PubMed

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

BMC Complement Med Ther. 2024 Nov 13;24(1):394. doi: 10.1186/s12906-024-04683-z.ABSTRACTBACKGROUND: Melaleuca species (family Myrtaceae) are characterized by their wide-ranging applications as antimicrobials and in skin-related conditions. Herein, we estimated the volatile profile and biological significance of M. rugulosa (Link) leaves for the first time supported by a dereplication protocol.MATERIALS AND METHODS: Volatile components were extracted using hydrodistillation (HD), supercritical fluid (SF), and headspace (HS) techniques and identified using GC/MS. The variations among the three extracts were assessed using principal component analysis and orthogonal partial least square discriminant analysis (OPLS-DA). The extracted volatiles were tested for radical scavenging activity, anti-aging, and anti-hyperpigmentation potential. Finally, disc diffusion and broth microdilution assays were implemented to explore the antibacterial capacity against Streptococcus pyogenes, Staphylococcus aureus, Clostridium perfringens, and Pseudomonas aeruginosa.RESULTS: The yield of the SF technique (0.8%) was three times higher than HD. GC/MS analysis revealed that the oxygenated compounds are the most proponents in the three extracts being 95.93% (HD), 80.94% (HS), and 48.4% (SF). Moreover, eucalyptol (1,8-cineol) represents the major component in the HD-EO (89.60%) and HS (73.13%) volatiles, while dl-α-tocopherol (16.27%) and α-terpineol (11.89%) represent the highest percentage in SF extract. Regarding the bioactivity profile, the HD-EO and SF-extract showed antioxidant potential in terms of oxygen radical absorbance capacity, and β- carotene assays, while exerting weak activity towards DPPH. In addition, they displayed potent anti-elastase and moderate anti-collagenase activities. The HD-EO exhibited potent anti-tyrosinase activity, while the SF extract showed a moderate level compared to tested controls. OPLS-DA and dereplication studies predicted that the selective antibacterial activity of HD-EO to S. aureus was related to eucalyptol, while SF extract to C. perfringens was related to α-tocopherol.CONCLUSIONS: M. rugulosa leaves are considered a vital source of bioactive volatile components that are promoted for controlling skin aging and infection. However, further safety and clinical studies are recommended.PMID:39538246 | DOI:10.1186/s12906-024-04683-z

J Anim Sci Biotechnol. 2024 Nov 14;15(1):157. doi: 10.1186/s40104-024-01108-2.ABSTRACTBACKGROUND: Research on low-protein-level diets has indicated that even though the profiles of essential amino acids (EAAs) follow the recommendation for a normal-protein-level diet, broilers fed low-protein diets failed to achieve productive performance compared to those fed normal diets. Therefore, it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance. Furthermore, identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology. In this study, 12 dietary treatments [Con(+), Con(-), L&A(-), L&A(+), M&C(-), M&C(+), BCAA (-), BCAA(+), Thr(-), Thr(+), Trp(-) and Trp(+)] were established by combining different EAAs including lysine and arginine, methionine and cysteine, branched-chain amino acid (BCAA), threonine, and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets. Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments, biomarkers associated with optimal and suboptimal amino acid balance were identified.RESULTS: Growth performance, carcass characteristics, hepatic enzyme activity, serum biochemical parameters, and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns. Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers. For the low-protein diet, the dietary concentrations of lysine, arginine, and tryptophan, but not of methionine, cystine, or threonine, needed to be increased. Therefore, further research on individual BCAA is required. For untargeted metabolomic analysis, Con(+) was selected as a normal diet (NP) while Con(-) represented a low-protein diet (LP). L&A(+) denotes a low-protein amino acid balanced diet (LPAB) and Thr(+) represents a low-protein amino acid imbalance diet (LPAI). The metabolites oxypurinol, pantothenic acid, and D-octopine in birds were significantly influenced by different dietary amino acid patterns.CONCLUSION: Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets. Oxypurinol, pantothenic acid, and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.PMID:39538238 | DOI:10.1186/s40104-024-01108-2

