Search Results (108)

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on Aspergillus terreus C23-3, a strain isolated from the coral Pavona cactus in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited A. terreus strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic–metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds. Full article

Hair, as a non-invasive biospecimen, retains metabolic deposits from sebaceous glands and capillaries, reflecting substances from the peripheral circulation, and provides valuable biochemical information linked to phenotypes, yet its application in animal disease research remains limited. This work applied ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) to compare the hair metabolomic characteristics of healthy forest musk deer (FMD, Moschus berezovskii) and those diagnosed with hemorrhagic pneumonia (HP), phytobezoar disease (PD), and abscess disease (AD). A total of 2119 metabolites were identified in the FMD hair samples, comprising 1084 metabolites in positive ion mode and 1035 metabolites in negative ion mode. Differential compounds analysis was conducted utilizing the orthogonal partial least squares–discriminant analysis (OPLS-DA) model. In comparison to the healthy control group, the HP group displayed 85 upregulated and 92 downregulated metabolites, the PD group presented 124 upregulated and 106 downregulated metabolites, and the AD group exhibited 63 upregulated and 62 downregulated metabolites. Functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the differential metabolites exhibited significant enrichment in pathways associated with cancer, parasitism, energy metabolism, and stress. Receiver operating characteristic (ROC) analysis revealed that both the individual and combined panels of differential metabolites exhibited area under the curve (AUC) values exceeding 0.7, demonstrating good sample discrimination capability. This research indicates that hair metabolomics can yield diverse biochemical insights and facilitate the development of non-invasive early diagnostic techniques for diseases in captive FMD. Full article

Olive leaves, the main byproducts of olive cultivation, are characterized by a plethora of bioactive metabolites with significant nutritional value. Their main pentacyclic triterpenes, Oleanolic Acid (OA) and Maslinic Acid (MA), are two high added-value compounds with remarkable activities. This study aimed to develop an efficient methodology for extracting and purifying OA and MA, utilizing Supercritical Fluid Extraction (SFE) and Centrifugal Partition Chromatography (CPC)—two modern, scalable, and green techniques. A total of 21 g of olive leaves were subjected to SFE using supercritical CO₂ and ethanol as co-solvent. The extraction employed a step gradient mode, starting with 100% CO₂ and incrementally increasing ethanol (0–10% w/w) every 20 min. Fractions rich in OA and MA (500 mg) were further purified via CPC, utilizing pH zone refining to exploit the protonation and deprotonation properties of acidic triterpenes. The biphasic solvent system consisted of n-hexane, ethyl acetate, ethanol, and water (8:2:5:5 v/v/v/v), with trifluoroacetic acid added to the stationary phase and triethylamine added to the mobile phase. This two-step process yielded 89.5 mg of OA and 28.5 mg of MA with over 95% purity, as confirmed by HPLC-ELSD and ¹H-NMR. Moreover, purified compounds and SFE fractions exhibited promising elastase and collagenase inhibition, highlighting them as dermocosmetic agents. Full article

Phenolic acids, as widely distributed secondary metabolites in plants, possess significant biological activities, such as antioxidant and anti-inflammatory effects. However, their practical applications are limited by low absorption rates and poor bioavailability. Biotransformation technology, with its advantages of strong substrate specificity and mild reaction conditions, has become an effective strategy for the directional modification of phenolic acid molecular structures and the preparation of high-value-added derivatives. Among the various methodologies, enzymatic methods stand out due to their high selectivity and specificity, establishing them as a key approach for phenolic acid biotransformation. The research indicates that coordinated multi-pathway approaches, including decarboxylation, reduction, and hydrolysis, can effectively enhance the efficiency of phenolic acid biotransformation. This review systematically examines the structure and mechanism of action of the key enzymes involved in the phenolic acid biotransformation process. It also proposes innovative pathways and future development directions for existing technologies. Furthermore, it provides an in-depth analysis of the specific application potential of these key enzymes within the food sector. The objective of this review is to furnish a theoretical foundation and technical support for the efficient application of enzymatic methods in phenolic acid biotransformation, thereby accelerating their practical implementation. Full article

