PubMed

Int J Mol Sci. 2023 Sep 11;24(18):13961. doi: 10.3390/ijms241813961.ABSTRACTLipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.PMID:37762264 | DOI:10.3390/ijms241813961

Int J Mol Sci. 2023 Sep 11;24(18):13959. doi: 10.3390/ijms241813959.ABSTRACTSymptoms of oral discomfort such as dry mouth are common in older people wearing dentures. Such symptoms are mainly treated symptomatically. Many of these symptoms are related to saliva, and associations with salivary volume have been reported. Although denture treatment improves symptoms by increasing the amount of saliva, the effects on salivary components remain unclear. This study aimed to investigate the effects of denture treatment on salivary metabolite changes based on salivary metabolome analyses. We enrolled 21 patients requiring denture treatment. At the first visit, and after completion of denture treatment, saliva outflow was measured under resting and stimulated conditions, samples for salivary metabolite analysis were collected, and masticatory efficiency was tested. In all participants, masticatory efficiency increased after denture treatment. Moreover, the amounts of resting and stimulated saliva were increased. Using salivary metabolome analysis, 61 salivary metabolites were detected. Substantial concentration changes were observed for 4 and 21 metabolites in resting and stimulated saliva, respectively. The four metabolites common to both saliva tests had significantly lower concentrations after treatment. These results suggest that the improvement in masticatory function by dentures is related not only to salivary secretion volume, but also to salivary metabolite composition.PMID:37762262 | DOI:10.3390/ijms241813959

Int J Mol Sci. 2023 Sep 11;24(18):13952. doi: 10.3390/ijms241813952.ABSTRACTThis study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect (p > 0.05) on growth performance. However, magnolol supplementation remarkably increased (p < 0.05) the serum content of albumin, total protein, immunoglobulin G, immunoglobulin M, and interleukin-22. In addition, dietary magnolol supplementation altered the amino acid (AA) profiles in serum and dorsal muscle and particularly increased (p < 0.05) the serum content of arginine and muscle glutamate. Simultaneously, the mRNA expression of genes associated with AA transport in jejunum (SLC38A2, SLC1A5, and SLC7A1) and ileum (SLC1A5 and SLC7A1) was higher (p < 0.05) in the Mag group than in the Con group. Additionally, the serum metabolomics analysis showed that the addition of magnolol significantly enhanced (p < 0.05) arginine biosynthesis, as well as D-glutamine and D-glutamate metabolism. Overall, these results suggested that dietary supplementation with magnolol has the potential to improve the accumulation of AAs, protein synthesis, immunity, and body health in growing pigs by increasing intestinal absorption and the transport of AAs.PMID:37762256 | DOI:10.3390/ijms241813952

Int J Mol Sci. 2023 Sep 8;24(18):13872. doi: 10.3390/ijms241813872.ABSTRACTBy means of liquid chromatography combined with high-resolution mass spectrometry, metabolite profiling was performed on an aqueous-ethanol extract from Spiraea hypericifolia (Rosaceae) collected in Siberia (Russia). Up to 140 compounds were found in the extract, of which 47 were tentatively identified. The identified compounds were amino acids, sugars, phenylpropanoids, fatty acids and their derivatives, triterpenoids, flavonoids, and others. A quantitative analysis showed the predominance of phenolcarboxylic acids and flavonoids in the studied extract, but a qualitative analysis revealed the higher structural diversity of flavonoids. Of the 23 identified flavonoids, 13 were flavonols: quercetin, hyperoside, isoquercitrin, reynoutrin, avicularin, rutin, quercetin-3-O-(6″-O-malonyl)-β-D-glucoside, 3-O-methylquercetin-3'-O-β-D-glucopyranoside, isorhamnetin, rhamnetin-3-O-β-D-xylopyranosyl-β-D-glucopyranoside, kaempferol, tiliroside, and trifolin; six were catechins: catechin, (-)-epicatechin, (+)-epicatechin, (+)-catechin-7-O-β-D-xyloside, (2S,3R)-3,5-dihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-yl-β-D-glucopyranoside, and catechin 7-O-apiofuranoside; two are isoflavones: genistin and genistein; and one was a flavone (luteolin-4'-O-β-D-glucopyranoside) and another was an anthocyanidin (pelargonidin). The aqueous-ethanol extract from S. hypericifolia showed antioxidant activity (half-maximal inhibitory concentration 102.95 μg/mL), which was likely related to the high concentrations of phenolcarboxylic acids (229.6 mg/g), flavonoids (118.3 mg/g), and tannins (62.9 mg/g).PMID:37762175 | DOI:10.3390/ijms241813872

