Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Integrated morphological, metabolome, and transcriptome analyses revealed the mechanism of exogenous gibberellin promoting petiole elongation in <em>Oenanthe javanica</em>

Wed, 02/08/2023 - 12:00
Front Plant Sci. 2023 Jul 17;14:1225635. doi: 10.3389/fpls.2023.1225635. eCollection 2023.ABSTRACTOenanthe javanica (Blume) DC. is a popular vegetable with unique flavor and its leaf is the main product organ. Gibberellin (GA) is an important plant hormone that plays vital roles in regulating the growth of plants. In this study, the plants of water dropwort were treated with different concentrations of GA3. The plant height of water dropwort was significantly increased after GA3 treatment. Anatomical structure analysis indicated that the cell length of water dropwort was elongated under exogenous application of GA3. The metabolome analysis showed flavonoids were the most abundant metabolites and the biosynthesis of secondary metabolites were also regulated by GA3. The exogenous application of GA3 altered the gene expressions of plant hormone signal transduction (GID and DELLA) and metabolites biosynthesis pathways to regulate the growth of water dropwort. The GA contents were modulated by up-regulating the expression of GA metabolism gene GA2ox. The differentially expressed genes related to cell wall formation were significantly enriched. A total of 22 cellulose synthase involved in cellulose biosynthesis were identified from the genome of water dropwort. Our results indicated that GA treatment promoted the cell elongation by inducing the expression of cellulose synthase and cell wall formation in water dropwort. These results revealed the molecular mechanism of GA-mediated cell elongation, which will provide valuable reference for using GA to regulate the growth of water dropwort.PMID:37528973 | PMC:PMC10389089 | DOI:10.3389/fpls.2023.1225635

Faecal bacteriome and metabolome profiles associated with decreased mucosal inflammatory activity upon anti-TNF therapy in paediatric Crohn's disease

Tue, 01/08/2023 - 12:00
J Crohns Colitis. 2023 Aug 1:jjad126. doi: 10.1093/ecco-jcc/jjad126. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Treatment by anti-TNFα antibodies (anti-TNF) changes the dysbiotic faecal bacteriome in Crohn's disease (CD). However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in faecal bacteriome and metabolome upon anti-TNF administration (and therapeutic response) in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis (JIA).METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed for bacteriome by massively parallel sequencing of the 16S rDNA (V4 region) and for faecal metabolome by 1H nuclear magnetic resonance. The response to treatment by mucosal healing was assessed by MINI index at three months after the treatment started. We also tested several representative gut bacterial strains for in-vitro growth inhibition by infliximab.RESULTS: We analysed 530 stool samples from 121 children (CD 54, JIA 18, healthy 49). Bacterial community composition reacted on anti-TNF in CD: three members of class Clostridia increased on anti-TNF, whereas class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response (mucosal healing) after anti-TNF. No significant changes in bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.PMID:37527838 | DOI:10.1093/ecco-jcc/jjad126

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

Tue, 01/08/2023 - 12:00
Cell Metab. 2023 Jul 26:S1550-4131(23)00261-9. doi: 10.1016/j.cmet.2023.07.002. Online ahead of print.ABSTRACTThere has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.PMID:37527658 | DOI:10.1016/j.cmet.2023.07.002

LC-MS/MS based metabolomic analysis of serum from patients with cerebrovascular stenosis

Tue, 01/08/2023 - 12:00
J Pharm Biomed Anal. 2023 Jul 28;235:115608. doi: 10.1016/j.jpba.2023.115608. Online ahead of print.ABSTRACTCerebrovascular stenosis (CVS) is the main cause of ischemic stroke, which greatly threatens human life. Hence, it's important to perform early screenings for CVS. Metabolomics is an emerging omics approach that has great advantages in disease screening and diagnosis. Therefore, we aim to elucidate the correlation between CVS and metabolomics, which can aid in conducting CVS screening at an early stage. Patients with CVS in Beijing Hospital were included in the study. A total of 36 participants, including 18 patients diagnosed with CVS and 18 healthy individuals, were recruited at Beijing Hospital between May 2022 and October 2021. The serum samples were analyzed for liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, multivariate statistical methods, including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed. Differential metabolites were obtained and demonstrated by volcano plot and heatmap. The study recruited 36 participants, including 18 patients with CVS and 18 healthy participants. A total of 150 metabolites were identified. Multivariate statistical analysis revealed significant differences between patients and healthy participants. Furthermore, 30 serum metabolites levels differed significantly between two groups. Differential metabolites were enriched in phenylalanine, tyrosine, and tryptophan biosynthesis; primary bile acid biosynthesis, and other pathways. This study identified differential metabolites in patients with CVS and elucidated the relevant metabolic pathways. Thus, these findings aid in the study of the pathogenesis of CVS and its early diagnosis. DATA AVAILABILITY STATEMENT: The datasets generated for this study are available on request to the corresponding author.PMID:37527609 | DOI:10.1016/j.jpba.2023.115608

