PubMed

J Pharm Anal. 2023 Aug;13(8):836-850. doi: 10.1016/j.jpha.2023.06.011. Epub 2023 Jun 30.ABSTRACTBioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information, with its application to neuroscience termed neuroinformatics. Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms, which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases. Importantly, integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile. In this review, we first summarize data mining studies utilizing datasets from the individual type of omics analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and spatial omics, pertaining to Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We then discuss multi-omics integration approaches, including independent biological integration and unsupervised integration methods, for more intuitive and informative interpretation of the biological data obtained across different omics layers. We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks. Finally, we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery, therapeutic development, and elucidation of disease mechanisms. We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.PMID:37719197 | PMC:PMC10499660 | DOI:10.1016/j.jpha.2023.06.011

J Pharm Anal. 2023 Aug;13(8):851-861. doi: 10.1016/j.jpha.2023.07.003. Epub 2023 Jul 13.ABSTRACTTumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures. By interacting with the microenvironment, tumor cells undergo dynamic changes in gene expression and metabolism, resulting in spatiotemporal variations in their capacity for proliferation and metastasis. In recent years, the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis. By preserving location information while obtaining a large number of gene and molecular data, spatially resolved metabolomics (SRM) and spatially resolved transcriptomics (SRT) approaches can offer new ideas and reliable tools for the in-depth study of tumors. This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques, as well as a review of their applications in cancer-related fields.PMID:37719191 | PMC:PMC10499658 | DOI:10.1016/j.jpha.2023.07.003

PeerJ. 2023 Sep 11;11:e16010. doi: 10.7717/peerj.16010. eCollection 2023.ABSTRACTBACKGROUND: Previous studies have discussed the effects of grazing and house feeding on yaks during the cold season when forage is in short supply, but there is limited information on the effects of these feeding strategies on Jersey cows introduced to the Tibetan Plateau. The objective of this study was to use genomics and metabolomics analyses to examine changes in rumen microbiology and organism metabolism of Jersey cows with different feeding strategies.METHODS: We selected 12 Jersey cows with similar body conditions and kept them for 60 days under grazing (n = 6) and house-feeding (n = 6) conditions. At the end of the experiment, samples of rumen fluid and serum were collected from Jersey cows that had been fed using different feeding strategies. The samples were analyzed for rumen fermentation parameters, rumen bacterial communities, serum antioxidant and immunological indices, and serum metabolomics. The results of the study were examined to find appropriate feeding strategies for Jersey cows during the cold season on the Tibetan plateau.RESULTS: The results of rumen fermentation parameters showed that concentrations of acetic acid, propionic acid, and ammonia nitrogen in the house-feeding group (Group B) were significantly higher than in the grazing group (Group G) (P < 0.05). In terms of the rumen bacterial community 16S rRNA gene, the Chao1 index was significantly higher in Group G than in Group B (P = 0.038), while observed species, Shannon and Simpson indices were not significantly different from the above-mentioned groups (P > 0.05). Beta diversity analysis revealed no significant differences in the composition of the rumen microbiota between the two groups. Analysis of serum antioxidant and immune indices showed no significant differences in total antioxidant capacity between Group G and Group B (P > 0.05), while IL-6, Ig-M , and TNF-α were significantly higher in Group G than in Group B (P < 0.05). LC-MS metabolomics analysis of serum showed that a total of 149 major serum differential metabolites were found in Group G and Group B. The differential metabolites were enriched in the metabolic pathways of biosynthesis of amino acids, protein digestion and absorption, ABC transporters, aminoacyl-tRNA biosynthesis, mineral absorption, and biosynthesis of unsaturated fatty acids. These data suggest that the house-feeding strategy is more beneficial to improve the physiological state of Jersey cows on the Tibetan Plateau during the cold season when forages are in short supply.PMID:37719116 | PMC:PMC10501371 | DOI:10.7717/peerj.16010

