Ultra-performance Liquid Chromatography-mass Research Articles

Jia Wei Qingxin Lotus Seed Drink ameliorates epithelial mesenchymal transition injury in diabetic kidney disease via inhibition of JMJD1C/SP1/ZEB1 signaling pathway

BackgroundDiabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes mellitus. In this condition, renal tubular epithelial mesenchymal transition (EMT) is an important factor accelerating the progression of DKD and a major cause of renal fibrosis and end-stage renal disease. However, the therapeutic effect is unsatisfactory because of the lack of effective drugs. Jia Wei Qingxin Lotus Seed Drink (QISD) is a traditional Chinese medicine compound formula that has shown to be effective in the clinical treatment of DKD. However, the potential of QISD in DKD-EMT treatment has yet to be fully explored. PurposeThis study aimed to investigate the role of QISD in ameliorating DKD-EMT injury and its mechanism. MethodsThe active ingredients of QISD were identified via ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). A DKD mouse model was constructed by high-fat diet feeding and intraperitoneal injection of STZ (60 mg/kg), and QISD (14.46, 28.92, and 57.84 g/kg/day) was administered by gavage for 12 consecutive weeks. Dapagliflozin (1 mg/kg/d) was used as a positive control. Renal pathological damage was observed by HE, PAS, and Masson staining. The expression levels of EMT-related proteins and pathway proteins were detected via immunohistochemistry, RT-qPCR, and western blot. In in vitro experiments, EMT injury was induced in human kidney tubular epithelial cells (HK-2) by using lipopolysaccharide (LPS). A combination of CCK8 assay, wound healing assay, small-molecule inhibitor intervention, and overexpression lentiviral transfection was used to investigate the effects of QISD on cell migration ability, adhesion ability, fibrotic factor formation, and mesenchymal properties. ResultsAnimal experiments showed that QISD improved blood glucose, body weight, symptoms of excessive drinking and eating, and renal pathological injury in mice, reduced extracellular matrix deposition, delayed renal EMT injury, and inhibited the activation of the histone demethylase JMJD1C. UHPLC-MS/MS and molecular docking indicated that baicalin, wogonoside, oroxylin A-7-O-β-D-glucuronide, and glulisine A found in QISD could bind to JMJD1C. The ameliorating effect of QISD on DKD-EMT injury might be related to JMJD1C. The improvement of DKD-EMT injury by QISD was accompanied by the reduction of SP1 and ZEB1 expression. The SP1 overexpression not only reversed the therapeutic effect of JIB-04, an inhibitor of JMJD1C, on DKD-EMT but also exacerbated the expression of ZEB1 and downstream EMT-related factors. Thus, QISD might affect the expression of the epithelial marker E-cadherin by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway, consequently preventing the transformation of epithelial cells to mesenchymal cells and ameliorating DKD-EMT injury. ConclusionThis study was the first to demonstrate that QISD might ameliorate DKD-EMT injury by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway. These findings provide strong pharmacologic evidence for the clinical use of QISD in the treatment of DKD.

Apixaban removal during emergency surgery for type A acute aortic dissection: a prospective cohort study

Background: Acute type A aortic dissection (ATAAD) has a high mortality, and acute aortic repair is the only curative treatment. In patients treated with factor Xa (FXa) inhibitors, the risk of severe disease-related complications such as cardiac tamponade and hemodynamic shock must be balanced against the potential for severe perioperative bleeding. The aim was to study intraoperative changes in plasma levels of the FXa inhibitor apixaban when using hemoadsorption during acute thoracic aortic repair. Materials and methods: This is a single-center prospective cohort study. Eight apixaban-treated patients presenting with ATAAD underwent acute thoracic aortic repair with intraoperative hemoadsorption with CytoSorb. Apixaban concentrations were measured at the start of cardiopulmonary bypass (CPB) and after 5, 15, 30, 60, and 90 min of CPB, at CPB weaning, 30 min after CPB weaning and 24 h postoperatively, using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). Results: After 30 min of CPB with hemoadsorption, mean apixaban concentration (±SD) was reduced by 59% from 108 (±69) µg/l to 44 (±20) µg/l (P=0.009). There was a further reduction to 37 (±17) µg/l at CPB weaning (P=0.008). Apixaban concentration displayed an increase to 56 (±29) µg/l 24 h postoperatively (P=0.01). In-hospital mortality was 25%. The mean 24H chest tube drainage volume was 621 (±136) ml. Conclusion: Intraoperative hemoadsorption lowers apixaban levels in patients undergoing emergency surgery for ATAAD. Further research is needed to determine its impact on perioperative bleeding complications and mortality.

