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

Biochar inoculated with Pseudomonas putida alleviates its inhibitory effect on biodegradation pathways in phenanthrene-contaminated soil

Wed, 20/09/2023 - 12:00
J Hazard Mater. 2023 Sep 14;461:132550. doi: 10.1016/j.jhazmat.2023.132550. Online ahead of print.ABSTRACTControversial results are reported whereby biodegradation of polycyclic aromatic hydrocarbons (PAHs) can be promoted or inhibited by biochar amendment of soil. Metabolomics was applied to analyze the metabolic profiles of amendment with biochar (BB) and biochar inoculated with functional bacteria (Pseudomonas putida) (BP) involved in phenanthrene (PHE) degradation. Additionally, metagenomic analysis was utilized to assess the impact of different treatments on PHE degradation by soil microorganisms. Results indicated that BB treatment decreased the PHE biodegradation of the soil indigenous bacterial consortium, but BP treatment alleviated this inhibitory effect. Metabolomics revealed the differential metabolite 9-phenanthrol was absent in the BB treatment, but was found in the control group (CK), and in the treatment inoculated with the Pseudomonas putida (Ps) and the BP treatment. Metagenomic analysis showed that biochar decreased the abundance of the cytochrome P450 monooxygenase (CYP116), which was detected in the Pseudomonas putida, thus alleviating the inhibitory effect of biochar on PHE degradation. Moreover, a noticeable delayed increase of functional gene abundance and enzymes abundance in the BB treatment was observed in the PHE degradation pathway. Our findings elucidate the mechanism of inhibition with biochar amendment and the alleviating effect of biochar inoculated with degrading bacteria.PMID:37729712 | DOI:10.1016/j.jhazmat.2023.132550

Composting Post-Anaerobic Digestion for Emerging Contaminant Biodegradation: Impacts of Operating Conditions

Wed, 20/09/2023 - 12:00
J Environ Qual. 2023 Sep 20. doi: 10.1002/jeq2.20515. Online ahead of print.ABSTRACTSustainable manure management technologies are needed, and combining anaerobic digestion (AD) for energy generation and aerobic composting (AC) to stabilize digestate and remove emerging contaminants (ECs), including veterinary pharmaceuticals and steroid hormones, is promising. This study identified post AD, AC operating conditions that maximized degradation of study ECs, expected to be present in cattle manure digested using treated municipal wastewater as the water source. Study ECs included sulfamethoxazole (SMX), chlortetracycline (CTC), oxytetracycline (OTC), estrone (E1), and naproxen (NPX). Composting conditions were simulated in bench-scale reactors, with microorganisms from digestate produced in an AD system (25L scale), by varying temperatures, pH, and carbon source compositions (representing food waste/manure co-digestion with different residence times). Results indicate maximum SMX biodegradation happened at 35°C, pH 7, and with high levels of easily degradable carbon (≥99, 99, 98%), and maximum E1 biodegradation occurred at 35°C, and with low levels of easily degradable carbon (≥97, 99%). Abiotic degradation was responsible for nearly complete removal of tetracyclines under all conditions and for partial degradation of NPX (between 20-48%). Microorganisms originating from the AD system putatively capable of SMX and E1 biodegradation, or of contributing to biodegradation during the AC phase, were identified, including phylotypes previously shown to biodegrade SMX (Brevundimonas and Alcaligenes). This article is protected by copyright. All rights reserved.PMID:37729590 | DOI:10.1002/jeq2.20515

Chemical Exposure Highlighted without Any <em>A Priori</em> Information in an Epidemiological Study by Metabolomic FT-ICR-MS Fingerprinting at High Throughput and High Resolution

