PubMed

bioRxiv [Preprint]. 2024 Dec 14:2024.12.06.627264. doi: 10.1101/2024.12.06.627264.ABSTRACTMetabolic reprogramming is a hallmark of cancer, enabling tumor cells to adapt to and exploit their microenvironment for sustained growth. The liver is a common site of metastasis, but the interactions between tumor cells and hepatocytes remain poorly understood. In the context of liver metastasis, these interactions play a crucial role in promoting tumor survival and progression. This study leverages multiomics coverage of the microenvironment via liquid chromatography and high-resolution, high-mass accuracy mass spectrometry-based untargeted metabolomics, 13 C-stable isotope tracing, and RNA sequencing to uncover the metabolic impact of co-localized primary hepatocytes and a colon adenocarcinoma cell line, SW480, using a 2D co-culture model. Metabolic profiling revealed disrupted Warburg metabolism with an 80% decrease in glucose consumption and 94% decrease in lactate production by hepatocyte-SW480 co-cultures relative to SW480 control cultures. Decreased glucose consumption was coupled with alterations in glutamine and ketone body metabolism, suggesting a possible fuel switch upon co-culturing. Further, integrated multiomic analysis indicates that disruptions in metabolic pathways, including nucleoside biosynthesis, amino acids, and TCA cycle, correlate with altered SW480 transcriptional profiles and highlight the importance of redox homeostasis in tumor adaptation. Finally, these findings were replicated in 3-dimensional microtissue organoids. Taken together, these studies support a bioinformatic approach to study metabolic crosstalk and discovery of potential therapeutic targets in preclinical models of the tumor microenvironment.PMID:39713297 | PMC:PMC11661097 | DOI:10.1101/2024.12.06.627264

ADMET DMPK. 2024 Dec 8;12(6):957-970. doi: 10.5599/admet.2476. eCollection 2024.ABSTRACTBACKGROUND AND PURPOSE: Glyphosate-based herbicides, extensively utilized worldwide, raise concerns regarding potential human risks due to the detection of glyphosate (GLY) in human body fluids. This study aims to address critical knowledge gaps regarding whether GLY undergoes metabolism in humans, particularly considering the limited information available on human metabolism.EXPERIMENTAL APPROACH: The study investigated GLY and its metabolites in eight amenity horticultural workers using proton nuclear magnetic resonance (1H-NMR) data analysis. Multiple spot urine samples were collected before and after herbicide applications.KEY RESULTS: Findings reveal the presence of GLY and its metabolites (AMPA, formaldehyde, sarcosine, glyoxylic acid, and methylamine). Results demonstrate a moderate correlation between median GLY concentration and its metabolites within the studied population.CONCLUSION: Persuasive evidence suggests the potential metabolism of GLY in humans. 1H-NMR data analysis might be a promising technique for determining the metabolism of GLY in humans, offering valuable insights into urinary excretion patterns.PMID:39713254 | PMC:PMC11661807 | DOI:10.5599/admet.2476

Food Chem X. 2024 May 31;23:101525. doi: 10.1016/j.fochx.2024.101525. eCollection 2024 Oct 30.ABSTRACTIn this study, three fermentation treatments of spontaneous fermentation (SF), direct inoculation of CECA (YF), and inoculation with CECA after addition of dimethyl dicarbonate (YDF) were carried out. Multivariate statistical analysis approved that CECA inoculation significantly influenced the composition of 141 metabolites (15 volatile organic compounds (VOCs) and 126 non-VOCs), mainly consisting of 36 acids and derivatives and 25 lipids and lipid-like molecules. YF and YDF wines exhibited similar correlations with aroma types, while there were differences in the kinds and number of VOCs. Moreover, CECA-inoculated fermentation was more favorable to the formation of aftertaste-A, umami, sourness, and richness. The KEGG metabolic pathway analysis indicated that the inoculation strategy significantly affected the amino acid metabolism. The antimicrobial treatment effectively enhanced bitterness, astringency, umami and saltiness while reducing acidity. Further studies are needed to assess the effects of antimicrobial treatment on lipid metabolism.PMID:39713187 | PMC:PMC11662240 | DOI:10.1016/j.fochx.2024.101525