Sex-Gender-Based Differences in Metabolic Diseases

Tue, 01/08/2023 - 12:00
Handb Exp Pharmacol. 2023 Aug 2. doi: 10.1007/164_2023_683. Online ahead of print.ABSTRACTSexual dimorphism creates different biological and cellular activities and selective regulation mechanisms in males and females, thus generating differential responses in health and disease. In this scenario, the sex itself is a source of physiologic metabolic disparities that depend on constitutive genetic and epigenetic features that characterize in a specific manner one sex or the other. This has as a direct consequence a huge impact on the metabolic routes that drive the phenotype of an individual. The impact of sex is being clearly recognized also in disease, whereas male and females are more prone to the development of some disorders, or have selective responses to drugs and therapeutic treatments. Actually, very less is known regarding the probable differences guided by sex in the context of inherited metabolic disorders, owing to the scarce consideration of sex in such restricted field, accompanied by an intrinsic bias connected with the rarity of such diseases. Metabolomics technologies have been ultimately developed and adopted for being excellent tools for the investigation of metabolic mechanisms, for marker discovery or monitoring, and for supporting diagnostic procedures of metabolic disorders. Hence, metabolomic approaches can excellently embrace the discovery of sex differences, especially when associated to the outcome or the management of certain inborn errors of the metabolism.PMID:37528324 | DOI:10.1007/164_2023_683

The plasma metabolome of long COVID patients two years after infection

Tue, 01/08/2023 - 12:00
Sci Rep. 2023 Aug 1;13(1):12420. doi: 10.1038/s41598-023-39049-x.ABSTRACTOne of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as "long COVID") which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.PMID:37528111 | DOI:10.1038/s41598-023-39049-x

Understanding quality differences between kiwifruit varieties during softening

Tue, 01/08/2023 - 12:00
Food Chem. 2023 Jul 24;430:136983. doi: 10.1016/j.foodchem.2023.136983. Online ahead of print.ABSTRACTResearch into variations between kiwifruit varieties particularly their softening quality during storage is important in improving kiwifruit quality. The potential reasons for ripening quality differences between 'Cuixiang' (CX) and 'Hayward' (HWD) kiwifruit were analyzed by physiology and metabolomic data combined with the random forests learning algorithm. The results showed that the storability difference between the two varieties mainly resulted from differences in polygalacturonase (PG) and β-galactosidase activities. The 1 °C slowed the fruit softening process of both varieties by decreasing their PG activities. A total of 368 metabolites were identified and amino acid, carbohydrate, cofactors and vitamins, as well as nucleotide metabolism are key metabolic modules that affect the ripening differences of CX and HWD kiwifruit. A total of 30 metabolites showed remarkable ability in distinguish the ripening quality of CX and HWD kiwifruit, in which d-glucose, d-maltose, 2-hydroxybutyric acid, phenyllactate, and vitamin B2 were noteworthy for their potential application on the evaluation of kiwifruit taste and nutritional value. These findings provide positive insights into the underlying mechanism of ripening quality differences between CX and HWD kiwifruit and new ideas for identifying key metabolic markers in kiwifruit.PMID:37527582 | DOI:10.1016/j.foodchem.2023.136983

Evolutionary signatures of a trade-off in direct and indirect defenses across the wild grape genus Vitis

