PubMed

Nutr Metab Cardiovasc Dis. 2022 Dec 17:S0939-4753(22)00498-7. doi: 10.1016/j.numecd.2022.12.011. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: The association between the metabolic syndrome (MetS) and plasminogen activator inhibitor-1 (PAI-1) has been well established in cross-sectional studies. It is less clear whether this translates into decreased clot lysis rates and very little information is available on non-European populations. Little is known regarding prospective associations and whether clot lysis progressively worsens in MetS individuals over time. We determined the prospective association of MetS with PAI-1 activity (PAI-1act) and clot lysis time (CLT) over a 10-year period.METHODS AND RESULTS: As many as 2010 African men and women aged ≥30 years were stratified according to MetS status and number of MetS criteria (0-5). We also determined the contribution of the PAI-1 4G/5G polymorphism to these associations and identified which MetS criteria had the strongest associations with PAI-1act and CLT. Both PAI-1act and CLT remained consistently elevated in individuals with MetS throughout the 10-year period. PAI-1act and CLT did not increase more over time in MetS individuals than in controls. The 4G/5G genotype did not influence the association of PAI-1act or clot lysis with MetS. Increased waist circumference, increased triglycerides and decreased HDL-C were the main predictors of PAI-1act and CLT.CONCLUSIONS: Black South Africans with MetS had increased PAI-1act and longer CLTs than individuals without MetS. The inhibited clot lysis in MetS did, however, not deteriorate over time compared to controls. Of the MetS criteria, obesity and altered lipids were the main predictors of PAI-1act and CLT and are thus potential targets for prevention strategies to decrease thrombotic risk.PMID:36646603 | DOI:10.1016/j.numecd.2022.12.011

Environ Pollut. 2023 Jan 13:121081. doi: 10.1016/j.envpol.2023.121081. Online ahead of print.ABSTRACTMicroplastics (MPs) are a global threat to the environment, and plant uptake of MP particles (≤0.2 μm) is a particular cause for concern. However, physiological and molecular mechanisms underlying MP-induced growth inhibition need to be clarified. Towards this goal, we conducted a hydroponic experiment to investigate the accumulation of MPs, changes in physiology, gene expression, and metabolites in lettuce from a series of concentrations of fluorescence-labelled polystyrene MPs (0, 10, 20, 30, 40, 50 mg L-1, ∼0.2 μm). Our results showed that MPs accumulated in the lettuce root tips and leaf veins, resulting in the hypertonic injury of lettuce, and the down-regulation of genes related to ion homeostasis. Stress-related genes were up-regulated, and sphingolipid metabolism increased in response to MP additions, causing increased biosynthesis of ascorbic acid, terpenoid, and flavonoids in root exudates. Our findings provide a molecular-scale perspective on the response of leafy vegetables to MP-stress at a range of concentrations. This enables more comprehensive evaluation of the risks of MPs to human health and the ecological environment.PMID:36646407 | DOI:10.1016/j.envpol.2023.121081

Environ Pollut. 2023 Jan 13:121071. doi: 10.1016/j.envpol.2023.121071. Online ahead of print.ABSTRACTToxic effects of exposure to microplastics (MPs) on living organisms and humans have attracted global concern. However, most previous studies exposed animals to only one type of MP (mainly polystyrene) to assess the health risk of MPs for animals. Therefore, we conducted a laboratory gavage experiment on rats based on the types and concentration of MPs to which humans are exposed in their daily life. The purpose of this study is to use Sprague-Dawley (SD) rat models to assess the potential health risks in mammals from co-exposure to various MPs. In the present study, SD rats were exposed to 12 mg/kg bw/day mixed-MPs (containing 10 types of MPs) for 42 days, and then examined the alteration of gut microbes and serum metabolites. The results showed that 6 gut microbes at the family level (f_Muribaculaceae, f_Oscillospiraceae, f_Bacteroidaceae, f_Neisseriaceae, f_Prevotellaceae, and f_Veillonellaceae) were significantly perturbed (t-test, p < 0.05) in rats after MP exposure. After MP intervention, 47 metabolites significantly regulated in SD rat serum, mainly including lipids and lipid-like molecules (e.g., fatty acids), organic acids and derivatives (e.g., phosphoric acids), and isoflavonoids (e.g., daidzein). These findings contribute to assessing the health risks of various MP co-exposure in mammals in the actual environment and provide a novel insight into the toxicity mechanism of MPs.PMID:36646405 | DOI:10.1016/j.envpol.2023.121071

