Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Age and sex dependent effects of metabolic response to muscle contraction

Mon, 03/07/2023 - 12:00
bioRxiv. 2023 Jun 1:2023.05.30.542769. doi: 10.1101/2023.05.30.542769. Preprint.ABSTRACTSarcopenia, the age-related loss of muscle mass and function, contributes to decreased quality of life in the elderly and increased healthcare costs. Decreased skeletal muscle mass, specific force, increased overall fatty depositions in the skeletal muscle, frailty and depressed energy maintenance are all associated with increased oxidative stress and the decline in mitochondrial function with age. We hypothesized that elevated mitochondrial stress with age alters the capacity of mitochondria to utilize different substrates following muscle contraction. To test this hypothesis, we designed two in vivo muscle-stimulation protocols to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise to characterize the effect of age and sex on mitochondrial substrate utilization in skeletal muscle following muscle contraction. Following HII stimulation, mitochondria from young skeletal muscle increased fatty acid oxidation compared to non-stimulated control muscle; however, mitochondria from aged muscle decreased fatty acid oxidation. In contrast, following LISS, mitochondrial from young skeletal muscle decreased fatty acid oxidation, whereas aged mitochondria increased fatty acid oxidation. We also found that HII can inhibit mitochondrial oxidation of glutamate in both stimulated and non-stimulated aged muscle, suggesting HII initiates circulation of an exerkine capable of altering whole-body metabolism. Analyses of the muscle metabolome indicates that changes in metabolic pathways induced by HII and LISS contractions in young muscle are absent in aged muscle. Treatment with elamipretide, a mitochondrially targeted peptide, restored glutamate oxidation and metabolic pathway changes following HII suggesting rescuing redox status and improving mitochondrial function in aged muscle enhances the metabolic response to muscle contraction.PMID:37398086 | PMC:PMC10312519 | DOI:10.1101/2023.05.30.542769

In Vivo Tissue Distribution of Microplastics and Systemic Metabolomic Alterations After Gastrointestinal Exposure

Mon, 03/07/2023 - 12:00
bioRxiv. 2023 Jun 3:2023.06.02.542598. doi: 10.1101/2023.06.02.542598. Preprint.ABSTRACTGlobal plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored. To investigate the impact of ingested MPs on target metabolomic pathways, mice were subjected to either polystyrene microspheres or a mixed plastics (5 µm) exposure consisting of polystyrene, polyethylene and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid). Exposures were performed twice a week for four weeks at a dose of either 0, 2, or 4 mg/week via oral gastric gavage. Our findings demonstrate that, in mice, ingested MPs can pass through the gut barrier, be translocated through the systemic circulation, and accumulate in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolomic changes that occur in the colon, liver and brain which show differential responses that are dependent on dose and type of MPs exposure. Lastly, our study provides proof of concept for identifying metabolomic alterations associated with MPs exposure and adds insight into the potential health risks that mixed MPs contamination may pose to humans.PMID:37398080 | PMC:PMC10312509 | DOI:10.1101/2023.06.02.542598

The landscape of cancer rewired GPCR signaling axes

Mon, 03/07/2023 - 12:00
bioRxiv. 2023 Jun 3:2023.03.13.532291. doi: 10.1101/2023.03.13.532291. Preprint.ABSTRACTWe explored the dysregulation of GPCR ligand signaling systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived a network of interacting ligands and biosynthetic enzymes of organic ligands to infer extracellular activation processes, which we combined with cognate GPCRs and downstream effectors to predict GPCR signaling pathway activation. We found multiple GPCRs that are differentially regulated together with their ligands across cancers and revealed a widespread perturbation of these signaling axes in specific cancer molecular subtypes. We showed that biosynthetic pathway enrichment from enzyme expression recapitulated pathway activity signatures from metabolomics datasets, therefore providing valuable surrogate information for GPCRs responding to organic ligand systems. The expression of several GPCRs signaling components was significantly associated with patient survival in a cancer subtype specific fashion. In particular, the expression of both receptor-ligand, as well as receptor-biosynthetic enzymes interaction partners improved the stratification of patients based on survival, suggesting a potential synergistic role for the activation of specific GPCR networks in modulating cancer phenotypes. Remarkably, we identified many receptor-ligand or enzyme pairs to be significantly associated with patient survival across several cancer molecular subtypes. Furthermore, we found that GPCRs from these actionable axes are the targets of multiple drugs displaying anti-growth effects in large, drug repurposing screens in cancer cells. This study provides a comprehensive map of GPCR signaling axes that can be exploited as actionable targets for personalized cancer treatments. We have made the results generated in this study freely available for further exploration to the community through a webapp (gpcrcanceraxes.bioinfolab.sns.it).PMID:37398064 | PMC:PMC10312480 | DOI:10.1101/2023.03.13.532291