Tue, 01/08/2023 - 12:00
Evolution. 2023 Aug 1:qpad140. doi: 10.1093/evolut/qpad140. Online ahead of print.ABSTRACTEvolutionary correlations between chemical defense and protection by mutualist bodyguards have been long predicted, but tests of these pattern remain rare. We use a phylogenetic framework to test for evolutionary correlations indicative of trade-offs or synergisms between direct defense in the form of plant secondary metabolism, and indirect defense in the form of leaf domatia, across 33 species in the wild grape genus, Vitis. We also performed a bioassay with a generalist herbivore to associate our chemical phenotypes with herbivore palatability. Finally, we tested whether defensive traits correlate with the average abiotic characteristics of each species' contemporary range and whether these correlations were consistent with plant defense theory. We found a negative evolutionary correlation between domatia size and the diversity of secondary metabolites in Vitis leaf tissue across the genus, and also that leaves with a higher diversity and richness of secondary metabolites were less palatable to a generalist herbivore, consistent with a trade-off in chemical and mutualistic defense investment. Predictions from plant defense theory were not supported by associations between investment in defense phenotypes and abiotic variables. Our work demonstrates an evolutionary pattern indicative of a trade-off between indirect and direct defense strategies across the Vitis genus.PMID:37527551 | DOI:10.1093/evolut/qpad140

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies

Tue, 01/08/2023 - 12:00
PLoS One. 2023 Aug 1;18(8):e0289285. doi: 10.1371/journal.pone.0289285. eCollection 2023.ABSTRACTINTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of hematopoietic cells with a variable clinical spectrum characterized by intravascular hemolysis, high risk of thrombosis, and cytopenias. To understand the biochemical shifts underlying PNH, this study aimed to search for the dysfunctional pathways involved in PNH physiopathology by comparing the systemic metabolic profiles of affected patients to healthy controls and the metabolomic profiles before and after the administration of eculizumab in PNH patients undergoing treatment.METHODS: Plasma metabolic profiles, comprising 186 specific annotated metabolites, were quantified using targeted quantitative electrospray ionization tandem mass spectrometry in 23 PNH patients and 166 population-based controls. In addition, samples from 12 PNH patients on regular eculizumab maintenance therapy collected before and 24 hours after eculizumab infusion were also analyzed.RESULTS: In the PNH group, levels of the long-chain acylcarnitines metabolites were significantly higher as compared to the controls, while levels of histidine, taurine, glutamate, glutamine, aspartate and phosphatidylcholines were significantly lower in the PNH group. These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis. In 12 PNH patients who were receiving regular eculizumab therapy, the concentrations of acylcarnitine C6:1, the C14:1/C6 ratio (reflecting the impaired action of the medium-chain acyl-Co A dehydrogenase), and the C4/C6 ratio (reflecting the impaired action of short-chain acyl-Co A dehydrogenase) were significantly reduced immediately before eculizumab infusion, revealing impairments in the Acyl CoA metabolism, and reached levels similar to those in the healthy controls 24 hours after infusion.CONCLUSIONS: We demonstrated significant differences in the metabolomes of the PNH patients compared to healthy controls. Eculizumab infusion seemed to improve deficiencies in the acyl CoA metabolism and may have a role in the mitochondrial oxidative process of long and medium-chain fatty acids, reducing oxidative stress, and inflammation.PMID:37527257 | DOI:10.1371/journal.pone.0289285

GWAS reveals genomic associations with swine inflammation and necrosis syndrome

Tue, 01/08/2023 - 12:00
Mamm Genome. 2023 Aug 1. doi: 10.1007/s00335-023-10011-6. Online ahead of print.ABSTRACTThe recently identified swine inflammation and necrosis syndrome (SINS) occurs in high prevalence from newborn piglets to fattening pigs and resembles an important concern for animal welfare. The primary endogenous syndrome affects the tail, ears, teats, coronary bands, claws and heels. The basis of clinical inflammation and necrosis has been substantiated by histopathology, metabolomic and liver transcriptomic. Considerable variation in SINS scores is evident in offspring of different boars under the same husbandry conditions. The high complexity of metabolic alterations and the influence of the boar led to the hypothesis of a polygenic architecture of SINS. This should be investigated by a genome-wide association study. For this purpose, 27 sows were simultaneously inseminated with mixed semen from two extreme boars. The mixed semen always contained ejaculate from a Pietrain boar classified as extremely SINS susceptible and additionally either the ejaculate from a Pietrain boar classified as SINS stable or from a Duroc boar classified as SINS stable. The 234 piglets were phenotyped on day 3 of life, sampled and genetically assigned to the respective boar. The piglets showed the expected genetic differentiation with respect to SINS susceptibility. The suspected genetic complexity was confirmed both in the number and genome-wide distribution of 221 significantly associated SNPs, and led to 49 candidate genes. As the SNPs were almost exclusively located in noncoding regions, functional nucleotides have not yet been identified. The results suggest that the susceptibility of piglets to SINS depends not only on environmental conditions but also on genomic variation.PMID:37526658 | DOI:10.1007/s00335-023-10011-6

