PubMed

Front Neurol. 2023 Mar 16;13:1109019. doi: 10.3389/fneur.2022.1109019. eCollection 2022.ABSTRACTINTRODUCTION: Screening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI.METHODS: Based on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism.RESULTS: According to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996.CONCLUSION: HCC-associated metabolic DEGs may influence the development of VCI in HCC patients.PMID:37008043 | PMC:PMC10062391 | DOI:10.3389/fneur.2022.1109019

Front Physiol. 2023 Mar 16;14:1164926. doi: 10.3389/fphys.2023.1164926. eCollection 2023.ABSTRACTIntroduction: Eicosanoids are bioactive lipids present in packed red blood cells (PRBCs), and might play a role in transfusion-related immunomodulation (TRIM). We tested the feasibility of analyzing eicosanoid profiles in PRBC supernatant and in plasma samples of postoperative intensive care unit (ICU) patients transfused with one unit of PRBCs. Methods: We conducted a prospective, observational feasibility study enrolling postoperative ICU patients: 1) patients treated with acetylsalicylic acid following abdominal aortic surgery (Aorta); 2) patients on immunosuppressants after bilateral lung transplantation (LuTx); and 3) patients undergoing other types of major surgery (Comparison). Abundances of arachidonic acid (AA) and seven pre-defined eicosanoids were assessed by liquid chromatography and tandem mass spectrometry. PRBC supernatant was sampled directly from the unit immediately prior to transfusion. Spearman's correlations between eicosanoid abundance in PRBCs and storage duration were assessed. Patient plasma was collected at 30-min intervals: Three times each before and after transfusion. To investigate temporal changes in eicosanoid abundances, we fitted linear mixed models. Results: Of 128 patients screened, 21 were included in the final analysis (Aorta n = 4, LuTx n = 8, Comparison n = 9). In total, 21 PRBC and 125 plasma samples were analyzed. Except for 20-hydroxyeicosatetraenoic acid (HETE), all analyzed eicosanoids were detectable in PRBCs, and their abundance positively correlated with storage duration of PRBCs. While 5-HETE, 12-HETE/8-HETE, 15-HETE, 20-HETE, and AA were detectable in virtually all plasma samples, 9-HETE and 11-HETE were detectable in only 57% and 23% of plasma samples, respectively. Conclusions: Recruitment of ICU patients into this transfusion study was challenging but feasible. Eicosanoid abundances increased in PRBC supernatants during storage. In plasma of ICU patients, eicosanoid abundances were ubiquitously detectable and showed limited fluctuations over time prior to transfusion. Taken together, larger clinical studies seem warranted and feasible to further investigate the role of PRBC-derived eicosanoids in TRIM.PMID:37008004 | PMC:PMC10060532 | DOI:10.3389/fphys.2023.1164926

Front Physiol. 2023 Mar 16;14:1130861. doi: 10.3389/fphys.2023.1130861. eCollection 2023.ABSTRACTPost-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of redox biology. Redox molecules are free radical and/or reactive species that are generated as a consequence of the necessity of electron movement for life. These reactive molecules, too, are essential for life, but in excess are denoted as "oxidative stress" and often associated with many diseases. The few studies that have examined redox biology parameters have often utilized outdated and nonspecific methods, as well as have reported confounding results, which has made it difficult to conclude the role for redox in PTSD. Herein, we provide a foundation of how redox biology may underlie diseases like PTSD, critically examine redox studies of PTSD, and provide future directions the field can implement to enhance standardization, reproducibility, and accuracy of redox assessments for the use of diagnosis, prognosis, and therapy of this debilitating mental health disorder.PMID:37007993 | PMC:PMC10060537 | DOI:10.3389/fphys.2023.1130861

