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Fenugreeks (Trigonella L. spp.), are well-known herbs belonging to the family Fabaceae, whose fresh and dried leaves have nutritional and medicinal value. In the present study, the content of phytochemical traits (essential oil, diosgenin, trigonelline, total phenol, total flavonoid, total saponins, and total tannins), bitterness value, pigments (chlorophyll, carotenoid, β-carotene, and anthocyanin), vitamins (group B vitamins and ascorbic acid), minerals, and antioxidant activity of thirty cultivated populations belonging to ten Trigonella species were evaluated. The species and populations were significantly different in all studied parameters. A significant positive and negative correlation (p < 0.05) was also observed between the studied parameters. In total, T. teheranica, T. elliptica, and T. foenum-graecum were distinguished as superior species. The results showed that fenugreeks leaves can be considered as a valuable source of food and phytochemical compounds. The obtained data can be help to expand the inventory of wild and cultivated Trigonella species for further exploitation of rich chemotypes in the new foods and specific applications. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor characterized by rapid progression, poor prognosis, and high mortality rates. Understanding the relationship between cerebrospinal fluid (CSF) metabolites and GBM is crucial for identifying potential biomarkers and pathways involved in the pathogenesis of this devastating disease. Methods: In this study, Mendelian randomization (MR) analysis was employed to investigate the causal relationship between 338 CSF metabolites and GBM. The data for metabolites were obtained from a genome-wide association study summary dataset based on 291 individuals, and the GBM data was derived from FinnGen included 91 cases and 174,006 controls of European descent. The Inverse Variance Weighted method was utilized to estimate the causal effects. Supplementary comprehensive assessments of causal effects between CSF metabolites and GBM were conducted using MR-Egger regression, Weighted Median, Simple Mode, and Weighted Mode methods. Additionally, tests for heterogeneity and pleiotropy were performed. Results: Through MR analysis, a total of 12 identified metabolites and 2 with unknown chemical properties were found to have a causal relationship with GBM. 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), 7-alpha-hydroxy-3-oxo-4-cholestenoate, Alpha-tocopherol, Behenoyl sphingomyelin (d18:1/22:0), Cysteinylglycine, Maleate, Uracil, Valine, X-12,101, X-12,104 and Butyrate (4:0) are associated with an increased risk of GBM. N1-methylinosine, Stachydrine and Succinylcarnitine (c4-dc) are associated with decreased GBM risk. Conclusion: In conclusion, this study sheds light on the intricate interplay between CSF metabolites and GBM, offering novel perspectives on disease mechanisms and potential treatment avenues. By elucidating the role of CSF metabolites in GBM pathogenesis, this research contributes to the advancement of diagnostic capabilities and targeted therapeutic interventions for this aggressive brain tumor. Further exploration of these findings may lead to improved management strategies and better outcomes for patients with GBM. [ABSTRACT FROM AUTHOR]

Although intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites. Based on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD. MR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of 4 metabolite-mediated mediation relationships were revealed (3 b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine). The findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research. [ABSTRACT FROM AUTHOR]

Alternative mRNA splicing promotes the diversity of protein isoforms. Metabolic regulation of mRNA splicing enables cells to adapt their proteome to external stimuli. The interplay between metabolites and alternative mRNA splicing can take place through biochemical and biophysical changes of cellular compartments in which splicing takes place and/or through interactions between metabolites and splicing factors. Central cell signaling pathways that are regulated by metabolites crosstalk with alternative splicing regulators. Alternative mRNA splicing enables the diversification of the proteome from a static genome and confers plasticity and adaptiveness on cells. Although this is often explored in development, where hard-wired programs drive the differentiation and specialization, alternative mRNA splicing also offers a way for cells to react to sudden changes in outside stimuli such as small-molecule metabolites. Fluctuations in metabolite levels and availability in particular convey crucial information to which cells react and adapt. We summarize and highlight findings surrounding the metabolic regulation of mRNA splicing. We discuss the principles underlying the biochemistry and biophysical properties of mRNA splicing, and propose how these could intersect with metabolite levels. Further, we present examples in which metabolites directly influence RNA-binding proteins and splicing factors. We also discuss the interplay between alternative mRNA splicing and metabolite-responsive signaling pathways. We hope to inspire future research to obtain a holistic picture of alternative mRNA splicing in response to metabolic cues. [ABSTRACT FROM AUTHOR]

This study investigated if paraxanthine (PX) impacts energy expenditure, lipolysis and perceptual responses. In a randomized, double-blind, placebo-controlled, crossover fashion, 21 adults (13 M, 8 F; 26.0 ± 6.4 years, 174.9 ± 11.5 cm, 81.0 ± 15.7 kg body mass, 26.3 ± 3.4 kg/m2) consumed a placebo (PLA), 100 mg (PX100), 200 mg (PX200), and 300 mg of PX (PX300, enfinity®, Ingenious Ingredients, L.P. Lewisville, TX, USA). Venous blood was collected 0, 30, 60, 90, 120 and 180 min (min) after ingestion and analyzed for glycerol and free fatty acids. Resting hemodynamics, metabolic rate and perceptual indicators of hunger, appetite and anxiety were evaluated. Mixed factorial analysis of variance were used to evaluate changes time within and between groups. Heart rate decreased in PX100 compared to PLA 60 (p =.022) and 180 min (p =.001). Blood pressure did not change. Hunger ratings in PLA increased 30 (p =.05), 60 (p =.04), 90 (p =.02), and 180 min (p =.05) after ingestion when compared to PX200. PX200 increased energy expenditure (all p <.05) when compared to PLA. Rates of fat oxidation tended to increase 90 (p =.056) and 120 min (p =.066) in PX200 compared to PLA. Free fatty acids increased in PX300 compared to PLA (p =.002). Glycerol did not change. Ingestion of PX200 augmented energy expenditure and hunger ratings when compared to PLA without impacting hemodynamics or lipolysis. [ABSTRACT FROM AUTHOR]

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP. [ABSTRACT FROM AUTHOR]

Background: Black rice is rich in various nutrients, such as anthocyanins, which may undergo some changes during cooking. However, previous studies have been mainly focused on a single substance and paid less attention to the changes in overall nutrient components. Here, we performed widely targeted metabolomics analysis on the chemical compositional changes in a new black rice variety ('Huamoxiang No.3') under three cooking modes, including bottom heating (BH), induction heating (IH), and IH + pressure. Results: Among the detected 1458 metabolites, 276 and 108 metabolites were differential metabolites after cooking and in three cooking modes, respectively. Cooking increased the contents of most peptides, phenolic acids, and organic acid compounds but significantly decreased those of lipids and flavonoids, particularly anthocyanins. However, phenolic acids such as chlorogenic acid, erucic acid, and p‐coumaric acid increased significantly, possibly due to the release of bound phenols and degradation of flavonoids to phenolic acids, such as thermal degradation of C3G to protocatechuic acid and among the three heating modes, the IH + pressure mode resulted in the most significant changes. Conclusion: Although cooking reduced the content of flavonoids and anthocyanins, the increase in phenolic acids and other substances contributed to the healthy effect of cooked black rice, and the content of these active substances increased more significantly in the IH + pressure mode. [ABSTRACT FROM AUTHOR]