Antibiotic exposure and risk of overweight/obesity in children: a biomonitoring-based study from eastern Jiangsu, China.

To describe antibiotic exposure in children and explore its association with overweight/obesity. In June 2022, 328 kindergarten and primary school children were selected from Nantong city in Jiangsu Province. Questionnaires were distributed, and morning urine samples were obtained. Total urinary concentrations of 41 antibiotics were measured using ultra-performance liquid chromatography and tandem mass spectrometry. The rates of antibiotic exposure were expressed as percentages (%), specific percentiles (P 95 and P 99), and the maximum values were used to describe the concentration of antibiotics. The association between urinary antibiotic creatinine-adjusted and overweight/obesity was analyzed using logistic regression. A total of 328 children were initially recruited, of which 295 aged 3-8 years met the inclusion criteria and were finally included in the study. The biomonitoring results revealed that 35 antibiotics were detected, with a total detection frequency of 98.31%. Among the included children, 24.75% were classified as overweight/obesity. Multinomial logistic regression analyses revealed significant associations between overweight/obese and exposure to veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs). After adjusting for various overweight/obesity-relevant variables, higher exposure to sulfamethoxazole [OR = 2.35, 95% confidence interval (CI):1.17-4.70], norfloxacin (OR = 2.66, 95% CI: 1.01-7.08), and fluoroquinolones (OR = 1.97, 95% CI: 1.02-3.78) were significantly associated with overweight/obesity (p < 0.05). In addition, after stratification by sex and adjustment for confounding variables, sex-specific differences were observed in the association between antibiotic exposure and overweight/obesity. Notably, these associations were predominantly observed among boys. Children were extensively exposed to antibiotics. Exposure to certain types of veterinary antibiotics and preferred veterinary antibiotic exposure, mainly through food or drinking water, are associated with an increased risk of overweight/obesity in children.

Huaxian formula prevents the progression of radiation-induced pulmonary fibrosis by inhibiting the pro-fibrotic effects of macrophages

Ethnopharmacological relevanceThe Huaxian formula (HXF), a traditional Chinese medicine (TCM) remedy, specifically targets the pathological factors of “heat toxicity” and “phlegm stasis” induced by radiation in radiation-induced pulmonary fibrosis (RIPF). It works by clearing heat and invigorating the blood, addressing these key factors in the development of RIPF. Aim of the studyThe HXF has demonstrated potential in preventing RIPF, although its underlying mechanisms remain unclear. This study aims to investigate the efficacy, molecular targets, and mechanisms of action of HXF. Materials and methodsThe major constituents of the HXF were identified by ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS). C57BL/6j mice were divided into four groups: control (Ctrl), HXF alone (HXF), 17Gy-irradiation alone (IR), and irradiation plus HXF (IR + HXF). Lung damage and fibrosis were assessed by histopathological staining, and the flow cytometry and immunohistochemistry (IHC) were used to detect the macrophages phenotype of lung tissues in vivo at 16 weeks post-irradiation. Transcriptomic sequencing and bioinformatics analyses identified key genes modulated by HXF. In vitro assays included flow cytometry, western bolt, and quantitative PCR (qPCR) explored the impact of HXF on macrophage polarization and fibrotic activity, while co-culture experiments of the macrophage conditional medium and mouse embryo fibroblast NIH/3T3 investigated macrophage-fibroblast interactions. Results20 major constituents of HXF were identified. And the in vivo results revealed significant lung damage and fibrosis in the IR group, which were notably mitigated in the IR + HXF group. And HXF has been shown to significantly inhibit the infiltration of M2-type macrophages in lung tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) such as Arg1, Mmp10, and Fgf23. Bioinformatics enrichment analysis indicated that these DEGs are involved in pathways related to the inhibition of extracellular matrix formation and inflammation. In vitro, HXF-containing serum reduced M2-type macrophage polarization and decreased the secretion of Arginase1 and TGFβ1. Conditioned medium from HXF-treated macrophages suppressed fibroblast activation. ConclusionHXF's preventive effects on RIPF involve multiple targets and mechanisms, including the modulation of Arg1, Mmp10, and Fgf23 expression. By inhibiting the pro-fibrotic capacity of macrophages, HXF suppresses fibroblast activation and collagen production, thereby alleviating lung fibrosis. These findings underscore the potential of HXF as a preventive strategy in managing RIPF.