Clin Immunol. 2023 Jan 13:109230. doi: 10.1016/j.clim.2023.109230. Online ahead of print.ABSTRACTBACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal adverse event resulting from immunotherapy in patients with malignant tumors. However, the pathogenesis of CIP remains poorly understood.METHODS: We collected bronchoalveolar lavage fluid (BALF) from cohorts of patients with CIP, new-onset lung cancer (LC), and idiopathic pulmonary fibrosis (IPF). Non-targeted metabolomics analysis was conducted to analyze metabolic signatures. Flow cytometry was used to evaluate immune cell subsets.RESULTS: Lymphocytes were predominant in the BALF of patients with CIP. A total of 903 metabolites were identified, among which lipid compounds were the most abundant. In a comparison between patients with CIP and LC, enrichment analysis of the altered metabolites showed suppressed amino sugar metabolism, and spermidine and spermine biosynthesis in the CIP group. Metabolism of alpha linolenic acid, linoleic acid, and their fatty acid derivatives was enriched in the CIP group relative to the IPF group. The twelve metabolites found to be enriched in the CIP group were positively correlated with the proportion of CD8+ T cells. One cluster of BALF metabolites, 57.14% of which were lipid molecules, was inversely correlated with the proportion of natural killer cells.CONCLUSIONS: In this study, the metabolomic landscape of BALF in patients with CIP was determined. We elucidated suppressed tumor metabolic signatures, enhanced pulmonary inflammatory signaling, and the characteristics of responsible immune cells, which helps to understand the pathogenesis of CIP.PMID:36646189 | DOI:10.1016/j.clim.2023.109230

Neuroendocrinology. 2023 Jan 16. doi: 10.1159/000529146. Online ahead of print.ABSTRACTIntroduction The present study aimed to prove the metyrapone short test in a day clinic to be suitable for examining the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with suspected secondary and tertiary adrenal insufficiency and to identify novel effector molecules in acute stress response. Methods 44 patients were prospectively enrolled. Based on stimulated 11-deoxycortisol levels, patients were divided into a physiological (11-deoxycortisol ≥70 µg/l) and a pathological (11-deoxycortisol <70 µg/l) response group. Clinical follow-up examination was performed for validation. Ultra-performance-liquid-chromatography-tandem-mass-spectrometry and a Fourier-transform-ion-cyclotron-resonance-mass-spectrometry were used for targeted and untargeted steroid metabolomics. Results At baseline, lower levels of cortisone (42 vs. 50 nmol/l, p=0.048) and 17-OH-progesterone (0.6 vs. 1.2 nmol/l, p=0.041) were noted in the pathological response group. After metyrapone administration, the pathological response group exhibited significantly lower 11-deoxycortisol (39.0 vs. 94.2 µg/l, p<0.001) and ACTH (49 vs. 113 pg/ml, p<0.001) concentrations as well as altered upstream metabolites. Untargeted metabolomics identified a total of 76 metabolites to be significantly up- or downregulated by metyrapone. A significant increase of the bile acid glycochenodeoxycholic acid (GCDC, p<0.01) was detected in both groups with an even stronger increase in the physiological response group. After a mean follow-up of 17.2 months, an 11-deoxycortisol cut-off of 70 µg/l showed a high diagnostic performance (sensitivity 100%, specificity 96%). Conclusion The metyrapone short test is safe and feasible in a day clinic setting. The alterations of the bile acid GCDC indicate that the liver might be involved in the acute stress response of the HPA axis.PMID:36646062 | DOI:10.1159/000529146

