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Biological Trace Element Research Sep 2023Conditions associated with selenium (Se) and/or vitamin E (VitE) deficiency are still being reported in high-yielding pigs fed the recommended amounts. Here, the dietary...
Conditions associated with selenium (Se) and/or vitamin E (VitE) deficiency are still being reported in high-yielding pigs fed the recommended amounts. Here, the dietary effects of Se source (sodium selenite, NaSe, 0.40 or 0.65 mg Se/kg; L-selenomethionine, SeMet, 0.19 or 0.44 mg Se/kg; a NaSe-SeMet mixture, SeMix, 0.44-0.46 mg Se/kg) and VitE concentration (27, 50-53 or 101 mg/kg) on the antioxidant status of finisher pigs were compared with those in pigs fed non-Se-supplemented diets (0.08-0.09 mg Se/kg). Compared to NaSe-enriched diets, SeMet-supplemented diets resulted in significantly (p < 0.0018) higher plasma concentrations of total Se (14-27%) and selenospecies (GPx3, SelP, SeAlb; 7-83%), significantly increased the total Se accumulation in skeletal muscles, myocardium, liver and brain (10-650%), and enhanced the VitE levels in plasma (15-74%) and tissues (8-33%) by the end of the 80-day trial, proving better Se distribution and retention in pigs fed organic Se. Injecting lipopolysaccharide (LPS) intravenously half-way into the trial provoked a pyrogenic response in the pigs followed by a rapid increase of inorganic Se after 5-12 h, a drastic drop of SeMet levels between 12 and 24 h that recovered by 48 h, and a small increase of SeCys by 24-48 h, together with a gradual rise of GPx3, SelP and SeAlb in plasma up to 48 h. These changes in Se speciation in plasma were particularly significant (0.0024 > p > 0.00007) in pigs receiving SeMet- (0.44 mg Se/kg, above EU-legislated limits) or SeMix-supplemented (SeMet and NaSe both at 0.2 mg Se/kg, within EU-legislated limits) diets, which demonstrates Se metabolism upregulation to counteract the LPS-induced oxidative stress and a strengthened antioxidant capacity in these pigs. Overall, a Se source combination (without exceeding EU-legislated limits) and sufficient VitE supplementation (≥ 50 mg/kg) improved the pigs' antioxidant status, while doubling the allowed dietary organic Se increased the Se in tissues up to sixfold without compromising the animal's health due to toxicity. This study renders valuable results for revising the current dietary SeMet limits in swine rations.
Topics: Animals; Antioxidants; Dietary Supplements; Lipopolysaccharides; Selenium; Selenomethionine; Sodium Selenite; Swine; Vitamin E
PubMed: 36577830
DOI: 10.1007/s12011-022-03516-9 -
Environmental Analysis, Health and... Mar 2024The research determined the anthropogenic source and risk evaluation of total petroleum hydrocarbons of some ground water sources within Orji auto repair workshops,...
The research determined the anthropogenic source and risk evaluation of total petroleum hydrocarbons of some ground water sources within Orji auto repair workshops, Owerri, Imo State, Nigeria. The concentrations of total petroleum hydrocarbons in different groundwater samples within this vicinity were determined by selecting samples from five sampling locations using the liquid-liquid extraction process and gas chromatography fitted with a flame ionization detector. The concentrations of TPHs were determined with C15 (Pentadecane) and C30 (Triaconate) having the highest total concentrations in all sample locations of 29.67μg/mL and 23.17 μg/mL respectively while C13 (Tridecane) had the lowest combined concentration of 0.13 μg/mL with the presence of both low molecular weight and high molecular weight TPHs, an indication that the water samples had significant levels of carcinogens. Diagnostic ratio and correlation analyses of the samples analyzed showed contamination of the groundwater sources were both of petrogenic and pyrogenic sources. TPHs concentrations found in this study also revealed considerable amount of pollution with respect to contamination factors, pollution load index and degree of contamination. Elevated hazard index was equally observed for adults and children indicating a potential harm to the health of children and adults suggesting a higher risk of cancer from interaction with the polluted water. These results indicate that in remediation actions needs to be carried out before consumption to avoid fatal long term heath consequences.
