Metabolomics Profiling of Tunisian Sonchus oleraceus L. Extracts and Their Antioxidant Activities.

Sonchus oleraceus (L.) L. (Asteraceae) is an edible wild plant, known for its uses in traditional medicine. The aim of this study is to explore the phytochemical composition of the aerial parts (AP) and roots (R) of aqueous extracts of Sonchus oleraceus L. growing in Tunisia, using liquid chromatography-tandem mass spectrometry(LC/MS/MS), and determine the content of polyphenols and antioxidant activities. Results showed that aqueous extracts of AP and R contained, respectively, 195.25±33 µg/g and 118.66±14 µg/g gallic acid equivalent (GAE), and 52.58±7 µg/g and 3.2±0.3µg/g quercetin equivalent. AP and R extracts also contained tannins, 581.78±33 µg/g and 948.44±19 µg/g GAE. The AP extract in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activities, hydroxyl radical scavenging (OH-) and in cupric reducing antioxidant activity (CUPRAC) assays were respectively 0.325±0.036 mg/mL, 0.053±0.018 mg/mL, 0.696±0.031 mg/mL and 60.94±0.004 µMTE/g, while the R extract using the same assays showed, 0.209±0.052 mg/mL, 0.034±0.002 mg/mL, 0.444±0.014 mg/mL and 50.63±0.006 µM Trolox equivalent/g, respectively. A total of 68 compounds were tentatively identified by LC/MS/MS in both extracts in which quinic acid, pyrogallol, osthrutin, piperine, gentisic acid, fisetin, luteolin, caffeic acid, gingerol, were the most abundant in the LC/MS/MS spectrum. Many of these metabolites were found for the first time in Tunisian Sonchus oleraceus L. which may take account for the antioxidant activities exhibited by the plant.

Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor.

BACKGROUND: Desmoid tumor (DT), also known as desmoid-type fibromatosis (DTF) or aggressive fibromatosis (AF) is a rare mesenchymal tumor affecting both children and adults. It is non-metastasis but infiltrative, growing with a high recurrence rate to even cause serious health problems. This study investigates the biology of desmoid tumors through integrated multi-omics studies. METHODS: We systematically investigated the clinical data of 98 extra-abdominal cases in our pediatric institute and identified some critical clinical prognostic factors. Moreover, our integrated multi-omics studies (Whole Exome Sequencing, RNA sequencing, and untargeted metabolomics profiling) in the paired PDT tumor/matched normal tissues identified more novel mutations, and potential prognostic markers and therapeutic targets for PDTs. RESULTS: The top mutation genes, such as CTNNB1 (p.T41A and p.S45F) and MUC4 (p.T3775T, p.S3450S, etc.), were observed with a mutation in more than 40% of PDT patients. We also identified a panel of genes that are classed as the FDA-approved drug targets or Wnt/ß-catenin signaling pathway-related genes. The integrated analysis identified pathways and key genes/metabolites that may be important for developing potential treatment of PDTs. We also successfully established six primary PDT cell lines for future studies. CONCLUSIONS: These studies may promote the development of novel drugs and therapeutic strategies for PDTs.

Metabolomic profiling of brassinolide and abscisic acid in response to high-temperature stress.

KEY MESSAGE: Hormone treatment enhanced the content of osmotic substances under high-temperature conditions. The effect of ABA and BR treated separately is better than treated together. To determine the effect of abscisic acid (ABA), brassinolide (BR) and ABA + BR on grape quality under high-temperature stress, various metabolites were analyzed. Compared with the control (CK), DL-tryptophan, D-raffinose, geniposidic acid, dodecanedioic acid and polyphenols were found to be higher after ABA treatment. After BR treatment, amino acids and poricoic acid B were higher than in CK. And carbohydrates and amino acids were up-regulated after ABA + BR treatment. BR and ABA + BR treatment also induced higher endogenous ABA and epibrassinolide contents. In addition, treated grape had higher soluble solid concentrations and soluble sugar content, and delayed the degradation of middle lamella and microfibrils. Antioxidant and heat shock-related genes were examined, which significantly increased in treated grape. The finding of this study suggested that ABA, BR and ABA + BR are very useful for alleviating high-temperature damage by increasing the accumulation of osmotic adjustment substances, and endogenous hormones content.

Untargeted 1 H-NMR Metabolome of Celery During Fusarium Wilt: Implications for Vegetable Quality.

