Search NASA⌕ Search

SEARCH · Search NASA

Results for “LIVER”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

High-density binding to Plasmodium falciparum circumsporozoite protein repeats by inhibitory antibody elicited in mouse with human immunoglobulin repertoire

Antibodies targeting the human malaria parasite Plasmodium falciparum circumsporozoite protein (PfCSP) can prevent infection and disease. PfCSP contains multiple central repeating NANP motifs; some of the most potent anti-infective antibodies against malaria bind to these repeats. Multiple antibodies can bind the repeating epitopes concurrently by engaging into homotypic Fab-Fab interactions, which results in the ordering of the otherwise largely disordered central repeat into a spiral. Here, we characterize IGHV3-33/IGKV1-5-encoded monoclonal antibody (mAb) 850 elicited by immunization of transgenic mice with human immunoglobulin loci. mAb 850 binds repeating NANP motifs with picomolar affinity, potently inhibits Plasmodium falciparum (Pf) in vitro and, when passively administered in a mouse challenge model, reduces liver burden to a similar extent as some of the most potent anti-PfCSP mAbs yet described. Like other IGHV3-33/IGKV1-5-encoded anti-NANP antibodies, mAb 850 primarily utilizes its HCDR3 and germline-encoded aromatic residues to recognize its core NANP motif. Biophysical and cryo-electron microscopy analyses reveal that up to 19 copies of Fab 850 can bind the PfCSP repeat simultaneously, and extensive homotypic interactions are observed between densely-packed PfCSP-bound Fabs to indirectly improve affinity to the antigen. Together, our study expands on the molecular understanding of repeat-induced homotypic interactions in the B cell response against PfCSP for potently protective mAbs against Pf infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Early Lab scientists had questions, Plastic Man gave them answers

He was a willing subject in countless scientific experiments, a superstar of health physics, as well as a favorite photo prop -- and not just around Halloween time. He was Plastic Man. Beginning in the mid-1950s, the Lab (then called Los Alamos Scientific Laboratory) often relied on several life-sized synthetic test subjects to avoid experimenting on people. In the early days of the Laboratory, not much was known about how different radioisotopes interacted with the human body and how much it absorbed from different radiation sources. Answering queries like these is where Plastic Man came in. For example, during the 1950s and 1960s, the Lab was tasked with developing nuclear rockets for space exploration under the Rover Program. One of the concerns was how astronauts might be affected when exposed to radiation from these rocket engines. So, the Lab’s health group set up an experiment in which Plastic Man was placed in close proximity to an experimental Rover nuclear rocket engine. Running experiments like this using Plastic Man kept humans safer. How life-like was he? There were actually two variations of Plastic Man. Both had hard plastic exteriors, but one of the models encased a real human skeleton. They also had movable joints and simulated organs, such as a liver, a spleen, kidneys, lungs and a thyroid. Although Plastic Man in its entirety was used in experiments, much of the data collected were from research conducted inside on these replicated organs. In time, technology advanced and Plastic Man was able to retire from the Lab. He found a new home in 1964 as a display at the Laboratory’s science museum, and is sometimes displayed today in the Bradbury Science Museum in downtown Los Alamos.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2022

Computational Engineering of Human Apolipoprotein for Enhanced Interaction with Bacterial Toxins

Sepsis is caused by an over-activation of the immune system in response to the presence of bacterial endotoxins in the bloodstream. LPS exemplifies a potent immune stimulator which can lead to an excessive activation leading to an overly pro-inflammatory reaction and if left untreated results in multi-organ failure and death. Human lipoproteins (HLP) have been shown to neutralize LPS and facilitate its clearance from circulation via the liver. However, host-derived lipoproteins are inhomogeneous in content and size, presenting a challenge for therapeutic applications. In this work, we have used IC facilities in order to computationally engineer HLP for an enhanced interaction with LPS. This work is a continuation of our previous efforts to derive an optimal Nanodisc (ND) lipid mixture for enhanced association with the endotoxin. We have performed fully atomistic Molecular dynamic (MD) simulations in order to carefully identify the most optimal residues in HLP, which can potentially lead to a stronger association to LPS.

42 ENGINEERING↗
DOE OSTI2022

Holiday Cooking: Make something from this historic Los Alamos cookbook and tell us about it!

