PubMed

PLoS One. 2023 Aug 23;18(8):e0289272. doi: 10.1371/journal.pone.0289272. eCollection 2023.ABSTRACTQuercus mongolica is a common landscape, afforestation, and construction timber species in northern China with high ecological, economic, and ornamental value. Leaf senescence is a complex process that has important implications for plant growth and development. To explore changes of metabolites during the ageing of Quercus mongolica leaves, we investigated physiological responses and metabolite composition in ageing leaves harvested from 15-20-year-old Quercus mongolica. Leaf samples of Q. mongolica were collected when they were still green (at maturity) (stage 1), during early senescence (stage 2), and during late senescence (stage 3). These leaves were then subjected to physiological index and metabolome sequencing analyses. The physiological analysis showed that the leaves of Q. mongolica changed from green to yellow during senescence, which induced significant accumulation of soluble sugar and significant reductions in the concentration of soluble protein and chlorophyll. Peroxidase and catalase were the main antioxidant enzymes mitigating leaf senescence. Metabolomic analysis identified 797 metabolites during leaf senescence. Compared to stage 1, 70 differential metabolites were screened in stage 2 and 72 were screened in stage 3. Differential metabolites in the two senescent stages were principally enriched in amino acid metabolism, lipid metabolism and secondary metabolite biosynthesis. The contents of N-oleoylethanolamine and N, N-dimethylglycine were significantly increased only in stage 2, while the contents of trifolin, astragalin, valine, isoleucine, leucine, and citric acid were significantly increased only in stage 3. Histidine, homoserine, tryptophan, tyrosine, phenylalanine, proline, norleucine, N-glycyl-L-leucine, linoleic acid, linolenic acid, gallic acid, 3-indoleacrylic acid, 3-amino-2-naphthoic acid, 3-hydroxy-3-methylpentane-1,5-dioic acid, 2,3,4-trihydroxybenzoic acid, trifolin, astragalin, DL-2-aminoadipic acid, pinoresinol dimethyl ether, dimethylmatairesinol, and lysophosphatidylcholine increased during both stage 2 and stage 3. Increasing contents of these metabolites may constitute the main mechanism by which Q. mongolica leaves adapt to senescence.PMID:37611226 | DOI:10.1371/journal.pone.0289272

Hum Cell. 2023 Aug 23. doi: 10.1007/s13577-023-00967-7. Online ahead of print.ABSTRACTThe identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13+CD166- cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13+CD166- cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13+CD166- cells with other cell sub-populations and identified nine overexpressed genes (ENPP2, SCGN, FGFR4, MCOLN3, KCNJ16, SMIM22, SMIM24, SERPINH1, and TMPRSS2) in CD13+CD166- cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis-mass spectrometry showed that two metabolic pathways, "Alanine, aspartate and glutamate metabolism" and "Arginine biosynthesis" were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma.PMID:37610679 | DOI:10.1007/s13577-023-00967-7

Curr Nutr Rep. 2023 Aug 23. doi: 10.1007/s13668-023-00491-y. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Existing dietary and lifestyle interventions and recommendations, to improve the risk factors of obesity and type 2 diabetes with the target to mitigate this double global epidemic, have produced inconsistent results due to interpersonal variabilities in response to these conventional approaches, and inaccuracies in dietary assessment methods. Precision nutrition, an emerging strategy, tailors an individual's key characteristics such as diet, phenotype, genotype, metabolic biomarkers, and gut microbiome for personalized dietary recommendations to optimize dietary response and health. Precision nutrition is suggested to be an alternative and potentially more effective strategy to improve dietary intake and prevention of obesity and chronic diseases. The purpose of this narrative review is to synthesize the current research and examine the state of the science regarding the effect of precision nutrition in improving the risk factors of obesity and type 2 diabetes.RECENT FINDINGS: The results of the research review indicate to a large extent significant evidence supporting the effectiveness of precision nutrition in improving the risk factors of obesity and type 2 diabetes. Deeper insights and further rigorous research into the diet-phenotype-genotype and interactions of other components of precision nutrition may enable this innovative approach to be adapted in health care and public health to the special needs of individuals. Precision nutrition provides the strategy to make individualized dietary recommendations by integrating genetic, phenotypic, nutritional, lifestyle, medical, social, and other pertinent characteristics about individuals, as a means to address the challenges of generalized dietary recommendations. The evidence presented in this review shows that precision nutrition markedly improves risk factors of obesity and type 2 diabetes, particularly behavior change.PMID:37610590 | DOI:10.1007/s13668-023-00491-y

