Search

Piercing/sucking insects such as green peach aphid (GPA) (Myzus persicae) cause direct damage by obtaining phloem nutrients and indirect damage by spreading plant viruses. To investigate the response of peach trees (Prunus persica) to aphids, the leaf transcriptome and metabolome of two genotypes with different sensitivities to GPA were studied. The gene expression of aphid-susceptible plants infested with aphids was similar to that of control plants, whereas the gene expression of aphid-resistant plants infested with aphids showed strong induced changes in gene expression compared with control plants. Furthermore, gene transcripts in defense-related pathways, including plant–pathogen interaction, MAPK signaling, and several metabolic pathways, were strongly enriched upon aphid infestation. Untargeted secondary metabolite profiling confirmed that aphid infestation induced larger changes in aphid-resistant than in aphid-susceptible peaches. Consistent with transcriptomic alterations, nine triterpenoids showed highly significant GPA-induced accumulation in aphid-resistant peaches, whereas triterpenoid abundance remained predominantly unchanged or undetected in aphid-susceptible peaches. Furthermore, some types of transcription factors (including WRKYs, ERFs, and NACs) were strongly induced upon GPA infestation in aphid-resistant, but not in aphid-susceptible peaches. These results suggested that the accumulation of specialized triterpenoids and the corresponding pathway transcripts may play a key role in peach GPA resistance. [ABSTRACT FROM AUTHOR]

The worm Caenorhabditis elegans, with its short lifecycle and well-known genetic and metabolic pathways, stands as an exemplary model organism for biological research. Its simplicity and genetic tractability make it an ideal system for investigating the effects of different conditions on its metabolism. The chemical analysis of this nematode was performed to identify specific metabolites produced by the worms when fed with either self- or nonself-DNA. A standard diet with OP50 feeding was used as a control. Different development stages were sampled, and their chemical composition was assessed by liquid chromatography–mass spectrometry combined with chemometrics, including both principal component analysis and orthogonal partial least squares discriminant analysis tools. The obtained data demonstrated that self-DNA-treated larvae, when arrested in their cycle, showed significant decreases in dynorphin, an appetite regulator of the nematode, and in N-formyl glycine, a known longevity promoter in C. elegans. Moreover, a substantial decrease was also recorded in the self-DNA-fed adults for the FMRF amide neuropeptide, an embryogenesis regulator, and for a dopamine derivative modulating nematode locomotion. In conclusion, this study allowed for the identification of key metabolites affected by the self-DNA diet, providing interesting hints on the main molecular pathways involved in its biological inhibitory effects. [ABSTRACT FROM AUTHOR]

Detection of biomarkers was extremely important for the early diagnosis, prognosis, and therapy optimization of diseases. The purpose of this study was to investigate the differences in serum metabolites between patients with heart failure (HF) and healthy control (HC) and to diagnose HF qualitatively. In this study, serum samples from 83 patients with HF and 35 HCs were used as the research subjects for untargeted metabolomic analysis using ultraperformance liquid chromatography combined with quadrupole‐time of flight mass spectrometry (UPLC‐QTOF/MS) technology. Potential biomarkers were screened and validated using the orthogonal partial least squares discriminant analysis (OPLS‐DA), random forest (RF), binary logistic regression (BLR), and receiver operating characteristic (ROC) analysis. The results indicated that a total of 43 metabolites were considered as differentially expressed metabolites (DEMs). Among these DEMs, glycodeoxycholate was identified as a specific biomarker of HF. A ROC curve analysis for HC versus HF discrimination showed an area under the ROC curve (AUC) of 0.9853 (95% CI: 0.9859–1.0000), a sensitivity of 95%, and a specificity of 100%. Hence, glycodeoxycholate might serve as a potential biomarker for HF. Furthermore, the amino acid metabolism was screened as the most significantly altered pathway in patients with HF. By identifying serum biomarkers and analyzing metabolic pathways, our study provided opportunities to enhance the understanding of the pathogenesis and early diagnosis of HF. [ABSTRACT FROM AUTHOR]

Root-knot nematode, Meloidogyne incognita Kofoid and White, 1919 is a major endoparasite that causes significant economic losses in several Solanaceous crops worldwide, including chilli (Capsicum annuum). In the present study, 66 accessions were screened for sources of resistance to M. incognita Race 1. The accessions EC399535 and EC402105 showed less than 10 number of galls and egg mass per root system [RKI:2 (1–10 galls or egg mass/ root system)] and identified as resistant accessions against M. incognita. Further, metabolic profiling analysis in the roots of resistant and susceptible (EC378632 and Arka Lohit) accessions exposed to M. incognita was carried out using gas chromatography-mass spectrometry (GC-MS). Non-targeted metabolic analysis detected 116 metabolites, which were further subjected to partial least squares-discriminant analysis (PLS-DA) with variable importance in projection (VIP) score to measure accumulation pattern in resistant and susceptible genotypes. VIP score revealed that 14 metabolites showed higher accumulation (> 1.5 VIP score) in resistant germplasm compared to susceptible germplasm. Specific metabolites viz., phytosterols, delta-tocopherol and squalene showed > 2.0 VIP score. Heatmap analysis differentiated metabolite abundance in each germplasm under M. incognita-infected and non-infected conditions. Dendrogram clustering analysis of metabolites data clearly separated resistant and susceptible accessions. The most significant metabolic pathways activated in M. incognita-resistance were phenylalanine metabolism (0.23529 impact), and sesquiterpenoid and triterpenoid biosynthesis (0.21622 impact) and alanine, aspartate and glutamate metabolism (0.19784 impact). This study provides valuable insights into compounds involved in defense activities against M. incognita. However, more research on the nematostatic or nematicidal activities of these metabolites including chemical inhibition or gene silencing of metabolites in plants is required for understanding the resistance mechanism and utilizing these metabolites as a biomarkers in resistance breeding programme. [ABSTRACT FROM AUTHOR]

White pepper, used both as a seasoning in people's daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper. [ABSTRACT FROM AUTHOR]

Abstract Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed. Graphical Abstract