Third Lab Director Harold Agnew’s barbecue sauce. Applesauce meatballs from the wife of Nobel laureate Frederick Reines. Two different recipes for chopped liver. And dozens more for soups, salads, meats, breads, desserts, drinks – plus a big taste of the past. What’s Cooking was published in Los Alamos in 1955 and recently discovered in a used bookstore in Santa Fe by Lab physicist Roseanne Cheng. “It was buried and on a forgotten shelf,” Cheng said. “I started flipping through it and I couldn’t believe all the (recognizable) names inside.” The wives of Lab staff, including prominent scientists, and Los Alamos community members had submitted recipes to the Los Alamos Chapter of Hadassah, which compiled them and printed the book.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2021

Illuminating gut microbiome signaling pathways that regulate host circadian rhythms

The gut microbiome affects host physiology by modulating nutrient acquisition and creating chemical signals that are received by host receptors. The molecular details of the orchestration of these microbial signaling processes remain largely unclear. We used a function-centric approach to interrogate the mechanistic links between gut microbiome metabolism and host circadian rhythms. We used rodent models, including germ-free mice, to determine how the gut microbiome influences host chronobiology by assaying metabolites in the gut and in circulation, and we used activity-based protein profiling to provide direct functional links to individual taxa. We specifically investigated how externally imposed behavioral schedules, such as feeding schedules, can desynchronize biological rhythms in metabolic organs (e.g., the gut, pancreas, and liver) from the central circadian rhythms regulated by the brain. We hypothesize that the gut microbiome creates chemical signals that can be entrained by feeding/fasting schedule to induce internal metabolic misalignment. Elaborating on the findings of this project will elucidate the chemical signals from the microbiome that modulate biological rhythms in the host’s metabolic organs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Two MCNP Models for Computational Performance Benchmarking

The purpose of this report is to describe two non-trivial MCNP models and execution configurations that are suitable to characterizing computational performance. To that end, this report uses a constructive solid geometry (CSG) representation of the Oak Ridge National Laboratory (ORNL) Pool Critical Assembly (PCA) [1–3] to perform a k-eigenvalue calculation and an unstructured mesh (UM) representation of the International Commission on Radiological Protection (ICRP) publication 145 (ICRP145) male human phantom [4, 5] to perform a fixed-source calculation assuming that a 1 MeV photon source is distributed throughout the phantom’s liver.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling

Background:: The fibroblast growth factor (FGF) family is comprised of 23 highly regulatedmonomeric proteins that regulate a plethora of developmental and pathophysiological processes,including tissue repair, wound healing, angiogenesis, and embryonic development. Binding ofFGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan,heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediateinduction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, andSTAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification,FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions.Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis,and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiologicalchanges. Objective:: This comprehensive review will discuss the biology, chemistry, and functions of FGFs,and its current applications toward wound healing, diabetes, repair and regeneration of tissues, andfatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFRand aid in mitigating various disorders, such as cancer, are also discussed in detail. Conclusion:: Inhibitors of FGFR signaling are promising drugs in the treatment of several types ofcancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activationof other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activityon FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFRtargeting therapies is the recent focus of several preclinical and clinical studies.

Pharmacology & Pharmacy↗
DOE OSTI2023

Evaluation of Candidate Theranostics for 227 Th/ 89 Zr Paired Radioimmunotherapy of Lymphoma

