PubMed

Am J Med Genet A. 2023 May;191(5):1141-1142. doi: 10.1002/ajmg.a.62806.NO ABSTRACTPMID:37026622 | DOI:10.1002/ajmg.a.62806

Exp Physiol. 2023 Apr 7. doi: 10.1113/EP091134. Online ahead of print.ABSTRACTNEW FINDINGS: What is the central question of this study? Can we manipulate muscle recruitment to differentially enhance skeletal muscle fatigue resistance? What is the main finding and its importance? Through manipulation of muscle activation patterns, it is possible to promote distinct microvascular growth. Enhancement of fatigue resistance is closely associated with the distribution of the capillaries within the muscle, not necessarily with quantity. Additionally, at the acute stages of remodelling in response to indirect electrical stimulation, the improvement in fatigue resistance appears to be primarily driven by vascular remodelling, with metabolic adaptation of secondary importance.ABSTRACT: Exercise involves a complex interaction of factors influencing muscle performance, where variations in recruitment pattern (e.g., endurance vs. resistance training) may differentially modulate the local tissue environment (i.e., oxygenation, blood flow, fuel utilization). These exercise stimuli are potent drivers of vascular and metabolic change. However, their relative contribution to adaptive remodelling of skeletal muscle and subsequent performance is unclear. Using implantable devices, indirect electrical stimulation (ES) of locomotor muscles of rat at different pacing frequencies (4, 10 and 40 Hz) was used to differentially recruit hindlimb blood flow and modulate fuel utilization. After 7 days, ES promoted significant remodelling of microvascular composition, increasing capillary density in the cortex of the tibialis anterior by 73%, 110% and 55% for the 4 Hz, 10 and 40 Hz groups, respectively. Additionally, there was remodelling of the whole muscle metabolome, including significantly elevated amino acid turnover, with muscle kynurenic acid levels doubled by pacing at 10 Hz (P < 0.05). Interestingly, the fatigue index of skeletal muscle was only significantly elevated in 10 Hz (58% increase) and 40 Hz (73% increase) ES groups, apparently linked to improved capillary distribution. These data demonstrate that manipulation of muscle recruitment pattern may be used to differentially expand the capillary network prior to altering the metabolome, emphasising the importance of local capillary supply in promoting exercise tolerance.PMID:37026596 | DOI:10.1113/EP091134

Curr Mol Med. 2023 Apr 7. doi: 10.2174/1566524023666230407123727. Online ahead of print.ABSTRACTIn the last years, with the increase in the average life expectancy, the world's population is progressively aging, which entails social, health and economic problems. In this sense, the need to better understand the physiology of the aging process becomes an urgent need. Since the study of aging in humans is challenging, cellular and animal models are widely used as alternatives. Omics, namely metabolomics, have emerged in the study of aging, with the aim of biomarker discovering, which may help to uncomplicate this complex process. This paper aims to summarize different models used for aging studies with their advantages and limitations. Also, this review gathers the published articles referring to biomarkers of aging already discovered using metabolomics approaches, comparing the results obtained in the different studies. Finally, the most frequently used senescence biomarkers are described, along with their importance in understanding aging.PMID:37026499 | DOI:10.2174/1566524023666230407123727

J Vector Borne Dis. 2023 Jan-Mar;60(1):11-17.ABSTRACTWith the advancements in analytical and molecular techniques, Dried Blood Spots (DBS) are re-emerging as attractive and cost-effective alternatives for global health surveillance. The use of DBS has been well-characterized in the neonatal screening of metabolic diseases, therapeutic screening as well as in epidemiological studies for biomonitoring. Malaria is one such infectious disease where DBS use can expedite molecular surveillance for assessing drug resistance and for refining drug usage policies. In India, malaria cases have reduced significantly over the past decade but to achieve malaria elimination by 2030, country-wide DBS-based screening should be conducted to identify the presence of molecular markers of artemisinin resistance and to study parasite reservoirs in asymptomatic populations. DBS has wide applications in genomics, proteomics, and metabolomic studies concerning both host and pathogen factors. Hence, it is a comprehensive tool for malaria surveillance that can capture both host and parasite information. In this review, we elucidate the current and prospective role of DBS in malaria surveillance and its applications in studies ranging from genetic epidemiology, parasite and vector surveillance, drug development and polymorphisms to ultimately how they can pave the roadmap for countries aiming malaria elimination.PMID:37026215

