PubMed

mBio. 2023 Mar 20:e0007323. doi: 10.1128/mbio.00073-23. Online ahead of print.ABSTRACTThe cytosol of eukaryotic host cells is an intrinsically hostile environment for bacteria. Understanding how cytosolic pathogens adapt to and survive in the cytosol is critical to developing novel therapeutic interventions against these pathogens. The cytosolic pathogen Listeria monocytogenes requires glmR (previously known as yvcK), a gene of unknown function, for resistance to cell-wall stress, cytosolic survival, inflammasome avoidance, and, ultimately, virulence in vivo. In this study, a genetic suppressor screen revealed that blocking utilization of UDP N-acetylglucosamine (UDP-GlcNAc) by a nonessential wall teichoic acid decoration pathway restored resistance to lysozyme and partially restored virulence of ΔglmR mutants. In parallel, metabolomic analysis revealed that ΔglmR mutants are impaired in the production of UDP-GlcNAc, an essential peptidoglycan and wall teichoic acid (WTA) precursor. We next demonstrated that purified GlmR can directly catalyze the synthesis of UDP-GlcNAc from GlcNAc-1P and UTP, suggesting that it is an accessory uridyltransferase. Biochemical analysis of GlmR orthologues suggests that uridyltransferase activity is conserved. Finally, mutational analysis resulting in a GlmR mutant with impaired catalytic activity demonstrated that uridyltransferase activity was essential to facilitate cell-wall stress responses and virulence in vivo. Taken together, these studies indicate that GlmR is an evolutionary conserved accessory uridyltransferase required for cytosolic survival and virulence of L. monocytogenes. IMPORTANCE Bacterial pathogens must adapt to their host environment in order to cause disease. The cytosolic bacterial pathogen Listeria monocytogenes requires a highly conserved protein of unknown function, GlmR (previously known as YvcK), to survive in the host cytosol. GlmR is important for resistance to some cell-wall stresses and is essential for virulence. The ΔglmR mutant is deficient in production of an essential cell-wall metabolite, UDP-GlcNAc, and suppressors that increase metabolite levels also restore virulence. Purified GlmR can directly catalyze the synthesis of UDP-GlcNAc, and this enzymatic activity is conserved in both Bacillus subtilis and Staphylococcus aureus. These results highlight the importance of accessory cell wall metabolism enzymes in responding to cell-wall stress in a variety of Gram-positive bacteria.PMID:36939339 | DOI:10.1128/mbio.00073-23

mSystems. 2023 Mar 20:e0108622. doi: 10.1128/msystems.01086-22. Online ahead of print.NO ABSTRACTPMID:36939333 | DOI:10.1128/msystems.01086-22

J Food Sci. 2023 Mar 20. doi: 10.1111/1750-3841.16534. Online ahead of print.ABSTRACTTo explore the mechanism of Rosa roxburghii juice browning, this experiment was based on nontargeted metabolomics to study the effects of browning on the nutrition, flavor, metabolites, and metabolic pathways of R. roxburghii juice before and after storage. The results showed that the total soluble solids, superoxide dismutase (SOD), vitamin C (VC ), total phenol, and total flavonoid of R. roxburghii juice decreased significantly before and after storage. The color difference value ∆E, browning index, and flavor and taste of R. roxburghii juice changed significantly (p < 0.05). A total of 541 metabolites were detected before and after browning of R. roxburghii juice by nontargeted metabolomics, including 435 differential metabolites, of which 221 were upregulated, and 214 were downregulated. The differential metabolites were mainly amino acids and peptides, carbohydrates, and carbohydrate conjugates. There were a total of 76 metabolic pathways enriched by differential metabolites, involving mainly galactose metabolism; alanine, aspartate and glutamate metabolism; and pantothenate and CoA biosynthesis. The experimental results showed that after browning of R. roxburghii juice, VC , total phenol, total flavonoid, and SOD activity were seriously lost, and the flavor deteriorated. The contribution of differential metabolites and metabolic pathways to the browning of R. roxburghii juice was sugar metabolism > amino acid metabolism > ascorbate and aldarate metabolism > phenols.PMID:36939010 | DOI:10.1111/1750-3841.16534

Clin Transl Med. 2023 Mar;13(3):e1225. doi: 10.1002/ctm2.1225.NO ABSTRACTPMID:36938989 | DOI:10.1002/ctm2.1225

Environ Sci Technol. 2023 Mar 20. doi: 10.1021/acs.est.2c08747. Online ahead of print.ABSTRACTAquatic organisms are frequently exposed to various nanoparticles (NPs) in the natural environment. Thus, studies of NP bioaccumulation should include organisms that have been previously exposed to NPs. Our study investigated the effects of pre-exposure of Tetrahymena thermophila (T. thermophila) to Fe2O3 or TiO2 NPs on the protozoan's subsequent uptake of 55Fe-labeled Fe2O3 (55Fe2O3) NPs. Molecular mechanisms underlying the pre-exposure effects were explored in transcriptomic and metabolomic experiments. Pre-exposure to either NPs inhibited the subsequent uptake of 55Fe2O3 NPs. The results of the transcriptomic experiment indicated that NP pre-exposure influenced the expression of genes related to phagosomes and lysosomes and physiological processes such as glutathione and lipid metabolism, which are closely associated with the endocytosis of 55Fe2O3 NPs. The differentially expressed metabolites obtained from the metabolomic experiments showed an enrichment of energy metabolism and antioxidation pathways in T. thermophila pre-exposed to NPs. Together, these results demonstrate that the pre-exposure of T. thermophila to Fe2O3 or TiO2 NPs inhibited the protozoan's subsequent uptake of 55Fe2O3 NPs, possibly by mechanisms involving the alteration of endocytosis-related organelles, the induction of oxidative stress, and a lowering of the intracellular energy supply. Thus, NP pre-exposure represents a scenario which can inform increasingly realistic estimates of NP bioaccumulation.PMID:36938933 | DOI:10.1021/acs.est.2c08747

