PubMed

Fitoterapia. 2024 May 25:106036. doi: 10.1016/j.fitote.2024.106036. Online ahead of print.ABSTRACTThe variety of bioactive compounds found in different species of Amaranthus, an herb that is a staple food in many parts of India. The plethora of herb Amaranthus has been a rich source of bioactive compounds like essential oils, sesquiterpenes, diterpenes, triterpenes, phenolic acids, flavonoids, etc. The traditional uses of Amaranthus, spp. have been established scientifically and were shown due to the presence of different phytochemicals. Although the pharmacological activities of Amaranthus genus have been well-documented, further studies are needed to fully understand their mechanisms of action and clinical applications. In conclusion, the phytochemistry and pharmacological activity of genus Amaranthus make it a promising source of natural products for drug discovery and development. The present is review mainly concise to the ethnopharmacological relevance and pharmacological studies of Amaranthus species. This conclusive review work may on Amaranthus species provided the interconnection of bioactive molecules with its ethno pharmacological utility of plant species.PMID:38801891 | DOI:10.1016/j.fitote.2024.106036

Environ Pollut. 2024 May 25:124231. doi: 10.1016/j.envpol.2024.124231. Online ahead of print.ABSTRACTNanocolloids (Nc) are widespread in natural water environment, whereas the potential effects of Nc on dissemination of antibiotic resistance remain largely unknown. In this study, Nc collected from the Yellow River in Henan province was tested for its ability to influence the conjugative transfer of resistant plasmid in aqueous environment. The results revealed that the conjugative transfer of RP4 plasmid between Escherichia coli was down-regulated by 52%-91% upon exposure to 1-10 mg/L Nc and the reduction became constant when the dose became higher (20-200 mg/L). Despite the exposure of Nc activated the anti-oxidation and SOS response in bacteria through up-regulating genes involved in glutathione biosynthesis and DNA recombination, the inhibition on the synthesis and secretion of extracellular polysaccharide induced the prevention of cell-cell contact, leading to the reduction of plasmid transfer. This was evidenced by the decreased bacterial adhesion and lowered levels of genes and metabolites relevant to transmembrane transport and D-glucose phosphorylation, as clarified in phenotypic, transcriptomics and metabolomics analysis of E. coli. The significant down-regulation of glycolysis/gluconeogenesis and TCA cycle was associated with the shortage of ATP induced by Nc. The up-regulation of global regulatory genes (korA and trbA) and the reduction of plasmid genes (trfAp, trbBp, and traG) expression also contributed to the suppressed conjugation of RP4 plasmid. The obtained findings remind that the role of ubiquitous colloidal particles is nonnegligible when practically and comprehensively assessing the risk of antibiotic resistance in the environment.PMID:38801878 | DOI:10.1016/j.envpol.2024.124231

Int J Biol Macromol. 2024 May 25:132667. doi: 10.1016/j.ijbiomac.2024.132667. Online ahead of print.ABSTRACTFibroblast growth factor 21 (FGF21) is one endogenous metabolic molecule that functions as a regulator in glucose and lipid homeostasis. However, the effect of FGF21 on L-lactate homeostasis and its mechanism remains unclear until now. Forty-five Six-week-old male C57BL/6 mice were divided into three groups: control, L-lactate, and FGF21 (1.5 mg/kg) groups. At the end of the treatment, nuclear magnetic resonance-based metabolomics, and key proteins related to L-lactate homeostasis were determined respectively to evaluate the efficacy of FGF21 and its mechanisms. The results showed that, compared to the vehicle group, the L-lactate-treated mice displayed learning and memory performance impairments, as well as reduced hippocampal ATP and NADH levels, but increased oxidative stress, mitochondrial dysfunction, and apoptosis, which suggesting inhibited L-lactate-pyruvate conversion in the brain. Conversely, FGF21 treatment ameliorated the L-lactate accumulation state, accompanied by restoration of the learning and memory defects, indicating enhanced L-lactate uptake and utilization in hippocampal neurons. We demonstrated that maintaining constant L-lactate-pyruvate flux is essential for preserving neuronal bioenergetic and redox levels. FGF21 contributed to preparing the brain for situations of high availability of L-lactate, thus preventing neuronal vulnerability in metabolic reprogramming.PMID:38801850 | DOI:10.1016/j.ijbiomac.2024.132667