227 Th is a promising radioisotope for targeted α-particle therapy. It produces 5 α-particles through its decay, with the clinically approved 223 Ra as its first daughter. There is an ample supply of 227 Th, allowing for clinical use; however, the chemical challenges of chelating this large tetravalent f-block cation are considerable. Using the CD20-targeting antibody ofatumumab, we evaluated chelation of 227 Th 4+ for α-particle–emitting and radiotheranostic applications. Methods: We compared 4 bifunctional chelators for thorium radiopharmaceutical preparation: S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 2-(4-isothicyanatobenzyl)-1,2,7,10,13-hexaazacyclooctadecane-1,4,7,10,13,16-hexaacetic acid (p-SCN-Bn-HEHA), p-isothiacyanatophenyl-1-hydroxy-2-oxopiperidine-desferrioxamine (DFOcyclo*-p-Phe-NCS), and macrocyclic 1,2-HOPO N-hydroxysuccinimide (L804-NHS). Immunoconstructs were evaluated for yield, purity, and stability in vitro and in vivo. Tumor targeting of the lead 227 Th-labeled compound in vivo was performed in CD20-expressing models and compared with a companion 89 Zr-labeled PET agent. Results: 227 Th-labeled ofatumumab-chelator constructs were synthesized to a radiochemical purity of more than 95%, excepting HEHA. 227 Th-HEHA-ofatumumab showed moderate in vitro stability. 227 Th-DFOcyclo*-ofatumumab presented excellent 227 Th labeling efficiency; however, high liver and spleen uptake was revealed in vivo, indicative of aggregation. 227 Th-DOTA-ofatumumab labeled poorly, yielding no more than 5%, with low specific activity (0.08 GBq/g) and modest long-term in vitro stability (<80%). 227 Th-L804-ofatumumab coordinated 227 Th rapidly and efficiently at high yields, purity, and specific activity (8 GBq/g) and demonstrated extended stability. In vivo tumor targeting confirmed the utility of this chelator, and the diagnostic analog, 89 Zr-L804-ofatumumab, showed organ distribution matching that of 227 Th to delineate SU-DHL-6 tumors. Conclusion: Commercially available and novel chelators for 227 Th showed a range of performances. The L804 chelator can be used with potent radiotheranostic capabilities for 89 Zr/ 227 Th quantitative imaging and α-particle therapy.

227Th↗
DOE OSTI2023

Evaluation of 134 Ce/ 134 La as a PET Imaging Theranostic Pair for 225 Ac α-Radiotherapeutics

225 Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator 134 Ce/ 134 La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides 225 Ac and 227 Th. In this report, we detail efficient radiolabeling methods using the 225 Ac-chelators DOTA and MACROPA. These methods were applied to radiolabeling of prostate cancer imaging agents, including PSMA-617 and MACROPA-PEG 4 -YS5, for evaluation of their in vivo pharmacokinetic characteristics and comparison to the corresponding 225 Ac analogs. Methods: Radiolabeling was performed by mixing DOTA/MACROPA chelates with 134 Ce/ 134 La in NH 4 OAc, pH 8.0, at room temperature, and radiochemical yields were monitored by radio–thin-layer chromatography. In vivo biodistributions of 134 Ce-DOTA/MACROPA.NH 2 complexes were assayed through dynamic small-animal PET/CT imaging and ex vivo biodistribution studies over 1 h in healthy C57BL/6 mice, compared with free 134 CeCl 3 . In vivo, preclinical imaging of 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5 was performed on 22Rv1 tumor–bearing male nu/nu-mice. Ex vivo biodistribution was performed for 134 Ce/ 225 Ac-MACROPA-PEG 4 -YS5 conjugates. Results: 134 Ce-MACROPA.NH 2 demonstrated near-quantitative labeling with 1:1 ligand-to-metal ratios at room temperature, whereas a 10:1 ligand-to-metal ratio and elevated temperatures were required for DOTA. Rapid urinary excretion and low liver and bone uptake were seen for 134 Ce/ 225 Ac-DOTA/MACROPA. NH 2 conjugates in comparison to free 134 CeCl 3 confirmed high in vivo stability. An interesting observation during the radiolabeling of tumor-targeting vectors PSMA-617 and MACROPA-PEG 4 -YS5—that the daughter 134 La was expelled from the chelate after the decay of parent 134 Ce—was confirmed through radio–thin-layer chromatography and reverse-phase high-performance liquid chromatography. Both conjugates, 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5, displayed tumor uptake in 22Rv1 tumor–bearing mice. The ex vivo biodistribution of 134 Ce-MACROPA.NH 2 , 134 Ce-DOTA and 134 Ce-MACROPA-PEG 4 -YS5 corroborated well with the respective 225 Ac-conjugates. Conclusion: These results demonstrate the PET imaging potential for 134 Ce/ 134 La-labeled small-molecule and antibody agents. The similar 225 Ac and 134 Ce/ 134 La-chemical and pharmacokinetic characteristics suggest that the 134 Ce/ 134 La pair may act as a PET imaging surrogate for 225 Ac-based radioligand therapies.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2022

Acid external and internal environment exchange the Oreochromis niloticus tissue immune gene expression compared to the mouse macrophage polarization model

