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Caffeine is an ergogenic substance that is consumed globally in many forms. The use of buccally absorbable formulations instead of gastrointestinal uptake has become increasingly popular over the years, especially when accelerated absorption with minimal gastrointestinal stress is desired. This study investigated the impact of five different formulations and administration routes of caffeine on the whole blood concentrations of caffeine, paraxanthine, and theobromine: caffeinated capsules, tablets, shots, pouches, and chewing gums. A uniform dose of caffeine (200 mg) was administered to 16 healthy recreational athletes (26.0 ± 2.1 years) using a randomized crossover design. Samples were taken in the form of dried blood spots at 16 different time points in a 2-hr timeframe after drug administration. The samples were analyzed using a validated liquid chromatography–tandem mass spectrometry method. The results for caffeine showed no significant differences in the overall bioavailability (area under the concentration–time curve), maximal concentration, and time to maximum concentration. However, when analyzing the bioavailability of caffeine in the first 5, 10, and 15 min, the liquid caffeine formulation was superior to other administered forms (p <.05). This indicates that caffeine solubility has a major influence on its absorption rate. In sports, the rate of caffeine absorption must be considered, not only when ingesting anhydrous caffeine, but also when choosing buccal absorption. These findings imply that general guidelines for ergogenic caffeine use should consider the formulation used and, accordingly, the corresponding route of absorption. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations. [ABSTRACT FROM AUTHOR]

Today, colorectal cancer (CRC) diagnosis is performed using colonoscopy, which is the current, most effective screening method. However, colonoscopy poses risks of harm to the patient and is an invasive process. Recent research has proven metabolomics as a potential, non-invasive detection method, which can use identified biomarkers to detect potential cancer in a patients body. The aim of this study is to develop a machine-learning (ML) model based on chemical descriptors that will recognize CRC-associated metabolites. We selected a set of metabolites found as the biomarkers of CRC, confirmed that they participate in cancer-related pathways, and used them for training a machine-learning model for the diagnostics of CRC. Using a set of selective metabolites and random compounds, we developed a range of ML models. The best performing ML model trained on Stage 0-2 CRC metabolite data predicted a metabolite class with 89.55% accuracy. The best performing ML model trained on Stage 3-4 CRC metabolite data predicted a metabolite class with 95.21% accuracy. Lastly, the best-performing ML model trained on Stage 0-4 CRC metabolite data predicted a metabolite class with 93.04% accuracy. These models were then tested on independent datasets, including random and unrelated-disease metabolites. In addition, six pathways related to these CRC metabolites were also distinguished: aminoacyl-tRNA biosynthesis; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; and alanine, aspartate, and glutamate metabolism. Thus, in this research study, we created machine-learning models based on metabolite-related descriptors that may be helpful in developing a non-invasive diagnosis method for CRC.

Summary: Plants, as a sessile organism, produce various secondary metabolites to interact with the environment. These chemicals have fascinated the plant science community because of their ecological significance and notable biological activity. However, predicting the complete biosynthetic pathways from target molecules to metabolic building blocks remains a challenge.Here, we propose retrieval‐augmented dual‐view retrosynthesis (READRetro) as a practical bio‐retrosynthesis tool to predict the biosynthetic pathways of plant natural products. Conventional bio‐retrosynthesis models have been limited in their ability to predict biosynthetic pathways for natural products. READRetro was optimized for the prediction of complex metabolic pathways by incorporating cutting‐edge deep learning architectures, an ensemble approach, and two retrievers.Evaluation of single‐ and multi‐step retrosynthesis showed that each component of READRetro significantly improved its ability to predict biosynthetic pathways. READRetro was also able to propose the known pathways of secondary metabolites such as monoterpene indole alkaloids and the unknown pathway of menisdaurilide, demonstrating its applicability to real‐world bio‐retrosynthesis of plant natural products.For researchers interested in the biosynthesis and production of secondary metabolites, a user‐friendly website (https://readretro.net) and the open‐source code of READRetro have been made available. [ABSTRACT FROM AUTHOR]

Melatonin, a hormone synthesized in various tissues, plays a crucial role in modulating sperm characteristics, yet its protective function on boar sperm remains poorly understood. This study aimed to investigate the expression and localization of melatonin-related proteins (AANAT, ASMT, MT1, MT2, and NQO2) in pig tissues, assess the impact of melatonin on pig sperm motility parameters and quality, and elucidate the underlying molecular mechanisms. Our results revealed widespread expression of AANAT, ASMT, MT1, MT2, and NQO2 proteins in pig tissues, particularly in the testis. Specific localization patterns were observed in Leydig cells, reproductive epithelium, and columnar epithelium cells in the testis and cauda epididymis. Additionally, melatonin membrane receptors MT1 and MT2 were detected in boar sperm. Melatonin treatment significantly enhanced boar sperm motility parameters and quality, particularly with 10 nM melatonin treatment. Inhibition of the MT1 receptor, but not the MT2 receptor, resulted in decreased sperm motility, highlighting the pivotal role of the MT1 receptor in mediating melatonin's effects on boar sperm. Metabolomic analysis revealed significant alterations in sperm metabolites following melatonin supplementation, particularly in amino acid metabolism. Overall, our findings provide comprehensive insights into melatonin's mechanisms in improving boar sperm quality, suggesting its potential as a therapeutic agent for enhancing male fertility. • Comprehensive study shows melatonin boosts boar sperm motility and quality, mainly via the MT1 receptor. • Melatonin-related proteins in pig tissues suggest roles in testicular physiology and sperm protection. • Melatonin alters seminal plasma metabolites, showing diverse impacts on sperm function and metabolism. [ABSTRACT FROM AUTHOR]

We have created a novel synthetic biology expression system allowing easy refactoring of biosynthetic gene clusters (BGCs) as monocistronic transcriptional units. The system is based on a set of plasmids containing a strong kasOp* promoter, RBS and terminators. It allows the cloning of biosynthetic genes into transcriptional units kasOp *-gene(s)-terminator flanked by several rare restriction cloning sites that can be sequentially combined into the artificial BGC in three compatible Streptomyces integration vectors. They allow a simultaneous integration of these BGCs at three different attB sites in the Streptomyces chromosome. The system was validated with biosynthetic genes from two known BGCs for aromatic polyketides landomycin and mithramycin. • A new synthetic biology-based system for investigating antibiotic biosynthesis. • Efficient rabelomycin production using the initial landomycin biosynthetic genes. • Efficient 4-DMPC production using the initial mithramycin biosynthetic genes. [ABSTRACT FROM AUTHOR]