Background: While intervertebral disc degeneration (IVDD) is crucial in numerous spinally related illnesses and is common among the elderly, the complete understanding of its pathogenic mechanisms is still an area of ongoing study. In recent years, it has revealed that liposomes are crucial in the initiation and progression of IVDD. However, their intrinsic mediators and related mechanisms remain unclear. With the development of genomics, an increasing amount of data points to the contribution of genetics in the etiology of disease. Accordingly, this study explored the causality between liposomes and IVDD by Mendelian randomization (MR) analysis and deeply investigated the intermediary roles of undetected metabolites. Methods: According to MR analysis, 179 liposomes and 1400 metabolites were evaluated for their causal association with IVDD. Single nucleotide polymorphisms (SNPs) are strongly associated with the concentrations of liposomes and metabolites. Consequently, they were employed as instrumental variables (IVs) to deduce if they constituted risk elements or protective elements for IVDD. Furthermore, mediation analysis was conducted to pinpoint possible metabolic mediators that link liposomes to IVDD. The inverse variance weighting (IVW) was the main analytical technique. Various confidence tests in the causality estimates were performed, including consistency, heterogeneity, pleiotropy, and sensitivity analyses. Inverse MR analysis was also utilized to estimate potential reverse causality. Results: MR analysis identified 13 liposomes and 79 metabolites markedly relevant to IVDD. Moreover, the mediation analysis was carried out by choosing the liposome, specifically the triacylglycerol (48:2) levels, which were found to be most notably associated with an increased risk of IVDD. In all, three metabolite-associated mediators were identified (3-methylcytidine levels, inosine 5'-monophosphate (IMP) to phosphate ratio, and adenosine 5'-diphosphate (ADP) to glycine ratio). Conclusion: The analysis's findings suggested possible causal connections between liposomes, metabolites, and IVDD, which could act as both forecast and prognosis clinical indicators, thereby aiding in the exploration of the pathogenesis behind IVDD. [ABSTRACT FROM AUTHOR]

Background and aims: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes. Methods: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results. Results: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes. Conclusion: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients. [ABSTRACT FROM AUTHOR]

Introduction: Probiotics, especially Lactic Acid Bacteria (LAB), can promote the health of host animals in a variety of ways, such as regulating intestinal flora and stimulating the host's immune system. Methods: In this study, 206 LAB strains were isolated from 48 canine fecal samples. Eleven LAB strains were selected based on growth performance, acid and bile salt resistance. The 11 candidates underwent comprehensive evaluation for probiotic properties, including antipathogenic activity, adhesion, safety, antioxidant capacity, and metabolites. Results: The results of the antipathogenic activity tests showed that 11 LAB strains exhibited strong inhibitory effect and co-aggregation ability against four target pathogens (E. coli, Staphylococcus aureus, Salmonella braenderup, and Pseudomonas aeruginosa). The results of the adhesion test showed that the 11 LAB strains had high cell surface hydrophobicity, self-aggregation ability, biofilm-forming ability and adhesion ability to the Caco-2 cells. Among them, Lactobacillus acidophilus (L177) showed strong activity in various adhesion experiments. Safety tests showed that 11 LAB strains are sensitive to most antibiotics, with L102, L171, and L177 having the highest sensitivity rate at 85.71%, and no hemolysis occurred in all strains. Antioxidant test results showed that all strains showed good H2O2 tolerance, high scavenging capacity for 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH) and hydroxyl (OH-). In addition, 11 LAB strains can produce high levels of metabolites including exopolysaccharide (EPS), γ-aminobutyric acid (GABA), and bile salt hydrolase (BSH). Discussion: This study provides a thorough characterization of canine-derived LAB strains, highlighting their multifunctional potential as probiotics. The diverse capabilities of the strains make them promising candidates for canine dietary supplements, offering a holistic approach to canine health. Further research should validate their efficacy in vivo to ensure their practical application. [ABSTRACT FROM AUTHOR]

Semen cryopreservation results in the differential remodeling of the molecules presented in sperm, and these alterations related to reductions in sperm quality and its physiological function have not been fully understood. Given this, this study aimed to investigate the cryoinjury mechanism of goat sperm by analyzing changes of the metabolic characteristics in sperm during the cryopreservation process. The ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) technique was performed to explore metabolite profiles of fresh sperm (C group), equilibrated sperm (E group), and frozen–thawed sperm (F group). In total, 2570 metabolites in positive mode and 2306 metabolites in negative mode were identified, respectively. After comparative analyses among these three groups, 374 differentially abundant metabolites (DAMs) in C vs. E, 291 DAMs in C vs. F, and 189 DAMs in E vs. F were obtained in the positive mode; concurrently, 530 DAMs in C vs. E, 405 DAMs in C vs. F, and 193 DAMs in E vs. F were obtained in the negative mode, respectively. The DAMs were significantly enriched in various metabolic pathways, including 31 pathways in C vs. E, 25 pathways in C vs. F, and 28 pathways in E vs. F, respectively. Among them, 65 DAMs and 25 significantly enriched pathways across the three comparisons were discovered, which may be tightly associated with sperm characteristics and function. Particularly, the functional terms such as TCA cycle, biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycine, serine and threonine metabolism, alpha-linolenic acid metabolism, and pyruvate metabolism, as well as associated pivotal metabolites like ceramide, betaine, choline, fumaric acid, L-malic acid and L-lactic acid, were focused on. In conclusion, our research characterizes the composition of metabolites in goat sperm and their alterations induced by the cryopreservation process, offering a critical foundation for further exploring the molecular mechanisms of metabolism influencing the quality and freezing tolerance of goat sperm. Additionally, the impacts of equilibration at low temperature on sperm quality may need more attentions as compared to the freezing and thawing process. [ABSTRACT FROM AUTHOR]