Discovery and validation of metabolite markers in bloodstains for bloodstain age estimation

Tue, 01/08/2023 - 12:00
Analyst. 2023 Aug 1. doi: 10.1039/d3an00603d. Online ahead of print.ABSTRACTBloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain metabolites as markers for estimating bloodstain age, none have considered sex, age-related metabolomic differences, or long-time bloodstain age. Therefore, we aimed to identify metabolite markers for estimating the age of bloodstains at weekly intervals within 28 days and validate them through multiple reaction monitoring. Adenosine 5'-monophosphate, choline, and pyroglutamic acid were selected as markers. Seven metabolites were validated, including five previously reported metabolites, ergothioneine, hypoxanthine, L-isoleucine, L-tryptophan, and pyroglutamic acid. Choline and hypoxanthine can be used to differentiate bloodstains between days 0 and 14 after deposition at weekly intervals, whereas L-isoleucine and L-tryptophan can help distinguish bloodstains between 7 days before and 14 days after deposition. Evaluation of the changes in metabolite levels according to sex and age revealed that the average levels of all seven metabolites were higher in women on day 0. Moreover, the level of ergothioneine was significantly higher in elderly individuals than in young individuals at all time points. In this study, we confirmed the potential effectiveness of metabolites in bloodstains as forensic markers and provided a new perspective on metabolomic approaches linked to forensic science.PMID:37526270 | DOI:10.1039/d3an00603d

Serum amino acid profiling in differentiating clinical outcomes of multiple sclerosis

Tue, 01/08/2023 - 12:00
Neurol Neurochir Pol. 2023 Aug 1. doi: 10.5603/PJNNS.a2023.0054. Online ahead of print.ABSTRACTAIM OF THE STUDY: Amino acid metabolism is crucial for regulating immune responses and can be monitored in blood serum samples. This study aimed to analyse serum amino acid profiles in people with multiple sclerosis (pwMS), taking into account differences depending on the disease outcomes.CLINICAL RATIONALE FOR THE STUDY: Serum amino acid profiling is a promising, reproducible and minimally invasive technology, available at different stages of the disease, enabling the search for a specific biomarker to differentiate MS clinical outcomes.MATERIAL AND METHODS: The serum concentrations of 29 amino acids were determined using high-performance liquid chromatography mass spectrometry.RESULTS: A total of 121 pwMS (41 relapsing-remitting MS-RRMS; 55 secondary progressive MS - SPMS; and 25 primary progressive MS-RRMS) with a median Expanded Disability Status Scale (EDSS) score of 6 and 53 healthy controls (HCs) were included. We found significantly higher serum total amino acids concentrations in pwMS compared to HCs. Serum concentrations of arginine, 1-methyl-L-histidine and proline were higher in pwMS, while circulating citrulline, α-aminobutyric acid and tryptophan were lower in pwMS. We observed significant differences in serum total amino acids concentrations depending on MS type, with the highest level in the PPMS group and the lowest in the RRMS group. We found significantly higher serum levels of beta-aminoisobutyric acid in PPMS patients compared to those with RRMS and SPMS, and significantly higher serum levels of aspartic acid in PPMS patients compared to RRMS patients. From visual inspection, no trend was observed in total amino acids concentration with respect to the EDSS score. When analysing serum total amino acids concentration in pwMS with EDSS ≤ 5 compared to those with EDSS > 5, no significant differences were found.CONCLUSIONS AND CLINICAL IMPLICATIONS: Amino acid metabolism is altered in pwMS and depends on the clinical type of the disease. Further studies are needed to determine whether serum metabolomic profiling of amino acids may have an application in the search for clinical phenotype-specific MS biomarkers.PMID:37526173 | DOI:10.5603/PJNNS.a2023.0054

Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death

Tue, 01/08/2023 - 12:00
J Clin Invest. 2023 Aug 1;133(15):e168575. doi: 10.1172/JCI168575.ABSTRACTBACKGROUNDChronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic cell transplantation (HCT). More accurate information regarding the risk of developing cGVHD is required. Bone marrow (BM) grafts contribute to lower cGVHD, which creates a dispute over whether risk biomarker scores should be used for peripheral blood (PB) and BM.METHODSDay 90 plasma proteomics from PB and BM recipients developing cGVHD revealed 5 risk markers that were added to 8 previous cGVHD markers to screen 982 HCT samples of 2 multicenter Blood and Marrow Transplant Clinical Trials Network (BMTCTN) cohorts. Each marker was tested for its association with cause-specific hazard ratios (HRs) of cGVHD using Cox-proportional-hazards models. We paired these clinical studies with biomarker measurements in a mouse model of cGVHD.RESULTSSpearman correlations between DKK3 and MMP3 were significant in both cohorts. In BMTCTN 0201 multivariate analyses, PB recipients with 1-log increase in CXCL9 and DKK3 were 1.3 times (95% CI: 1.1-1.4, P = 0.001) and 1.9 times (95%CI: 1.1-3.2, P = 0.019) and BM recipients with 1-log increase in CXCL10 and MMP3 were 1.3 times (95%CI: 1.0-1.6, P = 0.018 and P = 0.023) more likely to develop cGVHD. In BMTCTN 1202, PB patients with high CXCL9 and MMP3 were 1.1 times (95%CI: 1.0-1.2, P = 0.037) and 1.2 times (95%CI: 1.0-1.3, P = 0.009) more likely to develop cGVHD. PB patients with high biomarkers had increased likelihood to develop cGVHD in both cohorts (22%-32% versus 8%-12%, P = 0.002 and P < 0.001, respectively). Mice showed elevated circulating biomarkers before the signs of cGVHD.CONCLUSIONBiomarker levels at 3 months after HCT identify patients at risk for cGVHD occurrence.FUNDINGNIH grants R01CA168814, R21HL139934, P01CA158505, T32AI007313, and R01CA264921.PMID:37526081 | DOI:10.1172/JCI168575

Hirami lemon (<em>Citrus reticulata</em> var. <em>depressa</em>) modulates the gut-brain axis in a chronic mild stress-induced depression mouse model

Tue, 01/08/2023 - 12:00
Food Funct. 2023 Aug 1. doi: 10.1039/d3fo01301d. Online ahead of print.ABSTRACTCitrus reticulata var. depressa, commonly known as Hirami lemon, is a native citrus species found in Taiwan and Okinawa islands of Japan. While several Citrus species are known to possess antidepressant activity by modulating the gut microbiota, the antidepressant effect of Hirami lemon and its underlying mechanisms have not been thoroughly investigated. In this study, we explored the potential antidepressant efficacy of the fruit extract (CD) and the essential oil (CDE) from Hirami lemon peel using a chronic mild stress (CMS)-induced mouse model and analyzed the association of gut microbiome changes. Our findings revealed that mice subjected to CMS exhibited anxiety- and depression-like behaviors as assessed by elevated plus-maze and forced swimming tests, respectively. Significantly, oral administration of CDE and CD notably reversed CMS-induced depression- and anxiety-like behaviors in CMS-induced mice. Moreover, compared to the non-stressed group, CMS significantly altered the gut microbiome, characterized by highly diverse bacterial communities, reduced Bacteroidetes, and increased Firmicutes. However, oral administration of CDE and CD restored gut microbiota dysbiosis. We also performed a qualitative analysis of CD and CDE using UPLC-MS and GC-MS, respectively. The CD contained 25 compounds, of which 3 were polymethoxy flavones and flavanones. Three major compounds, nobiletin, tangeretin and hesperidin, accounted for 56.88% of the total relative peak area. In contrast, the CDE contained 11 terpenoids, of which 8 were identified as major compounds, with D-limonene (45.71%) being the most abundant, followed by γ-terpinene (34.65%), linalool (6.46%), p-cymene (2.57%), α-terpineol (2.04%), α-pinene (1.89%), α-terpinolene (1.46%), and β-pinene (1.16%), accounting for 95.94% of the total oil. In conclusion, our study demonstrated the potential of Hirami lemon as a source of natural antidepressant agents for the prevention and treatment of major depressive disorders.PMID:37526032 | DOI:10.1039/d3fo01301d

A Metabolomics-Based Study on NMDAR-Mediated Mitochondrial Damage through Calcium Overload and ROS Accumulation in Myocardial Infarction

