Search Results (1,123)

Background/Objectives: Propolis is a complex bee product with a composition that varies according to local vegetation, environmental conditions, and bee foraging behaviours. Recently, gas chromatography–mass spectrometry (GC–MS) has been employed in Uganda to analyse its volatile components. This study examined Ugandan propolis non-volatile metabolites to determine chemotypes and identify antibacterial compounds. Methods: Ethanolic extracts were analysed using liquid chromatography–high-resolution quadrupole time-of-flight mass spectrometry (LC-HR-QTOF-MS) in an untargeted MS/MS mode. Data processing was carried out using MZmine, then annotated with Global Natural Products Social Molecular Networking (GNPS) and SIRIUS. Chemometric methods assisted in identifying regional chemical signatures. Metabolites highlighted by the heatmap were evaluated for antibacterial activity using molecular docking against bacterial targets, followed by ADMET (absorption, distribution, metabolism, excretion, and toxicity) assessments. Results: Out of 3252 features, 234 and 52 putative compounds were annotated in GNPS and SIRIUS, respectively, as indicated by molecular networking, suggesting high chemical complexity. The chemical space mainly comprises flavonoids (including glycosides, aglycones, methylated, and prenylated derivatives), phenolic acids, amides, hydroxycinnamate derivatives, lignans, megastigmanes, and various diterpenoid skeletons. Multivariate analyses clearly distinguish geographical chemotypes, separating flavonoid-rich regions from diterpenoid-rich regions. Docking studies revealed flavonoids, diterpenoids, and lignans with strong predicted antibacterial activities and favourable ADMET profiles. Conclusions: This study provides the first LC–MS characterisation of the non-volatile metabolome of Ugandan propolis, thereby expanding its chemical diversity. Metabolomics and computational approaches lay a foundation for future ecological, chemotaxonomic, and pharmacological research. Full article

The presence of Alternaria mycotoxins in hepatic tissue of both human and animal origin remains unexplored. This work describes the development of an analytical method based on salt-assisted liquid–liquid extraction (SALLE) and ultrahigh-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) for the determination of six main Alternaria mycotoxins and related metabolites. Sample treatment was fully optimized, including sample mass, extraction solvent, and volume and sodium chloride mass. The method was validated, achieving calibration curve R² values above 0.99 and limits of detection between 0.01 and 1.46 µg kg⁻¹. Moreover, satisfactory trueness (apparent recoveries between 84% to 111%) and precision (RSD values below 10%) were achieved, complying with EU requirements. Matrix effects in terms of signal suppression/enhancement varied between 53% for TeA and 78% for AME. Applied to real liver samples (20 human and 20 animal), alternariol monomethyl ether (AME) was found in pig liver, while alternariol (AOH) and tentoxin (TEN) were found in human forensic liver tissues. No other Alternaria mycotoxin metabolites were detected. This methodology is the first validated approach for determining Alternaria mycotoxins in liver tissue. Full article

Citrus fruits are susceptible to ‘Huanglongbing’, leading to widespread antibiotic use during planting. Additionally, to enhance economic efficiency, plant growth regulators (PGRs) are also applied to citrus fruits. To rapidly screen for antibiotics and plant growth regulators in citrus fruits, a method was developed for the simultaneous detection of exogenous contaminants in mandarin, orange, pomelo, and lemon using QuEChERS combined with liquid chromatography–quadrupole/orbitrap mass spectrometry. By comparing the responses or recoveries of compounds under different conditions, the optimal extraction and purification were determined. The method was used to verify the methodological parameters for four citrus fruits. The results showed that the detection limits for 10 antibiotics and 53 plant growth regulators in the four citrus fruits ranged from 1 to 50 μg/kg, and the limits of quantitation ranged from 1 to 80 μg/kg. And the coefficient of determination (R²) was ≥ 0.99. The recovery of all compounds was between 60% and 120%, and the relative standard deviation (RSD) was less than 20%. The method was applied to the 42 real samples, and a total of nine compounds were detected at concentrations ranging from 0.002 to 0.852 mg/kg. The results demonstrated that the method was simple, sensitive, accurate, and reliable, making it suitable for detecting antibiotics and plant growth regulators in citrus fruits. Full article