Front Public Health. 2023 Mar 21;11:1069906. doi: 10.3389/fpubh.2023.1069906. eCollection 2023.ABSTRACTINTRODUCTION: The metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers.METHODS: Thirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation.RESULTS: Metabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively.DISCUSSION: PM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD.PMID:37026137 | PMC:PMC10070744 | DOI:10.3389/fpubh.2023.1069906

Front Immunol. 2023 Mar 21;14:1135701. doi: 10.3389/fimmu.2023.1135701. eCollection 2023.ABSTRACTINTRODUCTION: The mechanism of the immediate adverse drug reactions (ADRs) induced by ShenMai injection (SMI) has not been completely elucidated. Within 30 minutes, the ears and lungs of mice injected with SMI for the first time showed edema and exudation reactions. These reactions were different from the IV hypersensitivity. The theory of pharmacological interaction with immune receptor (p-i) offered a new insight into the mechanisms of immediate ADRs induced by SMI.METHODS: In this study, we determined that the ADRs were mediated by thymus-derived T cells through the different reactions of BALB/c mice (thymus-derived T cell normal) and BALB/c nude mice (thymus-derived T cell deficient) after injecting SMI. The flow cytometric analysis, cytokine bead array (CBA) assay and untargeted metabolomics were used to explain the mechanisms of the immediate ADRs. Moreover, the activation of the RhoA/ROCK signaling pathway was detected by western blot analysis.RESULTS: In BALB/c mice, the vascular leakage and histopathology results showed the occurrence of the immediate ADRs induced by SMI. The flow cytometric analysis revealed that CD4+ T cell subsets (Th1/Th2, Th17/Treg) were imbalanced. And the levels of cytokines such as IL-2, IL-4, IL12P70 and INF-γ increased significantly. However, in BALB/c nude mice, all the indicators mentioned above have not changed significantly. The metabolic profile of both BALB/c mice and BALB/c nude mice was significantly changed after injecting SMI, and the notable increase in lysolecithin level might have a greater association with the immediate ADRs induced by SMI. The Spearman correlation analysis revealed that LysoPC (18:3(6Z,9Z,12Z)/0:0) showed a significant positive correlation with cytokines. After injecting SMI, the levels of RhoA/ROCK signaling pathway-related protein increased significantly in BALB/c mice. Protein-protein interaction (PPI) showed that the increased lysolecithin levels might be related to the activation of the RhoA/ROCK signaling pathway.DISCUSSION: Together, the results of our study revealed that the immediate ADRs induced by SMI were mediated by thymus-derived T cells, and elucidated the mechanisms of such ADRs. This study provided new insights into the underlying mechanism of immediate ADRs induced by SMI.PMID:37026017 | PMC:PMC10070857 | DOI:10.3389/fimmu.2023.1135701

