PubMed

Heliyon. 2024 Mar 16;10(6):e27983. doi: 10.1016/j.heliyon.2024.e27983. eCollection 2024 Mar 30.ABSTRACTGlobal increase in recurrence of bacterial vaginosis (BV) and worrisome rise in antimicrobial resistance pose an urgent call for new/novel antibacterial agents. In light of the circumstance, the present study demonstrates the in vitro and in vivo antibacterial activity of a phytochemical citral, with a particular emphasis to elucidate its mechanistic action against Gardnerella vaginalis -a potential cause of BV. Out of 21 phytochemicals screened initially against G. vaginalis, citral was envisaged to be a phenomenal antibacterial agent showing MIC and MBC at 128 μg/mL. Citral's rapid killing ability was revealed by a time-killing kinetics assay supported by CFU, signifying that it completely killed the given inoculum of planktonic G. vaginalis cells within 60 min. Further, citral was found to exhibit 1 min contact-killing efficacy together with mature-biofilm disintegrating ability at increasing MICs. To further understand the molecular action of citral, in vitro investigations such as ROS estimation, PI staining and intracellular protein release assay were performed, which demonstrated that citral deteriorated the membrane integrity of G. vaginalis. Galleria mellonella, a simple invertebrate model used to evaluate citral's non-toxic and antibacterial activity in vivo, demonstrates that citral completely restored the larvae from G. vaginalis infection. The metabolite level investigation using LC-MS revealed that citral had negative impact on biotin metabolism (via., biotin), spermidine metabolism (via., 5'-methylthioadenosine and spermidine) and nucleotide metabolism (via., guanine, adenine and uridine). Since that biotin is associated with seven different metabolic pathways, it is conceivable that citral could target biotin biosynthesis or its metabolism and as a result, disrupt other metabolic pathways, such as lipid and fatty acid synthesis, which is essential for the creation of cell membranes. Thus, the current study is the first of its kind to delineate the promising in vitro and in vivo antibacterial efficacy of citral and decipher its plausible antibacterial action mechanism through metabolomic approach, which concomitantly emphasizes citral as a viable natural therapeutic alternative to manage and control BV.PMID:38545203 | PMC:PMC10966606 | DOI:10.1016/j.heliyon.2024.e27983

Biomed Rep. 2024 Mar 12;20(5):75. doi: 10.3892/br.2024.1763. eCollection 2024 May.ABSTRACTThe present study investigated the inhibitory and neuroprotective effects of Rubia yunnanensis alcohol extract (RY-A) on oxidative stress induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 cells. In vitro cultured HT22 cells were randomly divided into control, OGD/R, OGD/R + 100 µmol/l edaravone and OGD/R + 10, 20 and 40 µg/ml RY-A groups. Oxygen-sugar deprivation was performed with 10 mmol/l sodium dithionite combined with sugar-free DMEM medium for 2 h, followed by re-glycolization and reoxygenation for 2 h to establish an in vitro OGD/R model. Cell morphology was observed under a phase contrast microscope. Cell survival rate was detected by thiazolyl blue and lactate dehydrogenase and oxidative stress-related indexes were detected by commercial kits. The effects and metabolic alterations of RY-A treatment after OGD/R were evaluated using ultra-high performance liquid chromatography and mass spectrometry. Protein levels were further examined by western blotting. The results showed that cells in the OGD/R group were swollen and lacked protrusions, had significantly reduced viability and had significantly elevated oxidative stress-related indexes of reactive oxygen species, nitric oxide levels and malondialdehyde content and significantly reduced activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared with controls. Compared with the OGD/R group, the RY-A group had significantly improved cell morphology and significantly increased cell viability and in terms of oxidative stress, exhibited significantly reduced reactive oxygen species, nitric oxide levels and malondialdehyde content, as well as significantly increased superoxide dismutase and glutathione peroxidase activities. Metabolomic analysis identified changes in 20 metabolites, including L-tryptophan, ornithine, eicosapentaenoic acid-d5, isosafrole and xanthine. Metabolomics analysis showed that the pathways affected included those related to phenylalanine, tyrosine and tryptophan biosynthesis, the prolactin signaling pathway and amphetamine addiction. These results suggested that RY-A had significant preventive effects on an in vitro model of cerebral ischemia-reperfusion injury simulated by OGD/R and the mechanism may be related to increased tryptophan content, activation of indoleamine 2,3-dioxygenase enzymes and inhibition of oxidative stress.PMID:38544959 | PMC:PMC10963945 | DOI:10.3892/br.2024.1763

