PubMed

Int J Tryptophan Res. 2023 Dec 22;16:11786469231220781. doi: 10.1177/11786469231220781. eCollection 2023.ABSTRACTBACKGROUND: Around 10% of people who had COVID-9 infection suffer from persistent symptoms such as fatigue, dyspnoea, chest pain, arthralgia/myalgia, sleep disturbances, cognitive dysfunction and impairment of mental health. Different underlying pathomechanisms appear to be involved, in particular inflammation, alterations in amino acid metabolism, autonomic dysfunction and gut dysbiosis.AIM: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis.PATIENTS AND METHODS: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (n = 25; 20 women, 5 men) in comparison to healthy controls (Ctrl, n = 8; 7 women, 1 man) and individuals with ME/CFS (n = 8; 2 women, 6 men). Concentrations of neurotransmitter precursors tryptophan, phenylalanine and their downstream metabolites, as well as their association with symptoms (fatigue, anxiety and depression) in the patients were examined.RESULTS AND CONCLUSION: Phenylalanine levels were significantly lower in both the LC and ME/CFS patient groups when compared to the Ctrl group. In many LC patients, the concentrations of downstream metabolites of tryptophan and tyrosine, such as serotonin, dopamine and catecholamines, deviated from the reference ranges. Several symptoms (sleep disturbance, pain or autonomic dysfunction) were associated with certain metabolites. Patients experiencing fatigue had lower levels of kynurenine, phenylalanine and a reduced kynurenine to tryptophan ratio (Kyn/Trp). Lower concentrations of gamma-aminobutyric acid (GABA) and higher activity of kynurenine 3-monooxygenase (KMO) were observed in patients with anxiety. Conclusively, our results suggest that amino acid metabolism and neurotransmitter synthesis is disturbed in patients with LC and ME/CFS. The identified metabolites and their associated dysregulations could serve as potential biomarkers for elucidating underlying pathomechanisms thus enabling personalized treatment strategies for these patient populations.PMID:38144169 | PMC:PMC10748708 | DOI:10.1177/11786469231220781

ACS Omega. 2023 Dec 7;8(50):48557-48571. doi: 10.1021/acsomega.3c08583. eCollection 2023 Dec 19.ABSTRACTThoroughbred (TB) racehorses undergo rigorous conditioning programs to optimize their physical and mental capabilities through varied exercise sessions. While conventional investigations focus on limited hematological and biochemical parameters, this field study employed untargeted metabolomics to comprehensively assess metabolic responses triggered by exercise sessions routinely used in TB conditioning. Blood samples were collected pre- and post-exercise from ten racehorses, divided into two groups based on exercise intensity: high intensity (n = 6, gallop at ± 13.38 m/s, 1400 m) and moderate intensity (n = 4, soft canter at ± 7.63 m/s, 2500 m). Intensity was evaluated through monitoring of the speed, heart rate, and lactatemia. Resting and 30 min post-exercise plasma samples were analyzed using ultraperformance liquid chromatography coupled with high-resolution mass spectrometry. Unsupervised principal component analysis revealed exercise-induced metabolome changes, with high-intensity exercise inducing greater alterations. Following high-intensity exercise, 54 metabolites related to amino acid, fatty acid, nucleic acid, and vitamin metabolism were altered versus 23 metabolites, primarily linked to fatty acid and amino acid metabolism, following moderate-intensity exercise. Metabolomics confirmed energy metabolism changes reported by traditional biochemistry studies and highlighted the involvement of lipid and amino acid metabolism during routine exercise and recovery, aspects that had previously been overlooked in TB racehorses.PMID:38144146 | PMC:PMC10733985 | DOI:10.1021/acsomega.3c08583

