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

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae

Tue, 02/04/2024 - 12:00
Sci Total Environ. 2024 Mar 31:172125. doi: 10.1016/j.scitotenv.2024.172125. Online ahead of print.ABSTRACTDespite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.PMID:38565353 | DOI:10.1016/j.scitotenv.2024.172125

Phytochemical diversity and their adaptations to abiotic and biotic pressures in fine roots across a climatic gradient

Tue, 02/04/2024 - 12:00
Sci Total Environ. 2024 Mar 31:172051. doi: 10.1016/j.scitotenv.2024.172051. Online ahead of print.ABSTRACTPhytochemicals and their ecological significance are long ignored in trait-based ecology. Moreover, the adaptations of phytochemicals produced by fine roots to abiotic and biotic pressures are less understood. Here, we explored the fine roots metabolomes of 315 tree species and their rhizosphere microbiome in southwestern China spanning tropical, subtropical, and subalpine forest ecosystems, to explore phytochemical diversity and endemism patterns of various metabolic pathways and phytochemical-microorganism interactions. We found that subalpine species showed higher phytochemical diversity but lower interspecific variation than tropical species, which favors coping with high abiotic pressures. Tropical species harbored higher interspecific phytochemical variation and phytochemical endemism, which favors greater species coexistence and adaptation to complex biotic pressures. Moreover, there was evidence of widespread chemical niche partitioning of closely related species in all regions, and phytochemicals showed a weak phylogenetic signal, but were regulated by abiotic and biotic pressures. Our findings support the Latitudinal Biotic Interaction Hypothesis, i.e., the intensity of phytochemical-microorganism interactions decreases from tropical to subalpine regions, which promotes greater microbial community turnover and phytochemical niche partitioning of host plants in the tropics than in higher latitude forests. Our study reveals the convergent phytochemical diversity patterns of various pathways and their interactions with microorganism, thus promoting species coexistence.PMID:38565347 | DOI:10.1016/j.scitotenv.2024.172051

Metabolomics analysis revealed the neuroprotective role of 2-phosphoglyceric acid in hypoxic-ischemic brain damage through GPX4/ACSL4 axis regulation

Tue, 02/04/2024 - 12:00
Eur J Pharmacol. 2024 Mar 31:176539. doi: 10.1016/j.ejphar.2024.176539. Online ahead of print.ABSTRACTHypoxic-ischemic brain damage (HIBD) is a cerebral injury resulting from the combination of ischemia and hypoxia in neonatal brain tissue. Presently, there exists no efficacious remedy for HIBD. A mounting body of evidence indicates that dynamic metabolites formed during metabolic procedures assume a vital role in neuronal maturation and recuperation. However, it remains unclear whether any endogenous metabolites are involved in the pathogenesis of HIBD. Here, an untargeted metabolomics analysis was conducted by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry (GC/LC-MS) in OGD/R (oxygen-glucose deprivation/reoxygenation)-induced HT-22 cells. We observed that ferroptosis signaling plays an essential role in HI-induced neuronal injury. Interestingly, we also found that the differentially expressed metabolite, 2-phosphoglyceric acid, significantly improved the neuronal cell survival of OGD/R HT-22 cells by inhibiting ferroptosis. Moreover, 2-phosphoglyceric acid effectively rescued the cell activity of HT-22 cells treated with the ferroptosis inducer RSL-3. Furthermore, 2-phosphoglyceric acid alleviated cerebral infarction and reduced HIBD-induced neuronal cell loss of the central nervous system in neonatal rats by regulating GPX4 expression. Taken together, we found that 2-phosphoglyceric acid, which was downregulated in HT-22 cells induced by OGD/R, exerted neuronal protective effects on OGD/R-treated HT-22 cells and HIBD-induced neonatal rats by inhibiting hypoxic-ischemic-induced ferroptosis through the regulation of the GPX4/ACSL4 axis.PMID:38565342 | DOI:10.1016/j.ejphar.2024.176539

Novel protocol for multiple-dose oral administration of the L-type Ca<sup>2+</sup> channel blocker isradipine in mice: A dose-finding pharmacokinetic study