Sweet potatoes (Ipomoea batatas (L.) Lam.) are known for their anti-inflammatory effects, which are attributed to their phytochemical content. Our previous study revealed that ethanol extracts of sweet potato storage roots (SP-EtOH-Ex) inhibit interleukin-6 (IL-6) production in RAW264.7 cells stimulated with lipopolysaccharide (LPS). However, the causative compounds responsible for the anti-inflammatory effect have not yet been identified. This study aims to identify the compounds responsible for the anti-inflammatory effect of SP-EtOH-Ex using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). The unknown compounds were measured using the auto MS/MS mode (data-dependent acquisition; DDA) of LC-Q-TOF-MS, and the resulting data were analyzed using MS-DIAL and MS-FINDER and also compared with those of the corresponding reference standards in terms of retention time and fragment ions. As a result, β-sitosterol (2.527–4.850 µg/mL), campesterol (75.74–93.63 ng/mL), and lauroyl diethanolamide (4.568–9.260 ng/mL) were identified and quantified in SP-EtOH-Ex. Moreover, the anti-inflammatory effect of these three compounds against RAW264.7 cells was investigated at varying concentrations of β-sitosterol (1 µg/mL, 5 µg/mL, 10 µg/mL), campesterol (10 ng/mL, 100 ng/mL, 1000 ng/mL), and lauroyl diethanolamide (1 ng/mL, 10 ng/mL, 100 ng/mL). The phytosterols β-sitosterol and campesterol suppressed LPS-induced IL-6 production at concentrations comparable to those present in SP-EtOH-Ex. In contrast, lauroyl diethanolamide did not similarly suppress LPS-induced IL-6 production. These results suggest that β-sitosterol and campesterol in sweet potato storage roots contribute to their anti-inflammatory effects. The lack of activity in lauroyl diethanolamide further supports that phytosterols are the primary anti-inflammatory constituents. The edible portion of sweet potatoes holds promise as a promising raw material with anti-inflammatory properties. Full article

Breast cancer remains one of the most prevalent and lethal malignancies affecting women worldwide, underscoring the need for safer and more effective therapeutic strategies. This study investigated the phytochemical composition, antioxidant activity, and antiproliferative potential of POW9™, a proprietary botanical blend formulated from nine medicinal plant extracts. Comprehensive phytochemical profiling was performed using ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) in both positive and negative ionization modes. A total of 34 compounds were identified in negative mode and 27 compounds in positive mode, comprising flavonoids, terpenoids, steroids, organic acids, peptides, glycosides, and lipids. POW9™ exhibited high total phenolic content (190.3 ± 3.5 mg gallic acid equivalents/g) and total flavonoid content (115.2 ± 1.5 mg quercetin equivalents/g), along with strong antioxidant activity, demonstrated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging with a half-maximal inhibitory concentration (IC₅₀) of 1.66 mg/mL (33.73 mg Trolox equivalents/g). Cytotoxicity assessment revealed minimal toxicity toward normal Vero cells. In contrast, POW9™ significantly inhibited the proliferation of human breast cancer cell lines in a concentration- and time-dependent manner. The IC₅₀ values were 6.75 mg/mL for MCF-7 cells and 18.08 mg/mL for MDA-MB-231 cells after 72 h of treatment, while prolonged exposure (96 h) further enhanced antiproliferative efficacy, reducing the IC₅₀ to 2.34 mg/mL. These findings demonstrate that POW9™ is a chemically diverse herbal formulation with potent antioxidant and selective anti-breast cancer activities, supporting its potential development as a complementary therapeutic or nutraceutical agent for breast cancer management. Full article