BMC Plant Biol. 2024 Nov 14;24(1):1074. doi: 10.1186/s12870-024-05773-3.ABSTRACTBACKGROUND: Chilling stress is a key abiotic stress that severely restricts the growth and quality of melon (Cucumis melo L.). Few studies have investigated the mechanism of response to chilling stress in melon.RESULTS: We characterized the physiological, transcriptomic, and metabolomic response of melon to chilling stress using two genotypes with different chilling sensitivity ("162" and "13-5A"). "162" showed higher osmotic regulation ability and antioxidant capacity to withstand chilling stress. Transcriptome analysis identified 4395 and 4957 differentially expressed genes (DEGs) in "162" and "13-5A" under chilling stress, respectively. Metabolome analysis identified 615 and 489 differential enriched metabolites (DEMs) were identified in "162" and "13-5A" under chilling stress condition, respectively. Integrated transcriptomic and metabolomic analysis showed enrichment of glutathione metabolism, and arginine (Arg) and proline (Pro) metabolism, with differential expression patterns in the two genotypes. Under chilling stress, glutathione metabolism-related DEGs, 6-phosphogluconate dehydrogenase (G6PDH), glutathione peroxidase (GPX), and glutathione s-transferase (GST) were upregulated in "162," and GSH conjugates (L-gamma-glutamyl-L-amino acid and L-glutamate) were accumulated. Additionally, "162" showed upregulation of DEGs encoding ornithine decarboxylase, Pro dehydrogenase, aspartate aminotransferase, pyrroline-5-carboxylate reductase, and spermidine synthase and increased Arg, ornithine, and Pro. Furthermore, the transcription factors (TFs), MYB, ERF, MADS-box, and bZIP were significantly upregulated, suggesting their crucial role in chilling tolerance of melon.CONCLUSIONS: These findings elucidate the molecular response mechanism to chilling stress in melon and provide insights for breeding chilling-tolerant melon.PMID:39538130 | DOI:10.1186/s12870-024-05773-3

Metabolomics. 2024 Nov 13;20(6):130. doi: 10.1007/s11306-024-02190-3.ABSTRACTINTRODUCTION: Tempeh is an antioxidant-rich soybean fermentation product from Java, Indonesia. Cooking methods have an impact on the nutritional value and bioactivity of food.OBJECTIVE: This study aims to investigate how the cooking process affects the metabolites and antioxidant activity in tempeh using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS).METHODS: A nontargeted UHPLC-HRMS metabolomics and chemometric analysis were used to evaluate metabolite profiles and antioxidant activity changes because of food processing in tempeh.RESULTS: The score plots of tempeh produced by boiling and frying methods displayed a distinct separation from raw tempeh, revealing that the cooking process altered the metabolite composition of tempeh. Due to processing, L-glutamic acid, L-pyroglutamic acid, DL-glutamine, and D-( +)-proline became the most affected metabolites on tempeh. There were 70 metabolites that showed antioxidant activity using the DPPH assay; 23 metabolites significantly differ from DPPH and control for antioxidant activity for all processing tempeh. Metabolites with significantly different antioxidant activity in raw and processed tempeh were dominated by flavonoids, vitamin E, and bioactive lipids.CONCLUSION: The DPPH antioxidant assay using UHPLC-HRMS is promising as a fast antioxidant assay by simplifying the conventional DPPH antioxidant assay. Further, it can be used to identify the name of metabolites responsible for its antioxidant activity.PMID:39538093 | DOI:10.1007/s11306-024-02190-3

Inflammation. 2024 Nov 14. doi: 10.1007/s10753-024-02182-4. Online ahead of print.ABSTRACTPristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.PMID:39538091 | DOI:10.1007/s10753-024-02182-4

Plant Mol Biol. 2024 Nov 13;114(6):124. doi: 10.1007/s11103-024-01517-x.ABSTRACTExistence of potent in vitro regeneration system is a prerequisite for efficient genetic transformation and functional genomics of crop plants. In this study, two contrasting cultivars differencing in their in vitro regeneration efficiency were identified. Tissue culture friendly cultivar Golden Promise (GP) and tissue culture resistant DWRB91(D91) were selected as contrasting cultivars to investigate the molecular basis of regeneration efficiency through multiomics analysis. Transcriptomics analysis revealed 1487 differentially expressed genes (DEGs), in which 795 DEGs were upregulated and 692 DEGs were downregulated in the GP-D91 transcriptome. Genes encoding proteins localized in chloroplast and involved in ROS generation were upregulated in the embryogenic calli of GP. Moreover, proteome analysis by LC-MS/MS revealed 3062 protein groups and 16,989 peptide groups, out of these 1586 protein groups were differentially expressed proteins (DEPs). Eventually, GC-MS based metabolomics analysis revealed the higher activity of plastids and alterations in key metabolic processes such as sugar metabolism, fatty acid biosynthesis, and secondary metabolism. TEM analysis also revealed differential plastid development. Higher accumulation of sugars, amino acids and metabolites corresponding to lignin biosynthesis were observed in GP as compared to D91. A comprehensive examination of gene expression, protein profiling and metabolite patterns unveiled a significant increase in the genes encompassing various functions, such as ion homeostasis, chlorophyll metabolic process, ROS regulation, and the secondary metabolic pathway.PMID:39538083 | DOI:10.1007/s11103-024-01517-x

Pflugers Arch. 2024 Nov 14. doi: 10.1007/s00424-024-03041-9. Online ahead of print.ABSTRACTWestern dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.PMID:39537965 | DOI:10.1007/s00424-024-03041-9