Int J Biol Macromol. 2024 May 25:132683. doi: 10.1016/j.ijbiomac.2024.132683. Online ahead of print.ABSTRACTGRAM (Glucosyltransferases-like GTPase activators and Myotubularin) domain-encoding proteins play pivotal roles in plant growth and responses to biotic stresses. Yet, their influence on abiotic stress responses has remained enigmatic. This study unveils a novel nucleus-localized OsGRAM57, a GRAM protein-encoding gene and its profound regulatory functions in enhancing salt stress tolerance using Arabidopsis thaliana as a model plant. OsGRAM57-OEX (OsGRAM57-OEX) lines displayed significant enhancement in salt tolerance, modulated physiological, biochemical, K+/Na+ ratios, and enzymatic indices as compared to their wild-type (WT). Furthermore, OsGRAM57-OEX seedlings demonstrate increased levels of endogenous abscisic acid (ABA) and other phytohormones, while metabolic profiling revealed enhanced carbohydrate metabolism. Delving into the ABA signaling pathway, OsGRAM57 emerged as a central regulator, orchestrating the expression of genes crucial for salt stress responses, carbohydrate metabolism, and ABA signaling. The observed interactions with target genes and transactivation assays provided additional support for OsGRAM57's pivotal role. These findings underscore OsGRAM57's positive influence on the ABA pathway and affirm its capacity to enhance salt tolerance through an ABA-dependent pathway and fine-tuned carbohydrate metabolism. In summary, this new study reveals the previously undiscovered regulatory roles of OsGRAM57 in Arabidopsis abiotic stress responses, offering promising ways for strengthening plant resilience in the face of adverse environmental conditions.PMID:38801846 | DOI:10.1016/j.ijbiomac.2024.132683

Environ Int. 2024 May 22;188:108766. doi: 10.1016/j.envint.2024.108766. Online ahead of print.ABSTRACTEarly-life exposure to natural and synthetic chemicals can impact acute and chronic health conditions. Here, a suspect screening workflow anchored on high-resolution mass spectrometry was applied to elucidate xenobiotics in breast milk and matching stool samples collected from Nigerian mother-infant pairs (n = 11) at three time points. Potential correlations between xenobiotic exposure and the developing gut microbiome, as determined by 16S rRNA gene amplicon sequencing, were subsequently explored. Overall, 12,192 and 16,461 features were acquired in the breast milk and stool samples, respectively. Following quality control and suspect screening, 562 and 864 features remained, respectively, with 149 of these features present in both matrices. Taking advantage of 242 authentic reference standards measured for confirmatory purposes of food bio-actives and toxicants, 34 features in breast milk and 68 features in stool were identified and semi-quantified. Moreover, 51 and 78 features were annotated with spectral library matching, as well as 416 and 652 by in silico fragmentation tools in breast milk and stool, respectively. The analytical workflow proved its versatility to simultaneously determine a diverse panel of chemical classes including mycotoxins, endocrine-disrupting chemicals (EDCs), antibiotics, plasticizers, perfluorinated alkylated substances (PFAS), and pesticides, although it was originally optimized for polyphenols. Spearman rank correlation of the identified features revealed significant correlations between chemicals of the same classification such as polyphenols. One-way ANOVA and differential abundance analysis of the data obtained from stool samples revealed that molecules of plant-based origin elevated as complementary foods were introduced to the infants' diets. Annotated compounds in the stool, such as tricetin, positively correlated with the genus Blautia. Moreover, vulgaxanthin negatively correlated with Escherichia-Shigella. Despite the limited sample size, this exploratory study provides high-quality exposure data of matched biospecimens obtained from mother-infant pairs in sub-Saharan Africa and shows potential correlations between the chemical exposome and the gut microbiome.PMID:38801800 | DOI:10.1016/j.envint.2024.108766