World J Gastroenterol. 2024 Dec 21;30(47):5076-5080. doi: 10.3748/wjg.v30.i47.5076.ABSTRACTIn this manuscript, we comment on the article by Liu et al published in the recent issue of the journal. Hyperuricemia (HUA) has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout. This discussion focuses on the targets and clinical application value of traditional Chinese medicine (TCM) extracts in the treatment of HUA and gout, emphasizing the role of gut microbiota. Liu et al's study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms, including inhibition of uric acid (UA) reabsorption, promotion of UA excretion, repair of intestinal barrier function, and regulation of gut microbiota and metabolome. Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat, which have clear and single targets, many TCMs have multi-target effects. However, the active components and mechanisms of TCMs are not fully understood, limiting their clinical application in the treatment of HUA and gout. Additionally, the role of gut microbiota in UA metabolic homeostasis needs to be further explored.PMID:39713159 | PMC:PMC11612855 | DOI:10.3748/wjg.v30.i47.5076

Front Bioeng Biotechnol. 2024 Dec 6;12:1493766. doi: 10.3389/fbioe.2024.1493766. eCollection 2024.ABSTRACTIn this study, a strain isolated from the surface of flue-cured tobacco leaves, identified as Bacillus velezensis HJ-16, was applied in the solid-state fermentation of tobacco leaves. This strain, known for producing thermally stable enzymes, including amylase, cellulase, and protease, significantly improved the sensory qualities of tobacco, enhancing aromatic intensity, density, and softness, while reducing irritation. Whole-genome sequencing and functional annotation revealed that B. velezensis HJ-16 possesses a single circular chromosome containing genes associated with enzyme production and metabolic activities, particularly in carbohydrate metabolism and amino acid metabolism. Untargeted metabolomics analysis identified significant changes in non-volatile metabolites induced by fermentation. These metabolites were enriched in pathways related to flavonoid biosynthesis, alkaloid biosynthesis, aromatic amino acid metabolism, lipid metabolism, and carbon metabolism. Metagenomic analysis showed that Bacillus became the dominant genus on the tobacco leaf surface following inoculation with B. velezensis HJ-16, altering the microbial community composition, reducing diversity and evenness, and enhancing microbial metabolic activity. These findings underscore the potential of B. velezensis HJ-16 as a biotechnological tool to improve tobacco leaf quality.PMID:39713101 | PMC:PMC11659759 | DOI:10.3389/fbioe.2024.1493766

ACS Meas Sci Au. 2024 Oct 21;4(6):668-677. doi: 10.1021/acsmeasuresciau.4c00035. eCollection 2024 Dec 18.ABSTRACTAmbient mass spectrometry (MS) technologies have been applied to spatial metabolomic profiling of various samples in an attempt to both increase analysis speed and reduce the length of sample preparation. Recent studies, however, have focused on improving the spatial resolution of ambient approaches. Finer resolution requires greater analysis times and commensurate computing power for more sophisticated data analysis algorithms and larger data sets. Higher resolution provides a more detailed molecular picture of the sample; however, for some applications, this is not required. A liquid microjunction surface sampling probe (LMJ-SSP) based MS platform combined with unsupervised multivariant analysis based hyperspectral visualization is demonstrated for the metabolomic analysis of marine bacteria from the genus Pseudoalteromonas to create a rapid and robust spatial profiling workflow for microbial natural product screening. In our study, metabolomic profiles of different Pseudoalteromonas species are quickly acquired without any sample preparation and distinguished by unsupervised multivariant analysis. Our robust platform is capable of automated direct sampling of microbes cultured on agar without clogging. Hyperspectral visualization-based rapid spatial profiling provides adequate spatial metabolite information on microbial samples through red-green-blue (RGB) color annotation. Both static and temporal metabolome differences can be visualized by straightforward color differences and differentiating m/z values identified afterward. Through this approach, novel analogues and their potential biosynthetic pathways are discovered by applying results from the spatial navigation to chromatography-based metabolome annotation. In this current research, LMJ-SSP is shown to be a robust and rapid spatial profiling method. Unsupervised multivariant analysis based hyperspectral visualization is proven straightforward for facile/rapid data interpretation. The combination of direct analysis and innovative data visualization forms a powerful tool to aid the identification/interpretation of interesting compounds from conventional metabolomics analysis.PMID:39713036 | PMC:PMC11659995 | DOI:10.1021/acsmeasuresciau.4c00035