NOVEL METHOD FOR DETERMINATION OF POMALIDOMIDE IN HUMAN PLASMA BY ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY MASS SPECTROSCOPY / MASS SPECTROSCOPY

The current investigation studied and verified an accurate Ultra performance liquid chromatography mass spectroscopy/ mass spectroscopy technique for the high-throughput detection of pomalidomide in human plasma with celecoxib as an internal standard. Chromatographic studies were carried out on Hypersil BDS (50 mm x 4.1 mm, 5m) with an isocratic mobile phase of acetonitrile: ammonium formate (80:20, V/V), at a flow rate of 0.5 mL min-1 and a total run time of 3 min. A triple quadruple Tandem Mass spectroscopy with electrospray ionization in positive mode was utilized to identify the analyte. Using multiple reaction monitoring modes and precursor-to-product ion transitions of 274.43 m/z for pomalidomide and 382.12 m/z for standard, respectively, pomalidomide and internal standard were measured. The developed technique was verified as per the regulatory standards for bioanalytical procedures validation. Other validation results also match.

Understory growth of Paris polyphylla accumulates a reservoir of secondary metabolites of plants.

Paris polyphylla is an important traditional medicinal plant of the Himalayan region. It is extensively used for the production of natural steroidal saponins and flavonoids. Although seed dormancy of wild plants can be broken to be artificially maintained and regenerated through micropropagation in the laboratory, the success of secondary metabolite production in higher quantities and the synthesis of superior plant metabolites have been very limited. In this study, we present differential metabolic profiling of P. polyphylla plants maintained for 8 years in natural and greenhouse conditions. Untargeted profiling of the metabolites through ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), followed by statistical analysis, identified secondary metabolites that were enriched in the naturally occurring plant roots compared with the greenhouse plant roots. A multivariate statistical analysis revealed the differential distribution of the compounds between the two groups. Overall, we identified 1,182 secondary metabolites, with 116 metabolites being differentially upregulated and 256 metabolites being downregulated. Moreover, 810 metabolites showed no significant variation under both growing conditions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the naturally forest-grown P. polyphylla plants were significantly enriched in steroidal saponins, lipids, vitamins, flavonoids, and flavonols. An analysis of the top 10 differentially upregulated secondary metabolites indicated a significantly enriched quantity of spirost-5-en-3,12-diol and kaempferol synthesis pathways, which are known to reduce the effect of free radicals scavengers inside the cell. In addition, veratramine alkaloids were also enriched under natural conditions. Our findings indicated that naturally maintained P. polyphylla plants are suitable for the extraction of medicinally important compounds. Our study established a causal relationship between the metabolic composition of the roots and their natural growth condition. This study highlighted the importance of environmental conditions in the biosynthesis of secondary metabolites of plants.

Purchasing “Nootropics” Online: Identification and Quantification of Ingredients in Phenibut-Containing Products

Background and Objectives: Phenibut is a central nervous system drug that is registered and used in clinical practice as a prescription medication. In recent decades, the drug has become popular as a “nootropic and cognition enhancer” because of its active marketing as a dietary or food supplement sold online. This has resulted in a growing number of case reports on acute toxicity and withdrawal symptoms and has raised concerns about the quality of phenibut-containing products. Materials and Methods: We used high-performance liquid chromatography with diode-array detection and ultra-performance liquid chromatography–mass spectrometry to investigate the quality of six phenibut-containing samples purchased from three internet suppliers. Results: Substantially lower levels of the active pharmaceutical ingredient than claimed on the packaging were found for three of the supplements tested. A considerably higher level of phenibut was present in one product. All online-purchased phenibut-containing capsules included declared and undeclared ingredients found in various dietary supplements claiming to have metabolic, neurotropic, antioxidant, anti-inflammatory, and neuroprotective properties. Conclusions: The online-purchased phenibut products contained undeclared ingredients and the content of phenibut differed from the declared. The combinations of these additional ingredients with phenibut have not been tested for activity or safety and their use warrants further attention to avoid potential health problems.

