PubMed

Environ Pollut. 2024 Nov 12:125302. doi: 10.1016/j.envpol.2024.125302. Online ahead of print.ABSTRACTData on airborne microorganisms, particularly in Southeast Asia, are more limited compared to chemical data. This study is the first to examine the community and diversity of microorganisms on PM2.5 in an urban area of Northern Thailand during both smoke haze and non-smoke haze periods of 2020. This study evaluated the composition of airborne bacteria and fungi and analyzed their association with the chemical composition of PM2.5 and meteorological variables. Significantly higher concentrations of PM2.5 and more chemical compounds were observed during the smoke haze period compared to the non-smoke haze period. Increased PM2.5 concentrations significantly altered both bacterial and fungal communities. The diversity and richness of airborne bacteria increased, whereas those of fungi decreased. The level of PM2.5 concentration (the carrier), the chemical composition of PM2.5 (the resources for survival), and the local meteorological conditions (relative humidity (RH)) were associated with the differences in bacterial and fungal populations. In addition, air originating from the west of the receptor site, influenced by both terrestrial and marine air mass routes, contributed to higher bacterial diversity and richness during the smoke haze period. In contrast, fungal diversity and richness were greater when the air came from the southwest, following a marine route. However, the primary health concern is pathogens, which were present in both periods (such as Clostridium, Aspergillus, and Cladosporium) and were especially abundant during smoke haze periods. This study highlights those airborne microorganisms, along with the particles and their chemical composition, are important components that can impact health, including that of humans, animals, and the environment.PMID:39542164 | DOI:10.1016/j.envpol.2024.125302

Lab Invest. 2024 Nov 12:102186. doi: 10.1016/j.labinv.2024.102186. Online ahead of print.ABSTRACTMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from peripheral nerves, accounting for 3-5% of soft tissue sarcomas. MPNSTs often recur locally, leading to poor survival. Achieving tumor-free surgical margins is essential to prevent recurrence, but current methods for determining tumor margins are limited, highlighting the need for improved biomarkers. In this study we investigated the degree to which MPNST extends into nerves adjacent to tumors. Alterations to the lipidome of MPNST and adjacent peripheral nerves were assessed using spatial lipidomics. Tissue samples from 5 MPNST patients were analyzed, revealing alterations of the lipid profile extending into the peripheral nerves beyond what was expected based on macroscopic and histological observations. Integration of spatial lipidomics and high-resolution accurate mass profiling identified distinct lipid profiles associated with healthy nerves, connective tissue, and tumors. Notably, histologically normal nerves exhibited myelin degradation and infiltration of pro-tumoral M2 macrophages, particularly near the tumor. Furthermore, aberrant osmium staining patterns and loss of H3K27me3 staining in absence of atypia were observed in a case with tumor recurrence. This exploratory study thereby highlights the changes occurring in the nerves affected by MPNST beyond what is visible on H&E, and provides leads for further biomarker studies, including aberrant osmium staining, to assess resection margins in MPNST.PMID:39542102 | DOI:10.1016/j.labinv.2024.102186

Bioresour Technol. 2024 Nov 12:131818. doi: 10.1016/j.biortech.2024.131818. Online ahead of print.ABSTRACTAgar production is accompanied by a large amount of wastewater, which threatens the ecological environment and wastes biomass resources. The high-value utilization of biomass resources in wastewater is one of the key factors in wastewater treatment. We investigated the conversion process and antifungal mechanism of large molecule polysaccharides in wastewater into small molecule substances with antifungal activity through anaerobic fermentation. The results indicated that anaerobic fermentation of GAW achieved inhibition rates of 91.06 % and 88.94 % against Alternaria alternata and Alternaria spp. 16S rDNA sequencing and metabolomics revealed that dominant species such as Blautia, Agathobacter and Sphingomonas converted polysaccharide into phenolic acids like procyanidin C and columbidin. These substances disrupted the integrity of fungal cells, leading to their death. The preparation of composite antifungal agents using fermentation products effectively inhibited cherry tomato spoilage and toxin production. This study provided reliable technical support for the reuse of seaweed waste resources.PMID:39542052 | DOI:10.1016/j.biortech.2024.131818

Cell Host Microbe. 2024 Nov 13;32(11):1927-1943.e9. doi: 10.1016/j.chom.2024.10.008.ABSTRACTHyperplasia of mesenteric tissues in Crohn's disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.PMID:39541945 | DOI:10.1016/j.chom.2024.10.008