Front Immunol. 2023 Mar 21;14:961642. doi: 10.3389/fimmu.2023.961642. eCollection 2023.ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of COVID-19, causing hundreds of millions of confirmed cases and more than 18.2 million deaths worldwide. Acute kidney injury (AKI) is a common complication of COVID-19 that leads to an increase in mortality, especially in intensive care unit (ICU) settings, and chronic kidney disease (CKD) is a high risk factor for COVID-19 and its related mortality. However, the underlying molecular mechanisms among AKI, CKD, and COVID-19 are unclear. Therefore, transcriptome analysis was performed to examine common pathways and molecular biomarkers for AKI, CKD, and COVID-19 in an attempt to understand the association of SARS-CoV-2 infection with AKI and CKD. Three RNA-seq datasets (GSE147507, GSE1563, and GSE66494) from the GEO database were used to detect differentially expressed genes (DEGs) for COVID-19 with AKI and CKD to search for shared pathways and candidate targets. A total of 17 common DEGs were confirmed, and their biological functions and signaling pathways were characterized by enrichment analysis. MAPK signaling, the structural pathway of interleukin 1 (IL-1), and the Toll-like receptor pathway appear to be involved in the occurrence of these diseases. Hub genes identified from the protein-protein interaction (PPI) network, including DUSP6, BHLHE40, RASGRP1, and TAB2, are potential therapeutic targets in COVID-19 with AKI and CKD. Common genes and pathways may play pathogenic roles in these three diseases mainly through the activation of immune inflammation. Networks of transcription factor (TF)-gene, miRNA-gene, and gene-disease interactions from the datasets were also constructed, and key gene regulators influencing the progression of these three diseases were further identified among the DEGs. Moreover, new drug targets were predicted based on these common DEGs, and molecular docking and molecular dynamics (MD) simulations were performed. Finally, a diagnostic model of COVID-19 was established based on these common DEGs. Taken together, the molecular and signaling pathways identified in this study may be related to the mechanisms by which SARS-CoV-2 infection affects renal function. These findings are significant for the effective treatment of COVID-19 in patients with kidney diseases.PMID:37026010 | PMC:PMC10070855 | DOI:10.3389/fimmu.2023.961642

Front Immunol. 2023 Mar 21;14:1121973. doi: 10.3389/fimmu.2023.1121973. eCollection 2023.ABSTRACTRecurrent disease emerges in the majority of patients with ovarian cancer (OVCA). Adoptive T-cell therapies with T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) are considered promising solutions for less-immunogenic 'cold' ovarian tumors. In order to treat a broader patient population, more TCRs targeting peptides derived from different TAAs binding in various HLA class I molecules are essential. By performing a differential gene expression analysis using mRNA-seq datasets, PRAME, CTCFL and CLDN6 were selected as strictly tumor-specific TAAs, with high expression in ovarian cancer and at least 20-fold lower expression in all healthy tissues of risk. In primary OVCA patient samples and cell lines we confirmed expression and identified naturally expressed TAA-derived peptides in the HLA class I ligandome. Subsequently, high-avidity T-cell clones recognizing these peptides were isolated from the allo-HLA T-cell repertoire of healthy individuals. Three PRAME TCRs and one CTCFL TCR of the most promising T-cell clones were sequenced, and transferred to CD8+ T cells. The PRAME TCR-T cells demonstrated potent and specific antitumor reactivity in vitro and in vivo. The CTCFL TCR-T cells efficiently recognized primary patient-derived OVCA cells, and OVCA cell lines treated with demethylating agent 5-aza-2'-deoxycytidine (DAC). The identified PRAME and CTCFL TCRs are promising candidates for the treatment of patients with ovarian cancer, and are an essential addition to the currently used HLA-A*02:01 restricted PRAME TCRs. Our selection of differentially expressed genes, naturally expressed TAA peptides and potent TCRs can improve and broaden the use of T-cell therapies for patients with ovarian cancer or other PRAME or CTCFL expressing cancers.PMID:37026005 | PMC:PMC10070997 | DOI:10.3389/fimmu.2023.1121973

Heliyon. 2023 Mar 23;9(4):e14779. doi: 10.1016/j.heliyon.2023.e14779. eCollection 2023 Apr.ABSTRACTBACKGROUND: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disease, whose pathogenesis remains unclear. Here, we conducted untargeted metabolomics and lipidomics to identify seminal plasma signatures of nCHH, and to study the effect of LH and FSH deficiency on semen.METHODS: Twenty-five diagnosed patients with nCHH (HH group) and twenty-three healthy participants (HC group) were enrolled. Laboratory parameters, seminal plasma samples and patients' medical data were collected. Untargeted metabolomics and lipidomic profiling were performed using mass spectrometry (MS).RESULTS: The metabolomics profiling are altered among patients with nCHH and healthy controls. There are 160 kinds of differential metabolites and the main different lipid species are TAG, PC, SM and PE.CONCLUSIONS: The metabolomics profiles in patients with nCHH changed. We hope that this work provides important insights into the pathophysiology of nCHH.PMID:37025907 | PMC:PMC10070097 | DOI:10.1016/j.heliyon.2023.e14779

