PubMed

Food Funct. 2023 Nov 13. doi: 10.1039/d3fo03867j. Online ahead of print.ABSTRACTThe wide application of immune checkpoint blockade (ICB) therapy is impeded by the development of ICB-induced colitis, a condition intricately linked to alterations in the gut microbiota. In our previous study, Ligilactobacillus salivarius CCFM 1266 and Bacteroides fragilis HCK-B3 exhibited anti-inflammatory properties. In this research, treatment with both L. salivarius CCFM 1266 and B. fragilis HCK-B3 significantly ameliorated body weight loss and colonic inflammation in murine colitis models induced by intravenous ipilimumab injection, with L. salivarius CCFM 1266 demonstrating superior effectiveness. This amelioration was characterized by an augmented ratio of Treg cells and M2 macrophages, a diminishment in pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-23), and an elevation in the anti-inflammatory cytokine IL-10. The ingestion of L. salivarius CCFM 1266 exerted a discernible influence on the composition of the gut microbiota. Untargeted metabolomics revealed an increase in colonic nicotinic acid levels following the administration of L. salivarius CCFM 1266, potentially initiating the activation of the colonic GPR109a pathway. This mechanism likely serves as the fundamental basis for the protective capacity of L. salivarius CCFM 1266 against ICB-induced colitis. Importantly, L. salivarius CCFM 1266 did not interfere with the anti-tumor immune response elicited by ipilimumab. Probiotic intervention thus emerges as a promising approach for alleviating ICB-induced colitis.PMID:37953676 | DOI:10.1039/d3fo03867j

Nucleic Acids Res. 2023 Nov 11:gkad980. doi: 10.1093/nar/gkad980. Online ahead of print.ABSTRACTPlants are unique with tremendous chemical diversity and metabolic complexity, which is highlighted by estimates that green plants collectively produce metabolites numbering in the millions. Plant metabolites play crucial roles in all aspects of plant biology, like growth, development, stress responses, etc. However, the lack of a reference metabolome for plants, and paucity of high-quality standard compound spectral libraries and related analytical tools, have hindered the discovery and functional study of phytochemicals in plants. Here, by leveraging an advanced LC-MS platform, we generated untargeted mass spectral data from >150 plant species collected across the five major phyla. Using a self-developed computation protocol, we constructed reference metabolome for 153 plant species. A 'Reference Metabolome Database for Plants' (RefMetaPlant) was built to encompass the reference metabolome, integrated standard compound mass spectral libraries for annotation, and related query and analytical tools like 'LC-MS/MS Query', 'RefMetaBlast' and 'CompoundLibBlast' for searches and profiling of plant metabolome and metabolite identification. Analogous to a reference genome in genomic research, RefMetaPlant provides a powerful platform to support plant genome-scale metabolite analysis to promote knowledge/data sharing and collaboration in the field of metabolomics. RefMetaPlant is freely available at https://www.biosino.org/RefMetaDB/.PMID:37953341 | DOI:10.1093/nar/gkad980

Mol Hortic. 2023 Nov 13;3(1):24. doi: 10.1186/s43897-023-00073-0.ABSTRACTStorage or transportation temperature is very important for preserving the quality of fruit. However, low temperature in sensitive fruit such as peach can induce loss of quality. Fruit exposed to a specific range of temperatures and for a longer period can show chilling injury (CI) symptoms. The susceptibility to CI at low temperature varies among cultivars and genetic backgrounds. Along with agronomic management, appropriate postharvest management can limit quality losses. The importance of correct temperature management during postharvest handling has been widely demonstrated. Nowadays, due to long-distance markets and complex logistics that require multiple actors, the management of storage/transportation conditions is crucial for the quality of products reaching the consumer.Peach fruit exposed to low temperatures activate a suite of physiological, metabolomic, and molecular changes that attempt to counteract the negative effects of chilling stress. In this review an overview of the factors involved, and plant responses is presented and critically discussed. Physiological disorders associated with CI generally only appear after the storage/transportation, hence early detection methods are needed to monitor quality and detect internal changes which will lead to CI development. CI detection tools are assessed: they need to be easy to use, and preferably non-destructive to avoid loss of products.PMID:37953307 | DOI:10.1186/s43897-023-00073-0

Nucleic Acids Res. 2023 Nov 11:gkad976. doi: 10.1093/nar/gkad976. Online ahead of print.ABSTRACTFirst released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.PMID:37953279 | DOI:10.1093/nar/gkad976