There is an urgent need to explore natural sources like Caulerpa racemosa (Försskal) J. Agardh for bioactive compounds with strong antioxidant and therapeutic potential, providing sustainable alternatives for health and pharmaceutical innovation. This study aimed to determine the phytochemical profile and biological activities of extracts from edible green algae–known as sea grapes (C. racemosa). This present study has successfully identified secondary metabolites through untargeted metabolomic profiling by liquid chromatography-high resolution mass spectrometry (LC-HRMS) as well as a bioactive peptide. The antioxidant activity and cytotoxicity of extracts from C. racemosa and compounds were determined. A total of 103 metabolites were identified in the C. racemosa extract obtained by the maceration (ME), while 48 metabolites were detected in the soxhlet extract (SE). The sequence of the identified peptide was ELWKTF (Glu-Leu-Trp-Lys-Thr-Phe; C41H58N8O) and its abundance was identified in the α-chymotrypsin hydrolysate of C. racemosa. In the antioxidant activity test, SE and purified fraction 1 (PF1) had EC50

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed. [ABSTRACT FROM AUTHOR]

Pritelivir is a helicase‐primase inhibitor active against HSV. Two human mass balance trials (a multiple‐dose trial and a single‐dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C‐pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half‐life of pritelivir was 63‐67 hours. Overall, 92% and 66% of the administered dose was recovered in the multiple and single dose trials, respectively. The low recovery after the single dose (66%) was most likely related to the formulation used. The major metabolic pathway was amide hydrolysis leading to amino thiazole sulfonamide (ATS) and pyridinyl phenyl acetic acid (PPA). In plasma, pritelivir, ATS, PPA, and PPA‐acyl glucuronide accounted for 40.6%, 9.4%, 5.1%, and 0.2% of total radioactivity. More than 90% of drug‐related material was eliminated 624 hours postdose. The majority was excreted in urine (75% and 77%), followed by feces (16% and 23%). The main components in urine were PPA‐acyl glucuronide (and its isomers), ATS, and its N‐demethylated isomers. Only minor metabolites were observed in feces. In conclusion, the major metabolic pathways of pritelivir have been identified with the primary excretion route being renal. [ABSTRACT FROM AUTHOR]

Aims: Soil metabolites have a great influence on regulating the growth and development of plants and microbes in forest ecosystems. This study aims to reveal the characteristic metabolite profiles and their enriched metabolic pathways in the rhizosphere soil of Masson pine plantations at three different ages. Method: The rhizosphere soil of Masson pine from 10, 31, and 52 years plantation was collected. The metabolites were analyzed using a soil pseudotargeted metabolomics approach and then the relationships between soil metabolites and chemical properties, enzyme activities were established. Results: A total of 172 rhizosphere soil metabolites in 26 classes were identified. There was a decreasing trend in the total concentration of rhizosphere soil metabolites with increasing stand age. Seventy-two characteristic metabolites were screened, mainly saccharides, fatty acids, amino acids, phenolic acids, polyols and terpenoids. Among them, benzoic acid and galactonic acid contributed the most to the young forest, and stearic acid had the greatest influence on the near-mature forest plantation. Erythritol had great effects on the mature forest plantation. Seven metabolic pathways changed with increasing stand age. Correlation analysis showed that available potassium (AK) and soil alkaline protease (S-ALPT) were significantly positively correlated with phenolic acids, polyhydroxy carboxylic acids, etc. Conclusion: The rhizosphere soil of Masson pine had different metabolite profiles at different developmental stages, and the soil nutrient pools were effectively improved. These results provide a reference for plantation management in Masson pine and a deeper understanding of forest metabolic characteristics. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) supplementation can rescue poor oocyte quality and overcome embryonic arrest. Here, we investigated a series of sexually mature pigs generated through autologous and heterologous mtDNA supplementation. Brain, liver and heart tissues underwent metabolite profiling using gas chromatography–mass spectrometry and gene expression analysis through RNA-seq. They were then assessed for mRNA–metabolite interactions. The comparison between overall mtDNA supplemented and control pigs revealed that mtDNA supplementation reduced the lipids stearic acid and elaidic acid in heart tissue. However, heterologous mtDNA supplemented-derived pigs exhibited lower levels of abundance of metabolites when compared with autologous-derived pigs. In the brain, these included mannose, mannose 6-phosphate and fructose 6-phosphate. In the liver, maltose and cellobiose, and in the heart, glycine and glutamate were affected. mRNA–metabolite pathway analysis revealed a correlation between malate and CS, ACLY, IDH2 and PKLR in the liver and glutamate and PSAT1, PHGDH, CDO1 and ANPEP in the heart. Our outcomes demonstrate that mtDNA supplementation, especially heterologous supplementation, alters the metabolite and transcriptome profiles of brain, liver, and heart tissues. This is likely due to the extensive resetting of the balance between the nuclear and mitochondrial genomes in the preimplantation embryo, which induces a series of downstream effects.

The aroma-active compounds produced by Saccharomyces cerevisiae during the fermentation of wort are key to the unique aroma and flavour profiles of beer. In commercial fermentations, there is batch-to-batch variation depending on yeast “brewing fitness” or the health of the yeast, but how does yeast health impact fermentation performance and metabolite production during fermentation? To address this, daily samples were collected from three full-scale commercial fermentations. The specific gravity was measured immediately, and samples were collected for carbohydrate analysis by High-Performance Liquid Chromatography and volatile compound analysis by Head-Space Gas Chromatography Mass Spectrometry (HS-GC-MS). Acetate esters (3), medium-chain fatty acid ethyl esters (7), hop-derived compounds (3), and an off-flavour (1) were detected and identified, and their relative signal was recorded for each sample. While there did not appear to be an effect of generational age on the duration of fermentation, age, in terms of the number of generations from serial re-pitching, impacted the ratios of volatile compounds. This difference in ratios was observed as early as Day 2, resulting in a difference in the volatile compound profiles of finished beers, therefore resulting in inconsistency in the product. This is important knowledge for brewers as generational age must be considered when fermenting high-quality, consistent products and monitoring fermentation progress/duration may not be enough to determine the ability of yeast to produce balanced flavour profiles.

The worm Caenorhabditis elegans, with its short lifecycle and well-known genetic and metabolic pathways, stands as an exemplary model organism for biological research. Its simplicity and genetic tractability make it an ideal system for investigating the effects of different conditions on its metabolism. The chemical analysis of this nematode was performed to identify specific metabolites produced by the worms when fed with either self- or nonself-DNA. A standard diet with OP50 feeding was used as a control. Different development stages were sampled, and their chemical composition was assessed by liquid chromatography–mass spectrometry combined with chemometrics, including both principal component analysis and orthogonal partial least squares discriminant analysis tools. The obtained data demonstrated that self-DNA-treated larvae, when arrested in their cycle, showed significant decreases in dynorphin, an appetite regulator of the nematode, and in N-formyl glycine, a known longevity promoter in C. elegans. Moreover, a substantial decrease was also recorded in the self-DNA-fed adults for the FMRF amide neuropeptide, an embryogenesis regulator, and for a dopamine derivative modulating nematode locomotion. In conclusion, this study allowed for the identification of key metabolites affected by the self-DNA diet, providing interesting hints on the main molecular pathways involved in its biological inhibitory effects.