Dissecting the effects of paraquat-induced pulmonary injury in rats using UPLC-Q-TOF-MS/MS-based metabonomics

Mon, 03/07/2023 - 12:00
Toxicol Res (Camb). 2023 May 31;12(3):527-538. doi: 10.1093/toxres/tfad040. eCollection 2023 Jun.ABSTRACTOBJECTIVE: Paraquat (PQ) is a toxic compound that selectively accumulates in the lungs, inducing severe pulmonary inflammation and fibrosis. However, data on the metabolomic changes induced by the PQ remain scant. This study aimed to determine the metabolic changes in Sprague-Dawley rats subjected to PQ using UPLC-Q-TOF-MS/MS.METHODS: We established groups of PQ-induced pulmonary injury rats for 14 or 28 days.RESULTS: Our data showed that PQ decreased the survival of the rats and induced pulmonary inflammation at day 14 or pulmonary fibrosis at day 28. There was upregulation of IL-1β expression in the inflammation group as well as upregulation of fibronectin, collagen and α-SMA in the pulmonary fibrosis group. OPLS-DA revealed differential expression of 26 metabotites between the normal and the inflammation groups; 31 plasma metabotites were also differently expressed between the normal and the fibrosis groups. There was high expression of lysoPc160-, hydroxybutyrylcarnitine, stearic acid, and imidazolelactic acid in the pulmonary injury group compared to the normal group.CONCLUSION: Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. This study gives insights into the mechanisms of PQ-induced lung injury and highlights the potential therapeutic targets.NONSTRUCTURED ABSTRACT: The effect of PQ on lung injury in rats was detected by metabonomics, and the possible metabolic mechanism was investigated by KEGG analysis. OPLS-DA revealed the differential expression of 26 metabotites and 31 plasma metabotites between the normal and the pulmonary injury groups. Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. Oleoylethanolamine, stearic acid, and imidazolelactic acid are potential molecular markers in PQ-induced pulmonary injury.PMID:37397915 | PMC:PMC10311158 | DOI:10.1093/toxres/tfad040

Metabolic and transcriptomic analyses elucidate a novel insight into the network for biosynthesis of carbohydrate and secondary metabolites in the stems of a medicinal orchid <em>Dendrobium nobile</em>

Mon, 03/07/2023 - 12:00
Plant Divers. 2022 Oct 27;45(3):326-336. doi: 10.1016/j.pld.2022.10.004. eCollection 2023 May.ABSTRACTDendrobium nobile is an important medicinal and nutraceutical herb. Although the ingredients of D. nobile have been identified as polysaccharides, alkaloids, amino acids, flavonoids and bibenzyls, our understanding of the metabolic pathways that regulate the synthesis of these compounds is limited. Here, we used transcriptomic and metabolic analyses to elucidate the genes and metabolites involved in the biosynthesis of carbohydrate and several secondary metabolites in the stems of D. nobile. A total of 1005 metabolites and 31,745 genes were detected in the stems of D. nobile. The majority of these metabolites and genes were involved in the metabolism of carbohydrates (fructose, mannose, glucose, xylulose and starch), while some were involved in the metabolism of secondary metabolites (alkaloids, β-tyrosine, ferulic acid, 4-hydroxybenzoate and chrysin). Our predicted regulatory network indicated that five genes (AROG, PYK, DXS, ACEE and HMGCR) might play vital roles in the transition from carbohydrate to alkaloid synthesis. Correlation analysis identified that six genes (ALDO, PMM, BGLX, EGLC, XYLB and GLGA) were involved in carbohydrate metabolism, and two genes (ADT and CYP73A) were involved in secondary metabolite biosynthesis. Our analyses also indicated that phosphoenol-pyruvate (PEP) was a crucial bridge that connected carbohydrate to alkaloid biosynthesis. The regulatory network between carbohydrate and secondary metabolite biosynthesis established will provide important insights into the regulation of metabolites and biological systems in Dendrobium species.PMID:37397599 | PMC:PMC10311107 | DOI:10.1016/j.pld.2022.10.004