ACS Omega. 2023 Dec 7;8(50):48233-48250. doi: 10.1021/acsomega.3c07424. eCollection 2023 Dec 19.ABSTRACTRetinoblastoma (Rb) is the most common pediatric eye cancer. To identify the biomarkers for early diagnosis and monitoring the progression of Rb in patients, mapping of the alterations in their metabolic profiles is essential. The present study aims at exploring the metabolic disparity in serum from Rb patients and controls using NMR-based metabolomics. A total of 72 metabolites, including carbohydrates, amino acids, and organic acids, were quantified in serum samples from 24 Rb patients and 26 controls. Distinct clusters of Rb patients and controls were obtained using the partial least-squares discriminant analysis (PLS-DA) model. Further, univariate and multivariate analyses of unilateral and bilateral Rb patients with respect to their age-matched controls depicted their distinct metabolic fingerprints. Metabolites including 2-phosphoglycerate, 4-aminobutyrate, proline, O-phosphocholine, O-phosphoethanolamine, and Sn-glycero-3-phosphocholine (Sn-GPC) showed significant perturbation in both unilateral and bilateral Rb patients. However, metabolic differences among the bilateral Rb cases were more pronounced than those in unilateral Rb cases with respect to controls. In addition to major discriminatory metabolites for Rb, unilateral and bilateral Rb cases showed specific metabolic changes, which might be the result of their differential genetic/somatic mutational backgrounds. This further suggests that the aberrant metabolic perturbation in bilateral patients signifies the severity of the disease in Rb patients. The present study demonstrated that identified serum metabolites have potential to serve as a noninvasive method for detection of Rb, discriminate bilateral from unilateral Rb patients, and aid in better understanding of the RB tumor biology.PMID:38144138 | PMC:PMC10733957 | DOI:10.1021/acsomega.3c07424

Food Chem X. 2023 Dec 3;20:101044. doi: 10.1016/j.fochx.2023.101044. eCollection 2023 Dec 30.ABSTRACTThe thermophilic phase of Daqu fermentation is considered the key period for aroma production in Daqu, but little is known about the changes in substances during this phase. In this study, we combined a metabolomics approach with high-throughput sequencing to analyze the metabolic profiles and identify metabolism-associated microbes during the thermophilic phase of Daqu fermentation. The results revealed that the metabolic sets after 5 and 9 days of fermentation in the thermophilic phase were similar, and several amino acid and biosynthesis-related metabolic pathways were significantly enriched. In addition, pyrazines and alkanes increased and esters decreased significantly after the thermophilic phase. The metabolism of substances during the thermophilic phase involved 38 genera, and the main metabolic pathways involved were glycolysis, TCA cycle, butyric acid metabolism, and five amino acid metabolic pathways. In summary, this study points in the direction for unravelling the mechanism of aroma production in Daqu.PMID:38144852 | PMC:PMC10739848 | DOI:10.1016/j.fochx.2023.101044

Food Chem X. 2023 Oct 31;20:100972. doi: 10.1016/j.fochx.2023.100972. eCollection 2023 Dec 30.ABSTRACTApple fruit is susceptible to compression damage within the postharvest supply chain given its thin peels and brittle texture, which can result in decay and deterioration and have a substantial impact on its marketability and competitiveness. Thorough bioinformatics investigations are lacking on postharvest compression damage stress-induced alterations in genes and metabolic regulatory networks in fruits. In the present study, a comprehensive analysis of both the transcriptome and metabolome was conducted on 'Red Fuji' apples experiencing compression-induced damage. During the storage after damage has occurred, the gene expression of MdOFUT19, MdWRKY48, MdCBP60E, MdCYP450 and MdSM-like of the damaged apples was consistently higher than that of the control group. The damaged apples also had higher contents of some metabolites such as procyanidin A1, Dl-2-Aminooctanoic acid, 5-O-p-Coumaroyl shikimic acid and 5,7-Dihydroxy-3',4',5'-trimethoxyflavone. Analysis of genes and metabolites with distinct expressions on the common annotation pathway suggested that the fruit may respond to compression stress by promoting volatile ester and lignin synthesis. The above results can deepen the comprehension of the response mechanisms in apple fruits undergoing compression-induced damage.PMID:38144847 | PMC:PMC10740140 | DOI:10.1016/j.fochx.2023.100972

