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

Metabolomics analysis of rice fermented by medicinal fungi providing insights into the preparation of functional food

Wed, 10/07/2024 - 12:00
Food Chem. 2024 Jul 6;459:140372. doi: 10.1016/j.foodchem.2024.140372. Online ahead of print.ABSTRACTRice, a primary staple food, may be improved in value via fermentation. Here, ten medicinal basidiomycetous fungi were separately applied for rice fermentation. After preliminary screening, Ganoderma boninense, Phylloporia pulla, Sanghuangporus sanghuang and Sanghuangporus weigelae were selected for further LC-MS based determination of the changes in metabolic profile after their fermentation with rice, and a total of 261, 296, 312, and 355 differential compounds were identified, respectively. Most of these compounds were up-regulated and involved in the metabolic pathways of amino acid metabolism, lipid metabolism, carbohydrate metabolism and the biosynthesis of other secondary metabolites. Sanghuangporus weigelae endowed the rice with the highest nutritional and bioactive values. The metabolic network of the identified differential compounds in rice fermented by S. weigelae illustrated their close relationships. In summary, this study provides insights into the preparation and application of potential functional food via the fermentation of rice with medicinal fungi.PMID:38986207 | DOI:10.1016/j.foodchem.2024.140372

Field isolates of Beauveria bassiana exhibit biological heterogeneity in multitrophic interactions of agricultural importance

Wed, 10/07/2024 - 12:00
Microbiol Res. 2024 Jun 29;286:127819. doi: 10.1016/j.micres.2024.127819. Online ahead of print.ABSTRACTBeauveria bassiana (Bb) is a widespread entomopathogenic fungus widely used in agriculture for crop protection. Other than pest control, fungi belonging to the B. bassiana complex represent an important microbial resource in agroecosystems, considering their multiple interactions with other microorganisms as antagonists of phytopathogens, or with plants as endophytic colonizers and growth promoters. Here, we characterised field collected or commercial isolates of B. bassiana relative to the environmental factors that affect their growth. We further compared the metabolome, the entomopathogenic potential and biocontrol activity of the tested isolates respectively on the insect pest Spodoptera littoralis or against the fungal plant pathogen Fusarium oxysporum. Our analysis revealed that the B. bassiana complex is characterised by a high level of inter-isolate heterogeneity in terms of nutritional requirements, establishment of intra- or inter-kingdom interactions, and the nature of metabolites produced. Interestingly, certain B. bassiana isolates demonstrated a preference for low nutrient plant-derived media, which hints at their adaptation towards an endophytic lifestyle over a saprophytic one. In addition, there was a noticeable variation among different B. bassiana isolates in their capacity to kill S. littoralis larvae in a contact infection test, but not in an intrahaemocoelic injection experiment, suggesting a unique level of adaptability specific to the host. On the other hand, most B. bassiana isolates exhibited similar biocontrol efficacy against the soil-dwelling ascomycete F. oxysporum f. sp. lycopersici, a pathogen responsible for vascular wilt disease in tomato plants, effectively averting wilting. Overall, we show that the effectiveness of B. bassiana isolates can greatly vary, emphasising the importance of isolate selection and nutritional adaptability consideration for their use in sustainable agriculture.PMID:38986181 | DOI:10.1016/j.micres.2024.127819

Sepsis Research Using Omics Technology in the European Union and the United Kingdom: Maps, Trends, and Future Implications

Wed, 10/07/2024 - 12:00
OMICS. 2024 Jul;28(7):357-366. doi: 10.1089/omi.2024.0089.ABSTRACTHigh-throughput omics technologies have become valuable tools for systems science research and clinical management of sepsis. This article analyzes sepsis research using omics technologies in the European Union (EU) and the United Kingdom from 1990 to May 2023 using bibliometric data from the Web of Science database. Using VOSviewer for network analysis, we examined the distribution patterns, funding characteristics, and collaborations among the states, noting trends of convergence and divergence. The analysis included 2078 articles, revealing an increasing rate of publications on sepsis research using omics approaches. The United Kingdom's research output is notably high, contributing 28.3% of the total research from the EU and United Kingdom combined. Germany, France, the Netherlands, and Italy together account for 56.9% of the publications from the EU member states. The United States is the leading international collaborator, particularly with the United Kingdom, followed by Germany and France. The EU-15 countries have significantly more publication outputs in this domain with growing but limited inclusion of the newer members of the EU. We suggest that the role of EU member states and the United Kingdom in sepsis research using omics technologies can be advanced by facilitating high-value, technology-driven health research, fostering collaboration, convergence, and equity in global health and biomedical research.PMID:38986085 | DOI:10.1089/omi.2024.0089

Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis

Wed, 10/07/2024 - 12:00
J Proteome Res. 2024 Jul 10. doi: 10.1021/acs.jproteome.4c00153. Online ahead of print.ABSTRACTDupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment. At v10 versus v2, the percentages of CD4+ interleukin-producing cells showed a decreasing trend in ISF L and NL, unbound IL-4 levels in plasma were increased, IL-5 levels in ISF L reduced, and levels of factors involved in anti-inflammatory pathways and re-epithelization increased. At v2, ISF L showed that AD lesions might have altered amino acid pathways and lipid signaling compared to ISF NL. At v10, ISF L exhibited raised levels of long- and very-long-chain fatty acids and lipids compared to v2. Furthermore, dupilumab administration caused reduced expression of miR-155-5p and miR-378a-3p in ISF L. In conclusion, results from the present study provided novel knowledge by linking local immune and metabolic alterations to AD pathogenesis and treatment response.PMID:38986055 | DOI:10.1021/acs.jproteome.4c00153

Comparative metabolomics reveals how the severity of predation by the invasive insect Cydalima perspectalis modulates the metabolism re-orchestration of native Buxus sempervirens

Wed, 10/07/2024 - 12:00
Plant Biol (Stuttg). 2024 Jul 10. doi: 10.1111/plb.13691. Online ahead of print.ABSTRACTThe recent biological invasion of box tree moth Cydalima perspectalis on Buxus trees has a major impact on European boxwood stands through severe defoliation. This can hinder further regrowth and threaten survival of populations. In a mesocosm approach and controlled larval density over a 2-month period, responses of B. sempervirens essential and specialized metabolites were characterized using metabolomics, combining 1H-NMR and LC-MS/MS approaches. This is the first metabolome depiction of major Buxus responses to boxwood moth invasion. Under severe predation, remaining green leaves accumulate free amino acids (with the noticeable exception of proline). The leaf trans-4-hydroxystachydrine and stachydrine reached 10-13% and 2-3% (DW), while root content was lower but also modulated by predation level. Larval predation promoted triterpenoid and (steroidal) alkaloid synthesis and diversification, while flavonoids did not seem to have a relevant role in Buxus resistance. Our results reveal the concomitant responses of central and specialized metabolism, in relation to severity of predation. They also confirm the potential of metabolic profiling using 1H-NMR and LC-MS to detect re-orchestration of metabolism of native boxwood after severe herbivorous predation by the invasive box-tree moth, and thus their relevance for plant-insect relationships and ecometabolomics.PMID:38985650 | DOI:10.1111/plb.13691

Unravelling the metabolic rewiring in the context of doxorubicin-induced cardiotoxicity: Fuel preference changes from fatty acids to glucose oxidation

Wed, 10/07/2024 - 12:00
Vascul Pharmacol. 2024 Jun;155:107324. doi: 10.1016/j.vph.2024.107324.ABSTRACTDoxorubicin (DOX) is a highly effective chemotherapeutic agent whose clinical use is hindered by the onset of cardiotoxic effects, resulting in reduced ejection fraction within the first year from treatment initiation. Recently it has been demonstrated that DOX accumulates within mitochondria, leading to disruption of metabolic processes and energetic imbalance. We previously described that phosphoinositide 3-kinase γ (PI3Kγ) contributes to DOX-induced cardiotoxicity, causing autophagy inhibition and accumulation of damaged mitochondria. Here we intend to describe the maladaptive metabolic rewiring occurring in DOX-treated hearts and the contribution of PI3Kγ signalling to this process. Metabolomic analysis of DOX-treated WT hearts revealed an accumulation of TCA cycle metabolites due to a cycle slowdown, with reduced levels of pyruvate, unchanged abundance of lactate and increased Acetyl-CoA production. Moreover, the activity of glycolytic enzymes was upregulated, and fatty acid oxidation downregulated, after DOX, indicative of increased glucose oxidation. In agreement, oxygen consumption was increased in after pyruvate supplementation, with the formation of cytotoxic ROS rather than energy production. These metabolic changes were fully prevented in KD hearts. Interestingly, they failed to increase glucose oxidation in response to DOX even with autophagy inhibition, indicating that PI3Kγ likely controls the fuel preference after DOX through an autophagy-independent mechanism. In vitro experiments showed that inhibition of PI3Kγ inhibits pyruvate dehydrogenase (PDH), the key enzyme of Randle cycle regulating the switch from fatty acids to glucose usage, while decreasing DOX-induced mobilization of GLUT-4-carrying vesicles to the plasma membrane and limiting the ensuing glucose uptake. These results demonstrate that PI3Kγ promotes a maladaptive metabolic rewiring in DOX-treated hearts, through a two-pronged mechanism controlling PDH activation and GLUT-4-mediated glucose uptake.PMID:38985581 | DOI:10.1016/j.vph.2024.107324