Food Chem (Oxf). 2024 Mar 11;8:100199. doi: 10.1016/j.fochms.2024.100199. eCollection 2024 Jul 30.ABSTRACTThe food waste of the fruit processing industry is rich in many bio-active components such as polysaccharides, polyphenols, peptides, etc. that own multifaceted health benefits. The valorization of this waste is an intriguing optimization method for various dairy products. Meanwhile, LC-MS-based foodomics has been an emerging approach for the quantitative and qualitative analysis of dairy foods. Untargeted metabolomics has been done of the optimized functional yogurt that contains different levels of unripened papaya peel powder (UPPP) using high-resolution mass spectroscopy for analysis of added bio-active components in the matrix. UPPP comprises a high content of phytochemicals which could give functionality and therapeutic effect to the Greek yogurt. A total of 36 functional metabolites have been identified which have various health-beneficial attributes. Kaempferol, ostruthin, putative carpaine derivatives, etc. are some of the metabolites of high importance with a wide area coverage in the metabolome. This work highlights the bioactivity of the UPPP and its prebiotic properties added to the functional yogurt as an independent ingredient. The incorporated plant-based ingredients like UPPP can effectively enhance the functional attributes of Greek yogurt, which is a potential synbiotic food.PMID:38544783 | PMC:PMC10966443 | DOI:10.1016/j.fochms.2024.100199

Front Nutr. 2024 Mar 13;11:1368789. doi: 10.3389/fnut.2024.1368789. eCollection 2024.ABSTRACTChicken soup is popular among consumers because of its delicious taste, strong flavor, and abundant nutritional value. Twenty-four Yunnan local hens were stewed by adding different amounts of NaCl [1.5, 2, 2.5, 3%, m/m, calculated based on chicken carcass weight; chicken: water = 1:2 (m/m)] to study the effect of salt addition on taste- and flavor-related compounds in chicken soup. Sensory evaluation results showed that the 2 and 2.5% NaCl treatment groups had higher scores. Water-soluble small molecule compounds were detected by LC-Q/TOF-MS based metabolomics approach, among which amino acids and their derivatives, nucleic acids, and small peptides were the main components. The concentration of Water-soluble small molecule substances in chicken soup samples with different salt additions showed a clear trend of separation and reached the highest in the 2.5% NaCl treatment group. Volatile flavor compounds in the chicken soup were analyzed by HS-SPME-GC-MS, including aldehydes, and alcohols, and the relative concentration of flavor compounds in the 2.5% salt treatment group was the highest. In summary, the addition of salt could improve the overall flavor of chicken broth, and the optimal salt addition of NaCl in chicken soup is 2.5%.PMID:38544751 | PMC:PMC10965538 | DOI:10.3389/fnut.2024.1368789

Toxicol Sci. 2024 Mar 27:kfae040. doi: 10.1093/toxsci/kfae040. Online ahead of print.ABSTRACTExposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at two concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 hours after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3,446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only one gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 (EIF2) stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.PMID:38544285 | DOI:10.1093/toxsci/kfae040