Ecotoxicol Environ Saf. 2024 Nov 13;287:117325. doi: 10.1016/j.ecoenv.2024.117325. Online ahead of print.ABSTRACTStreptomycin (Str) and oxytetracycline (Otc) are widely used antibiotics to manage bacterial diseases in citrus and other crops. However, their impacts on the rhizosphere bacterial assembly and plant physiology are poorly understood. The aim of this study was to examine the effects of Str and Otc on the physiology (assimilation, transpiration rate, intracellular CO2, and stomatal conductance to water vapor), rhizosphere bacterial assemblages (16S rRNA gene high-throughput amplicon sequencing), and rhizosphere metabolite profiles in healthy Citrus reticulata trees. The results indicated a reduction in photosynthesis after Str and Otc treatments, whereas CO2 outflow stayed constant. Both antibiotics decreased the culturable numbers of bacteria. Analysis of the microbiome showed changes in relative abundance of bacterial groups, specifically Pseudomonas, Agrobacterium, and Streptomyces, in response to the antibiotics. Metabolite profiles changed in streptomycin- and oxytetracycline-treated citrus plants suggesting response to microbe targets or induction of stress responses. This study advances knowledge of antibiotic-driven effects on the rhizosphere microbiome, rhizosphere metabolome, and plant physiology, which is essential for managing plant diseases while safeguarding rhizosphere ecology and long-term plant health.PMID:39541699 | DOI:10.1016/j.ecoenv.2024.117325

Food Chem. 2024 Nov 5;465(Pt 1):141918. doi: 10.1016/j.foodchem.2024.141918. Online ahead of print.ABSTRACTQuinoa is an ancient Andean crop with a significant interest due to its nutritional and health benefits. This work provides a comprehensive metabolite profiling of five commercially available quinoa grains from diverse geographical origins. GC-MS analysis of primary metabolites identified sugars, sugar derivatives, and lipids as the predominant classes. LC-QTOF-MS/MS metabolomics and molecular networking facilitated the identification of 151 secondary metabolites, including 20 flavonoids, 14 saponins, and 20 lipids, which were reported for the first time in quinoa. In the AChE inhibition assay, USA white quinoa exhibited the highest activity. Chemometric analyses indicated that flavonoids and saponins were crucial for distinguishing quinoa grains. Notably, flavonoid glycosides and saponins were positively correlated with AChE inhibition. This study represents the first MS-based metabolomics investigation using molecular networking and chemometrics to explore the metabolome heterogeneity of commercial quinoa grains, underscoring their potential as a promising natural source for combating Alzheimer's disease.PMID:39541691 | DOI:10.1016/j.foodchem.2024.141918

Food Chem. 2024 Nov 9;465(Pt 1):141972. doi: 10.1016/j.foodchem.2024.141972. Online ahead of print.ABSTRACTExudate is the liquid released from meat during storage or processing. This study investigated the influence of exudate removal on the quality of pressed and freeze-thawed chicken meat during 36 h storage, focusing on exudate metabolites. Incorporating exudate increased lipid oxidation but only slightly affected TVB-N values in pressed and defrozen samples. This may be due to the high concentration of phospholipids and their derivatives in the exudate, which are prone to oxidation. For pressed samples, adding exudate raised total bacterial count (from 5.88 to 6.13 log cfu/g) and pH (from 6.14 to 6.17) at 36 h storage point, but no significant changes were observed in defrozen samples. While exudate removal had little effect on cooking loss and texture of cooked meat, it improved the meat's ability to maintain its structure and flavor during storage. These findings suggest removing exudate chicken meat processing can improve its quality and shelf life.PMID:39541679 | DOI:10.1016/j.foodchem.2024.141972

Blood. 2024 Nov 14:blood.2024026109. doi: 10.1182/blood.2024026109. Online ahead of print.ABSTRACTRed blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.PMID:39541586 | DOI:10.1182/blood.2024026109

Science. 2024 Nov 15;386(6723):eado8548. doi: 10.1126/science.ado8548. Epub 2024 Nov 15.ABSTRACTAdvances in genomics, proteomics, and metabolomics have revealed associations between specific microbiota species in health and disease. However, the precise mechanism(s) of action for many microbiota species and molecules have not been fully elucidated, limiting the development of microbiota-based diagnostics and therapeutics. In this Review, we highlight innovative chemical and genetic approaches that are enabling the dissection of microbiota mechanisms and providing causation in health and disease. Although specific microbiota molecules and mechanisms have begun to emerge, new approaches are still needed to go beyond phenotypic associations and translate microbiota discoveries into actionable targets and therapeutic leads to prevent and treat diseases.PMID:39541443 | DOI:10.1126/science.ado8548