Bio Protoc. 2023 Sep 5;13(17):e4808. doi: 10.21769/BioProtoc.4808. eCollection 2023 Sep 5.ABSTRACTThe flux in photosynthesis can be studied by performing 13CO2 pulse labelling and analysing the temporal labelling kinetics of metabolic intermediates using gas or liquid chromatography linked to mass spectrometry. Metabolic flux analysis (MFA) is the primary approach for analysing metabolic network function and quantifying intracellular metabolic fluxes. Different MFA approaches differ based on the metabolic state (steady vs. non-steady state) and the use of stable isotope tracers. The main methodology used to investigate metabolic systems is metabolite steady state associated with stable isotope labelling experiments. Specifically, in biological systems like photoautotrophic organisms, isotopic non-stationary 113C metabolic flux analysis at metabolic steady state with transient isotopic labelling (13C-INST-MFA) is required. The common requirement for metabolic steady state, alongside its very short half-timed reactions, complicates robust MFA of photosynthetic metabolism. While custom gas chambers design has addressed these challenges in various model plants, no similar tools were developed for liquid photosynthetic cultures (e.g., algae, cyanobacteria), where diffusion and equilibration of inorganic carbon species in the medium entails a new dimension of complexity. Recently, a novel tailor-made microfluidics labelling system has been introduced, supplying short 13CO2 pulses at steady state, and resolving fluxes across most photosynthetic metabolic pathways in algae. The system involves injecting algal cultures and medium containing pre-equilibrated inorganic 13C into a microfluidic mixer, followed by rapid metabolic quenching, enabling precise seconds-level label pulses. This was complemented by a 13CO2-bubbling-based open labelling system (photobioreactor), allowing long pulses (minutes-hours) required for investigating fluxes into central C metabolism and major products. This combined labelling procedure provides a comprehensive fluxome cover for most algal photosynthetic and central C metabolism pathways, thus allowing comparative flux analyses across algae and plants.PMID:37719071 | PMC:PMC10501915 | DOI:10.21769/BioProtoc.4808

Mol Microbiol. 2023 Sep 17. doi: 10.1111/mmi.15167. Online ahead of print.ABSTRACTHoney bees have emerged as a new model to study the gut-brain axis, as they exhibit complex social behaviors and cognitive abilities, while experiments with gnotobiotic bees have revealed that their gut microbiota alters both brain and behavioral phenotypes. Furthermore, while honey bee brain functions supporting a broad range of behaviors have been intensively studied for over 50 years, the gut microbiota of bees has been experimentally characterized only recently. Here, we combined six published datasets from metabolomic analyses to provide an overview of the neuroactive metabolites whose abundance in the gut, hemolymph and brain varies in presence of the gut microbiota. Such metabolites may either be produced by gut bacteria, released from the pollen grains during their decomposition by bacteria, or produced by other organs in response to different bacterial products. We describe the current state of knowledge regarding the impact of such metabolites on brain function and behavior and provide further hypotheses to explore in this emerging field of research.PMID:37718573 | DOI:10.1111/mmi.15167

Environ Pollut. 2023 Sep 15:122542. doi: 10.1016/j.envpol.2023.122542. Online ahead of print.ABSTRACTInsects are a diverse group of organisms that provide important ecosystem services like pollination, pest control, and decomposition and rely on olfaction to perform these services. In the Anthropocene, increasing concentrations of oxidant pollutants such as ozone have been shown to corrupt odor-driven behavior in insects by chemically degrading e.g. flower signals or insect pheromones. The degradation, however, does not only result in a loss of signals, but also in a potential enrichment of oxidation products, predominantly small carbonyls. Whether and how these oxidation products affect insect olfactory perception remains unclear. We examined the effects of ozone-generated small carbonyls on the olfactory behavior of the vinegar fly Drosophila melanogaster. We compiled a broad collection of neurophysiologically relevant odorants for the fly from databases and literature and predicted the formation of the types of stable small carbonyl products resulting from the odorant's oxidation by ozone. Based on these predictions, we evaluated the olfactory detection and behavioral impact of the ten most frequently predicted carbonyl products in the fly using single sensillum recordings (SSRs) and behavioral tests. Our results demonstrate that the fly's olfactory system can detect the oxidation products, which then elicit either attractive or neutral behavioral responses, rather than repulsion. However, certain products alter behavioral choices to an attractive odor source of balsamic vinegar. Our findings suggest that the enrichment of small carbonyl oxidation products due to increased ozone levels can affect olfactory guided insect behavior. Our study underscores the implications for odor-guided foraging in insects and the essential ecosystem services they offer under carbonyl enriched environments.PMID:37717892 | DOI:10.1016/j.envpol.2023.122542