Celery is a vegetable widely consumed as a condiment to prepare diverse dishes around the world. Nevertheless, this plant is susceptible to the attack of several phytopathogens including those of the Fusarium genus which is translated into devastating losses for the production chain. Herein we report on the metabolic changes produced during the celery wilt caused by Fusarium oxysporum which was determined through untargeted 1 H-NMR metabolomics. The changes in the metabolite content of celery were measured at 16, 24, and 32 days post-inoculation using viable conidia obtained from the native F. oxysporum strain FO3. Our results demonstrated that the parasitic activity of the fungus reduced the endogenous levels of free sugars (fructose, galactose, glucose isomers, mannose, Myo-inositol, mannitol, and sucrose) amino acids (alanine, aspartate GABA, glutamate, glutamine, histidine, isoleucine, leucine, methionine, proline, threonine, tyrosine, and valine), nucleosides (adenosine, cytidine, guanosine, and uridine) and organic acids (citric acid, fumaric acid, malic acid, and succinic acid). Interestingly, the levels of tyrosine and tryptophan were triggered as a consequence of F. oxysporum infection. This tendency was correlated with an increase in the levels of chlorogenic acid, apiin, and apigenin derivatives, suggesting their involvement in the chemical defense of celery against fungal colonization. According to principal component analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) methanol was the main differential metabolite and it was considered as a new chemical marker associated with F. oxysporum infection. Our results demonstrate that infected celery plants dramatically reduced their nutritional and nutraceutical contents during Fusarium wilt after 32 days post-inoculation. However, these findings also suggest that the phenylpropanoid pathway is strongly related with the chemical defense of celery against F. oxysporum.

Integrated metabolomic and transcriptomic analysis reveals factors underlying differences in fruit quality between Fragaria nilgerrensis and Fragaria pentaphylla.

BACKGROUND: Strawberries have become one of the most popular fruits because of their unique flavor and high nutritional value. Fruit quality and price are the most important criteria that determine consumer acceptability. Fragaria nilgerrensis and Fragaria pentaphylla are two wild Asian diploid strawberry species that differ in fruit color, taste, and aroma. To understand the molecular mechanisms involved in the formation of high-quality strawberry fruit, we integrated transcriptomics and metabolomics research methods to compare the metabolic and biosynthetic mechanisms of the two Fragaria species. RESULTS: F. nilgerrensis fruit has higher amino acid and lipid contents and a higher sugar-to-acid ratio than F. pentaphylla fruit does, underlying their superior nutritional value, aroma, firmness, and taste. Compared with F. nilgerrensis fruit, F. pentaphylla fruit contained more flavonoids, indicating its enhanced color and health benefits. In addition, candidate structural genes that regulate the biosynthesis of flavonoids, amino acids, and glycerophospholipids in the two strawberry fruit were screened. CONCLUSIONS: The differences in aroma, firmness, and taste between F. nilgerrensis fruit and F. pentaphylla fruit are probably due to differences in their amino acid and lipid contents, as well as the difference in their sugar-to-acid ratios. Eight key structural genes that may play important roles in the biosynthesis of amino acids, lipids, and flavonoids were identified. © 2021 Society of Chemical Industry.

Osteogenic Response of Human Mesenchymal Stem Cells Analysed Using Combined Intracellular and Extracellular Metabolomic Monitoring.

BACKGROUND/AIMS: The skeleton is a metabolically active organ undergoing continuous remodelling initiated by mesenchymal progenitors present in bone and bone marrow. Under certain pathological conditions this remodelling balance shifts towards increased resorption resulting in weaker bone microarchitecture, and there is consequently a therapeutic need to identify pathways that could inversely enhance bone formation from stem cells. Metabolomics approaches recently applied to stem cell characterisation could help identify new biochemical markers involved in osteogenic differentiation. METHODS: Combined intra- and extracellular metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS) on human mesenchymal stem cells (MSCs) undergoing osteogenic differentiation in vitro. Using a combination of univariate and multivariate analyses, changes in metabolite and nutrient concentration were monitored in cultures under osteogenic treatment over 10 days. RESULTS: A subset of differentially detected compounds was identified in differentiating cells, suggesting a direct link to metabolic processes involved in osteogenic response. CONCLUSION: These results highlight new metabolite candidates as potential biomarkers to monitor stem cell differentiation towards the bone lineage.