Tue, 01/08/2023 - 12:00
Front Biosci (Landmark Ed). 2023 Jul 19;28(7):140. doi: 10.31083/j.fbl2807140.ABSTRACTBACKGROUND: Coronary artery disease is a leading public health problem. However, the mechanisms underlying mitochondrial damage remain unclear. The present study verified and explored the novel mechanisms underlying ischemic injury based on a metabolomic analysis.METHODS: Mouse models of acute myocardial infarction were established, and serum samples were collected for targeted liquid chromatography with tandem mass spectrometry analysis. Based on metabolomic analyses, the N-methyl-d-aspartic acid receptor (NMDAR)-related calcium transporting signaling pathway was selected. Primary cardiomyocyte cultures were used, and N-methyl-d-aspartic acid (NMDA) was used as an agonist to confirm the role of NMDAR in ischemic injury. In addition, Bax, Bcl-2, mitochondrial calcium, potential, and mitochondrial reactive oxygen species accumulation were used to explore the role of NMDAR in mitochondrial damage-induced apoptosis.RESULTS: Glutamate-related metabolism was significantly altered following in acute myocardial infarction. NMDA induces apoptosis under hypoxic conditions NMDAR was translocated to the mitochondrial-related membrane after activation, and its mitochondrial expression was significantly increased (p < 0.05). Mitochondrial damage-induced apoptosis was significantly inhibited by a selective NDMAR antagonist (p < 0.05), while Bax expression was remarkably decreased and Bcl-2 expression was increased (p < 0.05). To further explore the mechanism of NMDAR, mitochondrial calcium, membrane potential, and reactive oxygen species were detected. With NMDAR inhibition under hypoxic conditions, mitochondrial morphology and function were preserved (p < 0.05).CONCLUSIONS: Our metabolomic study identified NMDAR as a promising target. In conclusion, our study provides solid data for further studies of the role of NMDAR in cardiovascular diseases and a promising target to interfere with apoptosis in acute myocardial infarction.PMID:37525913 | DOI:10.31083/j.fbl2807140

Early Identification of Serum Biomarkers and Pathways of Sepsis Through GC-MS-Based Metabolomics Analysis

Tue, 01/08/2023 - 12:00
Front Biosci (Landmark Ed). 2023 Jul 24;28(7):145. doi: 10.31083/j.fbl2807145.ABSTRACTBACKGROUND: Early identification of sepsis improves the survival rate; however, it is one of the most challenging tasks for physicians, especially since symptoms are easily confused with those of systemic inflammatory response syndrome (SIRS). Our aim was to explore biomarkers for early identification of sepsis that would aid in its differential diagnosis.METHODS: Eight patients with SIRS, eight with sepsis, and eight healthy controls were included in this study. Metabolites were screened using gas chromatography-mass spectrometry (GC-MS). Metabolism profiles were analyzed using the untargeted database of GC-MS from Lumingbio (LUG) database, and metabolic pathways were enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The S-plot was used to screen the potential biomarkers distinguishing between patients with SIRS, sepsis, and healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate potential biomarkers between SIRS and sepsis patients. Correlation analysis was used to measure the degree of correlation between differential metabolites. Correlation analysis between 2-deoxy-d-erythro-pentofuranose-5-phosphate and clinical indicators was performed.RESULTS: There were 51 metabolites that were distributed in the SIRS group, and they were enriched with 18 metabolic pathways compared with healthy controls. Moreover, 63 metabolites in the sepsis group were significantly distinguishable compared to the healthy controls, and were associated with 21 metabolic pathways. Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine were found to be candidate biomarkers for distinguishing between SIRS, sepsis, and healthy controls using the S-plot model. Only four differential metabolites, including 2-deoxy-d-erythro-pentofuranose-5-phosphate, terbutaline, allantoic acid, and homovanillic acid (HVA), were enriched in the dopaminergic synapse and tyrosine metabolism pathways when sepsis patients were compared with SIRS patients. The Area Under Curve (AUC) of 2-deoxy-d-erythro-pentofuranose-5-phosphate was 0.9297, indicating a strong diagnostic ability for sepsis. A significant negative correlation was identified between 2-deoxy-d-erythro-pentofuranose-5-phosphate and lactate (r = -0.8756, p = 0.0044).CONCLUSIONS: Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine may be used as candidate biomarkers to distinguish SIRS and sepsis patients from healthy controls using GC-MS. 2-deoxy-d-erythro-pentofuranose-5-phosphate may be the candidate biomarker to distinguish sepsis from SIRS. Our study explored candidate biomarkers for the early identification of sepsis, which is vital for improving its prognosis.PMID:37525905 | DOI:10.31083/j.fbl2807145