The water environment plays an important role in animal physiology. In this study, we sought to evaluate the effect of the acid environment on the Oreochromis niloticus (Nile tilapia) internal microenvironment immune response compare to the mouse macrophage model (J77A.1). The acid environment treated mouse macrophage J774A.1 model have shown that acidic treatment is able to polarize macrophages into M2-like macrophages via an increase in Ym1, Tgm2, Arg1, Fizz1, and IL-10 expression. Metabolic analysis of mouse macrophages (J774A.1) at pH 2 vs. pH 7 and pH 4 vs. pH 7 have been shown to promote the expression of intracellular acetylcholine, choline, prochlorperazine, L-leucine, and bisphenol A,2-amino-3-methylimidazo[4,5-f] quinolone metabolites in the M2-like macrophage. Immune gene expression of the O. niloticus spleen and liver treated at pH 2, 4, and 7 was shown to reduce TNF-α, IL-1 β, IL-8, and IL-12 expression compared to pH 7 treatment. Immune gene was induced in O. niloticus following culture at pH 5, 6, and 7 fresh water environment. Taken together, we found that the acid internal environment polarizes tissues into an M2 macrophage developmental microenvironment. However, if the external environment is acid, tissues are exposed to an M1 macrophage developmental microenvironment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A novel candidate hepatitis C virus genotype 4 subtype identified by next generation sequencing full-genome characterization in a patient from Saudi Arabia

Background and aim: Hepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C. Methods: We analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing. Results: Our phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV. Conclusion: This discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Beyond microbial abundance: metadata integration enhances disease prediction in human microbiome studies

Multiple studies have highlighted the interaction of the human microbiome with physiological systems such as the gut, immune, liver, and skin, via key axes. Advances in sequencing technologies and high-performance computing have enabled the analysis of large-scale metagenomic data, facilitating the use of machine learning to predict disease likelihood from microbiome profiles. However, challenges such as compositionality, high dimensionality, sparsity, and limited sample sizes have hindered the development of actionable models. One strategy to improve these models is by incorporating key metadata from both the human host and sample collection/processing protocols. This remains challenging due to sparsity and inconsistency in metadata annotation and availability. In this paper, we introduce a machine learning-based pipeline for predicting human disease states by integrating host and protocol metadata with microbiome abundance profiles from 68 different studies, processed through a consistent pipeline. Our findings indicate that metadata can enhance machine learning predictions, particularly at higher taxonomic ranks like Kingdom and Phylum, though this effect diminishes at lower ranks. Our study leverages a large collection of microbiome datasets comprising 11,208 samples, therefore enhancing the robustness and statistical confidence of our findings. This work is a critical step toward utilizing microbiome and metadata for predicting diseases such as gastrointestinal infections, diabetes, cancer, and neurological disorders.

Mathematics and Computing↗
DOE OSTI2022

The Supplementation of FloraMax-B11 Did Not Affect the Bile Acid Neosynthesis and the Enterohepatic Circulation in Broiler Chickens

Most probiotics possess bile salt hydrolase enzymes and may increase bile acid excretion and negatively affect fat digestion and absorption. Therefore, the study objective was to determine the time course effects of a commercial probiotic (P) FloraMax-B11 (FM) supplementation on bile acid neosynthesis and enterohepatic circulation in broiler chickens. Fertile Ross 708 eggs were incubated under standard commercial conditions. At hatch, chicks (n = 550) were randomly assigned to 5 treatment groups (n = 5 replicates per treatment group) with 22 birds per pen. The 5 treatment groups consisted of: control group (C, normal water from hatch to 35 days of age without supplements); P3, water supplemented with FM for the first 3 days post-hatch followed by normal water until day 35; P10, water supplemented with FM for the first 10 days post-hatch followed by normal water until day 35; P35, water supplemented with FM from hatch to day 35; and AGP, water supplemented with antibiotic growth promoter (AGP) from hatch until day 35. Ileum, liver, and plasma were collected at hatch, days 3, 10, 21, and 35 post-hatch. The relative mRNA expression of genes involved in bile acid synthesis (CYP7A1, CYP8B1, FXR, FGFR4, and FGF19) and transport (ASBT, I-BABP, OSTα, OSTβ, and BSEP) as well as ileal deoxycholic acid and plasma cholic acid were determined. There was no FM and AGP interaction for any of the response criteria. No FM or AGP effects were observed (p > 0.05) for any genes, except FGF19, which expression was increased (p < 0.0001) in AGP compared to P35. No FM or AGP effects were observed (p > 0.05) for levels of deoxycholic and cholic acids. However, all the genes, deoxycholic acid, and plasma cholic acid were affected by age (p < 0.0001). In general, the data indicate that FM did not negatively impact bile acid metabolism and enterohepatic circulation, which appeared to be age dependent. However, more research should be conducted to confirm these results and investigate the effects of FM on bile acid metabolism, fat digestion, and intestinal microbiota in broiler chickens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Dietary Strategies to Modulate the Health Condition and Immune Responses in Gilthead Seabream (Sparus aurata) Juveniles Following Intestinal Inflammation