Tue, 02/04/2024 - 12:00
Channels (Austin). 2024 Dec;18(1):2335469. doi: 10.1080/19336950.2024.2335469. Epub 2024 Apr 2.ABSTRACTStudies in genetically modified animals and human genetics have recently provided new insight into the role of voltage-gated L-type Ca2+ channels in human disease. Therefore, the inhibition of L-type Ca2+ channels in vivo in wildtype and mutant mice by potent dihydropyridine (DHP) Ca2+ channel blockers serves as an important pharmacological tool. These drugs have a short plasma half-life in humans and especially in rodents and show high first-pass metabolism upon oral application. In the vast majority of in vivo studies, they have therefore been delivered through parenteral routes, mostly subcutaneously or intraperitoneally. High peak plasma concentrations of DHPs cause side effects, evident as DHP-induced aversive behaviors confounding the interpretation of behavioral readouts. Nevertheless, pharmacokinetic data measuring the exposure achieved with these applications are sparse. Moreover, parenteral injections require animal handling and can be associated with pain, discomfort and stress which could influence a variety of physiological processes, behavioral and other functional readouts. Here, we describe a noninvasive oral application of the DHP isradipine by training mice to quickly consume small volumes of flavored yogurt that can serve as drug vehicle. This procedure does not require animal handling, allows repeated drug application over several days and reproducibly achieves peak plasma concentrations over a wide range previously shown to be well-tolerated in humans. This protocol should facilitate ongoing nonclinical studies in mice exploring new indications for DHP Ca2+ channel blockers.PMID:38564754 | DOI:10.1080/19336950.2024.2335469

Correction: The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth

Tue, 02/04/2024 - 12:00
PLoS One. 2024 Apr 2;19(4):e0301870. doi: 10.1371/journal.pone.0301870. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0145919.].PMID:38564617 | DOI:10.1371/journal.pone.0301870

Tailored Mass Spectral Data Exploration Using the SpecXplore Interactive Dashboard

Tue, 02/04/2024 - 12:00
Anal Chem. 2024 Apr 2. doi: 10.1021/acs.analchem.3c04444. Online ahead of print.ABSTRACTUntargeted metabolomics promises comprehensive characterization of small molecules in biological samples. However, the field is hampered by low annotation rates and abstract spectral data. Despite recent advances in computational metabolomics, manual annotations and manual confirmation of in-silico annotations remain important in the field. Here, exploratory data analysis methods for mass spectral data provide overviews, prioritization, and structural hypothesis starting points to researchers facing large quantities of spectral data. In this research, we propose a fluid means of dealing with mass spectral data using specXplore, an interactive Python dashboard providing interactive and complementary visualizations facilitating mass spectral similarity matrix exploration. Specifically, specXplore provides a two-dimensional t-distributed stochastic neighbor embedding embedding as a jumping board for local connectivity exploration using complementary interactive visualizations in the form of partial network drawings, similarity heatmaps, and fragmentation overview maps. SpecXplore makes use of state-of-the-art ms2deepscore pairwise spectral similarities as a quantitative backbone while allowing fast changes of threshold and connectivity limitation settings, providing flexibility in adjusting settings to suit the localized node environment being explored. We believe that specXplore can become an integral part of mass spectral data exploration efforts and assist users in the generation of structural hypotheses for compounds of interest.PMID:38564584 | DOI:10.1021/acs.analchem.3c04444

Differences of Typical Wuyi Rock Tea in Taste and Nonvolatiles Profile Revealed by Multisensory Analysis and LC-MS-Based Metabolomics