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether‐macrocyclic peptide (teMP) library construction/selection technology, so‐called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp‐C3‐prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product. This unique enzyme exhibited remarkably broad substrate tolerance, capable of modifying various Trp‐containing teMPs to install a prenylated residue with tricyclic constrained structure. We constructed a vast library of prenylated teMPs and subjected it to in vitro selection against a phosphoglycerate mutase. This selection platform has led to the identification of a pseudo‐natural prenylated teMP inhibiting the target enzyme with an IC50 of 30 nM. Importantly, the prenylation was essential for the inhibitory activity, enhanced serum stability, and cellular uptake of the peptide, highlighting the benefits of peptide prenylation. This work showcases the de novo discovery platform for pseudo‐natural prenylated peptides, which is readily applicable to other drug targets. [ABSTRACT FROM AUTHOR]

Plant-derived extracellular vesicles (EVs), containing a myriad of bioactive proteins, microRNAs, lipids, and secondary metabolites, have recently become the focus of rising interest due to their important roles in various applications. The widely accepted method for isolating plant EVs is differential ultracentrifugation plus density gradient centrifugation. However, the combination of differential ultracentrifugation and density gradient centrifugation for the isolation of plant EVs is time-consuming and labor-intensive. Hence, there is a need for more efficient methods to perform the separation of plant EVs. In this study, EVs were separated from Arabidopsis thaliana leaves by a cost-effective polyethylene glycol (PEG)-based precipitation approach. The mean size of purified Arabidopsis thaliana EVs determined by dynamic light scattering was 266 nm, which is consistent with nanoparticle tracking analysis. The size was also confirmed via transmission electron microscopy with morphology of a cup-shaped appearance which is the typical mammalian exosome's morphology. Additionally, Western blotting of the purified Arabidopsis thaliana EVs, using commercially available mammalian exosomal kits, displayed surface marker tetraspanin proteins (CD9, CD63, and CD81), and endosomal sorting complexes required for transport (ESCRT)-associated proteins (TSG101 and ALIX). This demonstrates that the purified Arabidopsis thaliana EVs reveal the typical proteins reported in mammalian exosomes. [ABSTRACT FROM AUTHOR]

Dichondra (Dichondra repens) is an important ground cover plant for landscaping and establishment of green space, but adaptive mechanism of drought tolerance is not well understood in this species. This study was conducted to compare differential response to drought stress among three genotypes (Dr5, Duliujiang, and Dr29) based on integrated physiological, ultrastructural, and metabolic assays. Results showed that drought significantly inhibited photosynthesis, accelerated lipids peroxidation, and also disrupted water balance and cellular metabolism in dichondra plants. Dr5 showed better photochemical efficiency of photosystem II and water homeostasis, less oxidative damage, and more stable chlorophyll metabolism than Duliujinag or Dr29 in response to drought stress. In addition, Dr5 accumulated more amino acids, organic acids, and other metabolites, which was good for maintaining better antioxidant capacity, osmotic homeostasis, and energy metabolism under drought stress. Drought tolerance of Duliujiang was lower than Dr5, but better than Dr29, which could be positively correlated with accumulations of sucrose, maltitol, aconitic acid, isocitric acid, and shikimic acid due to critical roles of these metabolites in osmotic adjustment and metabolic homeostasis. Current findings provide insights into understanding of underlying mechanism of metabolic regulation in dichondra species. Dr5 could be used as an important drought-tolerant resource for cultivation and water-saving breeding. [ABSTRACT FROM AUTHOR]

It remains unclear whether dosage adjustment of intravenous lidocaine is necessary during general anesthesia for elderly patients over 75 years old. This study aimed to investigate the effects of age on the pharmacokinetics (PK) and safety of intravenous lidocaine in patients undergoing general anesthesia. A total of 599 plasma samples were collected from 76 general anesthesia patients across three age groups: 18–64, 65–74, and ≥ 75 years. Lidocaine was administered intravenously at a dose of 1.5 mg/kg for the 18–64 and 65–74 years groups, while the dose was adjusted to 1.0 mg/kg for the ≥ 75 years group. The plasma concentrations of lidocaine and its active metabolites were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were analyzed using a noncompartmental analysis. The results revealed no significant age-related differences in the PK of lidocaine and its metabolites. Among the three age groups, over 90 % of patient achieved a lidocaine concentration within a safe and effective range when the dosage was normalized to 1.5 mg/kg. In conclusion, age-based dosage adjustment was unnecessary for intravenous lidocaine in patients below 86 years undergoing general anesthesia. [ABSTRACT FROM AUTHOR]

This study explores the association between phthalates and total vitamin D levels and the link between phthalates exposure and subclinical inflammation using monocyte percentage to high-density lipoprotein cholesterol ratio (MHR), utilizing three National Health and Nutrition Examination Survey (NHANES) survey cycles 2013-2018. This study is cross-sectional, utilizing one-time urine samples from randomly selected NHANES participants to assess phthalate metabolites. An inverse association between vitamin D and all Di(2-ethylhexyl) phthalate (DEHP) metabolites was found. The molar sum of DEHP metabolites was inversely associated with vitamin D (β −2.329; 95% CI −3.937,−0.720). An inverse association was observed between monocarboxynonyl phthalate and vitamin D (β −0.0278; 95% CI −0.0527,−0.00298). A similar relationship was found between monocarboxyoctyl phthalate and vitamin D (β −0.0160; 95% CI −0.0242,−0.00775). There was no association between phthalate metabolites and MHR. Stratified analysis showed that the association between phthalate metabolites and MHR may vary according to vitamin D status. [ABSTRACT FROM AUTHOR]