Int J Mol Sci. 2023 Sep 7;24(18):13787. doi: 10.3390/ijms241813787.ABSTRACTThe COVID-19 pandemic has raised questions about indirect impact in pregnant women on the development of their future children. Investigating the characteristics of lipid metabolism in the "mother-placenta-fetus" system can give information about the pathophysiology of COVID-19 infection during pregnancy. A total of 234 women were included in study. Maternal plasma, cord blood, and amniotic fluid lipidome were analyzed using HPLC-MS/MS. Differences in lipid profile were searched by Mann-Whitney and Kruskall-Wallis test, and diagnostic model based on logistic regression were built by AIC. Elevated levels of lysophospholipids, triglycerides, sphingomyelins, and oxidized lipids were registered in patients' maternal and cord plasma after COVID-19 infection. An increase in maternal plasma sphingomyelins and oxidized lipids was observed in cases of infection during the second trimester. In amniotic fluid, compared to the control group, nine lipids were reduced and six were elevated. Levels of phosphoglycerides, lysophosphoglycerides, and phosphatidylinositols decreased during infection in the second and third trimesters of pregnancy. A health diagnostic model for newborns based on maternal plasma was developed for each group and exhibited good diagnostic value (AUC > 0.85). Maternal and cord plasma's lipidome changes during delivery, which are associated with COVID-19 infection during pregnancy, are synergistic. The most significant disturbances occur with infections in the second trimester of pregnancy.PMID:37762087 | DOI:10.3390/ijms241813787

Int J Mol Sci. 2023 Sep 7;24(18):13784. doi: 10.3390/ijms241813784.ABSTRACTClostridium butyricum, a new probiotic in recent years, can produce butyric acid and short-chain fatty acids. It has the characteristics of strong acid and alkali resistance, high temperature resistance, and strong resistance to most antibiotics, and has more advantages than other probiotics. However, the action mechanism of C. butyricum on Eriocheir sinensis is still unclear and needs further study. In this study, when C. butyricum was added to the basic diet, the number of living bacteria was 0, 1 × 106 and 1 × 108 CFU/g, respectively. The E. sinensis were randomly divided into three groups: (blank control group, experimental group 1 (1 × 106 CFU/g) and experimental group 2 (1 × 108 CFU/g)). They were fed an experimental diet for 28 days. The effects of C. butyricum on E. sinensis were studied by detecting the differences in non-specific immune indexes, intestinal microflora, and metabolites between serum and hepatopancreas. The results showed that C. butyricum could improve the antioxidant ability of E. sinensis serum and hepatopancreas, protect intestinal tissues, and promote the absorption of nutrients. At the same time, it can enhance the microbial diversity and richness of the E. sinensis gut flora. LC-MS metabolomics was used to detect the metabolism of intestinal flora. It was found that C. butyricum could up-regulate lysophosphatidylcholine in the intestine. Through the KEGG enrichment pathway, it was found that significantly different metabolites were mainly concentrated in six metabolic pathways. The purine metabolism and alanine, aspartate, and glutamate metabolism pathways showed a downward trend, indicating that the addition of C. butyricum to feed could reduce purine metabolism, promote the water-salt balance of the organism's cells, and reduce inflammation. In this study, it was found that the addition of certain concentrations of C. butyricum to feed could improve the antioxidant ability of E. sinensis, improve the intestinal flora environment, and promote the growth of beneficial bacteria in the gut. This can promote the body's metabolism, which is more conducive to its growth.PMID:37762084 | DOI:10.3390/ijms241813784

