Search Results (83)

Background: Secondary (nosocomial) bacterial meningitis remains a serious problem in patients with severe brain damage. The aim of this study was to assess the differences in the aromatic metabolites of tryptophan, phenylalanine, and tyrosine, in serum and cerebrospinal fluid (CSF) samples collected simultaneously from patients with long-term sequelae of severe brain damage with suspected secondary bacterial meningitis. Methods: Group I included 16 paired serum and CSF samples from patients (N = 11) without secondary bacterial meningitis; group II included 13 paired serum and CSF samples from patients (N = 4) with secondary bacterial meningitis. Results: The median concentrations of serum 5-hydroxyindole-3-acetic, CSF 4-hydroxyphenyllactic (p-HPhLA), CSF 4-hydroxyphenylacetic, CSF phenyllactic, and indole-3-lactic acids in serum and CSF were statistically higher in group II compared to group I (p-value ≤ 0.03), while 4-hydroxyphenylpropionic and indole-3-acetic in serum were lower in group II compared to group I (p-value = 0.04). In group I, p-HPhLA serum concentrations were greater than or equal to its CSF concentrations in 14 paired samples; in group II, p-HPhLA concentrations in serum were lower than in CSF in all paired samples. Conclusions: The obtained results demonstrate the differences in the profile of aromatic metabolites in serum and CSF and may confirm the hypothesis of the p-HPhLA microbial origin in the CSF of patients with secondary bacterial meningitis. Full article

Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against Staphylococcus aureus and Escherichia coli, obtaining preliminary and promising results. Full article

Background: The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance. Full article

Parkinson’s disease (PD) progression appears closely tied to gut microbiota alterations, with microbial metabolites potentially influencing neurodegeneration. This pilot study employed GC-MS and LC-MS/MS to analyze the urinary levels of gut-derived metabolites—including succinic acid, p-hydroxyphenylacetic acid, homovanillic acid (HVA), vanillylmandelic acid (VMA), adipic acid, and trimethylamine N-oxide (TMAO)—in 20 PD patients versus 20 age-matched controls. The key findings revealed that PD patients exhibited significantly elevated succinic acid (p = 0.0018) and HVA (p = 0.0002) levels alongside reduced TMAO (p = 1.65 × 10⁻⁵). Notably, succinic acid showed an inverse correlation with disease severity (Hoehn and Yahr scale: r = −0.63; p = 0.0028), while TMAO demonstrated a strong positive association (r = 0.81; p = 0.00001). The elevated HVA, a dopamine metabolite, may serve as a potential biomarker for monitoring levodopa treatment efficacy. These results suggest that gut microbiota metabolites contribute to PD pathogenesis, with TMAO and succinic acid emerging as promising biomarkers for tracking disease progression. This study highlights the clinical potential of non-invasive urinary metabolite profiling using GC-MS and LC-MS/MS techniques. However, further investigation through larger-scale studies is needed to confirm these findings and elucidate the underlying mechanisms connecting gut microbiota dysbiosis to PD neurodegeneration. Full article

Background/Objectives: Iron deficiency anemia remains a primary global health concern, affecting millions worldwide. Despite the widespread availability of iron supplements, their efficacy is often hindered by poor bioavailability and adverse gastrointestinal effects. This study explores the potential of probiotics to enhance the bioavailability of Fe₃O₄ NPs through probiotic-mediated mechanisms. Methods: Lactobacillus fermentum, Lactobacillus rhamnosus, and Lactobacillus plantarum were utilized to investigate their interactions with Fe₃O₄ NPs, synthesized via co-precipitation and characterized using transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Results: The results indicated that probiotics adhere to the nanoparticle surface, with L. fermentum exhibiting the highest adhesion and internalization capacity, leading to a significant increase in 4-hydroxyphenylacetic acid (4-HPLA) production (11.73 ± 0.09 mg/mL at 24 h, p < 0.05). Spectroscopic analyses further revealed that probiotic metabolism facilitates the oxidation of Fe₃O₄ to Fe₂O₃. Additionally, Fe₃O₄ nanoparticle-treated cultures demonstrated enhanced bacterial viability and metabolic activity, highlighting a synergistic effect between probiotics and iron nanoparticles. Conclusions: These findings provide compelling evidence for probiotic-assisted iron supplementation as a promising strategy to enhance iron bioavailability while mitigating the gastrointestinal side effects of conventional iron supplements. Full article