Front Physiol. 2023 Mar 13;14:1151268. doi: 10.3389/fphys.2023.1151268. eCollection 2023.ABSTRACTIntroduction: Exercise intolerance is a common clinical manifestation in patients with sickle cell disease (SCD), though the mechanisms are incompletely understood. Methods: Here we leverage a murine mouse model of sickle cell disease, the Berkeley mouse, to characterize response to exercise via determination of critical speed (CS), a functional measurement of mouse running speed upon exerting to exhaustion. Results: Upon observing a wide distribution in critical speed phenotypes, we systematically determined metabolic aberrations in plasma and organs-including heart, kidney, liver, lung, and spleen-from mice ranked based on critical speed performances (top vs. bottom 25%). Results indicated clear signatures of systemic and organ-specific alterations in carboxylic acids, sphingosine 1-phosphate and acylcarnitine metabolism. Metabolites in these pathways showed significant correlations with critical speed across all matrices. Findings from murine models were thus further validated in 433 sickle cell disease patients (SS genotype). Metabolomics analyses of plasma from 281 subjects in this cohort (with HbA < 10% to decrease confounding effects of recent transfusion events) were used to identify metabolic correlates to sub-maximal exercise test performances, as measure by 6 min walking test in this clinical cohort. Results confirmed strong correlation between test performances and dysregulated levels of circulating carboxylic acids (especially succinate) and sphingosine 1-phosphate. Discussion: We identified novel circulating metabolic markers of exercise intolerance in mouse models of sickle cell disease and sickle cell patients.PMID:37007990 | PMC:PMC10053510 | DOI:10.3389/fphys.2023.1151268

Front Genet. 2023 Mar 16;14:1141201. doi: 10.3389/fgene.2023.1141201. eCollection 2023.ABSTRACTThe causal agent of rust, Uromyces appendiculatus is a major constraint for common bean (Phaseolus vulgaris) production. This pathogen causes substantial yield losses in many common bean production areas worldwide. U. appendiculatus is widely distributed and although there have been numerous breakthroughs in breeding for resistance, its ability to mutate and evolve still poses a major threat to common bean production. An understanding of plant phytochemical properties can aid in accelerating breeding for rust resistance. In this study, metabolome profiles of two common bean genotypes Teebus-RR-1 (resistant) and Golden Gate Wax (susceptible) were investigated for their response to U. appendiculatus races (1 and 3) at 14- and 21-days post-infection (dpi) using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-qTOF-MS). Non-targeted data analysis revealed 71 known metabolites that were putatively annotated, and a total of 33 were statistically significant. Key metabolites including flavonoids, terpenoids, alkaloids and lipids were found to be incited by rust infections in both genotypes. Resistant genotype as compared to the susceptible genotype differentially enriched metabolites including aconifine, D-sucrose, galangin, rutarin and others as a defence mechanism against the rust pathogen. The results suggest that timely response to pathogen attack by signalling the production of specific metabolites can be used as a strategy to understand plant defence. This is the first study to illustrate the utilization of metabolomics to understand the interaction of common bean with rust.PMID:37007949 | PMC:PMC10060544 | DOI:10.3389/fgene.2023.1141201

Clin Kidney J. 2022 Dec 8;16(4):711-721. doi: 10.1093/ckj/sfac262. eCollection 2023 Apr.ABSTRACTBACKGROUND: Acute kidney injury (AKI) is often iatrogenic and potentially preventable. Reduced renal nicotinamide adenine dinucleotide (NAD+) is reported to increase the susceptibility of AKI. The present study explored the predictive value of urinary de novo NAD+ synthetic metabolites for AKI using two independent cohorts.METHODS: The expression of de novo NAD+ synthetic enzymes in human kidney was examined by immunohistochemistry and single-cell transcriptomes. Urine samples were collected from two independent cohorts: the methotrexate (MTX) cohort with high-dose MTX treatment for lymphoma (n = 189) and the liver transplantation cohort with orthotopic liver transplantation (n = 49). Urinary metabolomics study of NAD+ de novo synthesis was performed by liquid chromatography with mass spectrometry, screening for AKI predictive biomarkers. Nephroseq database and immunohistochemistry were used to analyze kidney de novo NAD+ synthetic enzymes expression in AKI-susceptible conditions.RESULTS: Human proximal tubule was the main structure in the kidney that expressed the necessary enzymes for NAD+ de novo synthesis. In the MTX cohort, the urinary quinolinic acid (QA)/3-hydroxyanthranilic acid (3-OH AA) ratio before chemotherapy was significantly lower in those who developed AKI after chemotherapy compared with those who did not. This finding was consistent in the liver transplantation cohort. The area under the receiver-operating characteristic curve (AUC) of urinary QA/3-OH AA for AKI prediction was 0.749 and 0.729 in two cohorts, respectively. 3-Hydroxyanthranilic acid dioxygenase (HAAO), the enzyme catalyzing QA synthesis from 3-OH AA, decreased in AKI-susceptible diabetic kidneys.CONCLUSIONS: The human proximal tubules were important source of NAD+ from the de novo pathway. Reduced urinary QA/3-OH AA ratio, which possibly suggested decreased HAAO activity, could be a potential AKI predictive biomarker.PMID:37007695 | PMC:PMC10061430 | DOI:10.1093/ckj/sfac262

