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Background: Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. Methods: During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. Results: In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). Conclusion: CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Bovine milk contains a rich matrix of nutrients such as carbohydrates, fat, protein and various vitamins and minerals, the composition of which is altered by factors including dietary regime. Objectives: The objective of this research was to investigate the impact of dietary regime on the metabolite composition of bovine whole milk powder and buttermilk. Methods: Bovine whole milk powder and buttermilk samples were obtained from spring-calving cows, consuming one of three diets. Group 1 grazed outdoors on perennial ryegrass which was supplemented with 5% concentrates; group 2 were maintained indoors and consumed a total mixed ration diet; and group 3 consumed a partial mixed ration diet consisting of perennial ryegrass during the day and total mixed ration maintained indoors at night. Results: Metabolomic analysis of the whole milk powder (N = 27) and buttermilk (N = 29) samples was preformed using liquid chromatography-tandem mass spectrometry, with 504 and 134 metabolites identified in the samples respectively. In whole milk powder samples, a total of 174 metabolites from various compound classes were significantly different across dietary regimes (FDR adjusted p-value ≤ 0.05), including triglycerides, of which 66% had their highest levels in pasture-fed samples. Triglycerides with highest levels in pasture-fed samples were predominantly polyunsaturated with high total carbon number. Regarding buttermilk samples, metabolites significantly different across dietary regimes included phospholipids, sphingomyelins and an acylcarnitine. Conclusion: In conclusion the results reveal a significant impact of a pasture-fed dietary regime on the metabolite composition of bovine dairy products, with a particular impact on lipid compound classes. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary neuroendocrine neoplasms (NENs) are a challenging type of lung cancer due to their varied clinical features and aggressive behavior. This study aimed to find specific metabolomic profiles in the blood of patients with different subtypes of lung NENs, which could help in early diagnosis. By analyzing 153 metabolites in the plasma of 120 NEN patients and comparing them with healthy individuals and patients with other lung cancers, we identified specific metabolic changes. These findings could lead to new biomarkers for early detection and better management of lung NENs, ultimately improving patient outcomes. Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review and meta-analysis of case–control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. Background: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. Methods: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle–Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. Results: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case–control analyses lacking an independent replication group. Conclusion: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC. [ABSTRACT FROM AUTHOR]

We aimed to elucidate the toxic effects and biological activities of 3-phenoxybenzoic acid (3PBA) and its metabolite products. Numerous in silico methods were used to identify the toxic effects and biological activities of 3PBA, including PASS online, molecular docking, ADMETlab 2.0, ADMESWISS, MetaTox, and molecular dynamic simulation. Ten metabolite products were identified via Phase II reactions (O-glucuronidation, O-sulfation, and methylation). All of the investigated compounds were followed by Lipinski's rule, indicating that they were stimulants or inducers of hazardous processes. Because of their high gastrointestinal absorption and ability to reach the blood-brain barrier, the studied compounds' physicochemical and pharmacokinetic properties matched existing evidence of harmful effects, including haematemesis, reproductive dysfunction, allergic dermatitis, toxic respiration, and neurotoxicity. The studied compounds have been linked to the apoptotic pathway, the reproductivity system, neuroendocrine disruptors, phospholipid-translocating ATPase inhibitors, and JAK2 expression. An O-glucuronidation metabolite product demonstrated higher binding affinity and interaction with CYP2C9, CYP3A4, caspase 3, and caspase 8 than 3PBA and other metabolite products, whereas metabolite products from methylation were predominant and more toxic. Our in silico findings partly meet the 3Rs principle by minimizing animal testing before more study is needed to identify the detrimental effects of 3PBA on other organs (liver, kidneys). Future research directions may involve experimental validation of in silico predictions, elucidation of molecular mechanisms, and exploration of therapeutic interventions. These findings contribute to our understanding of the toxicological profile of 3PBA and its metabolites, which has implications for risk assessment and regulatory decisions. Key properties & pharmacokinetics of 3PBA & its metabolites were reported Metabolite products from methylation were predominant and more toxic Main toxics: haematemesis, reproductive dysfunction, toxic respiration, dermatitis [ABSTRACT FROM AUTHOR]

Background and Aims: Acute‐on‐chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. Methods: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post‐HA and TPE sessions on days 7 and 14 using high‐resolution mass spectrometry. Results: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p <.05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine‐proline metabolism (6 metabolites) and microbial metabolism respectively (p <.05). Metabolites linked to taurine‐hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post‐TPE therapy (p <.05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post‐HA therapy compared to TPE and SMT (p <.05). Higher baseline plasma level of 11‐deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p <.05) and mortality (log‐rank‐p <.05). Notably, 51 of the 64 metabolite signatures (ACLF non‐survivor) were reversed post‐HA treatment compared to TPE and SMT(p <.05). Conclusion: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11‐deoxycorticosterone level correlates with early mortality in ACLF patients. [ABSTRACT FROM AUTHOR]