Int J Mol Sci. 2023 Sep 6;24(18):13732. doi: 10.3390/ijms241813732.ABSTRACTCurrently, the leaves of the hop plant (Humulus lupulus L.) are an unexploited and still little-investigated agricultural by-product. In our study, with the aim of exploring the metabolome of dried hop leaves (Chinook cultivar), a metabolomic approach was applied using multiple analytical tools such as SPME/GC-MS, GC-MS, PTR-ToF-MS, and NMR to identify the secondary metabolites. The obtained results showed the presence of a high number of components belonging to different chemical classes. In fact, thanks to the multi-methodological approach, volatile organic compounds (VOCs) with low molecular weight, terpenic compounds, fatty acids, sugars, amino acids, organic acids, and alcohols have been detected and identified. Among the revealed terpenes in the untreated matrix, the sesquiterpenes α-humulene, β-caryophyllene, and α-copaene were the most abundant. Among the saturated and unsaturated fatty acids, palmitic and linolenic acids, respectively, were those with the highest relative percentages. Particularly relevant was the sugar content, where sucrose was the main exponent while glutamate and asparagine were the principal detected amino acids. Conversely, alcohols and organic acids were the least abundant compound classes, and xanthohumol was also identified in the methanolic extract.PMID:37762036 | DOI:10.3390/ijms241813732

Int J Mol Sci. 2023 Sep 6;24(18):13724. doi: 10.3390/ijms241813724.ABSTRACTGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An uncontrolled GDM can lead to an increased risk of morbidity in the fetus and newborn, and an increased risk of obesity or developing type 2 diabetes, hypertension or neurocognitive developmental impairment in adulthood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS) to analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) with the aim of identifying biomarkers useful for the monitoring of NDMs and for early diagnosis of predisposition to develop related chronic diseases. A total of 26 newborns were recruited: 21 children of diabetic mothers, comprising 13 in diet therapy (NDM-diet) and 8 in insulin therapy (NDM-insulin), and 5 control children of non-diabetic mothers (CTR). Urine samples were collected at five time points: at birth (T1), on the third day of life (T2), one week (T3), one month (T4) and six months postpartum (T5). At T1, variations were observed in the levels of seven potential biomarkers (acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine and N-carbamoyl-aspartate) in NMD-insulin infants compared to NDM-diet and CTR infants. In particular, the altered metabolites were found to be involved in several metabolic pathways such as citrate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism, and pyruvate metabolism. In contrast, these changes were not visible at subsequent sampling times. The impact of early nutrition (maternal and formula milk) on the metabolomic profile was considered as a potential contributing factor to this finding.PMID:37762025 | DOI:10.3390/ijms241813724

Int J Mol Sci. 2023 Sep 5;24(18):13695. doi: 10.3390/ijms241813695.ABSTRACTThe purpose of this study was to elucidate the metabolic action patterns of P. forrestii against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of P. forrestii against RA were confirmed; second, the chemical composition of P. forrestii was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (-log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson's analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the P. forrestii treatment of RA, which showed a high correlation between five blood-absorbed components and P. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes for P. forrestii clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of P. forrestii were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.PMID:37761998 | DOI:10.3390/ijms241813695

Biochemistry (Mosc). 2023 Aug;88(8):1061-1069. doi: 10.1134/S0006297923080023.ABSTRACTActivation of the constitutive androstane receptor (CAR, NR1I3) by chemical compounds induces liver hyperplasia in rodents. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a mouse CAR agonist, is most often used to study chemically induced liver hyperplasia and hepatocyte proliferation in vivo. TCPOBOP is a potent murine liver chemical mitogen, which induces rapid liver hyperplasia in mice independently of liver injury. In recent years, great amount of data has been accumulated on the transcription program that characterizes the TCPOBOP-induced hepatocyte proliferation. However, there are only few data about the metabolic requirements of hepatocytes that divide upon exposure to xenobiotics. In the present study, we have employed liquid chromatography - mass spectrometry technology combined with statistical analysis to investigate metabolite profile of small biomolecules, in order to identify key metabolic changes in the male mouse liver tissue after TCPOBOP administration. Analysis of biochemical pathways of the differentially affected metabolites in the mouse liver demonstrated significant TCPOBOP-mediated enrichment of several processes including those associated with nucleotide metabolism, amino acid metabolism, and energy substrate metabolism. Our findings provide evidence to support the conclusion that the CAR agonist, TCPOBOP, initiates an intracellular program that promotes global coordinated metabolic activities required for hepatocyte proliferation. Our metabolic data might provide novel insight into the biological mechanisms that occur during the TCPOBOP-induced hepatocyte proliferation in mice.PMID:37758307 | DOI:10.1134/S0006297923080023