Wed, 20/09/2023 - 12:00
Chem Res Toxicol. 2023 Sep 20. doi: 10.1021/acs.chemrestox.3c00158. Online ahead of print.ABSTRACTEpidemiological studies aim to assess associations between diseases and risk factors. Such investigations involve a large sample size and require powerful analytical methods to measure the effects of risk factors, resulting in a long analysis time. In this study, chemical exposure markers were detected as the main variables strongly affecting two components coming from a principal component analysis (PCA) exploration of the metabolomic data generated from urinary samples collected on a cohort of about 500 individuals using direct introduction coupled with a Fourier-transform ion cyclotron resonance instrument. The assignment of their chemical identity was first achieved based on their isotopic fine structures detected at very high resolution (Rp > 900,000). Their identification as dimethylbiguanide and sotalol was obtained at level 1, thanks to the available authentic chemical standards, tandem mass spectrometry (MS/MS) experiments, and collision cross section measurements. Epidemiological data confirmed that the subjects discriminated by PCA had declared to be prescribed these drugs for either type II diabetes or cardiac arrhythmia. Concentrations of these drugs in urine samples of interest were also estimated by rapid quantification using an external standard calibration method, direct introduction, and MS/MS experiments. Regression analyses showed a good correlation between the estimated drug concentrations and the scores of individuals distributed on these specific PCs. The detection of these chemical exposure markers proved the potential of the proposed high-throughput approach without any prior drug exposure knowledge as a powerful emerging tool for rapid and large-scale phenotyping of subjects enrolled in epidemiological studies to rapidly characterize the chemical exposome and adherence to medical prescriptions.PMID:37729183 | DOI:10.1021/acs.chemrestox.3c00158

Metabolic implications of amino acid metabolites in chronic kidney disease progression: a metabolomics analysis using OPLS-DA and MBRole2.0 database

Wed, 20/09/2023 - 12:00
Int Urol Nephrol. 2023 Sep 20. doi: 10.1007/s11255-023-03779-8. Online ahead of print.ABSTRACTBACKGROUND: As chronic kidney disease (CKD) progresses, metabolites undergo diverse transformations. Nevertheless, the impact of these metabolic changes on the etiology, progression, and prognosis of CKD remains uncertain. Our objective is to conduct a metabolomics analysis to scrutinize metabolites and identify significant metabolic pathways implicated in CKD progression, thereby pinpointing potential therapeutic targets for CKD management.METHODS: We recruited 145 patients with CKD and determined their mGFR by measuring the plasma iohexol clearance, whereupon we partitioned them into four groups based on their mGFR values. Non-targeted metabolomics analysis was conducted using UPLC-MS/MS assays. Differential metabolites were identified via one-way ANOVA, PCA, PLS-DA, and OPLS-DA analyses employing the MetaboAnalyst 5.0 platform. Ultimately, we performed differential metabolite pathway enrichment analysis, using both the MetaboAnalyst 5.0 platform and the MBRole2.0 database.RESULTS: According to the findings of the MBRole2.0 and MetaboAnalyst 5.0 enrichment analysis, six amino acid metabolism pathways were discovered to have significant roles in the progression of CKD, with the glycine, serine, and threonine metabolism pathway being the most prominent. The latter enriched 14 differential metabolites, of which six decreased while two increased concomitantly with renal function deterioration.CONCLUSIONS: The metabolic analysis unveiled that glycine, serine, and threonine metabolism plays a pivotal role in the progression of CKD. Specifically, glycine was found to increase while serine decreased with the deterioration of CKD.PMID:37728808 | DOI:10.1007/s11255-023-03779-8

Influence of soil depth, irrigation, and plant genotype on the soil microbiome, metaphenome, and carbon chemistry