Food Chem X. 2023 Nov 28;20:101031. doi: 10.1016/j.fochx.2023.101031. eCollection 2023 Dec 30.ABSTRACTLactuca indica L. cv. Mengzao (LIM), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. This research delves into the influence of various harvest periods (vegetative, budding, blossom, and fruiting) on distinct medicinal parts (roots, stems, leaves, flowers, and seeds) of LIM, employing plant metabolomics to assess its chemical constituents. A total of 66 chemical constituents were identified in LIM, with 11 chemical components emerging as potential markers for distinguish medicinal parts. Notably, nutritional organs exhibited elevated levels of cichoric acid, rutin and chlorogenic acid. Specifically, leaves during the budding stage displayed the highest chicoric acid content at 11.70 mg·g-1. Conversely, reproductive organs showed heightened concentrations of cichoric acid, rutin and chlorogenic acid, with seeds exhibiting the peak cichoric acid content at 4.53 mg g-1. This study enriches our understanding of LIM by offering novel insights into quality assessment and the comprehensive utilization of its diverse parts.PMID:38144840 | PMC:PMC10740015 | DOI:10.1016/j.fochx.2023.101031

Food Chem X. 2023 Oct 27;20:100966. doi: 10.1016/j.fochx.2023.100966. eCollection 2023 Dec 30.ABSTRACTThis study aimed to characterize the metabolic profile of Salmonella enteritidis (S. enteritidis) in chicken matrix and to identify metabolic biomarkers of S. enteritidis in chicken. The UHPLC-QTRAP-MS high-throughput targeted metabolomics approach was employed to analyze the metabolic profiles of contaminated and control group chickens. A total of 348 metabolites were quantified, and the application of deep learning least absolute shrinkage and selection operator (LASSO) modelling analysis obtained eight potential metabolite biomarkers for S. enteritidis. Metabolic abundance change analysis revealed significantly enriched abundances of anthranilic acid, l-pyroglutamic acid, 5-hydroxylysine, n,n-dimethylarginine, 4-hydroxybenzoic acid, and menatetrenone in contaminated chicken samples. The receiver operating characteristic (ROC) curve analysis demonstrated the strong ability of these six metabolites as biomarkers to distinguish S. enteritidis contaminated and fresh chicken samples. The findings presented in this study offer a theoretical foundation for developing an innovative approach to identify and detect foodborne contamination caused by S. enteritidis.PMID:38144757 | PMC:PMC10740086 | DOI:10.1016/j.fochx.2023.100966

Food Chem X. 2023 Nov 11;20:101000. doi: 10.1016/j.fochx.2023.101000. eCollection 2023 Dec 30.ABSTRACTOats is a cereal well known for its high nutritional value and unique flavor. This study investigated the metabolomics data from oats, wheat, and barley using broadly targeted GC-MS metabonomic techniques. A total of 437 volatile organic compounds (VOCs) were identified, of which 414 were shared metabolites, with three metabolites unique to oats. Three hundred and seven differentially accumulated metabolites (DAMs) were screened from all the comparison groups, of which 27 metabolites were shared by oats and barley, and 121 shared by oats and wheat. Terpenoids and esters were the key metabolites determining the differences in flavor. A KEGG analysis indicated that the alpha-linolenic acid and phenylalanine pathways were the most significant metabolic pathways. The 42 DAMs found may be the main substances leading to the flavor differences between the different varieties. Overall, this study reveals the main reasons for the unique flavor of oats through metabolomic evidence.PMID:38144731 | PMC:PMC10740038 | DOI:10.1016/j.fochx.2023.101000