Tue, 02/04/2024 - 12:00
J Agric Food Chem. 2024 Apr 2. doi: 10.1021/acs.jafc.3c08694. Online ahead of print.ABSTRACTWuyi Rock tea, specifically Shuixian and Rougui, exhibits distinct sensory characteristics. In this study, we investigated the sensory and metabolite differences between Shuixian and Rougui. Quantitative description analysis revealed that Rougui exhibited higher intensity in bitter, thick, harsh, and numb tastes, while Shuixian had stronger salty and umami tastes. Nontargeted metabolomics identified 151 compounds with 66 compounds identified as key differential metabolites responsible for metabolic discrimination. Most of the catechins and flavonoids were enriched in Rougui tea, while epigallocatechin-3,3'-di-O-gallate, epigallocatechin-3,5-di-O-gallate, gallocatechin-3,5-di-O-gallate, isovitexin, and theaflavanoside I were enriched in Shuixian tea. Catechins, kaempferol, quercetin, and myricetin derivatives were positively correlated with bitter taste and numb sensation. Sour taste was positively correlated to organic acids. Amino acids potentially contributed to salty and umami tastes. These results provide further insights into the taste characteristics and the relationship between taste attributes and specific metabolites in Wuyi Rock tea.PMID:38564531 | DOI:10.1021/acs.jafc.3c08694

Metabolomic and genomic insights into TMA degradation by a novel halotolerant strain - Paracoccus sp. PS1

Tue, 02/04/2024 - 12:00
Arch Microbiol. 2024 Apr 2;206(4):201. doi: 10.1007/s00203-024-03931-7.ABSTRACTTrimethylamine N-oxide (TMAO) is a gut metabolite that acts as a biomarker for chronic diseases, and is generated by the oxidation of trimethylamine (TMA) produced by gut microflora. Since, microbial degradation of TMA is predicted to be used to restrict the production of TMAO, we aimed to isolate bacterial strains that could effectively degrade TMA before being oxidized to TMAO. As marine fish is considered to have a rich content of TMAO, we have isolated TMA degrading isolates from fish skin. Out of the fourteen isolates, depending on their rapid TMA utilization capability in mineral salt medium supplemented with TMA as a sole carbon and nitrogen source, isolate PS1 was selected as our desired isolate. Its TMA degrading capacity was further confirmed through spectrophotometric, Electrospray Ionization Time-of-Flight Mass Spectrometry (ESI TOF-MS) and High performance liquid chromatography (HPLC) analysis and in silico analysis of whole genome (WG) gave further insights of protein into its TMA degradation pathways. PS1 was taxonomically identified as Paracoccus sp. based on its 16S rRNA and whole genome sequence analysis. As PS1 possesses the enzymes required for degradation of TMA, clinical use of this isolate has the potential to reduce TMAO generation in the human gut.PMID:38564030 | DOI:10.1007/s00203-024-03931-7

Benzoxazinoids secreted by wheat root weaken the pathogenicity of Fusarium oxysporum f. sp. fabae by inhibiting linoleic acid and nucleotide metabolisms

Tue, 02/04/2024 - 12:00
Plant Cell Rep. 2024 Apr 2;43(4):109. doi: 10.1007/s00299-024-03188-w.ABSTRACTThe regulatory action of BXs secreted by wheat on the pathogenicity of FOF causing Fusarium wilt in faba bean were analyzed. DIMBOA and MBOA weakened the pathogenicity of FOF. A large number of pathogenic bacteria in continuous cropping soil infect faba bean plants, leading to the occurrence of wilt disease, which restricts their production. Faba bean-wheat intercropping is often used to alleviate this disease. This study investigates the effect of benzoxazinoids (BXs) secreted by wheat root on the pathogenicity of Fusarium oxysporum f. sp. Fabae (FOF) and underlying molecular mechanisms. The effects of DIMBOA(2,4-dihydroxy-7-methoxy-1,4-benzoxazine-4-one) and MBOA(6-methoxybenzoxazolin-2-one) on the activity of cell-wall-degrading enzymes in FOF(cellulase, pectinase, amylase, and protease), FOF Toxin (fusaric acid, FA) content were investigated through indoor culture experiments. The effect of BXs on the metabolic level of FOF was analyzed by metabonomics to explore the ecological function of benzoxazines intercropping control of Fusarium wilt in faba bean. The results show that the Exogenous addition of DIMBOA and MBOA decreased the activity of plant-cell-wall-degrading enzymes and fusaric acid content and significantly weakened the pathogenicity of FOF. DIMBOA and MBOA significantly inhibited the pathogenicity of FOF, and metabolome analysis showed that DIMBOA and MBOA reduced the pathogenicity of FOF by down-regulating related pathways such as nucleotide metabolism and linoleic acid metabolism, thus effectively controlling the occurrence of Fusarium wilt in faba bean.PMID:38564014 | DOI:10.1007/s00299-024-03188-w