Microalgae are a subject of interest not only for fundamental research but for various biotechnological applications as well. In this study, the ability of newly isolated strains, i.e., Picochlorum costavermella VAS2.5, Picochlorum oklahomense SAG4.4, Microchloropsis gaditana VON5.3, and Nephroselmis pyriformis PAT2.7, to grow when cultured in an open raceway pond under laboratory conditions and produce various metabolites of high-added value was evaluated. N. pyriformis PAT2.7 and P. costavermella VAS2.5 were the greatest in biomass production (exceeding 0.4 g/L), while P. costavermella VAS2.5 and M. gaditana VON5.3 were the greatest in lipid production (reaching approximately 18%, wt/wt). The lipid fraction of glycolipids and sphingolipids was predominant (43.6–55.4%, wt/wt), followed by neutral lipids (27.1–50.1%, wt/wt) and phospholipids (6.9–17.4%, wt/wt). Picochlora and M. gaditana VON5.3 lipids were rich in ^{Δ5,8,11,14,17}C20:5 and/or ^Δ9,12,15C18:3, while N. pyriformis PAT2.7 synthesized ^Δ9C16:1 in large quantities (30–40%, wt/wt). All strains showed remarkable yields in polysaccharide and protein production, demonstrated a well-balanced amino acid profile, and synthesized pigments in amounts comparable to other studies. The biochemical profiles of these strains showcased their suitability for use primarily in the aquaculture sector. Full article

Background: Efforts have been joined to set the parameters for the reliability of glucometers, yet once they are on the market, they are not further tested for the maintenance of accuracy, specificity, or precision. Methods: This comparative analytical study investigated the precision of commonly used glucometers in Saudi Arabia, namely Accu-Chek Instant^®, On-Call Sharp^®, and ConTour^®, as well as the effects of vitamin C, acetaminophen, and maltose on glucose readings. Ten milliliters of blood was drawn in lithium heparin from healthy volunteers (n = 9). Six samples were divided into two groups of three. One group was designed for normal glucose levels. The second group was designed for high glucose levels by adding a dextrose solution. The last three samples were designed for low glucose levels by leaving the sample for 24 h at room temperature and then following with centrifuge and plasma extraction. Results: This study showed that only Accu-Chek Instant met the International Organization for Standardization (ISO) standard for precision across all dextrose concentrations, along with intra-class correlation values ranging from 0.95–1 (p < 0.001). By spiking the plasma samples with sub-therapeutic, therapeutic, and overdose concentrations of the metabolites, we found that vitamin C had a more evident interference on glucose readings compared to acetaminophen and maltose. Conclusions: The ascertainment of the precision of glucometers and the effects of interferences on them are vital in preventing the improper administration of insulin, which can lead to serious complications. Full article

The microalgal strains Picochlorum costavermella VAS2.5, Picochlorum oklahomense SAG4.4, Picochlorum oklahomense PAT3.2B, Microchloropsis gaditana VON5.3, and Nephroselmis pyriformis PAT2.7 were cultured in a Stirred Tank Reactor at 25 °C or 20 °C in modified artificial seawater and their biotechnological potential was assessed. VAS2.5, VON5.3, and PAT2.7 were high in biomass production at both temperatures (i.e., 438.8–671.3 mg/L and 418.4–546.7 mg/L at 25 °C and 20 °C, respectively), though P. oklahomense strains grew only at 25 °C. The highest lipid percentage was recorded for the cultures of VAS2.5 (19.3 ± 0.7%) and VON5.3 (16.4 ± 1.5%) at 25 °C, notably rich in ^{Δ5,8,11,14,17}C20:5, while PAT2.7 proved a major producer of ^Δ9C16:1. The predominant lipid fraction was glycolipids and sphingolipids (41.3–57.4%) for VAS2.5, PAT2.7 at 25 °C and VON5.3 at 20 °C and neutral lipids (55.6–63.5%) in the other cultures, indicating the different effect of temperature on lipid synthesis of the various microalgae. Additionally, almost all strains stood out for their high protein content, exceeding 50% in the culture of PAT3.2B, but polysaccharide and pigment content were not high. The biochemical profiles of the isolates showcased their suitability for use primarily as feed additives in the aquaculture sector. Full article

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation during vinification affects Moldova red wine quality. Total phenolic/flavonoid contents, DPPH, and FRAP assays were measured via spectrophotometry, anthocyanins, and tryptophan metabolites using UPLC-MS/MS and UPLC-FLD, as well as cytotoxicity with the MTT assay. Results showed that addition of melatonin during the winemaking process increased total phenolic/flavonoid content, as well as the antioxidant capacity evidenced by increased anti-DPPH radical activity. These effects might be due to the stimulation of phenolic compound biosynthesis, particularly anthocyanins malvidin-3-O-glucoside, peonidin-3-O-glucoside, and delphinidin 3-O-glucoside, which were found to be increased in the treated wine. Additionally, the study revealed that melatonin-enriched wine exhibited increased cytotoxicity against two cancer cell lines, HCT116 and PANC-1. Finally, melatonin supplementation enhanced the concentration of kynurenic acid, which, due to its cytoprotective and antioxidant properties, could further increase the health benefits of the resulting wine. These findings offer promising avenue for future research of melatonin-driven functional properties of wine and provide step forward to a natural product with added value. Full article