Wed, 20/09/2023 - 12:00
mBio. 2023 Sep 20:e0175823. doi: 10.1128/mbio.01758-23. Online ahead of print.ABSTRACTClimate change is causing an increase in drought in many soil ecosystems and a loss of soil organic carbon. Calcareous soils may partially mitigate these losses via carbon capture and storage. Here, we aimed to determine how irrigation-supplied soil moisture and perennial plants impact biotic and abiotic soil properties that underpin deep soil carbon chemistry in an unfertilized calcareous soil. Soil was sampled up to 1 m in depth from irrigated and planted field treatments and was analyzed using a suite of omics and chemical analyses. The soil microbial community composition was impacted more by irrigation and plant cover treatments than by soil depth. By contrast, metabolomes, lipidomes, and proteomes differed more with soil depth than treatments. Deep soil (>50 cm) had higher soil pH and calcium concentrations and higher levels of organic acids, bicarbonate, and triacylglycerides. By contrast, surface soil (0-5 cm) had higher concentrations of soil organic matter, organic carbon, oxidizable carbon, and total nitrogen. Surface soils also had higher amounts of sugars, sugar alcohols, phosphocholines, and proteins that reflect osmotic and oxidative stress responses. The lipidome was more responsive to perennial tall wheatgrass treatments compared to the metabolome or proteome, with a striking change in diacylglyceride composition. Permanganate oxidizable carbon was more consistently correlated to metabolites and proteins than soil organic and inorganic carbon and soil organic matter. This study reveals specific compounds that reflect differences in organic, inorganic, and oxidizable soil carbon fractions that are impacted by interactions between irrigation-supplied moisture and plant cover in calcareous soil profiles. IMPORTANCE Carbon is cycled through the air, plants, and belowground environment. Understanding soil carbon cycling in deep soil profiles will be important to mitigate climate change. Soil carbon cycling is impacted by water, plants, and soil microorganisms, in addition to soil mineralogy. Measuring biotic and abiotic soil properties provides a perspective of how soil microorganisms interact with the surrounding chemical environment. This study emphasizes the importance of considering biotic interactions with inorganic and oxidizable soil carbon in addition to total organic carbon in carbonate-containing soils for better informing soil carbon management decisions.PMID:37728606 | DOI:10.1128/mbio.01758-23

Ascophyllum nodosum as a nutrient supporting oral health in dogs and cats: a review

Wed, 20/09/2023 - 12:00
Pol J Vet Sci. 2023 Sep 20;26(3):511-520. doi: 10.24425/pjvs.2023.145053.ABSTRACTHome dental care is a key element of periodontal therapy in veterinary patients. Among many strategies of passive home dental care there is a supplementation of animal diet with seaweed Ascophyllum nodosum which have been shown to reduce both calculus and plaque accumulation after oral administration in both dogs and cats. Ascophyllum nodosum contains numerous biologically active ingredients, including micro-elements, vitamins, and several other compounds, however the exact mechanism of its beneficial action remains unclear. The very first metabolomic data suggest that it could change the composition of dog saliva. Several products containing Ascophyllum nodosum had been assessed clinically according to standards and requirements provided by the Veterinary Oral Health Council. The conducted clinical trials in dogs and cats revealed that Ascophyllum nodosum exerts the strongest preventive action as powder, followed by dental bites and dry pet food. The data concerning its curative action are limited to one study in cats in which no beneficial action has been observed. Based on available clinical data it is recommended to administer Ascophyllum nodosum to dogs and cats after oral cavity prophylactic procedure to reduce the recurrence of plaque and calculus formation.PMID:37727971 | DOI:10.24425/pjvs.2023.145053

Mathematical modeling for freshness/spoilage of chicken breast using chemometric analysis

Wed, 20/09/2023 - 12:00
Curr Res Food Sci. 2023 Sep 10;7:100590. doi: 10.1016/j.crfs.2023.100590. eCollection 2023.ABSTRACTChicken meat spoilage is a significant concern for food safety and quality, and this study aims to predict the spoilage point of chicken breast meat through various attributes and metabolites. Chicken meat was stored in anaerobic packaging at 4 °C for 13 days, and various meat quality attributes (pH, drip loss, color, volatile basic nitrogen [VBN], total aerobic bacteria [TAB], and metabolites) were examined. First, the spoiled point (VBN >20 mg/100 g and/or TAB >7 log CFU/g) of the chicken breast meat was determined. Using univariate and multivariate analyses, twenty-four candidate metabolites were identified. A receiver operating characteristic (ROC) analysis was used to validate the obtained binary logistic regression model using nine metabolites (proline, methionine, glutamate, threonine, acetate, uridine 5'-monophosphate, hypoxanthine, glycine, and glutamine). The results showed a high area under the ROC curve value (0.992). Thus, this study confirmed the predictability of spoilage points in chicken breast meat through these nine metabolites.PMID:37727874 | PMC:PMC10506101 | DOI:10.1016/j.crfs.2023.100590

Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19

Wed, 20/09/2023 - 12:00
ERJ Open Res. 2023 Sep 18;9(5):00206-2023. doi: 10.1183/23120541.00206-2023. eCollection 2023 Sep.ABSTRACTBACKGROUND: Although rapid screening for and diagnosis of coronavirus disease 2019 (COVID-19) are still urgently needed, most current testing methods are long, costly or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time mass spectrometry breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19.METHODS: In two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19. Artificial intelligence and machine learning techniques were used to build mathematical models based on breath analysis data either alone or combined with patient metadata.RESULTS: We obtained breath samples from 173 participants, of whom 67 had proven COVID-19. After using machine learning algorithms to process breath analysis data and further enhancing the model using patient metadata, our method was able to differentiate between COVID-19-positive and -negative participants with a sensitivity of 98%, a specificity of 74%, a negative predictive value of 98%, a positive predictive value of 72% and an area under the receiver operating characteristic curve of 0.961. The predictive performance was similar for asymptomatic, weakly symptomatic and symptomatic participants and was not biased by COVID-19 vaccination status.CONCLUSIONS: Real-time, noninvasive, artificial-intelligence-enhanced mass spectrometry breath analysis might be a reliable, safe, rapid, cost-effective, high-throughput method for COVID-19 screening.PMID:37727677 | PMC:PMC10505950 | DOI:10.1183/23120541.00206-2023

Insulin and the sebaceous gland function

Wed, 20/09/2023 - 12:00
Front Physiol. 2023 Sep 1;14:1252972. doi: 10.3389/fphys.2023.1252972. eCollection 2023.ABSTRACTInsulin affects metabolic processes in different organs, including the skin. The sebaceous gland (SG) is an important appendage in the skin, which responds to insulin-mediated signals, either directly or through the insulin growth factor 1 (IGF-1) axis. Insulin cues are differently translated into the activation of metabolic processes depending on several factors, including glucose levels, receptor sensitivity, and sebocyte differentiation. The effects of diet on both the physiological function and pathological conditions of the SG have been linked to pathways activated by insulin and IGF-1. Experimental evidence and theoretical speculations support the association of insulin resistance with acne vulgaris, which is a major disorder of the SG. In this review, we examined the effects of insulin on the SG function and their implications in the pathogenesis of acne.PMID:37727660 | PMC:PMC10505787 | DOI:10.3389/fphys.2023.1252972

Untargeted plasma metabolome identifies biomarkers in patients with extracranial arteriovenous malformations

Wed, 20/09/2023 - 12:00
Front Physiol. 2023 Sep 1;14:1207390. doi: 10.3389/fphys.2023.1207390. eCollection 2023.ABSTRACTObjective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM patients and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to analyze the metabolic profiles of both groups. Metabolic pathway enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes (KEGG) database and MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO) and random forest (RF) were conducted to screen characteristic metabolites. The effectiveness of the serum biomarkers for AVM was evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites were screened in this study, with 110 metabolites in positive ion mode and 74 metabolites in negative mode. Lipids and lipid-like molecules were the predominant metabolites detected in both positive and negative ion modes. Several significant metabolic pathways were enriched in AVMs, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and protein translation. Through machine learning algorithms, nine metabolites were identify as characteristic metabolites, including hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic acid, and dihydrojasmonic acid. Conclusion: Patients with extracranial AVMs exhibited significantly altered metabolic patterns compared to healthy controls, which could be identified using plasma metabolomics. These findings suggest that metabolomic profiling can aid in the understanding of AVM pathophysiology and potentially inform clinical diagnosis and treatment.PMID:37727659 | PMC:PMC10505742 | DOI:10.3389/fphys.2023.1207390

Metabolic impact of polyphenol-rich aronia fruit juice mediated by inflammation status of gut microbiome donors in humanized mouse model