Maize grain samples collected from 129 small-scale farmers' stores in southern and southwestern Ethiopia were analysed by LC-MS/MS for a total of 218 mycotoxins and other fungal metabolites of which 15% were regulated mycotoxins. Mycotoxins produced by Penicillium, Aspergillus, and Fusarium accounted for 31%, 17%, and 12% of the metabolites, respectively. Most of the current samples were contaminated by masked and/or emerging mycotoxins with moniliformin being the most prevalent one, contaminating 93% of the samples. Each sample was co-contaminated by 3 to 114 mycotoxins/fungal metabolites. Zearalenone, fumonisin B1, and deoxynivalenol were the dominant mycotoxins, occurring in 78%, 61%, and 55% of the samples with mean concentrations of 243, 429, and 530 µg/kg, respectively. The widespread co-occurrence of several mycotoxins in the samples may pose serious health risks due to synergistic/additional effects. [ABSTRACT FROM AUTHOR]

Summary: Nutritional benefits of legumes make them an important part of sustainable diets. They are rich not only in dietary fibres, proteins, and micronutrients but also in the bioactive compounds that can exhibit various biological activities. In the present study, we aimed to investigate the nutritional analysis, phytochemical composition, and in vitro anti‐obesity activity of two varieties of legumes indigenous to India namely, adzuki beans (Vigna angularis) and mung beans (Vigna radiata). GC–MS, UHPLC‐QTOF‐MS, ICP‐MS analyses were done for bioactive compounds, fatty acids, macro‐elements, micro‐elements, protein, and non‐proteinogenic amino acids. GC–MS analysis showed that the major constituents identified were hydrocarbons, fatty acids, and terpenes, while the presence of various secondary metabolites, macro‐ and micro‐nutrients were detected using UHPLC‐QTOF‐MS and ICP‐MS, respectively. FAME analysis revealed a higher concentration of linoleic acid in adzuki beans, which is nutritionally beneficial for human consumption. Amino acid profiling revealed the presence of essential, non‐essential, and non‐proteinogenic amino acids. Further, adzuki beans and mung beans were screened for cytotoxicity on 3T3‐cell line and it was observed that adzuki beans were less cytotoxic as compared to mung beans. Adzuki beans showed higher HMG‐Co‐A reductase enzyme inhibition activity (60%) as compared to mung beans (2.79%). The results indicate that these two legumes are a very good source of bioactive metabolites and can be developed into novel cholesterol‐lowering and anti‐obesity functional foods. [ABSTRACT FROM AUTHOR]

We established an efficient analytical approach for simultaneous determination of benthiavalicarb-isopropyl and its four metabolites (KIF-230-M1, KIF-230-M3, KIF-230-M4, and KIF-230-M5) in fruits and vegetables. Samples were extracted with acidified acetonitrile, with octadecylsilane and graphitised carbon black as sorbent for clean-up, and UHPLC-MS/MS for determination. The approach was determined at spikes of 5, 50, and 500 μg kg−1. The recoveries of the six matrices analyzed ranged from 74.5% to 115.6% with 0.5–12.6% for intra-day RSDr (n = 5), and 0.4–13.8% for inter-day RSDR (n = 15). The five analytes in all matrices achieved high linearity (R2 > 0.9917). The limit of quantification (LOQ) of benthiavalicarb-isopropyl as well as its four metabolites in all matrices was 5 μg kg−1. This analytical approach allows for monitoring residues of benthiavalicarb-isopropyl and its metabolites in vegetables and fruits. [ABSTRACT FROM AUTHOR]

Bacterial pigments stand out as exceptional natural bioactive compounds with versatile functionalities. The pigments represent molecules from distinct chemical categories including terpenes, terpenoids, carotenoids, pyridine, pyrrole, indole, and phenazines, which are synthesized by diverse groups of bacteria. Their spectrum of physiological activities encompasses bioactive potentials that often confer fitness advantages to facilitate the survival of bacteria amid challenging environmental conditions. A large proportion of such pigments are produced by bacterial pathogens mostly as secondary metabolites. Their multifaceted properties augment potential applications in biomedical, food, pharmaceutical, textile, paint industries, bioremediation, and in biosensor development. Apart from possessing a less detrimental impact on health with environmentally beneficial attributes, tractable and scalable production strategies render bacterial pigments a sustainable option for novel biotechnological exploration for untapped discoveries. The review offers a comprehensive account of physiological role of pigments from bacterial pathogens, production strategies, and potential applications in various biomedical and biotechnological fields. Alongside, the prospect of combining bacterial pigment research with cutting-edge approaches like nanotechnology has been discussed to highlight future endeavours. [ABSTRACT FROM AUTHOR]

Genetically engineered cyanobacterial strains that have improved growth rate, biomass productivity, and metabolite productivity could be a better option for sustainable bio-metabolite production. The global demand for biobased metabolites with nutraceuticals and health benefits has increased due to their safety and plausible therapeutic and nutritional utility. Cyanobacteria are solar-powered green cellular factories that can be genetically tuned to produce metabolites with nutraceutical and pharmaceutical benefits. The present review discusses biotechnological endeavors for producing bioprospective compounds from genetically engineered cyanobacteria and discusses the challenges and troubleshooting faced during metabolite production. This review explores the cyanobacterial versatility, the use of engineered strains, and the techno-economic challenges associated with scaling up metabolite production from cyanobacteria. Challenges to produce cyanobacterial bioactive compounds with remarkable nutraceutical values have been discussed. Additionally, this review also summarises the challenges and future prospects of metabolite production from genetically engineered cyanobacteria as a sustainable approach. [ABSTRACT FROM AUTHOR]

5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA. [ABSTRACT FROM AUTHOR]

Secondary metabolites are often among the major players in plants' function, stability, support, bioactivities, defense mechanisms, and therapeutic applications. One of the major components of these metabolites is volatile oils. Essential oils are considered one of the most important ways in which plants express themselves through aroma. The oils are also one of the reasons for therapy, mood-upliftment, life processes, plants and dependent organisms' survival, joy, happiness, aesthetic beauty, and attractions in several realms, as well as for various interactive species, including insects, animals, and humans. In addition, essential oils participate in modern industries and worldwide healthcare systems. Aromatic plants and their extracted and distilled volatile oils have been used in different systems of traditional medicine and in all ancient civilizations. They are also still used as part of modern healthcare systems and in folkloric therapeutic and prophylactic applications. Therefore, the chemistry, bio-based diversity, geographic sources, biological activities, and clinical applications of volatile oils have gained the momentum and continued attention of researchers, culminating in several thousand publications each year. This review provides updated information on the biological activities and current applications of essential oils in medicine and other healthcare uses. The underlined biomechanistic details of the volatile oils' biological effects are also encompassed. The collected data unambiguously supported the biological importance of this class of secondary metabolites, especially in cancer, inflammation, and microbial infection management. The information contained in the data also highlighted the therapeutic importance of these molecules in various aspects of medicine. [Display omitted] • The sources and biogenesis of essential oils (EOs) were discussed. • The review provides updated information on the biological activities and applications of EOs. • Detailed biomechanistic of the EOs' biological effects were encompassed. • The data supported the importance of EOs in cancer, inflammation, and infection management. • The review highlighted the therapeutic importance of volatile oils in medicine. [ABSTRACT FROM AUTHOR]