Bioinformatics. 2023 Aug 23:btad523. doi: 10.1093/bioinformatics/btad523. Online ahead of print.ABSTRACTMOTIVATION: The method of GWAS and metabolomics combined provide an quantitative approach to pinpoint metabolic pathways and genes linked to specific diseases; however, such analyses require both genomics and metabolomics datasets from the same individuals/samples. In most cases, this approach is not feasible due to high costs, lack of technical infrastructure, unavailability of samples, and other factors. Therefore, an unmet need exists for a bioinformatics tool that can identify gene loci-associated polymorphic variants for metabolite alterations seen in disease states using standalone metabolomics.RESULTS: Here, we developed a bioinformatics tool, metGWAS 1.0, that integrates independent GWAS data from the GWAS database and standalone metabolomics data using a network-based systems biology approach to identify novel disease/trait-specific metabolite-gene associations. The tool was evaluated using standalone metabolomics datasets extracted from two metabolomics-GWAS case studies. It discovered both the observed and novel gene loci with known single nucleotide polymorphisms when compared to the original studies.AVAILABILITY AND IMPLEMENTATION: The developed metGWAS 1.0 framework is implemented in an R pipeline and available at: https://github.com/saifurbd28/metGWAS-1.0.PMID:37610350 | DOI:10.1093/bioinformatics/btad523

mSystems. 2023 Aug 23:e0066123. doi: 10.1128/msystems.00661-23. Online ahead of print.ABSTRACTDespite multiple vaccine doses early in life, a substantial proportion of infants do not mount protective responses. In this study, we followed a cohort of children over the first 2 years of life, collecting microbiome and metabolome data longitudinally to investigate correlates of lower and higher responses to primary vaccinations. We found that the stool and nasopharyngeal microbiome developed with age, though demonstrated divergent timing and patterns in maturation. When measured at child age 2 months, evenness of genera in the stool microbiome correlated with lower vaccine responses, upregulated metabolome genes that encode for lipid A biosynthesis and oxidative phosphorylation correlated with higher vaccine responses, and abundance of phenylpyruvic acid in serum correlated with lower vaccine responses, measured 10 months later. Antibiotic exposure was associated with low vaccine response, and microbiome/metabolome features at child age 2 months, before childhood vaccinations commenced, correlated with variations in vaccine responses measured at child age 1 year. These results indicate that there may be potential to intervene before first childhood vaccinations to improve later protection. IMPORTANCE We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.PMID:37610205 | DOI:10.1128/msystems.00661-23

J Asthma. 2023 Aug 23:1-15. doi: 10.1080/02770903.2023.2251062. Online ahead of print.ABSTRACTOBJECTIVE: Asthma, a common disease among children and adolescents, poses a great health risk when ignored; therefore, a thorough follow-up to prevent exacerbations is emphasized. The aim of the present study is to investigate asthma exacerbation in children during the Coronavirus disease 2019 (COVID-19) era.Data Sources: This narrative review has been done by searching the PubMed and Embase databases using Asthma, COVID-19, Pandemic, and Symptom flare up as keywords.Study Selections: Studies related to asthma exacerbation in COVID-19 pandemic were included.RESULTS: Based on studies, controlled or mild to moderate asthma has not been considered a risk factor for COVID-19 severity and has not affected hospitalization, intensive care unit (ICU) admission, and mortality. Surprisingly, emergent and non-emergent visits and asthmatic attacks decreased during the pandemic. The three main reasons for decreased incidence and exacerbation of asthma episodes in the COVID-19 era included reduced exposure to environmental allergens, increasing the acceptance of treatment by pediatrics and caregivers, and decreased risk of other respiratory viral infections. Based on the available studies, COVID-19 vaccination had no serious side effects, except in cases of uncontrolled severe asthma, and can be injected in these children. Also, there was no conclusive evidence of asthma exacerbation after the injection of COVID-19 vaccines.CONCLUSION: Further studies are recommended to follow the pattern of asthma in the post-pandemic situation and to become prepared for similar future conditions.PMID:37610180 | DOI:10.1080/02770903.2023.2251062

Nat Prod Res. 2023 Aug 23:1-5. doi: 10.1080/14786419.2023.2248648. Online ahead of print.ABSTRACTAntimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography-mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon.PMID:37610160 | DOI:10.1080/14786419.2023.2248648