A high proteolytic-resistant hexapeptide (α_s1-CN 181–186) (1) along with two known 2,5-diketopiperazines, namely cyclo-(L-Pro-L-Phe) (2) and cyclo-(L-Pro-L-Tyr) (3), as well as the carboxylic acid 2-hydroxyphenylacetic acid (4), were isolated from the actinomycete strain CA287887. The morphological 16S rRNA gene sequence and phylogenetic data of the strain exhibited high similarity with members of the genus Actinomycetospora. The structure of 1 was thoroughly investigated for the first time through the extensive use of 1D and 2D NMR experiments while its absolute configuration was determined by Marfey’s analysis. The anti-tyrosinase effects of the aforementioned compounds were investigated in vitro using kojic acid as the positive control (IC₅₀ 14.07 μΜ). Compound 3 exhibited the highest activity (IC₅₀ 28.69 μΜ), followed by compound 4 (IC₅₀ 98.29 μΜ). Compound 1 was further evaluated for cytotoxicity against HepG2, A2058, A549, and MiaPaca-2 cell lines. At all the tested concentrations (0.01–200 μg/mL), no cytotoxic effect was observed. Full article

Background: Semiliquidambar cathayensis Chang is an extremely valuable and endangered medicinal plant. To investigate the exploitation and rational utilization of S. cathayensis, this study conducted metabolomics analysis of the leaves and bark of artificially cultivated S. cathayensis at different developmental stages. Methods: These metabolites were detected and identified by Ultra-Performance Liquid Chromatography–tandem Mass Spectrometry (UPLC-MS/MS) technology, and then univariate statistical analyses, multivariate pattern analyses, and pathway analyses were carried out. Results: As a result, a total of 801 metabolites were detected in S. cathayensis; differential metabolites in leaves at different developmental stages were mainly enriched in pathways related to flavonoids, whereas differential metabolites in bark at different developmental stages were mainly aromatic compounds, amino acids, and flavonoids, among others. This study revealed that young leaves are ideal for use in treating rheumatism, regulating blood pressure, and lowering blood glucose, while old leaves are better suited for skincare products and extracting materials to prevent neurodegenerative diseases and support women’s ovarian health. As for bark, four-year-old S. cathayensis bark is optimal for extracting myricetin. If the pharmaceutical, chemical, food, and industrial fields require extensive extraction of L-phenylalanine, trans-3-hydroxycinnamate, and 4-hydroxyphenylacetate, and if the medical field needs to extract anti-allergy, liver protection, and anti-coagulant ingredients, the two-year-old S. cathayensis bark is the best choice. Conclusions: Thus, this study established a solid theoretical framework for the rational, effective, and sustainable utilization of S. cathayensis leaves and bark. Full article

Endolichenic fungi represent an important ecological group of microorganisms that form associations with photobionts in the lichen thallus. These endofungi that live in and coevolve with lichens are known for synthesizing secondary metabolites with novel structures and diverse chemical skeletons making them an unexplored microbial community of great interest. As part of our search for new phytoprotectants, in this work, we studied the endolichenic fungus Xylaria sp. isolated from the lichen Hypogymnia tubulosa, which grows as an epiphyte on the bark of the endemic Canarian tree Pinus canariensis. From the extract of the liquid fermentation, we isolated two unreported piliformic derivatives, (+)-9-hydroxypiliformic acid (1) and (+)-8-hydroxypiliformic acid (2), along with four previously reported compounds, (+)-piliformic acid (3), hexylaconitic acid A anhydride (4), 2-hydroxyphenylacetic acid (5), and 4-hydroxyphenylacetic acid (6). Their structures were elucidated based on NMR and HRESIMS data. The extract and the isolated compounds were tested for their insect antifeedant (Myzus persicae, Rhopalosiphum padi, and Spodoptera littoralis), antifungal (Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum), nematicidal (Meloidogyne javanica), and phytotoxic effects on mono- and dicotyledonous plant models (Lolium perenne and Lactuca sativa). Compounds 4, 5, and 6 were effective antifeedants against M. persicae and 4 was also active against R. padi. Moreover, 3 and 4 showed antifungal activity against B. cinerea and 4 was the only nematicidal. The extract had a strong phytotoxic effect on L. sativa and L. perenne growth, with compounds 3, 4, and 5 identified as the phytotoxic agents, while at low concentrations compounds 3 and 4 stimulated L. sativa root growth. Full article