Background: Studies present ambiguous findings regarding the role of tryptophan and its metabolites, kynurenine and serotonin in chronic musculoskeletal pain. This systematic review aimed to investigate the expression of tryptophan and its metabolites, serotonin and kynurenine in patients with local and generalized chronic musculoskeletal pain in comparison with pain‐free controls. Methods: An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to 21 April 2023. Out of 6734 articles, a total of 17 studies were included; 12 studies were used in the meta‐analysis of serotonin, 3 regarding tryptophan and 2 studies for a narrative synthesis regarding kynurenine. Risk of bias was assessed using the quality assessment tool for observational cohort and cross‐sectional studies of the National Heart, Lung, and Blood Institute, while the certainty of evidence was by GRADE. Results: All included studies showed a low risk of bias. The meta‐analysis showed lower blood levels of tryptophan (p <.001; very low quality of evidence) and higher blood levels of serotonin (p <.001; very low‐quality evidence) in patients with generalized musculoskeletal pain, when compared to pain‐free individuals. In local chronic musculoskeletal pain, there were higher blood levels of serotonin (p=.251; very low quality of evidence) compared to pain‐free individuals. Regarding kynurenine, the studies reported both higher and lower blood levels in generalized chronic musculoskeletal pain compared to pain‐free individuals. Conclusions: The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold‐standard measurements. Methods: We used cross‐sectional data from 329 children at mid‐childhood (age 5.3 ± 0.3 years; BMI 15.7 ± 1.5 kg/m2) from the Genetics of Glucose regulation in Gestation and Growth (Gen3G), a prospective pre‐birth cohort. We quantified 1038 plasma metabolites and measured body composition using the gold‐standard dual‐energy x‐ray absorptiometry (DXA), in addition to skinfold, waist circumference, and BMI. We applied weighted‐correlation network analysis to identify a network of highly correlated metabolite modules. Spearman's partial correlations were applied to determine the associations of adiposity with metabolite modules and individual metabolites with false discovery rate (FDR) correction. Results: We identified a 'green' module of 120 metabolites, primarily comprised of lipids (mostly sphingomyelins and phosphatidylcholine), that showed positive correlations (all FDR p < 0.05) with DXA estimates of total and truncal fat (ρadjusted = 0.11–0.19), skinfold measures (ρadjusted = 0.09–0.26), and BMI and waist circumference (ρadjusted = 0.15 and 0.18, respectively). These correlations were similar when stratified by sex. Within this module, sphingomyelin (d18:2/14:0, d18:1/14:1)*, a sphingomyelin sub‐specie that is an important component of cell membranes, showed the strongest associations. Conclusions: A module of metabolites was associated with adiposity measures in childhood. [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]

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]

Aim: The relationship between the gut microbiota, metabolites and body fat percentage (BFP) remains unexplored. We systematically assessed the causal relationships between gut microbiota, metabolites and BFP using Mendelian randomization analysis. Materials and Methods: Single nucleotide polymorphisms associated with gut microbiota, blood metabolites and BFP were screened via a genome‐wide association study enrolling individuals of European descent. Summary data from genome‐wide association studies were extracted from the MiBioGen consortium and the UK Biobank. The inverse variance‐weighted model was the primary method used to estimate these causal relationships. Sensitivity analyses were performed using pleiotropy, Mendelian randomization‐Egger regression, heterogeneity tests and leave‐one‐out tests. Results: In the aspect of phyla, classes, orders, families and genera, we observed that o_Bifidobacteriales [β = −0.05; 95% confidence interval (CI): −0.07 to −0.03; false discovery rate (FDR) = 2.76 × 10−3], f_Bifidobacteriaceae (β = −0.05; 95% CI: −0.07 to −0.07; FDR = 2.76 × 10−3), p_Actinobacteria (β = −0.06; 95% CI: −0.09 to −0.03; FDR = 6.36 × 10−3), c_Actinobacteria (β = −0.05; 95% CI: −0.08 to −0.02; FDR = 1.06 × 10−2), g_Bifidobacterium (β = −0.05; 95% CI: −0.07 to −0.02; FDR = 1.85 × 10−2), g_Ruminiclostridium9 (β = −0.03; 95% CI: −0.06 to −0.01; FDR = 4.81 × 10−2) were negatively associated with BFP. G_Olsenella (β = 0.02; 95% CI: 0.01‐0.03; FDR = 2.16 × 10−2) was positively associated with BFP. Among the gut microbiotas, f_Bifidobacteriales, o_Bifidobacteriales, c_Actinobacteria and p_Actinobacteria were shown to be significantly associated with BFP in the validated dataset. In the aspect of metabolites, we only observed that valine (β = 0.77; 95% CI: 0.5‐1.04; FDR = 8.65 × 10−6) was associated with BFP. Conclusions: Multiple gut microbiota and metabolites were strongly associated with an increased BFP. Further studies are required to elucidate the mechanisms underlying this putative causality. In addition, BFP, a key indicator of obesity, suggests that obesity‐related interventions can be developed from gut microbiota and metabolite perspectives. [ABSTRACT FROM AUTHOR]