Saliva, which contains molecular information that may reflect an individual's health status, has become a valuable tool for discovering biomarkers of oral and general diseases. Due to the high vascularization of the salivary glands, there is a molecular exchange between blood and saliva. However, the composition of saliva is complex and influenced by multiple factors. This study aimed to investigate the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using 1H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole-saliva samples collected concurrently from the same individuals using multivariate and univariate statistical analysis. Our results show that serum is more concentrated and less variable for most of the shared metabolites than the three saliva types. While we found moderate to strong correlations between serum and saliva concentrations of specific metabolites, saliva is not simply an ultrafiltrate of blood. The intense oral metabolism prevents very strong correlations between serum and salivary concentrations. This study contributes to a better understanding of salivary metabolic composition, which is crucial for utilizing saliva in laboratory diagnostics. [ABSTRACT FROM AUTHOR]

Adenanthera pavonina is a medicinal species, which economic value depends on the richness of its phytocompounds. Extreme climatic conditions are becoming frequent worldwide, but despite their impact on plant productivity these weather events also modulate plants' metabolism increasing the production of important phytocompounds. We aimed to characterize the physiological and metabolite adjustments in A. pavonina leaves induced by drought and UV-B radiation. Plants were exposed to drought (DS), UV-B radiation (UV-B), and drought + UV-B (DS + UV-B), and photosynthesis, lipophilic metabolites, and antioxidant status were evaluated. The stress conditions compromised the photosynthetic performance and induced oxidative stress (DS and UV-B plants). However, plants activated protective mechanisms (increased antioxidant activity and flavonoids in all treatments, total phenols in DS and DS + UV-B, and catechols in UV-B and DS + UV-B) and modulated their lipophilic profiles (accumulation of fatty acids and TCA cycle-related metabolites, and reduction of carbohydrates) to cope with the stress. We demonstrate for the first time that DS and UV-B radiation can enrich A. pavonina leaves with antioxidants and fatty acids increasing their medicinal value. [ABSTRACT FROM AUTHOR]

Abstract Background Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection. Methods This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis. Results The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum. Conclusions This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.

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

Du-Zhi pill (DZP) is widely used as a Chinese medicine in treating cerebral ischemia. UHPLC-Q-TOF-MS/MS techniques were used to detect and identify the metabolites in rat brain samples of normal and middle cerebral artery occlusion (MCAO) model rats administered with DZP. It was tentatively found that 43 prototypes and 93 metabolites could be identified in rat brain samples. Normal and MCAO model rat brain samples contained 19 prototype components. Eight prototype components were only detected in normal rat brain samples, while 16 were found only in MCAO model rat brain samples. It was determined that 47 metabolites had been identified in the normal rats, while 86 had been placed in MCAO model rats. There were 40 common metabolites in both normal and MCAO model rat brain samples. Seven metabolites were only detected in normal rat brain samples, while 46 were found only in MCAO rat brain samples. The comparison of metabolites in brain samples of normal and MCAO rats showed apparent differences. It was discovered that glucuronidation, methylation, acetylation, and sulfation are phase II metabolic routes of DZP, while hydrogenation, hydroxylation, and dehydroxylation are phase I metabolic routes. Moreover, hydrogenation, glucuronidation, hydroxylation, and methylation were the main metabolic pathways because of the number of metabolites identified in these metabolic pathways. The results provide a valuable reference for further research into effective substances of DZP for treating cerebral ischemia.

Cowpea is considered an important food in the Southwest Maluku (SWM) District with high morphogenetic diversity. However, information on nutrition and metabolite profiles of the cowpea from SWM has been unrevealed for a new food ingredient for local people of SWM. The laboratory work was conducted descriptively to reveal the nutrient composition of the metabolite profile of some local cowpeas from SWM, Indonesia using High-Performance Liquid Chromatography (HPLC) and Gas Chromatography -Mass Spectrometry (GC-MS) methods. Key chemical profiles of amino acids, fatty acids, flavonoids, phenolic acids, and other secondary metabolites in cowpeas were analyzed using PCA. The results showed that there were fifteen amino acids, 35 fatty acids, and 52 secondary metabolites identified. The highest amino acid content found in all varieties was glutamic acid at 4.32 ± 0.31%. The highest fatty acid content was identified as arachidic acid at 15.83 ± 3.94%. The plant sterol identified in all varieties was stigmasterol with an average of 3.05 ± 0.43%. The KM7 variety had the highest amino acid in contrast to the KM6 variety. The highest stigmasterol, total flavonoids, and total phenolic content were found in the KM3 variety. These results reveal that local cowpeas have the potential for nutritional and functional food development.

Plant and soil biodiversity can have significant effects on herbivore resistance mediated by plant metabolites. Here, we disentangled the independent effects of plant diversity and soil legacy on constitutive and herbivore‐induced plant metabolomes of three plant species in two complementary microcosm experiments. First, we grew plants in sterile soil with three different plant diversity levels. Second, single plant species were grown on soil with different plant diversity‐induced soil legacies. We infested a subset of all plants with Spodoptera exigua larvae, a generalist leaf‐chewing herbivore, and assessed foliar and root metabolomes. Neither plant diversity nor soil legacy had significant effects on overall foliar, root, or herbivore‐induced metabolome composition. Herbivore‐induced metabolomes, however, differed from those of control plants. We detected 139 significantly regulated metabolites by comparing plants grown in monocultures with conspecifics growing in plant or soil legacy mixtures. Moreover, plant–plant and plant–soil interactions regulated 141 metabolites in herbivore‐induced plants. Taken together, plant diversity and soil legacy independently alter the concentration and induction of plant metabolites, thus affecting the plant's defensive capability. This is a first step toward disentangling plant and soil biodiversity effects on herbivore resistance, thereby improving our understanding of the mechanisms that govern ecosystem functioning. [ABSTRACT FROM AUTHOR]