Wed, 20/09/2023 - 12:00
Front Nutr. 2023 Sep 1;10:1244692. doi: 10.3389/fnut.2023.1244692. eCollection 2023.ABSTRACTBACKGROUND: The Aronia melanocarpa fruit is emerging as a health food owing to its high polyphenolic content and associated antioxidant activity. Antioxidant-rich foods, such as Aronia fruit, may counter inflammatory stimuli and positively modulate the gut microbiome. However, a comprehensive study characterizing the impact of Aronia fruit supplementation has not been completed. Therefore, we completed analyses measuring the metabolic, microbial, and inflammatory effects of a diet supplemented with Aronia fruit juice.METHOD: Humanized mice were generated by colonizing gnotobiotic mice with microbiomes from human donors presenting disparate inflammation levels. Blood and fecal samples were collected throughout the course of an 8-week dietary intervention with either Aronia juice or a carbohydrate-matched beverage alone (2 weeks) or in combination with a high-fat diet to induce inflammation (6 weeks). Samples were analyzed using 16S rRNA gene sequencing (stool) and liquid chromatography-mass spectrometry (serum).RESULTS: We demonstrated transfer of microbiome composition and diversity and metabolic characteristics from humans with low and high inflammation levels to second-generation humanized mice. Aronia supplementation provided robust protection against high-fat diet induced metabolic and microbiome changes that were dependent in part on microbiome donor. Aronia induced increases in bacteria of the Eggerthellaceae genus (7-fold) which aligns with its known ability to metabolize (poly)phenols and in phosphatidylcholine metabolites which are consistent with improved gut barrier function. The gut microbiome from a low inflammation phenotype donor provided protection against high-fat diet induced loss of microbiome β-diversity and global metabolomic shifts compared to that from the high inflammation donor.CONCLUSION: These metabolic changes elucidate pathway-specific drivers of reduced inflammation stemming from both Aronia and the gut microbiota.PMID:37727634 | PMC:PMC10505616 | DOI:10.3389/fnut.2023.1244692

Comprehensive profiling of the metabolome in corn silage inoculated with or without <em>Lactiplantibacillus plantarum</em> using different untargeted metabolomics analyses

Wed, 20/09/2023 - 12:00
Arch Anim Nutr. 2023 Sep 19:1-19. doi: 10.1080/1745039X.2023.2247824. Online ahead of print.ABSTRACTSilage fermentation is a complicated biochemical process involving interactions between microbes and metabolites. However, the overall metabolome feature of ensiled forage and its response to lactic acid bacteria inoculation is poorly understood. Hence, in this study metabolome profiles of whole-plant corn silage inoculated with or without Lactiplantibacillus plantarum were characterised via solid-phase microextraction/gas chromatography/mass spectrometry (SPME-GC-MS), gas chromatography/time-of-flight mass spectrometry (GC-TOF-MS), and Liquid chromatography/Q Exactive HFX mass spectrometry (LC-QE-MS/MS) analysis. There were 2087 identified metabolites including 1143 reliably identified metabolites in fresh and ensiled whole-plant corn. After ensiling, the increased metabolites in whole-plant corn were mainly composed of organic acids, volatile organic compounds (VOC), benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, flavonoids, indoles and derivatives, organooxygen compounds (including amines and amides), phenols, pyridines and derivatives, and steroids and steroid derivatives, which includes neurotransmitters and metabolites with aromatic, antioxidant, anti-inflammatory, and antimicrobial activities. Phenylacetaldehyde was the most abundant aromatic metabolite after ensiling. L-isoleucine and oxoproline were the major free amino acids in silage. Ensiling markedly increased the relative abundances of 3-phenyllactic acid, chrysoeriol, 6-O-acetylaustroinulin, acetylcholine, γ-aminobutyric acid, pyridoxine, and alpha-linoleic acid. Inoculation with L. plantarum remarkably changed silage VOC composition, and essential amino acids, 3-phenyllactic acid, and cinnamaldehyde compared with untreated silage. The present study does not only provide a deeper insight into metabolites of the ensiled whole-plant corn but also reveals metabolites with specific biological functions that could be much helpful in screening novel lactic acid bacteria to well ensile forages. Inoculation with L. plantarum significantly affects the metabolome in ensiled whole-plant corn.PMID:37726873 | DOI:10.1080/1745039X.2023.2247824