Viruses. 2024 Mar 13;16(3):449. doi: 10.3390/v16030449.ABSTRACTAfrican swine fever (ASF) is a highly contagious and hemorrhagic disease caused by infection with the African swine fever virus (ASFV), resulting in a mortality rate of up to 100%. Currently, there are no effective treatments and commercially available vaccines for ASF. Therefore, it is crucial to identify biochemicals derived from host cells that can impede ASFV replication, with the aim of preventing and controlling ASF. The ASFV is an acellular organism that promotes self-replication by hijacking the metabolic machinery and biochemical resources of host cells. ASFV specifically alters the utilization of glucose and glutamine, which are the primary metabolic sources in mammalian cells. This study aimed to investigate the impact of glucose and glutamine metabolic dynamics on the rate of ASFV replication. Our findings demonstrate that ASFV infection favors using glutamine as a metabolic fuel to facilitate self-replication. ASFV replication can be substantially inhibited by blocking glutamine metabolism. The metabolomics analysis of the host cell after late-stage ASFV infection revealed a significant disruption of normal glutamine metabolic pathways due to the abundant expression of PLA (phenyllactic acid). Pretreatment with PLA also inhibited ASFV proliferation and glutamine consumption following infection. The metabolomic analysis also showed that PLA pretreatment greatly slowed down the metabolism of amino acids and nucleotides that depend on glutamine. The depletion of these building blocks directly hindered the replication of ASFV by decreasing the biosynthetic precursors produced during the replication of ASFV's progeny virus. These findings provide valuable insight into the possibility of pursuing the development of antiviral drugs against ASFV that selectively target metabolic pathways.PMID:38543813 | DOI:10.3390/v16030449

Microorganisms. 2024 Mar 15;12(3):590. doi: 10.3390/microorganisms12030590.ABSTRACTAcidophiles are capable of surviving in extreme environments with low pH. Acidithiobacillus ferrooxidans is a typical acidophilic bacterium that has been extensively studied when grown chemoautotrophically, i.e., when it derives energy from oxidation of Fe2+ or reduced inorganic sulfur compounds (RISCs). Although it is also known to grow with electrons supplied by solid electrodes serving as the sole source of energy, the understanding of its electroautotrophic growth is still limited. This study aimed to compare the growth characteristics of A. ferrooxidans under electroautotrophic (ea) and chemoautotrophic (ca) conditions, with an attempt to elucidate the possible mechanism(s) of extracellular electron flow into the cells. Jarosite was identified by Raman spectroscopy, and it accumulated when A. ferrooxidans used Fe2+ as the electron donor, but negligible mineral deposition occurred during electroautotrophic growth. Scanning electron microscopy (SEM) showed that A. ferrooxidans possesses more pili and extracellular polymeric substances (EPSs) under electroautotrophic conditions. A total of 493 differentially expressed genes (DEGs) were identified, with 297 genes being down-regulated and 196 genes being up-regulated in ea versus ca conditions. The genes known to be essential for chemoautotrophic growth showed a decreased expression in the electroautotrophic condition; meanwhile, there was an increased expression of genes related to direct electron transfer across the cell's outer/inner membranes and transmembrane proteins such as pilin and porin. Joint analysis of DEGs and differentially expressed metabolites (DEMs) showed that galactose metabolism is enhanced during electroautotrophic growth, inducing A. ferrooxidans to produce more EPSs, which aids the cells in adhering to the solid electrode during their growth. These results suggested that electroautotrophy and chemoautotrophy of A. ferrooxidans have different extracellular electron uptake (EEU) pathways, and a model of EEU during electroautotrophic growth is proposed. The use of extracellular electrons as the sole energy source triggers A. ferrooxidans to adopt metabolic and subsequently phenotypic modifications.PMID:38543641 | DOI:10.3390/microorganisms12030590