Purpose: To determine the chemical composition of fruit (apple and orange) and vegetable (carrot) pomaces in order to assess their potential use in value-added products. Methods: A range of bromatological and mass spectrometry-based metabolomic analyses were employed to chemically characterise apple, orange, and carrot pomaces. Results: Dietary fibre was the most abundant component of the substrates, comprising most by cellulose and pectin. Another major component of the pomaces were soluble sugars. Nevertheless, all pomaces showed low levels of lipids (below 5%) with most of the fatty acids being unsaturated. Besides, each pomace was found to have a more diverse metabolomic composition than earlier described, and the variation between batches was not significantly different for most parameters tested. Conclusion: This study shows that these food-grade pomaces have good potential for bioconversion into high-value-added products via microbial fermentation, and not solely for the extraction of a small number of chemical compounds. In addition, untargeted metabolomic tools showed great potential in providing a more comprehensive analysis of waste biomass composition, as well as potentially being useful in food and feed safety assessment. [ABSTRACT FROM AUTHOR]

Background: Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection. Methods: This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis. Results: The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum. Conclusions: This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography–tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis. [ABSTRACT FROM AUTHOR]

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

Cyanobacteria have demonstrated their therapeutic potential for many human diseases. In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives—two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Cassava mosaic disease (CMD) of cassava (Manihot esculenta Crantz) has expanded across many continents. Sri Lankan cassava mosaic virus (SLCMV; family Geminiviridae), which is the predominant cause of CMD in Thailand, has caused agricultural and economic damage in many Southeast Asia countries such as Vietnam, Loas, and Cambodia. The recent SLCMV epidemic in Thailand was commonly found in cassava plantations. Current understanding of plant–virus interactions for SLCMV and cassava is limited. Accordingly, this study explored the metabolic profiles of SLCMV-infected and healthy groups of tolerant (TME3 and KU50) and susceptible (R11) cultivars of cassava. Findings from the study may help to improve cassava breeding, particularly when combined with future transcriptomic and proteomic research. Results SLCMV-infected and healthy leaves were subjected to metabolite extraction followed by ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS/MS). The resulting data were analyzed using Compound Discoverer software, the mzCloud, mzVault, and ChemSpider databases, and published literature. Of the 85 differential compounds (SLCMV-infected vs healthy groups), 54 were differential compounds in all three cultivars. These compounds were analyzed using principal component analysis (PCA), hierarchical clustering dendrogram analysis, heatmap analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Chlorogenic acid, DL-carnitine, neochlorogenic acid, (E)-aconitic acid, and ascorbyl glucoside were differentially expressed only in TME3 and KU50, with chlorogenic acid, (E)-aconitic acid, and neochlorogenic acid being downregulated in both SLCMV-infected TME3 and KU50, DL-carnitine being upregulated in both SLCMV-infected TME3 and KU50, and ascorbyl glucoside being downregulated in SLCMV-infected TME3 but upregulated in SLCMV-infected KU50. Furthermore, 7-hydroxycoumarine was differentially expressed only in TME3 and R11, while quercitrin, guanine, N-acetylornithine, uridine, vorinostat, sucrose, and lotaustralin were differentially expressed only in KU50 and R11. Conclusions Metabolic profiling of three cassava landrace cultivars (TME3, KU50, and R11) was performed after SLCMV infection and the profiles were compared with those of healthy samples. Certain differential compounds (SLCMV-infected vs healthy groups) in different cultivars of cassava may be involved in plant–virus interactions and could underlie the tolerance and susceptible responses in this important crop.

White pepper, used both as a seasoning in people’s daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.

Abstract Plant and soil biodiversity can have significant effects on herbivore resistance mediated by plant metabolites. Here, we disentangled the independent effects of plant diversity and soil legacy on constitutive and herbivore‐induced plant metabolomes of three plant species in two complementary microcosm experiments. First, we grew plants in sterile soil with three different plant diversity levels. Second, single plant species were grown on soil with different plant diversity‐induced soil legacies. We infested a subset of all plants with Spodoptera exigua larvae, a generalist leaf‐chewing herbivore, and assessed foliar and root metabolomes. Neither plant diversity nor soil legacy had significant effects on overall foliar, root, or herbivore‐induced metabolome composition. Herbivore‐induced metabolomes, however, differed from those of control plants. We detected 139 significantly regulated metabolites by comparing plants grown in monocultures with conspecifics growing in plant or soil legacy mixtures. Moreover, plant–plant and plant–soil interactions regulated 141 metabolites in herbivore‐induced plants. Taken together, plant diversity and soil legacy independently alter the concentration and induction of plant metabolites, thus affecting the plant's defensive capability. This is a first step toward disentangling plant and soil biodiversity effects on herbivore resistance, thereby improving our understanding of the mechanisms that govern ecosystem functioning.

Gansuibanxia decoction (GSBXD), a traditional Chinese medicine (TCM) formula with 2000 years of history, has good efficacies on treating cancerous ascites, pleural effusion, etc. However, little is known about its metabolite profiles owing to the lack of in vivo studies. In this study, we explored the prototypes and metabolites of GSBXD in rat plasma and urine using UHPLC–Q‐TOF/MS technology. A total of 82 GSBXD‐related xenobiotic bioactive components (38 prototypes and 44 metabolites) were confirmed or tentatively characterized, including 32 prototypes and 29 metabolites in plasma, and 25 prototypes and 29 metabolites in urine. The results showed that the bioactive components absorbed in vivo mainly contained diterpenoids, triterpenoids, flavonoids and monoterpene glycosides. Both phase I reactions (methylation, reduction, demethylation, hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation and sulfation) were involved in the metabolism of GSBXD in vivo. This study will provide a foundation for the quality control, pharmacological study and clinical application of GSBXD. [ABSTRACT FROM AUTHOR]

Graviera is a very popular yellow hard cheese produced in mainland Greece and the Aegean islands, and in three PDO (protected denomination of origin) locations. Apart from geographic location, type of milk and production practices are also factors that affect cheese composition, and make this dairy product unique in taste and aroma. In this work, 1H nuclear magnetic resonance (NMR) spectroscopy in combination with chemometrics has been used to determine the metabolite profile (40 compounds) of graviera cheese produced in different geographic locations, with emphasis on cheeses produced on the island of Crete. Organic acids and amino acids were the main components quantified in the polar cheese fraction, while the fatty acid (FA) composition of the lipid fraction was also obtained. Analysis of variance (Anova) of the dataset showed that γ-aminobutyric acid (GABA), conjugated linoleic acids (CLA) and linoleic acid differentiate gravieras produced in different areas of Crete, and that the total amino acid content was higher in cheeses produced in eastern Crete. Targeted discriminant analysis models classified gravieras produced in mainland Greece, Cyclades and Crete based on differences in 1,2-diglycerides, sterols, GABA and FA composition. Targeted and untargeted orthogonal partial least squares discriminant analysis (OPLS-DA) models were capable of differentiating gravieras produced in the island of Crete and hold promise as the basis for the authentication of PDO graviera products. [ABSTRACT FROM AUTHOR]