J Clin Endocrinol Metab. 2024 Nov 14:dgae797. doi: 10.1210/clinem/dgae797. Online ahead of print.ABSTRACTCONTEXT AND OBJECTIVE: Identifying the risk of malignancy and genetic status in primary paraganglioma or pheochromocytoma (PPGL) is a key challenge. The aim was to assess the diagnostic accuracy of genomic, metabolomic and histopathological biomarkers for predicting metastatic and genetic status.DESIGN, SETTING, AND PATIENTS: COMETE-TACTIC is a prospective study (NCT02672020) conducted from November 2015 to March 2019 across 16 referral centers. Tumor samples and liquid biopsies from 231 consecutive patients with PPGL were collected.MAIN OUTCOME MEASURES: Germline and somatic genetic status were determined by NGS. SDHB, SDHA and CA9 immunohistochemistries were performed on tumor tissues. TERT promoter methylation was assessed by pyrosequencing. Metabolomic profile and circulating miRNAs were measured in liquid biopsies by gas chromatography MS/MS and TaqMan assay quantified by droplet digital PCR, respectively.RESULTS: Tumor analysis outperformed germline analysis for determining genetic status. Positive SDHA and SDHB staining combined with negative CA9 labeling indicated the absence of SDHx and VHL variants. Plasma succinate levels above 4.94µM identified SDHx mutation carriers with 65% sensitivity and 92% specificity (AUC-ROC 0.82, 95%CI 0.70-0.93). Among circulating miRNAs, miR-483-5p was the best classifier of metastatic status (AUC-ROC 0.64, 95%CI 0.52-0.77). A sum of dinucleotide methylation rate of TERT promoter CpGs above 42% predicted metastatic status (AUC-ROC 0.75, 95%CI 0.65-0.85). Multivariate analyses showed that biomarker combinations significantly predicted SDHx status (AUC-ROC 0.99, 95%CI 0.98-1.00) and metastatic potential (AUC-ROC 0.93, 95%CI 0.84-1).CONCLUSIONS: Circulating miR-483-5p, plasma succinate, TERT promoter methylation, and SDHB immunostaining are valuable for PPGL risk stratification. Combining biomarkers with clinical data provides excellent diagnostic accuracy for metastatic patients (AUC-ROC 0.97, 95%CI 0.93-1).PMID:39541377 | DOI:10.1210/clinem/dgae797

Inflamm Bowel Dis. 2024 Nov 14:izae238. doi: 10.1093/ibd/izae238. Online ahead of print.ABSTRACTINTRODUCTION: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.METHODS: We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls.RESULTS: Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S.DISCUSSION: Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.PMID:39541261 | DOI:10.1093/ibd/izae238

Connect Tissue Res. 2024 Nov 14:1-14. doi: 10.1080/03008207.2024.2425867. Online ahead of print.ABSTRACTPURPOSE/AIM: Metabolic disorders are risk factors for rotator cuff injuries, which suggests that the rotator cuff is sensitive to local metabolic fluctuations. However, the link between the metabolic microenvironment and pathologic features of acute tear versus chronic degeneration is currently unknown. The overarching goal of this study was to evaluate alterations in tendon metabolite profiles following acute tear or chronic degeneration of the rotator cuff. We hypothesized that injury types (acute tear vs. chronic degeneration) would result in distinct metabolite profiles relative to clinically unaffected tendon controls.MATERIALS AND METHODS: We utilized untargeted metabolomics to identify pathways that were altered at the time of rotator cuff repair (RCR; acute tear) or reverse total shoulder arthroplasty (rTSA; chronic degeneration) relative to total shoulder arthroplasty controls (TSA; tendon clinically unaffected).RESULTS: Acute tears to the rotator cuff were associated with an overall decrease in tendon metabolites. This global decrease was primarily associated with glycolic acid and decreased tricarboxylic acid (TCA) cycle activity. Conversely, chronic tendon specimens from patients undergoing rTSA showed an overall increase in metabolites. Most notably, chronic injury was associated with increased levels of multiple amino acids including alanine, aspartate, lysine, and proline.CONCLUSIONS: Overall, this study demonstrates that distinct metabolite profiles are associated with injury types, and that therapeutic strategies should address both cellular and matrix components regardless of injury induction. The specific pathways identified paired with validated, established, treatment methods may serve as novel therapeutic targets for patients who suffer from rotator cuff injuries.PMID:39540635 | DOI:10.1080/03008207.2024.2425867