Allergol Int. 2023 Nov 10:S1323-8930(23)00112-0. doi: 10.1016/j.alit.2023.10.008. Online ahead of print.ABSTRACTBACKGROUND: Lactobacillus paracasei has been known to reduce airway resistance and inflammation in asthma. However, the therapeutic effect of its extracellular vesicles (EVs) in patients with asthma remains unclear.METHODS: To validate the clinical relevance of L. paracasei-derived EVs (LpEV) in asthma, the composition of gut microbial EVs was verified by metagenomics in LPS-induced C57BL/6 mice. The components of proteins and metabolites in LpEV were identified by peptide mass fingerprinting and metabolomic analysis. The serum levels of specific IgG1 or IgG4 antibodies to LpEV were compared by ELISA between patients with eosinophilic asthma (EA, n = 10) and those with neutrophilic asthma (NA, n = 10) as well as with healthy controls (HCs, n = 10). Finally, therapeutic effects of LpEV and their metabolites in asthma were validated in vivo/in vitro.RESULTS: Significantly lower proportions of EVs derived from Lactobacillus at the genus level were noted in mice with NA than in control mice. Moreover, the serum levels of LpEV-specific IgG4, but not IgG1, were lower in patients with NA than in those with EA or in HCs and positively correlated with FEV1 (%) values. In addition, oral administration of LpEV reduced airway resistance and inflammation in mice with NA. Finally, LpEV and their 3 metabolites (dodecanoic acid, palmitoleic acid, and D-(-)-tagatose) significantly inhibited JNK phosphorylation/IL-8 production in airway epithelium in vitro.CONCLUSIONS: These findings suggest that LpEV may have a therapeutic potential targeting NA by suppressing the JNK pathway and proinflammatory cytokine production in airway epithelium.PMID:37953104 | DOI:10.1016/j.alit.2023.10.008

Am J Med Genet A. 2023 Nov 12. doi: 10.1002/ajmg.a.63461. Online ahead of print.ABSTRACTThe MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child with heteroplasmy for this variant who developed neurological regression and stroke-like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z-scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke-like episodes. The use of intravenous arginine during stroke-like episodes and daily enteral L-citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1-methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N-acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT-TL2 m.12315G>A to include neurological regression and a MELAS-like phenotype. Individuals with this variant should undergo in-depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.PMID:37953071 | DOI:10.1002/ajmg.a.63461

Transl Res. 2023 Nov 10:S1931-5244(23)00182-2. doi: 10.1016/j.trsl.2023.11.002. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM) that poses a serious risk as it can lead to end-stage renal disease (ESRD). DKD is linked to changes in the diversity, composition, and functionality of the microbiota present in the gastrointestinal tract. The interplay between the gut microbiota and the host organism is primarily facilitated by metabolites generated by microbial metabolic processes from both dietary substrates and endogenous host compounds. The production of numerous metabolites by the gut microbiota is a crucial factor in the pathogenesis of DKD. However, a comprehensive understanding of the precise mechanisms by which gut microbiota and its metabolites contribute to the onset and progression of DKD remains incomplete. This review will provide a summary of the current scenario of metabolites in DKD and the impact of these metabolites on DKD progression. We will discuss in detail the primary and gut-derived metabolites in DKD, and the mechanisms of the metabolites involved in DKD progression. Further, we will address the importance of metabolomics in helping identify potential DKD markers. Furthermore, the possible therapeutic interventions and research gaps will be highlighted.PMID:37952771 | DOI:10.1016/j.trsl.2023.11.002