ACS Meas Sci Au. 2024 Oct 4;4(6):695-701. doi: 10.1021/acsmeasuresciau.4c00044. eCollection 2024 Dec 18.ABSTRACTAssessing the quality of wheat, one of humanity's most important crops, in a straightforward manner, is essential. In this study, analysis of variance (ANOVA) simultaneous component analysis (ASCA) paired with near-infrared spectroscopy (NIRS) was used as an easy-to-implement and environmentally friendly tool for this purpose. The capabilities of combining NIRS with ASCA were demonstrated by studying the effects of sampling site and year on the quality of 180 Austrian wheat samples across four sites over 3 years. It was found that the year, sample site, and their combination significantly (p < 0.001) affect the NIR spectra of wheat. NIR spectral preprocessing tools, usually employed in chemometric workflows, notably influence the results obtained by ASCA, particularly in terms of the variance attributed to annual and regional effects. The influence of the year was identified as the dominant factor, followed by region and the combined effect of year and sampling site. Interpretation of the loading plots obtained by ASCA demonstrates that wheat components such as proteins, carbohydrates, moisture, or fat contribute to annual and regional differences. Additionally, the protein, starch, moisture, fat, fiber, and ash contents of wheat samples obtained using a NIR-based calibration were found to be significantly influenced by year, sampling site, or their combination using ANOVA. This study shows that the combination of ASCA with NIRS simplifies NIR-based quality assessment of wheat without the need for time- and chemical-consuming calibration development.PMID:39713033 | PMC:PMC11659997 | DOI:10.1021/acsmeasuresciau.4c00044

ACS Meas Sci Au. 2024 Oct 14;4(6):702-711. doi: 10.1021/acsmeasuresciau.4c00047. eCollection 2024 Dec 18.ABSTRACTSample normalization is a crucial step in metabolomics for fair quantitative comparisons. It aims to minimize sample-to-sample variations due to differences in the total metabolite amount. When samples lack a specific metabolic quantity to accurately represent their total metabolite amounts, post-acquisition sample normalization becomes essential. Despite many proposed normalization algorithms, understanding remains limited of their differences, hindering the selection of the most suitable one for a given metabolomics study. This study bridges this knowledge gap by employing data simulation, experimental simulation, and real experiments to elucidate the differences in the mechanism and performance among common post-acquisition sample normalization methods. Using public datasets, we first demonstrated the dramatic discrepancies between the outcomes of different sample normalization methods. Then, we benchmarked six normalization methods: sum, median, probabilistic quotient normalization (PQN), maximal density fold change (MDFC), quantile, and class-specific quantile. Our results show that most normalization methods are biased when there is unbalanced data, a phenomenon where the percentages of up- and downregulated metabolites are unequal. Notably, unbalanced data can be sourced from the underlying biological differences, experimental perturbations, and metabolic interference. Beyond normalization algorithms and data structure, our study also emphasizes the importance of considering additional factors contributed by data quality, such as background noise, signal saturation, and missingness. Based on these findings, we propose an evidence-based normalization strategy to maximize sample normalization outcomes, providing a robust bioinformatic solution for advancing metabolomics research with a fair quantitative comparison.PMID:39713024 | PMC:PMC11659990 | DOI:10.1021/acsmeasuresciau.4c00047

EFSA J. 2024 Dec 20;22(Suppl 1):e221115. doi: 10.2903/j.efsa.2024.e221115. eCollection 2024 Dec.ABSTRACTThis study provides a comprehensive proteomic and metabolomic analysis of novel anthocyanin- and carotenoid-rich wheat varieties to assess their immunogenicity in the context of Celiac Disease. Using (semi)-quantitative mass spectrometry, the research found that gliadin expression and peptide release, particularly those containing immunostimulatory γ-gliadin epitopes, vary significantly across different wheat varieties. While non-targeted mass spectrometry provided valuable insights, the study acknowledged potential methodological biases, such limitations of ion current intensity as a measure of peptide abundance. Despite promising results, further research is required to determine the safety and efficacy of coloured wheat varieties for Celiac Disease patients, considering the complex interplay of gluten proteins, food processing, digestion and matrix effects. The ongoing studies hold potential for developing nutritionally beneficial wheat alternatives for Celiac Disease management.PMID:39712908 | PMC:PMC11659743 | DOI:10.2903/j.efsa.2024.e221115