J Agric Food Chem. 2024 Nov 14. doi: 10.1021/acs.jafc.4c08213. Online ahead of print.ABSTRACTSome oligopeptides can impart kokumi flavor to foods and beverages, a topic still not addressed in wine. A targeted ultra-high performance liquid-chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics method capable of quantifying both amino acids and oligopeptides in wines was therefore developed and validated, confirming the presence of 50 oligopeptides in wine, most of which had been previously unexplored. In silico screening of the affinity of these oligopeptides to interact with CaSR, the protein necessary to activate kokumi sensations, highlighted 8 dipeptides and 3 tripeptides as putative kokumi compounds. These compounds were ubiquitous in a representative set of Trentodoc classic method sparkling wines, with an average concentration of kokumi oligopeptides of 19.8 mg/L, ranging between 9.1 and 33.3 mg/L. Half of the sparkling wine samples also contained glutamic acid at concentrations equal to or greater than the threshold for the umami taste in wine, namely, 48 mg/L. Sensory tests on the dipeptide Gly-Val confirmed the ability of this novel kokumi compound to significantly modify the perception of complex real wine matrices but not of the simple model one. Preliminary laboratory-scale fermentation tests showed that the oligopeptide profile in wines is linked to the starting grape matrix and that the patterns change by fermenting barley or apple juice with the same yeast.PMID:39540612 | DOI:10.1021/acs.jafc.4c08213

Adv Sci (Weinh). 2024 Nov 14:e2404210. doi: 10.1002/advs.202404210. Online ahead of print.ABSTRACTThe utilization of urban waste for land management plays a crucial role in reshaping material flows between human activities and the environment. Sewage sludge alkaline thermal hydrolysis (ATH) produces sludge-derived plant biostimulants (SPB), which have garnered attention due to the presence of indole-3-acetic acid. However, there remains a gap in understanding SPB's molecular-level effects and its comprehensive impact on crops throughout their growth cycle. In this study, non-targeted and targeted metabolomic approaches are employed to analyze 51 plant hormones and 1,177 metabolites, revealing novel insights. The findings demonstrate that low concentrations of SPB exerted multiple beneficial effects on rice roots, leaves, and the root-soil system, facilitating rapid cell division and enhancing antioxidant defense mechanisms. These results provide a vital foundation for understanding ATH metabolic pathways and advocating for widespread SPB application, offering significant implications for sustainable land management.PMID:39540297 | DOI:10.1002/advs.202404210

Front Mol Biosci. 2024 Oct 30;11:1421330. doi: 10.3389/fmolb.2024.1421330. eCollection 2024.ABSTRACTVolatile organic compounds (VOCs) are carbon-containing molecules with high vapor pressure and low water solubility that are released from biotic and abiotic matrices. Because they are in the gaseous phase, these compounds tend to remain undetected when using conventional metabolomic profiling methods. Despite this omission, efforts to profile VOCs can provide useful information related to metabolic status and identify potential signaling pathways or toxicological impacts in natural or engineered environments. Over the past several decades mass spectrometry (MS) platform innovation has instigated new opportunities for VOC detection from previously intractable matrices. In parallel, volatilome research linking VOC profiles to other forms of multi-omic information (DNA, RNA, protein, and other metabolites) has gained prominence in resolving genotype/phenotype relationships at different levels of biological organization. This review explores both on-line and off-line methods used in VOC profiling with MS from different matrices. On-line methods involve direct sample injection into the MS platform without any prior compound separation, while off-line methods involve chromatographic separation prior to sample injection and analyte detection. Attention is given to the technical evolution of platforms needed for increasingly resolved VOC profiles, tracing technical progress over time with particular emphasis on emerging microbiome and diagnostic applications.PMID:39539739 | PMC:PMC11557394 | DOI:10.3389/fmolb.2024.1421330