J Ethnopharmacol. 2023 Nov 10:117405. doi: 10.1016/j.jep.2023.117405. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Allergic asthma is a recurring respiratory condition that typically manifests during childhood or adolescence. It is characterized by a dominant type II immune response triggered by the identification and capturing of inhaled allergens by dendritic cells (DCs). Jiangqi Pingxiao Formula (JQPXF), a prescription medicine used for the treatment of pediatric asthma, has been clinically proven to be both safe and effective. However, its mechanism of action in the treatment of asthma has not been fully been fully elucidated. Recent research suggests that several natural compounds have the potential to target dendritic cells (DCs) and alleviate ovalbumin (OVA)-induced asthma, which may also be found within JQPXF.AIM OF THE STUDY: This study aimed to elucidate the effect of JQPXF on OVA-induced asthma model and its molecular mechanism targeting DCs.MATERIALS AND METHODS: The main constituents of JQPXF were analyzed by ultra performance liquid chromatography (UPLC). An asthma model was established by OVA. Hematoxylin-eosin staining and measurement of respiratory function was used to evaluate the treatment effect of JQPXF on asthmatic mice. Cytokine (IL-5, IL-13 and IgE) concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to evaluate inflammatory cell infiltration (T helper 2 cells and DCs) in vivo and DC survival in vivo and vitro. Western blot and immunofluorescence were used to verify the molecular mechanisms.RESULTS: The results suggest that JQPXF can ameliorate pathological conditions and improve lung function in asthmatic mice, as well as the Th2 cells. Treatment with JQPXF significantly reduced the number of DCs and increased the number of Propidium iodide+ (PI) DCs. Furthermore, JQPXF upregulated protein levels of the pro-apoptotic factors Cleaved-caspase-3 and Bax, while downregulating the anti-apoptotic factor Bcl-2. Simultaneously, JQPXF increased autophagy levels by facilitating p62 degradation and promoting translation from LC3B I to LC3B II of DCs in vitro, as well as reducing the integrated optical density (IOD) of p62 within the CD11c-positive area in the lung. 3-Methyladenine (3-MA) was used to block autophagic flux and the apoptotic effect of JQPXF on DCs was abolished in vitro, with the number of DCs decreased by JQPXF being reversed in vivo. We further investigated the upstream key regulator of autophagy, the AMPK/mTOR pathway, and found that JQPXF increased AMPK phosphorylation while decreasing mTOR phosphorylation levels. Additionally, we employed Compound C (CC) as an AMPK inhibitor to inhibit this signaling pathway, and our findings revealed that both autophagic flux and apoptotic levels in DCs were abolished in vitro.CONCLUSIONS: In summary, we have demonstrated that JQPXF could alleviate type II inflammation in an asthmatic model by promoting the apoptosis of DCs through an autophagy-dependent mechanism, achieved by regulating the AMPK/mTOR signaling pathway.PMID:37952734 | DOI:10.1016/j.jep.2023.117405

Sci Total Environ. 2023 Nov 10:168498. doi: 10.1016/j.scitotenv.2023.168498. Online ahead of print.ABSTRACTConsumption of cadmium (Cd) contaminated rice is the main dietary source of Cd exposure and toxicity. To protect humans from Cd toxicity, it is pivotal to fully understand the sex-dependent toxicity of subchronic rice-Cd exposure. However, the sex-dependent effects of subchronic rice-Cd exposure on body weight gain, gut microflora, and kidney metabolomics are still unclear. In this study, a Cd-free and a Cd-contaminated rice (0.005 and 0.74 mg Cd kg-1) were fed to both female and male mice for one month, with changes in body weight gain, Cd accumulation in tissue, bone mineral concentration, expression of intestinal channels involving in Cd and calcium (Ca) absorption, gut microbiota, and kidney metabolites assessed for both genders. Results showed that female mice had normal body weight gain after rice-Cd exposure, while body weight of male mice was decreased from 19.8 to 17.5 g over the one-month consumption of the Cd-contaminated rice (0.74 mg kg-1), suggesting specific toxicity on growth of male mice. Rice-Cd exposure had limited effects on gut microbiota for both genders. However, higher Cd accumulation in liver and femur was observed in male mice than in females, which may be due to higher intestinal expression of Ca channels involving in intestinal Cd absorption in male mice with rice-Cd exposure. Greater risk of osteoporosis was also observed in male mice. In addition, kidney metabolomic profiling showed special disruption of adrenocortical hormone homeostasis for male mice with rice-Cd exposure. Particularly, expression of cortisol in kidneys of male mice was elevated 37.1-fold with rice-Cd exposure, likely resulting in Cushing's syndrome and contributing to growth retardation. This study advances our understanding of the sex-dependent toxicity of rice-Cd exposure, and highlights the priority of protecting males from the adrenocortical hormone disrupting effects of rice-Cd exposure.PMID:37952668 | DOI:10.1016/j.scitotenv.2023.168498