Editorial: Hallmark of cancer: avoiding immune suppression

Mon, 03/07/2023 - 12:00
Front Oncol. 2023 Jun 16;13:1211456. doi: 10.3389/fonc.2023.1211456. eCollection 2023.NO ABSTRACTPMID:37397369 | PMC:PMC10313128 | DOI:10.3389/fonc.2023.1211456

Molecular networking identifies an AHR-modulating benzothiazole from white button mushrooms (<em>Agaricus bisporus</em>)

Mon, 03/07/2023 - 12:00
J Funct Foods. 2023 Jul;106:105602. doi: 10.1016/j.jff.2023.105602. Epub 2023 Jun 7.ABSTRACTDiet-derived aryl hydrocarbon receptor (AHR) ligands have potential to maintain gut health. However, among the myriad bioactive compounds from foods, identifying novel functional ligands which would significantly impact gastrointestinal health is a challenge. In this study, a novel AHR modulator is predicted, identified, and characterized in the white button mushroom (Agaricus bisporus). Using a molecular networking approach, a methylated analog to benzothiazole was indicated in white button mushrooms, which was subsequently isolated and identified as 2-amino-4-methyl-benzothiazole(2A4). Cell-based AHR transcriptional assays revealed that 2-amino-4-methyl-benzothiazole possesses agonistic activity and upregulated CYP1A1 expression. This contrasts with previous findings that whole white button mushroom extract has overall antagonistic activity in vivo, underscoring the importance of studying the roles each chemical component plays in a whole food. The findings suggest that 2-amino-4-methyl-benzothiazole is a previously unidentified AHR modulator from white button mushroom and demonstrate that molecular networking has potential to identify novel receptor modulators from natural products.PMID:37397272 | PMC:PMC10312048 | DOI:10.1016/j.jff.2023.105602

Metabolomics in aging research: aging markers from organs

Mon, 03/07/2023 - 12:00
Front Cell Dev Biol. 2023 Jun 16;11:1198794. doi: 10.3389/fcell.2023.1198794. eCollection 2023.ABSTRACTMetabolism plays an important role in regulating aging at several levels, and metabolic reprogramming is the main driving force of aging. Due to the different metabolic needs of different tissues, the change trend of metabolites during aging in different organs and the influence of different levels of metabolites on organ function are also different, which makes the relationship between the change of metabolite level and aging more complex. However, not all of these changes lead to aging. The development of metabonomics research has opened a door for people to understand the overall changes in the metabolic level in the aging process of organisms. The omics-based "aging clock" of organisms has been established at the level of gene, protein and epigenetic modifications, but there is still no systematic summary at the level of metabolism. Here, we reviewed the relevant research published in the last decade on aging and organ metabolomic changes, discussed several metabolites with high repetition rate, and explained their role in vivo, hoping to find a group of metabolites that can be used as metabolic markers of aging. This information should provide valuable information for future diagnosis or clinical intervention of aging and age-related diseases.PMID:37397261 | PMC:PMC10313136 | DOI:10.3389/fcell.2023.1198794

Integrated metabolomics and peptidomics to delineate characteristic metabolites in milk fermented with novel <em>Lactiplantibacillus plantarum</em> L3