A simple ultraperformance liquid chromatography mass spectrometry method for the determination of cortisol level in sea bass plasma

A simple, precise, and rapid ultra-performance liquid chromatography method for cortisol quantification in sea bass plasma, based on LC-ESI-UHR-QqTOF-MS, was optimised using tolperisone as internal standard. Sea bass plasma samples containing cortisol were spiked with tolperisone as internal standard and extracted with acetonitrile. Samples were vortexed and centrifuged at 15,000g for 10 min at 4 °C. The final extract, diluted in ammonium formate (1:1), was injected in the LC-ESI-UHR-QqTOF-MS system for analysis. Mass spectrometry acquisition parameters were set using positive ionisation mode over a m/z range from 150 to 2200. Cortisol and tolperisone were detected and quantified at m/z 363.21 and 246.18, respectively, in an Auto MS (MS/MS) mode. The detection and quantification limits of cortisol in sea bass plasma were 0.01 and 0.02 μg/mL, respectively. The mean extraction recovery of cortisol was of 99.1 ± 4.0 %. The within- and between-day precision presents a relative standard deviation (RSD) below 2.9 % and 5.3, respectively. Furthermore, the effect of four different diets (fish feed 1–4) in the basal and stress-induced plasma cortisol levels of sea bass was also assessed.

Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Twelve MMD patients-six children and six adults-along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms.

Ultra-performance liquid chromatography-mass spectrometry methods for the determination of the residual quantities of ramipril and hydrochlorothiazide for controlling the cleaning of equipment

Monitoring the completeness of equipment cleaning is essential to prevent cross-contamination of medicinal products. Therefore, it is necessary to develop fast and sensitive methods for studying residual quantities of active ingredients on the surfaces of technological equipment. The aim of the work was to develop and validate analytical methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry method. Materials and methods. In the study, standard samples of ramipril (USP RS) and hydrochlorothiazide (USP RS), as well as class A reagents, were used. Samples were analysed on a liquid chromatograph with an MS detector (Agilent 6420 and Waters Xevo TQD ACQUITY). We used the Kinetex C18 column (2.1 mm × 30 mm × 1.7 μm); mobile phase – 0.1% formic acid solution in deionised water – Acetonitrile (ratio 73:27 for the determination of ramipril and 91.5:8.5 for the determination of hydrochlorothiazide); mobile phase rate of 0.4 mL/min for the determination of ramipril and 0.35 mL/min for the determination of hydrochlorothiazide; column temperature 45 °C for the determination of ramipril and 40 °C for the determination of hydrochlorothiazide, ionisation mode - electric spray in positive mode; The detection parameters are the mode of registration of the daughter ion 417 → 234 m/z for the determination of ramipril and 298 → 281 m/z for the determination of hydrochlorothiazide. Results and discussion. Methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry have been developed. The developed methods have sufficient linearity, correctness and precision. The sensitivity of the techniques was confirmed at the level of 0.0026 μg/ml. The techniques can be used in the concentration range of 0.0026 – 0.0255 μg/ml Conclusions. Analytical methods for determining ramipril and hydrochlorothiazide in wash waters have been developed and validated.

Short communications: Exploring temporal fluorescent changes in the composition of human semen stains

Semen traces are considered important pieces of evidence in forensic investigations, especially those involving sexsual offenses. Recently, our research group developed a fluorescence-based technique to accurately determine the age of semen traces. However, the specific compounds resonsible for the fluoresescent behaviour of ageing semens remain unknown. As such, in this exploratory study, the aim is to identify the components associated with the fluorescent behavior of ageing semen traces. In this investigation semen stains and various biofluorophores commonly found in body fluids were left to aged for 0, 2, 4, 7, 14 and 21 days. Subsequently, thin-layer chromatography (TLC) and ultra-performance liquid chromatography (UPLC) mass spectrometry were performed to identify the biofluorophores present in semen. Several contributors to the autofluorescence could be identified in semen stain, these include tryptophan, kynurenine, kynurenic acid, and norharman. The study sheds light on the.