Coenzyme Q10 (CoQ10), a high-value-added nutraceutical antioxidant, exhibits an excellent ability to prevent cardiovascular disease. Here, a novel Cereibacter azotoformans strain, designated YS02, was isolated for its ability to produce CoQ10 and genetically characterized by whole genome sequencing (WGS). The CoQ10 biosynthesis and metabolism differences of YS02 under various culture conditions were also systematically investigated. Phylogenetic analysis based on 16 S rRNA genes, along with taxonomic verification using average nucleotide identity (ANI) analysis, confirmed its classification as C. azotoformans. Enzymatic genes dxs, dxr, idi, ubiA, and ubiG were annotated in YS02, which are critical genetic hallmarks for CoQ10 biosynthesis. Under aerobic–dark cultivation, YS02 grows well, and CoQ10 production can reach 201 mg/kg. A total of 542 small-molecule metabolites were identified from YS02 in aerobic–dark and anaerobic–light cultivation via ultra-high performance liquid chromatography–coupled quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS). Additionally, 40 differential metabolites were screened through multivariate statistical analysis. Metabolic pathway analysis revealed that the biosynthesis of phenylalanine, tyrosine, and tryptophan might be latent factors influencing CoQ10 production discrepancies within YS02 under both cultural modes. These findings represent new insights into the metabolic mechanism of YS02 and underscore its potential as an alternative strain source for industrial CoQ10 production, enriching the existing resources. Full article

The production of microbial metabolites such as (exo)polysaccharides, lipids, or mannitol through the cultivation of microorganisms on sustainable, low-cost carbon sources is of high interest within the framework of a circular economy. In the current study, two non-extensively studied, non-conventional yeast strains, namely, Cutaneotrichosporon curvatus NRRL YB-775 and Papiliotrema laurentii NRRL Y-3594, were evaluated for their capability to grow on semi-defined lactose-, glycerol-, or glucose-based substrates and produce value-added metabolites. Three different nitrogen-to-carbon ratios (i.e., 20, 80, 160 mol/mol) were tested in shake-flask batch experiments. Pretreated secondary cheese whey (SCW) was used for fed-batch bioreactor cultivation of P. laurentii NRRL Y-3594, under nitrogen limitation. Based on the screening results, both strains can grow on low-cost substrates, yielding high concentrations of microbial biomass (>20 g/L) under nitrogen-excess conditions, with polysaccharides comprising the predominant component (>40%, w/w, of dry biomass). Glucose- and glycerol-based cultures of C. curvatus promote the secretion of mannitol (13.0 g/L in the case of glucose, under nitrogen-limited conditions). The lipids (maximum 2.2 g/L) produced by both strains were rich in oleic acid (≥40%, w/w) and could potentially be utilized to produce second-generation biodiesel. SCW was nutritionally sufficient to grow P. laurentii strain, resulting in exopolysaccharides secretion (25.6 g/L), along with dry biomass (37.9 g/L) and lipid (4.6 g/L) production. Full article