Water Res. 2023 Oct 30;247:120816. doi: 10.1016/j.watres.2023.120816. Online ahead of print.ABSTRACTAs one of five Laurentian Great Lakes, Lake Erie ranks among the top freshwater drinking sources and ecosystems globally. Historical and current agriculture mismanagement and climate change sustains the environmental landscape for late summer cyanobacterial harmful algal blooms, and consequently, cyanotoxins such as microcystin (MC). Microcystin microbial degradation is a promising mitigation strategy, however the mechanisms controlling the breakdown of MCs in Lake Erie are not well understood. Pelee Island, Ontario, Canada is located in the western basin of Lake Erie and the bacterial community in the sand has demonstrated the capacity of metabolizing the toxin. Through a multi-omic approach, the metabolic, functional and taxonomical signatures of the Pelee Island microbial community during MC-LR degradation was investigated over a 48-hour period to comprehensively study the degradation mechanism. Cleavage of bonds surrounding nitrogen atoms and the upregulation of nitrogen deamination (dadA, alanine dehydrogenase, leucine dehydrogenase) and assimilation genes (glnA, gltB) suggests a targeted isolation of nitrogen by the microbial community for energy production. Methylotrophic pathways RuMP and H4MPT control assimilation and dissimilation of carbon, respectively and differential abundance of Methylophilales indicates an interconnected role through electron exchange of denitrification and methylotrophic pathways. The detected metabolites did not resolve a clear breakdown pathway, but rather the diversity of products in combination with taxonomic and functional results supports that a variety of strategies are applied, such as epoxidation, hydroxylation, and aromatic degradation. Annual repeated exposure to the toxin may have allowed the community to adaptatively establish a novel pathway through functional plasticity and horizontal gene transfer. The culmination of these results reveals the complexity of the Pelee Island sand community and supports a dynamic and cooperative metabolism between microbial species to achieve MC degradation.PMID:37952399 | DOI:10.1016/j.watres.2023.120816

J Chromatogr A. 2023 Oct 31;1712:464479. doi: 10.1016/j.chroma.2023.464479. Online ahead of print.ABSTRACTThe analysis of the brain extracellular metabolome is of interest for numerous subdomains within neuroscience. Not only does it provide information about normal physiological functions, it is even more of interest for biomarker discovery and target discovery in disease. The extracellular analysis of the brain is particularly interesting as it provides information about the release of mediators in the brain extracellular fluid to look at cellular signaling and metabolic pathways through the release, diffusion and re-uptake of neurochemicals. In vivo samples are obtained through microdialysis, cerebral open-flow microperfusion or solid-phase microextraction. The analytes of potential interest are typically low in concentration and can have a wide range of physicochemical properties. Liquid chromatography coupled to mass spectrometry has proven its usefulness in brain metabolomics. It allows sensitive and specific analysis of low sample volumes, obtained through different approaches. Several strategies for the analysis of the extracellular fluid have been proposed. The most widely used approaches apply sample derivatization, specific stationary phases and/or hydrophilic interaction liquid chromatography. Miniaturization of these methods allows an even higher sensitivity. The development of chiral metabolomics is indispensable, as it allows to compare the enantiomeric ratio of compounds and provides even more challenges. Some limitations continue to exist for the previously developed methods and the development of new, more sensitive methods remains needed. This review provides an overview of the methods developed for sampling and liquid chromatography-mass spectrometry analysis of the extracellular metabolome.PMID:37952387 | DOI:10.1016/j.chroma.2023.464479

J Hazard Mater. 2023 Nov 7;464:132953. doi: 10.1016/j.jhazmat.2023.132953. Online ahead of print.ABSTRACTSelenium (Se) can be absorbed by plants, thereby affects plant physiological activity, interferes gene expression, alters metabolite content and influences plant growth. However, the molecular mechanism underlying the plant response to Se remains unclear. In this study, apple plants were exposed to Se at concentrations of 0, 3, 6, 9, 12, 24, and 48 μM. Low concentrations of Se promoted plant growth, while high Se concentrations (≥24 μM) reduced photosynthesis, disturbed carbon and nitrogen metabolism, damaged the antioxidant system, and ultimately inhibited plant growth. The transcriptome and metabolome revealed that Se mainly affected three pathways, namely the 'biosynthesis of amino acids', 'starch and sucrose metabolism', and 'phenylpropanoid biosynthesis' pathways. 9 μM Se improved the synthesis, catabolism and utilization of amino acids and sugars, ultimately promoted plant growth. However, 24 μM Se up-regulated the related genes expression of PK, GPT, P5CS, SUS, SPS and CYP98A, and accumulated a large number of osmoregulation substances, such as citric acid, L-proline, D-sucrose and chlorogenic acid in the roots, ultimately affected the balance between plant growth and defense. In conclusion, this study reveals new insights into the key metabolic pathway in apple plants responses to Se.PMID:37952334 | DOI:10.1016/j.jhazmat.2023.132953