Progression of leaf senescence consists of both degenerative and nutrient recycling processes in crops including wheat. However, the levels ofmetabolites in flag leaves in spring-cultivated wheat, as well as biosynthetic pathways involved under different nitrogen fertilization regimes, are largely unknown. Therefore, the present study employed a widely untargeted metabolomic profiling strategy to identify metabolites and biosynthetic pathways that could be used in a wheat improvement program aimed at manipulating the rate and onset of senescence by handling spring wheat (Dingxi 38) flag leaves sampled from no-, low-, and highnitrogen (N) conditions (designated Groups 1, 2, and 3, respectively) across three sampling times: anthesis, grain filling, and end grain filling stages. Through ultrahighperformance liquid chromatography--tandem mass spectrometry, a total of 826 metabolites comprising 107 flavonoids, 51 phenol lipids, 37 fatty acyls, 37 organooxygen compounds, 31 steroids and steroid derivatives, 18 phenols, and several unknown compounds were detected. Upon the application of the stringent screening criteria for differentially accumulated metabolites (DAMs), 28 and 23 metabolites were differentially accumulated in Group 1_vs_Group 2 and Group 1_vs_Group 3, respectively. From these, 1-O-Caffeoylglucose, Rhoifolin, Eurycomalactone;Ingenol, 4-Methoxyphenyl beta-D-glucopyranoside, and Baldrinal were detected as core conserved DAMs among the three groups with all accumulated higher in Group 1 than in the other two groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that tropane, piperidine, and pyridine alkaloid biosynthesis; acarbose and validamycin biosynthesis; lysine degradation; and biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid pathways were the most significantly (p < 0.05) enriched in Group 1_vs_Group 2, while flavone and flavonol as well as anthocyanins biosynthetic pathways were the most significantly (p < 0.05) enriched in Group 1_vs_Group 3. The results from this study provide a foundation for themanipulation of the onset and rate of leaf senescence and N remobilization in wheat. [ABSTRACT FROM AUTHOR]

The brown seaweed Alaria esculenta is the second most cultivated species in Europe, and it is therefore of interest to expand its application by developing food products. In this study, a lactic acid bacteria consortium (LAB consortium) consisting of three Lactiplantibacillus plantarum strains (relative abundance ~94%) and a minor amount of a Levilactobacillus brevis strain (relative abundance ~6%) was investigated for its ability to ferment carbohydrates available in brown seaweed. The consortium demonstrated the ability to ferment glucose, mannitol, galactose, mannose, and xylose, of which glucose and mannitol were the most favored substrates. No growth was observed on fucose, mannuronic and guluronic acid. The consortium used different pathways for carbohydrate utilization and produced lactic acid as the main metabolite. In glucose fermentation, only lactic acid was produced, but using mannitol as a carbohydrate source resulted in the co-production of lactic acid, ethanol, and succinate. Xylose fermentation resulted in acetate production. The consortium was also able to utilize laminari-oligosaccharides (DP2-4), obtained after enzymatic hydrolysis of laminarin, and produced lactic acid as a metabolite. The consortium could grow directly on A. esculenta, resulting in a pH decrease to 3.8 after 7 days of fermentation. Incubation of the same seaweed in corresponding conditions without inoculation resulted in spoilage of the seaweed by endogenous bacteria. [ABSTRACT FROM AUTHOR]

Aluminum (Al) toxicity causes a substantial crop productivity loss in acid soil. Here, we evaluated the antioxidant responses and metabolic adjustments in soybean roots after Al exposure and demonstrated that different genotypes from the same species can present distinctive strategies to avoid Al toxicity. Soybean genotypes were exposed to nutrient Clark solution (pH 4.0) under two cultivation conditions: 0 µM (control) and 100 µM AlCl3 for 24, 48, and 72 h. Our results demonstrated that the soybean genotypes 'P98Y70' and 'Conquista' present different tolerance to Al. The root growth of P98Y70 genotype was impaired under Al treatment. Besides, this genotype showed a delay and lower activities in their antioxidant enzymes, which culminates in a high accumulation of reactive oxygen species (ROS). On the other hand, the Conquista genotype showed an early antioxidant enzymatic response through the increase in the superoxide dismutase (SOD), catalase (CAT), and total peroxidase (POX) activities at 24 h of Al exposure, whereas P98Y70 showed high SOD and POX activities only at 72 h. Besides, the Conquista genotype presented high levels of ascorbate, fructose-6-phosphate (F6P), and high activity in the glutathione peroxidase (GPX), which culminated in a low accumulation of ROS and less oxidative stress. Therefore, these traits can be used as biomarkers of Al tolerance in soybean plants when associated with an early response against Al. [ABSTRACT FROM AUTHOR]