Biochimie. 2023 Sep 25:S0300-9084(23)00248-1. doi: 10.1016/j.biochi.2023.09.021. Online ahead of print.ABSTRACTSenescence due to exogenous and endogenous stresses triggers metabolic reprogramming and is associated with many pathologies, including cancer. In solid tumors, senescence promotes tumorigenesis, facilitates relapse, and changes the outcomes of anti-cancer therapies. Hence, cellular and molecular mechanisms regulating senescent pathways make attractive therapeutic targets. Cancer cells undergo metabolic reprogramming to sustain the growth-arrested state of senescence. In the present study, we aimed to understand the metabolic reprogramming in MCF-7 breast tumor cells in response to two independent inducers of DNA damage-mediated senescence, including ionizing radiation and doxorubicin. Increased DNA double-strand breaks, as demonstrated by γH2AX staining, showed a senescence phenotype, with expression of senescence-associated β-galactosidase accompanied by the upregulation of p21 and p16 in both groups. Further, untargeted analysis of the senescence-related extracellular metabolome profile of MCF-7 cells showed significantly reduced concentrations of carnitine and pantothenic acid and increased levels of S-adenosylhomocysteine in doxorubicin-treated cells, indicating the accumulation of ROS mediated DNA damage and impaired mitochondrial membrane potential. Similarly, a significant decline in the creatine level was observed in radiation-exposed cells, suggesting an increase in oxidative stress-mediated DNA damage. Our study, therefore, provides key effectors of the metabolic changes in doxorubicin and radiation-induced early senescence in MCF-7 breast cancer cells.PMID:37758157 | DOI:10.1016/j.biochi.2023.09.021

Brain Behav Immun. 2023 Sep 25:S0889-1591(23)00282-9. doi: 10.1016/j.bbi.2023.09.018. Online ahead of print.ABSTRACTThe gastrointestinal microbiota has received increasing recognition as a key mediator of neurological conditions with neuroinflammatory features, through its production of the bioactive metabolites, short-chain fatty acids (SCFAs). Although neuroinflammation is a hallmark shared by the neuropsychological complications of chemotherapy (including cognitive impairment, fatigue and depression), the use of microbial-based therapeutics has not previously been studied in this setting. Therefore, we aimed to investigate the effect of a high fibre diet known to modulate the microbiota, and its associated metabolome, on neuroinflammation caused by the common chemotherapeutic agent 5-fluorouracil (5-FU). Twenty-four female C57Bl/6 mice were treated with 5-FU (400 mg/kg, intraperitoneal, i.p.) or vehicle control, with or without a high fibre diet (constituting amylose starch; 4.7 % crude fibre content), given one week prior to 5-FU and until study completion (16 days after 5-FU). Faecal pellets were collected longitudinally for 16S rRNA gene sequencing and terminal SCFA concentrations of the caecal contents were quantified using gas chromatography-mass spectrometry (GC-MS). Neuroinflammation was determined by immunofluorescent analysis of astrocyte density (GFAP). The high fibre diet significantly altered gut microbiota composition, increasing the abundance of Bacteroidaceae and Akkermansiaceae (p < 0.0001 and p = 0.0179) whilst increasing the production of propionate (p = 0.0097). In the context of 5-FU, the diet reduced GFAP expression in the CA1 region of the hippocampus (p < 0.0001) as well as the midbrain (p = 0.0216). Astrocyte density negatively correlated with propionate concentrations and the abundance of Bacteroidaceae and Akkermansiaceae, suggesting a relationship between neuroinflammatory and gastrointestinal markers in this model. This study provides the first evidence of the neuroprotective effects of fibre via dietary intake in alleviating the neuroimmune changes seen in response to systemically administered 5-FU, indicating that the microbiota-gut-brain axis is a targetable mediator to reduce the neurotoxic effects of chemotherapy treatment.PMID:37757978 | DOI:10.1016/j.bbi.2023.09.018