Sci Total Environ. 2023 Sep 15:167043. doi: 10.1016/j.scitotenv.2023.167043. Online ahead of print.ABSTRACTBACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear.METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups.RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group.CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.PMID:37717771 | DOI:10.1016/j.scitotenv.2023.167043

J Chromatogr A. 2023 Sep 9;1708:464370. doi: 10.1016/j.chroma.2023.464370. Online ahead of print.ABSTRACTVarious forms of mycotoxins commonly exist in food and pose a significant risk to human health. Here a comprehensive suspect and nontarget screening strategy for both parent and modified mycotoxins was developed using ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLCHRMS). We constructed an in-house MS/MS database containing 82 mycotoxins in 8 categories. Then fragmentation characteristics of different classes of mycotoxins were rapidly extracted by a Python program "Fragmentation pattern screener (FPScreener)" and nontarget screening rules were determined by analyzing the frequencies and average intensities of fragmentation characteristics. Using the suspect and nontarget screening strategy, we successfully identified six parent mycotoxins and eight modified mycotoxins with different confidence levels in contaminated wheat and flour samples. This strategy enables screening of unknown parents and modified mycotoxins in food matrices with corresponding fragmentation characteristics.PMID:37717452 | DOI:10.1016/j.chroma.2023.464370

J Chromatogr A. 2023 Sep 3;1708:464343. doi: 10.1016/j.chroma.2023.464343. Online ahead of print.ABSTRACTMicrobial natural products, particularly nonribosomal peptides (NRPs), have attracted significant attention due to their structural diversity and therapeutic potential. Nocardia, a genus of Actinomyces, is an important reservoir for natural products, especially NRPs. However, rediscovery is a significant challenge for mining new specialized metabolites from Nocardia, as well as from other sources. To overcome this challenge, we developed a strategy that combines comparative genomics with tandem mass-based molecular networking, which allows to efficiently discover new NRPs from Nocardia spp.. As a proof of concept, all genomes of Norcardia in NCBI database, including three strains from our lab, were compared with each other to prioritize unique biosynthetic gene clusters (BGCs) in the three in-house Nocardia strains, particularly those containing nonribosomal peptide synthases (NRPSs). Subsequently, the metabolomics data of those three in-house strains were analyzed employing tandem mass-based molecular networking. This led to the identification of a known lipopeptide, nocarjamide (1), and five new congeners (2-6) of nocarjamide, as well as a new decalipopeptide, nocarlipoamide (7), along with nocardimicin, a known compound found in Nocardia. The structure of the new decalipopeptide 7 was further extensively characterized using NMR, MS/MS, Marfey's analysis, and X-ray. In addition, the biosynthesis pathways for 1-7 were proposed through bioinformatics analysis, and thus the gene clusters responsible for biosynthesizing them were confirmed. Our results indicate that this strategy enables prompt dereplication of known compounds, rapid linkage of identified compounds with their biosynthesis gene cluster, and efficient discovery of new compounds.PMID:37717450 | DOI:10.1016/j.chroma.2023.464343