Tryptophan-Kynurenine Pathway Activation and Cognition in Virally Suppressed Women With HIV

Wed, 10/07/2024 - 12:00
J Acquir Immune Defic Syndr. 2024 Aug 15;96(5):494-500. doi: 10.1097/QAI.0000000000003454. Epub 2024 Jul 9.ABSTRACTBACKGROUND: Immune and cognitive dysfunction persists even in virally suppressed women with HIV (VS-WWH). Since inflammation and HIV proteins induce the enzyme indoleamine 2,3-dioxygenase (IDO), converting tryptophan (T) to kynurenine (K) while producing downstream neurotoxic metabolites, we investigated IDO activation (KT ratio) in relation to cognition in VS-WWH and demographically similar women without HIV (WWoH).METHODS: Ninety-nine VS-WWH on stable antiretroviral therapy and 102 WWoH (median age 52 vs 54 years; 73% vs 74% Black, respectively) from the New York and Chicago sites of the Women's Interagency HIV Study (WIHS) completed a neuropsychological test battery assessing motor function, processing speed, attention/working memory, verbal fluency, verbal learning and memory, and executive function and had plasma measured for tryptophan-kynurenine metabolites through liquid chromatography-tandem mass spectrometry and monocyte-derived [soluble cluster of differentiation-14 (sCD14), soluble cluster of differentiation-163 (sCD163), monocyte chemoattractant protein-1 (MCP-1)] plus general inflammatory markers [tumor necrosis factor alpha-2 receptor (TNF-R2), high-sensitivity C-reactive protein, high-sensitivity interleukin-6] through enzyme-linked immunosorbent assays between 2017 and 2020.RESULTS: VS-WWH had a higher KT ratio (P < 0.01) and higher sCD14 levels (P < 0.05) compared with WWoH. Higher sCD163 was associated with higher KT ratio (R = 0.29, P < 0.01) and worse fine motor function in VS-WWH; after adjusting for sCD163 and sCD14 in multivariable regressions, higher KT ratio remained significantly associated with impaired fine motor function in VS-WWH only (standardized β = -0.29, P < 0.05). IDO activation was not associated with cognition in WWoH.CONCLUSIONS: IDO activation (K:T) was associated with worse fine motor control in VS-WWH independent of measured systemic inflammation. Further studies investigating biological mechanisms linking IDO activation to fine motor function among VS-WWH are warranted.PMID:38985447 | DOI:10.1097/QAI.0000000000003454

Plant Tissue Culture and Metabolite Profiling for High-Value Natural Product Synthesis

Wed, 10/07/2024 - 12:00
Methods Mol Biol. 2024;2827:405-416. doi: 10.1007/978-1-0716-3954-2_27.ABSTRACTThe engineering of plant cell cultures to produce high-value natural products is suggested to be a safe, low-cost, and environmentally friendly route to produce a wide range of chemicals. Given that the expression of heterologous biosynthetic pathways in plant tissue culture is limited by a lack of detailed protocols, the biosynthesis of high-value metabolites in plant cell culture is constrained compared with that in microbes. However, both Arabidopsis thaliana and Nicotiana benthamiana can be efficiently transformed with multigene constructs to produce high-value natural products in stable plant cell cultures. This chapter provides a detailed protocol as to how to engineer the plant cell culture as bio-factories for metabolite biosynthesis.PMID:38985285 | DOI:10.1007/978-1-0716-3954-2_27