The Cannabis species is one of the potent ancient medicinal plants acclaimed for its medicinal properties and recreational purposes. The plant parts are used and exploited all over the world for several agricultural and industrial applications. For many years Cannabis spp. has proven to present a highly diverse metabolomic profile with a pool of bioactive metabolites used for numerous pharmacological purposes ranging from anti-inflammatory to antimicrobial. Cannabis sativa has since been an extensive subject of investigation, monopolizing the research. Hence, there are fewer studies with a comprehensive understanding of the composition of bioactive metabolites grown in different environmental conditions, especially C. indica and a few other Cannabis strains. These pharmacological properties are mostly attributed to a few phytocannabinoids and some phytochemicals such as terpenoids or essential oils which have been tested for antimicrobial properties. Many other discovered compounds are yet to be tested for antimicrobial properties. These phytochemicals have a series of useful properties including anti-insecticidal, anti-acaricidal, anti-nematicidal, anti-bacterial, anti-fungal, and anti-viral properties. Research studies have reported excellent antibacterial activity against Gram-positive and Gram-negative multidrug-resistant bacteria as well as methicillin-resistant Staphylococcus aureus (MRSA). Although there has been an extensive investigation on the antimicrobial properties of Cannabis, the antimicrobial properties of Cannabis on phytopathogens and aquatic animal pathogens, mostly those affecting fish, remain under-researched. Therefore, the current review intends to investigate the existing body of research on metabolomic profile and anti-microbial properties whilst trying to expand the scope of the properties of the Cannabis plant to benefit the health of other animal species and plant crops, particularly in agriculture. [ABSTRACT FROM AUTHOR]

Traditionally, indigenous African leafy vegetables such as Amaranthus, blackjack, jute mallow, cleome monophyla, and spider plants have been conventionally and organically grown as weeds in open fields. However, the lack of land space due to the increase in population has resulted in unconventional, modern, and advanced agricultural farming. The introduction of a greenhouse has recently become the second most popular growing system alongside shade net and glasshouse to increase productivity and meet consumers' demand. Several studies on Amaranthus species have solely focused on physiological parameters and nutritional composition, leaving a huge gap on their metabolomic profile of the leaves which is crucial to comprehend when growing Amaranthus species in different cropping systems. Therefore, the study aimed to determine the influence of different cropping systems on the release of metabolites of two commonly consumed Amaranthus species in South Africa. H1 -Nuclear Magnetic Resonance (NMR) tool was used to profile the untargeted metabolites of green (Amaranthus graecizans L.) and red (Amaranthus cruentus L.) species. A total of 12 metabolites—trehalose, betaine, glutamine, choline, sucrose, caprate, adenosine, asparagine, carnitine, caffeine, aspartate, and alanine—were detected in green amaranth grown in open fields. Except for caffeine, aspartate, and caprate, which were found in the green amaranth grown in open fields, all the other metabolites were detected in the greenhouse grown once. Interestingly, allantoin, which serves as an allelochemical, was the sole distinct metabolite detected in greenhouse cultivated green amaranth. On the contrary, seven similar metabolites were quantified in red amaranth grown in both open fields and greenhouses, apart from caffeine, which was only detected in greenhouse-cultivated red amaranth. [ABSTRACT FROM AUTHOR]

Mung bean (Vigna radiata (L.) Wilczek) sprouts are popular over the world because of their taste, nutritional value, well-balanced biochemical composition, and other properties beneficial for human health. Germination conditions affect the composition of metabolites in mung bean sprouts, so a detailed study into its variability is required. This article presents the results of a comparison of the metabolite composition in the leaves of mung bean sprouts germinated first in the dark (DS) and then in the light (LS). Gas chromatography with mass spectrometry (GC–MS) made it possible to identify more than 100 compounds representing various groups of phytochemicals. Alcohols, amino acids, and saccharides predominated in the total amount of compounds. The analysis of metabolomic profiles exposed a fairly high intra- and intervarietal variability in the metabolite content. DS and LS differed in the qualitative and quantitative content of the identified compounds. The intravarietal variability was more pronounced in DS than in LS. DS demonstrated higher levels of saccharides, fatty acids, acylglycerols, and phenolic compounds, while amino acids were higher in LS. Changes were recorded in the quantitative content of metabolites participating in the response of plants to stressors—ornithine, proline, GABA, inositol derivatives, etc. The changes were probably induced by the stress experienced by the sprouts when they were transferred from shade to light. The analysis of variance and principal factor analysis showed the statistically significant effect of germination conditions on the content of individual compounds in leaves. The identified features of metabolite variability in mung bean genotypes grown under different conditions will contribute to more accurate selection of an illumination pattern to obtain sprouts with desirable biochemical compositions for use in various diets and products with high nutritional value. [ABSTRACT FROM AUTHOR]

Culex pipiens (Linnaeus, 1758) mosquitoes search plant sources of sugars to cope with the energetic demand of various physiological processes. The crop as part of the digestive system is devoted to the storage of sugar-based meal obtained from various nectars sources. The profiling of sugars and metabolites in the Culex pipiens’ crop is scarce, and only few studies used Liquid Chromatography – Mass Spectrometry (LC-MS), which provides broad detection for biomonitoring environmental substances and even contaminants in the sugar diet of mosquitoes populations.Therefore, sugar and metabolite profiling were performed on crops obtained from mosquitoes exposed to plant nectar under laboratory or natural conditions by Ultra High-Performance LC-MS (UHPLC-MS). This method allowed us a precise quantitative and qualitative identification of sugar diet and associated environmental compounds in the crop of the mosquito C. pipiens. Under laboratory condition, mosquitoes were allowed to feed on either glucose solution, commercially-available flowers or field collected flowers. In addition, we collected mosquitoes from the field to compare those crop metabolomes with metabolome patterns occurring after nectar feeding in the lab.The sugar quantities and quality obtained from the crops of mosquitoes collected in the field were similar to those crops obtained from mosquitoes that fed on commercially-available flowers and from field collected flowers with a limit of detection of 10 μg/L for sucrose, glucose and sucrose. Next to sugar compounds, we identified 2 types of amino acids, 12 natural products, and 9 pesticides.Next to the diversity of sugar compounds, we could confirm that secondary metabolites and environmental pollutants are typically up taken from floral nectar sources by C. pipiens. The in-depth knowledge on mosquito–plant interactions may inspire the development and further optimization of mosquito trap systems and arboviral surveillance systems.