Gut Microbes. 2023 Dec;15(2):2246184. doi: 10.1080/19490976.2023.2246184.ABSTRACTOpioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.PMID:37610102 | DOI:10.1080/19490976.2023.2246184

Anal Chem. 2023 Aug 23. doi: 10.1021/acs.analchem.3c02583. Online ahead of print.ABSTRACTPeak alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based large-scale untargeted metabolomics workflows, as it enables the integration of metabolite peaks across multiple samples, which is essential for accurate data interpretation. Slight differences or fluctuations in chromatographic separation conditions, however, can cause the chromatographic retention time (RT) shift between consecutive analyses, ultimately affecting the accuracy of peak alignment between samples. Here, we introduce a novel RT shift correction method based on the retention index (RI) and apply it to peak alignment. We synthesized a series of N-acyl glycine (C2-C23) homologues via the amidation reaction between glycine with normal saturated fatty acids (C2-C23) as calibrants able to respond proficiently in both mass spectrometric positive- and negative-ion modes. Using these calibrants, we established an N-acyl glycine RI system. This RI system is capable of covering a broad chromatographic space and addressing chromatographic RT shift caused by variations in flow rate, gradient elution, instrument systems, and LC separation columns. Moreover, based on the RI system, we developed a peak shift correction model to enhance peak alignment accuracy. Applying the model resulted in a significant improvement in the accuracy of peak alignment from 15.5 to 80.9% across long-term data spanning a period of 157 days. To facilitate practical application, we developed a Python-based program, which is freely available at https://github.com/WHU-Fenglab/RI-based-CPSC.PMID:37609864 | DOI:10.1021/acs.analchem.3c02583

J Allergy Clin Immunol Glob. 2023 Aug;2(3):100115. doi: 10.1016/j.jacig.2023.100115. Epub 2023 May 5.ABSTRACTBACKGROUND: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population.OBJECTIVE: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles.METHODS: A total of 98 children aged 6 through 17 years with exacerbating asthma (n = 69) and stable asthma (n = 29) underwent clinical characterization procedures and submitted plasma samples for metabolomic analyses. High-confidence metabolites were retained and utilized for pathway enrichment analyses to identify the most relevant metabolic pathways that discriminated between groups.RESULTS: In all, 118 and 131 high-confidence metabolites were identified in positive and negative ionization mode, respectively. A total of 103 unique metabolites differed significantly between children with exacerbating asthma and children with stable asthma. In all, 8 significantly enriched pathways that were largely associated with alterations in arginine, phenylalanine, and glycine metabolism were identified. However, other metabolites and pathways of interest were also identified.CONCLUSION: Metabolomic analyses identified multiple perturbed metabolites and pathways that discriminated children with exacerbating asthma who were hospitalized for status asthmaticus. These results highlight the complex biology of inflammation in children with exacerbating asthma and argue for additional studies of the metabolic determinants of asthma exacerbations in children because many of the identified metabolites of interest may be amenable to targeted interventions.PMID:37609569 | PMC:PMC10443927 | DOI:10.1016/j.jacig.2023.100115

Front Plant Sci. 2023 Aug 7;14:1261685. doi: 10.3389/fpls.2023.1261685. eCollection 2023.NO ABSTRACTPMID:37609522 | PMC:PMC10441578 | DOI:10.3389/fpls.2023.1261685

Heliyon. 2023 Aug 7;9(8):e18991. doi: 10.1016/j.heliyon.2023.e18991. eCollection 2023 Aug.ABSTRACTChronic kidney disease (CKD) refers to a range of various pathophysiological processes correlated with abnormal renal function and a progressive loss in GFR. Just as dysbiosis and altered pathology of the gut are accompanied with hypertension, which is a significant CKD risk factor. Gut dysbiosis in CKD patients is associated with an elevated levels of uremic toxins, which in turn increases the CKD progression. According to research results, the gut-kidney axis has a role in the formation of kidney stones, also in IgAN. A number of researchers have categorized the gut microbiota as enterotypes, and others, skeptical of theory of enterotypes, have suggested biomarkers to describe taxa that related to lifestyle, nutrition, and disease status. Metabolome-microbiome studies have been used to investigate the interactions of host-gut microbiota in terms of the involvement of metabolites in these interactions and are yielded promising results. The correlation between gut microbiota and CKD requires further multi-omic researches. Also, with regard to systems biology, studies on the communication network of proteins and transporters such as SLC and ABC, can help us achieve a deeper understanding of the gut-liver-kidney axis communication and can thus provide promising new horizons in the treatment of CKD patients. Probiotic-based treatment is an approach to reduce uremic poisoning, which is accomplished by swallowing microbes those can catalyze URS in the gut. If further comprehensive studies are carried out, we will know about the probiotics impact in slowing the renal failure progression and reducing inflammatory markers.PMID:37609403 | PMC:PMC10440536 | DOI:10.1016/j.heliyon.2023.e18991