Microcystis aeruginosa is one of the most predominant freshwater bloom-forming cyanobacterium found globally which is capable of producing toxic secondary metabolites including microcystins that might intoxicate animals and humans when contaminated water or food is ingested. Salvinia auriculata Aubl is one of the plants that might possess bioactive compounds capable of controlling growth and reproduction of M. aeruginosa. The present study aimed to determine the presence of bioactive compounds in S. auriculata extracts and determine alterations occurred in growth and reproduction of M. aeruginosa when exposed to these plant extracts. In addition, this investigation aimed to examine the influence of S. auriculata on antioxidant enzymes detected in M. aeruginosa. The results obtained demonstrated that the aqueous and ethanolic extracts of S. auriculata presented potential for control of cyanobacteria populations, exhibiting algicidal action on M. aeruginosa as well as interfering in antioxidant enzymes activities and parameters associated with oxidative stress. Phytochemical analyses demonstrated the presence of polyphenols and flavonoids content in both extracts. In addition, application of S. auriculata extracts did not produce cytogenotoxicity and/or mutagenicity utilizing Allium cepa test. Therefore, further studies are needed in order to identify and characterize the compounds responsible for these effects on M. aeruginosa and provide information regarding the possible application of S. auriculata in the treatment of drinking water. [ABSTRACT FROM AUTHOR]

This study identified the relationship between energy balance and some blood metabolites in primiparous dairy cows with different calving conception interval. Twenty primiparous Holstein-Friesian dairy cows were grouped according to the interval (days) from calving to conception into early-conception (early-c; <100 days), mid-conception group (mid-c; 100 -- 150 days) or late-conception (late-c; >150 days) group; and evaluated on day -7 prior to parturition, and days 28, 56 and 90 postpartum. All groups presented positive energy balance, serum concentrations of HDL, urea-N and progesterone with no difference on days 28 and 56 of lactation. On day 90 of lactation all the cows presented negative energy balance; however, the early-c group presented a less intense (P < 0.05) net energy balance (-1.09 versus -2.15 and -1.86 Mcal/day), lower concentrations of serum urea-N (3.28 versus 4.22 and 4.88 mg/dL) and HDL cholesterol (0.84 versus 1.59 and 1.46 mmol/L) and greater serum concentration of progesterone (8.13 versus 4.54 and 1.83 ng/mL) than cows of mid-c and late-c groups, respectively. In conclusion, different from those usually observed for multiparous dairy cows, the energy balance during the first weeks of lactation was not a determining factor affecting the calving conception interval of primiparous dairy cows in the present study. Instead, the nutritional status and the serum concentration of urea-N and progesterone at a later stage, after 56 days of lactation, suggest having a role in delaying these cows' pregnant status. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log 2 -fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log 2 -fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log 2 -fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log 2 -fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA. [ABSTRACT FROM AUTHOR]

Elicitation, the process of stimulating plants to enhance the production of valuable secondary metabolites, has emerged as a significant avenue in the field of plant biotechnology. This review paper provides a comprehensive examination of elicitation, encompassing its mechanisms, the imperative for its utilization, and the diverse array of elicitors employed, including abiotic, biotic, and nanoparticle-based agents. By exploring the intricate signaling pathways and molecular responses triggered by external stimuli in this review, we gain insights into how plants tailor their metabolite production in reaction to their environment. Intricately intertwined with the mechanisms, the types of elicitors utilized are extensively discussed. Abiotic elicitors, encompassing physical factors and chemicals, biotic elicitors involving microbe-derived molecules, plant hormones and symbiotic microorganisms, and the emerging application of nanoparticles as elicitation agents are explored. The review further examines the application of these elicitors in both in-vitro and in-vivo cultures, showcasing their practical utility in controlled laboratory settings and real-world environments. By assessing the efficacy of diverse elicitors, this paper provides valuable insights into tailoring elicitation strategies to enhance secondary metabolite yields for various applications. Addressing the limitations and leveraging emerging technologies will undoubtedly steer elicitation research towards innovative breakthroughs, further enhancing our capacity to harness plants for sustainable and efficient secondary metabolite production. [ABSTRACT FROM AUTHOR]

Saponins are a diverse group of compounds (triterpenoid and steroid glycosides), widely distributed, and characterized by their structures, which differ in the number of sugar units linked in various positions. Saponins have emerged as commercially significant compounds with expanding applications in food, cosmetics, and other pharmaceutical applications as a result of consumer demand for their surfactant properties and have received significant attention due to their biological activities (such as anticancer, antimicrobial, antiprotozoal, delivery adjuvant, anticholesterol, and anti-inflammatory properties). To overcome the processing difficulties given by their complexity, new methods for their extraction and purification strategies must be developed in order to realize their full commercial potential. More attention must be paid to this group of metabolites because many of the active mechanisms are still unknown, and plant-derived saponins have great potential for replacing toxic synthetic or animal-derived surfactants in a wide range of modern commercial products. This review provides an update on the sources, structures, and pharmaceutical applications of phytosaponins and discusses the prospects and challenges of future saponin-based formulations or products. [ABSTRACT FROM AUTHOR]

Supra-optimal temperature adversely affects plant growth and development. Among different growth phases, the reproductive stage of plants is highly sensitive to high temperature stress. The heat tolerance of plants is reliant on a complex interplay of various factors, including the activation of heat stress responses, downstream signaling pathways, and biosynthesis of plant hormones. This intricate network of mechanisms results in the production of several secondary metabolites, which play a crucial role in enhancing the plant's ability to cope with high temperature stress. Many of these secondary metabolites are crucial for the reproductive performance of plants, as they are involved in the attraction of pollinators, pollen germination, pollen tube growth, pollen viability, pollen fertility, and fertilization. Reproductive tissues of plants are highly vulnerable to heat stress, but increased biosynthesis of secondary metabolites (flavonoids, polyamines, glutathione, etc.) induces reproductive thermotolerance through reactive oxygen species homeostasis, protecting the cellular membranes, improving pollen fertility, reducing anther abortion, regulating cellular signaling and activation of genes/transcription factors associated with metabolic pathway network. The identification and engineering of some genes controlling the secondary metabolic pathways network have proved effective in inducing terminal heat stress tolerance in transgenic plants. This review highlights the effect of heat stress on plant secondary metabolism and the role of different plant secondary metabolites in contributing to heat stress tolerance in reproductive tissues. The engineering of genes involved in plant secondary metabolic pathway and their effect on heat stress tolerance has also been discussed. [ABSTRACT FROM AUTHOR]