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic chemicals used in daily life and industrial production. Due to their widespread use, these compounds are frequently detected in environmental samples. Many studies have shown that PFAS pose a significant threat to both ecological environments and human health, leading to widespread public concern. This study developed and optimized an analytical method for the detection of 32 common PFAS compounds in chemical additives and environmental samples, including oil displacement agents, groundwater and soil, utilizing High-Performance Liquid Chromatography–Quadrupole-Orbitrap High-Resolution Mass Spectrometry (HPLC–Q-Orbitrap HRMS) technology. Applications in an eastern Chinese oilfield revealed significant PFAS accumulation, with ∑PFAS concentrations in groundwater and soil at the well site ranging from 212.29 to 262.80 ng/L and from 23.70 to 71.65 ng/g, respectively, exceeding background levels by 10-fold. The oil displacement agents used in oilfields are one of the important sources of PFAS, particularly p-perfluorous nonenoxybenzenesulfonate (OBS), a perfluorooctanesulfonic acid (PFOS) substitute. Soil analysis indicated greater mobility of short-chain PFAS, while long-chain compounds adsorbed more readily to surface layers. Molecular docking and quantitative structure–property relationship (QSPR) modeling suggest that the bioaccumulation potential of OBS is high and comparable to that of PFOS. Zebrafish embryo assays demonstrated that OBS induced significant concentration-dependent cardiac developmental toxicity, including pericardial edema and apoptosis, showing 1.5–2.4 times greater toxicity than PFOS across multiple endpoints. These findings reveal OBS as a pervasive contaminant with elevated environmental and health risks, necessitating urgent re-evaluation of its use as a PFOS substitute. Full article

Background: Cefepime/enmetazobactam (FEP/META) is a novel fixed-dose β-lactam/β-lactamase inhibitor combination. The objective was to study the physicochemical stability of the approved daily dose in polypropylene syringes and elastomeric devices over a 24 or 72 h period to understand the feasibility of using FEP/META in prolonged infusions and its use for outpatient parenteral antibiotic therapy (OPAT). Methods: Solutions of FEP/META were prepared in 0.9% NaCl or 5% dextrose (D5W) and stored in syringes (6 g/1.5 g/48 mL) or silicone and polyisoprene elastomeric devices (EDs) at 6 g/1.5 g/120 mL and 6 g/1.5 g/240 mL: syringes were tested at 22–25 °C over a 24 h period, polyisoprene EDs at 2–8 °C over 72 h period, and silicone and polyisoprene EDs at 32 °C over a 24 h period. The solution was considered stable if it retained more than 90% of its initial concentration (Ci), no pH variation (±1 unit), no significant visual change, and with compliant subvisual examination. Liquid Chromatography–Electrospray Ionization–Quadrupole Time-of-Flight–Mass Spectrometry was utilized to identify intermediate degradation products. Results: At the daily dose, FEP/META retained >90% of its Ci up to 12 h in 0.9% NaCl and 24 h in D5W when stored in syringes. In silicone ED, stability was enhanced up to 24 h in D5W at all concentrations. The solution was chemically stable for 24 h when stored in polyisoprene ED in 0.9% NaCl at 2–8 °C. Conclusions: FEP/META combination showed prolonged stability with physicochemical integrity up to 12–24 h in all containers and conditions. It appears to be stable for prolonged infusions and for OPAT. Full article

Bovine Parainfluenza Virus Type 3 (BPIV3) is a critical pathogen in the Bovine Respiratory Disease Complex (BRDC), leading to significant economic losses in the cattle industry. However, the metabolic reprogramming induced by BPIV3 in cattle remains poorly understood. This study aimed to investigate the impact of BPIV3 infection on the serum metabolome of Simmental cattle using untargeted metabolomics and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). The results revealed significant alterations in the lipidome, including the upregulation of phosphatidylcholine (PC) and phosphatidylglycerol (PG), and the downregulation of phosphatidylinositol (PI). Sphingolipid metabolism also showed considerable changes, with increased levels of Trihexosylceramide and D-erythro-Sphingosine C-17. Furthermore, metabolic pathway analysis identified enriched pathways related to lipid metabolism, amino acid metabolism, and energy sensing. These findings suggest that BPIV3 infection induces substantial shifts in lipid metabolism, which may facilitate viral replication and immune evasion. Our results provide a deeper understanding of the metabolic changes in BPIV3-infected cattle and propose potential targets for therapeutic intervention. Full article

Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography–mass spectrometry (Q-TOF LC/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares–discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut–joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions. Full article