Prediction of plant secondary metabolic pathways using deep transfer learning

Tue, 19/09/2023 - 12:00
BMC Bioinformatics. 2023 Sep 19;24(1):348. doi: 10.1186/s12859-023-05485-9.ABSTRACTBACKGROUND: Plant secondary metabolites are highly valued for their applications in pharmaceuticals, nutrition, flavors, and aesthetics. It is of great importance to elucidate plant secondary metabolic pathways due to their crucial roles in biological processes during plant growth and development. However, understanding plant biosynthesis and degradation pathways remains a challenge due to the lack of sufficient information in current databases. To address this issue, we proposed a transfer learning approach using a pre-trained hybrid deep learning architecture that combines Graph Transformer and convolutional neural network (GTC) to predict plant metabolic pathways.RESULTS: GTC provides comprehensive molecular representation by extracting both structural features from the molecular graph and textual information from the SMILES string. GTC is pre-trained on the KEGG datasets to acquire general features, followed by fine-tuning on plant-derived datasets. Four metrics were chosen for model performance evaluation. The results show that GTC outperforms six other models, including three previously reported machine learning models, on the KEGG dataset. GTC yields an accuracy of 96.75%, precision of 85.14%, recall of 83.03%, and F1_score of 84.06%. Furthermore, an ablation study confirms the indispensability of all the components of the hybrid GTC model. Transfer learning is then employed to leverage the shared knowledge acquired from the KEGG metabolic pathways. As a result, the transferred GTC exhibits outstanding accuracy in predicting plant secondary metabolic pathways with an average accuracy of 98.30% in fivefold cross-validation and 97.82% on the final test. In addition, GTC is employed to classify natural products. It achieves a perfect accuracy score of 100.00% for alkaloids, while the lowest accuracy score of 98.42% for shikimates and phenylpropanoids.CONCLUSIONS: The proposed GTC effectively captures molecular features, and achieves high performance in classifying KEGG metabolic pathways and predicting plant secondary metabolic pathways via transfer learning. Furthermore, GTC demonstrates its generalization ability by accurately classifying natural products. A user-friendly executable program has been developed, which only requires the input of the SMILES string of the query compound in a graphical interface.PMID:37726702 | DOI:10.1186/s12859-023-05485-9

Integrated omic profiling of the medicinal mushroom Inonotus obliquus under submerged conditions

Tue, 19/09/2023 - 12:00
BMC Genomics. 2023 Sep 19;24(1):554. doi: 10.1186/s12864-023-09656-z.ABSTRACTBACKGROUND: The Inonotus obliquus mushroom, a wondrous fungus boasting edible and medicinal qualities, has been widely used as a folk medicine and shown to have many potential pharmacological secondary metabolites. The purpose of this study was to supply a global landscape of genome-based integrated omic analysis of the fungus under lab-growth conditions.RESULTS: This study presented a genome with high accuracy and completeness using the Pacbio Sequel II third-generation sequencing method. The de novo assembled fungal genome was 36.13 Mb, and contained 8352 predicted protein-coding genes, of which 365 carbohydrate-active enzyme (CAZyme)-coding genes and 19 biosynthetic gene clusters (BCGs) for secondary metabolites were identified. Comparative transcriptomic and proteomic analysis revealed a global view of differential metabolic change between seed and fermentation culture, and demonstrated positive correlations between transcription and expression levels of 157 differentially expressed genes involved in the metabolism of amino acids, fatty acids, secondary metabolites, antioxidant and immune responses. Facilitated by the widely targeted metabolomic approach, a total of 307 secondary substances were identified and quantified, with a significant increase in the production of antioxidant polyphenols.CONCLUSION: This study provided the comprehensive analysis of the fungus Inonotus obliquus, and supplied fundamental information for further screening of promising target metabolites and exploring the link between the genome and metabolites.PMID:37726686 | DOI:10.1186/s12864-023-09656-z

Profile and potential bioactivity of the miRNome and metabolome expressed in Malva sylvestris L. leaf and flower