J Proteomics. 2023 Sep 25:105009. doi: 10.1016/j.jprot.2023.105009. Online ahead of print.ABSTRACTSeasonal weight loss (SWL), is a major limitation to animal production. In the Canary Islands, there are two dairy goat breeds with different levels of tolerance to SWL: Majorera (tolerant) and Palmera (susceptible). Our team has studied the response of these breeds to SWL using different Omics. The objective of this study was to integrate such results in a data driven approach and using dedicated tools, namely the DIABLO software. The outputs of our analysis mainly separate unrestricted from restricted goats. Metabolites behave as "hub" molecules, grouping interactions with several genes and proteins. Unrestricted goats upregulated protein synthesis, along with arginine catabolism and adipogenesis pathways, which are related with higher anabolic rates and a larger proportion of secretory tissue, in agreement with their higher milk production. Contrarily, restricted goats seemingly increased the synthesis of acetyl-CoA through serine and acetate conversion into pyruvate. This may have occurred to increase fatty acid synthesis and/or to use them as an energy source in detriment to glucose, which was more available in the diet of unrestricted goats. Lastly, restricted Palmera upregulated the expression of PEBP4 and GPD1 genes compared to all other groups, which might support their use as putative biomarkers for SWL susceptibility. SIGNIFICANCE: Seasonal weight loss (SWL) is a major issue influencing animal production in the tropics and Mediterranean. By studying its impact on the mammary gland of resilient and susceptible dairy goat breeds, using Omics, we aim at surveying the tissue for possible biomarkers that reflect these traits. In this study, data integration of three Omics (transcriptomics, proteomics and metabolomics) was performed using bioinformatic tools, to relate putative biomarkers and evaluate all three levels of information; in a novel approach. This information can enhance selection programs, lowering the impact of SWL on food production systems.PMID:37757955 | DOI:10.1016/j.jprot.2023.105009

Environ Pollut. 2023 Sep 25:122616. doi: 10.1016/j.envpol.2023.122616. Online ahead of print.ABSTRACTPolybrominated diphenyl ether contamination in sediments poses serious threats to human health and ecological safety. Despite the broad application of submerged macrophytes for remediating pollutants, their regulatory influence on bacterial communities in contaminated sediments remains unclear. Herein, we analyzed the effects of decabromodiphenyl ether (BDE-209) and Hydrilla verticillata on sediment bacterial community and function using 16S rRNA gene sequencing and sediment metabolomics. Results showed that BDE-209 significantly inhibited sediment bacterial diversity and metabolic functions. It also enhanced bacterial interactions and altered both the bacterial community and metabolite composition. Uridine and inosine were critical metabolites that positively co-occurred with bacterial taxa inhibited by BDE-209. Notably, planting H. verticillata effectively alleviated the adverse impacts of BDE-209 by reducing its residuals, increasing the total organic carbon, and modifying metabolic profiles. Such mitigation was evidenced by enhancing bacterial diversity, restoring metabolic functions, and attenuating bacterial interactions. However, mitigation effectiveness depended on treatment time. Additionally, propionic acid, palmitic acid, and palmitoleic acid may facilitate the restoration of phylum Proteobacteria and class Planctomycetacia in H. verticillata planted sediment. Together, these findings improve understanding of BDE-209's impacts on aquatic ecosystems and provide valuable insights for ecological restoration using submerged macrophytes.PMID:37757929 | DOI:10.1016/j.envpol.2023.122616

Environ Pollut. 2023 Sep 25:122613. doi: 10.1016/j.envpol.2023.122613. Online ahead of print.ABSTRACTLarge bone lead (Pb) resulting from high environmental exposure during childhood is an important source of endogenous Pb during pregnancy and lactation. Docosahexaenoic acid (DHA) attenuates Pb toxicity, however, the effect of DHA on bone Pb mobilisation during lactation has not been investigated. We aimed to study the effects of DHA supplementation during pregnancy and lactation on bone Pb mobilisation during lactation and its potential mechanisms. Weaning female rats were randomly divided into control (0.05% sodium acetate) and Pb-exposed (0.05% Pb acetate) groups, after a 4-week exposure by ad libitum drinking and a subsequent 4-week washout period, all female rats were mated with healthy males until pregnancy. Then exposed rats were randomly divided into Pb and Pb + DHA groups, and the latter was given a 0.14% DHA diet, while the remaining groups were given normal feed until the end of lactation. Pb and calcium levels, bone microarchitecture, bone turnover markers, mitochondrial function and serum metabolomics were analyzed. The results showed that higher blood and bone Pb levels were observed in the Pb group compared to the control, and there was a significant negative correlation between blood and bone Pb. Also, Pb increased trabecular bone loss along with slightly elevated serum C-telopeptide of type I collagen (CTX-I) levels. However, DHA reduced CTX-I levels and improved trabecular bone microarchitecture. Metabolomics showed that Pb affected mitochondrial function, which was further demonstrated in bone tissue by significant reductions in ATP levels, Na+-K+-ATPase, Ca2+-Mg2+-ATPase and CAT activities, and elevated levels of MDA, IL-1β and IL-18. However, these alterations were partially mitigated by DHA. In conclusion, DHA supplementation during pregnancy and lactation improved bone Pb mobilisation and mitochondrial dysfunction in lactating rats induced by pre-pregnancy Pb exposure, providing potential means of mitigating bone Pb mobilisation levels during lactation, but the mechanism still needs further study.PMID:37757928 | DOI:10.1016/j.envpol.2023.122613