Ann Transl Med. 2023 Mar 15;11(5):213. doi: 10.21037/atm-23-1074.ABSTRACTBACKGROUND: In previous studies, we found that smoking may participate in the pathogenesis of rheumatoid arthritis (RA) via the aryl hydrocarbon receptor (AhR) pathway. However, when we conducted a subgroup analysis, the expression of AhR and CYP1A1 in healthy people was higher than that in RA patients. We considered that endogenous AhR ligands may exist in vivo that activate AhR to play a protective role. Indole-3-pyruvic acid (IPA) is a tryptophan (Trp) metabolite produced by the indole pathway and serves as a ligand of AhR. This study aimed to reveal the effect and mechanism of IPA in RA.METHODS: A total of 14 patients with RA and 14 healthy volunteers were enrolled. The differential metabolites were screened with liquid chromatography-mass spectrometry (LC-MS) metabolomics technology. We also treated peripheral blood mononuclear cells (PBMCs) with IPA to evaluate the effect on the differentiation of T helper 17 (Th17) cells or regulatory T (Treg) cells. To determine whether IPA can be used to alleviate RA, we administered IPA to rats with collagen-induced arthritis (CIA). Methotrexate was used as a standard drug for CIA.RESULTS: When the dose reached 20 mg/kg/d, the severity of CIA was significantly reduced. In vitro experiments verified that IPA inhibited the differentiation of Th17 cells and promoted the differentiation of Treg cells, but this effect was weakened by CH223191.CONCLUSIONS: IPA is a protective factor for RA; it can restore the Th17/Treg cell balance through the AhR pathway, which can alleviate RA.PMID:37007545 | PMC:PMC10061485 | DOI:10.21037/atm-23-1074

Front Microbiol. 2023 Mar 15;14:1119981. doi: 10.3389/fmicb.2023.1119981. eCollection 2023.ABSTRACTPURPOSE: We aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations.METHODS: Thirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data.RESULTS: There was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively.CONCLUSION: Decreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.PMID:37007499 | PMC:PMC10050441 | DOI:10.3389/fmicb.2023.1119981

Front Microbiol. 2023 Mar 16;14:1138903. doi: 10.3389/fmicb.2023.1138903. eCollection 2023.ABSTRACTNecrotic enteritis (NE), especially subclinical NE (SNE), without clinical symptoms, in chicks has become one of the most threatening problems to the poultry industry. Therefore, increasing attention has been focused on the research and application of effective probiotic strains as an alternative to antibiotics to prevent SNE in broilers. In the present study, we evaluated the effects of Bacillus subtilis DSM29784 (BS) on the prevention of subclinical necrotic enteritis (SNE) in broilers. A total of 480 1-day-old broiler chickens were randomly assigned to four dietary treatments, each with six replicates pens of twenty birds for 63 d. The negative (Ctr group) and positive (SNE group) groups were only fed a basal diet, while the two treatment groups received basal diets supplemented with BS (1 × 109 colony-forming units BS/kg) (BS group) and 10mg/kg enramycin (ER group), respectively. On days 15, birds except those in the Ctr group were challenged with 20-fold dose coccidiosis vaccine, and then with 1 ml of C. perfringens (2 × 108) at days 18 to 21 for SNE induction. BS, similar to ER, effectively attenuated CP-induced poor growth performance. Moreover, BS pretreatment increased villi height, claudin-1 expression, maltase activity, and immunoglobulin abundance, while decreasing lesional scores, as well as mucosal IFN-γ and TNF-α concentrations. In addition, BS pretreatment increased the relative abundance of beneficial bacteria and decreased that of pathogenic species; many lipid metabolites were enriched in the cecum of treated chickens. These results suggest that BS potentially provides active ingredients that may serve as an antibiotic substitute, effectively preventing SNE-induced growth decline by enhancing intestinal health in broilers.PMID:37007491 | PMC:PMC10060821 | DOI:10.3389/fmicb.2023.1138903