The management of neuroendocrine neoplasms (NENs) involves the measurement of serum chromogranin A (s-CGA), serum neuro-specific enolase (s-NSE), and urinary 5-hydroxindolacetic acid (5-HIAA). Urinary para-hydroxyphenylacetic acid (u-pHPAA), a metabolite of tyrosine, has been proposed as a potential biomarker for these diseases. This study aims to evaluate the effectiveness of u-pHPAA and tyrosine as biomarkers. We measured the levels of s-CgA, s-NSE, u-5-HIAA, u-pHPAA, and tyrosine in blood or 24 h urine samples collected at baseline (T₀) and after 1 year of follow-up (T₁) from a limited cohort of patients enrolled at Istituto Nazionale Tumori-IRCCS-Fondazione “G. Pascale”. Biomarker values were normalized using the ratios between T₁ and T₀ values (T₁/T₀ parameters). The T₁/T₀ ratios for s-CgA and u-pHPAA were significantly associated with the outcome of death (p = 0.044 and p = 0.022, respectively). An ROC curve analysis demonstrated outstanding performances for these biomarkers (AUC = 0.958 and AUC = 1.00, respectively) and the Kaplan–Meier survival analysis showed significant Log-rank test results (p = 0.001 and p < 0.001, respectively). Additionally, T₀ serum tyrosine correlated with the outcome of death (p = 0.044), with the ROC curve showing good performance (AUC = 0.958) and the Kaplan–Meier analysis yielding significant Log-rank test results (p = 0.007). Our study confirms the role of s-CgA in the management of NEN patients and highlights the potential roles of u-pHPAA and serum tyrosine as biomarkers. Further research is needed to validate our findings in larger populations. Full article

Barley (Hordeum vulgare) is a major cereal grain grown in temperate climates globally and provides various nutrients in a peeled form after milling. However, milling causes changes in nutritional composition, including metabolites. Thus, a metabolomics study was conducted to monitor the changes in nutritional composition before and after the milling of Hordeum vulgare seeds (Saechalssal, Hinchalssal, and Yeongbaekchal) focusing on the development and application of new analytical methods for organic acids (OA) and amino acids (AA). Profiling analyses of OAs and AAs were performed using GC-MS/MS. This analytical method showed good linearity (r ≥ 0.995) with limit of detection (0.1 ng, 21.2 ng) and limit of quantitation (0.3 ng, 63.6 ng), respectively. Repeatability varied from 0.1 to 12.4 (% RSD) and accuracy varied from –12.3 to 14.8 (% RE), respectively. Altered levels of 36 metabolites (16 OAs, 20 AAs) were monitored post-milling and compared with pre-milling in the three Hordeum vulgare cultivars. Radar plots of OAs and AAs to corresponding mean levels of each pre-milling group in the three Hordeum vulgare cultivars were easily distinguished from those in each post-milling group. The pre-and post-milling groups of the three Hordeum vulgare cultivars were completely separated by partial least square discriminant analysis, and the lysine, cysteine, glutamic acid, asparagine, 4-hydroxyphenylacetic acid, and citric acid were significantly different. Therefore, this study will be useful for monitoring altered metabolites following milling and discrimination of varieties. Full article

Background: In the treatment of oncological diseases in children, the search for opportunities for the earlier detection of complications to improve treatment results is very important. Metabolomic studies are actively conducted to stratify different groups of patients in order to identify the most promising markers. Methods: Three groups of patients participated in this study: healthy children as a control group (n = 18), children with various malignant oncological diseases (leukemia, lymphoma, nephroblastoma, ependymoma, etc.) as patients (n = 40) without complications, and patients (n = 31) with complications (inflammatory and infectious). The mitochondrial metabolites (succinic and fumaric acids); biomarkers related to inflammation such as C-reactive protein (CRP), procalcitonin (PCT), and presepsin (PSP); and sepsis-associated aromatic metabolites, such as phenyllactic (PhLA), hydroxyphenyllactic (p-HPhLA), and hydroxyphenylacetic acids (p-HPhAA), were identified. Results: It was found that children with malignant oncological diseases had profound metabolic dysfunction compared to healthy children, regardless of the presence of systemic inflammatory response syndrome (SIRS) or sepsis. The prognostic ability of procalcitonin and presepsin for detecting sepsis was high: AUROC = 0.875, cut-off value (Youden index) = 0.913 ng/mL, and AUROC = 0.774, with cut-off value (Youden index) of 526 pg/mL, respectively. Conclusions: A significant increase in aromatic microbial metabolites and biomarkers in non-survivor patients that is registered already in the first days of the development of complications indicates the appropriateness of assessing metabolic dysfunction for its timely targeted correction. Full article