Abstract Background Wilson’s disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson’s disease patients (who exhibit similar symptoms but have normal copper levels). Results Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson’s disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson’s disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson’s disease). Conclusions Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson's disease patients (who exhibit similar symptoms but have normal copper levels). Results: Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson's disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson's disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson's disease). Conclusions: Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD. [ABSTRACT FROM AUTHOR]

The Cannabis species is one of the potent ancient medicinal plants acclaimed for its medicinal properties and recreational purposes. The plant parts are used and exploited all over the world for several agricultural and industrial applications. For many years Cannabis spp. has proven to present a highly diverse metabolomic profile with a pool of bioactive metabolites used for numerous pharmacological purposes ranging from anti-inflammatory to antimicrobial. Cannabis sativa has since been an extensive subject of investigation, monopolizing the research. Hence, there are fewer studies with a comprehensive understanding of the composition of bioactive metabolites grown in different environmental conditions, especially C. indica and a few other Cannabis strains. These pharmacological properties are mostly attributed to a few phytocannabinoids and some phytochemicals such as terpenoids or essential oils which have been tested for antimicrobial properties. Many other discovered compounds are yet to be tested for antimicrobial properties. These phytochemicals have a series of useful properties including anti-insecticidal, anti-acaricidal, anti-nematicidal, anti-bacterial, anti-fungal, and anti-viral properties. Research studies have reported excellent antibacterial activity against Gram-positive and Gram-negative multidrug-resistant bacteria as well as methicillin-resistant Staphylococcus aureus (MRSA). Although there has been an extensive investigation on the antimicrobial properties of Cannabis, the antimicrobial properties of Cannabis on phytopathogens and aquatic animal pathogens, mostly those affecting fish, remain under-researched. Therefore, the current review intends to investigate the existing body of research on metabolomic profile and anti-microbial properties whilst trying to expand the scope of the properties of the Cannabis plant to benefit the health of other animal species and plant crops, particularly in agriculture.

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

The genus Cecropia is used in the traditional medicine of Tabasco, Mexico, in diabetes and hypertension treatments, mainly without distinction of the species. This contribution aimed to carry out the metabolic analysis and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy-based fingerprinting of the hydroalcoholic leaf extracts of Cecropia peltata (Cp) and Cecropia obtusifolia (Co) collected in five sub-regions of the State of Tabasco (Cp1, "Centro"; Cp2, "Chontalpa"; Cp3, "Pantanos"; Cp4, "Ríos" and Co5, "Sierra"). Firstly, the extracts were evaluated for their Total Phenol Content (TPC) and Total Flavonoid Content (TFC) by spectrophotometric methods. In addition, metabolic analysis was performed using High-Performance Liquid Chromatography with Diode-Array Detection HPLC–DAD, which allowed the quantification of the chemical markers: chlorogenic acid, isoorientin, and orientin, as well as a vitexin analog. Finally, metabolomic analysis was carried out based on the 1H-NMR spectra. The Cp4 extract (C. peltata from the "Ríos" sub-region) presented the highest values of TPC (155 ± 9.1 mg GAE/g E) and TFC (724 ± 22.2 mg RE/g E). The metabolic analysis was similar among the five samples; the highest concentrations of the four chemical markers were found in Cp3 (C. peltata from the "Pantanos" sub-region) for chlorogenic acid (39.8 ± 2.3 mg/g) and isoorientin (51.5 ± 2.9 mg/g), in Cp4 for orientin (49.9 ± 0.6 mg/g), and in Cp2 (C. peltata from the "Chontalpa" sub-region) for the vitexin analog (6.2 ± 0.2 mg/g). The metabolic analysis and the 1H-NMR fingerprint analysis showed intraspecies differences among the C. peltata samples and interspecies between C. peltata and C. obtusifolia, which were attributed to variations in the metabolite groups as well as in the proportion of sugars such as glucose and xylose. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology. [ABSTRACT FROM AUTHOR]

Summary: Wheatgrass juice powder (WJP) obtained from four Indian wheat varieties grown under different photoperiod and temperature conditions were examined for growth parameters, chlorophyll content, mineral composition, protein and metabolomic profile. The percentage yield and total chlorophyll content of WJP varied from 2.5% to 9.12% and 1.08 to 4.76 mg g−1, respectively. The WJP obtained from PBW‐752 showed the highest yield and total chlorophyll content. The mineral composition (Na, K, Ca and Mg) of WJP also showed variation with different photoperiod and temperature conditions. The electrophoretic pattern of total soluble proteins of WJP showed variability in the accumulation of high and low molecular weight polypeptides against different photoperiod and temperature conditions. The comprehensive metabolites profile of WJP was analysed by UHPLC–QTOF–liquid chromatography/mass spectrometry. Based on the retention times and m/z values, 1012 feature peaks in positive ionisation mode were detected. The metabolomic profile of WJP revealed 180 different classes of primary and secondary metabolites. [ABSTRACT FROM AUTHOR]

Abstract Background Abnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships. Methods We examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9–11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%). Results Overall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07–2.14; P-values

Summary: Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side‐effects and treatment‐induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross‐sectional study with follow‐up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12‐month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow‐up or early second‐line therapies. [ABSTRACT FROM AUTHOR]