Mon, 03/07/2023 - 12:00
Food Chem X. 2023 Jun 1;18:100732. doi: 10.1016/j.fochx.2023.100732. eCollection 2023 Jun 30.ABSTRACTA novel wild-type Lactiplantibacillus plantarum (L. plantarum) L3 with good fermentation characteristics and protein degradation capacity was isolated from raw milk samples. In this study, the metabolites in milk fermented with L. plantarum L3 were investigated by metabolomic and peptidomics analyses. The metabolomics results revealed that the metabolites in milk fermented with L. plantarum L3 were Thr-Pro, Val-Lys, l-creatine, pyridoxine, and muramic acid, which improved the taste and nutritional qualities of the milk. Moreover, the water-soluble peptides derived from L3 fermented milk exhibited high antioxidant properties and angiotensin I-converting enzyme inhibitory (ACEI) activities. Additionally, 152 peptides were found using liquid chromatography-mass spectrometry (LC-MS/MS). Furthermore, endogenous enzymes secreted by L. plantarum L3 cleaved β- and α-casein to release six ACEI peptides (ACEIPs), nineteen antioxidant peptides (AOPs), and five antimicrobial peptides (AMPS). Overall, these findings could be valuable in improving the quality of fermented milk.PMID:37397209 | PMC:PMC10314206 | DOI:10.1016/j.fochx.2023.100732

Insight into the relationship between metabolite dynamic changes and microorganisms of sea urchin (<em>S. intermedius</em>) gonads during storage

Mon, 03/07/2023 - 12:00
Food Chem X. 2023 May 29;18:100727. doi: 10.1016/j.fochx.2023.100727. eCollection 2023 Jun 30.ABSTRACTSea urchin gonads have high nutritional value and degenerate rapidly during storage. Previous assessment of the freshness of sea urchin gonads was based on experience without valid biochemical indicators. Thus, the current study is to find biochemical indicators representing the freshness of sea urchin gonads. Results showed that the dominant genera of sea urchin gonads were changed from Psychromonas, Ralstonia, and Roseimarinus to Aliivibrio, Psychrilyobacter, and Photobacterium. The differential metabolites of sea urchin gonads were mainly produced through amino acids metabolism. Among them, GC-TOF-MS based differential metabolites had the greatest enrichment in the valine, leucine and isoleucine biosynthesis pathway, while LC-MS based differential metabolites had the greatest enrichment in the alanine, aspartate and glutamate metabolism pathway. The growth of dominant genus (Aliivibrio) had a great influence on the production of differential metabolites. These results will provide valuable information for accurately judging the freshness and shelf life of sea urchin gonads.PMID:37397197 | PMC:PMC10314180 | DOI:10.1016/j.fochx.2023.100727

Metabolomics revealed metabolite biomarkers of antioxidant properties and flavonoid metabolite accumulation in purple rice after grain filling

Mon, 03/07/2023 - 12:00
Food Chem X. 2023 May 24;18:100720. doi: 10.1016/j.fochx.2023.100720. eCollection 2023 Jun 30.ABSTRACTThe correlation between flavonoids, phenolic metabolites and the total antioxidant capacity is well established. However, specific biomarkers of metabolites with antioxidant properties in purple rice grains remain unidentified. This study integrated nontargeted metabolomics, quantitative detection of flavonoids and phenolic compounds, and physiological and biochemical data to identify metabolite biomarkers of the antioxidant properties of purple rice grains after filling. The findings demonstrated a significant enhancement in the biosynthesis of flavonoids during the middle and late filling stages in purple rice grains. Additionally, the pathways involved in anthocyanin and flavonoid biosynthesis were significantly enriched. Catalase (CAT), phenylalanine ammonia-lyase (PAL), total phenols (TP), flavonoids (FD), and oligomeric proanthocyanidin (OPC) were significantly correlated with philorizin, myricetin 3-galactoside, and trilobatin. Phlorizin, myricetin 3-galactoside, and trilobatin were metabolite biomarkers of antioxidant properties in purple rice grains. This study provides new ideas for the cultivation of high-quality coloured rice varieties with high antioxidant activity.PMID:37397194 | PMC:PMC10314141 | DOI:10.1016/j.fochx.2023.100720

