Liquid Chromatography-high Resolution Mass Spectrometry Research Articles

Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS) Fingerprinting and Chemometrics for Coffee Classification and Authentication.

Nowadays, the quality of natural products is an issue of great interest in our society due to the increase in adulteration cases in recent decades. Coffee, one of the most popular beverages worldwide, is a food product that is easily adulterated. To prevent fraudulent practices, it is necessary to develop feasible methodologies to authenticate and guarantee not only the coffee's origin but also its variety, as well as its roasting degree. In the present study, a C18 reversed-phase liquid chromatography (LC) technique coupled to high-resolution mass spectrometry (HRMS) was applied to address the characterization and classification of Arabica and Robusta coffee samples from different production regions using chemometrics. The proposed non-targeted LC-HRMS method using electrospray ionization in negative mode was applied to the analysis of 306 coffee samples belonging to different groups depending on the variety (Arabica and Robusta), the growing region (e.g., Ethiopia, Colombia, Nicaragua, Indonesia, India, Uganda, Brazil, Cambodia and Vietnam), and the roasting degree. Analytes were recovered with hot water as the extracting solvent (coffee brewing). The data obtained were considered the source of potential descriptors to be exploited for the characterization and classification of the samples using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). In addition, different adulteration cases, involving nearby production regions and different varieties, were evaluated by pairs (e.g., Vietnam Arabica-Vietnam Robusta, Vietnam Arabica-Cambodia and Vietnam Robusta-Cambodia). The coffee adulteration studies carried out with partial least squares (PLS) regression demonstrated the good capability of the proposed methodology to quantify adulterant levels down to 15%, accomplishing calibration and prediction errors below 2.7% and 11.6%, respectively.

A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease

Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using targeted and untargeted metabolomics analyses of serum and primary cell cultures using hyphenated ultra-high performance liquid chromatography high-resolution mass spectrometry. Targeted metabolomics revealed 11 discriminating metabolites in serum, which were enriched within the arginine and proline metabolism pathway. Based on untargeted metabolomics and discriminant analysis, 166 components showed a high predictive value. In addition, human intestinal fibroblasts isolated from stenotic tissue were characterized by differential levels of medium-chain dicarboxylic acids, which are proposed as an energy source through beta-oxidation, when oxidative phosphorylation is insufficient. Another energy providing pathway in such situations is anaerobic glycolysis, a theory supported by increased expression of hexokinase 2 and solute carrier family 16 member 1 in stenotic fibroblasts. Of interest, four (unannotated) metabolic components showed a negative correlation with hexokinase 2 gene expression. Together, this study provides a discriminative metabolic fingerprint in the serum and in intestinal fibroblasts of stenotic and non-stenotic patients with CD suggestive for increased production of building blocks for collagen synthesis and increased glycolysis.

Effect of temperature on growth and yessotoxin production of Protoceratium reticulatum and Lingulodinium polyedra (Dinophyceae) isolates from the Portuguese coast (NE Atlantic)

The dinoflagellates Protoceratium reticulatum and Lingulodinium polyedra are potential yessotoxin (YTX) producers, which have been associated with blooms responsible for economic, social, and ecological impacts around the world. They occur in Iberian waters, but in this region, little is known of their ecophysiology and toxin profiles. This study investigated the growth and toxin production of two strains of each species, from the Portuguese coast, at 15 °C, 19 °C, and 23 °C. Growth curves showed higher growth rates at 19 °C, for both species. YTX and three analogs (homo YTX; 45-OH YTX; 45-OH homo YTX) were investigated by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), and the presence of other analogs was investigated by Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS). No evidence of toxin production was found in L. polyedra. By contrast, YTX and 45,55-diOH-YTX were detected in both strains of P. reticulatum. These results confirm P. reticulatum as a source of yessotoxins along the Portuguese coast and add to the observed high intraspecific variability on YTX production of both species, at a global scale.

Mahamanalactone A, a new triterpenoid from Dysoxylum malabaricum bark: a case study for rapid identification of new metabolites via LC-HRMS profiling and database mining strategy

In this recent investigation, the focus centred on exploring the potential phytoconstituents within the bark of Dysoxylum malabaricum. A profiling strategy employing LC-HRMS (Liquid Chromatography-High Resolution Mass Spectrometry) was implemented for the rapid identification of compounds from the bark extract. The crude extract underwent fractionation, resulting in the isolation of four previously known compounds (1–4) and a novel cycloartane triterpenoid named Mahamanalactone A (5). Compound 5 represents a cycloartane triterpenoid with a modified ring-A, featuring £-caprolactone fusion at positions 4 and 5, distinguishing it from other reported compounds where £-caprolactone is typically fused at positions 3 and 4. Cytotoxicity assessment revealed that the newly identified compound 5 exhibited a moderate cytotoxic profile (IC50 29 to 78 µM) against a panel of cancer cell lines.

Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology.

The cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti-inflammatory mechanism in the treatment of RA by flexibly integrating the high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti-inflammatory role by regulating key targets such as IL-2, STAT1, JAK3, and MAPK8, inducing immune response through IL-17 signaling pathway, T-cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.

Quantitative lipidomics in green robusta coffees from the Brazilian Amazon by LC-HRMS

Lipids play an important role in coffee bean development and impact the coffee brew quality. The lipid fraction of raw coffee beans is mainly composed of triacylglycerols (TG) and other minor constituents, such as diterpenes, sterols, phospholipids (PL), and βN-alkanoyl-5-hydroxytryptamides (Cn-5HT). Despite these classes of compounds having been previously characterized by lipidomics, this approach was limited to semi-quantitative analysis. In this work, we developed a multiclass quantitative approach using liquid chromatography-high resolution mass spectrometry to quantify lipids in raw robusta coffees from different producers of the Brazilian Amazon region. The quantitative method for LPC, PC, PI, PG, DG, TG, and Cn-5HT classes was successfully developed and validated. The total lipid content in the robusta coffees ranged from 17.13 to 29.03 g 100 g−1 for TG, 1.44 2.10 g 100 g−1 for DG, 0.27–0.53 g 100 g−1 for PC, 0.34–0.36 g 100 g−1 for FI, 0.10–0.19 g 100 g−1 for Cn-5HT, and 0.01 g 100 g−1 for LPC. In addition, individual components from the Cn-5HT class were analyzed. PC, PI, TG, DG, and Cn-5HTs were relevant factors in discriminating the coffee samples according to their origin. Therefore, these results can help to further understand how the lipid composition of coffee beans is related to the place of harvest and the development of origin certificates of Amazon robusta coffees.

Surface multi-walled carbon nanotube modified quaternary amine-functionalized polymers for purification and determination of glyphosate and its four metabolites in plasma samples

The present study focused on the pretreatment and detection of GLY and its four metabolites AMPA, N-acetyl AMPA, N-methyl GLY and N-acetyl GLY in plasma samples. Multi-walled carbon nanotube-modified quaternary amine-functionalized polymers (QA-PDNV@MWCNTs) were synthesized in a controlled manner by self-assembly, and its morphology and composition were extensively characterized. The QA-PDNV@MWCNTs microspheres were then used as an SPE adsorbent for the preparation and rapid determination of GLY and its four metabolites in plasma samples combined with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). The SPE conditions based on QA-PDNV@MWCNTs were optimized for GLY and its metabolites to obtain the best purification efficiency. The experimental results show that when the adsorbent contains 8% MWCNTs, it can balance the adsorption of target analytes and the purification performance of the adsorbent for impurities. In addition, this study compared the QA-PDNV@MWCNTs based SPE method with the commercial Waters Oasis MAX SPE cartridge and the results showed that the developed method in this study has better resistance to matrix interference. Under optimal conditions, the recoveries of GLY and its metabolites spiked in plasma were 82.6-99.4% with relative standard deviations (RSDs) of 1.0-7.8%. The limits of detection (LODs, S/N≥3) and limits of quantification (LOQs, S/N≥9) of the method were 0.05-0.33 μg/L and 0.15-1.00 μg/L, respectively. Finally, the developed QA-PDNV@MWCNTs based SPE-UPLC-HRMS method was used to confirm GLY poisoning not only on the basis of the detection of the GLY prototype, but also on the basis of its four metabolites.

Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects.

Hydrogen sulfide (H2S) is a signaling molecule endogenously produced within mammals' cells that plays an important role in inflammation, exerting anti-inflammatory effects. In this view, the research has shown a growing interest in identifying natural H2S donors. Herein, for the first time, the potential of marine extract as a source of H2S-releasing agents has been explored. Different fractions obtained by the Indonesian ascidian Polycarpa aurata were evaluated for their ability to release H2S in solution. The main components of the most active fraction were then characterized by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and NMR spectroscopy. The ability of this fraction to release H2S was evaluated in a cell-free assay and J774 macrophages by a fluorimetric method, and its anti-inflammatory activity was evaluated in vitro and in vivo by using carrageenan-induced mouse paw edema. The anti-inflammatory effects were assessed by inhibiting the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6), coupled with a reduction in nitric oxide (NO) and IL-6 levels. Thus, this study defines the first example of a marine source able to inhibit inflammatory responses in vivo through the release of H2S.