Several feed additives have proved to be beneficial in eliciting fish health. Β-glucans and curcumin are compounds with immunomodulatory capacities known to increase growth performance, stimulate immunity, improve general health, and enhance disease resistance in fish. The present study aimed to evaluate the effects of dietary Phaeodactylum tricornutum extracts rich in β-glucans and curcumin on gilthead seabream health status prior to and following an intestinal inflammatory stimulus. Three experimental diets were formulated: a practical commercial-type diet (CTRL), a CTRL diet supplemented with 1% microalgae-derived β-glucans extract (BG), and a CTRL diet supplemented with 0.2% of curcumin (CUR). After 30 days of the feeding trial, fish were sampled and subjected to an oral administration of 1% dextran sodium sulphate (DSS) to induce intestinal inflammation. Four groups were considered: a group of fish continued to be fed on the CTRL diet while the remaining groups were exposed to DSS, including CTRL-D (CTRL + DSS), BG-D (BG + DSS), and CUR-D (CUR + DSS), for 6 days. Growth, plasma and gut humoral immunity, liver and gut oxidative stress biomarkers, and intestinal gene expression were evaluated. No significant differences were found in growth after 30 days of feeding; however, seabream fed BG had decreased anti-protease activity and nitric oxide concentration in plasma while those fed CUR had increased mRNA levels of the tnfα, csf1r, and hep genes compared to those fed CTRL. After the inflammatory stimulus, hematocrit was enhanced in fish fed BG-D and CUR-D while red blood cell counts increased in those fed CTRL-D. Superoxide dismutase activity decreased in the intestine of all DSS groups while lipid peroxidation increased in the gut of fish fed CTRL-D and BG-D compared to CTRL. Moreover, the mRNA expression levels of csfr1 and sod decreased in fish fed CTRL-D and BG-D compared to CTRL, respectively. Despite the mild intestinal inflammatory condition induced by DSS, CUR was able to partially ameliorate its effects, improving the hematological profile and assisting against the oxidative stress.

Teixeira, Carla↗
DOE OSTI2020

Supplemental Microalgal DHA and Astaxanthin Affect Astaxanthin Metabolism and Redox Status of Juvenile Rainbow Trout

Microalgal docosahexaenoic acid (DHA) and astaxanthin (AST) may substitute for fish oil and synthetic AST in aquafeeds. This study explored the effects and mechanisms of those substitutions on AST metabolism and redox status of rainbow trout fed plant protein meal (PM)- or fishmeal (FM)-based diets. Two parallel experiments (PM vs. FM) were performed with 612 juvenile rainbow trout for 16 weeks as a 2 × 3 factorial arrangement of treatments with two AST sources (synthetic (SA) vs. microalgal (AA), at 80 mg/kg) and three levels (0, 50, and 100%) of fish oil substitutions with DHA-rich microalgae. The fish oil substitutions exhibit main effects (p < 0.05) and/or interactive effects (p < 0.05) with the source of AST on AST deposition, malondialdehyde and glutathione concentrations, and mRNA levels and activities of major redox enzymes (glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD)) in the muscle and liver of trout fed both diet series. The AST source produced only differences in tissue AST deposition (p < 0.05) and number of metabolites. In conclusion, the substitutions of fish oil by the DHA-rich microalgae exerted more impacts than those of SA by AA on redox status and functional expression of antioxidant enzymes in the tissues of rainbow trout.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Early Immune Modulation in European Seabass (Dicentrarchus labrax) Juveniles in Response to Betanodavirus Infection