Front Nutr. 2024 Oct 30;11:1434170. doi: 10.3389/fnut.2024.1434170. eCollection 2024.ABSTRACTFlavonoids possess antioxidant properties and are crucial in enhancing plant resistance to abiotic stress. Exogenous calcium has been found to regulate the biosynthesis and accumulation of secondary metabolites, including flavonoids. However, the mechanism by which exogenous calcium influences flavonoid regulation in peanut roots under salt stress remains unclear. In this study, four treatment conditions were established: no salt stress, salt stress, exogenous calcium, and a combination of salt stress and exogenous calcium. The peanut root flavonoid profile was comprehensively analyzed using both a broadly targeted metabolomic approach and an absolute quantitative flavonoid metabolome. A total of 168 flavonoids were identified in the broad-target metabolome, while 68 were quantified in the absolute quantification analysis. The findings revealed that salt stress generally increased flavonoid content in peanut roots, while co-treatment with exogenous calcium significantly reduced this accumulation. Additionally, the activities of key enzymes and the expression of genes involved in the flavonoid biosynthesis pathway were upregulated under salt stress, but downregulated following the combined treatment. This study offers valuable insights into the physiological and ecological roles of flavonoids in response to environmental stressors in economically important crops.PMID:39539375 | PMC:PMC11557398 | DOI:10.3389/fnut.2024.1434170

J Agric Food Chem. 2024 Nov 13. doi: 10.1021/acs.jafc.4c07999. Online ahead of print.ABSTRACTPeanut (Arachis hypogaea L.) is an important source of edible vegetable oils and plant proteins globally. However, the complex mechanisms regulating the oil and protein contents of peanut seeds remain unclear. Here, comparative broad-target metabolomics and quantitative lipidomics, together with transcriptome analysis, of peanut seeds at four developmental stages from the high-oil content variety "YH15" and high-protein content variety "KB008" were performed to search for oil and protein content control genes. A total of 984 differential metabolites, including 128 amino acids and derivatives and 310 differentially accumulated lipids, were identified between "YH15" and "KB008" in four seed developmental stages. The weighted gene coexpression network analysis and module-trait relationship analysis revealed that MEbrown, MEyellow, and MEturquoise modules were key contributors to the quality discrepancies observed between "YH15" and "KB008." Crucial genes potentially regulating the differences in oil and protein contents between "YH15" and "KB008" were identified within the aforementioned three modules, including genes involved in amino acid synthesis and degradation, nitrogen allocation, triglyceride synthesis and degradation, and fatty acid synthesis and degradation, as well as transcription factors. Overall, this study provides valuable insights into the molecular regulation of oil and protein contents in peanut seeds and may help cultivate specialized peanut varieties with enhanced nutritional and economic values.PMID:39539052 | DOI:10.1021/acs.jafc.4c07999

Phytochem Anal. 2024 Nov 13. doi: 10.1002/pca.3477. Online ahead of print.ABSTRACTINTRODUCTION: Fibraurea tinctoria Lour. has long been used in traditional medicine to treat diabetes mellitus (DM). However, a comprehensive scientific understanding of its potential active compounds and underlying pharmacological mechanisms still needs to be unveiled.OBJECTIVE: This study, therefore, presents a novel approach by integrating metabolomic profiling, pharmacological network, and molecular docking analysis to investigate the potential of F. tinctoria as antidiabetes mellitus.METHODS: Active compounds were obtained through analysis using ultrahigh-performance liquid chromatography-quadrupole-orbital ion trap-high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and screening of active compounds using Lipinski rule of five and ADMET parameters. Potential targets of F. tinctoria compounds and DM-related targets were retrieved from public databases, such as DisGeNET, GeneCards, OMIM, PharmaGKB, and TTD. The targets' gene ontology (GO) was created using DAVID and protein-protein interactions using STRING. The plant-organ-compound-target-disease network was constructed using Cytoscape. Then, molecular docking analysis predicted and verified the interactions of essential bioactive compounds of F. tinctoria and DM core targets.RESULTS: The network pharmacology approach identified 35 active compounds, 565 compound-related targets, and 17,289 DM-related targets. EGFR, HSP90AA1, ESR1, HSP90AB1, and GSK3B were the core targets, whereas isolariciresinol, cubebin, corypalmine, (-)-8-oxocanadine, and (+)-N-methylcoclaurine were the most active compounds of F. tinctoria with DM potential. GO functional enrichment analysis revealed 483 biological processes, 485 cellular components, and 463 molecular functions. REACTOME pathway enrichment analysis yielded 463 significantly enriched signaling pathways. Of these pathways, the cytokine signaling in the immune system pathway may play a key role in treating DM. The results of molecular docking analysis showed that the core targets of DM, such as 5gnk, 3o0i, 6psj, 5ucj, and 1q5k, bind stably to the analyzed bioactive compounds of F. tinctoria.CONCLUSIONS: This study provides significant insights into the potential mechanism of F. tinctoria in treating DM. The main active compounds of F. tinctoria were found to interact with the core targets (EGFR, HSP90AA1, ESR1, HSP90AB1, and GSK3B) through the cytokine signaling pathway in the immune system, suggesting a potential therapeutic pathway for DM. However, it is essential to note that these findings are preliminary, and further research is necessary to validate them. Those research studies could involve in vitro and in vivo studies to confirm the bioactivity of the identified compounds and their interactions with the core targets. When the findings are confirmed, they could have significant clinical implications, potentially leading to developing new therapeutic strategies for DM.PMID:39539006 | DOI:10.1002/pca.3477