Soil rebuilding represents a major challenge in the recovery of abandoned quarries. In this study, we explored the possibility of using reconstructed Technosols, to achieve soil rebuilding goals at an abandoned quarry site. We first investigated the use of a mixture containing commercial manure and limestone debris (LD) as pedotechnomaterials for an "ad hoc" (re)constructed Technosol (CT), for the recovery of an opencast limestone quarry in one of most concentrated quarry areas in the world. In a field experiment, we tested and monitored different pedotechnosystems (PTSs) made up of constructed Technosol + pasture species + different Mediterranean plant species. Specifically, a control (CT, without any additional treatments) was compared to treatments with organic amendment (CTOA) and conventional fertilizers (CTCF). Data were collected over a 12-month period and included crop performance, plant nutritional state, soil physical-chemical parameters, and metabolites. Analysis of variance compared differences among treatments, while factor analysis (FA) interpreted multiple relationships while explaining observed variability. Results showed that CTOA had better soil physical-chemical properties, greater plant growth, and overall superior agronomic performances compared to all other treatments due to the improved substrate conditions. According to FA, these results appear related to the creation of fertile soil conditions, with most of the investigated metabolites (i) playing a pivotal role in observed outcomes, together with (ii) a clear potential in being considered as a reliable fingerprint for investigating plant responses in constructed PTSs. The proposed pedotechniques in CTOA development show a great potential for the full recovery of abandoned limestone quarries in degraded Mediterranean areas by providing an excellent medium for plant growth, facilitating environmental reclamation. [ABSTRACT FROM AUTHOR]

In mammals, the testis is the organ with the highest transcriptional activity. After gene transcription, translation, and post-translational protein modification, the transcriptional results are finally presented at the metabolic level. Metabolites not only essential for cell signaling and energy transfer, but also directly influenced by the physiological and pathological changes in tissues and accurately reflect the physiological changes. The fact that the testes are oxygen-deprived organs can explain why Sertoli cells and germ cells may use distinctive metabolic pathways to obtain energy in their different stages of development. Therefore, studying metabolic changes during testis development can better elucidate metabolic profile of the testis, which is essential to revealing characteristic metabolic pathways. The present study applied a widely targeted UPLC-MS/MS-based metabolomics approach with large-scale detection, identification and quantification to investigate the widespread metabolic changes during Tibetan sheep testis development. Firstly, a total of 847 metabolites were detected in the sheep testis, and their changes along with the three testis-development stages were further investigated. The results indicated that those metabolites were clustered into amino acids and their derivatives, carbohydrates and their derivatives, organic acids and their derivatives, benzene and substituted derivatives, alcohols and amines, lipids, nucleotides and their derivatives, bile acids, coenzymes and vitamins, hormones and hormone-related compounds, etc. Among them, the most abundant metabolites in the testis were amino acids and lipid metabolites. The results showed that most of the lipids, carbohydrates with their derivatives, as well as alcohol and amines metabolites were high in sexually immature sheep while organic acids, amino acids and nucleotides showed a continuously increasing trend along with testis development stages. Among them, the content of metabolites with antioxidant effects increased along with testis development, while those related with energy synthesis was downregulated with age. Further correlation analyses of each metabolite–metabolite pair emphasized the cross talk between differential metabolisms across testis development, suggesting a significant correlation between lipids and other metabolites. Finally, based on KEGG pathway analysis, we found that the metabolic pathways in Tibetan sheep testis development were mainly clustered into energy metabolism, gonadal development, and anti-oxidative stress. Reactive oxygen species (ROS) are by-products of normal cellular metabolism and are inevitable during testicular energy metabolism. Thus, the anti-oxidative stress function is a key process in maintaining the normal physiological function of testis. These results contributed to a broader view of the testis metabolome and a comprehensive analysis on metabolomic variation among different testis-development stages, providing a theoretical basis for us to understand the sheep testis metabolic mechanism. • 847 metabolites were identified during the Tibetan Sheep Testis Development. • The most abundant metabolites in testis were amino acids with their derivatives and lipid metabolites. • The level of accumulation of antioxidant substances in the testis increased significantly after sexual maturation. • The metabolic pathways were mainly clustered into energy metabolism, gonadal development, and anti-oxidative stress. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH—metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)—were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease. [ABSTRACT FROM AUTHOR]

Traditionally, indigenous African leafy vegetables such as Amaranthus, blackjack, jute mallow, cleome monophyla, and spider plants have been conventionally and organically grown as weeds in open fields. However, the lack of land space due to the increase in population has resulted in unconventional, modern, and advanced agricultural farming. The introduction of a greenhouse has recently become the second most popular growing system alongside shade net and glasshouse to increase productivity and meet consumers’ demand. Several studies on Amaranthus species have solely focused on physiological parameters and nutritional composition, leaving a huge gap on their metabolomic profile of the leaves which is crucial to comprehend when growing Amaranthus species in different cropping systems. Therefore, the study aimed to determine the influence of different cropping systems on the release of metabolites of two commonly consumed Amaranthus species in South Africa. H1 -Nuclear Magnetic Resonance (NMR) tool was used to profile the untargeted metabolites of green (Amaranthus graecizans L.) and red (Amaranthus cruentus L.) species. A total of 12 metabolites—trehalose, betaine, glutamine, choline, sucrose, caprate, adenosine, asparagine, carnitine, caffeine, aspartate, and alanine—were detected in green amaranth grown in open fields. Except for caffeine, aspartate, and caprate, which were found in the green amaranth grown in open fields, all the other metabolites were detected in the greenhouse grown once. Interestingly, allantoin, which serves as an allelochemical, was the sole distinct metabolite detected in greenhouse cultivated green amaranth. On the contrary, seven similar metabolites were quantified in red amaranth grown in both open fields and greenhouses, apart from caffeine, which was only detected in greenhouse-cultivated red amaranth.