Microorganisms. 2024 Mar 9;12(3):548. doi: 10.3390/microorganisms12030548.ABSTRACTNatural product (NP)-based pesticides have emerged as a compelling alternative to traditional chemical fungicides, attracting substantial attention within the agrochemical industry as the world is pushing toward sustainable and environmentally friendly approaches to safeguard crops. Microbes, both bacteria and fungi, are a huge source of diverse secondary metabolites with versatile applications across pharmaceuticals, agriculture, and the food industry. Microbial genome mining has been accelerated for pesticide/drug discovery and development in recent years, driven by advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, and synthetic biology. Here, we isolated and identified Pseudomonas vancouverensis that had shown antifungal activities against crop fungal pathogens Colletotrichum fragariae, Botrytis cinerea, and Phomopsis obscurans in a dual-plate culture and bioautography assay. Further, we sequenced the whole bacterial genome and mined the genome of this bacterium to identify secondary metabolite biosynthetic gene clusters (BGCs) using antiSMASH 7.0, PRISM 4, and BAGEL 4. An in-silico analysis suggests that P. vancouverensis possesses a rich repertoire of BGCs with the potential to produce diverse and novel NPs, including non-ribosomal peptides (NRPs), polyketides (PKs), acyl homoserine lactone, cyclodipeptide, bacteriocins, and ribosomally synthesized and post-transcriptionally modified peptides (RiPPs). Bovienimide-A, an NRP, and putidacin L1, a lectin-like bacteriocin, were among the previously known predicted metabolites produced by this bacterium, suggesting that the NPs produced by this bacterium could have biological activities and be novel as well. Future studies on the antifungal activity of these compounds will elucidate the full biotechnological potential of P. vancouverensis.PMID:38543599 | DOI:10.3390/microorganisms12030548

Microorganisms. 2024 Feb 29;12(3):498. doi: 10.3390/microorganisms12030498.ABSTRACTTerminalia ferdinandiana Exell, Terminalia grandiflora Benth., Terminalia microcarpa Decne., and Terminalia muelleri Benth. (family: Combretaceae) belong to the genus Terminalia. Plants of this genus have been extensively used as traditional medicines to treat a variety of illnesses, including pathogen infections. However, we were unable to find any studies that have investigated the antibacterial activity of T. microcarpa. Similarly, whilst some preliminary studies have examined the antimicrobial properties of T. muelleri and T. grandiflora, they did not test the extracts against antibiotic-resistant pathogens. This study screens the antimicrobial activity of T. grandiflora, T. microcarpa, and T. muelleri and compares it to that of T. ferdinandiana extracts prepared from both the fruit and leaves against a range of pathogens, including multi-antibiotic-resistant strains. Solvents with varying polarities were used to extract different phytochemical constituents from the leaves of T. grandiflora, T. microcarpa, and T. muelleri and from the fruit and leaves of T. ferdinandiana. The aqueous and methanolic extracts each displayed significant antimicrobial activity when tested against the bacterial pathogens, including against the multidrug-resistant strains. When these extracts were tested in combination with selected antibiotics, some extracts potentiated the antimicrobial activity. This study identifies twelve synergistic, fifty-eight additive, and sixty non-interactive combinations, as well as thirty antagonistic effects. The extracts were evaluated for toxicity using the Artemia franciscana nauplii lethality assay (ALA) and were each classified as non-toxic, with the exception of the methanolic and aqueous T. ferdinandiana fruit extracts and the aqueous and ethyl acetate T. ferdinandiana leaf extracts. Metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS) highlighted several flavonoids and tannins that may contribute to the antimicrobial activities reported herein. The potential antibacterial mechanism(s) of the T. ferdinandiana extracts are discussed in this study.PMID:38543548 | DOI:10.3390/microorganisms12030498