Metabolomics-driven gene mining and genetic improvement of tolerance to salt-induced osmotic stress in maize.

The farmland of the world's main corn-producing area is increasingly affected by salt stress. Therefore, the breeding of salt-tolerant cultivars is necessary for the long-term sustainability of global corn production. Previous studies have shown that natural maize varieties display a large diversity of salt tolerance, yet the genetic variants underlying such diversity remain poorly discovered and applied, especially those mediating the tolerance to salt-induced osmotic stress (SIOS). Here we report a metabolomics-driven understanding and genetic improvement of maize SIOS tolerance. Using a LC-MS-based untargeted metabolomics approach, we profiled the metabolomes of 266 maize inbred lines under control and salt conditions, and then identified 37 metabolite biomarkers of SIOS tolerance (METO1-37). Follow-up metabolic GWAS (mGWAS) and genotype-to-phenotype modeling identified 10 candidate genes significantly associating with the SIOS tolerance and METO abundances. Furthermore, we validated that a citrate synthase, a glucosyltransferase and a cytochrome P450 underlie the genotype-METO-SIOS tolerance associations, and showed that their favorable alleles additively improve the SIOS tolerance of elite maize inbred lines. Our study provides a novel insight into the natural variation of maize SIOS tolerance, which boosts the genetic improvement of maize salt tolerance, and demonstrates a metabolomics-based approach for mining crop genes associated with this complex agronomic trait.

Identification of potential serum metabolic biomarkers for patient with keratoconus using untargeted metabolomics approach.

This study aimed to investigate the metabolite differences between patients with keratoconus and control subjects and identify potential serum biomarkers for keratoconus using a non-targeted metabolomics approach. Venous blood samples were obtained from patients with keratoconus (n = 20) as well as from age-, gender- and race-matched control subjects (n = 20). Metabolites extracted from serum were separated and analyzed by liquid chromatography/quadrupole time-of-flight mass spectrometer. Processing of raw data and analysis of the data files was performed using Agilent Mass Hunter Qualitative software. The identified metabolites were subjected to a principal component and hierarchical cluster analysis. Appropriate statistical tests were used to analyze the metabolomic profiling data. Together, the analysis revealed that the dehydroepiandrosterone sulfate from the steroidal hormone synthesis pathway was significantly upregulated in patients with keratoconus (p < 0.05). Also, a combination of eicosanoids from the arachidonic acid pathway, mainly prostaglandin F2α, prostaglandin A2, 16,16-dimethyl prostaglandin E2, and 5-hydroxyeicosatetraenoic acid were collectively up-regulated as a group in keratoconus patients (p < 0.05). On the other hand, glycerophospholipid PS(17:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) was found to be significantly upregulated in the metabolomics profiles of control subjects (p < 0.05). The differently regulated metabolites provide insights into the pathophysiology of keratoconus and could potentially be used as biomarkers for keratoconus to aid in screening for individuals at risk hence, enabling early diagnosis and timely monitoring of disease.

Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats.

Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention.

Effects of Warmed and Humidified CO2 Surgical Site Insufflation in a Novel Experimental Model of Magnetic Compression Colonic Anastomosis.

Background. Pneumoperitoneum insufflation with warmed and humidified carbon dioxide (WH-CO2) can prevent heat loss and increase tissue oxygenation. We evaluated the impact of localized WH-CO2 insufflation on the anastomotic healing process. Methods. Sixty male Wistar rats were randomized: Group 1 (control, n = 12), Group 2 (cold and dry CO2, CD-CO2, n = 24), and Group 3 (WH-CO2, n = 24). A magnetic compression side-to-side colonic anastomosis was performed under 60-minute local abdominal CO2 flow insufflation. Animal temperature was recorded. IL-1, IL-6, and CRP levels were assessed before and after insufflation and on postoperative day (POD) 7 and POD 10. Endoscopic follow-up was performed on POD 7 and POD 10. A burst pressure (BP) test of the specimen was performed on POD 10, and histopathological analysis was then performed. Metabolomics of the anastomotic site was determined. Results. Seven rats (5 CD-CO2 group, 1 WH-CO2 group, and 1 control group) died during the survival period. Necropsies revealed intestinal occlusions (n = 2). One additional rat from the CD-CO2 group was sacrificed on POD 7 due to intestinal perforation. The postoperative course was uneventful in the remaining cases. There was no difference in BP among the groups. Thermal monitoring confirmed that WH-CO2 insufflation was effective to reduce heat loss. IL-1 levels were statistically and significantly lower on POD 10 in the WH-CO2 group than the CD-CO2 group but not lower than the control group. CRP levels, histopathology, and metabolomics did not show any difference between the 3 groups. Conclusions. WH-CO2 was effective to preserve core temperature. However, it did not improve anastomotic healing.