Rapid Commun Mass Spectrom. 2023 Jan 16:e9473. doi: 10.1002/rcm.9473. Online ahead of print.ABSTRACTRATIONALE: Anemarrhenae Rhizoma (AR) has been a often used traditional Chinese medicine (TCM) for a long time. Its salt processing is one of the most common application forms. Modern pharmacological research showed that the salt-processed product has significantly enhanced various pharmacological activities. However, the pharmacodynamic material basis of this change had not been yet known. The aim of this study was to develop a strategy to screen pharmacodynamic substances in AR and salt-processed Anemarrhenae Rhizoma (SAR).METHODS: An integrated strategy combined plant metabolomics with molecular docking technology was established to screen pharmacodynamic substances. The plant metabolomics analysis was performed to select the chemical markers between AR and SAR. Then, molecular docking technology was applied to explore the relationship between chemical markers and diabetes targets (α-glucosidase). Finally, potential quality control markers were screened.RESULTS: As a result, there were significant differences in the quantification of 9 steroidal saponins between AR and SAR. The results of plant metabolomics showed that a quite clear discrimination including 29 chemical markers between AR and SAR. Taking the hypoglycemic activity into consideration, 16 steroidal saponins were selected as the potential quality markers.CONCLUSION: The developed method not only supplied an optional solution to search for pharmacophores in AR and SAR, but also provided a foundation for the study of the differential components and pharmacodynamics in different processed products of TCM.PMID:36645740 | DOI:10.1002/rcm.9473

Metabolomics. 2023 Jan 16;19(2):6. doi: 10.1007/s11306-022-01968-7.ABSTRACTINTRODUCTION: Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated.OBJECTIVES: Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3).METHODS: Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting.RESULTS: Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect.CONCLUSIONS: All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.PMID:36645548 | DOI:10.1007/s11306-022-01968-7

J Sci Food Agric. 2023 Jan 16. doi: 10.1002/jsfa.12457. Online ahead of print.ABSTRACTBACKGROUND: Tilapia skin collagen hydrolysates (TSCHs) are the product of enzymatic hydrolysis of collagen, which is mainly extracted from tilapia skin. The components of TSCHs have recently been reported play a preventive role in dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). However, it has not been illustrated whether TSCHs can prevent against DSS-induced UC via the gut microbiota and its derived metabolites.RESULTS: TSCHs are mainly composed of amino acids, which have similar characteristics to collagen, with most having a molecular weight below 5 kDa. In a mouse model of UC, TSCHs had no toxic effect at a dose of 60 g kg-1 and could reduce body weight changes, colon length, histopathological changes and score, and the level of the serum inflammatory cytokine interleukin (IL)-6. Concurrently, 16S rRNA sequencing showed that TSCHs significantly reduced the abundance of Bacteroidetes and Proteobacteria at the phylum level and norank_f__Muribaculaceae and Escherichia-Shigella at the genus level, while they increased the abundance of Firmicutes at the phylum level and Lachnoclostridium, Allobaculum, Enterorhabdus, and unclassified__f__Ruminococcaceae at the genus level. Target metabolomic analysis showed that TSCHs elevated the concentration of total acid, acetic acid, propanoic acid, and butanoic acid, but reduced isovaleric acid concentrations. Moreover, Pearson correlation analysis revealed that Allobaculum, unclassified_Ruminococcaceae, and Enterorhabdus were positively correlated with acetic acid and butyric acid, but not Escherichia-Shigella.CONCLUSION: These findings suggest that TSCHs can prevent UC by modulating gut microbial and microbiota-derived metabolites. This article is protected by copyright. All rights reserved.PMID:36645331 | DOI:10.1002/jsfa.12457