• Sodium salts with Cl− and SO42− anions promoted Cd translocation into wheat tissues. • High levels of sodium salts in the soil triggered an up-regulation of the TCA cycle. • Accumulation of organic acids in the rhizosphere facilitated migration of soil Cd. • Salts altered Cd mobility by mediating soil metabolite profiles and physicochemical properties. Soil salinity is known to improve cadmium (Cd) mobility, especially in arid soils. However, the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant system remain poorly understood. This study was designed to investigate the effects of salinity-induced changes in soil metabolites on Cd bioavailability. Sodium salts in different combinations according to molar ratio (NaCl:Na 2 SO 4 =1:1; NaCl:Na 2 SO 4 :NaHCO 3 =1:2:1; NaCl:Na 2 SO 4 :NaHCO 3 :Na 2 CO 3 =1:9:9:1; NaCl:Na 2 SO 4 :NaHCO 3 :Na 2 CO 3 =1:1:1:1) were applied to the Cd-contaminated soils, which increased soil Cd availability by 22.36% and the Cd content in wheat grains by 36.61%, compared to the control. Salt stress resulted in soil metabolic reprogramming, which might explain the decreased growth of wheat plants and increased Cd transport from the soil into wheat tissues. For example, down-regulation of starch and sucrose metabolism reduced the production of sugars, which adversely affected growth; up-regulation of fatty acid metabolism allowed wheat plants to maintain a normal intracellular environment under saline conditions; up-regulation of the tricarboxylic acid (TCA) cycle was triggered, causing an increase in organic acid synthesis and the accumulation of organic acids, which facilitated the migration of soil Cd into wheat tissues. In summary, salt stress can facilitate Cd transport into wheat tissues by the direct effect of salt-based ions and the combined effect of altered soil physicochemical properties and soil metabolic profiles in Cd-contaminated soils. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Cassava mosaic disease (CMD) of cassava (Manihot esculenta Crantz) has expanded across many continents. Sri Lankan cassava mosaic virus (SLCMV; family Geminiviridae), which is the predominant cause of CMD in Thailand, has caused agricultural and economic damage in many Southeast Asia countries such as Vietnam, Loas, and Cambodia. The recent SLCMV epidemic in Thailand was commonly found in cassava plantations. Current understanding of plant–virus interactions for SLCMV and cassava is limited. Accordingly, this study explored the metabolic profiles of SLCMV-infected and healthy groups of tolerant (TME3 and KU50) and susceptible (R11) cultivars of cassava. Findings from the study may help to improve cassava breeding, particularly when combined with future transcriptomic and proteomic research. Results: SLCMV-infected and healthy leaves were subjected to metabolite extraction followed by ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS/MS). The resulting data were analyzed using Compound Discoverer software, the mzCloud, mzVault, and ChemSpider databases, and published literature. Of the 85 differential compounds (SLCMV-infected vs healthy groups), 54 were differential compounds in all three cultivars. These compounds were analyzed using principal component analysis (PCA), hierarchical clustering dendrogram analysis, heatmap analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Chlorogenic acid, DL-carnitine, neochlorogenic acid, (E)-aconitic acid, and ascorbyl glucoside were differentially expressed only in TME3 and KU50, with chlorogenic acid, (E)-aconitic acid, and neochlorogenic acid being downregulated in both SLCMV-infected TME3 and KU50, DL-carnitine being upregulated in both SLCMV-infected TME3 and KU50, and ascorbyl glucoside being downregulated in SLCMV-infected TME3 but upregulated in SLCMV-infected KU50. Furthermore, 7-hydroxycoumarine was differentially expressed only in TME3 and R11, while quercitrin, guanine, N-acetylornithine, uridine, vorinostat, sucrose, and lotaustralin were differentially expressed only in KU50 and R11. Conclusions: Metabolic profiling of three cassava landrace cultivars (TME3, KU50, and R11) was performed after SLCMV infection and the profiles were compared with those of healthy samples. Certain differential compounds (SLCMV-infected vs healthy groups) in different cultivars of cassava may be involved in plant–virus interactions and could underlie the tolerance and susceptible responses in this important crop. [ABSTRACT FROM AUTHOR]

Changes in cultivation conditions, in particular salinity and temperature, affect the production of secondary fungal metabolites. In this work, the extracts of fungus previously described as Penicillium dimorphosporum cultivated in various salinity and temperature conditions were investigated using HPLC UV/MS techniques, and their DPPH radical scavenging and cytotoxicity activities against human prostate cancer PC-3 cells and rat cardiomyocytes H9c2 were tested. In total, 25 compounds, including 13 desoxyisoaustamide-related alkaloids and eight anthraquinones, were identified in the studied extracts and their relative amounts were estimated. The production of known neuroprotective alkaloids 5, 6 and other brevianamide alkaloids was increased in hypersaline and high-temperature conditions, and this may be an adaptation to extreme conditions. On the other hand, hyposalinity stress may induce the synthesis of unidentified antioxidants with low cytotoxicity that could be very interesting for future investigation. The study of secondary metabolites of the strain KMM 4689 showed that although brevianamide-related alkaloids and anthraquinone pigments are widely distributed in various fungi, these metabolites have not been described for P. dimorphosporum and related species. For this reason, the strain KMM 4689 was re-sequenced using the β-tubulin gene and ITS regions as molecular markers and further identified as P. hispanicum. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an important signaling molecule that plays a pivotal role in stress tolerance. To study the role of NO in drought tolerance and elucidate the underlying mechanisms, NO (0 and 100 μM) was applied to drought-treated soybean plants. Drought stress was imposed by PEG (5% (W/V) of PEG 6000. Nitric oxide improved growth of soybean plants under drought as evidenced by enhanced dry weight (30%). Nitric oxide caused a remarkable increase in activities of catalase and superoxide dismutase (SOD) and SOD expression (14.8-fold), which led to a significant decline in malondealdehyde content under drought conditions. Nitric oxide induced proline biosynthesis due to enhancing pyrroline-5- carboxylate synthetase (P5CS) expression (43.66-fold). The growth-promoting effect of NO application in soybean plants was concomitant with change in metabolic profile (phenolic acid and flavonoid compounds). Nitric oxide up-regulated of phenylalanine ammonia-lyase (PAL) expression in drought-treated plants and may influence on the phenylpropanoid production. Nitric oxide increased salicylic acid (SA) content in soybean plants under stress. So, NO and SA are jointly responsible for boosted tolerance to drought stress in soybean plants. The decrease in unsaturated fatty acid through NO application might reflect a reduction in oxidative damage. These results propose a multifaceted contribution of NO through regulation of physiological and metabolic processes in response to drought stress. [ABSTRACT FROM AUTHOR]

Abstract Background The adaptation of cellular metabolism is considered a hallmark of cancer. Oncogenic signaling pathways support tumorigenesis and cancer progression through the induction of certain metabolic phenotypes associated with altered regulation of key metabolic enzymes. Hydroxycarboxylic acid receptor 2 (HCA2) is a G protein-coupled receptor previously shown to act as a tumor suppressor. Here, we aimed to unveil the connection between cellular metabolism and HCA2 in BT-474 cells. Moreover, we intend to clarify how well this metabolic phenotype is reflected in transcriptional changes and metabolite levels as determined by global metabolomics analyses. Methods We performed both, siRNA mediated knockdown of HCA2 and stimulation with the HCA2-specific agonist monomethyl fumarate. Seahorse technology was used to determine the role of HCA2 in BT-474 breast cancer cell metabolism and its potential to induce a switch in the metabolic phenotype in the presence of different energy substrates. Changes in the mRNA expression of metabolic enzymes were detected with real-time quantitative PCR (RT-qPCR). Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolic profiling was used to determine changes in metabolite levels. Results Knockdown or stimulation of HCA2 induced changes in the metabolic phenotype of BT474 cells dependent on the availability of energy substrates. The presence of HCA2 was associated with increased glycolytic flux with no fatty acids available. This was reflected in the increased mRNA expression of the glycolytic enzymes PFKFB4 and PKM2, which are known to promote the Warburg effect and have been described as prognostic markers in different types of cancer. With exogenous palmitate present, HCA2 caused elevated fatty acid oxidation and likely lipolysis. The increase in lipolysis was also detectable at the transcriptional level of ATGL and the metabolite levels of palmitic and stearic acid. Conclusions We combined metabolic phenotype determination with metabolomics and transcriptional analyses and identified HCA2 as a regulator of glycolytic flux and fatty acid metabolism in BT-474 breast cancer cells. Thus, HCA2, for which agonists are already widely used to treat diseases such as psoriasis or hyperlipidemia, may prove useful as a target in combination cancer therapy.