Mung bean (Vigna radiata (L.) Wilczek) sprouts are popular over the world because of their taste, nutritional value, well-balanced biochemical composition, and other properties beneficial for human health. Germination conditions affect the composition of metabolites in mung bean sprouts, so a detailed study into its variability is required. This article presents the results of a comparison of the metabolite composition in the leaves of mung bean sprouts germinated first in the dark (DS) and then in the light (LS). Gas chromatography with mass spectrometry (GC–MS) made it possible to identify more than 100 compounds representing various groups of phytochemicals. Alcohols, amino acids, and saccharides predominated in the total amount of compounds. The analysis of metabolomic profiles exposed a fairly high intra- and intervarietal variability in the metabolite content. DS and LS differed in the qualitative and quantitative content of the identified compounds. The intravarietal variability was more pronounced in DS than in LS. DS demonstrated higher levels of saccharides, fatty acids, acylglycerols, and phenolic compounds, while amino acids were higher in LS. Changes were recorded in the quantitative content of metabolites participating in the response of plants to stressors—ornithine, proline, GABA, inositol derivatives, etc. The changes were probably induced by the stress experienced by the sprouts when they were transferred from shade to light. The analysis of variance and principal factor analysis showed the statistically significant effect of germination conditions on the content of individual compounds in leaves. The identified features of metabolite variability in mung bean genotypes grown under different conditions will contribute to more accurate selection of an illumination pattern to obtain sprouts with desirable biochemical compositions for use in various diets and products with high nutritional value.

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis. Additionally, medium osmolarity is not experimentally adjusted prior to bioactivity assays. In this scenario, the methodological standardization and interdisciplinary approach of such processes will strengthen the interpretation, repeatability, and replicability of the empirical results on the compounds with bioactive properties present in camel urine. Furthermore, sample enlargement would also permit the evaluation of camel urine's intra- and interindividual variability in terms of chemical composition, bioactive effects, and efficacy, while it may also permit researchers to discriminate potential animal-intrinsic and extrinsic conditioning factors. Altogether, the results would help to evaluate the role of camel urine as a natural source for the identification and extraction of specific novel bioactive substances that may deserve isolated chemical and pharmacognostic investigations through preclinical tests to determine their biological activity and the suitability of their safety profile for their potential inclusion in therapeutic formulas for improving human and animal health. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NIRS) is an accurate, fast and safe technique whose full potential remains to be exploited. Lichens are a paradigm of symbiotic association, with extraordinary properties, such as abiotic stress tolerance and adaptation to anhydrobiosis, but subjacent mechanisms await elucidation. Our aim is characterizing the metabolomic NIRS fingerprints of Ramalina farinacea and Lobarina scrobiculata thalli, and of the cultured phycobionts Trebouxia lynnae and Trebouxia jamesii. Thalli collected in an air-dry state and fresh cultivated phycobionts were directly used for spectra acquisition in reflectance mode. Thalli water peaks were associated to the solvation shell (1354 nm) and sugar–water interactions (1438 nm). While northern–southern orientation related with two hydrogen bonded (S2) water, the site was related to one hydrogen bonded (S1). Water, lipids (saturated and unsaturated), and polyols/glucides contributed to the profiles of lichen thalli and microalgae. R. farinacea, with higher desiccation tolerance, shows higher S2 water than L. scrobiculata. In contrast, fresh phycobionts are dominated by free water. Whereas T. jamesii shows higher solvation water content, T. lynnae possesses more unsaturated lipids. Aquaphotomics demonstrates the involvement of strongly hydrogen bonded water conformations, polyols/glucides, and unsaturated/saturated fatty acids in the dehydration process, and supports a "rubbery" state allowing enzymatic activity during anhydrobiosis. [ABSTRACT FROM AUTHOR]

Increased soil salinity is one of the main concerns in agriculture and food production, and it negatively affects plant growth and crop productivity. In order to mitigate the adverse effects of salinity stress, plant biostimulants (PBs) have been indicated as a promising approach. Indeed, these products have a beneficial effect on plants by acting on primary and secondary metabolism and by inducing the accumulation of protective molecules against oxidative stress. In this context, the present work is aimed at comparatively investigating the effects of microbial (i.e., Azospirillum brasilense) and plant-derived biostimulants in alleviating salt stress in tomato plants by adopting a multidisciplinary approach. To do so, the morphological and biochemical effects were assessed by analyzing the biomass accumulation and root characteristics, the activity of antioxidant enzymes and osmotic stress protection. Furthermore, modifications in the metabolomic profiles of both leaves and root exudates were also investigated by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). According to the results, biomass accumulation decreased under high salinity. However, the treatment with A. brasilense considerably improved root architecture and increased root biomass by 156% and 118% in non-saline and saline conditions, respectively. The antioxidant enzymes and proline production were enhanced in salinity stress at different levels according to the biostimulant applied. Moreover, the metabolomic analyses pointed out a wide set of processes being affected by salinity and biostimulant interactions. Crucial compounds belonging to secondary metabolism (phenylpropanoids, alkaloids and other N-containing metabolites, and membrane lipids) and phytohormones (brassinosteroids, cytokinins and methylsalicylate) showed the most pronounced modulation. Overall, our results suggest a better performance of A. brasilense in alleviating high salinity than the vegetal-derived protein hydrolysates herein evaluated. [ABSTRACT FROM AUTHOR]