Effects of storage temperature and time on metabolite profiles measured in dried blood spots, dried blood microsamplers, and plasma

The practical advantages of capillary whole blood collection over venipuncture plasma collection for human exposome research are well known. However, before epidemiologists, clinicians, and public health researchers employ these microvolume sample collections, a rigorous evaluation of pre-analytical storage conditions is needed to develop protocols that maximize sample stability and reliability over time. Therefore, we performed a controlled experiment of dried whole blood collected on 10 μL Mitra microsamplers (DBM), 5-mm punches of whole blood from a dried blood spot (DBS), and 10 μL of plasma, and evaluated the effects of storage conditions at 4 °C, −20 °C, or −80 °C for up to 6 months on the resulting metabolite profiles measured with untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS). At −80 °C storage conditions, metabolite profiles from DBS, DBM, and plasma showed similar stability. While DBS and DBM metabolite profiles remained similarly stable at −20 °C storage, plasma profiles showed decreased stability at −20 °C compared to −80 °C storage. At refrigerated temperatures (4 °C), metabolite profiles collected on DBM were more stable than plasma or DBS, particularly for lipid classes. These results inform robust capillary blood sample storage protocols for DBM and DBS at potentially warmer temperatures than −80 °C, which may facilitate blood collections for populations outside of a clinical setting.

Comparative study of bioactive compound content and antioxidant activity in different extraction methods of Syzygium Polyanthum leaves

Link of Video Abstract: https://youtu.be/VtCPJX9TPg4 Background : Syzygium Polyanthum is classified among the 5,000 medicinal plant species documented in the Indonesian Medicinal Herb Index. It is utilised for a variety of purposes in traditional medicine and has potential health benefits. Extraction of medicinal plants is crucial to separate active plant materials or secondary metabolites. The aim of the study was to compare extracts of Syzygium Polyanthum Leaves using different methods: maceration and UAE in extracting flavonoids, phenolic compounds and antioxidant activity. Methods: the bioactive component content and antioxidant activity of Syzygium polyanthum leaves extracted using two different methods—maceration and ultrasound-assisted extraction (UAE)—are compared. 96% ethanol was employed as the extracting solvent in the maceration and UAE extraction processes for S. polyanthum.The bioactive substances in both extracts were determined using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). Result: The amount of total phenolic, flavonoid, and IC50 in S. polyanthum leaves was evaluated between the maceration extraction method and UAE. Liquid chromatography-high Resolution Mass Spectrometry (LC-HRMS) analysis was utilized to detect the presence of bioactive compounds, then classified according to the PubChem database's taxonomy. There were comparable amounts of flavonoids in both extracts (60.194 mg QE/g and 60.074 mg QE/g). According to the DPPH assay, the total phenol for the extracts obtained by maceration and UAE was 94.63 ± 2.18 mg GAE/g and 122.87 ± 5.99 mg GAE/g extracts respectively, and the IC50 for the extracts obtained by maceration and UAE were 88.21 ± 1.38 μg/mL and 41.23 ± 6.11 μg/mL. Conclusion: The findings of the study indicated that the ultrasonic-assisted extraction (UAE) approach yielded significantly greater quantities of total phenolic and flavonoid compounds, as well as exhibited stronger antioxidant activity, when compared to the maceration extraction method. The utilisation of the UAE approach resulted in a significant rise in the antioxidant activity of S. polyanthum leaves.

Screening and identification of unknown chemical contaminants in food based on liquid chromatography–high-resolution mass spectrometry and machine learning

Unknown or unexpected chemical contaminants and/or their transformation products in food that may be harmful to humans need to be discovered for comprehensive safety evaluation. Liquid chromatography–high-resolution mass spectrometry (LC-HRMS) is a powerful tool for detecting chemical contaminants in food samples. However, identifying all of peaks in LC-HRMS is not possible, but if class information is known in advance, further identification will become easier. In this work, a novel MS2 spectra classification-driven screening strategy was constructed based on LC-HRMS and machine learning. First, the classification model was developed based on machine learning algorithm using class information and experimental MS2 data of chemical contaminants and other non-contaminants. By using the developed artificial neural network classification model, in total 32 classes of pesticides, veterinary drugs and mycotoxins were classified with good prediction accuracy and low false-positive rate. Based on the classification model, a screening procedure was developed in which the classes of unknown features in LC-HRMS were first predicted through the classification model, and then their structures were identified under the guidance of class information. Finally, the developed strategy was tentatively applied to the analysis of pork and aquatic products, and 8 chemical contaminants and 11 transformation products belonging to 8 classes were found. This strategy enables screening of unknown chemical contaminants and transformation products in complex food matrices.