Lipidomics combined with random forest machine learning algorithms to reveal freshness markers for duck eggs during storage in different rearing systems

The differences in lipids in duck eggs between the 2 rearing systems during storage have not been fully studied. Herein, we propose untargeted lipidomics combined with a random forest (RF) algorithm to identify potential marker lipids based on ultra-performance liquid chromatography‒mass spectrometry (UPLPC-MS/MS). A total of 106 and 16 differential lipids (DL) were screened in egg yolk and white, respectively. In yolk, metabolic pathway analysis of DLs revealed that glycerophospholipid metabolism and sphingolipid metabolism were the key metabolic pathways in the traditional free-range system (TFS) during storage, glycosylphosphatidylinositol-anchored biosynthesis and glyceride metabolism were the key pathways in the floor-rearing system (FRS). In egg white, the key pathway in both systems is the biosynthesis of unsaturated fatty acids. Combined with RF algorithm, 12 marker lipids were screened during storage. Therefore, this study elucidates the changes in lipids in duck eggs during storage in 2 rearing systems and provides new ideas for screening marker lipids during storage. This approach is highly important for evaluating the quality of egg and egg products and provides guidance for duck egg production.

UV-B Stress-Triggered Amino Acid Reprogramming and ABA-Mediated Hormonal Crosstalk in Rhododendron chrysanthum Pall.

Increased UV-B radiation due to ozone depletion adversely affects plants. This study focused on the metabolite dynamics of Rhododendron chrysanthum Pall. (R. chrysanthum) and the role of ABA in mitigating UV-B stress. Chlorophyll fluorescence metrics indicated that both JA and ABA increased UV-B resistance; however, the effect of JA was not as strong as that of ABA. Metabolomic analysis using UPLC-MS/MS (ultra-performance liquid chromatography and tandem mass spectrometry) revealed significant fluctuations in metabolites under UV-B and ABA application. UV-B decreased amino acids and increased phenolics, suggesting antioxidant defense activation. ABA treatment upregulated lipids and phenolic acids, highlighting its protective role. Multivariate analysis showed distinct metabolic clusters and pathways responding to UV-B and ABA, which impacted amino acid metabolism and hormone signal transduction. Exogenous ABA negatively regulated the JA signaling pathway in UV-B-exposed R. chrysanthum, as shown by KEGG enrichment. This study deepens understanding of plant stress-tolerance mechanisms and has implications for enhancing plant stress tolerance through metabolic and hormonal interventions.

Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure–stability relationships of acylated derivatives

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group–conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Discovery and Characterization of a Novel Bacteriocin That Strongly Inhibits Staphylococcus aureus

Drug resistance in Staphylococcus aureus is a serious problem, and the development of new antimicrobial drugs to circumvent drug resistance has become a trend. In this study, we isolated a strain of Bacillus subtilis with high tolerance to alcohol, pH, NaCl, bile salt, surfactants, temperature, and simulated intestinal fluids. We optimized culture parameters to obtain the best fermentation conditions for the production of inhibitory compounds in cell-free culture media. The crude extract showed excellent stability when exposed to temperature, pH, and ultraviolet radiation, with almost no loss of bacteriostatic activity after treatment. After isolation and purification, the peptide sequences were identified using ultraperformance liquid chromatography–mass spectrometry (UPLC–MS), and the antibacterial sequences were analyzed using bioinformatics. The results of the identification showed that there was one novel bacteriocin (NSGGSYGSGGGGGGGNSHGY) with a molecular weight of 1513.58 Da. The minimum inhibitory concentration (MIC) of the B5 bacteriocin was 31.25 μg/mL against S. aureus, and it is noteworthy that bacteriocin B5 also showed weak antibacterial activity against Vibrio parahaemolyticus. In conclusion, this study developed a novel bacteriocin that has the potential to be used as an alternative to S. aureus antibiotics.

Chemical characterization and cytotoxic effect of three edible fungi (Morchella) against breast cancer cells: A therapeutic approach