At present, metabolomics is an intensively developing approach to the specific diagnosis of cardiovascular diseases. Metabolic analysis allows the study of complete metabolomic profiles and their deviations resulting from changes, for example, gene and RNA expression, protein activity, or environmental factors. Analysis of the metabolomic blood profile helps in solving a large number of scientific and clinical problems, one of which is the search for markers of diseases, in particular, cardiovascular diseases (CVD). Aim of the study was to investigate metabolomic markers used for the diagnosis of cardiovascular diseases on the basis of literature data. Material and methods. The literature data was analyzed for key words: cardiovascular diseases, metabolomics, metabolic profile, metabolomic markers in da- tabases PubMed, Scopus, Web of Science, CyberLeninka, PatentDB, Science Direct Open Access, eLibrary. Results. Analysis of literature data and patent search confirms the high importance of metabolomic markers in the diagnosis of CVD. In the patent literature, BNP/NT-proBNP is most common used as a metabolic marker of CVD (11.27 %). The use of CRP (8.99 %) and troponin (8.49 %) is also common. PICP (0.02 %), sVCAM-1 (0.09 %), stimulating growth factor ST-2 (0.12 %) and thrombomodulin (0.12 %) as metabolic markers of CVD. Conclusions. Against the backdrop of analytical methods, metabolomics is the most important diagnostic area. At the same time, it should be noted that by combining the results of the analysis of metabolic studies with others, for example, genomic and proteomic, one can get a complete picture of the pathogenesis of diseases, assess the risk of complications, and also determine the effectiveness of the treatment.

Background: Abnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships.Methods: We examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9-11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%).Results: Overall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07-2.14; P-values <5.2×10-5). By contrast, the ascorbate/aldarate metabolite oxalate, xenobiotics S-carboxymethyl-L-cysteine, fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and fibrinopeptide B (1-12) were related to reduced disease-specific mortality (fourth versus first quartile HRs=0.82-0.84; P-value <5.2×10-5). Further adjustment for years from blood collection to cancer diagnosis, body mass index, smoking intensity and duration, and serum total and high-density lipoprotein cholesterol did not alter the results. Participants with a higher metabolic score based on the discovery set had an elevated risk of prostate cancer-specific mortality in the replication set (fourth versus first quartile, HR=3.9, P-value for trend<0.0001).Conclusions: The metabolic traits identified in this study, including for choline, glutamate, arachidonate, gamma-glutamyl amino acids, fibrinopeptides, and endocannabinoid and redox pathways and their composite risk score, corroborate our previous analysis of fatal prostate cancer and provide novel insights and potential leads regarding the molecular basis of prostate cancer progression and mortality. [ABSTRACT FROM AUTHOR]

The genus Cecropia is used in the traditional medicine of Tabasco, Mexico, in diabetes and hypertension treatments, mainly without distinction of the species. This contribution aimed to carry out the metabolic analysis and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy-based fingerprinting of the hydroalcoholic leaf extracts of Cecropia peltata (Cp) and Cecropia obtusifolia (Co) collected in five sub-regions of the State of Tabasco (Cp1, “Centro”; Cp2, “Chontalpa”; Cp3, “Pantanos”; Cp4, “Ríos” and Co5, “Sierra”). Firstly, the extracts were evaluated for their Total Phenol Content (TPC) and Total Flavonoid Content (TFC) by spectrophotometric methods. In addition, metabolic analysis was performed using High-Performance Liquid Chromatography with Diode-Array Detection HPLC–DAD, which allowed the quantification of the chemical markers: chlorogenic acid, isoorientin, and orientin, as well as a vitexin analog. Finally, metabolomic analysis was carried out based on the 1H-NMR spectra. The Cp4 extract (C. peltata from the “Ríos” sub-region) presented the highest values of TPC (155 ± 9.1 mg GAE/g E) and TFC (724 ± 22.2 mg RE/g E). The metabolic analysis was similar among the five samples; the highest concentrations of the four chemical markers were found in Cp3 (C. peltata from the “Pantanos” sub-region) for chlorogenic acid (39.8 ± 2.3 mg/g) and isoorientin (51.5 ± 2.9 mg/g), in Cp4 for orientin (49.9 ± 0.6 mg/g), and in Cp2 (C. peltata from the “Chontalpa” sub-region) for the vitexin analog (6.2 ± 0.2 mg/g). The metabolic analysis and the 1H-NMR fingerprint analysis showed intraspecies differences among the C. peltata samples and interspecies between C. peltata and C. obtusifolia, which were attributed to variations in the metabolite groups as well as in the proportion of sugars such as glucose and xylose.

Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology.

Saliva is an ideal biofluid for monitoring oral and systemic health. Repeated mastication is a typical physical stimulus that improves salivary flow and oral hygiene. Recent metabolomic studies have shown the potential of salivary metabolomic components for various disease monitoring systems. Here, we evaluated the effect of long-term mastication on salivary metabolomic profiles. Young women with good oral hygiene (20.8 ± 0.3 years, n = 17) participated. They were prohibited from chewing gum during control periods (4 weeks each) and were instructed to chew a piece of gum base seven times a day for 10 min each time during the intervention period. Paired samples of unstimulated whole saliva collected on the last day of the control and intervention period were compared. Liquid chromatography–time-of-flight mass spectrometry successfully quantified 85 metabolites, of which 41 showed significant differences (p < 0.05, Wilcoxon paired test corrected by false discovery rate). Except for a few metabolites, such as citrate, most metabolites showed lower concentrations after the intervention. The pathways related to glycogenic amino acids, such as alanine, arginine, and glutamine, altered considerably. This study suggests that long-term mastication induces unstimulated salivary component-level changes. [ABSTRACT FROM AUTHOR]

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME. [ABSTRACT FROM AUTHOR]