Front Endocrinol (Lausanne). 2023 Dec 8;14:1261781. doi: 10.3389/fendo.2023.1261781. eCollection 2023.ABSTRACTINTRODUCTION: Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation.METHODS: In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry.RESULTS: We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice.CONCLUSION: The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.PMID:38144564 | PMC:PMC10748389 | DOI:10.3389/fendo.2023.1261781

iScience. 2023 Nov 24;26(12):108566. doi: 10.1016/j.isci.2023.108566. eCollection 2023 Dec 15.ABSTRACTIn pancreatic ductal adenocarcinomas (PDAC), the KRASG12D-NRF2 axis controls cellular functions such as redox homeostasis and metabolism. Disruption of this axis through suppression of NRF2 leads to profound reprogramming of metabolism. Unbiased transcriptome and metabolome analyses showed that PDAC cells with disrupted KRASG12D-NRF2 signaling (NRF2-/- cells) shift from aerobic glycolysis to metabolic pathways fed by amino acids. Metabolome, RNA-seq and qRT-PCR analyses revealed a blockade of the urea cycle, making NRF2-/- cells dependent on exogenous arginine for survival. Arginine is channeled into anabolic pathways, including the synthesis of phosphocreatine, which generates an energy buffer essential for cell growth. A similar switch was observed in tumor clones that had survived FOLFIRINOX therapy or blockade of KRAS signaling. Inhibition of the creatine pathway with cyclocreatine reduced both ATP and invasion rate in 3D spheroids from NRF2-deficient PDAC cells. Our study provides basis for the rational development of combination therapies for pancreatic cancer.PMID:38144458 | PMC:PMC10746371 | DOI:10.1016/j.isci.2023.108566

Front Nutr. 2023 Dec 8;10:1301715. doi: 10.3389/fnut.2023.1301715. eCollection 2023.ABSTRACTDuhaldea nervosa (Wallich ex Candolle) Anderberg has been widely used as medicine and food additive in China for a long history. Its roots, known as Xiaoheiyao, are the mainly used medicinal part, while the other tissues of D. nervosa are ignored as non-medicinal parts despite their high biomass, resulting in a huge waste of resources. To mine and expand the medicinal values of different parts of D. nervosa, metabolic analysis by GC/LC-MS and bioactivity evaluation were performed. Based on the antioxidant activity and correlation analysis, a metabolite-related network was constructed. A total of 45 volatile and 174 non-volatile compounds were identified. Among them, caffeoylquinic acids and derivatives were more abundant in roots and flowers, while coumaroyltartaric acids and derivatives were mainly present in stems and leaves. By multivariate analysis, 13 volatile and 37 non-volatile differential metabolites were found, respectively. In the bioactivity evaluation of different parts, the order of antioxidant capacity was flowers > roots > leaves or stems. The flowers showed the highest FRAP value (354.47 μM TE/g DW) and the lowest IC50 values in the DPPH (0.06 mg/mL) and ABTS (0.19 mg/mL) assay, while higher inhibitory activity against α-glucosidase was exhibited by flowers and leaves. This study first established the similarities and differences of phytochemicals and bioactivities in D. nervosa, providing a scientific basis for developing non-medicinal parts and guiding the clinical application of this medicinal and edible herb.PMID:38144429 | PMC:PMC10748410 | DOI:10.3389/fnut.2023.1301715

