Search Results (2,887)

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article

During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes—autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation—are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy–ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial–metabolic interactions. Full article

Enhancing forage protein is key to sustainable ruminant nutrition. The nutritive value of Hedysarum coronarium L. was investigated by studying different preservation systems (fresh vs. dehydrated pellet vs. hay) (Exp. 1) and morphological fractions (flowers vs. leaves vs. stems) (Exp. 2). For the fresh and pelleted systems, two cuts were used. Proximately, total polyphenols and condensed tannins were detected. In vitro fermentation characteristics were studied by incubating samples with buffered sheep rumen fluid, estimating methane production by volatile fatty acids. Fresh and pelleted sulla were more nutritionally advantageous than hay, in terms of metabolizable energy and protein-to-fiber ratio. Pelleting at the beginning of flowering proved to be a suitable forage for sheep feeding due to protein (15.1% DM), metabolizable energy (9.64 MJ/kg DM), structural carbohydrates (39.5% DM), and total polyphenols (13.5 GAE g/kg DM) content. This cut showed an in vitro fermentation rate (9.86 mL/h), organic matter degradability (55.7%), and volatile fatty acids (87.3 mmoL/g) that were higher (p < 0.05) than hay. Flowers and leaves showed higher (p < 0.05) levels of secondary metabolites than stems as well as lower methane production. These results suggest the potential influence of these compounds in reducing rumen emissions. Dehydration and pelleting resulted in an effective preservation method for maintaining nutrients in sulla forage. Full article

Background/Objectives: The breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene whose mutations are associated with increased susceptibility to develop breast or ovarian cancer. BRCA1 mainly exerts its protective effects through DNA double-strand break repair. Although not itself a transcriptional factor, BRCA1, through its multiple protein interaction domains, exerts transcriptional coregulation. In addition, BRCA1 expression alters cellular metabolism including inhibition of de novo fatty acid synthesis, changes in cellular bioenergetics, and activation of antioxidant defenses. Some of these actions may contribute to its global oncosuppressive effects. However, the breadth of metabolic pathways reprogrammed by BRCA1 is not fully elucidated. Methods: Breast cancer cells expressing BRCA1 were investigated by multiplatform metabolomics, metabolism-related transcriptomics, and joint metabolomics/transcriptomics data processing techniques, namely two-way orthogonal partial least squares and pathway analysis. Results: Joint analyses revealed the most important metabolites, genes, and pathways of metabolic reprogramming in BRCA1-expressing breast cancer cells. The breadth of metabolic reprogramming included fatty acid synthesis, bioenergetics, HIF-1 signaling pathway, antioxidation, nucleic acid synthesis, and other pathways. Among them, rewiring of glycerophospholipid (including phosphatidylcholine, -serine and -inositol) metabolism and increased arginine metabolism have not been reported yet. Conclusions: Rewired glycerophospholipid and arginine metabolism were identified as components of BRCA1-induced metabolic reprogramming in breast cancer cells. The study helps to identify metabolites that are candidate biomarkers of the BRCA1 genotype and metabolic pathways that can be exploited in targeted therapies. Full article

Wild Ganoderma lucidum from Nepal’s high-altitude regions was studied to identify key bioactive compounds and assess the influence of solvent type—water, ethanol, methanol, and acetone—on extraction efficiency and biological activity. Extracts were evaluated for antioxidant potential, cytotoxicity against HeLa cells, and phytochemical composition via gas chromatography–mass spectrometry (GC-MS). Solvent type significantly affected both yield and bioactivity. Acetone yielded the highest crude extract (5.01%), while ethanol extract exhibited the highest total phenolic (376.5 ± 9.3 mg PG/g) and flavonoid content (30.3 ± 0.5 mg QE/g). Methanol extract was richest in lycopene (0.07 ± 0.00 mg/g) and β-carotene (0.45 ± 0.02 mg/g). Ethanol extract demonstrated consistently strong DPPH, superoxide, hydroxyl, and nitric oxide radical scavenging activity, along with high reducing power. All extracts showed dose-dependent cytotoxicity against HeLa cells, with ethanol and water extracts showing the greatest inhibition (>65% at 1000 µg/mL). GC-MS profiling identified solvent-specific bioactive compounds including sterols, terpenoids, polyphenols, and fatty acids. Notably, pharmacologically relevant compounds such as hinokione, ferruginol, ergosterol, and geranylgeraniol were detected. These findings demonstrate the therapeutic potential of G. lucidum, underscore the importance of solvent selection, and suggest that high-altitude ecological conditions may influence its bioactive metabolite profile. Full article