Microb Biotechnol. 2024 May;17(5):e14476. doi: 10.1111/1751-7915.14476.ABSTRACTThis study aimed to investigate how parental genomes contribute to yeast hybrid metabolism using a metabolomic approach. Previous studies have explored central carbon and nitrogen metabolism in Saccharomyces species during wine fermentation, but this study analyses the metabolomes of Saccharomyces hybrids for the first time. We evaluated the oenological performance and intra- and extracellular metabolomes, and we compared the strains according to nutrient consumption and production of the main fermentative by-products. Surprisingly, no common pattern was observed for hybrid genome influence; each strain behaved differently during wine fermentation. However, this study suggests that the genome of the S. cerevisiae species may play a more relevant role in fermentative metabolism. Variations in biomass/nitrogen ratios were also noted, potentially linked to S. kudriavzevii and S. uvarum genome contributions. These results open up possibilities for further research using different "omics" approaches to comprehend better metabolic regulation in hybrid strains with genomes from different species.PMID:38801338 | DOI:10.1111/1751-7915.14476

JBRA Assist Reprod. 2024 May 23. doi: 10.5935/1518-0557.20240034. Online ahead of print.ABSTRACTFollowing the advancement of medically assisted reproduction (MAR) technology, and the rationale to extend the culture to the blastocyst stage, performing elective single embryo transfer (eSET), gamete quality and assessment have acquired large relevance in ART. Embryo quality is strictly correlated with gametes quality and culture conditions. Oocyte maturity assessment is therefore imperative for fertilization and embryo evolution. Mature oocytes at the metaphase II stage result in a higher fertilization rate compared to immature oocytes. Indeed, oocyte morphology evaluation represents an important and challenging task that may serve as a valuable prognostic tool for future embryo development and implantation potential. Different grading systems have been reported to assess human embryos, however, in many cases, it is still a major challenge to select the single embryo to transfer with the highest implantation potential. Further, eSET has conferred a challenge to embryologists, who must try to enhance embryo culture and selection to provide an adequate success rate, whilst reducing the overall number of embryos transferred. Above the standard morphological assessment, there are several invasive or non-invasive approaches for embryo selection such as preimplantation genetic testing, time-lapse technology, proteomics and metabolomics, as well as oxygen utilization and analysis of oxidative stress in culture medium. This short review is not designed to be a comprehensive review of all possible features that may influence oocyte quality. It does give, however, a brief overview and describes the prognostic value of the morphological characteristics of human oocytes on their developmental capacity following ART treatments.PMID:38801314 | DOI:10.5935/1518-0557.20240034

Physiol Plant. 2024 May-Jun;176(3):e14361. doi: 10.1111/ppl.14361.ABSTRACTNepenthes are carnivorous plants that colonize habitats poor in soil nutrients. To survive, Nepenthes develop pitchers capable of capturing and digesting attracted prey. Prey-derived nutrients are then absorbed to support plant growth and reproduction. So far, pitcher formation in Nepenthes is a poorly understood biological process. To shed light on the formation of Nepenthes pitchers, we grew dissected shoot apices of 3-month-old N. khasiana seedlings in Murashige and Skoog (MS) medium of varying strengths viz. full-strength MS (1 MS), quarter-strength MS (1/4 MS), and one-eighth strength MS (1/8 MS), including those lacking nitrogen (N), phosphorus (P), and potassium (K) and in the presence of N-1-naphthylphthalamic acid (NPA). We sequenced the transcriptome and performed gas chromatography-mass spectrometry to determine changes in gene expression patterns and primary metabolite accumulations in response to the varying nutrient conditions. Shoots grown in 1 MS or NPA-containing 1/4 MS and 1/8 MS failed to develop pitchers. Remarkably, pitcher formation is restored when N was removed from 1 MS. Transcriptomic response to nutrient-sufficient and nutrient-deficient conditions are associated with the enrichment of several defence-related genes, including two JA-mediated defence response genes, WRKY51 and WRKY11, respectively. Further, metabolomic response to the varying nutrient conditions identifies glutamic acid as a key metabolite, accumulating at lower and higher levels in shoots with and without pitchers, respectively. Together, our findings suggest that failure to form pitchers may be associated with the suppression of the JA-signalling pathway, whereas the induction of the JA-mediated defence response is linked to pitcher formation in N. khasiana.PMID:38801017 | DOI:10.1111/ppl.14361