PeerJ. 2023 Dec 19;11:e16611. doi: 10.7717/peerj.16611. eCollection 2023.ABSTRACTThis study aims to investigate the regulatory mechanism of choline (CH) on triglyceride (TG) synthesis in cows, with a specific focus on its potential association with high milk fat percentage in the gut of the Zhongdian yak. By employing combined metagenomics and metabolomics analysis, we establish a correlation between CH and milk fat production in yaks. Bovine mammary epithelial cells (MAC-T) were exposed to varying CH concentrations, and after 24 h, we analyzed the expression levels of key proteins (membrane glycoprotein CD36 (CD36); adipose differentiation-related protein (ADFP); and ubiquintin (UB)), cellular TG content, lipid droplets, and cell vitality. Additionally, we evaluated the genes potentially related to the CH-mediated regulation of TG synthesis using real-time qPCR. CH at 200 μM significantly up-regulated CD36, ADFP, UB, and TG content. Pathway analysis reveals the involvement of the ubiquitination pathway in CH-mediated regulation of TG synthesis. These findings shed light on the role of CH in controlling TG synthesis in MAC-T cells and suggest its potential as a feed additive for cattle, offering possibilities to enhance milk fat production efficiency and economic outcomes in the dairy industry.PMID:38144203 | PMC:PMC10740596 | DOI:10.7717/peerj.16611

ACS Omega. 2023 Dec 5;8(50):47573-47584. doi: 10.1021/acsomega.3c05597. eCollection 2023 Dec 19.ABSTRACTAmaranthus (family Amaranthaceae) is a potentially nutritious pseudocereal also known as a functional food owing to its high nutritional quality grains especially rich in essential amino acids. Emerging study, however, unambiguously indicates that apart from essential nutrients like protein, other phytochemicals present in amaranth seeds provide excellent health benefits. Squalene is one such phytonutrient found in Amaranthus seeds, which is also its largest vegetal source. In this research work, GC-MS and NMR spectroscopy-based metabolomics have been utilized for the compositional analysis of Amaranthus seeds coupled with a multivariate data set. Investigation of nonpolar and polar seed extracts of six different cultivars of amaranth identified 47 primary and secondary metabolites. One-way ANOVA showed significant quantitative metabolic variations in different cultivars of amaranth. Multivariate principal component analysis of both the GC-MS and NMR analyzed data broadly classified in two groups showed significant variations in the polar (lysine, arginine, GABA, and myoinositol) and nonpolar (squalene, tryptophan, and alkylated phenols, which are potential nutraceutical agents) metabolites. The squalene content estimated using HPLC varied significantly (1.61 to 4.72 mg g-1 seed dry weight) among six different cultivars. Positive correlations were found among the cellular antioxidant activity and squalene content. Cultivar AM-3 having the maximum squalene content showed the highest antioxidant activity evaluated on the cellular level over human embryonic kidney cells, clearly revealing potent intercellular reactive oxygen species scavenging capacity and strong membrane lipid peroxidation inhibition potential. Oxidative stress markers such as MDA, SOD, GSH, and CAT levels in cells further corroborated the research work. The study also indicated high concentrations of lysine (80.49 mg g-1 dry seeds) in AM-2, squalene (0.47% by weight) in AM-3, and 2,4-di-tert-butyl phenol (18.64% peak area) and myoinositol (79.07 mg g-1 dry seeds) in AM-5. This novel comparative metabolomic study successfully profiles the nutrient composition of amaranth cultivars and provides the opportunity for the development of nutraceuticals and natural antioxidants from this functional food.PMID:38144049 | PMC:PMC10733922 | DOI:10.1021/acsomega.3c05597