BIOCHEMICAL EVALUATION OF INDUS VIVA I PULSE NATURAL AYURVEDIC SYRUP AND IT’S IN SILICO – INTERACTION ANALYSIS

Objectives: In developing countries like India, diabetes mellitus and human bone cancer are progressively increasing which is global encumbrance. The objective of the study is to find out the phytoconstituents of Indus Viva I Pulse health drink extract that has undergone classical chemical characterization, molecular docking, anti-diabetic, anticancer, antibacterial and antifungal studies used as traditional and complementary medicine. The study aimed to evaluate the Gas Chromatography–Mass Spectrometry (GC-MS), High-Performance Liquid Chromatography (HPLC), Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS), anticancer, antidiabetic and spectral studies that are used to disclose phytochemicals and their medicinal properties. Methods: Infrared (IR), Ultraviolet (UV), 1H-NMR spectroscopic methods, GC-MS, HPLC and LC-HRMS instrumental detections were employed. Molecular docking, anti-diabetic, anticancer, antibacterial and antifungal studies were carried out using AutoDock 4.2.6. software program, α- Amylase method, Mosmann and Disk diffusion method respectively. Results: GC-MS and HPLC chromatogram of methanol extracts exhibited 12 and 6 peaks, respectively, confirming the presence of 12 phytoconstituents in Indus Viva I Pulse health drink (1I–12I). The total phenol and flavonoid content found in the extracted sample of Indus Viva I Pulse health drink were 0.16 and 0.36 mg/mL, respectively. It is a polyherbal formulation of brown-colored liquid of the UV spectrum in methanol is characteristic of an aromatic compound with λ max of 319 and 412 nm. IR spectrum gave peaks at 3,457, 2,922, 2,857, 2,121, 1,641, 1,055, 1,033 and 621 cm-1 indicating the presence of an alcoholic, alkyl, aldehyde or ketone, alkyne, carbonyl, anhydride and methyl group, respectively. Liquid Chromatography- High Resolution Mass Spectrometry (LC-HRMS) study gave these molecular weights (m/z): 1134. 7017, 1150.6475 and 1168.6797. Aromatic characteristics were confirmed through UV, IR, 1H-NMR, 13C-NMR and LC-HRMS spectral studies. 1H-NMR study indicates the presence of aromatic protons and methyl protons. Aqueous extract of Indus Viva I Pulse health drink was tested for Cytotoxicity Assay of human bone cancer (MG-63) cell lines and ptyalin prevent characters that exhibited a valid inhibitory value of 90.87% in 10 μg/mL for MG-63 and value of 74.41% in 500 μg/mL for alpha-amylase which is comparatively more efficient than the available standard drug. Cytotoxicity assay for human bone cancer (MG-63) cell lines and alpha-amylase both showed the inhibitory activity of IC50 68.95 and IC50 36.18 μg/mL, respectively. Conclusion: Based on the result of this research, it can be proposed that Indus Viva I Pulse health drink may serve as a potential remedy for human bone cancer (MG-63) cell line and that alpha-amylase inhibitory activity is proportional to the dose.

Spatial Distribution and Characterization of the Small-Molecule Metabolites and In Situ Hydrolyzed Oligosaccharides in the Rhizome of Glycyrrhiza uralensis by Desorption Electrospray Ionization-Mass Spectrometry Imaging and High-Resolution Liquid Chromatography-Mass Spectrometry.

Characterization and spatial distribution studies of the metabolome in plants are crucial for revealing the physiology of plants and developing functional foods. Using the rhizome of Glycyrrhiza uralensis as a case, we integrated desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) and high-resolution liquid chromatography/mass spectrometry approaches aimed at characterizing and locating both the small molecules and the macromolecular polysaccharides. Under the optimal conditions, 21 flavonoids and 12 triterpenoids were detected and characterized in different tissues of the rhizome and another 19 components were characterized exclusively by DESI-MSI. Combined with hydrophilic interaction chromatography/ion mobility-quadrupole time-of-flight mass spectrometry, eight different degrees of polymerization of oligosaccharides (after in situ acid hydrolysis) were characterized from the rhizome of G. uralensis. Majority of these metabolites are located in the cortex, phloem, and medulla, which lays the foundation for understanding the physiology of G. uralensis. The useful information can benefit the sustainable utilization and further development of Glycyrrhiza resource.