Study on taste quality formation and leaf conducting tissue changes in six types of tea during their manufacturing processes

Mon, 03/07/2023 - 12:00
Food Chem X. 2023 May 27;18:100731. doi: 10.1016/j.fochx.2023.100731. eCollection 2023 Jun 30.ABSTRACTThis study fristly investigated the taste quality formation and leaf conducting tissue changes in six types of Chinese tea (green, black, oolong, yellow, white, and dark) made from Mingke No.1 variety. Non-targeted metabolomics showed the vital manufacturing processes (green tea-de-enzyming, black tea-fermenting, oolong tea-turning-over, yellow tea-yellowing, white tea-withering, and dark tea-pile-fermenting) were highly related to their unique taste formation, due to different fermentation degree in these processes. After drying, the retained phenolics, theanine, caffeine, and other substances significantly impacted each tea taste quality formation. Meanwhile, the tea leaf conducting tissue structure was significantly influenced by high processing temperature, and the change of its inner diameter was related to moisture loss during tea processing, as indicated by its significant different Raman characteristic peaks (mainly cellulose and lignin) in each key process. This study provides a reference for process optimization to improve tea quality.PMID:37397192 | PMC:PMC10314197 | DOI:10.1016/j.fochx.2023.100731

Comparative study of leaf nutrient reabsorption by two different ecotypes of wild soybean under low-nitrogen stress

Mon, 03/07/2023 - 12:00
PeerJ. 2023 Jun 27;11:e15486. doi: 10.7717/peerj.15486. eCollection 2023.ABSTRACTWild soybean (Glycine soja), the ancestor of cultivated soybean, has evolved into many ecotypes with different adaptations to adversity under the action of divergent evolution. Barren-tolerant wild soybean has developed adaptation to most nutrient-stress environments, especially with respect to low nitrogen (LN) conditions. This study describes the differences in physiological and metabolomic changes between common wild soybean (GS1) and barren-tolerant wild soybean(GS2) under LN stress. Compared with plants grown under the unstressed control (CK) conditions, the young leaves of barren-tolerant wild soybean under LN conditions maintained relatively stable chlorophyll, concentration and rates of photosynthesis and transpiration, as well as increased carotenoid content, whereas the net photosynthetic rate (PN) of GS1 decreased significantly 0.64-fold (p < 0.05) in the young leaves of GS1. The ratio of internal to atmospheric CO2 concentrations increased significantly 0.07-fold (p < 0.05), 0.09-fold (p < 0.05) in the young leaves of GS1 and GS2, respectively, and increased significantly 0.05-fold (p < 0.05) and 0.07-fold (p < 0.05) in the old leaves of GS1 and GS2, respectively, relative to the CK. The concentration of chlorophylls a and b decreased significantly 0.45-fold (p < 0.05), 0.13-fold (p > 0.05) in the young leaves of GS1 and GS2, respectively, and decreased significantly 0.74-fold (p < 0.01) and 0.60-fold (p < 0.01) in the old leaves of GS1 and GS2, respectively. Under LN stress, nitrate concentration in the young leaves of GS1 and GS2 decreased significantly 0.69- and 0.50-fold (p < 0.01), respectively, relative to CK, and decreased significantly 2.10-fold and 1.77-fold (p < 0.01) in the old leaves of GS1 and GS2, respectively. Barren-tolerant wild soybean increased the concentration of beneficial ion pairs. Under LN stress, Zn2+ significantly increased by 1.06- and 1.35-fold (p < 0.01) in the young and old leaves of GS2 (p < 0.01), but there was no significant change in GS1. The metabolism of amino acids and organic acids was high in GS2 young and old leaves, and the metabolites related to the TCA cycle were significantly increased. The 4-aminobutyric acid (GABA) concertation decreased significantly 0.70-fold (p < 0.05) in the young leaves of GS1 but increased 0.21-fold (p < 0.05) significantly in GS2. The relative concentration of proline increased significantly 1.21-fold (p < 0.01) and 2.85-fold (p < 0.01) in the young and old leaves of GS2. Under LN stress, GS2 could maintain photosynthesis rate and enhance the reabsorption of nitrate and magnesium in young leaves, compared to GS1. More importantly, GS2 exhibited increased amino acid and TCA cycle metabolism in young and old leaves. Adequate reabsorption of mineral and organic nutrients is an important strategy for barren-tolerant wild soybeans to survive under LN stress. Our research provides a new perspective on the exploitation and utilization of wild soybean resources.PMID:37397019 | PMC:PMC10312162 | DOI:10.7717/peerj.15486