Front Microbiol. 2024 Dec 5;15:1486566. doi: 10.3389/fmicb.2024.1486566. eCollection 2024.ABSTRACTThis study investigated age-related changes in the gut microbiota and metabolome of Sapsaree dogs through metagenomic and metabolomic analyses. Using Illumina (short-read) and Nanopore (long-read) sequencing technologies, we identified both common and unique bacterial genera in the dogs across different age groups. In metagenomic analysis, Firmicutes were predominant at the family level. At the genus level, Lactobacillus, Streptococcus, Romboutsia, and Clostridium XI were the most abundant, and the bacterial genera typically considered beneficial were less prevalent in senior dogs, whereas the genera associated with pathogenicity were more abundant. These findings suggest age-related shifts in gut microbiota composition. Metabolomic analysis showed distinct clustering of metabolites based on the age group, with changes in metabolite profiles correlating with metagenomic findings. Although Illumina and Nanopore methods provided distinctive results, the genera detected by both methods exhibited similar trends across all age groups in Sapsaree dogs. These findings highlight the relationship between ages, metabolite profiles and gut microbiota composition in dogs, suggesting the need for further research to explore this relation in greater depth.PMID:39712896 | PMC:PMC11659757 | DOI:10.3389/fmicb.2024.1486566

Front Microbiol. 2024 Dec 6;15:1514825. doi: 10.3389/fmicb.2024.1514825. eCollection 2024.ABSTRACTUnderstanding the impact of antibiotics on bacterial metabolism is crucial for elucidating their mechanisms of action and developing more effective therapeutic strategies. β-lactam antibiotics, distinguished by their distinctive β-lactam ring structure, are widely used as antimicrobial agents. This study investigates the global metabolic alterations induced by three β-lactam antibiotics-meropenem (a carbapenem), ampicillin (a penicillin), and ceftazidime (a cephalosporin)-in Escherichia coli. Our comprehensive metabolic profiling revealed significant perturbations in bacterial metabolism, particularly in pathways such as glutathione metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and purine metabolism. Antibiotic treatment markedly increased reactive oxygen species levels, with meropenem reaching nearly 200 ± 7%, ampicillin at 174 ± 11%, and ceftazidime at 152 ± 7%. Additionally, β-lactam antibiotics elevated 8-OHdG levels to 4.73 ± 0.56-fold for meropenem, 2.49 ± 0.19-fold for ampicillin, and 3.19 ± 0.34-fold for ceftazidime; 8-OHG levels increased to 5.57 ± 0.72-fold for meropenem, 3.08 ± 0.31-fold for ampicillin, and 4.45 ± 0.66-fold for ceftazidime, indicating that oxidative stress enhances oxidative damage to bacterial DNA and RNA. Notably, we observed a selective upregulation of specific amino acids associated with cellular repair mechanisms, indicating a metabolic adaptation to counteract oxidative damage. These findings illustrate that β-lactam antibiotics induce a complex metabolic perturbations associated with ROS production, potentially compromising critical cellular components. This study enhances our understanding of the intricate relationship between antibiotic action and bacterial metabolism, providing valuable insights for developing effective strategies against antibiotic-resistant pathogens.PMID:39712889 | PMC:PMC11659197 | DOI:10.3389/fmicb.2024.1514825

Front Pharmacol. 2024 Dec 6;15:1470142. doi: 10.3389/fphar.2024.1470142. eCollection 2024.ABSTRACTBACKGROUND: Acid-sensing ion channels are activated during myocardial ischemia and are implicated in the mechanism of myocardial ischemia-reperfusion injury (MIRI). Acid-sensing ion channel 3 (ASIC3), the most pH-sensitive member of the ASIC family, is highly expressed in myocardial tissues. However, the role of ASIC3 in MIRI and its precise effects on the myocardial metabolome remain unclear. These unknowns might be related to the cardioprotective effects observed with APETx2 post-conditioning.METHOD: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, ASIC3 blockade (AP) group. Rat hearts in group AP were treated with the ASIC3-specific inhibitor APETx2 (630 nM). Molecular and morphological changes were observed to elucidate the role of ASIC3 in MIRI. Bioinformatics analyses identified differential metabolites and pathways associated with APETx2 post-conditioning.RESULTS: APETx2 post-conditioning stabilized hemodynamics in the isolated rat heart model of MIRI. It also reduced myocardial infarct size, mitigated mitochondrial damage at the ultrastructural level, and improved markers of myocardial injury and oxidative stress. Further more, we observed that phosphatidylcholine, phosphatidylethanolamine, citric acid, cyanidin 5-O-beta-D-glucoside, and L-aspartic acid decreased after MIRI. The levels of these metabolites were partially restored by APETx2 post-conditioning. These metabolites are primarily involved in autophagy and endogenous cannabinoid signaling pathways.CONCLUSION: ASIC3 is potentially a key player in MIRI. APETx2 post-conditioning may improve MIRI through specific metabolic changes. This study provides valuable data for future research on the metabolic mechanisms underlying the effects of APETx2 post-conditioning in MIRI.PMID:39712499 | PMC:PMC11658994 | DOI:10.3389/fphar.2024.1470142