Relaxation correction is an integral step in quantifying brain metabolite concentrations measured by in vivo magnetic resonance spectroscopy (MRS). While most quantification routines assume constant T1 relaxation across age, it is possible that aging alters T1 relaxation rates, as is seen for T2 relaxation. Here, we investigate the age dependence of metabolite T1 relaxation times at 3 T in both gray‐ and white‐matter‐rich voxels using publicly available metabolite and metabolite‐nulled (single inversion recovery TI = 600 ms) spectra acquired at 3 T using Point RESolved Spectroscopy (PRESS) localization. Data were acquired from voxels in the posterior cingulate cortex (PCC) and centrum semiovale (CSO) in 102 healthy volunteers across 5 decades of life (aged 20–69 years). All spectra were analyzed in Osprey v.2.4.0. To estimate T1 relaxation times for total N‐acetyl aspartate at 2.0 ppm (tNAA2.0) and total creatine at 3.0 ppm (tCr3.0), the ratio of modeled metabolite residual amplitudes in the metabolite‐nulled spectrum to the full metabolite signal was calculated using the single‐inversion‐recovery signal equation. Correlations between T1 and subject age were evaluated. Spearman correlations revealed that estimated T1 relaxation times of tNAA2.0 (rs = −0.27; p < 0.006) and tCr3.0 (rs = −0.40; p < 0.001) decreased significantly with age in white‐matter‐rich CSO, and less steeply for tNAA2.0 (rs = −0.228; p = 0.005) and (not significantly for) tCr3.0 (rs = −0.13; p = 0.196) in graymatter‐rich PCC. The analysis harnessed a large publicly available cross‐sectional dataset to test an important hypothesis, that metabolite T1 relaxation times change with age. This preliminary study stresses the importance of further work to measure age‐normed metabolite T1 relaxation times for accurate quantification of metabolite levels in studies of aging. [ABSTRACT FROM AUTHOR]

Cheese, a fundamental component of the human diet and a cornerstone of the global food economy, has a significance beyond its role as a commodity, playing a crucial part in the cultural identity of various communities. The intricate natural aging process known as maturation involves a series of reactions that induce changes in the cheese's physical, biochemical, microbiological, and particularly sensory characteristics, making it a complex aspect of cheese production. Recently, the adoption of omics sciences (e.g., metagenomics, metabolomics, proteomics) has emerged as a new trend in studies related to protected designation of origin (PDO) cheese. This mini‐summary aims to outline the relationship between omics studies in these food matrices and all the sustainability facets of the production chain in general, and to discuss and recognize that the importance of these studies goes beyond comprehending the cheese biome and extends to fostering and ensuring the sustainability of the production chain. In this context, numerous studies in recent years have linked the identification of intrinsic characteristics of PDO cheeses through omics sciences to crucial sustainability themes such as territoriality, biodiversity, and the preservation of product authenticity. The trajectory suggests that, increasingly, multidisciplinary studies spanning various omics sciences will not only contribute to the characterization of these products but will also address sustainability aspects directly related to the production chain (e.g., authenticity, microbial biodiversity, functionality). This expansion underscores the multidisciplinary nature of these studies, broadening their social impact beyond the academic realm. Consequently, these pivotal studies play a crucial role in advancing discussions on PDO products and sustainability. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine's protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis. [ABSTRACT FROM AUTHOR]

Background: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood. Method: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways. Results: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis. Conclusion: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Serial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for detection of OvCa. At a 98.5% specificity cutpoint, the metabolite test achieved sensitivity of 86.2% for detection of early-stage OvCa and was able to capture 64% of the cases with low CA125 levels (< 35 units/mL). In an independent test consisting of 65 early-stage OvCa cases and 141 female controls, the metabolite panel achieved sensitivity of 73.8% at a 91.4% specificity and captured 13 (44.8%) out of 29 early-stage cases with CA125 levels < 35 units/mL. The metabolite test has utility for ovarian cancer screening, capable of improving upon CA125 for detection of early-stage disease. [ABSTRACT FROM AUTHOR]

Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16- are positively correlated with the risk of epilepsy (p < 0.001, OR = 1.0826, 95% CI 1.0361–1.1312). Similarly, metabolites also exhibit a causal relationship with both immune cells (OR = 1.0438, 95% CI 1.0087–1.0801, p = 0.0140) and epilepsy (p = 0.0334, OR = 1.0897, 95% CI 1.0068–1.1795), and sensitivity analysis was conducted to further validate these relationships. Importantly, our intermediate MR results suggest that the metabolite Paraxanthine to linoleate (18:2n6) ratio may mediate the causal relationship between immune cell CD64 on CD14-CD16- and epilepsy, with a mediation effect of 5.05%. The results suggest the importance of specific immune cell levels and metabolites in understanding epilepsy's pathogenesis, which is significant for its prevention and treatment. [ABSTRACT FROM AUTHOR]

Objectives: The ascomycotic yeast-like fungus Aureobasidium exhibits the natural ability to synthesize several secondary metabolites, like polymalic acid, pullulan, or polyol lipids, with potential biotechnological applications. Combined with its polyextremotolerance, these properties make Aureobasidium a promising production host candidate. Hence, plenty of genomes of Aureobasidia have been sequenced recently. Here, we provide the annotated draft genome sequence of the polyol lipid-producing strain A. pullulans NRRL 62042. Data description: The genome of A. pullulans NRRL 62042 was sequenced using Illumina NovaSeq 6000. Genome assembly revealed a genome size of 24.2 Mb divided into 39 scaffolds with a GC content of 50.1%. Genome annotation using Genemark v4.68 and GenDBE yielded 9,596 genes. [ABSTRACT FROM AUTHOR]