Nucleic Acids Res. 2023 Sep 27:gkad777. doi: 10.1093/nar/gkad777. Online ahead of print.ABSTRACTLiquid biopsy has emerged as a promising non-invasive approach for detecting, monitoring diseases, and predicting their recurrence. However, the effective utilization of liquid biopsy data to identify reliable biomarkers for various cancers and other diseases requires further exploration. Here, we present cfOmics, a web-accessible database (https://cfomics.ncRNAlab.org/) that integrates comprehensive multi-omics liquid biopsy data, including cfDNA, cfRNA based on next-generation sequencing, and proteome, metabolome based on mass-spectrometry data. As the first multi-omics database in the field, cfOmics encompasses a total of 17 distinct data types and 13 specimen variations across 69 disease conditions, with a collection of 11345 samples. Moreover, cfOmics includes reported potential biomarkers for reference. To facilitate effective analysis and visualization of multi-omics data, cfOmics offers powerful functionalities to its users. These functionalities include browsing, profile visualization, the Integrative Genomic Viewer, and correlation analysis, all centered around genes, microbes, or end-motifs. The primary objective of cfOmics is to assist researchers in the field of liquid biopsy by providing comprehensive multi-omics data. This enables them to explore cell-free data and extract profound insights that can significantly impact disease diagnosis, treatment monitoring, and management.PMID:37757861 | DOI:10.1093/nar/gkad777

Plant Physiol Biochem. 2023 Sep 12;203:108033. doi: 10.1016/j.plaphy.2023.108033. Online ahead of print.ABSTRACTLeaf scald caused by the bacteria Xanthomonas albilineans is one of the major concerns to sugarcane production. To breed for resistance, mechanisms underlying plant-pathogen interaction need deeper investigations. Herein, we evaluated sugarcane defense responses against X. albilineans using molecular and biochemical approaches to assess pathogen-triggered ROS, phytohormones and metabolomics in two contrasting sugarcane genotypes from 0.5 to 144 h post-inoculation (hpi). In addition, the infection process was monitored using TaqMan-based quantification of X. albilineans and the disease symptoms were evaluated in both genotypes after 15 d post-inoculation (dpi). The susceptible genotype presented a response to the infection at 0.5 hpi, accumulating defense-related metabolites such as phenolics and flavonoids with no significant defense responses thereafter, resulting in typical symptoms of leaf scald at 15 dpi. The resistant genotype did not respond to the infection at 0.5 hpi but constitutively presented higher levels of salicylic acid and of the same metabolites induced by the infection in the susceptible genotype. Moreover, two subsequent pathogen-induced metabolic responses at 12 and 144 hpi were observed only in the resistant genotype in terms of amino acids, quinic acids, coumarins, polyamines, flavonoids, phenolics and phenylpropanoids together with an increase of hydrogen peroxide, ROS-related genes expression, indole-3-acetic-acid and salicylic acid. Multilevel approaches revealed that constitutive chemical composition and metabolic reprogramming hampers the development of leaf scald at 48 and 72 hpi, reducing the disease symptoms in the resistant genotype at 15 dpi. Phenylpropanoid pathway is suggested as a strong candidate marker for breeding sugarcane resistant to leaf scald.PMID:37757720 | DOI:10.1016/j.plaphy.2023.108033