The early host–pathogen interaction between European seabass (Dicentrarchus labrax) and Betanodavirus was examined by using juvenile fish infected intramuscularly with RGNNV (red-spotted grouper nervous necrosis virus). The time course selected for sampling (0–144 h post-infection (hpi)) covered the early stages of infection, with hematological, antioxidant and immunological responses examined. Early activation of the host’s immune system was seen in the first few hours post-infection (6 to 9 hpi), as evidenced by an increase in tnfα, cd28 and c3 expression in the head kidney of infected fish. Most hematological parameters that were examined showed significant differences between sampling times, including differences in the number of thrombocytes and various leukocyte populations. The plasma lysozyme concentration decreased significantly over the course of the trial, and most antioxidant parameters examined in the liver showed significant differences over the infection period. At 144 hpi, peak expression of tnfα and il-1β coincided with the appearance of disease symptoms, peak levels of virus in the brain and high levels of fish mortality. The results of the study show the importance of analyzing the early interactions between European seabass and Betanodavirus to establish early indicators of infection to prevent more severe outcomes of the infection from occurring.

Vaz, Mariana↗
DOE OSTI2020

Supplemental Microalgal Iron Helps Replete Blood Hemoglobin in Moderately Anemic Mice Fed a Rice-Based Diet

Iron deficiency anemia affects 1.2 billion people globally. Our objectives were to determine if (1) supplemental iron extracted from defatted microalgae (Nannochloropsis oceanica, DGM) and (2) a combination of minute amount of plant phytase and inulin could help replete hemoglobin in anemic mice. Mice (7 weeks old) were fed a control diet (6 mg Fe/kg). After 10 weeks, the mice were assigned to three treatments: control, control + DGM iron (Fe-DGM, 39 mg Fe/kg), or control + 1% inulin + 250 units of phytase/kg (INU–PHY, 6 mg Fe/kg). The mice had free access to diets and water for 6 weeks. The Fe-DGM group had elevated blood hemoglobin (p < 0.01) and a two-fold greater (p < 0.0001) liver non-heme iron over the control. Strikingly, the INU-PHY group had 34% greater non-heme iron than the control, despite the same concentrations of iron in their diets. Fe-DGM group had altered (p < 0.05) mRNA levels of hepcidin, divalent metal transporter 1, transferrin and transferrin receptor 1. Iron extracted from defatted microalgae seemed to be effective in alleviating moderate anemia, and INU-PHY enhanced utilization of intrinsic iron present in the rice diet. Our findings may lead to a novel formulation of these ingredients to develop safer and bioavailable iron supplements for iron-deficient populations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Enantioselectivity of Pentedrone and Methylone on Metabolic Profiling in 2D and 3D Human Hepatocyte-like Cells

Pentedrone and methylone can express stereoselectivity in toxicokinetic and toxicodynamic processes. Similarly, their chiral discrimination in metabolism, which was not yet evaluated, can result in different metabolic profiles and subsequent hepatotoxic effects. Therefore, the aim of this work was to assess, for the first time, both the hepatic cytotoxic and metabolic profile of pentedrone and methylone enantiomers using physiologically relevant in vitro models. The hepatotoxicity of these compounds was observed in a concentration-dependent manner in human stem-cell-derived hepatocyte-like cells (HLCs) cultured under 3D (3D-HLCs) and 2D (2D-HLCs) conditions. Enantioselectivity, on the other hand, was only shown for pentedrone (1 mM) in 3D-HLCs, being R-(−)-pentedrone the most cytotoxic. Furthermore, the metabolic profile was initially evaluated in human liver microsomes (HLM) and further demonstrated in 3D-HLCs and 2D-HLCs applying a gas chromatography coupled to a mass spectrometer (GC–MS) technique. Methylone and pentedrone showed distinct and preferential metabolic routes for their enantiomers, resulting in the production of differentiated metabolites; R-(+)-methylone and R-(−)-pentedrone are the most metabolized enantiomers. In conclusion, the results demonstrated enantioselectivity for pentedrone and methylone in the metabolic processes, with enantioselectivity in cytotoxicity for pentedrone.

Silva, Bárbara (ORCID:0000000173990197)↗