Environmental conditions greatly influence the quality of tomato fruit by affecting the expression of genes, the abundance of metabolites, and the perception of sensorial attributes. In this study, a fruit transcriptome investigation, a sensory test, and a metabolomic analysis were performed to evaluate the impact of the environment on two popular tomato cultivars grown in two Italian regions. The transcriptional profile of each cultivar, cultivated in two different areas, highlighted differential expression in genes involved in pathways related to cell wall components such as pectin, lignin, and hemicellulose and sugars as well as in amino acids, phenylpropanoids, and pigment synthesis. The cultivation area mainly affects sensory attributes related to texture and flavor and the metabolic pattern of cell wall precursors, sugars, glutamate, aspartate, and carotenoids. In the two genotypes cultivated in the same environment, some attributes and fruit-related quality processes are similarly affected, while others are differently influenced based on the specific genetic makeup of the tomato. A combination of transcriptomic, sensory, and metabolomic data obtained from the two tomato genotypes revealed that the environment has a profound effect on specific sensory traits, providing information on factors that shape the specific characteristics and genetic targets for improving tomato fruit characteristics. [ABSTRACT FROM AUTHOR]

Two years of monthly sampling and hydrological monitoring were performed at the outlet of a Mediterranean watershed in northern Tunisia to determine the contents of 469 pesticide active ingredients and metabolites in water and evaluate their behavior. Wadi Guenniche is a tributary of the Bizerte coastal lagoon, with a watershed area of 86 km2, which exhibits pluvial cereal, legume, and orchid cultivation and irrigated market gardening. Twenty-nine pesticide active ingredients and 2 metabolites were detected in water. Twenty-four pesticide active ingredients were authorized for use in Tunisia. Among them, 14 had never been mentioned in previous farmer surveys. Five herbicides and their metabolites were the most frequently detected: aminomethylphosphonic acid (AMPA) (100%), glyphosate (94%), simazine (94%), 2,4-D (70%), and deisopropylatrazine (DIA) (47%). The detection frequency and concentration range suggested that the phytosanitary pressure and resulting water contamination are close to those on the northern Mediterranean shore. These results, in addition to characterizing the pollution state, emphasized the need for additional studies on the use and fate of pesticides on the southern shore of the Mediterranean Sea, particularly in Tunisia. [ABSTRACT FROM AUTHOR]

Aging significantly influences cellular activity and metabolism in glucose‐responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell‐type responses has been lacking. This study integrates transcriptomic, methylomic, single‐cell RNA sequencing, and metabolomic data to investigate aging‐related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging‐associated network modules specific to certain cell types, including adipocytes and immune cells. Aging upregulates the metabolic functions of lysosomes and downregulates the branched‐chain amino acids (BCAAs) degradation pathway. Additionally, aging‐associated changes in cell proportions, methylation profiles, and single‐cell expressions were observed in the adipose. In the muscle tissue, aging was found to repress the metabolic processes of glycolysis and oxidative phosphorylation, along with reduced gene activity of fast‐twitch type II muscle fibers. Metabolomic profiling linked aging‐related alterations in plasma metabolites to gene expression in glucose‐responsive tissues, particularly in tRNA modifications, BCAA metabolism, and sex hormone signaling. Together, our multi‐omic analyses provide a comprehensive understanding of the impacts of aging on glucose‐responsive tissues and identify potential plasma biomarkers for these effects. [ABSTRACT FROM AUTHOR]

Bacteriocins produced by a number of lactic acid bacteria (LAB) comprise a variety of antimicrobial proteins that may be used as antibiotic alternative in food preservation. The present study aimed to isolate and characterize LAB-derived bacteriocin-like substances (BLS) from local fermented foods. A total of twenty-one bacterial strains were isolated and subjected to an antibacterial assay. Five isolates designated as AB1, AB2, AK1, AK2, AnK1 showed inhibitory activity against selected indicator organisms and were subjected to further characterization. Upon BLAST analysis of the 16S rRNA gene sequences, the isolates showed close relationship to Lactobacillus plantarum with similarity ranging from 91 to 97%. Moreover, the antibacterial metabolite production of the isolates was observed to peak on the 5th to 7th day of incubation. Since AnK1 showed the highest zone of inhibition among 5 isolates, it was selected for characterization of the BLS isolated by ammonium sulfate precipitation and anion exchange chromatography. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the AnK1-BLS had a single band and a molecular weight around 15 kDa, and a total protein concentration of 7.06 µg/mL. Interestingly, AnK1-BLS had a broad antimicrobial spectrum on both gram-negative and gram-positive food-borne pathogens, including Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Bacillus subtilis. Moreover, the purified AnK1-BLS exhibited good thermal stability when heated at 80‒121°C. Likewise, its inhibitory activity was not affected by pH in the range of 3.0 to 6.5, with maximum activity recorded at pH 3.0. The results suggest that AnK1-BLS may have application prospects in the food industry. Further studies on the complete protein characterization of AnK1-BLS is recommended to fully harness its capabilities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4′‐hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g−1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1–98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4′‐hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background Perturbation of gut microbiota has been linked to chronic kidney disease (CKD), which was correlated with a sophisticated milieu of metabolic and immune dysregulation. Methods To clarify the underlying host–microbe interaction in CKD, we performed multi-omics measurements, including systems-level gut microbiome, targeted serum metabolome and deep immunotyping, in a cohort of patients and non-CKD controls. Results Our analyses on functional profiles of the gut microbiome showed a decrease in the diversity and abundance of carbohydrate-active enzyme (CAZyme) genes but an increase in the abundance of antibiotic resistance, nitrogen cycling enzyme and virulence factor genes in CKD. Moreover, models generated using measurements of serum metabolites (amino acids, bile acids and short-chain fatty acids) or immunotypes were predictive of renal impairment but less so than many of the functional profiles derived from gut microbiota, with the CAZyme genes being the top-performing model to accurately predict the early stage of diseases. In addition, co-occurrence analyses revealed coordinated host–microbe relationships in CKD. Specifically, the highest fractions of significant correlations were identified with circulating metabolites by several taxonomic and functional profiles of gut microbiome, while immunotype features were moderately associated with the abundance of microbiome-encoded metabolic pathways and serum levels of amino acids (e.g. B cell cluster tryptophan and B cell cluster tryptophan metabolism). Conclusion Overall, our multi-omics integration revealed several signatures of systems-level gut microbiome in robust associations with host–microbe co-metabolites and renal function, which may have aetiological and diagnostic implications in CKD. [ABSTRACT FROM AUTHOR]