A Portable Infrared Attenuated Total Reflection Spectrometer for Food Analysis

Tue, 01/08/2023 - 12:00
Appl Spectrosc. 2023 Aug 1:37028231190660. doi: 10.1177/00037028231190660. Online ahead of print.ABSTRACTThe analytical performance of a compact infrared attenuated total reflection spectrometer using a pyroelectric detector array has been evaluated and compared to a conventional laboratory Fourier transform infrared system for applications in food analysis. Analytical characteristics including sensitivity, repeatability, linearity of the calibration functions, signal-to-noise ratio, and spectral resolution have been derived for both approaches. Representative analytes of relevance in food industries (i.e., organic solvents, fatty acids, and mycotoxins) have been used for the assessment of the performance of the device and to discuss the potential of this technology in food and feed analysis.PMID:37525897 | DOI:10.1177/00037028231190660

Serum metabolomics detected by LDI-TOF-MS can be used to distinguish between diabetic patients with and without diabetic kidney disease

Tue, 01/08/2023 - 12:00
FEBS Open Bio. 2023 Aug 1. doi: 10.1002/2211-5463.13683. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) is an important cause of end-stage renal disease with changes in metabolic characteristics. The objective of this study was to study changes in serum metabolic characteristics in patients with DKD and to examine metabolite panels to distinguish DKD from diabetes with MALDI-TOF-MS. We recruited 40 T2DM patients with or without DKD from a single center for a cross-sectional study. Serum metabolic profiling was performed with MALDI-TOF-MS using a vertical silicon nanowire array. Differential metabolites between DKD and diabetes patients were selected, and their relevance to the clinical parameters of DKD was analyzed. We applied machine learning methods to the differential metabolite panels to distinguish DKD patients from diabetes patients. Twenty-four differential serum metabolites between DKD patients and diabetes patients were identified, which were mainly enriched in butyrate metabolism, TCA cycle, and alanine, aspartate and glutamate metabolism. Among the metabolites, L-kynurenine was positively correlated with urinary microalbumin, urinary microalbumin/creatinine ratio (UACR), creatinine and urea nitrogen content. L-serine, pimelic acid, 5-methylfuran-2-carboxylic acid, 4-methylbenzaldehyde and dihydrouracil were associated with Glomerular filtration rate (eGFR). The panel of differential metabolites could be used to distinguish between DKD and diabetes patients with an AUC value reaching 0.9899-0.9949. Among the differential metabolites, L-kynurenine was related to the progression of DKD. The differential metabolites exhibited excellent performance at distinguishing between DKD and diabetes. This study provides a novel direction for metabolomics-based clinical detection of DKD.PMID:37525631 | DOI:10.1002/2211-5463.13683

The Gut-Heart Axis: Updated Review for The Roles of Microbiome in Cardiovascular Health

Tue, 01/08/2023 - 12:00
Korean Circ J. 2023 Jun 23. doi: 10.4070/kcj.2023.0048. Online ahead of print.ABSTRACTCardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.PMID:37525495 | DOI:10.4070/kcj.2023.0048

Untargeted metabolomics liquid chromatography-high resolution mass spectrometry approach for the geographical origin assessment of Italian dehydrated apples

Tue, 01/08/2023 - 12:00
J Mass Spectrom. 2023 Jul 31:e4954. doi: 10.1002/jms.4954. Online ahead of print.ABSTRACTGeographical provenience is nowadays a relevant aspect of the authenticity and the quality of many food commodities. Dehydrated apple cubes/slices represent an ingredient commonly used by food companies for bakery products. However, this apple-based matrix is not so known and studied from an analytical point of view. In the present work, seven compounds were identified as key molecules to distinguish between Italian and non-Italian samples, through an untargeted ultrahigh-pressure liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) approach. This methodology was merged with multivariate statistical analysis, and the principal features were studied and identified considering several identification steps. Samples from 2020 and 2021 harvesting campaigns, with partial and total dehydration rates, with or without peel, and from different apple varieties were considered for the study, for a total of 91 samples. Afterward, the same analysis protocol was applied to an external set (n = 12 samples), included in the statistical models, searching for the key compounds identified in the training set. Interesting and significant results underlined the potentiality of the UHPLC-HRMS technology as a confirmatory strategy for the geographical origin assessment of dehydrated apple commodities.PMID:37525466 | DOI:10.1002/jms.4954

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