Bioinformatics. 2023 Nov 11:btad684. doi: 10.1093/bioinformatics/btad684. Online ahead of print.ABSTRACTOnline assessment of tumor characteristics during surgery is important and has the potential to establish an intra-operative surgeon feedback mechanism. With the availability of such feedback, surgeons could decide to be more liberal or conservative regarding the resection of the tumor. While there are methods to perform metabolomics-based tumor pathology prediction, their model complexity predictive performance is limited by the small dataset sizes. Furthermore, the information conveyed by the feedback provided on the tumor tissue could be improved both in terms of content and accuracy. In this study, we propose a metabolic pathway-informed deep learning model (PiDeeL) to perform survival analysis and pathology assessment based on metabolite concentrations. We show that incorporating pathway information into the model architecture substantially reduces parameter complexity and achieves better survival analysis and pathological classification performance. With these design decisions, we show that PiDeeL improves tumor pathology prediction performance of the state-of-the-art in terms of the Area Under the ROC Curve (AUC-ROC) by 3.38% and the Area Under the Precision-Recall Curve (AUC-PR) by 4.06%. Similarly, with respect to the time-dependent concordance index (c-index), PiDeeL achieves better survival analysis performance (improvement of 4.3%) when compared to the state-of-the-art. Moreover, we show that importance analyses performed on input metabolite features as well as pathway-specific neurons of PiDeeL provide insights into tumor metabolism. We foresee that the use of this model in the surgery room will help surgeons adjust the surgery plan on the fly and will result in better prognosis estimates tailored to surgical procedures.AVAILABILITY: The code is released at https://github.com/ciceklab/PiDeeL. The data used in this study is released at https://zenodo.org/record/7228791.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:37952175 | DOI:10.1093/bioinformatics/btad684

Brief Funct Genomics. 2023 Nov 10:elad050. doi: 10.1093/bfgp/elad050. Online ahead of print.ABSTRACTHerbal medicines were widely used in ancient and modern societies as remedies for human ailments. Notably, the Papaveraceae family includes well-known species, such as Papaver somniferum and Chelidonium majus, which possess medicinal properties due to their latex content. Latex-bearing plants are a rich source of diverse bioactive compounds, with applications ranging from narcotics to analgesics and relaxants. With the advent of high-throughput technologies and advancements in sequencing tools, an opportunity exists to bridge the knowledge gap between the genetic information of herbs and the regulatory networks underlying their medicinal activities. This emerging discipline, known as herbgenomics, combines genomic information with other -omics studies to unravel the genetic foundations, including essential gene functions and secondary metabolite biosynthesis pathways. Furthermore, exploring the genomes of various medicinal plants enables the utilization of modern genetic manipulation techniques, such as Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR/Cas9) or RNA interference. This technological revolution has facilitated systematic studies of model herbs, targeted breeding of medicinal plants, the establishment of gene banks and the adoption of synthetic biology approaches. In this article, we provide a comprehensive overview of the recent advances in genomic, transcriptomic, proteomic and metabolomic research on species within the Papaveraceae family. Additionally, it briefly explores the potential applications and key opportunities offered by the -omics perspective in the pharmaceutical industry and the agrobiotechnology field.PMID:37952099 | DOI:10.1093/bfgp/elad050