Vigna mungo. L (Black gram) belonging to the Leguminosae family is a most abundant source of protein for human and animal diets. Over 8.5 million tonnes of black gram are being produced worldwide, and after confiscating the endosperm for the protein source, the seed coat is dumped as agro-waste and used as feed for the cattle. This study aims to investigate and profile the metabolites in three distinct parts of V. mungo seeds: coat, cotyledon, and intact seed. Also, it has been hypothesized that sugar methylation plays a pivotal role in facilitating black gram seed germination by serving as an energy source during metabolic processes. In our study, A total of forty-nine compounds belonging to the class such as fatty acids, saccharides, triterpenes, sterols, and vitamins were detected in various parts of V. mungo seed by gas chromatography-mass spectrometry (GC-MS). Most interestingly, 3-O-methyl-D-glucose (3-OMG) was commonly detected in methanolic extract of coat, intact seed, and cotyledon with peak area percentages of 3.076, 1.157, and 1.100 %, respectively. Based on the highest peak area percentage in the coat, this compound was purified by using a silica gel column with a mesh size of 60–120 followed by Biotage SNAP cartridge KP-C18-HS (12 g). The yield and purity of the purified fractions were found to be 11.78 & 94.19 %, respectively by high-performance liquid chromatography (HPLC) analysis. Further, the mass confirmation of purified fraction containing 3-OMG (m/z - 217.06 g/mol) was done by liquid chromatography-mass spectrometry (LC-MS/MS) and reconfirmed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). The MS/MS analysis of the fragment showed m/z 206.91 for 3-OMG which corresponds to the association of the sodium adduct. The concentration of 3-OMG was quantified as 332.65 µg/g of dry weight in the coat of V. mungo by HPLC analysis. Also, among the antioxidant assays conducted, such as DPPH, ABTS, FRAP, and NOS, it was observed that the methanolic extract of coat exhibited the most significant antioxidant activity. The 3-OMG is commonly used as a non-metabolized analogue of glucose by regulating glucose transporter, especially GLUT-4 that regulates the absorption of glucose by insulin into muscle and fat cells. This study supports the black gram seed with coat as an alternative medicine to regulate blood glucose. [Display omitted] • The analysis focuses on the seed of Vigna mungo L which is produced globally. • Fatty acids, saccharides, triterpenes, sterols, and vitamins were detected by GC-MS in various parts of the V. mungo seed. • 3-O-methyl-D-glucose was detected in the coat with a high peak area percentage using GC-MS.3-O-methyl-D-glucose (3-OMG) detected in coat, seed, and cotyledon with high peak. • The MS/MS fragment of purified fraction for 3-OMG showed m/z 217.06 and was quantified at 332.65 μg/g of dry weight by HPLC. • Methanolic extract of the coat exhibited the highest antioxidant. [ABSTRACT FROM AUTHOR]

Background: Coffee is one of the world's most popular beverages and is the main dietary source of caffeine for most people. The various molecular effects of caffeine suggest that it may enhance bone loss. The purpose of the present study was to investigate the relationship of coffee, coffee types, and caffeine metabolites with periodontitis. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009–2014. Total coffee and different types of coffee consumption were acquired through a 24‐h dietary recall. Urinary caffeine metabolites were quantified using high‐performance liquid chromatography–electrospray ionization–tandem quadrupole mass spectrometry (HPLC‒ESI‒MS/MS). The association of coffee, coffee types, and caffeine metabolites with periodontitis and its severity were assessed using multivariable logistic regression. Results: A total of 3309 eligible participants were included. After adjusting for potential confounding variables, a positive association was observed between coffee consumption (particularly certain types of coffee) and periodontitis. Notably, a positive correlation was also found between total coffee intake and the severity of periodontitis. Additionally, for urinary caffeine metabolites, there was a significant positive association between 1‐methyluric acid (1‐MU), 1,3‐dimethyluric acid (1,3‐DMU), 3,7‐dimethyluric acid (3,7‐DMU), 1,7‐dimethylxanthine (1,7‐DMX), or 5‐actlyamino‐6‐amino‐3‐methyluracil (AAMU) and periodontitis, with adjusted odds ratios and 95% confidence intervals of 1.10 (1.02, 1.19), 1.86 (1.05, 3.29), 0.94 (0.90, 0.98), 1.29 (1.03, 1.62), and 1.15 (1.05, 1.26), respectively. Conclusions: The present study suggests a positive association of coffee intake (especially certain coffee types) and caffeine metabolites (1‐MU, 1,3‐DMU, 3,7‐DMU, 1,7‐DMX, and AAMU) with periodontitis and its severity. [ABSTRACT FROM AUTHOR]

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The convenient and sensitive detection of metabolites is of great significance for understanding human health status and drug development. Solid-phase electrochemiluminescence (ECL) enzyme electrodes show great potential in metabolite detection based on the enzyme-catalyzed reaction product hydrogen peroxide (H2O2). Herein, a solid-phase ECL enzyme sensor was fabricated based on a confined emitter and an immobilized enzyme using electrostatic nanocage array, constructing a platform for the sensitive detection of cholesterol. The electrostatic cage nanochannel consists of a bipolar and bilayer vertically aligned mesoporous silica film (bp-VMSF). The upper layer of bp-VMSF is an amino-modified, positively charged VMSF (p-VMSF), and the lower layer is a negatively charged VMSF (n-VMSF). The most commonly used ECL probe tris(bipyridine)ruthenium(II) (Ru(bpy)32+) is fixed in n-VMSF by electrostatic adsorption from n-VMSF and electrostatic repulsion from the upper p-VMSF, generating significantly enhanced and stable ECL signals. The successful preparation of the electrostatic cage was characterized by scanning electron microscopy (SEM) and electrochemical methods. After amino groups on the outer surface of bp-VMSF were derivatized with aldehyde, cholesterol oxidase (ChOx) molecules were covalently immobilized. The successful construction of the enzyme electrode was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). When the corresponding enzyme substrate, cholesterol, was present in the solution, the ECL signal of Ru(bpy)32+ was quenched by the enzyme-catalyzed reaction product H2O2, enabling the high-sensitivity detection of cholesterol. The linear range for detecting cholesterol was from 0.05 mM to 5.0 mM, with a limit of detection (LOD) of 1.5 μM. [ABSTRACT FROM AUTHOR]