1 H-NMR metabolomics profiling of recombinant tobacco plants holding a promoter of a sesquiterpene cyclase.

INTRODUCTION: Nicotiana tabacum is a plant model intensively used in the bio-engineering pharmaceutical industry as a platform to produce drugs and therapeutic agents. Currently, no information regarding the non-targeted metabolome of transgenic tobacco containing recombinant regulatory sequences is available. OBJECTIVE: To compare the proton nuclear magnetic resonance (1 H-NMR) metabolomics profiling of a recombinant Nicotiana tabacum strain containing a promoter of a sesquiterpene cyclase from Capsicum annuum driving GUS expression, versus wild-type samples. Methodology The non-targeted 1 H-NMR metabolome was obtained and processed by principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). The differential metabolites were quantified by quantitative NMR. RESULTS: PCA and OPLS-DA revealed 37 metabolites including 16 discriminant compounds for transgenic samples. Ethanol (0.4 mg g-1 ), the main differential compound, was exclusively detected in transgenic tobacco; however, high levels of formate (0.28 mg g-1 ) and acetate (0.3 mg g-1 ) were simultaneously observed in the same group of samples. Cembratriene-4,6-diol, an antitumour and neuroprotective compound, and capsidiol, a known phytoalexin, increased by about 30% in transgenic samples. In addition, the endogenous levels of the antioxidant caffeoylquinic acid isomers increased by 50% in comparison to those of wild-type tobaccos. CONCLUSION: Our results support the occurrence of metabolic differences between wild type and transgenic tobacco containing a promoter of a Capsicum sesquiterpene cyclase gene. Interestingly, the recombinant transgenic strain studied accumulated high amounts of added value compounds with biological activity.

A quantitative multimodal metabolomic assay for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery.

Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with complex CNS and somatic pathology due to a deficiency in α-N-acetylglucosaminidase (NAGLU). Using global metabolic profiling by mass spectrometry targeting 361 metabolites, this study detected significant decreases in 225 and increases in six metabolites in serum samples from 7-month-old MPS IIIB mice, compared to wild-type (WT) mice. The metabolic disturbances involve virtually all major pathways of amino acid, peptide (58/102), carbohydrate (18/28), lipid (111/139), nucleotide (12/24), energy (2/9), vitamin and cofactor (11/16), and xenobiotic (11/28) metabolism. Notably, the reduced metabolites included eight essential amino acids, vitamins (C, E, B2, and B6), and neurotransmitters (serotonin, glutamate, aspartate, tryptophan, and N-acetyltyrosine). The metabolic impairments appear to emerge early during disease progression before the age of 2 months. Importantly, the restoration of NAGLU activity with an intravenous (i.v.) injection of rAAV9-hNAGLU vector led to near-complete correction of all serum metabolite abnormalities, with 201 (87%) metabolites normalized and 30 (13%) over-corrected. While the mechanisms are unclear, our data demonstrate that the lack of NAGLU activity triggers profound functional metabolic disturbances in MPS IIIB. These metabolic impairments respond well to a systemic rAAV9-hNAGLU gene delivery, supporting the surrogate biomarker potential of serum metabolomic profiles for MPS IIIB therapies.

Metabolomics profiling reveals the mechanism of increased pneumocandin B0 production by comparing mutant and parent strains.

Metabolic profiling was used to discover mechanisms of increased pneumocandin B0 production in a high-yield strain by comparing it with its parent strain. Initially, 79 intracellular metabolites were identified, and the levels of 15 metabolites involved in six pathways were found to be directly correlated with pneumocandin B0 biosynthesis. Then by combining the analysis of key enzymes, acetyl-CoA and NADPH were identified as the main factors limiting pneumocandin B0 biosynthesis. Other metabolites, such as pyruvate, α-ketoglutaric acid, lactate, unsaturated fatty acids and previously unreported metabolite γ-aminobutyric acid were shown to play important roles in pneumocandin B0 biosynthesis and cell growth. Finally, the overall metabolic mechanism hypothesis was formulated and a rational feeding strategy was implemented that increased the pneumocandin B0 yield from 1821 to 2768 mg/L. These results provide practical and theoretical guidance for strain selection, medium optimization, and genetic engineering for pneumocandin B0 production.

Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB.

The monogenic defects in specific lysosomal enzymes in mucopolysaccharidosis (MPS) III lead to lysosomal storage of glycosaminoglycans and complex CNS and somatic pathology, for which the detailed mechanisms remain unclear. In this study, serum samples from patients with MPS IIIA (age 2-9 yr) and MPS IIIB (2-13 yr) and healthy controls (age 2-9 yr) were assayed by global metabolomics profiling of 658 metabolites using mass spectrometry. Significant alterations were detected in 423 metabolites in all MPS III patients, of which 366 (86.5%) decreased and 57 (13.5%) increased. Similar profiles were observed when analyzing data from MPS IIIA and MPS IIIB samples separately, with only limited age variations in 36 metabolites. The observed metabolic disturbances in MPS III patients involve virtually all major pathways of amino acid (101/150), peptide (17/21), carbohydrate (19/23), lipid (221/325), nucleotide (15/25), energy (8/9), vitamins and co-factors (8/21), and xenobiotics (34/84) metabolism. Notably, detected serum metabolite decreases involved all key amino acids, all major neurotransmitter pathways, and broad neuroprotective compounds. The elevated metabolites are predominantly lipid derivatives, and also include cysteine metabolites and a fibrinogen peptide fragment, consistent with the status of oxidative stress and inflammation in MPS III. This study demonstrates that the lysosomal glycosaminoglycans storage triggers profound metabolic disturbances in patients with MPS III disorders, leading to severe functional depression of virtually all metabolic pathways, which emerge early during the disease progression. Serum global metabolomics profiling may provide an important and minimally invasive tool for better understanding the disease mechanisms and identification of potential biomarkers for MPS III.

Metabolism-Guided Bowel Resection: Potential Role and Accuracy of Instant Capillary Lactates to Identify the Optimal Resection Site.

BACKGROUND: Strip-based handheld devices can measure lactatemia on capillary blood obtained by needle puncturing. We aimed to assess the kinetic of bowel capillary lactates, metabolomics profiling, and mitochondria respiratory rate in a prolonged model of bowel hypoperfusion. MATERIALS AND METHODS: In 6 pigs, a 3- to 4-cm ischemic segment was created in 6 small bowel loops (total = 36 loops) by clamping the vascular supply, for a duration of 1 to 6 hours. Hourly, 5 blood samples were obtained by puncturing the serosa, and lactates were measured using a handheld analyzer. Samples were made at the following regions of interest (ROIs): center of the ischemic area (1), proximal and distal clinical margins of resection (2a-2b), and vascularized zones (3a-3b). Every hour, surgical biopsies of ROIs were sampled. Activity of bowel mitochondria complexes was measured after 1, 3, and 5 hours of ischemia. Quantification of metabolites was performed on all samples (total N = 180). RESULTS: Capillary lactates were significantly higher at ROI 1 versus ROI 3ab at all time points. After 1 hour lactates at the margins were significantly higher than those at vascularized areas (P = .0095), showing a mismatch between visual assessment and actual perfusion status. From 2 to 6 hours, there was no difference in lactates between ROIs 2a-2b and 3a-3b. Maximal tissue respiration decreased significantly after 1 hour (ROI 1 vs ROI 3ab). Seven metabolites (lactate, glucose, aspartate, choline, creatine, taurine, and tyrosine) expressed significantly different evolutions between ROIs. CONCLUSIONS: Capillary lactates could help precisely estimate local bowel perfusion status.

Serum metabolism distribution in individuals exposed to dioxins: A case study of residents near the municipal solid waste incinerators in China.

Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) have attracted considerable attention owing to their environmental persistence, bioaccumulation, and high toxicity. This study aimed to investigate changes in serum metabolites following exposure to PCDD/Fs and to reveal a novel pathogenesis of PCDD/Fs. Serum samples were collected from 75 residents living near a municipal solid waste incinerator in China to analyse the relationship between PCDD/Fs and serum metabolic components. The serum level in the low-exposure group [19.07 (13.44-23.89) pg-TEQ/L] was significantly lower than that in the high-exposure group [115.60 (52.28-592.65) pg-TEQ/L]. Non-targeted metabolomic studies based on liquid chromatography-high resolution mass spectrometry have been applied to the metabolomic analysis of serum. Thirty-seven metabolites with significant differences among the different groups were identified as biomarkers. Pathway analysis revealed that high dioxin exposure perturbed various biological processes, including glycerol phospholipid metabolism and the interconversion of pentose and glucuronate. The results of a population health survey showed that the serum dioxin concentration in patients with diabetes was significantly higher than that in the control population. These findings suggest that dioxin exposure is associated with several potential adverse health risks, including inflammation, diabetes, and cardiovascular disease, through metabolic changes.

Co-occurrence network analysis reveals the alterations of the skin microbiome and metabolome in adults with mild to moderate atopic dermatitis.

Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

Discovery of two novel bioactive algicidal substances from Brevibacillus sp. via metabolomics profiling and back-validation.

Identifying potent bacterial algicidal agents is essential for the development of effective, safe, and economically viable algaecides. Challenges in isolating and purifying these substances from complex secretions have impeded progress in this field. Metabolomics profiling, an efficient strategy for identifying metabolites, was pioneered in identifying bacterial algicidal substances in this study. Extracellular secretions from different generations of the algicidal bacterium Brevibacillus sp. were isolated for comprehensive analysis. Specifically, a higher algicidal efficacy was observed in the secretion from Generation 3 (G3) of Brevibacillus sp. compared to Generation 1 (G1). Subsequent metabolomics profiling comparing G3 and 1 revealed 83 significantly up-regulated metabolites, of which 9 were identified as potential algicidal candidates. Back-validation highlighted the potency of 4-acetamidobutanoic acid (4-ABC) and 8-hydroxyquinoline (8-HQL), which exhibited robust algicidal activity with 3d-EC50 values of 6.40 mg/L and 92.90 µg/L, respectively. These substances disrupted photosynthetic activity in M. aeruginosa by ceasing electron transfer in PSⅡ, like the impact exerted by Brevibacillus sp. secretion. These findings confirmed that 4-ABC and 8-HQL were the main algicidal components derived from Brevibacillus sp.. Thus, this study presents a streamlined strategy for identifying bacterial algicidal substances and unveils two novel and highly active algicidal substances. ENVIRONMENTAL IMPLICATION: Harmful cyanobacterial blooms (HCBs) pose significant environmental problems and health effects to humans and other organisms. The increasing frequency of HCBs has emerged as a pressing global concern. Bacterial-derived algicidal substances are expected to serve as effective, safe, and economically viable algaecides against HCBs. This study presents a streamlined strategy for identifying bacterial algicidal substances and unveils two novel substances (4-ABC and 8-HQL). These two substances demonstrate remarkable algicidal activity and disrupt the photosynthetic system in M. aeruginosa. They hold potential as prospective algaecides for addressing HCBs.

Development of a Novel Non-invasive Metabolomics Assay to Predict Implantation Potential of Human Embryos.

Can a set of metabolites present in embryo culture media correlate with embryo implantation? Case-control study in two phases: discovery phase (101 samples) and validation phase (169 samples), collected between 2018 and 2022, with a total of 218 participants. Culture media samples with known implantation outcomes were collected after blastocyst embryo transfer (including both PGT and non-PGT cycles) and were analyzed using chromatography followed by mass spectrometry. The spectra were processed and analyzed using statistical and machine learning techniques to identify biomarkers associated with embryo implantation, and to develop a predictive model. In the discovery phase, 148 embryo implantation biomarkers were identified using high resolution equipment, and 47 of them were characterized. Our results indicate a significant enrichment of tryptophan metabolism, arginine and proline metabolism, and lysine degradation biochemical pathways. After transferring the method to a lower resolution equipment, a model able to assign a Metabolite Pregnancy Index (MPI) to each embryo culture media was developed, taking the concentration of 36 biomarkers as input. Applying this model to 20% of the validation samples (N=34) used as the test set, an accuracy of 85.29% was achieved, with a PPV (Positive Predictive Value) of 88% and a NPV (Negative Predictive Value) of 77.78%. Additionally, informative results were obtained for all the analyzed samples. Metabolite concentration in the media after in vitro culture shows correlation with embryo implantation potential. Furthermore, the mathematical combination of biomarker concentrations using Artificial Intelligence techniques can be used to predict embryo implantation outcome with an accuracy of around 85%.