J Am Heart Assoc. 2023 Jan 16:e026885. doi: 10.1161/JAHA.122.026885. Online ahead of print.ABSTRACTBackground The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45-75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow-up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age- and sex-adjusted analyses and P<0.05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N-acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, P=0.0054). Thirty-five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1-carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Conclusions Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.PMID:36645074 | DOI:10.1161/JAHA.122.026885

Bioinformatics. 2023 Jan 1;39(1):btad009. doi: 10.1093/bioinformatics/btad009.NO ABSTRACTPMID:36645047 | DOI:10.1093/bioinformatics/btad009

J Ginseng Res. 2023 Jan;47(1):44-53. doi: 10.1016/j.jgr.2022.07.001. Epub 2022 Jul 16.ABSTRACTBACKGROUND: The genus Panax in the Araliaceae family has been used as traditional medicinal plants worldwide and is known to biosynthesize ginsenosides and phytosterols. However, genetic variation between Panax species has influenced their biosynthetic pathways is not fully understood.METHODS: Simultaneous analysis of transcriptomes and metabolomes obtained from adventitious roots of two tetraploid species (Panax ginseng and P. quinquefolius) and two diploid species (P. notoginseng and P. vietnamensis) revealed the diversity of their metabolites and related gene expression profiles.RESULTS: The transcriptome analysis showed that 2,3-OXIDOSQUALENE CYCLASEs (OSCs) involved in phytosterol biosynthesis are upregulated in the diploid species, while the expression of OSCs contributing to ginsenoside biosynthesis is higher in the tetraploid species. In agreement with these results, the contents of dammarenediol-type ginsenosides were higher in the tetraploid species relative to the diploid species.CONCLUSION: These results suggest that a whole-genome duplication event has influenced the triterpene biosynthesis pathway in tetraploid Panax species during their evolution or ecological adaptation. This study provides a basis for further efforts to explore the genetic variation of the Panax genus.PMID:36644396 | PMC:PMC9834023 | DOI:10.1016/j.jgr.2022.07.001

J Ginseng Res. 2023 Jan;47(1):54-64. doi: 10.1016/j.jgr.2022.04.001. Epub 2022 Apr 18.ABSTRACTBACKGROUND: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD.METHODS: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS.RESULTS: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD.CONCLUSION: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host-flora co-metabolism pathway.PMID:36644384 | PMC:PMC9834002 | DOI:10.1016/j.jgr.2022.04.001

JACC Basic Transl Sci. 2022 Oct 31;7(12):1264-1266. doi: 10.1016/j.jacbts.2022.09.011. eCollection 2022 Dec.NO ABSTRACTPMID:36644280 | PMC:PMC9831924 | DOI:10.1016/j.jacbts.2022.09.011

Hortic Res. 2022 Oct 11;10(1):uhac228. doi: 10.1093/hr/uhac228. eCollection 2023.ABSTRACTMomordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.PMID:36643758 | PMC:PMC9832870 | DOI:10.1093/hr/uhac228

Hortic Res. 2022 Oct 26;10(1):uhac239. doi: 10.1093/hr/uhac239. eCollection 2023.ABSTRACTApple (Malus) and pear (Pyrus) are economically important fruit crops well known for their unique textures, flavours, and nutritional qualities. Both genera are characterised by a distinct pattern of secondary metabolites, which directly affect not only resistance to certain diseases, but also have significant impacts on the flavour and nutritional value of the fruit. The identical chromosome numbers, similar genome size, and their recent divergence date, together with DNA markers have shown that apple and pear genomes are highly co-linear. This study utilized comparative genomic approaches, including simple sequence repeats, high resolution single nucleotide polymorphism melting analysis, and single nucleotide polymorphism chip analysis to identify genetic differences among hybrids of Malus and Pyrus, and F2 offspring. This research has demonstrated and validated that these three marker types, along with metabolomics analysis are very powerful tools to detect and confirm hybridity of progeny derived from crosses between apple and pear in both cross directions. Furthermore, this work analysed the genus-specific metabolite patterns and the resistance to fire blight (Erwinia amylovora) in progeny. The findings of this work will enhance and accelerate the breeding of novel tree fruit crops that benefit producers and consumers, by enabling marker assisted selection of desired traits introgressed between pear and apple.PMID:36643755 | PMC:PMC9832871 | DOI:10.1093/hr/uhac239