Tue, 19/09/2023 - 12:00
BMC Plant Biol. 2023 Sep 19;23(1):439. doi: 10.1186/s12870-023-04434-1.ABSTRACTMalva sylvestris L. (common mallow) is a plant species widely used in phytotherapy and ethnobotanical practices since time immemorial. Characterizing the components of this herb might promote a better comprehension of its biological effects on the human body but also favour the identification of the molecular processes that occur in the plant tissues. Thus, in the present contribution, the scientific knowledge about the metabolomic profile of the common mallow was expanded. In particular, the phytocomplex of leaves and flowers from this botanical species and the extraction capacity of different concentrations of ethanol (i.e., 95%, 70%, 50%, and 0%; v/v in ddH2O) for it were investigated by spectrophotometric and chromatographic approaches. In detail, 95% ethanol extracts showed the worst capacity in isolating total phenols and flavonoids, while all the hydroalcoholic samples revealed a specific ability in purifying the anthocyanins. HPLC-DAD system detected and quantified 20 phenolic secondary metabolites, whose concentration in the several extracts depended on their own chemical nature and the percentage of ethanol used in the preparation. In addition, the stability of the purified phytochemicals after resuspension in pure ddH2O was also proved, considering a potential employment of them in biological/medical studies which include in vitro and in vivo experiments on mammalian models. Here, for the first time, the expressed miRNome in M. sylvestris was also defined by Next Generation Sequencing, revealing the presence of 33 microRNAs (miRNAs), 10 typical for leaves and 2 for flowers. Then, both plant and human putative mRNA targets for the detected miRNAs were predicted by bioinformatics analyses, with the aim to clarify the possible role of these small nucleic acids in the common mallow plant tissues and to try to understand if they could exert a potential cross-kingdom regulatory activity on the human health. Surprisingly, our investigations revealed that 19 miRNAs out of 33 were putatively able to modulate, in the plant cells, the expression of various chromosome scaffold proteins. In parallel, we found, in the human transcriptome, a total of 383 mRNAs involved in 5 fundamental mammalian cellular processes (i.e., apoptosis, senescence, cell-cycle, oxidative stress, and invasiveness) that theoretically could be bound and regulated by M. sylvestris miRNAs. The evidence collected in this work would suggest that the beneficial properties of the use of M. sylvestris, documented by the folk medicine, are probably linked to their content of miRNAs and not only to the action of phytochemicals (e.g., anthocyanins). This would open new perspectives about the possibility to develop gene therapies based on miRNAs isolated from medicinal plants, including M. sylvestris.PMID:37726667 | DOI:10.1186/s12870-023-04434-1

Amino acid metabolism dysregulation associated with inflammation and insulin resistance in HIV-infected individuals with metabolic disorders

Tue, 19/09/2023 - 12:00
Amino Acids. 2023 Sep 19. doi: 10.1007/s00726-023-03325-x. Online ahead of print.ABSTRACTAmino acid metabolic profile, particularly its association with clinical characteristics, remains unclear in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) combined with metabolic disorders. In this study, we performed targeted metabolomic analyses on 64 patients with HIV/AIDS and 21 healthy controls. Twenty-four amino acids and selected intermediate metabolites in the serum were quantitatively detected using high-performance liquid chromatography-tandem mass spectrometry, and characteristic changes and metabolic pathways were analyzed in HIV-infected patients with different degrees of abnormal glucose and lipid metabolism. Spearman's partial correlation was used to analyze the association between amino acids, biochemical parameters, and inflammatory cytokines. The results showed that the main metabolic pathways of the eighteen differential metabolites involved were arginine biosynthesis and metabolism, methionine cycle, and tryptophan metabolism. Fourteen differential amino acid metabolites were positively correlated with nine inflammatory cytokines, including TNF-α, C-reactive protein, IL-1β, and galectin-3 (FDR < 0.1). Kynurenine, ornithine, and homocysteine were positively correlated with fasting blood glucose and insulin resistance index (FDR < 0.1). Our study revealed a multi-pathway imbalance in amino acid metabolism in patients with HIV/AIDS, which was significantly correlated with inflammation and insulin resistance.PMID:37726575 | DOI:10.1007/s00726-023-03325-x

Untargeted metabolomics analysis of plasma metabolic characteristics in patients with acne and insulin resistance

Tue, 19/09/2023 - 12:00
Amino Acids. 2023 Sep 19. doi: 10.1007/s00726-023-03320-2. Online ahead of print.ABSTRACTAcne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.PMID:37726574 | DOI:10.1007/s00726-023-03320-2

Metabolomic profiling implicates mitochondrial and immune dysfunction in disease syndromes of the critically endangered black rhinoceros (Diceros bicornis)