Heliyon. 2023 Mar 27;9(4):e14949. doi: 10.1016/j.heliyon.2023.e14949. eCollection 2023 Apr.ABSTRACTThe brain is the main oxygen-consuming organ and is vulnerable to ischemic shock or insufficient blood perfusion. Brain hypoxia has a persistent and detrimental effect on resident neurons. Previous studies have identified alterations in genes and metabolites in ischemic brain shock by single omics, but the adaptive systems that neurons use to cope with hypoxia remain uncovered. In the present study, we constructed an acute hypoxia model and performed a multi-omics analysis from RNA-sequencing and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics on exploring potentially differentially expressed genes (DEGs) and metabolites (DEMs) in primary cortical neurons under severe acute hypoxic conditions. The TUNEL assay showed acute hypoxia-induced apoptosis in cortical neurons. Omics analysis identified 564 DEGs and 46 DEMs categorized in the Kyoto encyclopedia of genes and genomes (KEGG) database. Integrative pathway analysis highlighted that dysregulated lipid metabolism, enhanced glycolysis, and activated HIF-1 signaling pathways could regulate neuron physiology and pathophysiology under hypoxia. These findings may help us understand the transcriptional and metabolic mechanisms by which cortical neurons respond to hypoxia and identify potential targets for neuron protection.PMID:37025787 | PMC:PMC10070144 | DOI:10.1016/j.heliyon.2023.e14949

Front Mol Biosci. 2023 Mar 21;10:1074500. doi: 10.3389/fmolb.2023.1074500. eCollection 2023.ABSTRACTObjective: To explore the clinical efficacy and metabolic mechanism of Tongdu Huoxue Decoction (THD) in treating lumbar spinal stenosis (LSS). Methods: A total of 40 LSS patients and 20 healthy participants were recruited from January 2022 to June 2022. The patients' pre- and post-treatment visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores were recorded. ELISA kits were used to assess pre- and post-treatment levels of serum Interleukin-1beta (IL-1β), Alpha tumour necrosis factor (TNF-α) and prostaglandin E2 (PGE2). Finally, the patients' pre- and post-treatment and healthy human sera were subjected to extensively targeted metabolomics using Ultra Performance Liquid Chromatography (UPLC) to identify potential differential metabolites and metabolic pathways using multivariate statistical analysis. Results: Compared to the pre-treatment (group A), the patients' VAS scores decreased significantly (p < 0.05), while JOA scores increased significantly (p < 0.05) post-treatment (group B), indicating that THD could effectively improve the pain and lumbar spine function of LSS patients. Moreover, THD could effectively inhibit the expression of IL-1β, TNF-α and PGE2-associated inflammatory factors in serum. Regarding metabolomics, the levels of 41 differential metabolites were significantly different in the normal group (group NC) compared to group A, and those were significantly restored after treatment with THD, including chenodeoxycholic acid 3-sulfate, taurohyodeoxycholic acid, 3,5-Dihydroxy-4-methoxybenzoic acid, pinocembrin. These biomarkers are mainly involved in purine metabolism, steroid hormone biosynthesis and amino acid metabolism. Conclusion: This clinical trial demonstrated that THD is effective in improving pain, lumbar spine function and serum levels of inflammation in patients with LSS. Moreover, its mechanism of action is related to the regulation of purine metabolism, steroid hormone biosynthesis and the expression of key biomarkers in the metabolic pathway of amino acid metabolism.PMID:37025656 | PMC:PMC10070985 | DOI:10.3389/fmolb.2023.1074500