Current breast cancer therapeutics are associated with short-term efficacy, increased drug resistance, and severe adverse reactions, thus demanding the development of new therapeutic approaches. This present study aimed to explore the cytotoxic activity of Morchella extracts in the context of the MCF-7 cell line (breast cancer) and ultra-performance liquid chromatography mass spectroscopy (UPLC-MS) analysis. The cytotoxic activity of the Morchella conica, Morchella delicosa, and Morchella escuelnta extracts was examined against the breast cancer cell line (MCF-7), using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay (MTT assay). The Morchella extracts were screened for the presence of compounds using ultra-performance liquid chromatography mass spectroscopy (UPLC-MS/MS) based analysis. All the Morchella extracts actively restricted the viability and proliferation of breast cancer cells in a dose-dependent manner, with half maximal inhibitory concentration (IC50) values ranging from 0.017 to 0.68 mg/ml. The main compounds identified in Morchella include alkaloid, sterol, flavonoid, terpenoid, fatty acid, peptide, glutamic acid, amino acid, coumarin, and cyclopyrrolone. In conclusion, Morchella extracts exhibited cytotoxic effects against breast cancer cell lines and decreased the viability of MCF-7 cell line. The Morchella compounds might be the main components contributing to the inhibition of breast cancer cells. The findings of this research offer an innovative framework for advanced investigations for the development of cancer therapeutics from this fungus.

Tryptophan and Its Derived Metabolites as Biomarkers for Tuberculosis Disease: A Systematic Review

Feasible diagnostic assays are required to detect new tuberculosis (TB) cases and monitor treatment. This study aimed to evaluate evidence on tryptophan (Trp) and its metabolites as proposed biomarkers for TB. Through specific keyword searches, we identified 170 relevant literature sources and included seven publications (from 2013 to 2023). The biomarker used in these studies were indoleamine 2, 3-dioxygenase (IDO) activity, IDO-1 gene expression, and plasma IDO protein, measured using ELISA, liquid chromatography-mass spectrometry, ultraperformance liquid chromatography mass spectrometry, and transcriptional profiling. The studies encompassed a pediatric case-control and six studies involving adults, pregnant women with TB-HIV, and individuals with multidrug-resistant tuberculosis, active TB, and latent TB. The assessment of IDO activity and IDO protein level demonstrated promising performance in distinguishing active TB from controls and in evaluating treatment failure and recurrent cases to controls. Trp and its metabolites fulfilled nearly all of target product profile criteria for detecting active TB. This study highlights the potential of utilizing host Trp and its metabolites as non-sputum-based biomarker for TB infection.

Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring

BackgroundIntravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting.Patients and methodsRetrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated.ResultsTwo hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0–7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09–2.31), 1.46 (95%CI:1.03–2.07) and 1.73 (95%CI:1.27–2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44–0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39–0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css.ConclusionsWe provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs.Key pointsReal world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

Rapid determination of eight biogenic amines in air-dried yak meat by QuEChERS combined with ultra-performance liquid chromatography-mass spectrometry

A method for the determination of eight biogenic amines (BAs) in air-dried yak meat was established using ultra-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) without derivatization. The conditions of UPLC–MS/MS, pH, hydration volume, extraction solvent, extraction salt, and clean-up sorbent were optimized according to the characteristics of the BAs and the sample matrix. The samples were extracted with acetonitrile, the extract was purified using primary secondary amine (PSA) and C18. The BAs were determined using multiple reaction monitoring (MRM) within 5 min. The eight BAs exhibited good linearity, and the determination coefficient (R2) was greater than 0.997. The limits of detection (LODs) and the limits of quantification (LOQs) ranged from 0.40 to 2.50 μg/kg and from 1.25 to 7.50 μg/kg, respectively. The accuracy was between 80.3 % and 109.6 %, with relative standard deviations (RSDs) between 0.4–7.1 %. The method was applied in the detection of representative commercial samples of different processing techniques. In this method, the sample was pretreated free of derivatization and was simple, rapid, with minimum personal error, and high sensitivity. The method was assessed via GAPI and BAGI, verifying its environmental friendliness and applicability. It provides reliable methodological support for the determination of BAs in meat products.

Metabolite Profiles of Plant-Based Diets and Cardiometabolic Risk in the Mediators of Atherosclerosis in South Asians Living in America Study

BackgroundHealthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk. ObjectivesThis study aimed to identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D. MethodsWe included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultraperformance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index, and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable-adjusted linear and logistic regressions. ResultsMetabolite profiles for PDI, hPDI, and uPDI consisted of n = 51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower low density lipoprotein cholesterol and high density lipoprotein cholesterol. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin, lower odds of overweight (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.51, 0.81) and obesity (OR: 0.59; 95% CI: 0.48, 0.74), and lower odds of incident T2D (OR: 0.66; 95% CI: 0.45, 0.97). ConclusionsMetabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.