Front Physiol. 2023 Dec 7;14:1295852. doi: 10.3389/fphys.2023.1295852. eCollection 2023.ABSTRACTBackground: Metabolite-based sensors are attractive and highly valued for monitoring physiological parameters during rest and/or during physical activities. Owing to their molecular composition consisting of nucleic acids, proteins, and metabolites, extracellular vesicles (EVs) have become acknowledged as a novel tool for disease diagnosis. However, the evidence for sweat related EVs delivering information of physical and recovery states remains to be addressed. Methods: Taking advantage of our recently published methodology allowing the enrichment and isolation of sweat EVs from clinical patches, we investigated the metabolic load of sweat EVs in healthy participants exposed to exercise test or recovery condition. -Ten healthy volunteers (-three females and -seven males) were recruited to participate in this study. During exercise test and recovery condition, clinical patches were attached to participants' skin, on their back. Following exercise test or recovery condition, the patches were carefully removed and proceed for sweat EVs isolation. To explore the metabolic composition of sweat EVs, a targeted global metabolomics profiling of 41 metabolites was performed. Results: Our results identified seventeen metabolites in sweat EVs. These are associated with amino acids, glutamate, glutathione, fatty acids, creatine, and glycolysis pathways. Furthermore, when comparing the metabolites' levels in sweat EVs isolated during exercise to the metabolite levels in sweat EVs collected after recovery, our findings revealed a distinct metabolic profiling of sweat EVs. Furthermore, the level of these metabolites, mainly myristate, may reflect an inverse correlation with blood glucose, heart rate, and respiratory rate levels. Conclusion: Our data demonstrated that sweat EVs can be purified using routinely used clinical patches during physical activity, setting the foundations for larger-scale clinical cohort work. Furthermore, the metabolites identified in sweat EVs also offer a realistic means to identify relevant sport performance biomarkers. This study thus provides proof-of-concept towards a novel methodology that will focus on the use of sweat EVs and their metabolic composition as a non-invasive approach for developing the next-generation of sport wearable sensors.PMID:38143912 | PMC:PMC10748597 | DOI:10.3389/fphys.2023.1295852

Front Microbiol. 2023 Dec 8;14:1294055. doi: 10.3389/fmicb.2023.1294055. eCollection 2023.ABSTRACTBACKGROUND: Mycoplasmas are among the smallest prokaryotic microbes that can grow and proliferate on non-living media. They have reduced genomes, which may be associated with a concomitant reduction in their metabolic capacity. Mycoplasma capricolum subsp. capripneumoniae (Mccp) and Mycoplasma capricolum subsp. capricolum (Mcc), both belong to the Mycoplasma mycoides cluster, are significant important pathogenic Mycoplasma species in veterinary research field. They share high degree of genome homology but Mcc grows markedly faster and has higher growth titer than Mccp.METHODS: This study investigated the metabolites of these two pathogenic bacteria from the middle and late stages of the logarithmic growth phase through liquid chromatography-mass spectrometry-based metabolomics and targeted energy metabolomics. The multivariate analysis was conducted to identify significant differences between the two important Mycoplasma species.RESULTS: A total of 173 metabolites were identified. Of them, 33 and 34 metabolites involved in purine and pyrimidine, pyruvate metabolism, and amino acid synthesis were found to significantly differ in the middle and late stages, respectively. The abundance of fructose 1,6-bisphosphate, ADP, and pyruvate was higher in Mcc than in Mccp during the whole logarithmic period. Lactate was upregulated in slow-growing Mccp. The pH buffering agent N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] added to media effectively prevented pH reduction and increase bacterial viability and protein biomass. The multivariate analysis revealed that the two Mycoplasma species significantly differed in glucose metabolism, growth factor transport and metabolism, cholesterol utilization, and environmental regulation.CONCLUSION: The study data are beneficial for understanding the metabolomic characteristics of these two crucial Mycoplasma species and shedding more light on mycoplasma metabolism, and serve as a resource for the pathogenesis and development of related vaccines.PMID:38143857 | PMC:PMC10740972 | DOI:10.3389/fmicb.2023.1294055