Front Nutr. 2023 Mar 21;10:1124409. doi: 10.3389/fnut.2023.1124409. eCollection 2023.ABSTRACTMaintaining a nutritious diet is essential for humans if they want to live a healthier life. Several food businesses and food safety organizations play a significant role and offer useful ways for improving nutritional quality that assists consumers in making informed selections. Making poor food choices and consuming unhealthy meals are the main causes of non-communicable diseases (NCDs). Nutritional profiling (NP) models are developed to evaluate the nutritional value, calorie content, and the amount of micronutrients and macronutrients contained in a given food accompanied by additional details on the nutritional anomaly provided by published standard nutrients and nutritional databases. To construct an ideal nutritional model that can facilitate food consumption, bioanalytical methods such as chromatography, microscopic techniques, molecular assays, and metabolomics can be applied. With the use of these technologies, one can learn more about the health advantages of nutrition and how to prevent disease. A wider element of NP is also provided by the developing technologies in the area of nutrition research, such as nanotechnology, proteomics, and microarray technology. In this review, we are focusing on the different bioanalytical techniques and the various protocols of NP and their application and refinement of the models. We have evaluated various NP techniques currently used in the food industry for the detection of different components present in food items.PMID:37025612 | PMC:PMC10070841 | DOI:10.3389/fnut.2023.1124409

Front Oncol. 2023 Mar 21;13:1132344. doi: 10.3389/fonc.2023.1132344. eCollection 2023.ABSTRACTInfantile hemangioma (IH) is the most common benign tumor in children. However, the exact pathogenesis of IH remains unclear. Integrated nontargeted and targeted metabolic analyses were performed to obtain insight into the possible pathogenic mechanism of IH. The results of nontargeted metabolic analysis showed that 216 and 128 differential metabolites (DMs) were identified between hemangioma-derived endothelial cells (HemECs) and HUVECs in positive-ion and negative-ion models, respectively. In both models, these DMs were predominantly enriched in pathways related to amino acid metabolism, including aminoacyl-tRNA biosynthesis and arginine and proline metabolism. Then, targeted metabolic analysis of amino acids was further performed to further clarify HemEC metabolism. A total of 22 amino acid metabolites were identified, among which only 16 metabolites, including glutamine, arginine and asparagine, were significantly differentially expressed between HemECs and HUVECs. These significant amino acids were significantly enriched in 10 metabolic pathways, including 'alanine, aspartate and glutamate metabolism', 'arginine biosynthesis', 'arginine and proline metabolism', and 'glycine, serine and threonine metabolism'. The results of our study revealed that amino acid metabolism is involved in IH. Key differential amino acid metabolites, including glutamine, asparagine and arginine, may play an important role in regulating HemEC metabolism.PMID:37025602 | PMC:PMC10070834 | DOI:10.3389/fonc.2023.1132344

Curr Treat Options Neurol. 2022 Dec;24(12):605-618. doi: 10.1007/s11940-022-00742-3. Epub 2022 Sep 15.ABSTRACTPURPOSE OF REVIEW: Precision treatments to address the multifaceted pathophysiology of traumatic brain injury (TBI) are desperately needed, which has led to the intense study of fluid-based protein biomarkers in TBI. Mass Spectrometry (MS) is increasingly being applied to biomarker discovery and quantification in neurological disease to explore the proteome, allowing for more flexibility in biomarker discovery than commonly encountered antibody-based assays. In this narrative review, we will provide specific examples of how MS technology has advanced translational research in traumatic brain injury (TBI) focusing on clinical studies, and looking ahead to promising emerging applications of MS to the field of Neurocritical Care.RECENT FINDINGS: Proteomic biomarker discovery using MS technology in human subjects has included the full range of injury severity in TBI, though critically ill patients can offer more options to biofluids given the need for invasive monitoring. Blood, urine, cerebrospinal fluid, brain specimens, and cerebral extracellular fluid have all been sources for analysis. Emerging evidence suggests there are distinct proteomic profiles in radiographic TBI subtypes, and that biomarkers may be used to distinguish patients sustaining TBI from healthy controls. Metabolomics may offer a window into the perturbations of ongoing cerebral insults in critically ill patients after severe TBI.SUMMARY: Emerging MS technologies may offer biomarker discovery and validation opportunities not afforded by conventional means due to its ability to handle the complexities associated with the proteome. While MS techniques are relatively early in development in the neurosciences space, the potential applications to TBI and neurocritical care are likely to accelerate in the coming decade.PMID:37025501 | PMC:PMC10072855 | DOI:10.1007/s11940-022-00742-3