Background: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. Methods: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. Results: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. Limitations: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. Conclusions: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a critical inflammatory condition linked to diabetes, affecting millions worldwide. This study employs Mendelian randomization (MR) to explore the causal relationship between immune cell signatures and DN, analyzing over 731 immune signatures and incorporating data from 1400 metabolites to investigate potential mediators. Despite no statistically significant influence of DN on immunophenotypes after FDR correction, some phenotypes with unadjusted low P-values warranted mention, including CD34 on Hematopoietic Stem Cell (Myeloid cell Panel), CD45 on CD33− HLA DR− (Myeloid cell Panel). Furthermore, three immunophenotypes were identified to have a significant impact on DN risk: CD16−CD56 on HLA DR+ NK (TBNK Panel), CD45 on HLA DR+ T cell (TBNK Panel), and CD33dim HLA DR+ CD11b+ AC (Myeloid cell Panel). Our findings underscore the critical role of immune cells in DN, highlighting potential mediators and offering new insights into its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Weeds cause significant agricultural losses worldwide, and herbicides have traditionally been the main solution to this problem. However, the extensive use of herbicides has led to multiple cases of weed resistance, which could generate an increase in the application concentration and consequently a higher persistence in the environment, hindering natural degradation processes. Consequently, more environmentally friendly alternatives, such as microbial bioherbicides, have been sought. Although these bioherbicides are promising, their efficacy remains a challenge, as evidenced by their limited commercial and industrial production. This article reviews the current status of microbial-based bioherbicides and highlights the potential of cell-free metabolites to improve their efficacy and commercial attractiveness. Stirred tank bioreactors are identified as the most widely used for production-scale submerged fermentation. In addition, the use of alternative carbon and nitrogen sources, such as industrial waste, supports the circular economy. Furthermore, this article discusses the optimization of downstream processes using bioprospecting and in silico technologies to identify target metabolites, which leads to more precise and efficient production strategies. Bacterial bioherbicides, particularly those derived from Pseudomonas and Xanthomonas, and fungal bioherbicides from genera such as Alternaria, Colletotrichum, Trichoderma and Phoma, show significant potential. Nevertheless, limitations such as their restricted range of action, their persistence in the environment, and regulatory issues restrict their commercial availability. The utilization of cell-free microbial metabolites is proposed as a promising solution due to their simpler handling and application. In addition, modern technologies, including encapsulation and integrated management with chemical herbicides, are investigated to enhance the efficacy and sustainability of bioherbicides. [ABSTRACT FROM AUTHOR]

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Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A. [ABSTRACT FROM AUTHOR]

Background: Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions. Results: Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at . Conclusions: In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions. [ABSTRACT FROM AUTHOR]

Aging represents a multifaceted process culminating in the deterioration of biological functions. Despite the introduction of numerous anti‐aging strategies, their therapeutic outcomes have often been less than optimal. Consequently, discovering new targets to mitigate aging effects is of critical importance. We applied Mendelian randomization (MR) to identify potential pharmacological targets against aging, drawing upon summary statistics from both the Decode and FinnGen cohorts, with further validation in an additional cohort. To address potential reverse causality, bidirectional MR analysis with Steiger filtering was utilized. Additionally, Bayesian co‐localization and phenotype scanning were implemented to investigate previous associations between genetic variants and traits. Summary‐data‐based Mendelian randomization (SMR) analysis was conducted to assess the impact of genetic variants on aging via their effects on protein expression. Additionally, mediation analysis was orchestrated to uncover potential intermediaries in these associations. Finally, we probed the systemic implications of drug‐target protein expression across diverse indications by MR‐PheWas analysis. Utilizing a Bonferroni‐corrected threshold, our MR examination identified 10 protein‐aging associations. Within this cohort of proteins, MST1, LCT, GMPR2, PSMB4, ECM1, EFEMP1, and ISLR2 appear to exacerbate aging risks, while MAX, B3GNT8, and USP8 may exert protective influences. None of these proteins displayed reverse causality except EFEMP1. Bayesian co‐localization inferred shared variants between aging and proteins such as B3GNT8 (rs11670143), ECM1 (rs61819393), and others listed. Mediator analysis pinpointed 1,5‐anhydroglucitol as a partial intermediary in the influence LCT exhibits on telomere length. Circulating proteins play a pivotal role in influencing the aging process, making them promising candidates for therapeutic intervention. The implications of these proteins in aging warrant further investigation in future clinical research. [ABSTRACT FROM AUTHOR]

Background and Aim: The colostrum is essential for a kid's survival and development. The metabolomic profiles of mammary secretion in goats are limited. This study investigated the metabolomic profiles of mammary secretion in purebred Black Bengal goats and their relationships with litter size and parity number. Materials and Methods: 500 MHz nuclear magnetic resonance was used to analyze the metabolomic profiles of 43 colostrum and milk samples collected on delivery day and day 7 after parturition, respectively. Results: Fifty-one metabolites were distinguished between colostrum and milk based on heatmap visualization and hierarchical cluster analysis. In colostrum, most compounds were present in significantly greater amounts than in milk. Milk of goats with multiple litter sizes had higher levels of lactose while fat, protein, total solids, solid not fat, and most of the metabolites were lower. The parity number of dams shows no difference in the composition of all components between primiparous and multiparous goats. Conclusion: The components in colostrum were significantly more concentrated than those in milk. The multiple litter sizes in dams led to a significant impact on the composition of lactose and other milk metabolites. [ABSTRACT FROM AUTHOR]

The tractable preparation of Phase I drug metabolites is a critical step to understand the firstpass behaviour of novel chemical entities (NCEs) in drug discovery. In this study, we have developed a structure–electroactivity relationship (SeAR)-informed electrochemical reaction of the parent 2-chlorophenothiazine and the antipsychotic medication, chlorpromazine. With the ability to dial-in under current controlled conditions, the formation of S-oxide and novel S,S-dioxide metabolites has been achieved for the first time on a multi-milligram scale using a direct batch electrode platform. A potential rationale for the electrochemical formation of these metabolites in situ is proposed using molecular docking to a cytochrome P450 enzyme. [ABSTRACT FROM AUTHOR]

To gain a comprehensive understanding of the metabolite differences and metabolic pathways involved in the mycelium of Grifola frondosa during various culture periods, this study employed HPLC-MS/MS analysis to thoroughly investigate the mycelium cultured for 10, 20, 30 d. The results were as follows:(1)We identified a total of 584 metabolites belonging to 42 different categories. Notably, among these metabolites, 159, 47, and 165 metabolites exhibited distinct accumulation patterns in the control comparison groups of 10 d vs 20 d, 20 d vs 30 d, and 10 d vs 30 d, respectively. This significant variation in metabolite composition across different culture periods suggested that the metabolic activities of the mycelium were dynamically changing as it grew. (2)During the early stage of culturing(10 d), the mycelium produced a higher concentration of metabolites related to promoting its growth and oxidative energy supply. As the culture progressed to 20 d, the mycelium began to produce or accumulate various secondary metabolites that were beneficial to humans. These included compounds like oleuropein, glycyrrhetic acid, N-methyltyramine, and alprazolam, which were known for their biological activities and potential in health benefits. As the culture progressed to 30 d, the mycelium contained multiple compounds were associated with aroma production. (3)To further understand the underlying metabolic processes, we conducted KEGG metabolic pathway enrichment analysis. This analysis revealed that the comparison groups of 10 d vs 20 d, 20 d vs 30 d, and 10 d vs 30 d were enriched in 163, 81, and 137 metabolic pathways, respectively. Among these, amino acid metabolism emerged as the most significantly influenced pathway in different culture periods, and this finding underscored the importance of amino acid metabolism in driving the metabolic activities of the mycelium during its growth cycle. In conclusion, this study initially explores the differential metabolites and metabolic pathways of the mycelium of G. frondosa, and finds that there are significant differences in the metabolites of the mycelium of G. frondosa in different culture periods, and that the contents of some components in the mycelium is related to the culture time, which has a certain reference value for the quality control and mechanism research of the mycelium of G. frondosa. [ABSTRACT FROM AUTHOR]