The essential amino acid tryptophan yields a plethora of secondary metabolites with key roles in plants and animals. Its fate in different living organisms is crucial for their own health, and metabolic profiling is a valuable tool for investigating it. Among the various metabolites, those retaining the indole structure were examined for qualitative and quantitative profiling. Liquid chromatography coupled with a tandem mass spectrometry detector with an electrospray ionization source (HPLC-ESI-MS/MS), acquiring in multiple reaction monitoring (MRM) mode, was used to develop a selective and sensitive method for the simultaneous analysis of tryptophan and 10 indole structure-retaining metabolites of it. Satisfactory values were obtained for linearity (R² ≥ 0.99 for all compounds except two), sensitivity (LOD, within 6–31 ng/mL, and LOQ, within 17–94 ng/mL, where minimum and maximum values were relative to serotonin and 5-methoxytryptamin, respectively), reproducibility (interday and intraday precision and accuracy), and effect of the matrix (recovery and matrix effect). The method was then successfully applied to the analysis of different types of beverage, such as herbal products, like Eschscholzia californica and a sleep herbal tea marketed with added melatonin (consumed to reduce anxiety and improve sleep quality), and fermented beverages, like beer and kefir. High amounts of tryptophan (from 77 ng/mL in kefir to 26,974 ng/g in the sleep herbal tea) followed by lower contents of serotonin (from 29 ng/mL in kefir to 2207 ng/g in the sleep herbal tea), were found in all samples along with the serotonin pathway-related compounds 5-hydroxytryptophan and tryptamine. Melatonin was detected in the plant matrix Eschscholzia c. for the first time to our knowledge (446 ng/g) and in the fermented beverages (96 ng/mL in beer and 39 ng/mL in kefir), regardless of their vegetable or animal origin, along with the melatonin route metabolites 5-methoxytryptamine and tryptophan ethyl ester. The amount of melatonin in the sleep herbal tea (556,464 ng/g) was in strong agreement with the declared content. Suggested applications include the search for biomarkers in phytochemical characterization, mechanistic studies of tryptophan’s chemistry, valorization of foods, beverages, and tryptophan-rich agro-food by-products and waste for nutraceutical and pharmacological purposes. Full article

Insect metabolites are known for their preservative potential, but the time-consuming and unsustainable extraction process compromises their transferability. This study aimed to identify user-friendly solutions based on the use of insect meals that could improve microbiological safety as well as consumer acceptability. In this regard, the antimicrobial activity of Alphitobius diaperinus and Tenebrio molitor meals against surrogate strains of Gram-positive (Listeria monocytogenes) and Gram-negative (Escherichia coli) pathogenic bacteria and mycotoxin-producing fungi (Penicillium expansum) was evaluated. Minimum inhibitory concentration values of between 3.12 mg/mL vs. Listeria innocua and 12.50 mg/mL vs. Escherichia coli were found. Based on this finding, a model food was developed also considering consumer acceptance. Statistical analysis of food preferences showed that nutritional and sustainability claims were the independent variables of greatest interest. Therefore, waste or by-products from other food chains were selected as co-ingredients for sustainability, nutritional, and sensory claims. Analysis of the chemical composition showed that the insect bar-style snack qualifies as a “high-protein” food, as protein provides more than 20% of the energy value. Based on the moisture (30%) and water activity (0.77) values, the bar could be classified as an intermediate-moisture food. The challenge test showed that the insect meal prevented the proliferation of intentionally added undesirable microorganisms. Conclusively, the findings complement the knowledge on the antimicrobial activities of insect meals, offering new possibilities for their use as natural preservative ingredients with nutritionally relevant properties. Full article

Background: Due to scientific advancements in high-throughput data production technologies, omics studies, such as genomics and metabolomics, often give rise to numerous measurements per sample/subject containing several noisy variables that potentially cloud the true signals relevant to the desired study outcome(s). Therefore, correcting for multiple testing is critical while performing any statistical test of significance to minimize the chances of false or missed discoveries. Such correction practice is commonplace in genome-wide association studies (GWAS) but is also becoming increasingly relevant to metabolome-wide association studies (MWAS). However, many existing procedures may be too conservative or too lenient, only assume a linear association between the features, or have not been evaluated on metabolomics data. Methods: One such multiple testing correction strategy is to estimate the number of statistically independent tests, called the effective number of tests, based on the eigen-analysis of the correlation matrix between the features. This effective number is then used for a subsequent single-step adjustment to obtain the pointwise significance level. We propose a modification to the p-value adjustment based on a more general measure of association between two predictors, the distance correlation, with a specific focus on MWAS. Results: We assessed common GWAS p-value adjustment procedures and one tailored for MWAS, which rely on eigen-analysis of the Pearson’s correlation matrix. Our study, including varying sample size-to-feature ratios, response types, and metabolite groupings, highlights the superior performance of the distance correlation. Conclusion: We propose the distance-correlation-based p-value adjustment (DisCo P-ad) as a novel modification that can enhance existing eigen-analysis-based multiple testing correction procedures by increasing power or reducing false positives. While our focus is on metabolomics, DisCo P-ad can also readily be applied to other high-dimensional omics studies. Full article