Food Chem X. 2023 Mar 23;18:100660. doi: 10.1016/j.fochx.2023.100660. eCollection 2023 Jun 30.ABSTRACTThe objective of this study was to characterize the major proteomes and metabolites in beef exudate and determine their relationship to color and oxidative quality of beef muscles. Beef loin (LD) and tenderloin (PM) muscles were cut into sections, individually vacuum-packaged, and aged for 9, 16 and 23 days at 2 °C. Following aging, beef exudates were collected and analyzed for both proteomics and metabolomics profiles. Proteome analysis indicated clustering by muscle types, while metabolomics profiling further clustered the samples based on the aging periods. The PM exudate had a greater concentration of oxidative enzymes, while the LD exudate contained more glycolytic enzymes. Greater lipid, nucleotide, carnitine and glucoside metabolites were observed in LD and 23d exudates. HSP70 and laminin proteins, together with glucosides metabolites, were correlated to muscle oxidative stability. The results indicated that meat exudate could be a viable analytical matrix to determine changes in quality attributes of meat with aging.PMID:37025416 | PMC:PMC10070507 | DOI:10.1016/j.fochx.2023.100660

Drug Des Devel Ther. 2023 Mar 31;17:1007-1024. doi: 10.2147/DDDT.S399290. eCollection 2023.ABSTRACTBACKGROUND: Baicalin is an important active flavonoid isolated from the roots of Scutellaria baicalensis (S. baicalensis), a well-known traditional Chinese herb used in treating inflammatory bowel disease (IBD). The objectives of this study were to assess the potential benefit of baicalin in experimental colitis, as well as to investigate metabolic biomarkers of experimental colitis in conjunction with network pharmacology.METHODS: Using a widely utilized network pharmacology technique, baicalin's targets and pathways were predicted. Simultaneously, experimental colitis was induced by intrarectal administration of TNBS. Histopathology examinations were performed to confirm pathological changes. Plasma samples were examined by using an untargeted metabolomics technique based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen differential metabolites and associated metabolic pathways. Additionally, network pharmacology and integrated analysis of metabolomics were used to identify the primary targets.RESULTS: Through network pharmacology research, tumor necrosis factor (TNF), interleukin 6 (IL6), serine/threonine-protein kinase (AKT1), and other 7 proteins were found to be the main targets of baicalin against IBD. The untargeted metabolomics results showed that 47 metabolites in glycerophospholipids and sphingolipid metabolism were involved as key pathways in the experimental colitis model group. 19 metabolites, including Sphingomyelin (SM d42:2, SM d42:1, SM d34:1), Lysophosphatidic acids (LPA 18:4), 1-Palmitoylglycerophosphocholine, and 17(18)-EpETE were demonstrated as key metabolites for baicalin to exert effects. Moreover, udp-glucose ceramide glucosyltransferase (UGCG), sphingomyelin synthase 1 (SGMS1), and sphingosine kinase (SPHK1) were predicted as sphingolipids-linked targets of baicalin against experimental colitis by integrative analysis.CONCLUSION: Based on these results, it implies that sphingolipid metabolism and sphingolipid signaling pathway might be acted as therapeutic mechanism for baicalin against experimental colitis.PMID:37025160 | PMC:PMC10072146 | DOI:10.2147/DDDT.S399290