Front Pharmacol. 2024 Dec 6;15:1472437. doi: 10.3389/fphar.2024.1472437. eCollection 2024.ABSTRACTThe effects of Helicobacter pylori (Hp)-related chronic gastritis on gastrointestinal microorganisms or brain neurotransmitters are not fully understood. Here, this study selected SPF C57BL/6 mice to set up a Hp-related chronic gastritis experiment group and a blank control group, and used omics to explore the specific effects of Hp-related chronic gastritis on gastrointestinal microorganisms and brain neurotransmitters in mice. The Tyramine (TyrA) content in the female experiment group's brain was considerably reduced compared to the female control group (p < 0.01), and TyrA was strongly correlated with 13 gastrointestinal microorganisms with significant differences, such as Acinetobacter_baumannii (p < 0.05). The His content in the male experiment group's brain was significantly higher than that in the male control group (p < 0.05), and His was strongly correlated with four gastrointestinal microorganisms with significant differences, such as Acinetobacter_baumannii (p < 0.05). The Levodopa (DOPA) content in the female control group's brain was significantly lower than that in the male control group (p < 0.05), and DOPA was strongly correlated with 19 gastrointestinal microorganisms with significant differences, such as Achromobacter_xylosoxidans (p < 0.05). The contents of L-Glutamine (Gln), L-Glutamine (GABA), Noradrenaline hydrochloride (NE), and Adrenaline hydrochloride (E) in the female experiment group's brain were significantly lower than those in the male experiment group (p < 0.05), and Gln, GABA, NE, and E were strongly correlated with 41, 28, 40, and 33 gastrointestinal microorganisms with significant differences (p < 0.05), respectively. These results indicate that Hp-related chronic gastritis could affect gastrointestinal microorganisms and brain neurotransmitters in mice with certain gender differences, and the changes in brain neurotransmitters might be related to the changes in gastrointestinal microorganisms.PMID:39712493 | PMC:PMC11659015 | DOI:10.3389/fphar.2024.1472437

J Diabetes Metab Disord. 2024 Dec 20;24(1):23. doi: 10.1007/s40200-024-01507-2. eCollection 2025 Jun.ABSTRACTOBJECTIVES: This study aims to identify new variants and haplotypes associated with monogenic obesity by analyzing known obesity genes in whole exome sequencing (WES) data.METHODS: The monogenic obesity-associated genes were identified by using the National Institutes of Health (NIH) Genetic Testing Registry (GTR) monogenic obesity panels. WES was performed on (n = 49) extremely obese (children under 5 with weight-for-height greater than 3 standard deviations (SD) above the World Health Organization (WHO) Child Growth Standards median) and (n = 50) control nonobese (25 > body mass index (BMI) < 30) subjects without a history of childhood obesity, and also Iranome WES data of healthy subjects (n = 800).RESULTS: Seventy-four genes were included in WES analyses. After Bonferroni correction, the T allele of rs2275155 on SDCCAG8 was significantly associated with the increased risk of obesity for allelic and co-dominant models (p˂0.05). Also, a significant association was observed for the T allele of rs116167439 on CEP19 and the T allele of rs201676524 a rare variant on ADCY3; for allelic, dominant, overdominant, and co-dominant models (p˂0.05). In the haplotype association study, TC (on CEP19), CATA (on SDCCAG8), CAA, CTA, CAAA, and TTGA (on ADCY3) haplotypes showed significant associations with monogenic obesity (p < 0.05).CONCLUSIONS: This study suggested that the T allele of two common variants rs2275155 and rs116167439, also rare variant rs201676524 are associated with an increased risk of monogenic obesity. The significant haplotype associations indicate these variants may be in linkage with causative rare variants and should be considered in future studies.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-024-01507-2.PMID:39712340 | PMC:PMC11662120 | DOI:10.1007/s40200-024-01507-2

