PubMed

Genes Immun. 2024 Feb 20. doi: 10.1038/s41435-024-00259-6. Online ahead of print.NO ABSTRACTPMID:38378863 | DOI:10.1038/s41435-024-00259-6

Clin Chim Acta. 2024 Feb 18:117831. doi: 10.1016/j.cca.2024.117831. Online ahead of print.ABSTRACTBACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC.METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP).RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis.CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.PMID:38378104 | DOI:10.1016/j.cca.2024.117831

Cell Rep Med. 2024 Feb 10:101429. doi: 10.1016/j.xcrm.2024.101429. Online ahead of print.ABSTRACTObesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.PMID:38378003 | DOI:10.1016/j.xcrm.2024.101429

Mar Environ Res. 2024 Feb 6;196:106398. doi: 10.1016/j.marenvres.2024.106398. Online ahead of print.ABSTRACTNH3-N and NO2-N always co-exist in the aquatic environment, but there is not a clear opinion on their joint toxicities to the molluscs. Presently, clams Ruditapes philippinarum were challenged by environmental concentrations of NH3-N and NO2-N, singly or in combination, and analyzed by metabolomics approaches, enzyme assays and transmission electron microscope (TEM) observation. Results showed that some same KEGG pathways with different enriched-metabolites were detected in the three exposed groups within one day, and completely different profiles of metabolites were found in the rest of the exposure period. The combined exposure induced heavier and more lasting toxicities to the clams compared with their single exposure. ACP activity and the number of secondary lysosomes were significantly increased after the combined exposure. The present study shed light on the joint-toxicity mechanism of NH3-N and NO2-N, and provided fundamental data for the toxicity research on inorganic nitrogen.PMID:38377938 | DOI:10.1016/j.marenvres.2024.106398

Poult Sci. 2024 Feb 1;103(4):103524. doi: 10.1016/j.psj.2024.103524. Online ahead of print.ABSTRACTThe objective of this study was to investigate the effects of sex on meat quality and the composition of amino and fatty acids in the breast muscles of White King pigeon squabs. Untargeted metabolomics was also conducted to distinguish the metabolic composition of plasma in different sexes. Compared with male squabs, female squabs had greater intramuscular fat (IMF) deposition and lower myofiber diameter and hydroxyproline content, leading to a lower shear force. Female squabs also had higher monounsaturated fatty acid and lower n-6 and n-3 polyunsaturated fatty acid proportions in the breast muscle, and had greater lipogenesis capacity via upregulation of PPARγ, FAS and LPL gene expression. Moreover, female squabs had lower inosine 5'-monophosphate, essential, free and sweet-tasting amino acid contents. Furthermore, Spearman's correlations between the differential plasma metabolites and key meat parameters were assessed, and putrescine, N-acetylglutamic acid, phophatidylcholine (18:0/P-16:0) and trimethylamine N-oxide were found to contribute to meat quality. In summary, the breast meat of male squabs may have better nutritional value than that of females, but it may inferior in terms of sensory properties, which can be attributed to the lower IMF content and higher shear force value. Our findings enhance our understanding of sex variation in squab meat quality, providing a basis for future research on pigeon breeding.PMID:38377688 | DOI:10.1016/j.psj.2024.103524

ACS Chem Neurosci. 2024 Feb 20. doi: 10.1021/acschemneuro.3c00494. Online ahead of print.ABSTRACTGlutamate carboxypeptidase II (GCPII, also known as PSMA or FOLH1) is responsible for the cleavage of N-acetyl-aspartyl-glutamate (NAAG) to N-acetyl-aspartate and glutamate in the central nervous system and facilitates the intestinal absorption of folate by processing dietary folyl-poly-γ-glutamate in the small intestine. The physiological function of GCPII in other organs like kidneys is still not known. GCPII inhibitors are neuroprotective in various conditions (e.g., ischemic brain injury) in vivo; however, their utilization as potential drug candidates has not been investigated in regard to not yet known GCPII activities. To explore the GCPII role and possible side effects of GCPII inhibitors, we performed parallel metabolomic and lipidomic analysis of the cerebrospinal fluid (CSF), urine, plasma, and brain tissue of mice with varying degrees of GCPII deficiency (fully deficient in Folh1, -/-; one allele deficient in Folh1, +/-; and wild type, +/+). Multivariate analysis of metabolites showed no significant differences between wild-type and GCPII-deficient mice (except for NAAG), although changes were observed between the sex and age. NAAG levels were statistically significantly increased in the CSF, urine, and plasma of GCPII-deficient mice. However, no difference in NAAG concentrations was found in the whole brain lysate likely because GCPII, as an extracellular enzyme, can affect only extracellular and not intracellular NAAG concentrations. Regarding the lipidome, the most pronounced genotype-linked changes were found in the brain tissue. In brains of GCPII-deficient mice, we observed statistically significant enrichment in phosphatidylcholine-based lipids and reduction of sphingolipids and phosphatidylethanolamine plasmalogens. We hypothesize that the alteration of the NAA-NAAG axis by absent GCPII activity affected myelin composition. In summary, the absence of GCPII and thus similarly its inhibition do not have detrimental effects on metabolism, with just minor changes in the brain lipidome.PMID:38377674 | DOI:10.1021/acschemneuro.3c00494