J Hazard Mater. 2023 Sep 23;461:132620. doi: 10.1016/j.jhazmat.2023.132620. Online ahead of print.ABSTRACTPlastic pollution of the oceans is increasing, and toxic interactions between microplastics (MPs) and organic pollutants have become a major environmental concern. However, the combined effects of organic pollutants and MPs on microbiomes and metabolomes have not been studied extensively. In the present study, to evaluate whether MPs and phenanthrene (Phe) act synergistically in the guts of marine medaka (Oryzias melastigma), we performed toxicity assessments, 16 S rRNA gene sequencing, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Our investigations revealed increased toxicity induced by Phe, as well as disturbances in gut microbiota (known as dysbiosis) when MPs were present. Furthermore, combined exposure to Phe and MPs resulted in greater alterations to microbiota composition and metabolite profiles. Notably, MP exposure was distinctly associated with the abundance of Shewanella and Spongiibacteraceae, while Phe exposure was associated with the abundance of Marimicrobium. Among key microbiota, Marimicrobium and Roseibacillus were significantly correlated with metabolites responsible for coenzyme A and glycerophospholipid metabolism in medaka. These results suggest that interactions between Phe and MPs may have significant effects on the gut microbiota and metabolism of aquatic organisms and underscore the importance of acknowledging the interplay between MPs and contaminants in aquatic environments.PMID:37757554 | DOI:10.1016/j.jhazmat.2023.132620

Int J Epidemiol. 2023 Sep 28:dyad123. doi: 10.1093/ije/dyad123. Online ahead of print.ABSTRACTBACKGROUND: In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes.METHODS: We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age. Objective smoking status was defined based on detectable cotinine levels at each time point and objective caffeine exposure was based on tertiles of paraxanthine levels at each time point. We used logistic and linear regression to examine the association between cotinine, paraxanthine and the risk of pre-eclampsia, spontaneous pre-term birth (sPTB), fetal growth restriction (FGR), gestational diabetes mellitus and birthweight.RESULTS: There were 914 and 915 women in the smoking and caffeine analyses, respectively. Compared with no exposure to smoking, consistent exposure to smoking was associated with an increased risk of sPTB [adjusted odds ratio (aOR) = 2.58, 95% CI: 1.14 to 5.85)] and FGR (aOR = 4.07, 95% CI: 2.14 to 7.74) and lower birthweight (β = -387 g, 95% CI: -622 g to -153 g). On univariate analysis, consistently high levels of paraxanthine were associated with an increased risk of FGR but that association attenuated when adjusting for maternal characteristics and objective-but not self-reported-smoking status.CONCLUSIONS: Based on objective data, consistent exposure to smoking throughout pregnancy was strongly associated with sPTB and FGR. High levels of paraxanthine were not independently associated with any of the studied outcomes and were confounded by smoking.PMID:37759082 | DOI:10.1093/ije/dyad123

Nature. 2023 Sep 27. doi: 10.1038/s41586-023-06585-5. Online ahead of print.ABSTRACTPostnatal maturation of cardiomyocytes is characterized by a metabolic switch from glycolysis to fatty acid oxidation, chromatin reconfiguration and exit from the cell cycle, instating a barrier for adult heart regeneration1,2. Here, to explore whether metabolic reprogramming can overcome this barrier and enable heart regeneration, we abrogate fatty acid oxidation in cardiomyocytes by inactivation of Cpt1b. We find that disablement of fatty acid oxidation in cardiomyocytes improves resistance to hypoxia and stimulates cardiomyocyte proliferation, allowing heart regeneration after ischaemia-reperfusion injury. Metabolic studies reveal profound changes in energy metabolism and accumulation of α-ketoglutarate in Cpt1b-mutant cardiomyocytes, leading to activation of the α-ketoglutarate-dependent lysine demethylase KDM5 (ref. 3). Activated KDM5 demethylates broad H3K4me3 domains in genes that drive cardiomyocyte maturation, lowering their transcription levels and shifting cardiomyocytes into a less mature state, thereby promoting proliferation. We conclude that metabolic maturation shapes the epigenetic landscape of cardiomyocytes, creating a roadblock for further cell divisions. Reversal of this process allows repair of damaged hearts.PMID:37758950 | DOI:10.1038/s41586-023-06585-5