Large-Scale Production of Specialized Metabolites In Vitro Cultures

Wed, 10/07/2024 - 12:00
Methods Mol Biol. 2024;2827:303-322. doi: 10.1007/978-1-0716-3954-2_21.ABSTRACTFor centuries plants have been intensively utilized as reliable sources of food, flavoring, and pharmaceutical ingredients. However, plant natural habitats are being rapidly lost due to the climate change and agriculture. Plant biotechnology offers a sustainable approach for the bioproduction of specialized plant metabolites. The unique structural features of plant-derived specialized metabolites, such as their safety profile and multi-target spectrum, have led to the establishment of many plant-derived drugs. However, there are still many challenges to overcome regarding the production of these metabolites from plant in vitro systems and establish a sustainable large-scale biotechnological process. These challenges are due to the peculiarities of plant cell metabolism, the complexity of plant specialized metabolite pathways, and the correct selection of bioreactor systems and bioprocess optimization. In this book chapter, we attempted to focus on the advantages of plant in vitro systems and in particular plant cell suspensions for their cultivation as a source of plant-derived specialized metabolites. A state-of-the-art technological platform for plant cell suspension cultivation from callus induction to lab-scale cultivation, extraction, and purification is presented. Possibilities for bioreactor cultivation of plant cell suspensions in benchtop and large-scale volumes are highlighted, including several examples and patents for industrial production of specialized metabolites.PMID:38985279 | DOI:10.1007/978-1-0716-3954-2_21

An Introduction to Plant Cell, Tissue, and Organ Culture: Current Status and Perspectives

Wed, 10/07/2024 - 12:00
Methods Mol Biol. 2024;2827:1-13. doi: 10.1007/978-1-0716-3954-2_1.ABSTRACTPlant cell, tissue, and organ cultures (PCTOC) have been used as experimental systems in basic research, allowing gene function demonstration through gene overexpression or repression and investigating the processes involved in embryogenesis and organogenesis or those related to the potential production of secondary metabolites, among others. On the other hand, PCTOC has also been applied at the commercial level for the vegetative multiplication (micropropagation) of diverse plant species, mainly ornamentals but also horticultural crops such as potato or fruit and tree species, and to produce high-quality disease-free plants. Moreover, PCTOC protocols are important auxiliary systems in crop breeding crops to generate pure lines (homozygous) to produce hybrids for the obtention of polyploid plants with higher yields or better performance. PCTOC has been utilized to preserve and conserve the germplasm of different crops or threatened species. Plant genetic improvement through genetic engineering and genome editing has been only possible thanks to the establishment of efficient in vitro plant regeneration protocols. Different companies currently focus on commercializing plant secondary metabolites with interesting biological activities using in vitro PCTOC. The impact of omics on PCTOC is discussed.PMID:38985259 | DOI:10.1007/978-1-0716-3954-2_1

Lipidomic Profiling of Kidney Cortical Tubule Segments Identifies Lipotypes with Physiological Implications

Wed, 10/07/2024 - 12:00
Function (Oxf). 2024 Mar 30:zqae016. doi: 10.1093/function/zqae016. Online ahead of print.ABSTRACTA detailed knowledge of the lipid composition of components of nephrons is crucial for understanding physiological processes and the development of kidney diseases. However, the lipidomic composition of kidney tubular segments is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle's loop (cTAL) and the cortical collecting duct (CCD) from five lean and obese mice and subjected the samples to shotgun lipidomics analysis by high resolution mass spectrometry acquisition. Across all samples, more than five hundred lipid species were identified, quantified and compared. We observed significant compositional differences among the three tubular segments, which serve as true signatures. These intrinsic lipidomic features are associated with a distinct proteomic program that regulates highly specific physiological functions. The distinctive lipidomic features of each of the three segments are mostly based on the relative composition of neutral lipids, long-chain polyunsaturated fatty acids, sphingolipids, and ether phospholipids. These features support the hypothesis of a lipotype assigned to specific tubular segments. Obesity profoundly impacts the lipotype of proximal convoluted tubules. In conclusion, we present a comprehensive lipidomic analysis of three cortical segments of mouse kidney tubules. This valuable resource provides unparalleled detail that enhances our understanding of tubular physiology and the potential impact of pathological conditions.PMID:38985001 | DOI:10.1093/function/zqae016

Dysregulation of hepatic one-carbon metabolism in classical homocystinuria: Implications of redox-sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment

Wed, 10/07/2024 - 12:00
FASEB J. 2024 Jul 15;38(13):e23795. doi: 10.1096/fj.202302585R.ABSTRACTCystathionine beta-synthase-deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10-fold increase in hepatic levels of 5-methyl -THF and a 30-fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF-generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU-mediated induction of the 20-hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one-carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.PMID:38984928 | DOI:10.1096/fj.202302585R

Co-exposure to polyethylene fiber and Salmonella enterica serovar Typhimurium alters microbiome and metabolome of in vitro chicken cecal mesocosms

Wed, 10/07/2024 - 12:00
Appl Environ Microbiol. 2024 Jul 10:e0091524. doi: 10.1128/aem.00915-24. Online ahead of print.ABSTRACTHumans and animals encounter a summation of exposures during their lifetime (the exposome). In recent years, the scope of the exposome has begun to include microplastics. Microplastics (MPs) have increasingly been found in locations, including in animal gastrointestinal tracts, where there could be an interaction with Salmonella enterica serovar Typhimurium, one of the commonly isolated serovars from processed chicken. However, there is limited knowledge on how gut microbiomes are affected by microplastics and if an effect would be exacerbated by the presence of a pathogen. In this study, we aimed to determine if acute exposure to microplastics in vitro altered the gut microbiome membership and activity. The microbiota response to a 24 h co-exposure to Salmonella enterica serovar Typhimurium and/or low-density polyethylene (PE) microplastics in an in vitro broiler cecal model was determined using 16S rRNA amplicon sequencing (Illumina) and untargeted metabolomics. Community sequencing results indicated that PE fiber with and without S. Typhimurium yielded a lower Firmicutes/Bacteroides ratio compared with other treatment groups, which is associated with poor gut health, and overall had greater changes to the cecal microbial community composition. However, changes in the total metabolome were primarily driven by the presence of S. Typhimurium. Additionally, the co-exposure to PE fiber and S. Typhimurium caused greater cecal microbial community and metabolome changes than either exposure alone. Our results indicate that polymer shape is an important factor in effects resulting from exposure. It also demonstrates that microplastic-pathogen interactions cause metabolic alterations to the chicken cecal microbiome in an in vitro chicken cecal mesocosm.IMPORTANCE: Researching the exposome, a summation of exposure to one's lifespan, will aid in determining the environmental factors that contribute to disease states. There is an emerging concern that microplastic-pathogen interactions in the gastrointestinal tract of broiler chickens may lead to an increase in Salmonella infection across flocks and eventually increased incidence of human salmonellosis cases. In this research article, we elucidated the effects of acute co-exposure to polyethylene microplastics and Salmonella enterica serovar Typhimurium on the ceca microbial community in vitro. Salmonella presence caused strong shifts in the cecal metabolome but not the microbiome. The inverse was true for polyethylene fiber. Polyethylene powder had almost no effect. The co-exposure had worse effects than either alone. This demonstrates that exposure effects to the gut microbial community are contaminant-specific. When combined, the interactions between exposures exacerbate changes to the gut environment, necessitating future experiments studying low-dose chronic exposure effects with in vivo model systems.PMID:38984844 | DOI:10.1128/aem.00915-24

High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage

Wed, 10/07/2024 - 12:00
Environ Sci Technol. 2024 Jul 10. doi: 10.1021/acs.est.4c01156. Online ahead of print.ABSTRACTIn the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.PMID:38984754 | DOI:10.1021/acs.est.4c01156

Serum metabolomics reveals the metabolic profile and potential biomarkers of ankylosing spondylitis

Wed, 10/07/2024 - 12:00
Mol Omics. 2024 Jul 10. doi: 10.1039/d4mo00076e. Online ahead of print.ABSTRACTAnkylosing spondylitis (AS) is a chronic systemic inflammatory disease that significantly impairs physical function in young individuals. However, the identification of radiographic changes in AS is frequently delayed, and the diagnostic efficacy of biomarkers like HLA-B27 remains moderately effective, with unsatisfactory sensitivity and specificity. In contrast to existing literature, our current experiment utilized a larger sample size and employed both untargeted and targeted UHPLC-QTOF-MS/MS based metabolomics to identify the metabolite profile and potential biomarkers of AS. The results indicated a notable divergence between the two groups, and a total of 170 different metabolites were identified, which were associated with the 6 primary metabolic pathways exhibiting a correlation with AS. Among these, 26 metabolites exhibited high sensitivity and specificity with area under curve (AUC) values greater than 0.8. Subsequent targeted quantitative analysis discovered 3 metabolites, namely 3-amino-2-piperidone, hypoxanthine and octadecylamine, exhibiting excellent distinguishing ability based on the results of the ROC curve and the Random Forest model, thus qualifying as potential biomarkers for AS. Summarily, our untargeted and targeted metabolomics investigation offers novel and precise insights into potential biomarkers for AS, potentially enhancing diagnostic capabilities and furthering the comprehension of the condition's pathophysiology.PMID:38984672 | DOI:10.1039/d4mo00076e