Anim Nutr. 2024 Mar 30;17:283-296. doi: 10.1016/j.aninu.2024.03.009. eCollection 2024 Jun.ABSTRACTThis study was conducted to evaluate the effects of Monascus purpureus M-32 fermented soybean meal (MFSM) on growth, immunity, intestinal morphology, intestinal microbiota, and intestinal metabolome of Pacific white shrimp (Litopenaeus vannamei). Four groups of diets were formulated, including control group (30% fish meal and 30% soybean meal [SBM] included in the basal diet) and three experimental groups which MFSM replaced 20% (MFSM20), 40% (MFSM40), and 60% (MFSM60) of SBM in control group, respectively. Results showed that the soluble proteins larger than 49 kDa in MFSM were almost completely degraded. Meanwhile, the crude protein, acid-soluble protein, and amino acid in MFSM were increased. The results of shrimp culture experiment showed that the replacement of SBM with MFSM decreased FCR (P < 0.001) and content of malondialdehyde (P = 0.007) in the experimental groups, and increased weight gain rate (P = 0.006), specific growth rate (P = 0.002), survival rate (P = 0.005), intestinal villus height (P < 0.001), myenteric thickness (P = 0.002), the activities of superoxide dismutase (P = 0.002), and lysozyme (P = 0.006) in experimental groups, as well as increased content of calcium (Ca2+) and phosphorus (PO43-) in blood and muscle, and enhanced resistance to Vibrio parahaemolyticus infection. The gut microbiota of MFSM groups was significantly different from that of the control group, and the abundance of Actinobacteria and Verrucomicrobia increased significantly in the MFSM60 group, whereas Proteobacteria and Firmicutes decreased. Compared with the control group, there were significant changes in the levels of several intestinal metabolites in the MFSM60 group, including leukotriene C5, prostaglandin A1, taurochenodeoxycholic acid, carnosine, and itaconic acid. The fermentation of SBM by the strain M. purpureus M-32 has the potential to enhance the nutritional quality of SBM, promote the growth of L. vannamei, boost immune response, improve intestinal morphology and microbiota composition, as well as influence intestinal metabolites.PMID:38800738 | PMC:PMC11127234 | DOI:10.1016/j.aninu.2024.03.009

Anim Nutr. 2024 Mar 21;17:358-372. doi: 10.1016/j.aninu.2024.01.011. eCollection 2024 Jun.ABSTRACTThis study was to evaluate the effect of supplementing the diet of broilers with Neolamarckia cadamba leaf extract (NCLE) on meat quality by evaluating antioxidant parameters and the expression of genes in the p38 mitogen-activated protein kinase/nuclear factor-erythroid 2-related factor 2/antioxidant responsive element (p38 MAPK/Nrf2/ARE) signaling pathway, coupled with LC-MS-based metabolomic analysis. A total of 480 one-day-old male broilers were randomly allocated to four treatment groups-a control (CON) group, which was fed a basal diet, and three NCLE treatment groups, which were fed the basal diet supplemented with 100, 200, or 400 mg/kg NCLE (N1, N2, and N3 groups, respectively) for 42 d. Compared with the CON group, meat quality was improved in the N2 and N3 groups, as evidenced by the higher pH45min (P < 0.05) and lower shear force (P < 0.05) in breast muscle (BM) and lower drip loss at 48 h (P < 0.05) in leg muscle (LM). Moreover, BM antioxidant capacity was significantly enhanced in the N3 group, characterized by an increase in the total antioxidant capacity (T-AOC), the concentrations of glutathione peroxidase (GSH-Px) and catalase (CAT), and the relative mRNA expression of p38 MAPK, extracellular-signal regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), Nrf2, CAT, and GSH-Px (P < 0.05). Similarly, LM in the N3 group displayed higher T-AOC, increased GSH-Px and CAT concentrations, reduced malonaldehyde contents (P < 0.05), and upregulation of the relative mRNA levels of JNK, Nrf2, heme oxygenase, CAT, and superoxide dismutase (SOD) (P < 0.05). Metabolomics analysis revealed that D-arabinono-1,4-lactone and lyso-PAF C-16-d4 were negatively correlated with shear force and cooking loss (P < 0.05) and displayed increased abundance in BM of the N3 group. L-Serine levels were upregulated while D-fructose 1,6-diphosphate contents were downregulated in the three NCLE groups. Finally, the differential metabolites in both BM and LM were involved in amino acid metabolism pathways. Our results indicated that NCLE supplementation improved meat quality by enhancing antioxidant enzyme activities, promoting the expression of genes in the p38 MAPK/Nrf2/ARE signaling pathway, and regulating amino acid metabolism. The optimal NCLE concentration was found to be 400 mg/kg.PMID:38800732 | PMC:PMC11127102 | DOI:10.1016/j.aninu.2024.01.011