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation. [Display omitted] • A homogeneous polysaccharide from Phyllanthus Emblica L. (PEP-1) was characterized. • PEP-1 reshaped the gut bacteria composition. • PEP-1 regulated gut microbiome metabolites and corelated pathways. [ABSTRACT FROM AUTHOR]

The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells. [Display omitted] [ABSTRACT FROM AUTHOR]

The metabolites produced from choline contribute to atherosclerosis (AS) pathogenesis, and the gut microbiota is redundantly essential for this process. Indole-3-carbinol (I3C), found in cruciferous vegetables such as broccoli, cabbage, cauliflower and brussels sprouts, helps prevent hyperlipidemia, maintain the gut microbiota balance, and decrease the production of trimethylamine-N-oxide (TMAO) from choline in the diet. The objective of this research was to investigate the impact of I3C on choline-induced AS and to further elucidate the underlying mechanism involved. AS models of high-choline-induced ApoE-/- mice and TMAO-promoted foamy macrophages were established to observe the effect of I3C on the formation of atherosclerotic plaques and foam cells and changes in AS-related indicators (including blood biochemical indicators, TMA, TMAO, SRA, and SRB1), and integrated analyses of the microbiome and metabolome were used to reveal the mechanism of action of I3C. We found that I3C inhibited high-choline-induced atheroma formation (50–100 mg/kg/d, in vivo) and slightly improved the lipid profile (15 mg/kg/d, in vivo). Moreover, I3C suppressed lipid influx at a concentration of 40 µmol/L in vitro, enhanced the diversity of the gut microbiota and the abundance of the phylum Verrucomicrobia , and consequently modified the gut microbial metabolites at a dosage of 50 mg/kg/d in the mice. Associative analyses based on microbiome and metabolomics revealed that 1-methyladenosine was a key modulator of the protective effect of I3C against AS in high-choline-induced ApoE-/- mice. These findings demonstrate for the first time that I3C ameliorates AS progression through remodeling of the gut microbiome and metabolomics, which paves the way for the possible therapeutic use of this vegetable-derived natural compound and may reduce the clinical severity of AS-related cardiovascular diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Spontaneous fermentation is a critical processing step that determines the taste quality of fermented mandarin fish (Siniperca chuatsi). Here, untargeted metabolomics using ultra-high-performance liquid chromatography coupled with Q Exactive tandem mass spectrometry was employed to characterize the taste-related metabolite profiles during the fermentation of mandarin fish. The results demonstrated that the taste profiles of mandarin fish at different stages of fermentation could be distinguished using an electronic tongue technique. Sixty-two metabolites, including amino acids, small peptides, fatty acids, alkaloids, and organic acids, were identified in fermented mandarin fish samples. Additional quantitative analysis of amino acids revealed glutamic acid and aspartic acid as significant contributors to the fresh flavor. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that amino acid metabolism was the dominant pathway throughout the fermentation process. This study provides a scientific and theoretical reference for the targeted regulation of the quality of fermented mandarin fish. [ABSTRACT FROM AUTHOR]

Aim: A better knowledge of the biological consequences in the blood of these exercise-induced ischemic events in lower extremity artery disease (LEAD) may improve the prospects of disease management. We explored the preminus postexercise metabolomic difference in 39 patients with LEAD referred for a treadmill oximetry test [transcutaneous oximetry (TcPO2)]. Methods: Ischemia was estimated through the sum of decrease from rest of oxygen pressure (DROPs) (limb TcPO2 changes minus chest TcPO2 changes) at buttocks, thighs, and calves regions. Targeted metabolomic analyses measuring 188 metabolites were performed on a few microliters blood samples taken at the earlobe at rest and 3 min after exercise. Results: Maximum walking distance (MWD) was 290 m (120–652 m) and ankle brachial index (ABI) was 0.67 ± 0.17. Supervised paired partial least squares discriminant analysis based on 23,345 models showed good predictive performance for test sets with a median area under the receiver operating characteristic (AUROC) curve value of 0.99 and a p -value of 0.00049. The best discriminant metabolites contributing to the model included a subset of 71 (47%) of the 150 accurately measured metabolites in the plasma, comprising 3 acylcarnitines, 3 amino acids, 5 biogenic amines, 9 sphingomyelin, 7 lysophosphatidylcholines, and 44 phosphatidylcholines. In addition, 16 of these metabolites were found to correlate with one or more severity scores of the LEAD. Conclusion: Our results provide new insights into the biological changes that accompany exercise in LEAD and contribute to a better understanding of walking impairment pathophysiology in LEAD, highlighting new candidate biomarkers. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL/6J and BALB/c mice. In both mouse strains, the main traits of NASH—metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)—were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL/6J and BALB/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.

Aim: A better knowledge of the biological consequences in the blood of these exercise-induced ischemic events in lower extremity artery disease (LEAD) may improve the prospects of disease management. We explored the preminus postexercise metabolomic difference in 39 patients with LEAD referred for a treadmill oximetry test [transcutaneous oximetry (TcPO2)].Methods: Ischemia was estimated through the sum of decrease from rest of oxygen pressure (DROPs) (limb TcPO2 changes minus chest TcPO2 changes) at buttocks, thighs, and calves regions. Targeted metabolomic analyses measuring 188 metabolites were performed on a few microliters blood samples taken at the earlobe at rest and 3 min after exercise.Results: Maximum walking distance (MWD) was 290 m (120–652 m) and ankle brachial index (ABI) was 0.67 ± 0.17. Supervised paired partial least squares discriminant analysis based on 23,345 models showed good predictive performance for test sets with a median area under the receiver operating characteristic (AUROC) curve value of 0.99 and a p-value of 0.00049. The best discriminant metabolites contributing to the model included a subset of 71 (47%) of the 150 accurately measured metabolites in the plasma, comprising 3 acylcarnitines, 3 amino acids, 5 biogenic amines, 9 sphingomyelin, 7 lysophosphatidylcholines, and 44 phosphatidylcholines. In addition, 16 of these metabolites were found to correlate with one or more severity scores of the LEAD.Conclusion: Our results provide new insights into the biological changes that accompany exercise in LEAD and contribute to a better understanding of walking impairment pathophysiology in LEAD, highlighting new candidate biomarkers.