Front Endocrinol (Lausanne). 2024 Feb 5;15:1322563. doi: 10.3389/fendo.2024.1322563. eCollection 2024.ABSTRACTBACKGROUND/PURPOSE: Metabolic-associated fatty liver disease (MAFLD) is a major cause of chronic liver disease worldwide and is generally thought to be closely related to obesity and diabetes. However, it also affects non-obese individuals, particularly in Asian cultures.METHODS: Healthy physical examination subjects and MAFLD patients were included in the endocrinology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine. MAFLD was defined as fatty liver in imaging without virus infection, drug, alcohol, or other known causes of chronic liver disease. Non-obese MAFLD was defined as MAFLD in non-obese subjects (BMI<25 kg/m2).RESULTS: The final analysis comprised 1047 participants in total. Of 946 MAFLD patients, 162 (17.12%) were diagnosed with non-obese MAFLD. Non-obese MAFLD patients were older, had lower alanine aminotransferase (ALT), triglyceride, and waist circumference, but had higher high density lipoprotein cholesterol (HDL-c) than obese MAFLD patients. Compared with non-obese healthy controls, non-obese MAFLD patients had higher BMI, ALT, gamma-glutamyl transferase (GGT), uric acid (UA), triglycerides (TG), and low density lipoprotein cholesterol (LDL-c). In terms of body composition, body fat mass (BFM), waist-hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), and fat mass index (FMI) were lower in non-obese healthy controls than non-obese MAFLD patients. A binary logistic regression analysis revealed that non-obese MAFLD was linked with lower GGT and higher HDL-c.CONCLUSION: In this study cohort, non-obese MAFLD was present at a prevalence of 13.90%. In contrast to non-obese healthy controls, non-obese MAFLD patients exhibited different metabolic profiles, but they also had different body compositions.PMID:38375190 | PMC:PMC10876088 | DOI:10.3389/fendo.2024.1322563

Anal Chem. 2024 Feb 20. doi: 10.1021/acs.analchem.3c05002. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) is a high-throughput imaging technique capable of the qualitative and quantitative in situ detection of thousands of ions in biological samples. Ion image representation is a technique that produces a low-dimensional vector embedded with significant spectral and spatial information on an ion image, which further facilitates the distance-based similarity measurement for the identification of colocalized ions. However, given the low signal-to-noise ratios inherent in MSI data coupled with the scarcity of annotated data sets, achieving an effective ion image representation for each ion image remains a challenge. In this study, we propose DeepION, a novel deep learning-based method designed specifically for ion image representation, which is applied to the identification of colocalized ions and isotope ions. In DeepION, contrastive learning is introduced to ensure that the model can generate the ion image representation in a self-supervised manner without manual annotation. Since data augmentation is a crucial step in contrastive learning, a unique data augmentation strategy is designed by considering the characteristics of MSI data, such as the Poisson distribution of ion abundance and a random pattern of missing values, to generate plentiful ion image pairs for DeepION model training. Experimental results of rat brain tissue MSI show that DeepION outperforms other methods for both colocalized ion and isotope ion identification, demonstrating the effectiveness of ion image representation. The proposed model could serve as a crucial tool in the biomarker discovery and drug development of the MSI technique.PMID:38377545 | DOI:10.1021/acs.analchem.3c05002