Hortic Res. 2022 Oct 26;10(1):uhac238. doi: 10.1093/hr/uhac238. eCollection 2023.ABSTRACTTanshinone and phenolic acids are the most important active substances of Salvia miltiorrhiza, and the insight into their transcriptional regulatory mechanisms is an essential process to increase their content in vivo. SmMYB36 has been found to have important regulatory functions in the synthesis of tanshinone and phenolic acid; paradoxically, its mechanism of action in S. miltiorrhiza is not clear. Here, we demonstrated that SmMYB36 functions as a promoter of tanshinones accumulation and a suppressor of phenolic acids through the generation of SmMYB36 overexpressed and chimeric SmMYB36-SRDX (EAR repressive domain) repressor hairy roots in combination with transcriptomic-metabolomic analysis. SmMYB36 directly down-regulate the key enzyme gene of primary metabolism, SmGAPC, up-regulate the tanshinones biosynthesis branch genes SmDXS2, SmGGPPS1, SmCPS1 and down-regulate the phenolic acids biosynthesis branch enzyme gene, SmRAS. Meanwhile, SmERF6, a positive regulator of tanshinone synthesis activating SmCPS1, was up-regulated and SmERF115, a positive regulator of phenolic acid biosynthesis activating SmRAS, was down-regulated. Furthermore, the seven acidic amino acids at the C-terminus of SmMYB36 are required for both self-activating domain and activation of target gene expression. As a consequence, this study contributes to reveal the potential relevance of transcription factors synergistically regulating the biosynthesis of tanshinone and phenolic acid.PMID:36643739 | PMC:PMC9832864 | DOI:10.1093/hr/uhac238

Hortic Res. 2022 Oct 26;10(1):uhac241. doi: 10.1093/hr/uhac241. eCollection 2023.ABSTRACTThe genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.PMID:36643737 | PMC:PMC9832866 | DOI:10.1093/hr/uhac241

Transl Pediatr. 2022 Dec;11(12):2016-2029. doi: 10.21037/tp-22-637.ABSTRACTBACKGROUND: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics.METHODS: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy.RESULTS: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis.CONCLUSIONS: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.PMID:36643669 | PMC:PMC9834951 | DOI:10.21037/tp-22-637