Leaf epicuticular waxes provide important anatomical and chemical defences against fungi that infect leaves. In this study we analysed the leaf wax composition of Eucalyptus grandis × Eucalyptus urophylla hybrids with contrasting susceptibilities to Teratosphaeria leaf blight (TLB) caused by Teratosphaeria destructans, one of the most important foliar diseases of Eucalyptus. The Eucalyptus cuticular wax was extracted from non‐inoculated and inoculated genotypes with different levels of susceptibility to TLB and analysed by gas chromatography–mass spectrometry. The results showed that a triterpenoid, cycloartenol (CAS), was abundant in a resistant genotype and that hexanedioic acid content increased in the resistant genotypes in response to T. destructans infection. In contrast, palmitic acid was significantly more abundant in the inoculated highly susceptible genotype. In‐vitro and in‐planta T. destructans spore germination assays with pure compounds, showed that CAS and hexanedioic acid significantly inhibited spore germination. Application of these two compounds to the leaves of a susceptible host also significantly increased resistance to infection. In contrast, palmitic acid promoted spore germination and, when applied to the leaves of a resistant genotype, increased colonization by the pathogen. This is the first study providing insights into differences in the leaf wax composition of hosts with different levels of susceptibility to T. destructans. It also showed that leaf wax compounds can modulate spore germination and, ultimately, host resistance to infection. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets. Methods: A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses--including inverse variance weighting (IVW), weighted median, and mode-based methods--were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies. Results: Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate. Conclusion: The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. Method: The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). Results: Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. Conclusion: Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired production, leading to an elevated bleeding tendency. Recent studies have demonstrated an important link between the gut microbiota and the onset and progression of several immune diseases in humans, emphasizing that gut microbiota-derived metabolites play a non-negligible role in autoimmune diseases. The gut microbiota and its metabolites, such as short-chain fatty acids, oxidized trimethylamine, tryptophan metabolites, secondary bile acids and lipopolysaccharides, can alter intestinal barrier permeability by modulating immune cell differentiation and cytokine secretion, which in turn affects the systemic immune function of the host. It is therefore reasonable to hypothesize that ecological dysregulation of the gut microbiota may be an entirely new factor in the triggering of ITP. This article reviews the potential immune-related mechanisms of the gut microbiota and representative metabolites in ITP, as well as the important influence of leaky gut on the development of ITP, with a view to enriching the theoretical system of ITP-related gut microecology and providing new ideas for the study of ITP. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy. Methods: We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1,400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results. Results: MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI, -0.008, -30.6%, p = 0.049) of the effect of DN (CD4-CD8-) AC on epilepsy. 1-(1-enylstearoyl)- 2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI, 0.668, 10.6%, p = 0.026) and X-12544 levels (95%CI, -15.1, -0.856%, p = 0.028) contributed 5.63 and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy. Conclusion: This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives. [ABSTRACT FROM AUTHOR]

The gut microbiome plays important roles in metabolic and immune system related to the health of host. This study applied non-invasive sampling and 16S rDNA high-throughput sequencing to study the gut microbiota structure of red pandas (Ailurus fulgens) for the first time under different geographical latitudes in captivity. The results showed that the two predominant phyla Firmicutes (59.30%) and Proteobacteria (38.58%) constituted 97.88% of the total microbiota in all the fecal samples from north group (red pandas from Tianjin Zoo and Jinan Zoo) and south group (red pandas from Nanjing Hongshan Forest Zoo). The relative abundance of Cyanobacteria in north group was significantly higher than that in south group. At the genus level, Escherichia-Shigella (24.82%) and Clostridium_sensu_-stricto_1 (23.00%) were common dominant genera. The relative abundance of norank_f__-norank_-o__-Chloroplast, Terrisporobacter and Anaeroplasma from south group was significantly higher than that of north group. Alpha and Beta analysis consistently showed significant differences between north group and south group, however, themain functions of intestinal microbiota were basically the same, which play an important role in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in different environments, and amino acid biosynthesis. The variations in gut microbiota between the northern and southern populations of the same species, both kept in captivity, which are primarily driven by significant differences in climate and diet. These findings provide a deeper understanding of the gut microbiota in red pandas and have important implications for their conservation, particularly in optimizing diet and environmental conditions in captivity. [ABSTRACT FROM AUTHOR]

Biotransformation is a process in which molecules are modified in the presence of a biocatalyst or enzymes, as well as the metabolic alterations that occur in organisms from exposure to the molecules. Microbial biotransformation is an important process in natural product drug discovery as novel compounds are biosynthesised. Additionally, biotransformation products offer compounds with improved efficacy, solubility, reduced cytotoxic and allows for the understanding of structure activity relationships. One of the driving forces for these impeccable findings are associated with the presence of cytochrome P450 monooxygenases that is present in all organisms such as mammals, bacteria, and fungi. Numerous fungal strains have been used and reported for their ability to biotransform different compounds. This review focused on studies using Alternaria species as biocatalysts in the biotransformation of natural product compounds. Alternaria species facilitates reactions that favour stereoselectivity, regioselectivity under mild conditions. Additionally, microbial biotransformation products, their application in food, pharmaceutical and agricultural sector is discussed in this review. [ABSTRACT FROM AUTHOR]

In current work, we studied hairy root induction in Trigonella foenum graecum, which is an important medicinal plant, and examined the impact of different elicitors on some phytochemical characteristics and metabolites production in hairy root cultures. Accordingly, some factors such as five strain types of Agrobacterium rhizogenes (1724, 15834, A4, A13 and MSU) and three different explants, namely leaf, cotyledon and hypocotyl were studied. The results showed that different A. rhizogenes strains exhibited different infection efficiency. MSU and 15834 had highest efficiency of hairy root induction than other strains. Also, hairy root induction frequency in leaf explants was higher than in other explants. Salicylic acid (SA), nitric oxide (NO), CaCl2 and penconazole (PEN) were used in elicitation process. Hairy roots were treated with SA (0.1 and 0.5 mM), NO (10 and 50 µM), CaCl2 (5 and 10 mM) and PEN (5 and 10 mg/L). Applied elicitors enhanced antioxidant enzymes activities and reduced oxidative stress markers; this observation might be ascribed to regulation of the oxidative status of the elicited cells. Significant increase of antioxidant metabolites (total phenol, flavonoid and anthocyanin) in PEN-treated hairy roots was associated to phenylalanine ammonia lyase activity, indicating an up-regulation of phenylpropanoid/flavonoid metabolism. PEN and CaCl2 treatment enhanced steroidal sapogenin in hairy root cultures. These results suggested that use of elicitors can enhance the production of secondary metabolites in transformed hairy roots. Among the elicitors applied, CaCl2 and PEN were the most effective in increasing secondary metabolite production in transformed hairy roots of T. foenum graecum. [ABSTRACT FROM AUTHOR]