Insect herbivory is a key process in ecosystem functioning. While theory predicts that plant diversity modulates herbivory, the mechanistic links remain unclear. We postulated that the plant metabolome mechanistically links plant diversity and herbivory.In late summer and in spring, we assessed individual plant above‐ground herbivory rates and metabolomes of seven plant species in experimental plant communities varying in plant species diversity and resource acquisition strategies. In the same communities, we also measured plant individual biomass as well as soil microbial and nematode community composition.Herbivory rates decreased with increasing plant species richness. Path modelling revealed that plant species richness and community resource acquisition strategy correlated with soil community composition. In particular, changes in nematode community composition were related to plant metabolome composition and thereby herbivory rates.Synthesis. These results suggest that soil community composition plays an important role in reducing herbivory rates with increasing plant diversity by changing plant metabolomes. [ABSTRACT FROM AUTHOR]

Mannan oligosaccharides (MOSs) have been implicated in the animal growth rate, health indices, and lipid oxidative stability. MOSs have been indicated to maintain intestinal health and anti-inflammatory effects via modulation of gut microbiota. Furthermore, the role of MOSs in modulating skeletal muscle function is largely unknown. Here, this study aimed to investigate the effects of MOS supplementation on muscle function and muscle mass in mice. Additionally, the possible underlying mechanisms, including the contributions of gut microbiota and microbial metabolites, were explored. In our study, 3-week-old C57BL/6J male mice (body weight of approximately 10.7 ± 1.1 g) were given pure water or pure water with 1% MOS. To study the effect of MOSs on gut-microbiota-derived metabolites, serum metabolic profiles were analyzed through untargeted metabolomic profiling. Moreover, we detected the downstream signals of differential metabolites, and decanoic acid (DA) was selected as our target spot. Then, DA was used to treat C2C12 cells, and we found that DA promotes C2C12 cell differentiation via the GPR84 and PI3K/AKT signaling pathways. In conclusion, these results showed that MOS supplementation improves muscle function and muscle mass. Additionally, gut microbiome and microbial metabolites were regulated by MOSs, and DA may be one of the most important links between the gut microbiome and skeletal muscle function regulation. [ABSTRACT FROM AUTHOR]

Panax japonicus C. A. Meyer is a plant of the Araliaceae family, and its rhizomes can be used as dietary supplements. It is extremely rich in bioactive components ginsenosides with benefits to human health. However, the underlying mechanisms of ginsenosides biosynthesis in Panax japonicus remains poorly understood. Therefore, a comprehensive analysis of the metabolites, transcriptome, and proteome was conducted to investigate ginsenoside metabolism of Panax japonicus. Here, three types of ginsenosides were found to exhibited tissue-specific distribution using the liquid chromatography-mass spectrometry method. Next, differentially expressed gene analysis revealed that transcript levels of ginsenosides biosynthetic genes have significant differences between differential samples. In addition, correlation analysis showed that the ginsenosides content was closely related to the expression level of 29 cytochrome P450s and 92 Uridine diphosphate-glycosyltransferases. Finally, phylogenetic analysis was performed for the target proteins to conduct preliminary studies on their functions and classification. This study provides insight into the dynamic changes and biosynthetic pathway of ginsenosides and offers valuable information on the metabolic regulation of Panax japonicus. [ABSTRACT FROM AUTHOR]

Background: Excessive dietary sodium intake is an independent risk factor for hypertension and cardiovascular disease (CVD). Despite the large body of evidence concerning the effects of dietary interventions on blood pressure (BP) and CVD outcomes, trials have often reported low adherence to decreased sodium intake, likely due in part to heterogeneous BP responses. To address the challenges, recent clinical findings suggested a precise and personalized dietary approach that seeks to deliver more preventive and practical dietary advice than the "one-size-fits-all" guidelines and weighs the personal risk of developing specific diseases. Objective: The purpose of this pilot randomized controlled trial was to test the feasibility and preliminary efficacy of integrating the use of mobile technology and metabolomics with a low-sodium diet intervention in patients with hypertension to develop personalized low-sodium diet programs. Additionally, the study will examine the associations of urine metabolites with urinary sodium levels and BP control based on the hypothesis that targeted urine metabolites. In this report, we describe the design and protocol of the pilot trial. Methods: A total of 40 patients with hypertension will be randomly assigned to either a 8-week low-sodium diet group (n=20) or a standard care group (n=20). Each week, intervention participants went through individual sessions with an interventionist via videoconferencing to discuss low-sodium diet regimens, patients' food choices, and BP tracks on mobile apps. The control group followed their usual care for hypertension management. All participants in both groups monitored diet and BP using mobile apps for 8 weeks. A 24-hour urinary sodium excretion for the estimation of dietary sodium intake, systolic, and diastolic BPs were measured at the baseline and at 8 weeks. The primary outcomes of this study include the feasibility of conducting a randomized controlled trial (RCT) by reporting recruitment, retention, and completion statistics. The preliminary effects of intervention will be tested by a generalized estimating equation model. Results: This pilot RCT study was approved by the institutional review board at the University of Texas Health San Antonio in January 2021. The first participant was enrolled in April 2021, and currently, 26 participants were enrolled. All data collection is expected to conclude by March 2023, with data analysis and study results ready for reporting by December 2023. Findings from this pilot RCT will further guide the team in planning a future large-scale study. Conclusions: The findings of this proposed study will establish a comprehensive knowledge base for future research and development of personalized dietary interventions to promote adherence to dietary strategies and self-management of chronic disease using the Precision Health approach for millions of Americans who are struggling with uncontrolled hypertension. [ABSTRACT FROM AUTHOR]

Cyanobacteria have demonstrated their therapeutic potential for many human diseases. In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives—two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future.