Tue, 19/09/2023 - 12:00
Sci Rep. 2023 Sep 19;13(1):15464. doi: 10.1038/s41598-023-41508-4.ABSTRACTThe critically endangered black rhinoceros (Diceros bicornis; black rhino) experiences extinction threats from poaching in-situ. The ex-situ population, which serves as a genetic reservoir against impending extinction threats, experiences its own threats to survival related to several disease syndromes not typically observed among their wild counterparts. We performed an untargeted metabolomic analysis of serum from 30 ex-situ housed black rhinos (Eastern black rhino, EBR, n = 14 animals; Southern black rhino, SBR, n = 16 animals) and analyzed differences in metabolite profiles between subspecies, sex, and health status (healthy n = 13 vs. diseased n = 14). Of the 636 metabolites detected, several were differentially (fold change > 1.5; p < 0.05) expressed between EBR vs. SBR (40 metabolites), female vs. male (36 metabolites), and healthy vs. diseased (22 metabolites). Results suggest dysregulation of propanoate, amino acid metabolism, and bile acid biosynthesis in the subspecies and sex comparisons. Assessment of healthy versus diseased rhinos indicates involvement of arachidonic acid metabolism, bile acid biosynthesis, and the pentose phosphate pathway in animals exhibiting inflammatory disease syndromes. This study represents the first systematic characterization of the circulating serum metabolome in the black rhinoceros. Findings further implicate mitochondrial and immune dysfunction as key contributors for the diverse disease syndromes reported in ex-situ managed black rhinos.PMID:37726331 | DOI:10.1038/s41598-023-41508-4

Integrated meta-omics approaches reveal Saccharopolyspora as the core functional genus in huangjiu fermentations

Tue, 19/09/2023 - 12:00
NPJ Biofilms Microbiomes. 2023 Sep 19;9(1):65. doi: 10.1038/s41522-023-00432-1.ABSTRACTIdentification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjiu's metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products.PMID:37726290 | DOI:10.1038/s41522-023-00432-1

Physiological and metabolomic analyses reveal that Fe<sub>3</sub>O<sub>4</sub> nanoparticles ameliorate cadmium and arsenic toxicity in Panax notoginseng

Tue, 19/09/2023 - 12:00
Environ Pollut. 2023 Sep 17:122578. doi: 10.1016/j.envpol.2023.122578. Online ahead of print.ABSTRACTHeavy metal (loid)-contaminated available arable land seriously affects crop development and growth. Engineered nanomaterials have great potential in mitigating toxic metal (loid) stress in plants. However, there are few details of nanoparticles (NPs) involved in Panax notoginseng response to cadmium (Cd) and arsenic (As). Herein, integrating physiological and metabolomic analyses, we investigated the effects of Fe3O4 NPs on plant growth and Cd/As responses in P. notoginseng. Cd/As treatment caused severe growth inhibition. However, foliar application of Fe3O4 NPs increased beneficial elements in the roots and/or leaves, decreased Cd/As content by 10.38% and 20.41% in the roots, reduced membrane damage and regulated antioxidant enzyme activity, thereby alleviating Cd/As-induced growth inhibition, as indicated by increased shoot fresh weight (FW), the rootlet length and root FW by 40.14%, 15.74%, and 46.70% under Cd stress and promoted the shoot FW by 27.00% under As toxicity. Metabolomic analysis showed that 227 and 295 differentially accumulated metabolites (DAMs) were identified, and their accumulation patterns were classified into 8 and 6 clusters in the roots and leaves, respectively. Fe3O4 NPs altered metabolites significantly involved in key pathways, including amino sugar and nucleotide sugar metabolism, flavonoid biosynthesis and phenylalanine metabolism, thus mediating the trade-off between plant growth and defense under stress. Interestingly, Fe3O4 NPs recovered more Cd/As-induced DAMs to normal levels, further supporting that Fe3O4 NPs positively affected seedling growth under metal (loid)s stress. In addition, Fe3O4 NPs altered terpenoids when the seedlings were subjected to Cd/As stress, thus affecting their potential medicinal value. This study provides insights into using nanoparticles to improve potential active ingredients of medicinal plants in metal (loid)-contaminated areas.PMID:37726032 | DOI:10.1016/j.envpol.2023.122578

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