Plant Physiol. 2024 Feb 20:kiae077. doi: 10.1093/plphys/kiae077. Online ahead of print.ABSTRACTAs a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 towards C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis towards C4 photosynthesis remains elusive. Here, we provide evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increased in the C3-C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increases the concentrations of C4 related metabolites in C3-C4 and C4 species but not the activity of C4 related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3-C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitated the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanism. All these results provide insight into the mechanistic switch from C3-C4 intermediate to C4 photosynthesis.PMID:38377473 | DOI:10.1093/plphys/kiae077

Plant Physiol. 2024 Feb 20:kiae083. doi: 10.1093/plphys/kiae083. Online ahead of print.ABSTRACTCarbon-flow-regulator A (CfrA) adapts carbon flux to nitrogen conditions in non-diazotrophic cyanobacteria. Under nitrogen deficiency, CfrA leads to the storage of excess carbon, which cannot combine with nitrogen, mainly as glycogen. cfrA overexpression from the arsenite-inducible, nitrogen-independent ParsB promoter allows analysis of the metabolic effects of CfrA accumulation. Considering that the main consequence of cfrA overexpression is glycogen accumulation, we examined carbon distribution in response to cfrA expression in Synechocystis sp. PCC 6803 strains impaired in synthesizing this polymer. We carried out a comparative phenotypic analysis to evaluate cfrA overexpression in the wild-type strain and in a mutant of ADP-glucose pyrophosphorylase (ΔglgC), which is unable to synthesize glycogen. The accumulation of CfrA in the wild-type background caused a photosynthetic readjustment although growth was not affected. However, in a ΔglgC strain, growth decreased depending on CfrA accumulation and photosynthesis was severely affected. An elemental analysis of the H, C, and N content of cells revealed that cfrA expression in the wildtype caused an increase in the C/N ratio, due to decreased nitrogen assimilation. Metabolomic study indicated that these cells store sucrose and glycosylglycerol, in addition to the previously described glycogen accumulation. However, cells deficient in glycogen synthesis accumulated large amounts of Calvin-Benson cycle intermediates as cfrA was expressed. These cells also showed increased levels of some amino acids, mainly alanine, serine, valine, isoleucine and leucine. The findings suggest that by controlling cfrA expression, in different conditions and strains, we could change the distribution of fixed carbon, with potential biotechnological benefits.PMID:38377468 | DOI:10.1093/plphys/kiae083

Hepatology. 2024 Feb 20. doi: 10.1097/HEP.0000000000000777. Online ahead of print.ABSTRACTBACKGROUND: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in AH patients.METHODS: The study included 74 controls without alcohol use disorder (AUD), 97 patients with AUD and 330 AH patients from two different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours.RESULTS: Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p<0.001) and patients with AUD (1.59 vs. 0.93, p<0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity<2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity<2.09 group.CONCLUSION: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.PMID:38377466 | DOI:10.1097/HEP.0000000000000777

Hepatology. 2024 Feb 20. doi: 10.1097/HEP.0000000000000784. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Lymph node metastasis is a significant risk factor for cholangiocarcinoma patients, but the mechanisms underlying cholangiocarcinoma colonization in the lymph node microenvironment remain unclear. We aimed to determine whether metabolic reprogramming fueled the adaptation and remodeling of cholangiocarcinoma cells to the lymph node microenvironment.APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) of primary tumor lesions and paired lymph node metastases from cholangiocarcinoma patients and revealed significantly reduced inter-tumor heterogeneity and syntropic lipid metabolic reprogramming of cholangiocarcinoma after metastasis to lymph nodes, which was verified by pan-cancer scRNA-seq analysis, highlighting the essential role of lipid metabolism in tumor colonization in lymph nodes. Metabolomics and in vivo CRISPR/Cas9 screening identified PPARγ as a crucial regulator in fueling cholangiocarcinoma colonization in lymph node through the oleic acid-PPARγ-FABP4 positive feedback loop by up-regulating fatty acid uptake and oxidation. Patient-derived organoids and animal models have demonstrated that blocking this loop impairs cholangiocarcinoma proliferation and colonization in the lymph node microenvironment and is superior to systemic inhibition of fatty acid oxidation. PPARγ-regulated fatty acid metabolic reprogramming in cholangiocarcinoma also contributes to the immune-suppressive niche in lymph node metastases by producing kynurenine, and was found to be associated with tumor relapse, immune-suppressive lymph node microenvironment, and poor immune checkpoint blockade response.CONCLUSIONS: Our results reveal the role of the oleic acid-PPARγ-FABP4 loop in fueling cholangiocarcinoma colonization in lymph nodes, and demonstrate that PPARγ-regulated lipid metabolic reprogramming is a promising therapeutic target for relieving cholangiocarcinoma lymph node metastasis burden and reducing further progression.PMID:38377465 | DOI:10.1097/HEP.0000000000000784