Microbiome. 2023 Nov 11;11(1):251. doi: 10.1186/s40168-023-01707-7.ABSTRACTBACKGROUND: Alterations of the uterine microbiome are closely associated with various intrauterine diseases and physiological conditions, which are well-established in mammals. However, as representative oviparous animals, the research on the uterine microbial ecosystem and its functions with physiological homeostasis is limited in chickens. Additionally, continuous egg-laying disrupts the oviducal immune defenses of aged hens, susceptible to pathogen invasion, causing poor egg quality and food-borne infections in humans. Here, we investigated aging-related changes in the oviduct microbial colonization and transmission from the gut to eggs and their roles in a hen model.RESULTS: The results of 16S rDNA sequencing showed significant differences in the oviduct microbial composition between young (38 weeks) and aged (77 weeks) laying hens. SourceTracker analysis further revealed differences in the effects of microbial transmission on the oviducal microbiota between young and aged hens. Enhanced barrier defense with cell apoptosis suppression and cell cycle arrest of the uterus were observed in aged hens reducing microbial transmission from the lower to upper reproductive tract. In addition, a total of 361 significantly differential metabolites were identified using metabolomics in the aged uterine microbiota, especially in products of amino acid metabolism and biosynthesis of various secondary metabolites, which might have essential effects on cell apoptosis by regulating immune responses and cell cycle. Notably, antibiotics disrupted uterine microbiota by dietary intervention and direct perfusion did not retard aging-related physiological changes but further aggravated aging processes by disrupting the cell cycle and apoptosis.CONCLUSIONS: The microbiota continuum along the reproductive tract in aged birds differs from that in young birds, especially with a significant shift in the uterus. The aged uterine microbiota probably contributes to the regulation of cell cycle and apoptosis by microbial metabolites primarily involved in amino acid metabolism and biosynthesis of various secondary metabolites. These findings provide new insights into the roles of the reproductive tract microbiota in regulating the cell programming of the aged host, contributing to the exploration of the microbiome as a target for diagnosing aging health status and therapy for gynecological diseases in women. Video Abstract.PMID:37951950 | DOI:10.1186/s40168-023-01707-7

Harmful Algae. 2023 Nov;129:102529. doi: 10.1016/j.hal.2023.102529. Epub 2023 Oct 20.ABSTRACTThe increasing occurrence of harmful algal blooms, mostly of the dinoflagellate Alexandrium catenella in Canada, profoundly disrupts mussel aquaculture. These filter-feeding shellfish feed on A. catenella and accumulate paralytic shellfish toxins, such as saxitoxin, in tissues, making them unsafe for human consumption. Algal toxins also have detrimental effects upon several physiological functions in mussels, but particularly on the activity of hemocytes - the mussel immune cells. The objective of this work was to determine the effects of experimental exposure to A. catenella upon hemocyte metabolism and activity in the blue mussel, Mytilus edulis. To do so, mussels were exposed to cultures of the toxic dinoflagellate A. catenella for 120 h. The resulting mussel saxitoxin load had measurable effects upon survival of hemocytes and induced a stress response measured as increased ROS production. The neutral lipid fraction of mussel hemocytes decreased two-fold, suggesting a differential use of lipids. Metabolomic 1H nuclear magnetic resonance (NMR) analysis showed that A. catenella modified the energy metabolism of hemocytes as well as hemocyte osmolyte composition. The modified energy metabolism was reenforced by contrasting plasma metabolomes between control and exposed mussels, suggesting that the blue mussel may reduce feed assimilation when exposed to A. catenella.PMID:37951624 | DOI:10.1016/j.hal.2023.102529

Food Chem Toxicol. 2023 Nov 9:114183. doi: 10.1016/j.fct.2023.114183. Online ahead of print.ABSTRACTMycotoxins are secondary metabolites produced by fungi such as Aspergillus, Alternaria, and Penicillium, affecting nearly 80% of global food crops. Tenuazonic acid (TeA) is the major mycotoxin produced by Alternaria alternata, a prevalent pathogen affecting plants, fruits, and vegetables. TeA is notably prevalent in European diets, however, TeA biomarkers of exposure and metabolites remain unknown. This research aims to bridge this knowledge-gap by gaining insights about human TeA exposure and metabolization. Nine subjects were divided into two groups. The first group received a single bolus of TeA at the Threshold of Toxicological Concern (TTC) to investigate the presence of TeA urinary biomarkers, while the second group served as a control. Sixty-nine urinary samples were prepared and analyzed using UPLC-Xevo TQ-XS for TeA quantification and UPLC-Orbitrap Exploris for polar metabolome acquisition. TeA was rapidly excreted during the first 13 h and the fraction extracted was 0.39 ± 0.22. The polar metabolome compounds effectively discriminating the two groups were filtered using Orthogonal Partial Least Squares-Discriminant Analysis and subsequently annotated (n = 122) at confidence level 4. Finally, the urinary metabolome was compared to in silico predicted TeA metabolites. Nine metabolites, including oxidized, N-alkylated, desaturated, glucuronidated, and sulfonated forms of TeA were detected.PMID:37951345 | DOI:10.1016/j.fct.2023.114183