Front Mol Biosci. 2023 Dec 6;10:1249744. doi: 10.3389/fmolb.2023.1249744. eCollection 2023.ABSTRACTIntroduction: Cadmium (Cd) is a hazardous environmental pollutant present in soil, water, and food. Accumulation of Cd in organisms can cause systematic injury and damage to the kidney. The Masson pine pollen aqueous extract (MPPAE) has attracted increasing attention due to its antioxidant activity and ability to enhance immunity. Methods: In this study, we investigated the potential of MPPAE to protect against Cd-induced kidney damage in rats and the underlying mechanism. The transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, were explored. Results: The concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were both significantly altered after treatment with MPPAE. Furthermore, sequencing and analysis of the transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, revealed differential expression of numerous genes and metabolites compared with the untreated control rats. These differentially expressed genes (DEGs) included detoxification-related genes such as cytochrome P450 and the transporter. The differentially expressed metabolites (DEMs) included 4-hydroxybenzoic acid, L-ascorbate, and ciliatine. Conjoint transcriptome and metabolome analysis showed that several DEGs were correlated with DEMs. Conclusion: These preliminary findings indicate the potential of MPPAE for the treatment of toxic metal poisoning.PMID:38143799 | PMC:PMC10748820 | DOI:10.3389/fmolb.2023.1249744

Front Pharmacol. 2023 Dec 8;14:1320419. doi: 10.3389/fphar.2023.1320419. eCollection 2023.ABSTRACTNeuropathic pain often leads to negative emotions, which in turn can enhance the sensation of pain. This study aimed to investigate the molecular mechanisms mediating neuropathic pain and negative emotions. Chronic constriction injury (CCI) rats were used as model animals and behavioral tests were conducted to assess pain and negative emotions. Then, the rat anterior cingulate cortex (ACC) was analyzed using UPLC-MS/MS and subsequently integrated with our previously published transcriptome data. Metabolomics analysis revealed that 68 differentially expressed metabolites (DEMs) were identified, mainly in amino acid metabolites and fatty acyls. Combined with our previously published transcriptome data, we predicted two genes that potentially exhibited associations with these metabolites, respectively Apolipoprotein L domain containing 1 (Apold1) and WAP four-disulfide core domain 1 (Wfdc1). Taken together, our results indicated that peripheral nerve injury contributing to neuropathic pain and pain-related depression may be associated with these metabolites and genes. This research provides new insights into the molecular regulatory mechanism, which could serve as a reference for the treatment of neuropathic pain and pain-related depression.PMID:38143492 | PMC:PMC10739318 | DOI:10.3389/fphar.2023.1320419

Sci Total Environ. 2023 Dec 22:169487. doi: 10.1016/j.scitotenv.2023.169487. Online ahead of print.ABSTRACTUnsaturated fatty acids (UFA) are known to play a vital role in regulating stress resistance and metabolism in corals. Nevertheless, a comprehensive understanding of the microbial and functional composition of the UFA synthesis pathway (UFASP) remains lacking. This study employed metagenome and metabolome to investigate the microbial community, function, and metabolic response of UFASP in reef-building corals inhabiting the Nansha Islands. Our findings revealed significantly higher diversity for the UFASP microbe in bleached corals compared to unbleached corals. Furthermore, principal coordinates analysis (PCoA) and taxonomy assessments exhibited notable distinctions in the microbe between the two coral states. Notably, the dominant microorganisms involved in UFASP were Dinophyceae, Sordariomycetes, Ulvophyceae, and Chlorophyceae. Bleaching resulted in a considerable increase in fungal abundance within coral symbionts. A total of 12 KEGG Orthology (KO) were identified in UFASP, with PCoA analysis indicating significant differences in their abundance between bleached and unbleached corals. UFASP's beta-Oxidation module exhibited reduced abundance in bleached corals. Contribution analysis highlighted the participation of Symbiodiniaceae, Ascomycota, Chlorophyta, Proteobacteria, and Actinobacteria in UFASP. Notably, Symbiodiniaceae and Ascomycota were the major contributors to two UFASP modules, with the latter displaying greater involvement in bleached corals. Furthermore, significant differences in n3 and n6-family metabolites were observed between bleached and unbleached corals. Notably, bleaching induced a reduction in metabolites of Symbiodiniaceae, while an increase in the multiple UFAs abundance was detected in bleached corals. These findings suggest that bleaching-induced alterations coral symbionts composition directly impact the functionality of UFASP, ultimately affecting the corals' capacity to adapt to stress.PMID:38142991 | DOI:10.1016/j.scitotenv.2023.169487