Fetal tobacco exposure has persistent effects on growth and metabolism. The underlying mechanisms of these relationships are yet unknown. We investigated the associations of fetal exposure to maternal smoking with neonatal metabolite profiles. In a population-based cohort study among 828 mother-infant pairs, we assessed maternal tobacco use by questionnaire. Metabolite concentrations of amino acids, non-esterified fatty acids, phospholipids and carnitines were determined by using LC-MS/MS in cord blood samples. Metabolite ratios reflecting metabolic pathways were computed. Compared to non-exposed neonates, those exposed to first trimester only tobacco smoking had lower neonatal mono-unsaturated acyl-alkyl-phosphatidylcholines (PC.ae) and alkyl-lysophosphatidylcholines (Lyso.PC.e) 18:0 concentrations. Neonates exposed to continued tobacco smoking during pregnancy had lower neonatal mono-unsaturated acyl-lysophosphatidylcholines (Lyso.PC.a), Lyso.PC.e.16:0 and Lyso.PC.e.18:1 concentration (False discovery rate (FDR) p-values < 0.05). Dose-response associations showed the strongest effect estimates in neonates whose mothers continued smoking ≥5 cigarettes per day (FDR p-values < 0.05). Furthermore, smoking during the first trimester only was associated with altered neonatal metabolite ratios involved in the Krebs cycle and oxidative stress, whereas continued smoking during pregnancy was associated with inflammatory, transsulfuration, and insulin resistance markers (p-value < 0.05). Thus, fetal tobacco exposure seems associated with neonatal metabolite profile adaptations. Whether these changes relate to later life metabolic health should be studied further. [ABSTRACT FROM AUTHOR]

Medicinal plants are now widely used for various purposes, such as preventing and treating diseases. One of the medicinal plants widely used as traditional medicines and already commercialized is Sonchus arvensis, known as show thistle and S. arvensis in Indonesia. This review will highlight information about the traditional uses, phytochemical compounds, and biological activities of S. arvensis to increase our knowledge and understanding of this plant. We prepared this mini-review by finding sources of information in several scientific paper databases. As a traditional medicine, S. arvensis could be consumed to cure or prevent diseases. Secondary metabolites present in S. arvensis such as alkaloids, phenolics, flavonoids, and terpenoids are responsible for some biological activities of S. arvensis, such as antioxidant, antibacterial, antiinflammatory, antihypertensive, antihyperuricemic, and antidiabetic activities. [ABSTRACT FROM AUTHOR]

Holothuria atra is a species of sea cucumber that could be a source of cytotoxic compounds. The present work aimed to determine the effect of different drying techniques on the profile of metabolites and cytotoxicity of sea cucumber extracts. Sea cucumbers were dried in the sun for 3 d, and oven-dried at a temperature of 40, 50, and 60°C for 24 h. Fresh sea cucumbers without drying served as a control. The dried and fresh sea cucumbers were extracted by maceration for 12 h using ethanol. The metabolite profiling was performed using Fourier-transform infrared spectroscopy (FTIR) and highperformance liquid chromatography (HPLC) analyses, whereas the cytotoxicity was assayed by MTT method using the human breast ductal carcinoma cells (T47D). Analyses of FTIR and HPLC showed that the bioactive compounds of the ethanol extract were relatively stable during drying. This was in line with its cytotoxicity against T47D cells, which did not show significant differences between treatments. Based on these results, it was concluded that drying by sun or oven did not damage the bioactive compounds in the ethanolic extract of sea cucumber. [ABSTRACT FROM AUTHOR]

Key message: High pigment mutants in tomato (Solanum lycopersicum L.), a loss of function in the control of photomorphogenesis, with greater pigment production, show altered growth, greater photosynthesis, and a metabolic reprogramming. High pigment mutations cause plants to be extremely responsive to light and produce excessive pigmentation as well as fruits with high levels of health-beneficial nutrients. However, the association of these traits with changes in the physiology and metabolism of leaves remains poorly understood. Here, we performed a detailed morphophysiological and metabolic characterization of high pigment 1 (hp1) and high pigment 2 (hp2) mutants in tomato (Solanum lycopersicum L. 'Micro-Tom') plants under different sunlight conditions (natural light, 50% shading, and 80% shading). These mutants occur in the DDB1 (hp1) and DET1 (hp2) genes, which are related to the regulation of photomorphogenesis and chloroplast development. Our results demonstrate that these mutations delay plant growth and height, by affecting physiological and metabolic parameters at all stages of plant development. Although the mutants were characterized by higher net CO2 assimilation, lower stomatal limitation, and higher carboxylation rates, with anatomical changes that favour photosynthesis, we found that carbohydrate levels did not increase, indicating a change in the energy flow. Shading minimized the differences between mutants and the wild type or fully reversed them in the phenotype at the metabolic level. Our results indicate that the high levels of pigments in hp1 and hp2 mutants represent an additional energy cost for these plants and that extensive physiological and metabolic reprogramming occurs to support increased pigment biosynthesis. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is closely related to gut microbiota due to the hepatic portal system, and utilizing natural polysaccharides as prebiotics has become a prospective strategy for treating NAFLD. However, the therapeutic effects and potential molecular mechanisms of Lanzhou Lily polysaccharides (LLP) on NAFLD remains unclear. Therefore, the alleviating effects of LLP on NAFLD induced by high-fat diet (HFD) were investigated. LLP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFD-induced NAFLD mice, as evidenced by decreased serum levels of TG, TC, HDL-C and LDL-C. Furthermore, LLP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. LLP also inhibited the TNF-α and IL-1β expression, thereby reducing levels of hepatic proinflammatory cytokines. Furthermore, LLP restored gut microbiota dysbiosis (up-regulated Bacteroidota, Proteobacteria, Alistipes and Lachnospiraceae abundances, down-regulated Firmicutes, Verrucomicrobiota, Desulfobacterota and Turicibacter abundances), and regulated microbial metabolic pathways such as primary bile acid biosynthesis and amino acid metabolism. In addition, the resultes of Spearman's correlation analysis found that some key metabolites in these metabolic pathways were associated with intestinal microorganisms such as Desulfobacterota, Prevotellaceae-UCG-001, Colidextribacter and Alistipes. Therefore, our study suggests that LLP may has potential applications in the treatment of NAFLD by regulating gut microbiota and its metabolite profile., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)