Front Immunol. 2024 Dec 6;15:1503857. doi: 10.3389/fimmu.2024.1503857. eCollection 2024.ABSTRACTINTRODUCTION: Extracellular vesicles of Natural Killer cells (NKEV) exert an antitumor effect towards hematopoietic and solid tumors and have an immune modulating effect, suggesting a promising role in immune and biotherapy. In this study, a continuation of our former works, we demonstrated a network by mass spectrometry analysis between NKEV protein cargo and antitumor effects. Human healthy NKEV, both exosomes and microvesicles, have a significant and direct cytotoxic effect against human B cell lymphoma in in vitro and in vivo conditions.METHODS: We isolated extracellular vesicles from in vitro amplified healthy human NK cells and their treatment efficacy was monitored by cytometry analyses, in vivo MRI/MRS measurements, ex vivo MRS analyses and immunohistochemistry.RESULTS: We observed a remarkable NKEV cytotoxic effect, mainly by apoptosis, on B cell lymphoma in vitro when exosomes and microvesicles were administered simultaneously. In vivo results showed metabolic alterations in SCID mice xenografts after NKEV treatment, associated with a significant reduction of tumor growth (64%). In the in vivo 1H MR spectra we found a significant increase in the tumor lipid/lactate and in taurine signals, both considered as apotosis markers. Ex vivo lymphoma metabolomics revealed a significant increase in fatty acid (FA) pool and decrease in unsaturated and mono-unsaturated FA in treated groups, as compared to control one, thus suggesting an alteration of tumor homeostasis. Immunohistochemistry analyses confirmed the reduction of B-cell lymphoma proliferation rate, as well as the induction of apoptosis following the NKEV treatment.CONCLUSIONS: This study underscore the importance of NKEV as a novel biological acellular tool for B-cell lymphoma treatment, probably having a greater effect on combined treatment regimens. These nanovesicles have an extraordinary potential in innovative cancer immunotherapy, representing a safe and efficient tool naturally circulating in healthy individuals and ready to maintain the immune homeostasis, and therefore a good organism healthy state.PMID:39712029 | PMC:PMC11659271 | DOI:10.3389/fimmu.2024.1503857

Rev Bras Ortop (Sao Paulo). 2024 Dec 21;59(6):e958-e965. doi: 10.1055/s-0044-1790217. eCollection 2024 Dec.ABSTRACTObjective The present study aimed to evaluate the metabolic profile of synovial fluid in patients with knee osteoarthritis (KOA) and its correlation with clinical data. Materials and Methods We collected synovial fluid samples from the knees of 50 subjects with KOA undergoing total knee arthroplasty from October 2019 to December 2020. For each patient, we evaluated the clinical data from the medical record, the radiographic osteoarthritis grade, and the preoperative fasting blood glucose levels. The samples underwent metabolomic analysis by 1H magnetic resonance spectroscopy, and we compared the spectra using multivariate and univariate analyses. Results Most patients were female (66%). The subjects had an average age of 67.96 ± 7.08 years old and an average body mass index (BMI) of 32.51 ± 5.25 kg/m 2 . Clinical and metabolic evaluations revealed that 88% of patients were hypertensive and presented higher levels of valine, arginine, and citrate than non-hypertensive subjects. Conclusion Metabolomic analysis of synovial fluid cannot classify osteoarthritis patients per their clinical characteristics.PMID:39711625 | PMC:PMC11663051 | DOI:10.1055/s-0044-1790217

Res Sq [Preprint]. 2024 Dec 9:rs.3.rs-5530702. doi: 10.21203/rs.3.rs-5530702/v1.ABSTRACTNon-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase - 2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.PMID:39711561 | PMC:PMC11661377 | DOI:10.21203/rs.3.rs-5530702/v1