Front Endocrinol (Lausanne). 2024 May 10;15:1335855. doi: 10.3389/fendo.2024.1335855. eCollection 2024.ABSTRACTINTRODUCTION: Emerging data suggests liver disease may be initiated during development when there is high genome plasticity and the molecular pathways supporting liver function are being developed.METHODS: Here, we leveraged our Collaborative Cross mouse model of developmental vitamin D deficiency (DVD) to investigate the role of DVD in dysregulating the molecular mechanisms underlying liver disease. We defined the effects on the adult liver transcriptome and metabolome and examined the role of epigenetic dysregulation. Given that the parental origin of the genome (POG) influences response to DVD, we used our established POG model [POG1-(CC011xCC001)F1 and POG2-(CC001xCC011)F1] to identify interindividual differences.RESULTS: We found that DVD altered the adult liver transcriptome, primarily downregulating genes controlling liver development, response to injury/infection (detoxification & inflammation), cholesterol biosynthesis, and energy production. In concordance with these transcriptional changes, we found that DVD decreased liver cell membrane-associated lipids (including cholesterol) and pentose phosphate pathway metabolites. Each POG also exhibited distinct responses. POG1 exhibited almost 2X more differentially expressed genes (DEGs) with effects indicative of increased energy utilization. This included upregulation of lipid and amino acid metabolism genes and increased intermediate lipid and amino acid metabolites, increased energy cofactors, and decreased energy substrates. POG2 exhibited broader downregulation of cholesterol biosynthesis genes with a metabolomics profile indicative of decreased energy utilization. Although DVD primarily caused loss of liver DNA methylation for both POGs, only one epimutation was shared, and POG2 had 6.5X more differentially methylated genes. Differential methylation was detected at DEGs regulating developmental processes such as amino acid transport (POG1) and cell growth & differentiation (e.g., Wnt & cadherin signaling, POG2).CONCLUSIONS: These findings implicate a novel role for maternal vitamin D in programming essential offspring liver functions that are dysregulated in liver disease. Importantly, impairment of these processes was not rescued by vitamin D treatment at weaning, suggesting these effects require preventative measures. Substantial differences in POG response to DVD demonstrate that the parental genomic context of exposure determines offspring susceptibility.PMID:38800476 | PMC:PMC11116800 | DOI:10.3389/fendo.2024.1335855

Cell Stress. 2024 Apr 30;8:51-55. doi: 10.15698/cst2024.04.295. eCollection 2024.ABSTRACTIn a recent issue in Nature Cell Biology, Sung Min Son et al. unveil a novel layer in the regulation of the mTORC1/autophagy axis by EP300 which can undergo nucleocytoplasmic shuttling in response to alterations in nutrient availability. The study highlights that, in Hutchinson-Gilford progeria syndrome, overabundant cytoplasmic EP300 results in mTORC1 hyperactivation and impaired autophagy, potentially contributing to premature and accelerated aging.PMID:38800095 | PMC:PMC11118783 | DOI:10.15698/cst2024.04.295