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation

Tue, 02/04/2024 - 12:00
Appl Environ Microbiol. 2024 Apr 2:e0004624. doi: 10.1128/aem.00046-24. Online ahead of print.ABSTRACTDietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome.IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.PMID:38563787 | DOI:10.1128/aem.00046-24

Promising probiotic-fermented soymilk for alleviating acute diarrhea: insights into the microbiome and metabolomics

Tue, 02/04/2024 - 12:00
Food Funct. 2024 Apr 2. doi: 10.1039/d3fo05690b. Online ahead of print.ABSTRACTFermented soymilk (FSM4) has attracted much attention due to its nutritional and health characteristics. Exploring FSM4 products to alleviate diarrhea can ensure their effectiveness as a therapeutic food for alleviating gastrointestinal disorders. However, the relationship between gut microbiota and gut metabolite production remains unknown during diarrheal episodes. Therefore, the diarrhea-alleviating role and mechanisms of FSM4 in diarrhea rats were investigated via biochemical, gut microbiota, and serum metabolite analyses. The findings showed that consuming FSM4 improved diarrhea symptoms and reduced systemic inflammation better than non-fermented soymilk (NFSM). It is worth noting that FSM4 promoted the diversity, richness, structure, and composition of gut microbiota. It increased the ability to reduce inflammation associated with harmful bacteria (Anaerofilum, Flavonifractor, Bilophila, Anaerostipes, [Ruminococcus]_torques_group, Clostridium_sensu_stricto_1, Turicibacter, Ruminococcus_1, Ruminiclostridium_6, Prevotellaceae_NK3B31_group and Fusicatenibacter), while stimulating the growth of healthy species (Lactobacillus, Ruminococcaceae_UCG-014, Oscillibacter, [Eubacterium]_coprostanoligenes_group, Negativibacillus, and Erysipelotrichaceae_UCG-003). Moreover, metabolomics analysis showed that lipid metabolites such as lysophosphatidylethanolamine (LysoPE) and sphingolipids were upregulated in the NG group, closely related to pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and IFN-γ) and the aforementioned pathogenic bacteria. Notably, in treatment groups, especially FSM4, the accumulation of L-ornithine, aspartic acid, ursocholic acid, 18-oxooleate, and cyclopentanethiol was increased, which was robustly associated with the anti-inflammatory factor IL-10 and beneficial bacteria mentioned above. Therefore, it can be inferred that the amino acids, bile acid, 18-oxooleate, and cyclopentanethiol produced in the FSM4 group can serve as metabolic biomarkers, which synergistically act with the gut microbiota to help alleviate inflammation for diarrhea remission. Overall, FSM4 may provide a new alternative, as an anti-inflammatory diet, to alleviate diarrhea.PMID:38563684 | DOI:10.1039/d3fo05690b

Essential oil supplementation in milk replacers: short- and long-term impacts on feed efficiency, the faecal microbiota and the plasma metabolome in dairy calves

Tue, 02/04/2024 - 12:00
J Dev Orig Health Dis. 2024 Apr 2:1-11. doi: 10.1017/S2040174424000084. Online ahead of print.ABSTRACTEarly supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups (n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum. The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4+, CD8+, CD14+, CD21+ and WC1+), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period (P = 0.030). The EO group showed higher average CD14+ population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014, Faecalibacterium, Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia. The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.PMID:38563206 | DOI:10.1017/S2040174424000084

Identification and quantification of pigments in plant leaves using thin layer chromatography-Raman spectroscopy (TLC-Raman)