PubMed: 38631400
DOI: 10.5620/eaht.2024008 -
Environmental Science & Technology Feb 2024With the increased occurrences of wildfires worldwide, there has been an increase in scientific interest surrounding the chemistry of fire-derived "black" carbon (BC)....
With the increased occurrences of wildfires worldwide, there has been an increase in scientific interest surrounding the chemistry of fire-derived "black" carbon (BC). Traditionally, wildfire research has assumed that condensed aromatic carbon (ConAC) is produced via combustion, and thus, ConAC is equated to BC. However, the lack of correlations between ConAC in soils or rivers and wildfire history suggests that ConAC may be produced non-pyrogenically. Here, we show quantitative evidence that this occurs during the oxidation of biomass with environmentally ubiquitous hydroxyl radicals. Pine wood boards exposed to iron nails and natural weather conditions for 12 years yielded a charcoal-like ConAC-rich material. ConAC was also produced during laboratory oxidations of pine, maple, and brown-rotted oak woods, as well as algae, corn root, and tree bark. Back-of-the-envelope calculations suggest that biomass oxidation could be producing massive non-pyrogenic ConAC fluxes to terrestrial and aquatic environments. These estimates (e.g., 163-182 Tg-ConAC/year to soils) are much higher than the estimated pyrogenic "BC" fluxes (e.g., 128 Tg-ConAC/year to soils) implying that environmental ConAC is primarily non-pyrogenic. This novel perspective suggests that wildfire research trajectories should shift to assessing non-pyrogenic ConAC sources and fluxes, developing new methods for quantifying true BC, and establishing a new view of ConAC as an intermediate species in the biogeochemical processing of biomass during soil humification, aquatic photochemistry, microbial degradation, or mineral-organic matter interactions. We also advise against using BC or pyrogenic carbon (pyC) terminologies for ConAC measured in environmental matrices, unless a pyrogenic source can be confidently assigned.
Topics: Biomass; Carbon; Charcoal; Fires; Soot; Soil
PubMed: 38294931
DOI: 10.1021/acs.est.3c05448 -
Biomedicine & Pharmacotherapy =... Apr 2024Lipopolysaccharide (LPS, endotoxin) is ubiquitous and represents a harmful contaminant of pharmaceutical compounds, recombinant biologicals and drug products. The...
Lipopolysaccharide (LPS, endotoxin) is ubiquitous and represents a harmful contaminant of pharmaceutical compounds, recombinant biologicals and drug products. The pyrogen can induce severe immune responses and pathology in vitro and in vivo. Health authorities require strict control of endotoxin in parenteral drugs. However, for research and pre-clinical compound analysis, endotoxin testing is not a required quality control, which may cause potential drawbacks in the translational pipeline. Endotoxin testing is usually performed by the Limulus amebocyte lysate (LAL) assay, which is hampered by the so-called low endotoxin recovery (LER) effect when certain drug formulations are tested. A comprehensive study including structural, biophysical, and biological analyses was conducted to identify LER root cause for phosphate- and polysorbate-containing parenteral drug products. LPS in water showed extended ribbon-like aggregate structures. In placebo (formulation buffer without drug) and in drug product (drug in formulation buffer), a reaggregation of LPS into a network of interlinked micelles with hidden head group charges, and a strong reduction of the negative surface potential was observed. The non-accessibility of the LPS backbone has a direct impact leading (i) to a loss of activation of the LAL-cascade, (ii) reduced activation of the TLR4/MD-2 receptor system, and (iii) increased survival in a mouse model of endotoxemia. These data provide a structure-based explanation of the LER-underlying mechanisms. A human whole blood assay is shown to resolve LER and detect the pyrogenic activity of endotoxin with high sensitivity. This may open new test options to improve quality control in drug development and drug safety.