J Hazard Mater. 2023 Sep 6;461:132503. doi: 10.1016/j.jhazmat.2023.132503. Online ahead of print.ABSTRACTParticle size is one of the most important factors in determining the biological toxicity of microplastics (MPs). In this study, we attempted to examine the systemic toxicity of polystyrene MPs of different sizes (0.5 µm MP1 and 5 µm MP2) in C57BL/6 J mice. After the mice were given oral gavage of MPs for 8 consecutive weeks, histopathology and molecular biology assays, 16 S rRNA sequencing of the gut microbiota, and untargeted metabolomics were performed. The results showed that MPs were distributed in the organs in a size-dependent manner, with smaller particles demonstrating greater biodistribution. Further analysis indicated that exposure to MPs caused multi-organ damage through distinct toxicity pathways. Specifically, exposure to 0.5 µm MP1 led to excessive accumulation and induced more serious inflammation and mechanical damage in the spleen, kidney, heart, lung, and liver. However, 5 µm MP2 led to more severe intestinal barrier dysfunction, as well as gut dysbiosis and metabolic disorder in association with neuroinflammation. These results are helpful in expanding our knowledge of the toxicity of MPs of different sizes in mammalian models.PMID:37717443 | DOI:10.1016/j.jhazmat.2023.132503

Plant Physiol Biochem. 2023 Sep 13;203:108039. doi: 10.1016/j.plaphy.2023.108039. Online ahead of print.ABSTRACTArbuscular mycorrhiza (AM) has been reported to influence secondary metabolism of Ocimum tenuiflorum L., thereby improving its therapeutic and commercial importance. To explain changes in the secondary metabolite profile, the study reports effects of AM on leaf metabolome of two high yielding genotypes of O. tenuiflorum inoculated with Rhizophagus intraradices. NMR-based non-targeted metabolic fingerprinting was related to changes at physiological, biochemical, and molecular levels in mycorrhizal (M) plants. AM resulted in higher accumulation of sucrose, which could be related with enhanced photosynthesis by virtue of increased uptake of mineral nutrients. A strong positive correlation between sucrose and net photosynthetic rate and sucrose and mineral nutrients supported that AM-mediated increase in uptake of mineral nutrients is associated with enhanced photosynthetic rate and accumulation of sucrose. Further, higher sucrose synthase activity resulted in increased glucose. Hexokinase activity was also higher in M plants resulting in higher pyruvate accumulation. On the contrary, Krebs cycle was compromised in M plants as evident by lower activities of its enzymes and concentrations of organic and amino acids. Nevertheless, AM increased activities and expressions of enzymes of terpenoid biosynthesis, shikimate, and phenylpropanoid pathways, thereby resulting in augmented production of terpenoids, phenylalanine, and phenols, respectively. Thus, metabolic reprogramming downstream of glycolysis was apparent wherein AMF resulted in more allocation of carbon resources to secondary metabolism as opposed to primary metabolism, which was supported by Pearson's correlation analysis. Higher C:N ratio in M plants explains the provision of more carbon resources to secondary metabolism as against primary metabolism.PMID:37717347 | DOI:10.1016/j.plaphy.2023.108039

Phytomedicine. 2023 Sep 3;120:155060. doi: 10.1016/j.phymed.2023.155060. Online ahead of print.ABSTRACTBACKGROUND: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity.PURPOSE: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus.METHODS: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity.RESULTS: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MSE spectra were compared with comprehensive databases.CONCLUSION: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.PMID:37717309 | DOI:10.1016/j.phymed.2023.155060

Acta Biochim Pol. 2023 Sep 17. doi: 10.18388/abp.2020_6858. Online ahead of print.ABSTRACTThe aim of this review is to specify new potential reliable and non-invasive methods for the diagnosis of biliary atresia (BA) that could shorten the way to diagnose BA, and finally the surgical treatment. Apart from the biomarkers that have been proven helpful and are used nowadays in neonatal wards, there are several new potential biomarkers that researchers have found to be helpful in the diagnosis of biliary atresia. Circulating microRNAs, matrix metalloproteinase-7, stool proteins, interleukin-33, Th17-associated cytokines, urinary metabolomics, anti-smooth muscle antibodies, heat shock proteins 90 and positive biliary epithelial cells CD56 are among those presented in this summary. These markers may play a new significant role in BA diagnosis. The described methods include Nomogram, Circulating microRNAs (miRNAs), Matrix metalloproteinase-7 (MMP-7), Stool proteins, Interleukin-33 (IL-33), Th17-associated cytokines, Alpha-aminoadipic acid and N-acetyl-d-mannosamine in urine, Anti-smooth muscle antibodies (ASMA), Heat shock proteins 90 (HSP90), Positive biliary epithelial cells CD56.PMID:37717264 | DOI:10.18388/abp.2020_6858