Introduction/Objectives: Since the biological activities and toxicities of ‘foreign’ and/or excess levels of metal ions are predominantly determined by their precise molecular nature, here we have employed high-resolution ¹H NMR analysis to explore the ‘speciation’ of paramagnetic Ni(II) ions in human saliva, a potentially rich source of biomolecular Ni(II)-complexants/chelators. These studies are of relevance to the in vivo corrosion of nickel-containing metal alloy dental prostheses (NiC-MADPs) in addition to the dietary or adverse toxicological intake of Ni(II) ions by humans. Methods: Unstimulated whole-mouth human saliva samples were obtained from n = 12 pre-fasted (≥8 h) healthy participants, and clear whole-mouth salivary supernatants (WMSSs) were obtained from these via centrifugation. Microlitre aliquots of stock aqueous Ni(II) solutions were sequentially titrated into WMSS samples via micropipette. Any possible added concentration-dependent Ni(II)-mediated pH changes therein were experimentally controlled. ¹H NMR spectra were acquired on a JEOL JNM-ECZ600R/S1 spectrometer. Results: Univariate and multivariate (MV) metabolomics and MV clustering analyses were conducted in a sequential stepwise manner in order to follow the differential effects of increasing concentrations of added Ni(II). The results acquired showed that important Ni(II)-responsive biomolecules could be clustered into distinguishable patterns on the basis of added concentration-dependent responses of their resonance intensities and line widths. At low added concentrations (71 µmol/L), low-WMSS-level N-donor amino acids (especially histidine) and amines with relatively high stability constants for this paramagnetic metal ion were the most responsive (severe resonance broadenings were observed). However, at higher Ni(II) concentrations (140–670 µmol/L), weaker carboxylate O-donor ligands such as lactate, formate, succinate, and acetate were featured as major Ni(II) ligands, a consequence of their much higher WMSS concentrations, which were sufficient for them to compete for these higher Ni(II) availabilities. From these experiments, the metabolites most affected were found to be histidine ≈ methylamines > taurine ≈ lactate ≈ succinate > formate > acetate ≈ ethanol ≈ glycine ≈ N-acetylneuraminate, although they predominantly comprised carboxylato oxygen donor ligands/chelators at the higher added Ni(II) levels. Removal of the interfering effects arising from the differential biomolecular compositions of the WMSS samples collected from different participants and those from the effects exerted by a first-order interaction effect substantially enhanced the statistical significance of the differences observed between the added Ni(II) levels. The addition of EDTA to Ni(II)-treated WMSS samples successfully reversed these resonance modifications, an observation confirming the transfer of Ni(II) from the above endogenous complexants to this exogenous chelator to form the highly stable diamagnetic octahedral [Ni(II)-EDTA] complex (K_stab = 1.0 × 10¹⁹ M⁻¹). Conclusions: The results acquired demonstrated the value of linking advanced experimental design and multivariate metabolomics/statistical analysis techniques to ¹H NMR analysis for such speciation studies. These provided valuable molecular information regarding the identities of Ni(II) complexes in human saliva, which is relevant to trace metal ion speciation and toxicology, the in vivo corrosion of NiC-MADPs, and the molecular fate of ingested Ni(II) ions in this biofluid. The carcinogenic potential of these low-molecular-mass Ni(II) complexes is discussed. Full article

Olive leaf by-products may be an important feed source for ruminants in the Mediterranean area, due to their nutritional value and high levels of functional metabolites. Additionally, their use can enhance the environmental and economic sustainability of the productions. To evaluate the effect of olive leaf supplementation on the fatty acid profile of sheep cheese, two farms with Comisana breed sheep with free access to pasture and fedwith 300 g/head/day of concentrate were considered. One farm supplemented the feed with clover hay ad libitum (NOL) and the other farm replaced hay with olive leaves (OLI) in the autumn period. Cheese analyses were performed at 15, 30, and 60 days of ripening. Saturated fatty acids were lower in OLI cheese than NOL cheese, while MUFA and PUFA n-3 and n-6 were higher in OLI cheese. Myristic acid (C14:0) and palmitic acid (C16:0) were lower in OLI cheese compared to NOL (8.31% vs. 8.90% and 21.52% vs. 24.95%, respectively), while oleic acid (C18:1 cis-9) was higher in OLI cheese (20.66% vs. 18.78%). Also, CLA cis-9 trans-11 (0.98% vs. 0.84%), and other isomers were higher in OLI cheese. Health indexes, such as the thrombogenic and atherogenic index, were lower in OLI than in NOL cheese (1.96 vs. 2.38 and 1.69 vs. 2.05, respectively) showing the improvement in the health quality of cheese due to olive leaf integration in directly on farm sheep feeding. Full article