Tue, 02/04/2024 - 12:00
Anal Methods. 2024 Apr 2. doi: 10.1039/d4ay00082j. Online ahead of print.ABSTRACTCarotenoids are yellow, orange, and red pigments commonly found in plants. In leaves, these molecules are essential for photosynthesis, but they also play a major role in plant growth and development. Efficiently monitoring concentrations of specific carotenoids in plant tissues could help to explain plant responses to environmental stressors, infection and disease, fertilization, and other conditions. Previously, Raman methods have been used to demonstrate a correlation between plant fitness and the carotenoid content of leaves. Due to solvatochromatic effects and structural similarities within the carotenoid family, current Raman spectroscopy techniques struggle to assign signals to specific carotenoids with certainty, complicating the determination of amounts of individual carotenoids present in a sample. In this work, we use thin layer chromatography-Raman spectroscopy, or TLC-Raman, to identify and quantify carotenoids extracted from tomato leaves. These quick and accurate methods could be applied to study the relationship between pigment content and a number of factors affecting plant health.PMID:38563199 | DOI:10.1039/d4ay00082j

Metabolic regulation of longevity and immune response in <em>Caenorhabditis elegans</em> by ingestion of <em>Lacticaseibacillus rhamnosus</em> IDCC 3201 using multi-omics analysis

Tue, 02/04/2024 - 12:00
J Microbiol Biotechnol. 2024 Apr 3;34(5):1-10. doi: 10.4014/jmb.2402.02025. Online ahead of print.ABSTRACTProbiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotics properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.PMID:38563104 | DOI:10.4014/jmb.2402.02025

<em>Mycobacterium</em> dormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis

Tue, 02/04/2024 - 12:00
bioRxiv [Preprint]. 2024 Mar 19:2024.03.18.585612. doi: 10.1101/2024.03.18.585612.ABSTRACTTuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage, Mycobacterium tuberculosis resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can lead to a multisystemic diseases because M. tuberculosis invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing poor visual outcomes of OTB patients. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in the protection from the antibiotic effects, making them an anatomical niche for invading M. tuberculosis . RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed M. tuberculosis bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed M. tuberculosis are largely unknown. Here, liquid chromatography mass spectrometry (LC-MS) metabolomics was used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant M. tuberculosis bacilli and enhance the antibiotic tolerance. The results have led to propose a novel therapeutic option to synthetically kill the dormant M. tuberculosis inside the RPE cells by modulating the phenotypic state of M. tuberculosis , thus laying the foundation for a new, innovative regimen for treating OTB.IMPORTANCE: Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with M. tuberculosis and mycobacterial dormancy is crucial to identify new therapeutic methods to cure OTB. The present study showed that RPE cellular metabolism is altered to foster intracellular M. tuberculosis to enter into the dormant and drug tolerant state, thereby blunting the efficacy of anti-TB chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with H2O2 and M. tuberculosis infection showed that intracellular environment within RPE cells is enriched with greater level of oxidative stress. The antibiotic tolerance of intracellular M. tuberculosis within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.PMID:38562751 | PMC:PMC10983995 | DOI:10.1101/2024.03.18.585612

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species

Tue, 02/04/2024 - 12:00
Front Nutr. 2024 Mar 18;11:1335538. doi: 10.3389/fnut.2024.1335538. eCollection 2024.ABSTRACTThe Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.PMID:38562486 | PMC:PMC10982346 | DOI:10.3389/fnut.2024.1335538

Integration of widely targeted metabolomics and the e-tongue reveals the chemical variation and taste quality of Yunnan Arabica coffee prepared using different primary processing methods