Food Funct. 2024 Dec 23. doi: 10.1039/d4fo04019h. Online ahead of print.ABSTRACTFood allergies are pathological adverse reactions against harmless dietary proteins. While studies have shown the involvement of host metabolic changes (e.g., lipid metabolism and amino acid metabolism) in the development of food allergy (FA), the adaptive changes in glucose metabolism induced by food allergen exposure remain largely unclear. In this study, BALB/c mice were sensitized intraperitoneally with an ovalbumin (OVA)/aluminum adjuvant, followed by oral OVA challenges to induce anaphylaxis. Increased levels of serum OVA-specific IgE and MCPT-1, and Th2 response bias were also presented in FA mice. Subsequently, the intestinal untargeted metabolomic analysis revealed the signature enrichment of glycolysis, manifested by increases in glycolytic metabolites including glucose-6-phosphate, fructose-6-phosphate, 2-phosphoglycerate, and lactate in FA mice. Consistently, the serum lactate level was found to be significantly elevated in allergic mice. Oral administration of OVA also upregulated the expression of critical metabolic enzymes in glycolysis, namely hexokinase 2, phosphoglycerate mutase 1, and lactate dehydrogenase. Moreover, the hypoxia inducible factor-1 (HIF-1) signaling pathway was activated in FA mice, and the expression of HIF-1α, known as the upstream regulator of glycolysis, was increased after oral OVA challenges. In vitro inhibition of HIF-1α was found to impede mast cell inflammatory responses to allergens. In summary, this study demonstrated that OVA-induced FA exhibited a glucose metabolic feature of HIF-1α-mediated glycolysis upregulation, suggesting the potential of HIF-1α/glycolysis targeted strategies in the alleviation of FA.PMID:39711353 | DOI:10.1039/d4fo04019h

Nat Prod Res. 2024 Dec 23:1-6. doi: 10.1080/14786419.2024.2441494. Online ahead of print.ABSTRACTThe fall armyworm Spodoptera frugiperda is the most prevalent plague in crops associated with a reduction in corn production by up to 34%. Pesticides have been used to reduce this plague, but they cause several environmental problems including resistance, ecological imbalance, and toxicity to the final consumer. The use of plant extracts has been an effective manner of eradicating this plague from crop plantations. In this sense, the hexane, EtOAc, and EtOH/H2O fractions from EtOH extract from different parts of Cenostigma pluviosum were investigated against this fall armyworm leading to a percentage of mortality around 96% in the larval phase for the fraction EtOAc of fruits (FrEA). The fractions were analysed in HPLC-ESI-HRMS for dereplication. Additionally, using multivariate statistical analysis permitted the development of an O2PLS-DA method based on the chemical constitution of fractions shedding light on promising constituents to the insecticidal activity of C. pluviosum against the Spodoptera frugiperda.PMID:39711208 | DOI:10.1080/14786419.2024.2441494

NMR Biomed. 2025 Feb;38(2):e5304. doi: 10.1002/nbm.5304.ABSTRACTMagnetic resonance spectroscopic imaging (MRSI) enables the simultaneous noninvasive acquisition of MR spectra from multiple spatial locations inside the brain. Although 1H-MRSI is increasingly used in the human brain, it is not yet widely applied in the preclinical setting, mostly because of difficulties specifically related to very small nominal voxel size in the rat brain and low concentration of brain metabolites, resulting in low signal-to-noise ratio (SNR). In this context, we implemented a free induction decay 1H-MRSI sequence (1H-FID-MRSI) in the rat brain at 14.1 T. We combined the advantages of 1H-FID-MRSI with the ultra-high magnetic field to achieve higher SNR, coverage, and spatial resolution in the rat brain and developed a custom dedicated processing pipeline with a graphical user interface for Bruker 1H-FID-MRSI: MRS4Brain toolbox. LCModel fit, using the simulated metabolite basis set and in vivo measured MM, provided reliable fits for the data at acquisition delays of 1.30 ms. The resulting Cramér-Rao lower bounds were sufficiently low (< 30%) for eight metabolites of interest (total creatine, N-acetylaspartate, N-acetylaspartate + N-acetylaspartylglutamate, total choline, glutamine, glutamate, myo-inositol, and taurine), leading to highly reproducible metabolic maps. Similar spectral quality and metabolic maps were obtained with one and two averages, with slightly better contrast and brain coverage due to increased SNR in the latter case. Furthermore, the obtained metabolic maps were accurate enough to confirm the previously known brain regional distribution of some metabolites. The acquisitions proved high reproducibility over time. We demonstrated that the increased SNR and spectral resolution at 14.1 T can be translated into high spatial resolution in 1H-FID-MRSI of the rat brain in 13 min using the sequence and processing pipeline described herein. High-resolution 1H-FID-MRSI at 14.1 T provided robust, reproducible, and high-quality metabolic mapping of brain metabolites with minimal technical limitations.PMID:39711201 | DOI:10.1002/nbm.5304