Front Microbiol. 2023 Mar 17;14:1152632. doi: 10.3389/fmicb.2023.1152632. eCollection 2023.ABSTRACTCamellia oleifera (C. oleifera) is a unique edible oil crop in China cultivated in the hilly southern mountains. Although C. oleifera is classified as a drought-tolerant tree species, drought remains the main factor limiting the growth of C. oleifera in summer and autumn. Using endophytes to improve crop drought tolerance is one effective strategy to meet our growing food crop demand. In this study, we showed that endophyte Streptomyces albidoflavus OsiLf-2 could mitigate the negative impact of drought stress on C. oleifera, thus improving seed, oil, and fruit quality. Microbiome analysis revealed that OsiLf-2 treatment significantly affected the microbial community structure in the rhizosphere soil of C. oleifera, decreasing both the diversity and abundance of the soil microbe. Likewise, transcriptome and metabolome analyses found that OsiLf-2 protected plant cells from drought stress by reducing root cell water loss and synthesizing osmoregulatory substances, polysaccharides, and sugar alcohols in roots. Moreover, we observed that OsiLf-2 could induce the host to resist drought stress by increasing its peroxidase activity and synthesizing antioxidants such as cysteine. A multi-omics joint analysis of microbiomes, transcriptomes, and metabolomes revealed OsiLf-2 assists C. oleifera in resisting drought stress. This study provides theoretical and technical support for future research on endophytes application to enhance the drought resistance, yield, and quality of C. oleifera.PMID:37007482 | PMC:PMC10063849 | DOI:10.3389/fmicb.2023.1152632

Front Microbiol. 2023 Mar 17;14:1127858. doi: 10.3389/fmicb.2023.1127858. eCollection 2023.ABSTRACTIn this paper, the effect of Alcaligenes sp. on the corrosion process of X65 steel was investigated by using non-targeted metabolomics techniques for comprehensive characterization of metabolites, combined with surface analysis techniques and electrochemical testing. The results showed that the organic acids produced by Alcaligenes sp. accelerated the corrosion process of X65 steel in the early stage, and the presence of Alcaligenes sp. promoted the deposition of stable corrosion products and minerals in the middle and late stages. In addition, proteoglycans and corrosion inhibiting substances were enriched on the metal surface, which enhanced the stability of the film. The combined effect of multiple factors makes the mixed film of biofilm and corrosion products more dense and complete, which effectively inhibits the corrosion of X65 steel.PMID:37007476 | PMC:PMC10063886 | DOI:10.3389/fmicb.2023.1127858

Front Microbiol. 2023 Mar 16;14:1127018. doi: 10.3389/fmicb.2023.1127018. eCollection 2023.ABSTRACTA small subpopulation of Vibrio splendidus AJ01 that was exposed to tetracycline at 10 times the minimal inhibitory concentration (MIC) still survived, named tetracycline-induced persister cells in our previous work. However, the formation mechanisms of persister is largely unknown. Here, we investigated tetracycline-induced AJ01 persister cells by transcriptome analysis and found that the purine metabolism pathway was significantly downregulated, which was consistent with lower levels of ATP, purine, and purine derivatives in our metabolome analysis. Inhibition of the purine metabolism pathway by 6-mercaptopurine (6-MP, inhibits ATP production), increased persister cell formation and accompanied with the decreasing intracellular ATP levels and increasing cells with protein aggresome. On the other hand, the persister cells had reduced intracellular tetracycline concentrations and higher membrane potential after 6-MP treatment. Inhibition of the membrane potential by carbonyl cyanide m-chlorophenyl hydrazone reversed 6-MP-induced persistence and resulted in higher levels of intracellular tetracycline accumulation. Meanwhile, cells with 6-MP treatment increased the membrane potential by dissipating the transmembrane proton pH gradient, which activated efflux to decrease the intracellular tetracycline concentration. Together, our findings show that reduction of purine metabolism regulates AJ01 persistence and is associated with protein aggresome formation and intracellular tetracycline efflux.PMID:37007472 | PMC:PMC10060992 | DOI:10.3389/fmicb.2023.1127018