Mycotoxin contamination in agricultural products poses a serious challenge to food safety, severely threatening human and animal health and causing significant economic losses. This study aimed to investigate the degradation and detoxification capabilities of Trichoderma reesei GG-T40 against two representative mycotoxins—aflatoxin B₁ (AFB₁) and zearalenone (ZEN). The results showed that the degradation rates of AFB₁ and ZEN by this strain reached 98.6% and 88.4%, respectively. Using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS), the degradation products were systematically characterized, leading to the identification of six AFB₁ degradation products (C₁₇H₁₄O₇, AFD₁: C₁₆H₁₄O₅, C₁₁H₁₀O₄, C₁₄H₁₆O₄, C₁₅H₁₀O₄, and C₁₇H₁₄O₅) and two ZEN degradation products (α-ZOL and β-ZOL). Toxicity evaluation revealed that the key toxic structures of AFB₁ were disrupted, significantly reducing or even eliminating the toxicity of its degradation products; ZEN was mainly converted into β-ZOL (accounting for 91.5%), which has lower estrogenic activity. Further toxicological experiments in mice confirmed that the degradation products were non-toxic and non-pathogenic under actual testing conditions, demonstrating systematic verification of their safety. In conclusion, T. reesei GG-T40 can efficiently and safely degrade AFB₁ and ZEN, showing great potential for developing green control technologies for mycotoxin contamination in food and feed raw materials, with important application value for ensuring food safety. Full article

Background: Branched-chain amino acids (BCAAs) are popular as sports supplements due to their ability to enhance performance and recovery. However, the full spectrum of metabolic alterations triggered by acute supplementation with BCAAs in conjunction with exercise remains incompletely understood. Methods: A randomized crossover trial was conducted in 8 healthy active young males, who received either BCAA or placebo supplementation for three consecutive days prior to a high-intensity cycling test. Plasma samples were collected pre- and post-exercise and analyzed by ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry, followed by correlation and enrichment analyses. Results: Acute BCAA supplementation was significantly associated with enhanced fat oxidation and attenuated post-exercise increases in plasma ammonia, creatine kinase, and lactate dehydrogenase, suggesting the potential improvements in energy supply and membrane stability. Metabolomics analysis identified differential metabolites primarily involved in lipid, amino acid, and glucose metabolism. Pathway enrichment revealed coordinated regulation of fatty acid oxidation (FAO) and tryptophan-related pathways. Correlation analysis further showed that changes in metabolite profiles were strongly associated with biochemical outcomes, particularly linking enhanced fat oxidation and ammonia clearance with BCAA intake. Conclusions: Short-term BCAA supplementation could enhance FAO and membrane stability via coordinated regulation of lipid and amino acid metabolism post exercise, supporting its potential role as a precision nutrition strategy. Full article

Background: Oxazolidinone derivatives are a novel class of synthetic antibacterial agents, characterized by a five-membered heterocyclic ring containing oxygen and nitrogen and a carbonyl functionality at position 2. This pharmacophore is responsible not only for antibacterial activity but also for a variety of other biological activities, including anticancer activity, anticoagulant activity, and several others. A series of novel oxazolidinone derivatives containing a hydroxamic acid moiety were synthesized in our laboratories and identified as potent inhibitors of the enzyme 5-lipoxygenase (5-LO), a key enzyme involved in the biosynthesis of leukotrienes (LTs). LTs are proinflammatory mediators implicated in allergic and inflammatory diseases. Currently, zileuton is the only FDA-approved 5-LO inhibitor, emphasizing the need to develop new agents for the treatment of such diseases. This project aims to develop validated stability-indicating analytical methods for the four most potent novel 5-(hydroxamic acid)methyl oxazolidinone derivatives (PH-211, PH-247, PH-249, and PH-251). Methods: The compounds were analyzed using Waters Acquity Ultra-High-Performance Liquid Chromatography (UHPLC-UV) with an ultraviolet detector to determine their stability in human plasma and under various forced degradation conditions, including acidic, basic, oxidative, and thermal conditions. Liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QToF-MS) was used to identify possible degradation products. Results: The compounds were found to be stable in human plasma and under thermal degradation conditions with high extraction recoveries (82–90%) but unstable in acidic, basic, and oxidative conditions. Conclusions: The findings show that the compounds are stable in biological conditions; they hold promise for the treatment of inflammatory and allergic diseases. Full article