F1000Res. 2024 Mar 8;13:169. doi: 10.12688/f1000research.141056.1. eCollection 2024.ABSTRACTBACKGROUND: The U.S. Federal Government has supported the generation of extensive amounts of nanomaterials and related nano Environmental Health and Safety (nanoEHS) data, there is a need to make these data available to stakeholders. With recent efforts, a need for improved interoperability, translation, and sustainability of Federal nanoEHS data in the United States has been realized. The NaKnowBase (NKB) is a relational database containing experimental results generated by the EPA Office of Research and Development (ORD) regarding the actions of engineered nanomaterials on environmental and biological systems. Through the interaction of the National Nanotechnology Initiative's Nanotechnology Environmental Health Implications (NEHI) Working Group, and the Database and Informatics Interest Group (DIIG), a U.S. Federal nanoEHS Consortium has been formed.METHODS: The primary goal of this consortium is to establish a "common language" for nanoEHS data that aligns with FAIR data standards. A second goal is to overcome nomenclature issues inherent to nanomaterials data, ultimately allowing data sharing and interoperability across the diverse U.S. Federal nanoEHS data compendium, but also in keeping a level of consistency that will allow interoperability with U.S. and European partners. The most recent version of the EPA NaKnowBase (NKB) has been implemented for semantic integration. Computational code has been developed to use each NKB record as input, modify and filter table data, and subsequently output each modified record to a Research Description Framework (RDF). To improve the accuracy and efficiency of this process the EPA has created the OntoSearcher tool. This tool partially automates the ontology mapping process, thereby reducing onerous manual curation.CONCLUSIONS: Here we describe the efforts of the US EPA in promoting FAIR data standards for Federal nanoEHS data through semantic integration, as well as in the development of NAMs (computational tools) to facilitate these improvements for nanoEHS data at the Federal partner level.PMID:38800073 | PMC:PMC11128042 | DOI:10.12688/f1000research.141056.1

J Pharm Anal. 2024 Apr;14(4):100980. doi: 10.1016/j.jpha.2024.100980. Epub 2024 May 10.ABSTRACT[This corrects the article DOI: 10.1016/j.jpha.2023.09.007.].PMID:38800053 | PMC:PMC11121172 | DOI:10.1016/j.jpha.2024.100980

Front Vet Sci. 2024 May 10;11:1396051. doi: 10.3389/fvets.2024.1396051. eCollection 2024.ABSTRACTMicroencapsulated essential oils (MEO)have been used as antibiotic alternatives that can be applied to alleviate diarrhea in weaning piglet. We examined a large group of weaned piglets and incorporated essential oil containing thymol (2%), carvacrol (5%) and cinnamaldehyde (3%) in the feed of weaned piglets on an intensive production farm. The piglets were divided into four groups; Control (no additions) and chlortetracycline (Chl), essential oil (EO) and microencapsulated essential oil (MEO) were fed ad libitum over a 28-day trial period. We found MEO significantly reduced the incidence of diarrhea in the piglets that was also accompanied by increased average daily weight gains from days 14-28 (p < 0.05). MEO enhanced the antioxidant capacity in the piglets and serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-px) levels were significantly increased (p < 0.05). MEO also significantly reduced expression of genes related to ileal inflammation (IL-6, TNF-α and TGF-β1) (p < 0.05) and significantly (p < 0.05) increased in sIgA antibody levels. MEO influenced the composition of the intestinal microbiome and reduced Bacteroidota (p < 0.05) and thus altered the Firmicutes/Bacteroidota ratio. However, none of the treatments produced significant changes in the most common tetracycline resistance genes (p > 0.05). Metagenomic analysis indicated that MEO impacted DNA expression, virulence factors, antioxidant activity and antimicrobial activity. Metabolomic analysis of the intestinal content also indicated that MEO impacted tyrosine metabolism and primary bile acid biosynthesis suggesting improved intestinal health and nutrient absorption. This study paves the way for further research into the development and optimization of MEO-based interventions aimed at improving piglet health and performance while also providing a reference for reducing reliance on antibiotics in animal agriculture.PMID:38799727 | PMC:PMC11117338 | DOI:10.3389/fvets.2024.1396051

iScience. 2024 May 8;27(6):109949. doi: 10.1016/j.isci.2024.109949. eCollection 2024 Jun 21.ABSTRACTAs the global aging population rises, finding effective interventions to improve aging health is crucial. Drug repurposing, utilizing existing drugs for new purposes, presents a promising strategy for rapid implementation. We explored naltrexone from the Library of Integrated Network-based Cellular Signatures (LINCS) based on several selection criteria. Low-dose naltrexone (LDN) has gained attention for treating various diseases, yet its impact on longevity remains underexplored. Our study on C. elegans demonstrated that a low dose, but not high dose, of naltrexone extended the healthspan and lifespan. This effect was mediated through SKN-1 (NRF2 in mammals) signaling, influencing innate immune gene expression and upregulating oxidative stress responses. With LDN's low side effects profile, our findings underscore its potential as a geroprotector, suggesting further exploration for promoting healthy aging in humans is warranted.PMID:38799567 | PMC:PMC11126937 | DOI:10.1016/j.isci.2024.109949