Front Oncol. 2023 Mar 16;13:1116806. doi: 10.3389/fonc.2023.1116806. eCollection 2023.ABSTRACTBACKGROUND: The serum metabolome is a potential source of molecular biomarkers associated with the risk of breast cancer. Here we aimed to analyze metabolites present in pre-diagnostic serum samples collected from healthy women participating in the Norwegian Trøndelag Health Study (HUNT2 study) for whom long-term information about developing breast cancer was available.METHODS: Women participating in the HUNT2 study who developed breast cancer within a 15-year follow-up period (BC cases) and age-matched women who stayed breast cancer-free were selected (n=453 case-control pairs). Using a high-resolution mass spectrometry approach 284 compounds were quantitatively analyzed, including 30 amino acids and biogenic amines, hexoses, and 253 lipids (acylcarnitines, glycerides, phosphatidylcholines, sphingolipids, and cholesteryl esters).RESULTS: Age was a major confounding factor responsible for a large heterogeneity in the dataset, hence age-defined subgroups were analyzed separately. The largest number of metabolites whose serum levels differentiated BC cases and controls (82 compounds) were observed in the subgroup of younger women (<45 years old). Noteworthy, increased levels of glycerides, phosphatidylcholines, and sphingolipids were associated with reduced risk of cancer in younger and middle-aged women (≤64 years old). On the other hand, increased levels of serum lipids were associated with an enhanced risk of breast cancer in older women (>64 years old). Moreover, several metabolites could be detected whose serum levels were different between BC cases diagnosed earlier (<5 years) and later (>10 years) after sample collecting, yet these compounds were also correlated with the age of participants. Current results were coherent with the results of the NMR-based metabolomics study performed in the cohort of HUNT2 participants, where increased serum levels of VLDL subfractions were associated with reduced risk of breast cancer in premenopausal women.CONCLUSIONS: Changes in metabolite levels detected in pre-diagnostic serum samples, which reflected an impaired lipid and amino acid metabolism, were associated with long-term risk of breast cancer in an age-dependent manner.PMID:37007110 | PMC:PMC10061137 | DOI:10.3389/fonc.2023.1116806

J Inflamm Res. 2023 Mar 27;16:1357-1373. doi: 10.2147/JIR.S394608. eCollection 2023.ABSTRACTPURPOSE: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection.METHODS: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R-/- mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R-/- Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection.RESULTS: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R-/- Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R-/- Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R-/- Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice.CONCLUSION: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection.PMID:37006807 | PMC:PMC10065423 | DOI:10.2147/JIR.S394608

JACS Au. 2023 Mar 9;3(3):929-942. doi: 10.1021/jacsau.3c00025. eCollection 2023 Mar 27.ABSTRACTThe ability of Methylobacterium extorquens to grow on methanol as the sole carbon and energy source has been the object of intense research activity. Unquestionably, the bacterial cell envelope serves as a defensive barrier against such an environmental stressor, with a decisive role played by the membrane lipidome, which is crucial for stress resistance. However, the chemistry and the function of the main constituent of the M. extorquens outer membrane, the lipopolysaccharide (LPS), is still undefined. Here, we show that M. extorquens produces a rough-type LPS with an uncommon, non-phosphorylated, and extensively O-methylated core oligosaccharide, densely substituted with negatively charged residues in the inner region, including novel monosaccharide derivatives such as O-methylated Kdo/Ko units. Lipid A is composed of a non-phosphorylated trisaccharide backbone with a distinctive, low acylation pattern; indeed, the sugar skeleton was decorated with three acyl moieties and a secondary very long chain fatty acid, in turn substituted by a 3-O-acetyl-butyrate residue. Spectroscopic, conformational, and biophysical analyses on M. extorquens LPS highlighted how structural and tridimensional features impact the molecular organization of the outer membrane. Furthermore, these chemical features also impacted and improved membrane resistance in the presence of methanol, thus regulating membrane ordering and dynamics.PMID:37006758 | PMC:PMC10052234 | DOI:10.1021/jacsau.3c00025

Front Mol Biosci. 2023 Mar 16;10:1114594. doi: 10.3389/fmolb.2023.1114594. eCollection 2023.ABSTRACTDue to the lack of distinct early symptoms and specific biomarkers, most patients with hepatocellular carcinoma (HCC) are usually diagnosed at advanced stages, rendering the treatment ineffective and useless. Therefore, recognition of the malady at precancerous lesions and early stages is particularly important for improving patient outcomes. The interest in extracellular vesicles (EVs) has been growing in recent years with the accumulating knowledge of their multiple cargoes and related multipotent roles in the modulation of immune response and tumor progression. By virtue of the rapid advancement of high-throughput techniques, multiple omics, including genomics/transcriptomics, proteomics, and metabolomics/lipidomics, have been widely integrated to analyze the role of EVs. Comprehensive analysis of multi-omics data will provide useful insights for discovery of new biomarkers and identification of therapeutic targets. Here, we review the attainment of multi-omics analysis to the finding of the potential role of EVs in early diagnosis and the immunotherapy in HCC.PMID:37006626 | PMC:PMC10060991 | DOI:10.3389/fmolb.2023.1114594