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis. Additionally, medium osmolarity is not experimentally adjusted prior to bioactivity assays. In this scenario, the methodological standardization and interdisciplinary approach of such processes will strengthen the interpretation, repeatability, and replicability of the empirical results on the compounds with bioactive properties present in camel urine. Furthermore, sample enlargement would also permit the evaluation of camel urine’s intra- and interindividual variability in terms of chemical composition, bioactive effects, and efficacy, while it may also permit researchers to discriminate potential animal-intrinsic and extrinsic conditioning factors. Altogether, the results would help to evaluate the role of camel urine as a natural source for the identification and extraction of specific novel bioactive substances that may deserve isolated chemical and pharmacognostic investigations through preclinical tests to determine their biological activity and the suitability of their safety profile for their potential inclusion in therapeutic formulas for improving human and animal health.

Increased soil salinity is one of the main concerns in agriculture and food production, and it negatively affects plant growth and crop productivity. In order to mitigate the adverse effects of salinity stress, plant biostimulants (PBs) have been indicated as a promising approach. Indeed, these products have a beneficial effect on plants by acting on primary and secondary metabolism and by inducing the accumulation of protective molecules against oxidative stress. In this context, the present work is aimed at comparatively investigating the effects of microbial (i.e., Azospirillum brasilense) and plant-derived biostimulants in alleviating salt stress in tomato plants by adopting a multidisciplinary approach. To do so, the morphological and biochemical effects were assessed by analyzing the biomass accumulation and root characteristics, the activity of antioxidant enzymes and osmotic stress protection. Furthermore, modifications in the metabolomic profiles of both leaves and root exudates were also investigated by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). According to the results, biomass accumulation decreased under high salinity. However, the treatment with A. brasilense considerably improved root architecture and increased root biomass by 156% and 118% in non-saline and saline conditions, respectively. The antioxidant enzymes and proline production were enhanced in salinity stress at different levels according to the biostimulant applied. Moreover, the metabolomic analyses pointed out a wide set of processes being affected by salinity and biostimulant interactions. Crucial compounds belonging to secondary metabolism (phenylpropanoids, alkaloids and other N-containing metabolites, and membrane lipids) and phytohormones (brassinosteroids, cytokinins and methylsalicylate) showed the most pronounced modulation. Overall, our results suggest a better performance of A. brasilense in alleviating high salinity than the vegetal-derived protein hydrolysates herein evaluated.

Background: Being physically active has multiple salutary effects on human health, likely mediated by changes in energy metabolism. Recent reviews have summarized metabolomic responses to acute exercise. However, metabolomic profiles of individuals who exercise regularly are heterogeneous. Aim of review: We conducted a systematic review to identify metabolites associated with physical activity (PA), fitness, and sedentary time in community-dwelling adults and discussed involved pathways. Twenty-two studies were eligible because they (1) focused on community-dwelling adults from observational studies; (2) assessed PA, fitness, and/or sedentary time, (3) assessed metabolomics in biofluid, and (4) reported on relationships of metabolomics with PA, fitness, and/or sedentary time. Key scientific concepts of review: Several metabolic pathways were associated with higher PA and fitness and less sedentary time, including tricarboxylic acid cycle, glycolysis, aminoacyl-tRNA biosynthesis, urea cycle, arginine biosynthesis, branch-chain amino acids, and estrogen metabolism. Lipids were strongly associated with PA. Cholesterol low-density lipoproteins and triglycerides were lower with higher PA, while cholesterol high-density lipoproteins were higher. Metabolomic profiles of being physically active and less sedentary indicate active skeletal muscle biosynthesis supported by enhanced oxidative phosphorylation and glycolysis and associated with profound changes in lipid and estrogen metabolism. Future longitudinal studies are needed to understand whether these metabolomic changes account for health benefits associated with PA. [ABSTRACT FROM AUTHOR]

Aims: To estimate potential differences in neonatal metabolomic profiles at birth and at the time of newborn screening by delivery mode. Methods: A prospective study at Women's Clinic at Landspitali—The National University Hospital of Iceland. Women having normal vaginal birth or elective caesarean section from November 2013 to April 2014 were offered participation. Blood samples from mothers before birth and umbilical cord at birth were collected and amino acids and acylcarnitines measured by tandem mass spectrometry. Results from the Newborn screening programme in Iceland were collected. Amino acids and acylcarnitines from different samples were compared by delivery mode. Results: Eighty three normal vaginal births and 32 elective caesarean sections were included. Mean differences at birth were higher for numerous amino acids, and some acylcarnitines in neonates born vaginally compared to elective caesarean section. Maternal blood samples and newborn screening results showed small differences that lost significance after correction for multiple testing. Many amino acids and some acylcarnitines were numerically higher in cord blood compared to maternal. Many amino acids and most acylcarnitines were numerically higher in newborn screening results compared to cord blood. Conclusion: We observed transient yet distinct differences in metabolomic profiles between neonates by delivery mode. [ABSTRACT FROM AUTHOR]