Res Sq. 2023 Aug 11:rs.3.rs-3232670. doi: 10.21203/rs.3.rs-3232670/v1. Preprint.ABSTRACTBackground Tuberculosis (TB) infection is known to lead to the unbalance of the gut microbiota and act synergistically on the decline of the host immune response, when untreated. Moreover, previous work has found a correlation between dysbiosis in the gut microbiota composition and the use of antibiotics. However, there is a need for an in-depth understanding of the metabolic and immune consequences of antibiotic-related microbiome alterations during first-line TB treatment. Methods In a longitudinal cohort study, which included TB-infected cohorts and healthy individuals (control group), we studied the anti-TB-related changes in the gut microbiota composition and related functional consequences. Sputum, whole blood and stool samples were collected from participants at four time-points including before (Month-0), during (Month-2), at the end of drug treatment (Month-6) and 9 months after treatment (Month-15). Controls were sampled at inclusion and Month-6. We analyzed the microbiota composition and microbial functional pathways with shotgun metagenomics, analyzed the blood metabolomics using high-performance liquid chromatography (HPLC), and measured the levels of metabolites and cytokines with cytometric bead array. Results We found that the gut microbiota of patients infected with TB was different from that of the healthy controls. The gut microbiota became similar to healthy controls after treatment but was still significantly different after 6 months treatment and at the follow up 9 months after treatment. Our data also showed disturbance in the plasma metabolites such as tryptophan and tricarboxylic acids components of patients during TB treatment. Levels of IL-4, IL-6, IL-10, and IFN-γ decreased during treatment and levels were maintained after treatment completion, while IL-17A known to have a strong link with the gut microbiota was highly expressed during treatment period and longer than the 9-month post treatment completion. We found that some fatty acids were negatively correlated with the abundance of taxa. For example, Roseburia , Megasphaera , and alpha proteobacterium HIMB5 species were negatively correlated (rho = -0.6) with the quinolinate production. Conclusion Changes in the composition and function of gut microbiota was observed in TB patients before and after treatment compared to healthy controls. The differences persisted at nine months after treatment completion. Alterations in some bacterial taxa were correlated to the changes in metabolite levels in peripheral blood, thus the altered microbial community might lead to changes in immune status that influence the disease outcome and future resistance to infections.PMID:37609282 | PMC:PMC10441471 | DOI:10.21203/rs.3.rs-3232670/v1

bioRxiv. 2023 Aug 9:2023.06.19.544952. doi: 10.1101/2023.06.19.544952. Preprint.ABSTRACTThe disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies.HIGHLIGHTS: PCB 52 was present in adipose, brain, liver, and serum 3 weeks after PCB exposureLiver and serum contained hydroxylated, sulfated, and methylated PCB 52 metabolitesMetabolomics analysis revealed minor changes in endogenous serum metabolitesLevels of dopamine and its metabolites in the brain were not affected by PCB 52.PMID:37609242 | PMC:PMC10441371 | DOI:10.1101/2023.06.19.544952

bioRxiv. 2023 Aug 9:2023.08.08.550079. doi: 10.1101/2023.08.08.550079. Preprint.ABSTRACTThe human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarce on a time-resolved metabolome-wide level. Here, we present the HuMet Repository, a web-based resource for exploring dynamic metabolic responses to six physiological challenges (exercise, 36 h fasting, oral glucose and lipid loads, mixed meal, cold stress) in healthy subjects. For building this resource, we integrated existing and newly derived metabolomics data measured in blood, urine, and breath samples of 15 young healthy men at up to 56 time points during the six highly standardized challenge tests conducted over four days. The data comprise 1.1 million data points acquired on multiple platforms with temporal profiles of 2,656 metabolites from a broad range of biochemical pathways. By embedding the dataset into an interactive web application, we enable users to easily access, search, filter, analyze, and visualize the time-resolved metabolomic readouts and derived results. Users can put metabolites into their larger context by identifying metabolites with similar trajectories or by visualizing metabolites within holistic metabolic networks to pinpoint pathways of interest. In three showcases, we outline the value of the repository for gaining biological insights and generating hypotheses by analyzing the wash-out of dietary markers, the complementarity of metabolomics platforms in dynamic versus cross-sectional data, and similarities and differences in systemic metabolic responses across challenges. With its comprehensive collection of time-resolved metabolomics data, the HuMet Repository, freely accessible at https://humet.org/ , is a reference for normal, healthy responses to metabolic challenges in young males. It will enable researchers with and without computational expertise, to flexibly query the data for their own research into the dynamics of human metabolism.PMID:37609175 | PMC:PMC10441358 | DOI:10.1101/2023.08.08.550079