Data Brief. 2023 Jun;48:109089. doi: 10.1016/j.dib.2023.109089. Epub 2023 Mar 29.ABSTRACTThe dataset provided with this article describes a targeted lipidomics analysis performed on the serum of COVID-19 patients characterized by different degree of severity. As the ongoing pandemic has posed a challenging threat for humanity, the data here presented belong to one of the first lipidomics studies carried out on COVID-19 patients' samples collected during the first pandemic waves. Serum samples were obtained from hospitalized patients with a molecular diagnosis of SARS-CoV-2 infection detected after nasal swab, and categorized as mild, moderate, or severe according to pre-established clinical descriptors. The MS-based targeted lipidomic analysis was performed by MRM using a Triple Quad 5500+ mass spectrometer, and the quantitative data were acquired on a panel of 483 lipids. The characterization of this lipidomic dataset has been outlined using multivariate and univariate descriptive statistics and bioinformatics tools.PMID:37006392 | PMC:PMC10050192 | DOI:10.1016/j.dib.2023.109089

Front Immunol. 2023 Mar 15;14:1122451. doi: 10.3389/fimmu.2023.1122451. eCollection 2023.ABSTRACTA key aspect of parasitic nematode infection is the nematodes' ability to evade and/or suppress host immunity. This immunomodulatory ability is likely driven by the release of hundreds of excretory/secretory proteins (ESPs) during infection. While ESPs have been shown to display immunosuppressive effects on various hosts, our understanding of the molecular interactions between individual proteins released and host immunity requires further study. We have recently identified a secreted phospholipase A2 (sPLA2) released from the entomopathogenic nematode (EPN) Steinernema carpocapsae we have named Sc-sPLA2. We report that Sc-sPLA2 increased mortality of Drosophila melanogaster infected with Streptococcus pneumoniae and promoted increased bacterial growth. Furthermore, our data showed that Sc-sPLA2 was able to downregulate both Toll and Imd pathway-associated antimicrobial peptides (AMPs) including drosomycin and defensin, in addition to suppressing phagocytosis in the hemolymph. Sc-sPLA2 was also found to be toxic to D. melanogaster with the severity being both dose- and time-dependent. Collectively, our data highlighted that Sc-sPLA2 possessed both toxic and immunosuppressive capabilities.PMID:37006283 | PMC:PMC10050561 | DOI:10.3389/fimmu.2023.1122451

Front Immunol. 2023 Mar 17;14:1131146. doi: 10.3389/fimmu.2023.1131146. eCollection 2023.ABSTRACTDuring mucosal injury, intestinal immune cells play a crucial role in eliminating invading bacteria. However, as the excessive accumulation of immune cells promotes inflammation and delays tissue repair, it is essential to identify the mechanism that limits the infiltration of immune cells to the mucosal-luminal interface. Cholesterol sulfate (CS) is the lipid product of the sulfotransferase SULT2B1 and suppresses immune reactions by inhibiting DOCK2-mediated Rac activation. In this study, we aimed to elucidate the physiological role of CS in the intestinal tract. We found that, in the small intestine and colon, CS is predominantly produced in the epithelial cells close to the lumen. While dextran sodium sulfate (DSS)-induced colitis was exacerbated in Sult2b1-deficient mice with increased prevalence of neutrophils, the elimination of either neutrophils or intestinal bacteria in Sult2b1-deficient mice attenuated disease development. Similar results were obtained when the Dock2 was genetically deleted in Sult2b1-deficient mice. In addition, we also show that indomethacin-induced ulcer formation in the small intestine was exacerbated in Sult2b1-deficient mice and was ameliorated by CS administration. Thus, our results uncover that CS acts on inflammatory neutrophils, and prevents excessive gut inflammation by inhibiting the Rac activator DOCK2. The administration of CS may be a novel therapeutic strategy for inflammatory bowel disease and non-steroidal anti-inflammatory drug-induced ulcers.PMID:37006281 | PMC:PMC10063914 | DOI:10.3389/fimmu.2023.1131146

Front Immunol. 2023 Mar 15;14:1108895. doi: 10.3389/fimmu.2023.1108895. eCollection 2023.ABSTRACTBACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers.METHODS: Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE.RESULTS: French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets.CONCLUSIONS: Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.PMID:37006253 | PMC:PMC10050742 | DOI:10.3389/fimmu.2023.1108895