Lipophilic and Hydrophilic Metabolites as Descriptors of Different Coffee Beverages

Wed, 10/07/2024 - 12:00
J Agric Food Chem. 2024 Jul 10. doi: 10.1021/acs.jafc.4c03347. Online ahead of print.ABSTRACTCoffee is a widely consumed beverage rich in bioactive phytochemicals. This study investigated the effect of brewing method on the profile of potential bioactive compounds in different coffee beverages using metabolomics and lipidomics based on UHPLC-MS/QTOF. The oil contents of the espresso coffee (EC), pot coffee (PC), instant coffee (IC), and filter coffee (FC) beverages studied were 0.13% ± 0.002, 0.12% ± 0.001, 0.04% ± 0.002, and 0.03% ± 0.003, respectively. Univariate analysis indicated significant differences (P < 0.001) in oil content when EC and PC beverages were compared with IC and FC beverages. Principal component analysis revealed similarities in the lipid profiles of FC and EC beverages and the hydrophilic profiles of PC and FC beverages. The EC beverage had the highest intensity of hydrophilic compounds such as adenine, theobromine, chlorogenic acid, and caffeine. The PC beverage was the most abundant in triglycerides, phosphatidylcholine, and diterpenes. Cafestol and kahweol esters, but not their free forms, were the most abundant diterpenes in the PC beverage. This work provides information on the differences in the profile of potentially bioactive compounds in four commonly consumed coffee beverage types and, thus, on the possible differences in the health effects of these coffee beverage types.PMID:38984670 | DOI:10.1021/acs.jafc.4c03347

Prostaglandin A3 regulates the colony development of <em>Odontotermes formosanus</em> by reducing worker proportion

Wed, 10/07/2024 - 12:00
Crop Health. 2024;2(1):11. doi: 10.1007/s44297-024-00030-3. Epub 2024 Jul 2.ABSTRACTSubterranean termites cause significant economic losses worldwide due to their destruction of agricultural and forest plants. In the past, soil termiticides were commonly used to control subterranean termites because they were effective and affordable. However, due to growing environmental concerns, these harmful substances have become less popular as they cause damage to non-target organisms and lead to environmental contamination. Baits crafted from plants and other easily metabolized compounds serve as excellent alternatives. In this study, we gathered branches from the promising plant, Magnolia grandiflora L. (MGL), along with branches from five other tree species that are potential food for termites. These branches were used as food to observe the population growth of Odontotermes formosanus. Additionally, a mix of branches from all six species was used to feed the control group (MIX). The study results showed that MGL nutrition significantly inhibited worker development, resulting in a significantly lower worker-to-soldier ratio (WSR). Furthermore, LC‒MS/MS analysis revealed that the level of prostaglandin A3 (PGA3) in workers significantly increased when they were under MGL nutrition. Additionally, ICP-MS analysis indicated a significant increase in calcium concentrations in the branches of MGL and combs under MGL nutrition. Moreover, there was a significant increase in peroxidase (POD) activity in workers under MGL nutrition. These findings suggest that the inhibitory effect of MGL nutrition on worker development may be due to excessive PGA3 synthesis, as Ca2+ and POD are involved in the synthesis process of PGs in insects. Subsequent verification experiments strongly support this hypothesis, as the WSR of colonies fed PGA3-added MIX was significantly lower than that of the MIX alone. This study introduces a new concept for developing environmentally friendly biological control methods for O. formosanus and sheds light on the potential role of PGs in termite development.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44297-024-00030-3.PMID:38984319 | PMC:PMC11232360 | DOI:10.1007/s44297-024-00030-3

Soil pH, developmental stages and geographical origin differently influence the root metabolomic diversity and root-related microbial diversity of Echium vulgare from native habitats