iScience. 2024 Apr 16;27(6):109737. doi: 10.1016/j.isci.2024.109737. eCollection 2024 Jun 21.ABSTRACTLong-chain acyl-CoA synthetase family 4 (ACSL4) metabolizes long-chain polyunsaturated fatty acids (PUFAs), enriching cell membranes with phospholipids susceptible to peroxidation and drive ferroptosis. The role of ACSL4 and ferroptosis upon endoplasmic-reticulum (ER)-stress-induced acute kidney injury (AKI) is unknown. We used lipidomic, molecular, and cellular biology approaches along with a mouse model of AKI induced by ER stress to investigate the role of ACSL4 regulation in membrane lipidome remodeling in the injured tubular epithelium. Tubular epithelial cells (TECs) activate ACSL4 in response to STAT3 signaling. In this context, TEC membrane lipidome is remodeled toward PUFA-enriched triglycerides instead of PUFA-bearing phospholipids. TECs expressing ACSL4 in this setting are not vulnerable to ferroptosis. Thus, ACSL4 activity in TECs is driven by STAT3 signaling, but ACSL4 alone is not enough to sensitize ferroptosis, highlighting the significance of the biological context associated with the study model.PMID:38799564 | PMC:PMC11126884 | DOI:10.1016/j.isci.2024.109737

Front Immunol. 2024 May 10;15:1376860. doi: 10.3389/fimmu.2024.1376860. eCollection 2024.ABSTRACTINTRODUCTION: Aeromonas hydrophila, a bacterium widely distributed in the natural environment, causes multiple diseases in various animals. Exploring the mechanism of the host defense against A. hydrophila can help develop efficient strategies against Aeromonas infection.METHODS: Herein, we investigated the temporal influence of A. hydrophila on the Chinese soft-shelled turtle, an economically important species, at the biochemical, transcriptomic, and metabolomic levels. Plasma parameters were detected with the test kits. Transcriptome and metabolome were respectively applied to screen the differentially expressed genes and metabolites.RESULTS: The contents or activities of these plasma parameters were significantly increased at 24 hpi and declined at 96 hpi, indicating that 24 and 96 hpi were two important time points during infection. Totals of 3121 and 274 differentially expressed genes (DEGs) from the transcriptome while 74 and 91 differentially abundant metabolites (DAMs) from the metabolome were detected at 24 and 96 hpi. The top DEGs at 24 hpi included Ccl2, Ccl3, Ccl4, Il1β, Il6, Il7, Il15, Tnf, and Tnfr1 while Zap70, Cd3g, Cd8a, Itk, Pik3r3, Cd247, Malt1, and Cd4 were the most abundant at 96 hpi. The predominant DAMs included O-phospho-L-serine, γ-Aminobutyric acid, orotate, L-tyrosine, and L-tryptophan at 24 hpi, as well as L-glutamic acid, L-arginine, glutathione, glutathione disulfide, and citric acid at 96 hpi.DISCUSSION: The combined analysis of DEGs and DAMs revealed that tryptophan metabolism, nicotinate and nicotinamide metabolism, as well as starch and sucrose metabolism, were the most important signaling pathways at the early infective stage while tyrosine metabolism, pyrimidine metabolism, as well as alanine, aspartate and glutamate metabolism were the most crucial pathways at the later stage. In general, our results indicated that the Chinese soft-shelled turtle displays stage-specific physiological responses to resist A. hydrophila infection.PMID:38799475 | PMC:PMC11116567 | DOI:10.3389/fimmu.2024.1376860

Front Immunol. 2024 May 10;15:1353903. doi: 10.3389/fimmu.2024.1353903. eCollection 2024.ABSTRACTINTRODUCTION: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes.METHODS: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes.RESULTS: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods.CONCLUSIONS: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.PMID:38799469 | PMC:PMC11127595 | DOI:10.3389/fimmu.2024.1353903

Front Immunol. 2024 May 10;15:1337208. doi: 10.3389/fimmu.2024.1337208. eCollection 2024.ABSTRACTOBJECTIVE: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19.METHODS: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids.RESULTS: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19.CONCLUSION: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.PMID:38799463 | PMC:PMC11116732 | DOI:10.3389/fimmu.2024.1337208