J Basic Microbiol. 2023 Sep 17. doi: 10.1002/jobm.202300319. Online ahead of print.ABSTRACTEndophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.PMID:37717245 | DOI:10.1002/jobm.202300319

Nat Commun. 2023 Sep 16;14(1):5744. doi: 10.1038/s41467-023-41515-z.ABSTRACTExperimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.PMID:37717037 | DOI:10.1038/s41467-023-41515-z

Cardiovasc Diabetol. 2023 Sep 16;22(1):252. doi: 10.1186/s12933-023-01912-6.ABSTRACTBACKGROUND: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk.METHODS: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models.RESULTS: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile.CONCLUSIONS: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD.TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).PMID:37716984 | DOI:10.1186/s12933-023-01912-6

Sci Total Environ. 2023 Sep 14:167039. doi: 10.1016/j.scitotenv.2023.167039. Online ahead of print.ABSTRACTCadmium (Cd), a predominant environmental pollutant, is a canonical toxicant that acts on the kidneys. However, the nephrotoxic effect and underlying mechanism activated by chronic exposure to Cd remain unclear. In the present study, male mice (C57BL/6J, 8 weeks) were treated with 0.6 mg/L cadmium chloride (CdCl2) administered orally for 6 months, and tubular epithelial cells (TCMK-1 cells) were treated with low-dose (1, 2, and 3 μM) CdCl2 for 72 h (h). Our study results revealed that environmental Cd exposure triggered ferroptosis and renal dysfunction. Spatially resolved metabolomics enabled delineation of metabolic profiles and visualization of the disruption to glutathione homeostasis related to ferroptosis in mouse kidneys. Multiomics analysis revealed that chronic Cd exposure induced glutathione redox imbalance that depended on STEAP3-driven lysosomal iron overload. In particular, glutathione metabolic reprogramming linked to ferroptosis emerged as a metabolic hallmark in the blood of Cd-exposed workers. In conclusion, this study provides the first evidence indicating that chronic Cd exposure triggers ferroptosis and renal dysfunction that depend on STEAP3-mediated glutathione redox imbalance, greatly increasing our understanding of the metabolic reprogramming induced by Cd exposure in the kidneys and providing novel clues linking chronic Cd exposure to nephrotoxicity.PMID:37716689 | DOI:10.1016/j.scitotenv.2023.167039

Int J Biol Macromol. 2023 Sep 14:126860. doi: 10.1016/j.ijbiomac.2023.126860. Online ahead of print.ABSTRACTAtractylodes chinensis (DC.) Koidz. polysaccharide (AKP) has been shown to have hypoglycemic activity. In this study, the effects of AKP on fecal microbiota and metabolites in healthy subjects and patients with type 2 diabetes mellitus (T2DM) were investigated using an in vitro simulated digestive fermentation model. AKP were isolated and purified from Atractylodes chinensis (DC.) Koidz. Its main component AKP1 (AKP-0 M, about 78 % of AKP) has an average molecular weight of 3.25 kDa with monosaccharide composition of rhamnose, arabinose, and galactosamine in a molar ratio of 1: 1.25: 2.88. Notably, AKP fermentation might improve the intestinal microbiota of T2DM patients by the enrichment of some specific bacteria rather than the increase of microbial diversity. The addition of AKP specifically enriched Bifidobacteriaceae and weakened the proportion of Escherichia-Shigella. Moreover, AKP also increased the levels of short-chain fatty acids without affecting total gut gas production, suggesting that AKP could have beneficial effects while avoiding flatulence. Metabolomic analysis revealed that ARP fermentation caused changes in some metabolites, which were mainly related to energy metabolism and amino acid metabolism. Importantly, ARP fermentation significantly increased the level of myo-inositol, an insulin sensitizer. In addition, a significant correlation was observed between specific microbiota and differential metabolites. This study has laid a theoretical foundation for AKP application in functional foods.PMID:37716665 | DOI:10.1016/j.ijbiomac.2023.126860