Wed, 10/07/2024 - 12:00
Front Plant Sci. 2024 Jun 24;15:1369754. doi: 10.3389/fpls.2024.1369754. eCollection 2024.ABSTRACTImproved understanding of the complex interaction between plant metabolism, environmental conditions and the plant-associated microbiome requires an interdisciplinary approach: Our hypothesis in our multiomics study posited that several environmental and biotic factors have modulating effects on the microbiome and metabolome of the roots of wild Echium vulgare plants. Furthermore, we postulated reciprocal interactions between the root metabolome and microbiome. We investigated the metabolic content, the genetic variability, and the prokaryotic microbiome in the root systems of wild E. vulgare plants at rosette and flowering stages across six distinct locations. We incorporated the assessment of soil microbiomes and the measurement of selected soil chemical composition factors. Two distinct genetic clusters were determined based on microsatellite analysis without a consistent alignment with the geographical proximity between the locations. The microbial diversity of both the roots of E. vulgare and the surrounding bulk soil exhibited significant divergence across locations, varying soil pH characteristics, and within the identified plant genetic clusters. Notably, acidophilic bacteria were characteristic inhabitants of both soil and roots under acidic soil conditions, emphasizing the close interconnectedness between these compartments. The metabolome of E. vulgare significantly differed between root samples from different developmental stages, geographical locations, and soil pH levels. The developmental stage was the dominant driver of metabolome changes, with significantly higher concentrations of sugars, pyrrolizidine alkaloids, and some of their precursors in rosette stage plant roots. Our study featured the complex dynamics between soil pH, plant development, geographical locations, plant genetics, plant metabolome and microbiome, shedding light on existing knowledge gaps.PMID:38984162 | PMC:PMC11232435 | DOI:10.3389/fpls.2024.1369754

Volatile metabolomics and transcriptomics analyses provide insights into the mechanism of volatile changes during fruit development of 'Ehime 38' (Citrus reticulata) and its bud mutant

Wed, 10/07/2024 - 12:00
Front Plant Sci. 2024 Jun 26;15:1430204. doi: 10.3389/fpls.2024.1430204. eCollection 2024.ABSTRACTVolatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of 'Ehime 38' (Citrus reticulata) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4-2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus.PMID:38984161 | PMC:PMC11231921 | DOI:10.3389/fpls.2024.1430204

The growth-promoting and disease-suppressing mechanisms of <em>Trichoderma</em> inoculation on peanut seedlings

Wed, 10/07/2024 - 12:00
Front Plant Sci. 2024 Jun 25;15:1414193. doi: 10.3389/fpls.2024.1414193. eCollection 2024.ABSTRACTTrichoderma spp. is known for its ability to enhance plant growth and suppress disease, but the mechanisms for its interaction with host plants and pathogens remain unclear. This study investigated the transcriptomics and metabolomics of peanut plants (Arachis hypogaea L.) inoculated with Trichoderma harzianum QT20045, in the absence and presence of the stem rot pathogen Sclerotium rolfsii JN3011. Under the condition without pathogen stress, the peanut seedlings inoculated with QT20045 showed improved root length and plant weight, increased indole acetic acid (IAA) production, and reduced ethylene level, with more active 1-aminocyclopropane-1-carboxylate acid (ACC) synthase (ACS) and ACC oxidase (ACO), compared with the non-inoculated control. Under the pathogen stress, the biocontrol efficacy of QT20045 against S. rolfsii was 78.51%, with a similar effect on plant growth, and IAA and ethylene metabolisms to the condition with no biotic stress. Transcriptomic analysis of peanut root revealed that Trichoderma inoculation upregulated the expression of certain genes in the IAA family but downregulated the genes in the ACO family (AhACO1 and AhACO) and ACS family (AhACS3 and AhACS1) consistently in the absence and presence of pathogens. During pathogen stress, QT20045 inoculation leads to the downregulation of the genes in the pectinesterase family to keep the host plant's cell wall stable, along with upregulation of the AhSUMM2 gene to activate plant defense responses. In vitro antagonistic test confirmed that QT20045 suppressed S. rolfsii growth through mechanisms of mycelial entanglement, papillary protrusions, and decomposition. Our findings highlight that Trichoderma inoculation is a promising tool for sustainable agriculture, offering multiple benefits from pathogen control to enhanced plant growth and soil health.PMID:38984154 | PMC:PMC11231372 | DOI:10.3389/fpls.2024.1414193

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