Bioinformatics. 2024 Feb 20:btae098. doi: 10.1093/bioinformatics/btae098. Online ahead of print.ABSTRACTMOTIVATION: Missing values are commonly observed in metabolomics data from mass spectrometry (MS). Imputing them is crucial because it assures data completeness, increases the statistical power of analyses, prevents inaccurate results, and improves the quality of exploratory analysis, statistical modeling, and machine learning. Numerous Missing Value Imputation Algorithms (MVIAs) employ heuristics or statistical models to replace missing information with estimates. In the context of metabolomics data, we identified 52 MVIAs implemented across 70 R functions. Nevertheless, the usage of those 52 established methods poses challenges due to package dependency issues, lack of documentation and their instability.RESULTS: Our R package, imputomics, provides a convenient wrapper around 41 (plus random imputation as a baseline model) out of 52 MVIAs in the form of a command-line tool and a web application. In addition, we propose a novel functionality for selecting MVIAs recommended for metabolomics data with the best performance or execution time.AVAILABILITY: imputomics is freely available as an R package (github.com/BioGenies/imputomics) and a Shiny web application (biogenies.info/imputomics-ws). The documentation is available at biogenies.info/imputomics.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:38377398 | DOI:10.1093/bioinformatics/btae098

Mol Cancer Ther. 2024 Feb 20. doi: 10.1158/1535-7163.MCT-23-0550. Online ahead of print.ABSTRACTOne-carbon (C1) metabolism is compartmentalized between the cytosol and mitochondria with the mitochondrial C1 pathway as the major source of glycine and C1 units for cellular biosynthesis. Expression of mitochondrial C1 genes including SLC25A32, serine hydroxymethyl transferase (SHMT) 2, 5,10-methylene tetrahydrofolate dehydrogenase 2, and 5,10-methylene tetrahydrofolate dehydrogenase 1-like was significantly elevated in primary epithelial ovarian cancer (EOC) specimens compared to normal ovaries. 5-Substituted pyrrolo[3,2-d]pyrimidine antifolates (AGF347, AGF359, AGF362) inhibited proliferation of cisplatin sensitive (A2780, CaOV3, IGROV1) and resistant (A2780-E80, SKOV3) EOC cells. In SKOV3 and A2780-E80 cells, colony formation was inhibited. AGF347 induced apoptosis in SKOV3 cells. In IGROV1 cells, AGF347 was transported by folate receptor (FR) α. AGF347 was also transported into IGROV1 and SKOV3 cells by the proton-coupled folate transporter (SLC46A1) and the reduced folate carrier (SLC19A1). AGF347 accumulated to high levels in the cytosol and mitochondria of SKOV3 cells. By targeted metabolomics with [2,3,3-2H]L-serine, AGF347, AGF359 and AGF362 inhibited SHMT2 in the mitochondria. In the cytosol, SHMT1 and de novo purine biosynthesis (i.e., glycinamide ribonucleotide formyltransferase, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) were targeted; AGF359 also inhibited thymidylate synthase. Antifolate treatments of SKOV3 cells depleted cellular glycine, mitochondrial NADH and glutathione, and showed synergistic in vitro inhibition toward SKOV3 and A2780-E80 cells when combined with cisplatin. In vivo studies with subcutaneous SKOV3 EOC xenografts in SCID mice confirmed significant antitumor efficacy of AGF347. Collectively, our studies demonstrate a unique metabolic vulnerability in EOC involving mitochondrial and cytosolic C1 metabolism that offers a promising new platform for therapy.PMID:38377173 | DOI:10.1158/1535-7163.MCT-23-0550