Background: The causes of functional constipation (FC) in adults are unclear, but changes in the gut microbiome may play an important role. The present study aimed to assess the relationship between urinary metabolites of dopamine and serotonin and some dysbiosis indicators in patients with FC. The study included 40 healthy women and 40 women with FC aged 21–46 years. Methods: Urinary levels of homovanillic acid (HVA), 5-hydoxyindoleacetic acid (5-HIAA), p-hydroxyphenylacetic acid (PhAc), and 3-indoxyl sulfate, as final metabolites of dopamine, serotonin, and indole pathway, respectively, were determined using the LC-Ms/Ms method. However, hydrogen–methane and ammonia breath tests were performed. The GA-map Dysbiosis Test was used to identify and characterize the dysbiosis index (DI). Results: In patients with FC, the DI was significantly higher than in the control group: 4.05 ± 0.53 vs. 1.52 ± 0.81 points (p < 0.001), but the number of many types of bacteria varied among individuals. The levels of HVA were higher, while 5-HIAA levels were lower in patients. Moreover, the HVA/5-HIAA ratio had a positive correlation with DI as well as with the severity of symptoms. Conclusions: In patients with functional constipation, the balance in dopamine and serotonin secretion is disturbed, which is associated with changes in the gut microbiome. Full article

This study reports on the physicochemical and antioxidant properties of propolis samples from various regions across Western Australia and identifies some phenolic constituents using high-performance thin-layer chromatography (HPTLC). Total phenolic content (TPC) was determined using a modified Folin–Ciocalteu assay, and antioxidant activity was investigated with the Ferric Reducing Antioxidant Power (FRAP) assay and also visualised and semi-quantified by HPTLC-DPPH analysis. TPC values ranged from 9.26 to 59.3 mg gallic acid equivalent/g of raw propolis and FRAP assay data from 4.34 to 53.8 mmol Fe²⁺ mmol/kg of raw propolis, although some of these variations might be related to differences in extraction yields obtained with 70% ethanol. The presence of luteolin, taxifolin, naringenin, and 4-hydroxyphenylacetic acid was confirmed based on a comprehensive, validated matching approach against an HPTLC-derived database. The findings of the study highlight the importance of future research on the chemical composition and bioactivity of Western Australian propolis. Full article

Traditional isolation methods often lead to the rediscovery of known natural products. In contrast, genome mining strategies are considered effective for the continual discovery of new natural products. In this study, we discovered a unique prenyltransferase (PT) through genome mining, capable of catalyzing the transfer of a prenyl group to an aromatic nucleus to form C-C or C-O bonds. A pair of new hydroxyphenylacetic acid derivative enantiomers with prenyl units, (±)-peniprenydiol A (1), along with 16 known compounds (2–17), were isolated from a marine fungus, Penicillium sp. W21C371. The separation of 1 using chiral HPLC led to the isolation of the enantiomers 1a and 1b. Their structures were established on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS. The absolute configurations of the new compounds were determined by a modified Mosher method. A plausible biosynthetic pathway for 1 was deduced, facilitated by PT catalysis. In the in vitro assay, 2 and 3 showed promising inhibitory activity against Escherichia coli β-glucuronidase (EcGUS), with IC₅₀ values of 44.60 ± 0.84 μM and 21.60 ± 0.76 μM, respectively, compared to the positive control, D-saccharic acid 1,4-lactone hydrate (DSL). This study demonstrates the advantages of genome mining in the rational acquisition of new natural products. Full article

We aimed to investigate the characteristics of serum metabolomics in aneurysmal subarachnoid hemorrhage patients (aSAH) with different 3-month outcomes (good = modified Rankin score: 0–3 vs. poor = mRS 4–6). We collected serum samples from 46 aSAH patients at 24 (D1) and 168 (D7) hours after injury for analysis by liquid chromatography-mass spectrometry. Ninety-six different metabolites were identified. Groups were compared using multivariate (orthogonal partial least squares discriminant analysis), univariate, and receiving operator characteristic (ROC) methods. We observed a marked decrease in serum homocysteine levels at the late phase (D7) compared to the early phase (D1). At both D1 and D7, mannose and sorbose levels were notably higher, alongside elevated levels of kynurenine (D1) and increased 2-hydroxybutyrate, methyl-galactoside, creatine, xanthosine, p-hydroxyphenylacetate, N-acetylalanine, and N-acetylmethionine (all D7) in the poor outcome group. Conversely, levels of guanidinoacetate (D7) and several amino acids (both D1 and D7) were significantly lower in patients with poor outcomes. Our results indicate significant changes in energy metabolism, shifting towards ketosis and alternative energy sources, both in the early and late phases, even with adequate enteral nutrition, particularly in patients with poor outcomes. The early activation of the kynurenine pathway may also play a role in this process. Full article