Impact of cell-free supernatant of <em>lactic acid bacteria</em> on <em>Staphylococcus aureus</em> biofilm and its metabolites

Mon, 03/07/2023 - 12:00
Front Vet Sci. 2023 Jun 15;10:1184989. doi: 10.3389/fvets.2023.1184989. eCollection 2023.ABSTRACTINTRODUCTION: A safe bio-preservative agent, lactic acid bacteria (LAB) can inhibit the growth of pathogenic bacteria and spoilage organisms. Its cell-free supernatant (LAB-CFS), which is rich in bioactive compounds, is what makes LAB antibacterial work.METHODS: This study focused on the changes in biofilm activity and related metabolic pathways of S. aureus treated with lactic acid bacteria planktonic CFS (LAB-pk-CFS) and biofilm state (LAB-bf-CFS).RESULTS: The findings demonstrated that the LAB-CFS treatment considerably slowed Staphylococcus aureus (S. aureus) growth and prevented it from forming biofilms. Additionally, it inhibits the physiological traits of the S. aureus biofilm, including hydrophobicity, motility, eDNA, and PIA associated to the biofilm. The metabolites of S. aureus biofilm treated with LAB-CFS were greater in the LAB-bf-CFS than they were in the LAB-pk-CFS, according to metabolomics studies. Important metabolic pathways such amino acids and carbohydrates metabolism were among the most noticeably altered metabolic pathways.DISCUSSION: These findings show that LAB-CFS has a strong potential to combat S. aureus infections.PMID:37397004 | PMC:PMC10310794 | DOI:10.3389/fvets.2023.1184989

Microbiota-associated immunotherapy resistance caused by deficient PD-L2 - RGMb signaling

Mon, 03/07/2023 - 12:00
Oncoimmunology. 2023 Jun 28;12(1):2224679. doi: 10.1080/2162402X.2023.2224679. eCollection 2023.ABSTRACTIn a recent paper in Nature, Park et al. propose a mechanism through which intestinal dysbiosis compromises the efficacy of immunotherapy targeting the PD-L1/PD-1 interaction. Dysbiosis may upregulate a pair of checkpoint molecules, i.e. PD-L2 interacting with RGMb. Antibodies targeting PD-L2/RGMb can restore responses to PD-1 blockade in the context of dysbiosis.PMID:37396957 | PMC:PMC10308862 | DOI:10.1080/2162402X.2023.2224679

Multi-omics research on common allergens during the ripening of pollen and poplar flocs of <em>Populus deltoides</em>