Front Plant Sci. 2023 Mar 21;14:1110144. doi: 10.3389/fpls.2023.1110144. eCollection 2023.ABSTRACTCannabis sativa is a multi-use and chemically complex plant which is utilized for food, fiber, and medicine. Plants produce a class of psychoactive and medicinally important specialized metabolites referred to as phytocannabinoids (PCs). The phytohormone methyl jasmonate (MeJA) is a naturally occurring methyl ester of jasmonic acid and a product of oxylipin biosynthesis which initiates and regulates the biosynthesis of a broad range of specialized metabolites across a number of diverse plant lineages. While the effects of exogenous MeJA application on PC production has been reported, treatments have been constrained to a narrow molar range and to the targeted analysis of a small number of compounds. Using high-resolution mass spectrometry with data-dependent acquisition, we examined the global metabolomic effects of MeJA in C. sativa to explore oxylipin-mediated regulation of PC biosynthesis and accumulation. A dose-response relationship was observed, with an almost two-fold increase in PC content found in inflorescences of female clones treated with 15 mM MeJA compared to the control group. Comparison of the inflorescence metabolome across MeJA treatments coupled with targeted transcript analysis was used to elucidate key regulatory components contributing to PC production and metabolism more broadly. Revealing these biological signatures improves our understanding of the role of the oxylipin pathway in C. sativa and provides putative molecular targets for the metabolic engineering and optimization of chemical phenotype for medicinal and industrial end-uses.PMID:37025140 | PMC:PMC10070988 | DOI:10.3389/fpls.2023.1110144

Front Plant Sci. 2023 Mar 21;14:1124827. doi: 10.3389/fpls.2023.1124827. eCollection 2023.ABSTRACTThe metabolome of strawberries at harvest determines their storage capacity. Therefore, dynamics of volatile production during storage of strawberry cultivated under diverse drainage ratios, T1 (12.0%), T2 (25.3%), T3 (36.4%), and T4 (56.5%), were evaluated. Among the various non-target VOCs analysis, there were some groups including aldehydes, esters, and furans occupied over 5% with exhibiting high coefficient of determination (R2 ) following the days after storage (DAS). Aldehydes content decreased over the storage period, while the esters (methyl butanoate, methyl hexanoate, ethyl hexanoate, and benzyl acetate) and furanones (furaneol and mesifuran) were increased as representing aroma compounds in strawberry ripening. Even on the same day, it was investigated that the release of VOCs linked to fruit decay was delayed in the groups (T1 and T2) that were given relatively little water compared to T3 and T4. The hexanal and ethyl hexanoate as an over-ripened signal showed a rapid increase from 4 DAS to 5 DAS in T3 and T4, respectively, while T1 and T2 showed significant increase from 5 DAS to 6 DAS. Relatively slower over-ripening tendency of T1 and T2 was supported by changes of firmness, total soluble solid content, anthocyanin content, and antioxidant activity during storage. T1 and T2 showed higher antioxidant activity at the harvest time and lower anthocyanin accumulation than T3 and T4. The present study elucidated that the preharvest drainage changes during cultivation was involved in fruit quality during strawberry storage. Besides, volatilomics analysis depicted that T2 as an optimal ratio, could delay the occurrence of stress and senescence, and guaranteed the strawberry yield. In conclusion, this study provided evidence that the practical application of drainage ratios could improve horticultural product quality even with low water use and VOCs might be considered an early indicator for strawberry fruit shelf-life.PMID:37025137 | PMC:PMC10070737 | DOI:10.3389/fpls.2023.1124827

Metabol Open. 2023 Mar 23;18:100239. doi: 10.1016/j.metop.2023.100239. eCollection 2023 Jun.ABSTRACTBACKGROUND: Metabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens.METHOD: Targeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified.RESULTS: Several acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae.CONCLUSIONS: In this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.PMID:37025095 | PMC:PMC10070890 | DOI:10.1016/j.metop.2023.100239

Front Mol Biosci. 2023 Apr 6;10:1190730. doi: 10.3389/fmolb.2023.1190730. eCollection 2023.NO ABSTRACTPMID:37091869 | PMC:PMC10117775 | DOI:10.3389/fmolb.2023.1190730