Appl Environ Microbiol. 2024 Feb 20:e0193623. doi: 10.1128/aem.01936-23. Online ahead of print.ABSTRACTIn the context of sustainable diet, the development of soy-based yogurt fermented with lactic acid bacteria is an attractive alternative to dairy yogurts. To decipher the metabolism of Lactobacillus delbrueckii subsp. delbrueckii during soy juice (SJ) fermentation, the whole genome of the strain CIRM-BIA865 (Ld865) was sequenced and annotated. Then Ld865 was used to ferment SJ. Samples were analyzed throughout fermentation for their cell number, carbohydrate, organic acid, free amino acid, and volatile compound contents. Despite acidification, the number of Ld865 cells did not rise, and microscopic observations revealed the elongation of cells from 3.6 µm (inoculation) to 36.9 µm (end of fermentation). This elongation was observed in SJ but not in laboratory-rich medium MRS. Using transcriptomic analysis, we showed that the biosynthesis genes of peptidoglycan and membrane lipids were stably expressed, in line with the cell elongation observed, whereas no genes implicated in cell division were upregulated. Among the main sugars available in SJ (sucrose, raffinose, and stachyose), Ld865 only used sucrose. The transcriptomic analysis showed that Ld865 implemented the two transport systems that it contains to import sucrose: a PTS system and an ABC transporter. To fulfill its nitrogen needs, Ld865 probably first consumed the free amino acids of the SJ and then implemented different oligopeptide transporters and proteolytic/peptidase enzymes. In conclusion, this study showed that Ld865 enables fast acidification of SJ, despite the absence of cell division, leads to a product rich in free amino acids, and also leads to the production of aromatic compounds of interest.IMPORTANCETo reduce the environmental and health concerns related to food, an alternative diet is recommended, containing 50% of plant-based proteins. Soy juice, which is protein rich, is a relevant alternative to animal milk, for the production of yogurt-like products. However, soy "beany" and "green" off-flavors limit the consumption of such products. The lactic acid bacteria (LAB) used for fermentation can help to improve the organoleptic properties of soy products. But metabolic data concerning LAB adapted to soy juice are lacking. The aim of this study was, thus, to decipher the metabolism of Lactobacillus delbrueckii subsp. delbrueckii during fermentation of a soy juice, based on a multidisciplinary approach. This result will contribute to give tracks for a relevant selection of starter. Indeed, the improvement of the organoleptic properties of these types of products could help to promote plant-based proteins in our diet.PMID:38376234 | DOI:10.1128/aem.01936-23

Food Funct. 2024 Feb 20. doi: 10.1039/d3fo04761j. Online ahead of print.ABSTRACTHyperglycemia has become a global health problem due to changes in diet and lifestyle. Most importantly, persistent hyperglycemia can eventually develop into type II diabetes. While the usage of current drugs is limited by their side effects, stilbenes derived from fruits and herbal/dietary plants are considered as important phytochemicals with potential hypoglycemic properties. Herein, the most common stilbenoids in consumed foods, i.e. resveratrol, pterostilbene, piceatannol, oxyresveratrol, and 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucopyranoside (THSG), are reviewed in this paper. These stilbenes are found to regulate glucose homeostasis via (a) modulation of feeding behaviour and nutrition absorption; (b) restoration of insulin signalling by enhancing insulin production/insulin sensitivity; (c) improvement of gut permeability, gut microbial profile and resulting metabolomes; and (d) amelioration of circadian rhythm disruption. In this review, we have summarized the underlying mechanisms for the hypoglycemic effects of the five most common dietary stilbenoids listed above, providing a comprehensive framework for future study and applications.PMID:38376230 | DOI:10.1039/d3fo04761j

Oral Dis. 2024 Feb 20. doi: 10.1111/odi.14895. Online ahead of print.ABSTRACTBACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy affecting the head and neck region. The prognosis for OSCC patients remains unfavorable due to the absence of precise and efficient early diagnostic techniques. Metabolomics offers a promising approach for identifying distinct metabolites, thereby facilitating early detection and treatment of OSCC.OBJECTIVE: This review aims to provide a comprehensive overview of recent advancements in metabolic marker identification for early OSCC diagnosis. Additionally, the clinical significance and potential applications of metabolic markers for the management of OSCC are discussed.RESULTS: This review summarizes metabolic changes during the occurrence and development of oral squamous cell carcinoma and reviews prospects for the clinical application of characteristic, differential metabolites in saliva, serum, and OSCC tissue. In this review, the application of metabolomic technology in OSCC research was summarized, and future research directions were proposed.CONCLUSION: Metabolomics, detection technology that is the closest to phenotype, can efficiently identify differential metabolites. Combined with statistical data analyses and artificial intelligence technology, it can rapidly screen characteristic biomarkers for early diagnosis, treatment, and prognosis evaluations.PMID:38376209 | DOI:10.1111/odi.14895