PeerJ. 2023 Jan 9;11:e14647. doi: 10.7717/peerj.14647. eCollection 2023.ABSTRACTBactrian camels have specific mucosa-associated lymphoid tissue (MALT) throughout the large intestine, with species-unique cystic Peyer's patches (PPS) as the main type of tissue. However, detailed information about the molecular characteristics of PPS remains unclear. This study applied a transcriptomic analysis, untargeted metabolomics, and 16S rDNA sequencing to compare the significant differences between PPS and the adjacent normal intestine tissues (NPPS) during the healthy stage of three young Bactrian camels. The results showed that samples from PPS could be easily differentiated from the NPPS samples based on gene expression profile, metabolites, and microbial composition, separately indicated using dimension reduction methods. A total of 7,568 up-regulated and 1,266 down-regulated differentially expressed genes (DEGs) were detected, and an enrichment analysis found 994 DEGs that participated in immune-related functions, and a co-occurance network analysis identified nine hub genes (BTK, P2RX7, Pax5, DSG1, PTPN2, DOCK11, TBX21, IL10, and HLA-DOB) during multiple immunologic processes. Further, PPS and NPPS both had a similar pattern of most compounds among all profiles of metabolites, and only 113 differentially expressed metabolites (DEMs) were identified, with 101 of these being down-regulated. Deoxycholic acid (DCA; VIP = 37.96, log2FC = -2.97, P = 0), cholic acid (CA; VIP = 13.10, log2FC = -2.10, P = 0.01), and lithocholic acid (LCA; VIP = 12.94, log2FC = -1.63, P = 0.01) were the highest contributors to the significant dissimilarities between groups. PPS had significantly lower species richness (Chao1), while Firmicutes (35.92% ± 19.39%), Bacteroidetes (31.73% ± 6.24%), and Proteobacteria (13.96% ± 16.21%) were the main phyla across all samples. The LEfSe analysis showed that Lysinibacillus, Rikenellaceae_RC9_gut_group, Candidatus_Stoquefichus, Mailhella, Alistipes, and Ruminococcaceae_UCG_005 were biomarkers of the NPPS group, while Escherichia_Shigella, Synergistes, Pyramidobacter, Odoribacter, Methanobrevibacter, Cloacibacillus, Fusobacterium, and Parabacteroides were significantly higher in the PPS group. In the Procrustes analysis, the transcriptome changes between groups showed no significant correlations with metabolites or microbial communities, whereas the alteration of metabolites significantly correlated with the alteration of the microbial community. In the co-occurrence network, seven DEMs (M403T65-neg, M329T119-neg, M309T38-neg, M277T42-2-neg, M473T27-neg, M747T38-1-pos, and M482t187-pos) and 14 genera (e.g., Akkermansia, Candidatus-Stoquefichus, Caproiciproducens, and Erysipelatoclostridium) clustered much more tightly, suggesting dense interactions. The results of this study provide new insights into the understanding of the immune microenvironment of the cystic PPS in the cecum of Bactrian camels.PMID:36643630 | PMC:PMC9835693 | DOI:10.7717/peerj.14647

PeerJ. 2023 Jan 10;11:e14483. doi: 10.7717/peerj.14483. eCollection 2023.ABSTRACTBACKGROUND: Icaritin (ICT) has been previously demonstrated to display protective effects against cerebral ischemic reperfusion (I/R) by inhibiting oxidative stress, but the mechanism remains unclear. This study aimed to explore the mechanism from the perspective of metabolomics.METHODS: A mice cerebral artery occlusion/reperfusion (MCAO/R) model was explored to mimic cerebral ischemic reperfusion and protective effect of ICT was assessed by neurologic deficit scoring, infarct volume and brain water content. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-QE-Orbitrap-MS) based metabolomic was performed to explore potential biomarkers. Brain tissue metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. The protein levels of Nrf2, HO-1 and HQO1 were assayed by western blot. The release of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were detected using corresponding assay kits.RESULTS: The results showed that after ICT treatment, the neurological deficit, cerebral infarction area, brain edema and the level of MDA in brain tissue of MCAO/R mice were significantly reduced. Meanwhile, ICT enhanced the activity of SOD, CAT and GSH-Px. Western blot results confirmed that ICT up-regulated the protein levels of antioxidant-related protein including Nrf2, HO-1 and NQO1. According to the metabolomic profiling of brain tissues, clear separations were observed among the Sham, Model and ICT groups. A total of 44 biomarkers were identified, and the identified biomarkers were mainly related to linoleic acid metabolism, arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, arginine and proline metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism and purine metabolism, respectively. At the same time, the inhibitory effect of ICT on arachidonic acid and linoleic acid in brain tissue, as well as the promoting effect on taurine, GABA, NAAG, may be the key factors for the anti-neurooxidative function of mice after MCAO/R injury.CONCLUSION: Our results demonstrate that ICT has benefits for MCAO/R injury, which are partially related to the suppression of oxidative stress via stimulating the Nrf2 signaling and regulating the production of arachidonic acid, linoleic acid, taurine, GABA, NAAG in brain tissue.PMID:36643627 | PMC:PMC9838208 | DOI:10.7717/peerj.14483