Int J Biol Macromol. 2023 Sep 14:126831. doi: 10.1016/j.ijbiomac.2023.126831. Online ahead of print.ABSTRACTThe variety of species can be efficiently increased by interspecific hybridization. However, because the males in the hybrid progeny are usually sterile, this heterosis cannot be employed when other cattle and yaks are hybridized. While some system-level studies have sought to explore the etiological basis for male cattle-yak sterility, no systematic cellular analyses of this phenomenon have yet been performed. Here, single-cell RNA sequencing and UPHLC-MS/MS targeted metabolomics methods were used to study the differences in testicular tissue between 4-year-old male yak and 4-year-old male cattle-yak, providing new and comprehensive insights into the causes of male cattle-yak sterility. Cattle-yak testes samples detected 6 somatic cell types and one mixed germ cell type. Comparisons of these cell types revealed the more significant differences in Sertoli cells (SCs) and [Leydig cells and myoid cells (LCs_MCs)] between yak and cattle-yak samples compared to other somatic cell clusters. Even though the LCs and MCs from yaks and cattle-yaks were derived from the differentiation of the same progenitor cells, a high degree of overlap between LCs and MCs was observed in yak samples. Still, only a small overlap between LCs and MCs was observed in cattle-yak samples. Functional enrichment analyses revealed that genes down-regulated in cattle-yak SCs were primarily enriched in biological activity, whereas up-regulated genes in these cells were enriched for apoptotic activity. Furthermore, the genes of up-regulated in LCs_MCs of cattle-yak were significantly enriched in enzyme inhibitor and molecular function inhibitor activity. On the other hand, the genes of down-regulated in these cells were enriched for signal receptor binding, molecular function regulation, positive regulation of biological processes, and regulation of cell communication activity. The most significant annotated differences between yak and cattle-yak LCs_MCs were associated with cell-to-cell communication. While yak LCs_MCs regulated spermatogenic cells at spermatogonia, spermatocyte, and spermatid levels, no such relationships were found between cattle-yak LCs_MCs and germ cells. This may suggest that the somatic niche in male cattle-yak testes is a microenvironment that is ultimately not favorable for spermatogenesis.PMID:37716658 | DOI:10.1016/j.ijbiomac.2023.126831

Chemosphere. 2023 Sep 14:140189. doi: 10.1016/j.chemosphere.2023.140189. Online ahead of print.ABSTRACTCadmium sulfide nanomaterials are of great concern because of their potential toxicity and unavoidable releases due to multiple commercial applications of nanoparticles (NPs). Commercial NPs act as mediators of damage to plant cells and pose potential toxicity to plants and human health. In the current study, investigated the phytotoxicology, absorption, translocation, antioxidant enzyme activity, and metabolic profiles of maize (Zea mays L.) seedlings exposed to different hydroponic treatments for fifteen days. The different concentrations of CdS NPs (3, 15, 30, 50, and 100 mg/L), 0.3 mg/L Cd ions, and unexposed control were performed in treatments. The results indicated that CdS NPs could present phytotoxic effects on seed germination and root elongation. Compared to the control, the CdS NPs dramatically reduced the shoots and root biomass, as well as the shape of the roots. Transmission electron microscopy and energy-dispersive mapping confirmed that CdS NPs could penetrate the maize root epidermis and bioaccumulate in the shoots with high concentrations. According to metabolomics studies, exposure to CdS NPs and Cd ions would result in metabolic disruption. Based on the statistical analysis, 290 out of 336 metabolites (86.30%) were obviously inhibited. The findings of this study demonstrated possible risks of emerging potential toxic NPs, and the release of these NPs to environment is a serious concern for agricultural activities.PMID:37716569 | DOI:10.1016/j.chemosphere.2023.140189