Fitoterapia. 2023 Nov 9:105741. doi: 10.1016/j.fitote.2023.105741. Online ahead of print.ABSTRACTThe genus Acacia (Fabaceae) comprises >1350 species and has been used in traditional medicine as infusions and decoctions to treat wounds, sores, headaches, diarrhea, and cough. The leaf methanolic extracts of seven Acacia species growing in Egypt namely: Acacia saligna, Acacia seyal, Acacia xanthophloea, Acacia tortilis subsp. raddiana., Acacia tortilis, Acacia laeta, Acacia albida were analyzed using UPLC-QTOF-ESI-MS. A total of 37 polyphenols were identified and discussed in detail. They included phenolic acids, flavonoids, and procyanidins, among which sixteen polyphenols were identified in Acacia for the first time. Folin-ciocalteau assay and ferric reducing antioxidant power, cupric reducing antioxidant capacity, 2,20 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) cation radical and the scavenging capacity against 2,2-diphenyl-1- picrylhydrazyl radical were performed to investigate the total phenolic content and the antioxidant activity of the Acacia extracts, respectively. Furthermore, the absolute quantification of eighteen polyphenols common to most of the species was performed using UPLC-MS. It was evident that the differences in the chemical composition among the species accounted for the difference in antioxidant activity which was in line together with the total phenolic content.PMID:37951277 | DOI:10.1016/j.fitote.2023.105741

Sci Total Environ. 2023 Nov 9:168421. doi: 10.1016/j.scitotenv.2023.168421. Online ahead of print.ABSTRACTEngineered nanoparticles (ENPs) and nanoplastics (NPs) are typical nanoparticles in terrestrial environments. Till now, few studies have compared their toxicity and mechanism to plants. Here we investigated the effects of CuO, nZVI ENPs and polystyrene (PS) NPs on lettuce growth, metabolic functions, and microbial community structure. Results showed that low concentrations of nanoparticles decreased root biomass and promoted photosynthetic indicators, whereas increased reactive oxygen species (ROS) were detected in roots exposed to high concentrations of nanoparticles. High-dose CuO ENP exposure significantly raised the MDA content by 124.6 % compared to CK, causing the most severe membrane damage in the roots among the three types of nanoparticles. Although linoleic acid metabolism was down-regulated, the roots alleviated CuO stress by up-regulating galactose metabolism. Uptake of PS by roots similarly caused ROS production and activated the oxidative stress system by altering amino acid and vitamin metabolism. Faster microbial responses to nanoparticles were observed in the nZVI and PS networks. The root toxicity was indirectly mediated by ion release, NP uptake, or ROS generation, ultimately impacting root cell metabolism, rhizospheric microorganism and plant growth. These findings provide theoretical basis for assessing environmental impact of nanoparticles and their possible ecological risks.PMID:37951267 | DOI:10.1016/j.scitotenv.2023.168421

Sci Total Environ. 2023 Nov 9:168477. doi: 10.1016/j.scitotenv.2023.168477. Online ahead of print.ABSTRACTSoil contamination by indium, an emerging contaminant from electronics, has a negative impact on crop growth. Inhibition of root growth serves as a valuable biomarker for predicting indium phytotoxicity. Therefore, elucidating the molecular mechanisms underlying indium-induced root damage is essential for developing strategies to mitigate its harmful effects. Our transcriptomic findings revealed that indium affects the expression of numerous genes related to cell wall composition and metabolism in wheat roots. Morphological and compositional analysis revealed that indium induced a 2.9-fold thickening and a 17.5 % increase in the content of cell walls in wheat roots. Untargeted metabolomics indicated a substantial upregulation of the phenylpropanoid biosynthesis pathway. As the major end product of phenylpropanoid metabolism, lignin significantly accumulated in root cell walls after indium exposure. Together with increased lignin precursors, enhanced activity of lignin biosynthesis-related enzymes was observed. Moreover, analysis of the monomeric content and composition of lignin revealed a significant enrichment of p-hydroxyphenyl (H) and syringyl (S) units in root cell walls under indium stress. The present study contributes to the existing knowledge on indium toxicity and provides valuable insights for developing sustainable solutions to address the challenges posed by electronic waste and indium contamination on agroecosystems.PMID:37951262 | DOI:10.1016/j.scitotenv.2023.168477