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Ecological Applications : a Publication... Jun 2023Many invasive and some native tree species in North America exhibit strong allelopathic effects that may contribute to their local dominance. Pyrogenic carbon (PyC;...
Many invasive and some native tree species in North America exhibit strong allelopathic effects that may contribute to their local dominance. Pyrogenic carbon (PyC; including soot, charcoal, and black carbon) is produced by the incomplete combustion of organic matter and is widespread in forest soils. Many forms of PyC have sorptive properties that can reduce the bioavailability of allelochemicals. We investigated the potential for PyC produced by controlled pyrolysis of biomass ("biochar" [BC]) to reduce the allelopathic effects of black walnut (Juglans nigra) and Norway maple (Acer platanoides), a common native tree species and a widespread invasive species in North America, respectively. Seedling growth of two native tree species (Acer saccharinum [silver maple] and Betula papyrifera [paper birch]) in response to leaf-litter-incubated soils was examined; litter incubation treatments included leaves of black walnut, Norway maple, and a nonallelopathic species (Tilia americana [American basswood]) in a factorial design with varying dosages; responses to the known primary allelochemical of black walnut (juglone) were also examined. Juglone and leaf litter of both allelopathic species strongly suppressed seedling growth. BC treatments substantially mitigated these effects, consistent with the sorption of allelochemicals; in contrast no positive effects of BC were observed in leaf litter treatments involving controls or additions of nonallelopathic leaf litter. Treatments of leaf litter and juglone with BC increased the total biomass of silver maple by ~35% and in some cases more than doubled the biomass of paper birch. We conclude that BCs have the capacity to largely counteract allelopathic effects in temperate forest systems, suggesting the effects of natural PyC in determining forest community structure, and also the applied use of BC as a soil amendment to mitigate allelopathic effects of invasive tree species.
Topics: Trees; Charcoal; Silver; Soil; Seedlings; Plant Leaves
PubMed: 36864680
DOI: 10.1002/eap.2832 -
ALTEX 2021The use of in vitro assays to inform decision-making requires robust and reproducible results across studies, laboratories, and time. Experiments using positive control...
The use of in vitro assays to inform decision-making requires robust and reproducible results across studies, laboratories, and time. Experiments using positive control materials are an integral component of an assay procedure to demonstrate the extent to which the measurement system is performing as expected. This paper reviews ten characteristics that should be considered when selecting a positive control material for an in vitro assay: 1) the biological mechanism of action, 2) ease of preparation, 3) chemical purity, 4) verifiable physical properties, 5) stability, 6) ability to generate responses spanning the dynamic range of the assay, 7) technical or biological interference, 8) commercial availability, 9) user toxicity, and 10) disposability. Examples and a case study of the monocyte activation test are provided to demonstrate the application of these characteristics for identification and selection of potential positive control materials. Because specific positive control materials are often written into testing standards for in vitro assays, selection of the positive control material based on these characteristics can aid in ensuring the long-term relevance and usability of these standards.
Topics: Biological Assay; Laboratories; Research Design
PubMed: 33637998
DOI: 10.14573/altex.2102111 -
European Journal of Medicinal Chemistry May 2023Diabetes mellitus (DM) and its complications have become an important global public health issue, affecting human health and negatively impacting life and lifespan.... (Review)
Review
Diabetes mellitus (DM) and its complications have become an important global public health issue, affecting human health and negatively impacting life and lifespan. Pyroptosis is a recently discovered form of pro-inflammatory programmed cell death (PCD). To date, pyroptosis-associated inflammasome pathways have been identified primarily in the canonical and non-canonical inflammasome pathway, apoptotic caspase-mediated pathway, granzyme-mediated pathway, and streptococcal pyrogenic exotoxin B (SpeB)-mediated pathway. The activation of diabetes-mediated pyroptosis-associated factors play an important role in the pathophysiology of DM and its complications. Studies have shown that ginsenosides exert significant protective effects on DM and its complications. Through inhibiting the activation of pyroptosis-associated inflammasome pathways, and then the DM and its complications are improved. This review summarizes the subtypes of ginsenosides and their chemical characteristics, pharmacokinetics and side effects, the main pyroptosis-associated inflammasome pathways that have been discovered to date, and the potential mechanism of different subtypes of ginsenosides in the treatment of DM and its complications (such as diabetic cardiomyopathy, diabetic nephropathy, diabetic liver injury, diabetic retinopathy, and diabetic ischemic stroke) via anti-pyroptosis-associated inflammasome pathways. These findings may provide ideas for further research to explore ginsenoside mechanism in improving DM and its complications. However, many pyroptosis-associated inflammasome pathways and targets involved in the occurrence and development of DM and its complications are still unknown. In the future, further studies using in vitro cell models, in vivo animal models, and human disease models can be used to further elucidate the mechanism of ginsenosides in the treatment of DM and its complications.