In this study, we investigated the concurrent elimination of two distinct contaminants: organic matter in the form of dexamethasone phosphate (DexP) and an inorganic substance, chromium (Cr), employing UV irradiation. UV irradiation serves as a potent tool for breaking down organic materials, leading to the production of benign by-products, namely CO2 and H2O. Under optimal conditions characterized by a 30:1 DexP/Cr molar ratio and a pH level of 9, remarkable removal efficiencies were attained. In a mere 20 min, approximately 100% of DexP and 82.73% of Cr were effectively removed. Intriguingly, the removal of Cr exhibited an initially sluggish rate, with deposition commencing only after the breakdown of the DexP structure. This transformation was accompanied by the emergence of various sludge forms, each possessing unique characteristics. Utilizing Fourier-transform infrared (FTIR) analysis, we identified these sludge forms as chromium(III) hydroxide (green sludge), chromium(III) hydroxide (brown sludge), chromium(III) oxide (tiny green crystals), chromium(II) acetate chromium trioxide (red brick), and chromium oxide (black sludge). Further experimentation with varying concentrations of Cr and DexP, ranging from 50 to 150 mg L−1, yielded a range of rate constants (kobs) from 0.33 to 0.15 and removal efficiencies (robs) from 16.8 to 23.4% in the UV/DexP/Cr process. Energy efficiency output (EEO) calculations revealed that Cr precipitation ranged from 24.65 to 5.74 kW h m−3, whereas DexP EEO ranged from 12.54 to 4.73 kW h m−3. Of significant importance is the observation that when these two contaminants are removed simultaneously, the overall energy consumption is substantially lower compared to the scenario where pollutants are addressed individually. This finding underscores the efficiency and potential energy cost savings achievable through the concurrent removal of DexP and Cr using UV irradiation, making it a promising approach for environmental remediation. [ABSTRACT FROM AUTHOR]

It is estimated that approximately seven million people worldwide are affected by inflammatory bowel disease (IBD), causing a huge burden on healthcare systems and society. In the occurrence, progression, and treatment of IBD, the intestinal microbiota and its key metabolic product, bile acids, play a crucial role. The intestinal microbiota not only participates in the biotransformation of bile acids, enriching the diversity of bile acids, but also regulates their synthesis and transport through the farnesoid X receptor (FXR). Meanwhile, bile acids contribute to regulating the structure and function of the intestinal microbiota by supporting microbial diversity, exerting direct toxicity, participating in indirect antimicrobial pathways, and influencing microbial metabolic capabilities. Furthermore, under normal physiological conditions, intestinal microbiota-derived bile acids facilitate the repair process of the intestinal epithelial barrier. They also promote the balance of the immune system by modulating the functions of various immune cells including helper T (Th) cells 17, regulatory T (Treg) cells, CD8+ T cells and natural killer T(NKT) cells, thereby slowing down the development of IBD. This article focuses on exploring the role of intestinal microbiota and bile acids in the onset and progression of IBD, and investigating new effective treatment strategies by targeting intestinal microbiota and bile acids, such as bile acid receptor modulators, probiotics, prebiotics, fecal microbiota transplantation (FMT), and phage therapy. [ABSTRACT FROM AUTHOR]

Aim: To investigate the therapeutic effects of Dracocephalum moldavica L. extract (DME) against hypertension and elucidate the underlying molecular mechanism. Method: A two-kidney one-clip (2K1C) model was established in male Wistar rats, and DME or saline was administered via oral gavage for 4 weeks. Subsequently, the blood pressure was monitored. Fecal microRNAs (miRNAs), gut microbes, and host metabolites were evaluated through miRNA sequencing, 16S rRNA gene sequencing, and serum metabolomics analysis, respectively. Results: DME administration attenuated 2K1C-induced hypertension in rats. Additionally, DME alleviated the dysregulation of miRNA expression and gut microbiota dysbiosis in 2K1C rats. The correlation analysis confirmed the association of the differentially expressed miRNAs with gut microbes. Furthermore, non-targeted metabolomics analysis revealed different metabolic profiles in the serum of 2K1C rats compared to control rats. Interestingly, the changes in those serum metabolites were partially attenuated by DME. The metabolite enrichment analysis demonstrated that the differentially expressed metabolites were mainly involved in three metabolic pathways (Arachidonic acid metabolism, TCA cycle, and Alanine, aspartate and glutamate metabolism). Conclusion: DME can be suggested as an effective intervention in the prevention of hypertension through modulating the miRNAs, gut microbiota, and host metabolites. Our findings may give new insights regarding the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Water contamination with organochlorine pesticides (OCPs) is strongly linked to agricultural practices, and it still represents an environmental issue, despite the OCPs bans in many countries and despite the reported sustainable remediation technologies for their removal. Considering the environmental persistence of OCPs, the imbalances produced in the ecosystem, and the bioaccumulation tendency in living organisms through the food chain, the monitoring of OCPs and of their metabolites has crucial importance. The accuracy of the results obtained is strongly connected to the selection of reliable and accurate analytical procedures, especially considering the multitude of challenges related to OCP quantification. The purpose of this paper is to present an overview of the analytical techniques and protocols reported for OCP assessment in water, and to offer scientists a presentation of the current state of the literature on this subject. Nevertheless, it must be considered that each method has advantages and disadvantages, and, in most cases, the protocols reported in the literature must be adapted and improved. In addition, the levels of OCPs identified in surface water, groundwater, and rainwater have been reviewed. This review paper is directly connected to sustainability practices, since environmental sustainability is related to the responsibility to conserve natural resources and to prevent pollution, and for scientists, these objectives are fulfilled by conducting chemical analyses to track and quantify pollutants, as part of environmental studies. [ABSTRACT FROM AUTHOR]