Brain Behav Immun. 2023 Dec 22:S0889-1591(23)00405-1. doi: 10.1016/j.bbi.2023.12.023. Online ahead of print.ABSTRACTHuntington's disease (HD) is a neurodegenerative disorder involving psychiatric, cognitive, and motor deficits, as well as peripheral symptoms, including gastrointestinal dysfunction. The R6/1 HD mouse model expresses a mutant human huntingtin transgene and has been shown to provide an accurate disease model. Recent evidence of gut microbiome disruption was shown in preclinical and clinical HD. Therefore, we aimed to assess the potential role of gut microbial modulation in the treatment of HD. The R6/1 HD mice and wild-type littermate controls were randomised to receive diets containing different amounts of fibre: high-fibre (10 % fibre), control (5 % fibre), or zero-fibre (0 % fibre), from 6 to 20 weeks of age. We characterized the onset and progression of motor, cognitive and affective deficits as well as gastrointestinal function and gut morphological changes. Faeces were collected for gut microbiome profiling using 16S rRNA sequencing at 14 and 20 weeks of age. When compared to the control diet, high-fibre diet improved the performance of HD mice in behavioral tests of cognitive and affective function, as well as the gastrointestinal function of both HD and wild-type mice. While the diets changed the beta diversity of wild-type mice, no statistical significance was observed at 14 or 20 weeks of age within the HD group. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota composition, which identified differences, including a decreased relative abundance of the phyla Actinobacteriota, Campylobacterota and Proteobacteria and an increased relative abundance of the families Bacteroidaceae, Oscillospiraceae and Ruminococcaceae in HD mice when compared to wild-type after receiving high-fibre diet. PICRUSt2 revealed that high-fibre diet also decreased potentially pathogenic functional pathways in HD. In conclusion, high-fibre intake was effective in enhancing gastrointestinal function, cognition and affective behaviors in HD mice. These findings indicate that dietary fibre interventions may have therapeutic potential in Huntington's disease to delay clinical onset, and have implications for related disorders exhibiting dysfunction of the gut-brain axis.PMID:38142919 | DOI:10.1016/j.bbi.2023.12.023

Immunol Lett. 2023 Dec 22:S0165-2478(23)00204-3. doi: 10.1016/j.imlet.2023.12.003. Online ahead of print.ABSTRACTImmunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites during inflammation with the aim of controlling and re-wiring aberrant macrophages in inflammatory diseases. M-CSF and GM-CSF-differentiated macrophages play a key role in mounting successful innate immune responses. When a resolution phase is not achieved however, GM-CSF macrophages contribute substantially more towards an adverse inflammatory milieu than M-CSF macrophages, consequently driving disease progression. Whether there are specific immunometabolites that determine the homeostatic or inflammatory nature of M-CSF and GM-CSF-differentiated macrophages is still unknown. As such, we performed metabolomics analysis on LPS and IL-4-stimulated M-CSF and GM-CSF-differentiated human macrophages to identify differentially accumulating metabolites. Adenine was distinguished as a metabolite significantly higher in M-CSF-differentiated macrophages after both LPS or IL-4 stimulation. Human macrophages treated with adenine before LPS stimulation showed a reduction in inflammatory gene expression, cytokine secretion and surface marker expression. Adenine caused macrophages to become more quiescent by lowering glycolysis and OXPHOS which resulted in reduced ATP production. Moreover, typical metabolite changes seen during LPS-induced macrophage metabolic reprogramming were absent in the presence of adenine. Phosphorylation of metabolic signaling proteins AMPK, p38 MAPK and AKT were not responsible for the suppressed metabolic activity of adenine-treated macrophages. Altogether, in this study we highlight the immunomodulating capacity of adenine in human macrophages and its function in driving cellular quiescence.PMID:38142781 | DOI:10.1016/j.imlet.2023.12.003