Topics: Animals; Humans; Inflammasomes; Ginsenosides; Pyroptosis; Apoptosis; Diabetic Nephropathies; Diabetes Mellitus
PubMed: 37031528
DOI: 10.1016/j.ejmech.2023.115336 -
The Science of the Total Environment Dec 2022Prevailing global increases in population, urbanization, and agricultural production are causing increased pressures on water resources, especially as the use of... (Review)
Review
Prevailing global increases in population, urbanization, and agricultural production are causing increased pressures on water resources, especially as the use of chemicals in agriculture, industry, and medicine provide new challenges for water treatment and reuse. Organohalogen compounds are persistent contaminants that often evade current wastewater treatment technologies, resulting in their accumulation in the environment and posing a serious threat to ecosystem health. Recent advances in understanding pyrogenic carbons as electron shuttling and storing materials have exposed their potential for enhancing the dehalogenation and overall degradation of organohalide contaminants in soil, sediment, surface water, and wastewater systems. Biochar is a porous carbonaceous material produced during the thermochemical decomposition of biomass feedstock in the presence of little or no oxygen (pyrolysis). Interest in biochar for application towards environmental remediation is largely based on its three distinct benefits: I) carbon sequestration to offset greenhouse gas emissions, II) adsorption of (in-) organic contaminants and nutrients, and III) a strong electron exchange capacity. Due to the innate complexity of biochar materials, several electron transfer mechanisms exist by which biochar may mediate contaminant degradation. These electron transfer pathways include electron-accepting and donating cycles through redox-active functional groups and direct electron transfer via conductive carbon matrices. These mechanisms are responsible for biochar's participation in multiple redox-driven biogeochemical transformations with proven consequences for effective organohalogen remediation. This literature review summarizes the current knowledge on the mechanisms and processes through which biochar can directly or indirectly mediate the transformation of organohalogen compounds under various environmental conditions. Perspectives and research directions for future application of biochars for targeted remediation strategies are also discussed.
Topics: Ecosystem; Wastewater; Greenhouse Gases; Charcoal; Soil; Adsorption; Carbon
PubMed: 36055499
DOI: 10.1016/j.scitotenv.2022.158381 -
The Science of the Total Environment Sep 2019Endotoxins, also referred to as lipopolysaccharides or pyrogens, are major components embedded in the outer cell wall membrane of most Gram-negative bacteria and some... (Review)
Review
Endotoxins, also referred to as lipopolysaccharides or pyrogens, are major components embedded in the outer cell wall membrane of most Gram-negative bacteria and some cyanobacteria. As common pyrogens and strong immune stimulators, health hazards associated with endotoxins in water and wastewater have been attracting attention in recent years. In this paper, the characteristics, existing forms, and detection assays of endotoxins in water and wastewater are reviewed. Cellular response and pathophysiological effects, and main exposure tracts of endotoxins in water and wastewater are discussed. Levels of endotoxin contamination in water, wastewater, and their aerosols are presented. The removal effects of different water and wastewater treatment processes are summarized. Hence, it is important to: (i) Improve investigations into endotoxin contamination in water and wastewater in order to identify their source, occurrence, and fate. (ii) Implement water and wastewater treatment processes capable of ensuring low levels of endotoxins. This review aims to identify efficient water and wastewater treatment processes capable of ensuring the production of WTPs and WWTPs effluents with a low level of endotoxin activity, and to guarantee the reduction of endotoxin exposure risks to the consumers of water and wastewater.