BMC Res Notes. 2024 Nov 13;17(1):337. doi: 10.1186/s13104-024-06996-1.ABSTRACTOBJECTIVES: The primary metabolite contents of ripe fruits result from complex regulations during their development. For Solanaceae, these regulations have been widely studied in tomato. The fruit metabolite contents of other fruit species, such as pepper (Capsicum annuum L.) and eggplant (Solanum melongena L.), constitute a valuable resource for the community to study the regulation of fruit metabolism and identify common or species-dependent regulations. This dataset about major polar metabolites is part of a larger project that integrates other omics data for pepper and eggplant, and other fruit species for metabolomics and other omics.DATA DESCRIPTION: We provide quantitative metabolite data of pepper and eggplant fruit along development. We sampled pepper and eggplant fruit cultivated in a tunnel or a greenhouse at 10 or 11 stages from anthesis to ripe fruit. We used proton nuclear magnetic resonance (1H-NMR) metabolomic profiling of polar extracts to quantify the major metabolites and expressed the data in µmol per g fresh weight. Twenty-four metabolites were determined in pepper and 27 in eggplant. Nineteen common metabolites were quantified in both fruit species including three soluble sugars and one sugar-alcohol, five organic acids and nine free amino acids. These data can be combined with similar quantitative data on other species or complemented with other omics data to perform cross-species or cross-omics comparisons.PMID:39538352 | DOI:10.1186/s13104-024-06996-1

J Neuroinflammation. 2024 Nov 14;21(1):294. doi: 10.1186/s12974-024-03280-8.ABSTRACTBACKGROUND: Research on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential.METHODS: In the current study, an untargeted metabolomics approach was used to reveal brain metabolism changes in rats 24 h after a controlled cortical impact (CCI) injury, with or without EP treatment. Using principal component analysis (PCA), volcano plots, Random Forest and pathway analysis we differentiated the brain metabolomes of CCI and sham injured animals treated with saline (Veh) or EP, identifying key metabolites and pathways affected by injury. Additionally, the effect of EP on the non-injured brain was also explored.RESULTS: PCA showed a clear separation of the four study groups (sham-Veh, CCI-Veh, sham-EP, CCI-EP) based on injury. Following CCI injury (CCI-Veh), 109 metabolites belonging to the amino acid, carbohydrate, lipid, nucleotide, and xenobiotic families exhibited a twofold change at 24 h compared to the sham-Veh group, with 93 of these significantly increasing and 16 significantly decreasing (p < 0.05). CCI animals were treated with EP (CCI-EP) showed only 5 metabolites in the carbohydrate, amino acids, peptides, nucleotides, lipids, and xenobiotics super families that exhibited a twofold change, compared to the CCI-Veh group (p < 0.05). In the non-injured brain, EP treatment (sham-EP) resulted in a twofold change in 6 metabolites within the amino acid, peptide, nucleotide, and lipid super families compared to saline treated sham animals (sham-Veh, p < 0.05).CONCLUSIONS: This study delineates the unique metabolic signatures resulting from a CCI injury and those related to EP treatment in both the injured and non-injured brain, underscoring the metabolic adaptations to brain injury and the effects of EP. Our analysis uncovers significant shifts in metabolites associated with inflammation, energy metabolism, and neuroprotection after injury, and demonstrates how EP intervention after injury alters metabolites associated with mitigating inflammation and oxidative damage.PMID:39538295 | DOI:10.1186/s12974-024-03280-8