Tue, 02/04/2024 - 12:00
Food Chem X. 2024 Mar 15;22:101286. doi: 10.1016/j.fochx.2024.101286. eCollection 2024 Jun 30.ABSTRACTUPLC-Q-TOF-MS and electronic tongue analysis were applied to analyse the metabolic profile and taste quality of Yunnan Arabica coffee under seven primary processing methods. The total phenolic content ranged from 34.44 to 44.42 mg/g DW, the e-tongue results revealed the strongest umami sensor response value in the sample prepared with traditional dry processing, while the samples prepared via honey processing II had the strongest astringency sensor response value. Metabolomics analysis identified 221 differential metabolites, with higher contents of amino acids and derivatives within dry processing II sample, and increased contents of lipids and phenolic acids in the honey processing III sample. The astringency and aftertaste-astringency of the coffee samples positively correlated with the trigonelline, 3,5-di-caffeoylquinic acid and 4-caffeoylquinic acid content. The results contributed to a better understanding of how the primary processing process affects coffee quality, and supply useful information for the enrichment of coffee biochemistry theory.PMID:38562182 | PMC:PMC10982556 | DOI:10.1016/j.fochx.2024.101286

Editorial: Metabolic modulation of cellular function

Tue, 02/04/2024 - 12:00
Front Cell Dev Biol. 2024 Mar 18;12:1395922. doi: 10.3389/fcell.2024.1395922. eCollection 2024.NO ABSTRACTPMID:38562142 | PMC:PMC10982473 | DOI:10.3389/fcell.2024.1395922

Discovery of a Novel Bioactive Compound in Orange Peel Polar Fraction on the Inhibition of Trimethylamine and Trimethylamine N-Oxide through Metabolomics Approaches and In Vitro and In Vivo Assays: Feruloylputrescine Inhibits Trimethylamine via...

Tue, 02/04/2024 - 12:00
J Agric Food Chem. 2024 Apr 1. doi: 10.1021/acs.jafc.3c09005. Online ahead of print.ABSTRACTThis study compares the inhibitory effects of orange peel polar fraction (OPP) and orange peel nonpolar fraction (OPNP) on trimethylamine (TMA) and trimethylamine N-oxide (TMAO) production in response to l-carnitine treatment in vivo and in vitro. Metabolomics is used to identify bioactive compounds. The research demonstrates that the OPP effectively regulates atherosclerosis-related markers, TMA and TMAO in plasma and urine, compared to the OPNP. Our investigation reveals that these inhibitory effects are independent of changes in gut microbiota composition. The effects are attributed to the modulation of cntA/B enzyme activity and FMO3 mRNA expression in vitro. Moreover, OPP exhibits stronger inhibitory effects on TMA production than OPNP, potentially due to its higher content of feruloylputrescine, which displays the highest inhibitory activity on the cntA/B enzyme and TMA production. These findings suggest that the OPP containing feruloylputrescine has the potential to alleviate cardiovascular diseases by modulating cntA/B and FMO3 enzymes without directly influencing gut microbiota composition.PMID:38562057 | DOI:10.1021/acs.jafc.3c09005

Key transcription factors regulate fruit ripening and metabolite accumulation in tomato

Tue, 02/04/2024 - 12:00
Plant Physiol. 2024 Apr 2:kiae195. doi: 10.1093/plphys/kiae195. Online ahead of print.ABSTRACTFruit ripening is a complex process involving dynamic changes to metabolites and is controlled by multiple factors, including transcription factors (TFs). Several TFs are reportedly essential regulators of tomato (Solanum lycopersicum) fruit ripening. To evaluate the effects of specific TFs on metabolite accumulation during fruit ripening, we combined CRISPR/Cas9-mediated mutagenesis with metabolome and transcriptome analyses to explore regulatory mechanisms. Specifically, we generated various genetically engineered tomato lines that differed regarding metabolite contents and fruit colors. The metabolite and transcript profiles indicated that the selected TFs have distinct functions that control fruit metabolite contents, especially carotenoids and sugars. Moreover, a mutation to ELONGATED HYPOCOTYL5 (HY5) increased tomato fruit fructose and glucose contents by approximately 20% (relative to the wild-type levels). Our in vitro assay showed that HY5 can bind directly to the G-box cis-element in the Sugars Will Eventually be Exported Transporter (SWEET12c) promoter to activate expression, thereby modulating sugar transport. Our findings provide insights into the mechanisms regulating tomato fruit ripening and metabolic networks, providing the theoretical basis for breeding horticultural crops that produce fruit with diverse flavors and colors.PMID:38561990 | DOI:10.1093/plphys/kiae195

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