Background: Proteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor samples is facilitated by initiatives such as the QUOD biobank, an adequately powered biobank allowing exploration of recipient-related aspects in long-term transplant outcomes is missing. Rich, yet unverified resources of recipient material are the serum repositories present in the immunological laboratories of kidney transplant centers that prospectively collect recipient sera for immunological monitoring. However, it is yet unsure whether these samples are also suitable for -omics applications, since such clinical samples are collected and stored by individual centers using non-uniform protocols and undergo an undocumented number of freeze–thaw cycles. Whilst these handling and storage aspects may affect individual proteins and metabolites, it was reasoned that incidental handling/storage artifacts will have a limited effect on a theoretical network (pathway) analysis. To test the potential of such long-term stored clinical serum samples for pathway profiling, we submitted these samples to discovery proteomics and metabolomics. Methods: A mass spectrometry-based shotgun discovery approach was used to obtain an overview of proteins and metabolites in clinical serum samples from the immunological laboratories of the Dutch PROCARE consortium. Parallel analyses were performed with material from the strictly protocolized QUOD biobank. Results: Following metabolomics, more than 800 compounds could be identified in both sample groups, of which 163 endogenous metabolites were found in samples from both biorepositories. Proteomics yielded more than 600 proteins in both groups. Despite the higher prevalence of fragments in the clinical, non-uniformly collected samples compared to the biobanked ones (42.5% vs 26.5% of their proteomes, respectively), these fragments could still be connected to their parent proteins. Next, the proteomic and metabolomic profiles were successfully mapped onto theoretical pathways through integrated pathway analysis, which showed significant enrichment of 79 pathways. Conclusions: This feasibility study demonstrated that long-term stored serum samples from clinical biorepositories can be used for qualitative proteomic and metabolomic pathway analysis, a notion with far-reaching implications for all biomedical, long-term outcome-dependent research questions and studies focusing on rare events. [ABSTRACT FROM AUTHOR]

Background: Existing studies have presented limited and disparate findings on the nexus between immune cells, plasma metabolites, and metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to investigate the causal relationship between immune cells and MASLD. Additionally, we aimed to identify and quantify the potential mediating role of metabolites. Methods: A Mendelian randomization (MR) analysis was conducted using two samples of pooled data from genome-wide association studies on MASLD that included 2568 patients and 409,613 control individuals. Additionally, a mediated MR study was employed to quantify the metabolite-mediated immune cell effects on MASLD. Results: In this study, eight immunophenotypes were linked to the risk of MASLD, and thirty-five metabolites/metabolite ratios were linked to the occurrence of MASLD. Furthermore, a total of six combinations of immunophenotypic and metabolic factors demonstrated effects on the occurrence of MASLD, although the mediating effects of metabolites were not significant. Conclusion: Our study demonstrated that certain immunophenotypes and metabolite/metabolite ratios have independent causal relationships with MASLD. Furthermore, we identified specific metabolites/metabolite ratios that are associated with an increased risk of MASLD. However, their mediating role in the causal association between immunophenotypes and MASLD was not significant. It is important to consider immune and metabolic disorders among patients with MASLD in clinical practice. [ABSTRACT FROM AUTHOR]

Summary Aflatoxins are toxic secondary metabolites produced by Aspergillus spp., found in staple food commodities. Aflatoxins are carcinogenic, teratogenic, and mutagenic and pose a serious threat to the health of humans. The identification and quantification of aflatoxins in foods is a major challenge to guarantee food safety. Therefore, developing feasible, sensitive, and robust methods for decontamination is paramount, with short processing time and negligible impact on quality. This review evaluates recent novel technologies for aflatoxins decontamination by physical methods (microwave heating, Gama and electron beam irradiation, pulse light and ultraviolet), chemical methods (ozone, natural plant extracts, and organic acids), and biological methods (atoxigenic Aspergillus strains, Trichoderma spp., and bacteria and yeast). The study highlights on the cutting‐edge technologies of smart packaging and artificial intelligence (AI). To achieve more efficiency and adaptability to different food matrices in aflatoxins decontamination, the study suggests integrating multiple strategies. The study also recommends integrating Partnership for Delivery (P4D) to share the responsibility to increase the chance for success and control aflatoxins in foods. [ABSTRACT FROM AUTHOR]

Numerous observational studies have suggested a potential causal relationship between skipping breakfast and cardiovascular diseases, including heart failure (HF). However, these studies are susceptible to inherent confounders and the challenge of reverse causation, and the underlying metabolic factors are not yet clear. Therefore, our aim is to assess the causal impact of breakfast skipping on HF and the role of potential mediating metabolic products from a genetic perspective, by conducting Mendelian Randomization (MR) studies and mediation analysis. We leveraged summary data from the most extensive genome-wide association studies to date on breakfast skipping (with 193,860 participants), blood metabolites (with 118,461 participants), and HF (involving 47,309 cases and 930,014 controls). To explore the causal relationship between breakfast skipping and HF, as well as the role of 249 potential blood metabolite mediators, we conducted bidirectional MR and mediation MR analyses. We primarily employed the Inverse Variance Weighted (IVW) method, complemented by various other techniques to ensure the comprehensiveness and reliability of our analysis. Our research confirms a causal association between breakfast skipping and an increased risk of HF (odds ratio [OR]: 1.378, 95% confidence interval [CI]: 1.047–1.813; p = 0.022). Furthermore, our research findings demonstrate that breakfast skipping is positively correlated with 6 blood metabolites and negatively correlated with 2 others. Notably, our mediation MR analysis further reveals that three blood metabolites act as mediators in the relationship between breakfast skipping and the risk of HF. Specifically, the mediating effects are attributed to the ratio of docosahexaenoic acid (DHA) to total fatty acids (proportion mediated = 9.41%, 95% CI: 2.10–28.61%), glucose (proportion mediated = 6.17%, 95% CI: 0.97–28.53%), and glycoprotein acetyls (GlycA) (proportion mediated = 5.68%, 95% CI: 0.94–21.62%). The combined mediating effects of these three factors total 20.53% (95%CI: 8.59–91.06%). Our research confirms the causal relationship between genetically instrumented breakfast skipping and HF, underscoring the potential mediating roles played by three key blood metabolites: ratio of DHA to total fatty acids, glucose and GlycA. This discovery offers valuable perspectives for clinical strategies targeting HF. [ABSTRACT FROM AUTHOR]