The gut microbiome evolves in response to host development, health state, lifestyle, nutrition, and microbial interactions. The survival of gut microbiota depends on its ability to utilize its host-indigestible complex oligosaccharides. Certain gut microbes produce glycosidases that cleave N-glycoproteins to release N-glycans that are then used as a carbon source. However, commercial glycosidases are inefficient and, thus, require improved deglycosylation strategies to study their functions and scale up their production. Therefore, the main objective of this study was to recombinantly produce and characterize the novel endo-β-N-acetylglucosaminidase 2 (EndoBI-2) from Bifidobacterium longum subsp. infantis (B. infantis) and to evaluate its enzymatic performance for controlled N-glycan release. Furthermore, the optimum reaction conditions for EndoBI-2 were investigated on model glycoprotein RNAse B using model glycoprotein. The released N-glycans were profiled by hydrophilic interaction liquid chromatography-fluorescence detection-quadrupole time-of-flight tandem mass spectrometry (HILIC-FLD-QTOF-MS/MS). We demonstrated that EndoBI-2 possesses a strong temperature tolerance and efficiently cleaves N-glycans under mild reaction conditions, exhibiting high activity at pH 5. These findings highlight EndoBI-2 as a robust and efficient biocatalyst for the production of bioactive N-glycans from diverse N-glycoproteins, with potential applications in glycobiotechnology. Full article

Geographical origin constitutes one of the key factors that exert an influence on chemical compounds of Lonicerae japonicae flos (LJF). The present research was designed to explore differences among volatile organic compounds (VOCs) and non-VOCs among LJF samples from four geographical origins. Selection of 32 LJF samples with similar genetic backgrounds was performed using simple sequence repeat markers. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were utilized to analyze VOCs, while non-VOCs were detected via ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate statistical analyses were applied to screen differential compounds. The results indicated that HS-SPME-GC-MS and HS-GC-IMS identified 80 and 57 VOCs, respectively, with 34 key differential VOCs screened out, exhibiting significant variations among origins. For non-VOCs, 130 compounds were identified, with 19 key differential compounds showing geographical differences. This study further facilitates a comprehensive understanding of the chemical composition of LJF from different origins. Full article

Background/Objectives: Pregnancy represents a unique physiological state marked by extensive metabolic adaptations, particularly in lipid pathways essential for maternal adjustments, fetal development, and postpartum recovery. This study aimed to explore these changes through untargeted lipidomic profiling. Methods: This observational, comparative, non-interventional clinical study included 107 women, of which 65 were in the third trimester of pregnancy (mean age 27.9 ± 5 years) and 42 were in the early postpartum period (≤7 days, mean age 28.9 ± 5.9 years). Inclusion criteria were singleton, term pregnancies (37–41 weeks) with neonates weighing > 2500 g and no associated pregnancy-related pathologies; exclusion criteria included multiple gestation, use of lipid-altering medications, maternal age > 40 years, or diagnosed pregnancy complications. Plasma samples were analyzed using High-Performance Liquid Chromatography–Quadrupole Time-Of-Flight–Electrospray Ionization (positive mode)–Mass Spectrometry, data were processed with MetaboAnalyst 6.0 using multivariate and univariate analyses (Partial Least Squares–Discriminant Analysis, Volcano Plot, Random Forest, Receiver Operating Characteristic analysis), with statistical significance set at p < 0.05. Results: Multivariate analysis demonstrated a clear separation between groups with high predictive accuracy as reflected by strong classification metrics (Accuracy = 0.90, R² = 0.75, Q² = 0.68). Several discriminative lipids were consistently identified across statistical models, including 2-Methoxyestrone (AUC = 0.861), Eicosanedioic acid (AUC = 0.854), and Pregnenolone sulfate (AUC = 0.843). These biomarkers were further categorized into five major lipid classes: steroid hormones, long-chain fatty acids, lysophospholipids, ceramides/sphingolipids, and glycerolipids. Conclusions: Untargeted lipidomic profiling revealed distinct metabolic signatures that differentiate late pregnancy from early post-partum states. The identification of robust lipid biomarkers with high discriminative performance highlights their potential utility in maternal health monitoring, obstetric risk assessment, and postpartum recovery surveillance. Full article