Topics: Animals; Mice; Humans; Endotoxins; Lipopolysaccharides; Micelles; Limulus Test; Drug Compounding
PubMed: 38401515
DOI: 10.1016/j.biopha.2024.116286 -
Environmental Science & Technology May 2024CO is 45 to 50 times more concentrated in soil than in air, resulting in global diffusive fluxes that outpace fossil fuel combustion by an order of magnitude. Despite...
CO is 45 to 50 times more concentrated in soil than in air, resulting in global diffusive fluxes that outpace fossil fuel combustion by an order of magnitude. Despite the scale of soil CO emissions, soil-based climate change mitigation strategies are underdeveloped. Existing approaches, such as enhanced weathering and sustainable land management, show promise but continue to face deployment barriers. We introduce an alternative approach: the use of solid adsorbents to directly capture CO in soils. Biomass-derived adsorbents could exploit favorable soil CO adsorption thermodynamics while also sequestering solid carbon. Despite this potential, previous study of porous carbon CO adsorption is mostly limited to single-component measurements and conditions irrelevant to soil. Here, we probe sorption under simplified soil conditions (0.2 to 3% CO in balance air at ambient temperature and pressure) and provide physical and chemical characterization data to correlate material properties to sorption performance. We show that minimally engineered pyrogenic carbons exhibit CO sorption capacities comparable to or greater than those of advanced sorbent materials. Compared to textural features, sorbent carbon bond morphology substantially influences low-pressure CO adsorption. Our findings enhance understanding of gas adsorption on porous carbons and inform the development of effective soil-based climate change mitigation approaches.
Topics: Carbon Dioxide; Soil; Porosity; Adsorption; Carbon; Charcoal; Climate Change
PubMed: 38689207
DOI: 10.1021/acs.est.4c02015 -
MedRxiv : the Preprint Server For... Jan 2024Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling...
BACKGROUND
Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a self-blood collection tool (RNA) to profile detailed kinetics of the pre-symptomatic to convalescence host immunity to contemporaneous respiratory pathogens.
METHODS
We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the pre-shedding to post-acute phase of eight SARS-CoV-2-infected participants and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 773 host immune genes.
FINDINGS
Between June 2021 - April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection. With rapid dissemination of home self-collection kits, two and four COVID-19+ participants started collection prior to viral shedding and symptom onset, respectively, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. In pre-shedding samples, we observed transient but robust expression of T-cell response signatures, transcription factor complexes, prostaglandin biosynthesis genes, pyrogenic cytokines, and cytotoxic granule genes. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load. Finally, we observed increased expression of host defense peptides (HDPs) in exposed-uninfected individuals over the 4-week observational window.
INTERPRETATION
We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies. Expression of cytotoxic/T-cell signatures in pre-shedding samples preceding expansion of innate ISGs suggests a potential role for T-cell mediated pathogen control during early infection. Elevated expression of HDPs in exposed-uninfected individuals warrants further validation studies to assess their potential role in protective immunity during pathogen exposure.
FUNDING
This study was funded by R35GM128648 to ABT for in-lab developments of RNA, Packard Fellowship from the David and Lucile Packard Foundation to ABT, and R01AI153087 to AW.
PubMed: 37873251
DOI: 10.1101/2023.10.12.23296835 -
Stem Cell Research & Therapy Jun 2024There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening...
BACKGROUND
There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac).
METHODS
We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks.
RESULTS
The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone.
CONCLUSIONS
The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.
Topics: Humans; Induced Pluripotent Stem Cells; Macrophages; Bioreactors; Organoids; Cell Differentiation; Cell Culture Techniques; Hematopoiesis
PubMed: 38886860
DOI: 10.1186/s13287-024-03785-2 -
International Journal of Molecular... May 2024Macrophages are well known for their involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell...
Macrophages are well known for their involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses, particularly those of human cells. Isolation of tissue-resident macrophages from humans is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes and differentiation to monocyte-derived macrophages may provide a useful tool with which to further study these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the Regulatory Science Framework for Nano(bio)material-based Medical Products and Devices (REFINE) project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination, which may confound potential observations. The SOP was deployed in two partner institutions with broadly similar results. The work presented here shows the utility of this assay but highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some logistical challenges to the application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous non-human cell lines.