Pharmaceuticals (Basel). 2024 Mar 9;17(3):355. doi: 10.3390/ph17030355.ABSTRACTThe methods and solvents employed in routine extraction protocols essentially impact the composition of the resulting extracts, i.e., the relative abundances of individual biologically active metabolites and the quality and stability of the isolates. Natural deep eutectic solvents (NADESs) represent a new class of environmentally friendly solvents, which are recognized as promising extractants alternative to conventional organic liquids. However, their relative efficiencies when applied in different extraction workflows are still poorly characterized. Therefore, here, we compare the potential of three extraction methods for the extraction of biologically active natural products from Aralia elata var. mandshurica with selected natural deep eutectic solvents (NADESs) using a non-targeted metabolomics approach. The non-targeted metabolite profiling relied on reversed-phase ultra-high-performance liquid chromatography-high-resolution mass spectrometry (RP-UHPLC-HR-MS). The roots of A. elata were extracted by maceration, ultrasound-assisted extraction (UAE), and vibrocavitation-assisted extraction (VAE). Principal component analysis (PCA) revealed a clear separation of the extracts obtained with the three extraction methods employed with NADES1 (choline chloride/malic acid) and NADES2 (sorbitol/malic acid/water). Based on the results of the hierarchical clustering analysis obtained for the normalized relative abundances of individual metabolites and further statistical evaluation with the t-test, it could be concluded that NADES1 showed superior extraction efficiency for all the protocols addressed. Therefore, this NADES was selected to compare the efficiencies of the three extraction methods in more detail. PCA followed by the t-test yielded only 3 metabolites that were more efficiently extracted by maceration, whereas 46 compounds were more abundant in the extracts obtained by VAE. When VAE and UAE were compared, 108 metabolites appeared to be more abundant in the extracts obtained by VAE, whereas only 1 metabolite was more efficiently recovered by UAE. These facts clearly indicate the advantage of the VAE method over maceration and UAE. Seven of the twenty-seven metabolites tentatively identified by tandem mass spectrometry (MS/MS) were found in the roots of A. elata for the first time. Additional studies are necessary to understand the applicability of VAE for the extraction of other plant materials.PMID:38543141 | DOI:10.3390/ph17030355

Molecules. 2024 Mar 20;29(6):1385. doi: 10.3390/molecules29061385.ABSTRACTTerminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography-mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study.PMID:38543020 | DOI:10.3390/molecules29061385

Molecules. 2024 Mar 11;29(6):1240. doi: 10.3390/molecules29061240.ABSTRACTDisordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using μCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.PMID:38542877 | DOI:10.3390/molecules29061240

Nutrients. 2024 Mar 15;16(6):858. doi: 10.3390/nu16060858.ABSTRACTIn recent years, heightened attention has been devoted to unravelling the intricate interplay between genetic and environmental factors shaping the gut microbiota and its significance for human health. This study delves into exploring the plausible connection between Alopecia Areata (AA), an autoimmune disease, and the dynamics of the gut microbiome. Examining a cohort of healthy adults and individuals with AA, both the gut microbiota composition and volatile organic compound (VOC) metabolites from faeces and urine were analysed. While overall microbiota composition showed no significant differences, intra-individual variability revealed distinctions related to age, gender, and pathology status, with AA individuals exhibiting reduced species richness and evenness. Differential abundance analysis identified microbial biomarkers for AA, notably Firmicutes, Lachnospirales, and Blautia, while Coprococcus stood out for healthy individuals. The Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) method further supported these findings including metabolite biomarkers, such as esters of branched chain fatty acids and branched chain amino acids as predictors for AA, suggesting potential links to oxidative stress. Despite certain limitations, the study highlights the complexity of the gut microbiome and its metabolites in the context of AA, while the biomarkers identified could be useful starting points for upcoming studies.PMID:38542770 | DOI:10.3390/nu16060858

Nutrients. 2024 Mar 14;16(6):841. doi: 10.3390/nu16060841.ABSTRACTProbiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.PMID:38542752 | DOI:10.3390/nu16060841

Nutrients. 2024 Mar 12;16(6):803. doi: 10.3390/nu16060803.ABSTRACTObesity is a risk factor for many diseases, such as type 2 diabetes and cardiovascular diseases. In line with the need for precision medicine, the search for biomarkers reporting the progression of obesity- and diet-associated disorders is urgent. We used NMR to determine the metabolomics profile of key organs (lung, liver, heart, skeletal muscle, kidney, and brain) and serum from male C57Bl/6J mice (5 weeks old) fed for 6, 10, and 14 weeks on a high-fat and high-sucrose diet (HFHSD) vs. a standard diet (STD). We determined metabolite concentrations in the organs at each time point, which allowed us to discriminate age- and diet-related effects as well as the interactions between both, highlighting the need to evaluate the influence of age as a confounding factor on metabolic signatures. Notably, the analysis revealed the influence of time on metabolite concentrations in the STD condition, probably reflecting the juvenile-to-adult transition. Variations impacted the liver and lung metabolites, revealing the strong influence of the HFHS diet on normal metabolism maturation during youth.PMID:38542714 | DOI:10.3390/nu16060803