bioRxiv. 2023 Aug 10:2023.08.10.552811. doi: 10.1101/2023.08.10.552811. Preprint.ABSTRACTToxoplasma gondii , the causative agent of toxoplasmosis, is an obligate intracellular parasite that infects warm-blooded vertebrates across the world. In humans, seropositivity rates of T. gondii range from 10% to 90%. Despite its prevalence, few studies address how T. gondii infection changes the metabolism of host cells. Here, we investigate how T. gondii manipulates the host cell metabolic environment by monitoring metabolic response over time using non-invasive autofluorescence lifetime imaging of single cells, seahorse metabolic flux analysis, reactive oxygen species (ROS) production, and metabolomics. Autofluorescence lifetime imaging indicates that infected host cells become more oxidized and have an increased proportion of bound NAD(P)H with infection. These findings are consistent with changes in mitochondrial and glycolytic function, decrease of intracellular glucose, fluctuations in lactate and ROS production in infected cells over time. We also examined changes associated with the pre-invasion "kiss and spit" process using autofluorescence lifetime imaging, which similarly showed a more oxidized host cell with an increased proportion of bound NAD(P)H over 48 hours. Glucose metabolic flux analysis indicated that these changes are driven by NADH and NADP+ in T. gondii infection. In sum, metabolic changes in host cells with T. gondii infection were similar during full infection, and kiss and spit. Autofluorescence lifetime imaging can non-invasively monitor metabolic changes in host cells over a microbial infection time-course.PMID:37609172 | PMC:PMC10441426 | DOI:10.1101/2023.08.10.552811

Front Microbiol. 2023 Aug 7;14:1134585. doi: 10.3389/fmicb.2023.1134585. eCollection 2023.ABSTRACTElymus nutans is a perennial grass of the Gramineae family. Due to its cold-resistance and nutrition deficiency tolerance, it has been applied to the ecological restoration of degraded alpine grassland on the Qinghai-Tibet Plateau. As an important symbiotic microorganism, arbuscular mycorrhizal fungi (AMF) have been proven to have great potential in promoting the growth and stress resistance of Gramineae grasses. However, the response mechanism of the AMF needs to be clarified. Therefore, in this study, Rhizophagus irregularis was used to explore the mechanism regulating cold resistance of E. nutans. Based on pot experiments and metabolomics, the effects of R. irregularis were investigated on the activities of antioxidant enzyme and metabolites in the roots of E. nutans under cold stress (15/10°C, 16/8 h, day/night). The results showed that lipids and lipid molecules are the highest proportion of metabolites, accounting for 14.26% of the total metabolites. The inoculation with R. irregularis had no significant effects on the activities of antioxidant enzyme in the roots of E. nutans at room temperature. However, it can significantly change the levels of some lipids and other metabolites in the roots. Under cold stress, the antioxidant enzyme activities and the levels of some metabolites in the roots of E. nutans were significantly changed. Meanwhile, most of these metabolites were enriched in the pathways related to plant metabolism. According to the correlation analysis, the activities of antioxidant enzyme were closely related to the levels of some metabolites, such as flavonoids and lipids. In conclusion, AMF may regulate the cold-resistance of Gramineae grasses by affecting plant metabolism, antioxidant enzyme activities and antioxidant-related metabolites like flavonoids and lipids. These results can provide some basis for studying the molecular mechanism of AMF regulating stress resistance of Gramineae grasses.PMID:37608949 | PMC:PMC10440431 | DOI:10.3389/fmicb.2023.1134585