Yunnan semi-fine wool (YSFW) is a recently developed dual-purpose (meat and wool) sheep breed mainly found in Yunnan Province, China. Moreover, dietary calcium is essential for animal health and productivity. The current experiment aimed to investigate the impact of dietary calcium on sheep gut metabolite profile. For this, thirty YSFW rams (male, age = 10 months, and body weight = 40.37 ± 0.49 kg) were randomized into three groups (n = 10 rams/group), followed by a completely randomized design, and the groups were allotted to one of three dietary calcium levels (Q_1 = 0.50%, Q_3 = 0.73%, and Q_5 = 0.98% on a dry basis). The rams were fed ad libitum by feeding twice a day (at 08:00 and 17:00 h/day) throughout the experimental period (44 day). On the 21st day of the experiment, fecal samples were collected from 27 rams (9/group) and untargeted metabolite profiling was performed by using ultra-performance liquid chromatography. The PCA plot showed that the Q_5 group metabolites were clustered more tightly than for Q_1 and Q_3, respectively. The tightly clustering molecules were mainly alkaloids and their derivatives, benzenoids, lignans and related compounds, lipids, nucleotides, organic acids, and nitrogenous-based derivatives. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, these molecules potentially contribute to metabolic pathways, biosynthesis of secondary metabolites, proteinaceous compounds, and the metabolism of the protein derivatives, particularly amino acids. The PLS-DA plots revealed a significant difference between the Q_1, Q_3, and Q_5 groups, suggesting that Q_5 had a clear separation across the groups. Based on the metabolomic analysis, feeding different levels of dietary calcium significantly changed the metabolomic profile of YSFW rams, which primarily entails metabolic pathways such as energy, protein, and lipid metabolism. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate potential regulatory mechanisms of feed efficiency (FE) in sheep by linking rumen microbiota with its host by the multi-omics analysis. One hundred and ninety-eight hybrid female sheep (initial body weight = 30.88 ± 4.57 kg; 4-month-old) were selected as candidate sheep. Each test sheep was fed in an individual pen for 60 days, and the residual feed intake (RFI) was calculated. The ten candidate sheep with the highest RFI were divided into the Low-FE group, and the ten with the lowest RFI were divided into the High-FE group, all selected for sample collection. The RFI, average daily gain and average daily feed intake were highly significantly different between the two experimental groups (P

Diabetic kidney disease (DKD) is one of the main microvascular complications of diabetes mellitus, as well as the leading cause of end-stage renal disease. Intestinal microbiota has emerged as a crucial regulator of its occurrence and development. Dysbiosis of the intestinal microbiota can disrupt the intestinal mucosal barrier, abnormal immunological response, reduction in short-chain fatty acid metabolites, and elevation of uremic toxins, all closely related to the occurrence and development of DKD. However, the underlying mechanisms of how intestinal microbiota and its metabolites influence the onset and progression of DKD has not been fully elucidated. In the current review, we will try to summarize the microecological mechanism of DKD by focusing on three aspects: the intestinal microbiota and its associated metabolites, and the “gut–kidney axis,” and try to summarize therapies targeted at managing the intestinal microbiota, expecting to provide theoretical basis for the subsequent study of the relationship between intestinal homeostasis and DKD, and will open an emerging perspective and orientation for DKD treatment.

Background: MR spectroscopy is an additional sequence to evaluate lesion characteristics in the brain. Time Echo (TE) is crucial for analyzing MR spectroscopy metabolite. Purpose: This study aims to evaluate the best TE variations during MR spectroscopy examinations in brain lesions. Method: This research is an experimental quantitative study. Researchers used five samples focusing on the results of head multi-voxel spectroscopy charts with clinical lesions or masses that had been taken twice using TE 35 and TE 144. At each TE in each sample, three voxel areas were measured, namely normal, perilesional, and lesion. Each spectroscopy data result is processed individually through READY View software, automatically producing a spectroscopy graph pattern. The required data in this study is the value of each head spectroscopy metabolism: N-Acetyl Aspartate (NAA), Choline (Cho), Creatine (Cr), Myo-Inositol (MI), Lipids Lactate (LL). All statistical tests used the SPSS v.26 application. Result: Based on Paired T test results, NAA, Cho, Cr, and MI metabolites have p-values that account for 0.779 > 0.05; 0.179 > 0.05; 0.581 > 0.05; and 0.057 > 0.05. Based on the Wilcoxon Sign Rank test, the LL metabolite showed a p-value of 0.460 > 0.05. Conclusion: There is no significant difference between TE 35 ms and TE 144 ms during MR spectroscopy examinations.

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. Methods We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. Results Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. Limitations Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. Conclusions Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development.

Abstract Campanumoea javanica Bl. (CJ) traditionally used in Southwestern China, is now widely consumed as a health food across the nation. Due to its similar efficacy to Codonopsis Radix (CR) and their shared botanical family, CJ is often used as a substitute for CR. According to the Chinese Pharmacopoeia, Codonopsis pilosula var. modesta (Nannf.) L.T. Shen (CPM), Codonopsis pilosula (Franch.) Nannf. (CP), and Codonopsis tangshen Oliv. (CT) are the primary sources of CR. However, details on the differences in composition, effectiveness, and compositional between CJ and CR are still limited. Besides, there is little evidence to support the application of CJ as a drug. In this study, we employed widely targeted metabolomics, network pharmacology analysis, and molecular docking to explore the disparities in metabolite profiles between CJ and CR and to predict the pharmacological mechanisms of the dominant differential metabolites of CJ and their potential medicinal applications. The widely targeted metabolomics results indicated that 1,076, 1,102, 1,102, and 1,093 compounds, most phenolic acids, lipids, amino acids, and flavonoids, were characterized in CJ, CPM, CP, and CT, respectively. There were an average of 1061 shared compounds in CJ and CRs, with 95.07% similarity in metabolic profiles. Most of the metabolites in CJ were previously unreported. Twelve of the seventeen dominant metabolites found in CJ were directly associated with treating cancer and lactation, similar to the traditional medicinal efficacy. The molecular docking results showed that the dominant metabolites of CJ had good docking activity with the core targets PIK3R1, PIK3CA, ESR1, HSP90AA1, EGFR, and AKT1. This study provides a scientific basis for understanding the similarities and differences between CJ and CR at the metabolome level, offering a theoretical foundation for developing innovative medications from CJ. Additionally, it significantly enhances the metabolite databases for both CJ and CR.

Abstract Diabetic nephropathy (DN) is a critical inflammatory condition linked to diabetes, affecting millions worldwide. This study employs Mendelian randomization (MR) to explore the causal relationship between immune cell signatures and DN, analyzing over 731 immune signatures and incorporating data from 1400 metabolites to investigate potential mediators. Despite no statistically significant influence of DN on immunophenotypes after FDR correction, some phenotypes with unadjusted low P-values warranted mention, including CD34 on Hematopoietic Stem Cell (Myeloid cell Panel), CD45 on CD33− HLA DR− (Myeloid cell Panel). Furthermore, three immunophenotypes were identified to have a significant impact on DN risk: CD16−CD56 on HLA DR+ NK (TBNK Panel), CD45 on HLA DR+ T cell (TBNK Panel), and CD33dim HLA DR+ CD11b+ AC (Myeloid cell Panel). Our findings underscore the critical role of immune cells in DN, highlighting potential mediators and offering new insights into its underlying mechanisms.