Int J Mol Sci. 2024 Mar 21;25(6):3545. doi: 10.3390/ijms25063545.ABSTRACTX-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; p = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, p = 0.01). A total of 106 metabolites were identified. Acetylcarnitine (p = 0.03), pyruvate p = (0.04), ethanolamine (p = 0.03), and butyric acid (p = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.PMID:38542517 | DOI:10.3390/ijms25063545

Int J Mol Sci. 2024 Mar 20;25(6):3516. doi: 10.3390/ijms25063516.ABSTRACTDisuse muscle atrophy is a disease caused by restricted activity, affecting human health and animal protein quality. While extensive research on its mechanism has been studied in mammals, comparatively little is known about this process in chickens, which are a significant source of protein for human consumption worldwide. Understanding the mechanisms underlying skeletal muscle atrophy in chickens is crucial for improving poultry health and productivity, as well as for developing strategies to mitigate muscle loss. In this study, two groups of chickens were subjected to limb immobilization for two and four weeks, respectively, in order to induce disuse muscle atrophy and uniformly sampled gastrocnemius muscle at the fourth week. A combined analysis of the transcriptome and metabolome was conducted to investigate the mechanisms of disuse-induced muscle atrophy. Through H&E staining and immunofluorescence, we found that, compared to slow-twitch muscle fibers, the fast-twitch muscle fibers showed a greater reduction in cross-sectional area in the immobilized leg, and were also the main driver of changes in cross-sectional area observed in the non-immobilized leg. Integrated analysis revealed that differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly enriched in pathways related to energy metabolism, such as fatty acid metabolism, oxidative phosphorylation (OXPHOS), and glycolysis. These results provide important insights for further research on disuse muscle atrophy.PMID:38542488 | DOI:10.3390/ijms25063516

Int J Mol Sci. 2024 Mar 20;25(6):3495. doi: 10.3390/ijms25063495.ABSTRACTIn this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.PMID:38542465 | DOI:10.3390/ijms25063495

Int J Mol Sci. 2024 Mar 20;25(6):3475. doi: 10.3390/ijms25063475.ABSTRACTObesity is linked to cognitive decline and metabolic dysregulation in the brain, yet the role of sex is relatively unexplored. We sought to explore the effects of obesity and sex on the brain metabolome. In male and female ob/ob and wild-type mice, we assessed whole brain untargeted metabolomics by liquid chromatography-mass spectrometry, behavior by open field test, and cognitive function by Y-maze and Morris water maze. The metabolic profiles of ob/ob and wild-type mice differed in both sexes. There were more obesity-altered brain metabolites in males than females. Thirty-nine metabolites were unique to males, 15 were unique to females, and five were common to both sexes. Two of the common metabolites were involved in nicotinamide adenine dinucleotide homeostasis. A key feature of the metabolites identified in males was an increase in free fatty acids. In females, a unique feature was the presence of the neuro-modulatory metabolites 2-linoleoyl glycerol and taurine. The behavioral effects of obesity were only seen in females. These results demonstrate that most impacts of obesity on the brain metabolomic profile are sex-specific. Our work has implications for understanding the role of obesity in brain metabolism and the differential contribution of obesity to cognitive decline in males and females.PMID:38542451 | DOI:10.3390/ijms25063475

Int J Mol Sci. 2024 Mar 18;25(6):3424. doi: 10.3390/ijms25063424.ABSTRACTAspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-β-muricholic acid (T-β-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.PMID:38542397 | DOI:10.3390/ijms25063424