Front Microbiol. 2023 Aug 7;14:1182547. doi: 10.3389/fmicb.2023.1182547. eCollection 2023.ABSTRACTThe gut microbiome has been increasingly understood to play a critical role in carcinogenesis and cancer disease progression. The most recent research advancements have shown that different tools of microbiota manipulation contribute to gut microbiome-immune-oncology axis modulation, offering exciting opportunities for targeted interventions aimed at improving the efficacy of established anti-cancer therapy. Postbiotics are a new entry among the biotics showing beneficial effects on human health while not requiring living cells to obtain the health effect and therefore not subjected to food safety rules for live microorganisms. Postbiotics are recently defined as the "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" and have gradually become the focus of the scientific community. Since the beginning of research on this topic, numerous studies about postbiotics have been proven to strengthen the gut barrier, reduce inflammation, and promote antimicrobial activity. However, research on the potential application of cancer therapy is still at the early stages of its efforts to uncover all the secrets surrounding postbiotics. This review aims to increase our understanding of the anti-cancer effect of postbiotics throughout a "bibliographic journey" on the biological activity of their components, including exopolysaccharides, cell wall fragments, tryptophan metabolites, enzymes, bacterial lysates, extracellular vesicles, and short-chain fatty acids, highlighting their perspective as a new supportive therapeutic method of treatment and identifying the literature gaps where further research is needed.PMID:37608943 | PMC:PMC10440707 | DOI:10.3389/fmicb.2023.1182547

Front Pharmacol. 2023 Aug 7;14:1173747. doi: 10.3389/fphar.2023.1173747. eCollection 2023.ABSTRACTIntroduction: Corni Fructus (CF) is a Chinese herbal medicine used for medicinal and dietary purposes. It is available commercially in two main forms: raw CF (unprocessed CF) and wine-processed CF. Clinical observations have indicated that wine-processed CF exhibits superior hypoglycemic activity compared to its raw counterpart. However, the mechanisms responsible for this improvement are not well understood. Methods: To address this gap in knowledge, we conducted metabolomics analysis using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) to compare the chemical composition of raw CF and wine-processed CF. Subsequently, network analysis, along with immunofluorescence assays, was employed to elucidate the potential targets and mechanisms underlying the hypoglycemic effects of metabolites in CF. Results: Our results revealed significant compositional differences between raw CF and wine-processed CF, identifying 34 potential markers for distinguishing between the two forms of CF. Notably, wine processing led to a marked decrease in iridoid glycosides and flavonoid glycosides, which are abundant in raw CF. Network analysis predictions provided clues that eight compounds might serve as hypoglycemic metabolites of CF, and glucokinase (GCK) and adenylate cyclase (ADCYs) were speculated as possible key targets responsible for the hypoglycemic effects of CF. Immunofluorescence assays confirmed that oleanolic acid and ursolic acid, two bioactive compounds present in CF, significantly upregulated the expression of GCK and ADCYs in the HepG2 cell model. Discussion: These findings support the notion that CF exerted hypoglycemic activity via multiple components and targets, shedding light on the impact of processing methods on the chemical composition and hypoglycemic activity of Chinese herbal medicine.PMID:37608891 | PMC:PMC10440738 | DOI:10.3389/fphar.2023.1173747

Plant J. 2023 Aug 22. doi: 10.1111/tpj.16421. Online ahead of print.ABSTRACTStrigolactones are a class of phytohormones that are involved in many different plant developmental processes, including the rhizobium-legume nodule symbiosis. Although both positive and negative effects of strigolactones on the number of nodules have been reported, the influence of strigolactones on nodule development is still unknown. Here, by means of the ramosus (rms) mutants of Pisum sativum (pea) cv Terese, we investigated the impact of strigolactone biosynthesis (rms1 and rms5) and signaling (rms3 and rms4) mutants on nodule growth. The rms mutants had more red, that is, functional, and larger nodules than the wild-type plants. Additionally, the increased nitrogen fixation and senescence zones with consequently reduced meristematic and infection zones indicated that the rms nodules developed faster than the wild-type nodules. An enhanced expression of the nodule zone-specific molecular markers for meristem activity and senescence supported the enlarged, fast maturing nodules. Interestingly, the master nodulation regulator, NODULE INCEPTION, NIN, was strongly induced in nodules of all rms mutants but not prior to inoculation. Determination of sugar levels with both bulk and spatial metabolomics in roots and nodules, respectively, hints at slightly increased malic acid levels early during nodule primordia formation and reduced sugar levels at later stages, possibly the consequence of an increased carbon usage of the enlarged nodules, contributing to the enhanced senescence. Taken together, these results suggest that strigolactones regulate the development of nodules, which is probably mediated through NIN, and available plant sugars.PMID:37608631 | DOI:10.1111/tpj.16421