Combination of in silico prediction and convolutional neural network framework for targeted screening of metabolites from LC-HRMS fingerprints: A case study of “Pericarpium Citri Reticulatae - FructusAurantii”

In this study, a novel approach is introduced, merging in silico prediction with a Convolutional Neural Network (CNN) framework for the targeted screening of in vivo metabolites in Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) fingerprints. Initially, three predictive tools, supplemented by literature, identify potential metabolites for target prototypes derived from Traditional Chinese Medicines (TCMs) or functional foods. Subsequently, a CNN is developed to minimize false positives from CWT-based peak detection. The Extracted Ion Chromatogram (EIC) peaks are then annotated using MS-FINDER across three levels of confidence. This methodology focuses on analyzing the metabolic fingerprints of rats administered with "Pericarpium Citri Reticulatae - Fructus Aurantii" (PCR-FA). Consequently, 384 peaks in positive mode and 282 in negative mode were identified as true peaks of probable metabolites. By contrasting these with “blank serum” data, EIC peaks of adequate intensity were chosen for MS/MS fragment analysis. Ultimately, 14 prototypes (including flavonoids and lactones) and 40 metabolites were precisely linked to their corresponding EIC peaks, thereby providing deeper insight into the pharmacological mechanism. This innovative strategy markedly enhances the chemical coverage in the targeted screening of LC-HRMS metabolic fingerprints.

In vivo pharmacokinetic study of vanillic acid in monocrotaline-induced pulmonary arterial hypertension rats and its tissue distribution.

Vanillic acid (VA) is a bioactive chemical present in many food plants and fruits. It has been shown to have a protective effect on pulmonary tissues in monocrotaline-induced pulmonary arterial hypertension, as well as an intervention effect on right ventricular remodeling. The purpose of this study was to develop and test a reliable method for assessing VA utilizing ultra-performance liquid chromatography-high resolution mass spectrometry using caffeic acid as the internal standard. Across diverse substrates, the correlation coefficient for VA ranged from 0.9992 to 0.9995. The method's intraday precision was <13.53% (RSD), and its accuracy (RE) ranged from -9.88 to 4.35%. The precision across days was <13.69% (RSD), while the accuracy ranged from 2.16 to 10.94% (RE). The extraction recoveries ranged from 80.30 to 118.81%, with a lower limit of quantification of 20 ng/mL. The approach was successfully applied to pharmacokinetic and tissue distribution studies of VA in rat plasma after gavage administration, and the pharmacokinetic parameters of VA in the plasma of the monocrotaline-induced pulmonary arterial hypertension were significantly different from those of the control group.

Rapid Determination of Dapagliflozin in Rat Plasma by UHPLC-Q-Orbitrap MS and Its Application to a Pharmacokinetic Study.

Dapagliflozin (DAPA), sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is used to treat Type 2 diabetes. In this study, a highly sensitive and selective analytical method based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was established and validated for the determination of DAPA in rat plasma. The separation of DAPA and internal standard (DAPA-d5) were performed on a reversed-phase ACQUITY UPLC® BEH C18 column (100 × 3.0 mm, 1.7 µm). The mobile phase is composed of 0.1% formic acid in water (solvent A) and methanol (solvent B) in gradient elution. Under the negative ion mode, full MS/dd-MS2 was adopted to collect data via Q-Orbitrap. DAPA was effectively separated from matrix backgrounds within 10 min, and DAPA in plasma showed a good linear relationship in the range of 10-10000 µg/L. The determination coefficient (R2) was 0.9987, and the lower limit of quantification (LLOQ) was 10 µg/L. The precision and accuracy were all less than 10%, and the extraction recovery of DAPA was 86.16-96.06% from plasma. This study offered an efficient separation and quantification method for DAPA. The improved and validated method succeeded in evaluating the pharmacokinetics of DAPA in rat plasma samples after a single oral administration of 1 mg/kg.

