern for honey bee farming. The research for alternative products/methods for mites’ control is now mandatory. The aim of this study was to test whether Citrus spp. essential oils could diminish the growth of the V. destructor mite. In Calabria (southern Italy), plants of the Citrus genus are very common and grow both spontaneously and cultured. The essential oils used in this study were extracted from bergamot (Citrus bergamia), grapefruit (Citrus paradisi), lemon (Citrus limon), orange (Citrus sinensis), and mandarin (Citrus reticulata) by hydrodistillation. Every EO was in vitro tested against V. destructor. Each experimental replicate was performed using 35 viable adult female mites (5 for each EO) collected the same day from the same apiary and included negative controls (5 individuals exposed to acetone only) and positive controls (5 individuals exposed to Amitraz diluted in acetone). The essential oils (Eos) were diluted (0.5 mg/mL, 1 mg/mL, and 2 mg/mL) in HPLC grade acetone to obtain the working solution to be tested (50 µL/tube). Mite mortality was manually assessed after 1 h exposure under controlled conditions. The essential oils that showed the best effectiveness at 0.5 mg/mL were bergamot, which neutralized (dead + inactivated) 80% (p ≤ 0.001) of the parasites; grapefruit, which neutralized 70% (p ≤ 0.001); and lemon, which neutralized 69% of them. Interestingly, the positive control (Amitraz) at the same concentration neutralized 60% of the parasites. These results demonstrate that Calabrian bergamot, grapefruit, and lemon Eos consistently reduced V. destructor viability and open the possibility for their utilization to control this parasite in honey bee farming. [ABSTRACT FROM AUTHOR]

Abstract Background The regulatory definition(s) of nanomaterials (NMs) frequently uses the term ‘agglomerates and aggregates’ (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective. This knowledge gap greatly affects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nano-sized particles (1–100 nm in diameter) and considered safe as they form large aggregates (> 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes. Results We used a precipitated SAS dispersed by different methods, generating 4 ad-hoc suspensions with different aggregate size distributions. Their effect on cell metabolic activity, cell viability, epithelial barrier integrity, total glutathione content and, IL-8 and IL-6 secretion were investigated after 24 h exposure in human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic cells (THP-1). We observed that the de-aggregated suspension (DE-AGGR), predominantly composed of nano-sized aggregates, induced stronger effects in all the cell lines than the aggregated suspension (AGGR). We then compared DE-AGGR with 2 suspensions fractionated from AGGR: the precipitated fraction (PREC) and the supernatant fraction (SuperN). Very large aggregates in PREC were found to be the least cytotoxic/biologically active compared to other suspensions. SuperN, which contains aggregates larger in size (> 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR. Conclusion Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates > 100 nm were not necessarily less cytotoxic than their nano-sized counterparts. This study suggests that aggregates of SAS are toxicologically relevant for the definition of NMs.

Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC–MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity. [ABSTRACT FROM AUTHOR]

Background: Ocean acts as a wealthy resource of biological diversity producing prospective novel metabolites from the organisms present in the environment. Novel bioactive compounds from Echinoderms mainly from sea stars have been extensively studied procuring rich diverse compounds which exhibits in vitro cytotoxicity comparable to or better than those of the potent anticancer drug. These sea stars which reside in the benthic region serves as their habitat and they are therefore predators and persistently being attacked by various organisms subsequently they acclimatize the survival approach to defend themselves from the external pathogens. Since these metabolites are obscured as a metabolic product during their endurance an initial evaluation of these compounds is necessary to assess human risk. Objectives: The present study focuses in vitro toxicity evaluation of isolated sterol like isolate from echinoderm sea star Stellaster equestris by incorporating hemolytic, chromosomal aberration assay and the cell viability tryphan blue exclusion assay against human peripheral blood. Methods: The in vitro toxicity evaluation was studied against the human peripheral blood collected from the healthy donors with the defined concentration of the sterol like compound from the sea star Stellaster equestris. The hemolytic, cell viability trypan blue exclusion method and chromosomal aberration assay were performed to check the hemolytic, mutagenic and genotoxic effect against the lymphocytes and the red blood cells. Results and Discussion: The result suggested that the hemolytic assay and the cell viability assay even in a dose dependent manner were non-hemolytic and percentage of the viability was not affected due to the exposure of the compound. The absence of genotoxicity was evident for the chromosomal aberration assay indicated that the isolated compound from the sea star Stellaster equestris might be considered as effective novel compound. [ABSTRACT FROM AUTHOR]