Antimicrob Agents Chemother. 2024 Feb 20:e0108123. doi: 10.1128/aac.01081-23. Online ahead of print.ABSTRACTExtracellular bacterial metabolites have potential as markers of bacterial growth and resistance emergence but have not been evaluated in dynamic in vitro studies. We investigated the dynamic metabolomic footprint of a multidrug-resistant hypermutable Pseudomonas aeruginosa isolate exposed to ceftolozane/tazobactam as continuous infusion (4.5 g/day, 9 g/day) in a hollow-fiber infection model over 7-9 days in biological replicates (n = 5). Bacterial samples were collected at 0, 7, 23, 47, 71, 95, 143, 167, 191, and 215 h, the supernatant quenched, and extracellular metabolites extracted. Metabolites were analyzed via untargeted metabolomics, including hierarchical clustering and correlation with quantified total and resistant bacterial populations. The time-courses of five (of 1,921 detected) metabolites from enriched pathways were mathematically modeled. Absorbed L-arginine and secreted L-ornithine were highly correlated with the total bacterial population (r -0.79 and 0.82, respectively, P<0.0001). Ribose-5-phosphate, sedoheptulose-7-phosphate, and trehalose-6-phosphate correlated with the resistant subpopulation (0.64, 0.64, and 0.67, respectively, P<0.0001) and were likely secreted due to resistant growth overcoming oxidative and osmotic stress induced by ceftolozane/tazobactam. Using pharmacokinetic/pharmacodynamic-based transduction models, these metabolites were successfully modeled based on the total or resistant bacterial populations. The models well described the abundance of each metabolite across the differing time-course profiles of biological replicates, based on bacterial killing and, importantly, resistant regrowth. These proof-of-concept studies suggest that further exploration is warranted to determine the generalizability of these findings. The metabolites modeled here are not exclusive to bacteria. Future studies may use this approach to identify bacteria-specific metabolites correlating with resistance, which would ultimately be extremely useful for clinical translation.PMID:38376189 | DOI:10.1128/aac.01081-23

J Agric Food Chem. 2024 Feb 20. doi: 10.1021/acs.jafc.3c07736. Online ahead of print.ABSTRACTTheobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.PMID:38376143 | DOI:10.1021/acs.jafc.3c07736

Endocrinology. 2024 Feb 20:bqae023. doi: 10.1210/endocr/bqae023. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility and poor reproductive outcomes. The follicular fluid (FF) microenvironment plays a crucial role in oocyte development. This review summarizes evidence elucidating the alterations in FF composition in PCOS. Various studies demonstrated a pronounced proinflammatory milieu in PCOS FF, characterized by increased levels of cytokines, including but not limited to IL-6, TNF-α, CRP, and IL-1β, concomitant with a reduction in anti-inflammatory IL-10. T lymphocytes and antigen presenting cells are dysregulated in PCOS FF. PCOS FF exhibited heightened reactive oxygen species (ROS) production and the accumulation of lipid peroxidation byproducts, and impaired antioxidant defenses. Multiple miRNAs are dysregulated in PCOS FF, disrupting signaling critical to granulosa cell function. Proteomic analysis reveals changes in pathways related to immune responses, metabolic perturbations, angiogenesis, and hormone regulation. Metabolomics identify disturbances in glucose metabolism, amino acids, lipid profiles, and steroid levels with PCOS FF. Collectively, these pathological alterations may adversely impact oocyte quality, embryo development, and fertility outcomes. Further research on larger cohorts is needed to validate these findings and to forge the development of prognostic biomarkers of oocyte developmental competence within FF. Characterizing the follicular environment in PCOS is key to elucidate the mechanisms underlying subfertility in this challenging disorder.PMID:38375912 | DOI:10.1210/endocr/bqae023