Mon, 03/07/2023 - 12:00
Front Plant Sci. 2023 Jun 16;14:1136613. doi: 10.3389/fpls.2023.1136613. eCollection 2023.ABSTRACTBACKGROUND: Populus deltoides is widely cultivated in China and produces a large number of pollen and poplar flocs from March to June per year. Previous studies have found that the pollen of P. deltoides contains allergens. However, studies on the ripening mechanism of pollen/poplar flocs and their common allergens are very limited.METHODS: Proteomics and metabolomics were used to study the changes of proteins and metabolites in pollen and poplar flocs of P. deltoides at different developmental stages. Allergenonline database was used to identify common allergens in pollen and poplar flocs at different developmental stages. Western blot (WB) was used to detect the biological activity of common allergens between mature pollen and poplar flocs.RESULTS: In total, 1400 differently expressed proteins (DEPs) and 459 different metabolites (DMs) were identified from pollen and poplar flocs at different developmental stages. KEGG enrichment analysis showed that DEPs in pollen and poplar flocs were significantly enriched in ribosome and oxidative phosphorylation signaling pathways. The DMs in pollen are mainly involved in aminoacyl-tRNA biosynthesis and arginine biosynthesis, while the DMs in poplar flocs are mainly involved in glyoxylate and dicarboxylate metabolism. Additionally, 72 common allergens were identified in pollen and poplar flocs at different developmental stages. WB showed that there were distinct binding bands between 70 and 17KD at the two groups of allergens.CONCLUSIONS: A multitude of proteins and metabolites are closely related to the ripening of pollen and poplar flocs of Populus deltoides, and they contain common allergens between mature pollen and poplar flocs.PMID:37396639 | PMC:PMC10313134 | DOI:10.3389/fpls.2023.1136613

Role of untargeted omics biomarkers of exposure and effect for tobacco research

Mon, 03/07/2023 - 12:00
Addict Neurosci. 2023 Sep;7:100098. doi: 10.1016/j.addicn.2023.100098. Epub 2023 Apr 25.ABSTRACTTobacco research remains a clear priority to improve individual and population health, and has recently become more complex with emerging combustible and noncombustible tobacco products. The use of omics methods in prevention and cessation studies are intended to identify new biomarkers for risk, compared risks related to other products and never use, and compliance for cessation and reinitation. to assess the relative effects of tobacco products to each other. They are important for the prediction of reinitiation of tobacco use and relapse prevention. In the research setting, both technical and clinical validation is required, which presents a number of complexities in the omics methodologies from biospecimen collection and sample preparation to data collection and analysis. When the results identify differences in omics features, networks or pathways, it is unclear if the results are toxic effects, a healthy response to a toxic exposure or neither. The use of surrogate biospecimens (e.g., urine, blood, sputum or nasal) may or may not reflect target organs such as the lung or bladder. This review describes the approaches for the use of omics in tobacco research and provides examples of prior studies, along with the strengths and limitations of the various methods. To date, there is little consistency in results, likely due to small number of studies, limitations in study size, the variability in the analytic platforms and bioinformatic pipelines, differences in biospecimen collection and/or human subject study design. Given the demonstrated value for the use of omics in clinical medicine, it is anticipated that the use in tobacco research will be similarly productive.PMID:37396411 | PMC:PMC10310069 | DOI:10.1016/j.addicn.2023.100098

High-quality genome assembly and multi-omics analysis of pigment synthesis pathway in <em>Auricularia cornea</em>

Mon, 03/07/2023 - 12:00
Front Microbiol. 2023 Jun 15;14:1211795. doi: 10.3389/fmicb.2023.1211795. eCollection 2023.ABSTRACTOwing to its great market potential for food and health care, white Auricularia cornea, a rare edible fungus, has received increased attention in recent years. This study presents a high-quality genome assembly of A. cornea and multi-omics analysis of its pigment synthesis pathway. Continuous Long Reads libraries, combined with Hi-C-assisted assembly were used to assemble of white A. cornea. Based on this data, we analyzed the transcriptome and metabolome of purple and white strains during the mycelium, primordium, and fruiting body stages. Finally, we obtained the genome of A.cornea assembled from 13 clusters. Comparative and evolutionary analysis suggests that A.cornea is more closely related to Auricularia subglabra than to Auricularia heimuer. The divergence of white/purple A.cornea occurred approximately 40,000 years ago, and there were numerous inversions and translocations between homologous regions of the two genomes. Purple strain synthesized pigment via the shikimate pathway. The pigment in the fruiting body of A. cornea was γ-glutaminyl-3,4-dihydroxy-benzoate. During pigment synthesis, α-D-glucose-1P, citrate, 2-Oxoglutarate, and glutamate were four important intermediate metabolites, whereas polyphenol oxidase and other 20 enzyme genes were the key enzymes. This study sheds light on the genetic blueprint and evolutionary history of the white A.cornea genome, revealing the mechanism of pigment synthesis in A.cornea. It has important theoretical and practical implications for understanding the evolution of basidiomycetes, molecular breeding of white A.cornea, and deciphering the genetic regulations of edible fungi. Additionally, it provides valuable insights for the study of phenotypic traits in other edible fungi.PMID:37396365 | PMC:PMC10308021 | DOI:10.3389/fmicb.2023.1211795