Ultrafine bubbles (UFBs) represent an emerging technology with unique physicochemical properties. This study investigated the effects of air-filled UFBs infused in drinking water on gut microbiota composition and the associated health markers in Sprague Dawley rats over a 12-week period. Using a two-phase design, UFB concentration was increased from 1.7 × 10⁶ to 6.5 × 10⁹ UFBs/mL at week 7 to assess dose-dependent effects. Administration of UFBs in drinking water induced significant shifts in gut microbiome populations, characterized by increased Bacteroidetes (+122% weeks 8–12) and decreased Firmicutes (−43% weeks 8–12) compared to controls. These microbial shifts coincided with enhanced short-chain fatty acid production (butyrate +56.0%, p ≤ 0.001; valerate +63.1%, p ≤ 0.01) and reduced inflammatory markers (TNF-α −84.0%, p ≤ 0.05; IL-1β −41.0%, p ≤ 0.05; IL-10 −69.8%, p ≤ 0.05). UFB effects demonstrated systematic concentration-dependent threshold responses, with 85.7% of parameters exhibiting directional reversals between low (1.7 × 10⁶ UFBs/mL) and high (6.5 × 10⁹ UFBs/mL) concentration phases rather than linear dose–response relationships. The systematic nature of these threshold effects, with 71.4% of parameters achieving statistical significance (p ≤ 0.05), indicates concentration-dependent biological mechanisms rather than random effects on gut biology. Despite current metagenomic techniques identifying only 25% of the total gut microbiome, the observed changes in characterized species and metabolites demonstrate UFB technology’s therapeutic potential for conditions requiring microbiome modulation, providing new insights into UFB influence on complex biological systems. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article

A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article

The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic health. The aim of this review is therefore to provide an overview of the interactions between oral and gut microbiota, and the influence of diet and related metabolites on this axis. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can migrate to the gut through the enteral route, particularly in individuals with weakened gastrointestinal defenses or conditions like gastroesophageal reflux disease, contributing to disorders like inflammatory bowel disease and colorectal cancer. Bile acids, altered by gut microbes, also play a significant role in modulating these microbiota interactions and inflammatory responses. Oral bacteria can also spread via the bloodstream, promoting systemic inflammation and worsening some conditions like cardiovascular disease. Translocation of microorganisms can also take place from the gut to the oral cavity through fecal–oral transmission, especially within poor sanitary conditions. Some metabolites including short-chain fatty acids, trimethylamine N-oxide, indole and its derivatives, bile acids, and lipopolysaccharides produced by both oral and gut microbes seem to play central roles in mediating oral–gut interactions. The complex interplay between oral and gut microbiota underscores their crucial role in maintaining systemic health and highlights the potential consequences of dysbiosis at both the oral and gastrointestinal level. Some dietary patterns and nutritional compounds including probiotics and prebiotics seem to exert beneficial effects both on oral and gut microbiota eubiosis. A better understanding of these microbial interactions could therefore pave the way for the prevention and management of systemic conditions, improving overall health outcomes. Full article

The impact of seasonality on the aroma quality of tea has been documented in various tea types, but not specifically in oolong tea. This study is the first to explore the complex relationships between seasonality, volatile compounds, and aroma quality in oolong tea. Using Headspace Solid-Phase Microextraction Gas Chromatography–Mass Spectrometry (HS-SPME-GC-MS)-based untargeted metabolomics, we analyzed 266 samples of Tieguanyin oolong tea. The data identified linalool, linalool oxides (trans-linalool oxide (furanoid) and trans-linalool oxide (pyranoid)), and their metabolites (diendiol I; hotrienol) as key seasonal discriminants. Four out of the top ten key differential compounds for distinguishing aroma scores were metabolites from fatty acid degradation, namely trans-3-hexenyl butyrate, trans-2-hexenyl hexanoate, hexyl hexanoate, and hexyl 2-methyl butyrate. Approximately one-fifth of the seasonal discriminant volatile compounds were significant in influencing aroma quality. Overall, the impact of seasonality on the aroma quality of finished Tieguanyin oolong tea is marginal. These findings enhance our understanding of the interplay between seasonal variations, volatile composition, and aroma quality in oolong tea. Full article

Hydrogen sulfide (H₂S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H₂S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H₂S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H₂S precursor to test the effect of H₂S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H₂S selectively favors specific gut microbial processes. Full article

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

Transthyretin amyloidosis (ATTR) is a disease caused by the deposition of transthyretin-derived fibrils in the body. Despite extensive research conducted over the years, there are currently only four drugs available in clinical use to treat this condition, two of which are repurposed drugs used off-label. However, these treatments present several limitations; therefore, there is an urgent need for new therapeutic options. In this context, dietary supplements containing natural compounds capable of stabilizing the transthyretin (TTR) protein could represent a promising approach to contrast the disease progression, potentially supporting the therapeutic effects of the aforementioned drugs. In light of this, the present review highlights and analyzes the natural compounds that have most recently been reported in the literature as TTR stabilizers. In particular, the studies elucidating the potential of these compounds in the treatment of ATTR, along with the available crystallographic data explaining their binding mode to TTR, are reported. Overall, although the use of natural compounds as supplements shows promise in managing ATTR, further research is still needed to explore its feasibility and confirm its effectiveness. Hopefully, this work will help shed light on these issues and serve as a useful starting point for the development of new strategies to treat this disease. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article