Abstract Background Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions. Results Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at https://www.cellknowledge.com.cn/mrclinkdb/ . Conclusions In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions.

Objective: The study aimed to investigate the effects of Periplaneta americana glycoprotein (PAG) on the growth and metabolites of Lactobacillus plantarum and Bifidobacterium adolescentis. Methods: With inulin as a positive control, the probiotic bacteria were cultured in medium containing different concentrations of PAG (MRS medium with PAG concentrations of 0.5, 1.0, 2.0, and 4.0 mg/mL, respectively. TPY medium with PAG concentrations of 1.0, 2.0, 4.0, and 8.0 mg/mL, respectively) to determine the OD600 and pH, and the contents of lactic acid, short-chain fatty acid (SCFA, snamely acetic acid, propionic acid and butyric acid) in the bacterial solution. Results: The growth of Lactobacillus plantarum was greatest when the concentration of PAG reached 1.0 mg/mL, while Bifidobacterium adolescentis grew best with a PAG concentration of 2.0 mg/mL. The OD600 value, production of lactic acid and SCFAs of Lactobacillus plantarum solution at 1.0 mg/mL PAG were higher than those of inulin, while the pH value was significantly lower. In the bacterial solution of Bifidobacterium adolescentis with 2.0 mg/mL PAG, the values of OD600 and the production of propionic acid and butyric acid increased compared to the same concentration of inulin, the lactic acid production was better than that of inulin at 12 h, the acetic acid production was better than that of inulin at 24 h, and the pH value decreased, indicating that PAG and inulin had different effects on promoting Bifidobacterium adolescentis to produce lactic acid and SCFAs. Conclusion: The PAG could promote the proliferation and organic acid production of Lactobacillus plantarum and Bifidobacterium adolescentis, and the effect was better than that of inulin.

This study investigated within-subject variability in the circulating metabolome under controlled conditions, and whether divergent exercise training backgrounds were associated with alterations in the circulating metabolome assessed in resting samples. Thirty-seven men comprising of endurance athletes (END; body mass, 71.0 ± 6.8 kg; fat-free mass index, 16.9 ± 1.1 kg/m²), strength athletes (STR; 94.5 ± 8.8 kg; 23.0 ± 1.8 kg/m²), and recreationally active controls (CON; 77.6 ± 7.7 kg; 18.1 ± 1.0 kg/m²) provided blood samples after an overnight fast on two separate occasions controlled for time of day of sampling, recent dietary intake, time since last meal, and time since last exercise training session. A targeted profile of metabolites, performed using liquid chromatography and mass spectrometry on plasma samples, identified 166 individual metabolites and metabolite features, which were analyzed with intraclass correlation coefficients, a multilevel principal component analysis, and univariate t tests adjusted for multiple comparisons. The median intraclass correlation coefficient was .49, with 46 metabolites displaying good reliability and 31 metabolites displaying excellent reliability. No difference in the abundance of any individual metabolite was identified within groups when compared between visits, but a combined total of 44 metabolites were significantly different (false discovery rate <0.05) between groups (END vs. CON, 42 metabolites; STR vs. CON, 10 metabolites; and END vs. STR, five metabolites). Under similar measurement conditions, the reliability of resting plasma metabolite concentrations varies largely at the level of individual metabolites with ~48% of metabolites displaying good-to-excellent reliability. However, a history of exercise training was associated with alterations in the abundance of ~28% of metabolites in the targeted profile employed in this study. [ABSTRACT FROM AUTHOR]

The relationship between depression and gut microbiota remains unclear, but an important role of gut microbiota has been verified. The relationship between gut microbiota and antibiotic resistance genes (ARGs) may be a potential new explanatory pathway. We collected samples from 63 depressed patients and 30 healthy controls for metagenomic sequencing. The two groups' microbiota characteristics, functional characteristics, and ARG differences were analyzed. We obtained 30 differential KEGG orthologs (KOs) and their producers in 5 genera and 7 species by HUMAnN3. We found 6 KOs from Weissella_cibaria and Lactobacillus_plantaru are potentially coring functional mechanism of gut microbiota. Different metabolites including sphingolipids, pyrans, prenol lipids, and isoflavonoids also showed significance between MDD and HC. We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs, which indicated different mechanisms in affecting MDD. The present study needs to be replicated in different ethnic groups. At the same time, a larger Chinese cohort study and detailed experimental verification are also the key to further discussion. Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota. • We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. • Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). • Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs to affect MDD. [ABSTRACT FROM AUTHOR]

BackgroudAt present, there is no unified standard for the detection of glufosinate ammonium and three metabolites in urine, which affects the accurate assessment of occupational exposure risk to a certain extent. It is of great significance to establish a rapid and effective inspection method to ensure occupational safety and public health.ObjectiveTo establish an ultra performance liquid chromatography-tandem mass spectrometry for simultaneous determination of glufosinate ammonium and three metabolites in urine.MethodsThe effects of dilution solvents and dilution ratios on the response values of glufosinate ammonium and three metabolites were compared, and the retention capacities of solid phase extraction columns for targets as well as the effects of chromatographic columns and mobile phase systems on chromatographic peaks were analyzed. Samples were quantified by matrix effect matching external standard method. Accuracy of the method was evaluated by recovery rate of standard addition, and precision of the method was evaluated by relative standard deviation of intra-day and inter-day measurements. Urine samples of 30 health individuals were collected to evaluate the application of the method.ResultsThe urine samples were diluted with 0.2 mL water and 0.6 mL acetonitrile, purified by HLB solid phase extraction columns, and separated by Dikma Polyamino HILIC columns, and gradient elution was carried out with 0.5 mmol·L−1 ammonium acetate and 0.1% ammonia water as mobile phase, which achieved a good peak shape and mass spectrum response. The linearities of the four target compounds were good in the range of 0.5-50 ng·mL−1, and the correlation coefficients (r) were all greater than 0.998. The detection limits were 0.56-2.86 μg·L−1, the quantification limits were 1.87-29.54 μg·L−1, and the recovery rates of standard addition ranged from 75.0% to 103.6%, The relative standard deviations of intra-batch and inter-batch were from 2.5% to 8.1% and from 4.3% to 9.3% respectively. The method was applied to detect 30 urine samples of subjects, and no target was detected.ConclusionThe method is simple, rapid, sensitive, and accurate. It is suitable for the determination of glufosinate ammonium and its metabolites in human urine without derivatization.