Human blood plasma biomarkers of diet and weight loss among centrally obese subjects in a New Nordic Diet intervention

Mon, 03/07/2023 - 12:00
Front Nutr. 2023 Jun 15;10:1198531. doi: 10.3389/fnut.2023.1198531. eCollection 2023.ABSTRACTSCOPE: The New Nordic Diet (NND) has been shown to promote weight loss and lower blood pressure amongst obese people. This study investigates blood plasma metabolite and lipoprotein biomarkers differentiating subjects who followed Average Danish Diet (ADD) or NND. The study also evaluates how the individual response to the diet is reflected in the metabolic differences between NND subjects who lost or maintained their pre-intervention weight.METHODS: Centrally obese Danes (BMI >25) followed NND (90 subjects) or ADD (56 subjects) for 6 months. Fasting blood plasma samples, collected at three time-points during the intervention, were screened for metabolites and lipoproteins (LPs) using proton nuclear magnetic resonance spectroscopy. In total, 154 metabolites and 65 lipoproteins were analysed.RESULTS: The NND showed a relatively small but significant effect on the plasma metabolome and lipoprotein profiles, with explained variations ranging from 0.6% for lipoproteins to 4.8% for metabolites. A total of 38 metabolites and 11 lipoproteins were found to be affected by the NND. The primary biomarkers differentiating the two diets were found to be HDL-1 cholesterol, apolipoprotein A1, phospholipids, and ketone bodies (3-hydroxybutyric acid, acetone, and acetoacetic acid). The increased levels of ketone bodies detected in the NND group inversely associated with the decrease in diastolic blood pressure of the NND subjects. The study also showed that body weight loss among the NND subjects was weakly associated with plasma levels of citrate.CONCLUSION: The main plasma metabolites associated with NND were acetate, methanol and 3-hydroxybutyrate. The metabolic changes associated with the NND-driven weight loss are mostly pronounced in energy and lipid metabolism.PMID:37396134 | PMC:PMC10308042 | DOI:10.3389/fnut.2023.1198531

<em>In vivo</em> evaluation of an innovative synbiotics on stage IIIb-IV chronic kidney disease patients

Mon, 03/07/2023 - 12:00
Front Nutr. 2023 Jun 15;10:1215836. doi: 10.3389/fnut.2023.1215836. eCollection 2023.ABSTRACTBACKGROUND: Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in the presence of an altered intestinal permeability, gut-derived uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (PCS), can accumulate in the blood.METHODS: In a scenario facing the nutritional management as adjuvant therapy, the present study assessed the effectiveness of an innovative synbiotics for its ability to modulate the patient gut microbiota and metabolome by setting a randomized, single-blind, placebo-controlled, pilot trial accounting for IIIb-IV stage CKD patients and healthy controls. Metataxonomic fecal microbiota and fecal volatilome were analyzed at the run-in, after 2 months of treatment, and after 1 month of wash out.RESULTS: Significant changes in microbiota profile, as well as an increase of the saccharolytic metabolism, in feces were found for those CKD patients that were allocated in the synbiotics arm.CONCLUSIONS: Noteworthy, the here analyzed data emphasized a selective efficacy of the present synbiotics on a stage IIIb-IV CKD patients. Nonetheless, a further validation of this trial accounting for an increased patient number should be considered.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT03815786.PMID:37396126 | PMC:PMC10311028 | DOI:10.3389/fnut.2023.1215836

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