Topics: Endotoxins; Environmental Monitoring; Wastewater; Water; Water Pollutants, Chemical
PubMed: 31108357
DOI: 10.1016/j.scitotenv.2019.05.036 -
Nature Aug 2022
PubMed: 35896754
DOI: 10.1038/s41586-022-05109-x -
Scientific Reports Aug 2023Intrinsic or added immune activating molecules are key for most vaccines to provide desired immunity profiles but may increase systemic reactogenicity. Regulatory...
Intrinsic or added immune activating molecules are key for most vaccines to provide desired immunity profiles but may increase systemic reactogenicity. Regulatory agencies require rabbit pyrogen testing (RPT) for demonstration of vaccine reactogenicity. Recently, the monocyte activation test (MAT) gained popularity as in vitro alternative, yet this assay was primarily designed to test pyrogen-free products. The aim was to adjust the MAT to enable testing of pyrogen containing vaccines in an early stage of development where no reference batch is yet available. The MAT and RPT were compared for assessing unknown safety profiles of pertussis outer membrane vesicle (OMV) vaccine candidates to those of Bexsero as surrogate reference vaccine. Pertussis OMVs with wild-type LPS predominantly activated TLR2 and TLR4 and were more reactogenic than Bexsero. However, this reactogenicity profile for pertussis OMVs could be equalized or drastically reduced compared to Bexsero or a whole-cell pertussis vaccine, respectively by dose changing, modifying the LPS, intranasal administration, or a combination of these. Importantly, except for LPS modified products, reactogenicity profiles obtained with the RPT and MAT were comparable. Overall, we demonstrated that this pertussis OMV vaccine candidate has an acceptable safety profile. Furthermore, the MAT proved its applicability to assess reactogenicity levels of pyrogen containing vaccines at multiple stages of vaccine development and could eventually replace rabbit pyrogen testing.
Topics: Animals; Rabbits; Lipopolysaccharides; Whooping Cough; Pyrogens; Monocytes; Biological Assay
PubMed: 37542099
DOI: 10.1038/s41598-023-39908-7 -
Frontiers in Immunology 2023Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for...
Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of pro-inflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer.
Topics: Animals; Dogs; Humans; Mice; Adjuvants, Immunologic; Cytokines; Lipopolysaccharides; Liposomes; Toll-Like Receptor 4
PubMed: 37223101
DOI: 10.3389/fimmu.2023.1066402 -
Signal Transduction and Targeted Therapy Feb 2024Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines...
Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted 'reduction, replacement and refinement' principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.
Topics: Animals; Chlorocebus aethiops; Rabbits; Humans; Pyrogens; NF-kappa B; Vero Cells; Reproducibility of Results; Cell Line
PubMed: 38369543
DOI: 10.1038/s41392-024-01744-0 -
ALTEX 2021The whole blood pyrogen test invented 25 years ago, and its variant based on cryo-preserved blood one year later, brought momentum into the field of pyrogen testing,...
The whole blood pyrogen test invented 25 years ago, and its variant based on cryo-preserved blood one year later, brought momentum into the field of pyrogen testing, which, despite the broad application of the Limulus amebocyte lysate (LAL) assay, aka bacterial endotoxin test (BET), consumed several hundred thousand rabbits per year world-wide. The resulting international validation and lengthy acceptance and implementation process of what are called now monocyte activation tests (MATs) finally is impacting on animal numbers - at least in Europe - reducing them by more than 70% and counting. The author sees no reason for continuing any regulatory rabbit testing for pyrogens except the lack of acceptance of MATs in some regions of the world. The availability of MATs has opened also the discussion about the shortcomings of LAL/BET, namely its restriction to Gram-negative pyrogens, non-reflection of the potency of these in humans, interference and masking by many products, and animal welfare concerns for horseshoe crabs. The obvious advantages of MATs in all these respects should lead to a shift from LAL/BET to MATs. We are starting to see this for vac-cines and medical devices, but other areas like safety testing of blood transfusions, cell therapies and nanomaterials, and the assessment of air-borne pyrogens still need to grasp the opportunity provided by MATs. While the different MATs can jointly serve these needs, the whole blood MAT has some advantages as discussed here.
Topics: Animal Testing Alternatives; Animals; Biological Assay; Cryopreservation; Endotoxins; Horseshoe Crabs; Monocytes; Pyrogens; Rabbits
PubMed: 33452528
DOI: 10.14573/altex.2101051