Topics: Humans; Macrophages; Cell Differentiation; Monocytes; Biocompatible Materials; Phenotype; Cells, Cultured
PubMed: 38791527
DOI: 10.3390/ijms25105491 -
Scientific Reports Apr 2024The Danube is a significant transboundary river on a global scale, with several tributaries. The effluents from industrial operations and wastewater treatment plants...
The Danube is a significant transboundary river on a global scale, with several tributaries. The effluents from industrial operations and wastewater treatment plants have an impact on the river's aquatic ecosystem. These discharges provide a significant threat to aquatic life by deteriorating the quality of water and sediment. Hence, a total of 16 Polycyclic Aromatic Hydrocarbons (PAHs) compounds were analyzed at six locations along the river, covering a period of 12 months. The objective was to explore the temporal and spatial fluctuations of these chemicals in both water and sediment. The study revealed a significant fluctuation in the concentration of PAHs in water throughout the year, with levels ranging from 224.8 ng/L during the summer to 365.8 ng/L during the winter. Similarly, the concentration of PAHs in sediment samples varied from 316.7 ng/g in dry weight during the summer to 422.9 ng/g in dry weight during the winter. According to the Europe Drinking Water Directive, the levels of PAHs exceeded the permitted limit of 100 ng/L, resulting in a 124.8% rise in summer and a 265.8% increase in winter. The results suggest that the potential human-caused sources of PAHs were mostly derived from pyrolytic and pyrogenic processes, with pyrogenic sources being more dominant. Assessment of sediment quality standards (SQGs) showed that the levels of PAHs in sediments were below the Effect Range Low (ERL), except for acenaphthylene (Acy) and fluorene (Fl) concentrations. This suggests that there could be occasional biological consequences. The cumulative Individual Lifetime Cancer Risk (ILCR) exceeds 1/10 for both adults and children in all sites.
Topics: Child; Humans; China; Ecosystem; Environmental Monitoring; Geologic Sediments; Hungary; Polycyclic Aromatic Hydrocarbons; Risk Assessment; Rivers; Water; Water Pollutants, Chemical; Adult
PubMed: 38594356
DOI: 10.1038/s41598-024-58793-2 -
Regenerative Therapy Dec 2024Endotoxin is a typical pyrogen derived from the outer membrane of Gram-negative bacteria. In fabricating cell-based medicinal products, it is necessary to control...
INTRODUCTION
Endotoxin is a typical pyrogen derived from the outer membrane of Gram-negative bacteria. In fabricating cell-based medicinal products, it is necessary to control endotoxin in the process and the products. In the quality control tests of our clinical study, endotoxin concentration in the culture supernatant of autologous oral mucosal epithelial cell sheets exceeded the criterion value. Therefore, endotoxin measurements were conducted to clarify the cause of the endotoxin contamination.
METHODS
The reagents used to prepare the culture medium, the unused culture medium, and the culture supernatants were diluted with pure water. Endotoxin concentrations in the diluted samples were measured.
RESULTS
Endotoxin was detected in both the unused culture medium and the culture supernatant of the epithelial cell sheets at higher concentrations than the criterion value. Therefore, endotoxin concentrations in the reagents used to prepare the culture medium were measured and were found to be below the criterion value, except for cholera toxin. On the other hand, three lots of cholera toxin products were used for the measurement, and the endotoxin concentrations were higher than the criterion value. The results indicate that the endotoxin contamination is caused by the cholera toxin product.
CONCLUSIONS
To prevent endotoxin contamination in cell-based medicinal products, endotoxin concentrations in reagents used for the fabrication should be measured in the facility conducting clinical research or confirmed by an adequate certificate of analysis from the manufacturers of the reagents.
PubMed: 38596824
DOI: 10.1016/j.reth.2024.03.022