Determination of Methylphosphonic Acid and Alkyl Methylphosphonic Acid Esters in Soils by Liquid Chromatography–High-Resolution Mass Spectrometry

Determination of Methylphosphonic Acid and Alkyl Methylphosphonic Acid Esters in Soils by Liquid Chromatography–High-Resolution Mass Spectrometry

High-Grade Gliomas from Subventricular Zone: Proteomic Drivers of Aggressiveness Using Fluorescence-Guided Multiple Sampling.

High-grade gliomas (HGGs) are among the most aggressive brain tumors and are characterized by dismally low median survival time. Of the many factors influencing the survival of patients with HGGs, proximity to the subventricular zone (SVZ) is one of the key influencers. In this context, 5-amino levulinic acid fluorescence-guided multiple sampling (FGMS) offers the prospect of understanding patient-to-patient molecular heterogeneity driving the aggressiveness of these tumors. Using high-resolution liquid chromatography-mass spectrometry (MS)/MS proteomics for HGGs from seven patients (four SVZ associated and three SVZ nonassociated), this study aimed to uncover the mechanisms driving the aggressiveness in SVZ-associated (SVZ+) HGGs. Differential proteomics analysis revealed significant dysregulation of 11 proteins, of which 9 proteins were upregulated and 2 were downregulated in SVZ+ HGGs compared to SVZ-non-associated (SVZ-) HGGs. The gene set enrichment analysis (GSEA) of the proteomics dataset revealed enrichment of MYC targets V1 and V2, G2M checkpoints, and E2F targets in SVZ+ HGGs. With GSEA, we also compared the pathways enriched in glioma stem cell subpopulations and observed a similar expression trend for most pathways in our data. In conclusion, this study reveals new and emerging insights on pathways that may potentially contribute to greater aggressiveness in SVZ+ HGGs. Future studies using FGMS in larger cohorts are recommended to help uncover the proteomics and molecular basis of aggressiveness and stemness in HGGs.

Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies.

Anorexia nervosa (AN), a severe psychiatric disorder primarily affecting adolescents and young adults, is characterized by extreme dietary restriction and distorted body image. While the psychological aspects of AN are well-documented, its intricate metabolic underpinnings remain less explored. We think that metabolomic analysis of hair samples emerges as a promising tool to unveil the complex physiological alterations in AN. This study aims to comprehensively profile amino acid concentrations in hair samples from AN patients and healthy controls. Additionally, it seeks to elucidate potential correlations between amino acid alterations and appetite dysregulation in AN, thereby shedding light on the physiological basis of this debilitating disorder. A total of 25 AN patients and 25 age-matched healthy controls were recruited for this study. Hair samples were collected, and metabolites were extracted and analyzed using high-resolution liquid chromatography-mass spectrometry. Clinical data and biochemical markers were also gathered to characterize participants' demographic and clinical profiles. Metabolomic analysis revealed significant alterations in amino acid concentrations in AN patients compared to healthy controls. Notably, deficiencies in essential amino acids (EAAs) and branched-chain amino acids (BCAAs) were observed, highlighting potential contributors to muscle wasting and appetite dysregulation. Further analysis identified specific amino acids as robust biomarkers capable of distinguishing AN patients with high sensitivity and specificity. This study unveils the complex metabolic disturbances associated with AN and underscores the role of amino acid dysregulation in the disorder's pathophysiology. The identified biomarkers hold promise for diagnostic screening and potential therapeutic interventions, opening avenues for personalized approaches in AN treatment. Ultimately, this research contributes to our understanding of chronic disorders through the lens of metabolomics and the chemosensory underpinnings of appetite regulation.

Apple extract protects against indomethacin-induced gastric ulcers in rats by suppressing oxidative stress – The implication of Nrf-2/HO-1 signaling pathway: In silico and in vivo studies

Gastric ulcers represent a worldwide health problem, characterized by erosions with different degrees in the gastrointestinal mucosa. In the current study, we explore the protective effects of the extract of apple seeds (Malus domestica, family: Rosaceae), regarded as environmental wastes, against indomethacin-induced gastric ulcers in rats. The chemical composition of the seeds extract was investigated through liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS). The metabolomics profiling resulted in identification of 17 compounds (1–17) of different chemical classes. The gene ontology analysis demonstrated that the total extract of M. domestica seeds possess an antiulcer activity through PI3K-Akt signaling pathway as the top identified signaling pathway. The present research work evidenced the reuse of apple seeds waste as an effective therapy to treat NSAIDs-induced gastric ulcer, attributed to its anti-inflammatory and antioxidant properties. It is important to note that the extract does not cause the undesirable effects of traditional antisecretory drugs.