J Nat Prod. 2023 Mar 20. doi: 10.1021/acs.jnatprod.3c00019. Online ahead of print.ABSTRACTHuman pancreatic tumors are hypovascular in nature, and their tumor microenvironment is often characterized by hypoxia and severe nutrient deprivation due to uncontrolled heterogeneous growth, a phenomenon known as "austerity". However, pancreatic tumor cells have the inherent ability to adapt and thrive even in such low nutrient and hypoxic microenvironments. Anticancer drugs such as gemcitabine and paclitaxel, which target rapidly proliferating cells, are often ineffective against nutrient-deprived pancreatic cancer cells. In order to overcome this limitation, the search for novel agents that can eliminate cancer cells' adaptations to nutrition starvation, also known as "antiausterity" agents, represents a promising strategy to make the cancer cells susceptible to treatment. The natural product (+)-nicolaioidesin C (Nic-C) was found to have potent antiausterity activity against the PANC-1 human pancreatic cancer cell line in a nutrient-deprived condition. However, its efficacy in vivo remained untested. To address this, we synthesized Nic-C in its racemic form and evaluated its antitumor potential in a human pancreatic cancer xenograft model. Nic-C inhibited pancreatic cancer cell migration and colony formation and significantly inhibited tumor growth in MIA PaCa-2 xenografts in a dose-dependent manner. Furthermore, Nic-C inhibited the Akt/mTOR and autophagy signaling pathways in both in vitro and in vivo studies. Metabolomic profiling of in vivo tumor samples suggests that Nic-C downregulates amino acid metabolism while upregulating sphingolipid metabolism.PMID:36938707 | DOI:10.1021/acs.jnatprod.3c00019

Mol Omics. 2023 Mar 20. doi: 10.1039/d2mo00332e. Online ahead of print.ABSTRACTChronic stress, a leading factor for high blood pressure (BP) and even hypertension, affects health quality seriously. However, the management is rather difficult in our rapidly developing modern society, and the underlying mechanism that caused hypertension remains incompletely understood. In this study, we established a rat model of high BP induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS increased the BP and heart rate, as well as the concentrations of CORT, NA, and ACTH. Based on tandem mass tag (TMT)-labeled proteomics, 13 proteins changed in RVLM. Then, targeted metabolomics together with real-time qPCR were applied to validate the levels of the biomolecules quantitatively. The related molecules were confirmed to reveal that CUMS has a great role in the upregulation of muscle contraction, synthesis of cAMP and transport of metals, while down-regulating ralaxin signaling. This finding facilitates a better understanding of the mechanism of hypertension induced by chronic stress and could provide an insight into the prevention and treatment of hypertension.PMID:36938653 | DOI:10.1039/d2mo00332e

Analyst. 2023 Mar 20. doi: 10.1039/d3an00249g. Online ahead of print.ABSTRACTParacetamol (also known as acetaminophen) is an over-the-counter (OTC) drug that is commonly used as an analgesic for mild pain, headache, cold and flu. While in the short term it is a safe and effective medicine, it is sometimes used for attempted suicides particularly in young adults. In such circumstances it is important for rapid diagnosis of overdoses as antidotes can be given to limit liver damage from one of its primary metabolites N-acetyl-p-benzoquinone imine (NAPQI). Unfortunately, the demand for rapid and sensitive analytical techniques to accurately monitor the abuse of OTC drugs has significantly risen. Ideally these techniques would be highly specific, sensitive, reproducible, portable and rapid. In addition, an ideal point of care (PoC) test would enable quantitative detection of drugs and their metabolites present in body fluids. While Raman spectroscopy meets these specifications, there is a need for enhancement of the signal because the Raman effect is weak. In this study, we developed a surface-enhanced Raman scattering (SERS) methodology in conjunction with chemometrics to quantify the amount of paracetamol and its main primary metabolites (viz., paracetamol sulfate, p-acetamidophenyl β-D-glucuronide and NAPQI) in water and artificial urine. The enhancement of the SERS signals was achieved by mixing the drug or xenometabolites with a gold nanoparticle followed by aggregation with 0.045 M NaCl. We found that the SERS data could be collected directly, due to immediate analyte association with the Au surface and colloid aggregation. Accurate and precise measurements were generated, with a limit of detection (LoD) of paracetamol in water and artificial urine at 7.18 × 10-6 M and 2.11 × 10-5 M, respectively, which is well below the limit needed for overdose and indeed normal levels of paracetamol in serum after taking 1 g orally. The predictive values obtained from the analysis of paracetamol in water and artificial urine were also excellent, with the coefficient of determination (Q2) being 0.995 and 0.996, respectively (1 suggests a perfect model). It was noteworthy that when artificial urine was spiked with paracetamol, no aggregating agent was required due to the salt rich medium, which led to spontaneous aggregation. Moreover, for the xenometabolites of paracetamol excellent LoDs were obtained and these ranged from 2.6 × 10-4 M to 5 × 10-5 M with paracetamol sulfate and NAPQI having Q2 values of 0.934 and 0.892 and for p-acetamidophenyl β-D-glucuronide this was slightly lower at 0.6437.PMID:36938623 | DOI:10.1039/d3an00249g

Clin Pathol. 2023 Mar 13;16:2632010X221127683. doi: 10.1177/2632010X221127683. eCollection 2023 Jan-Dec.ABSTRACTBACKGROUND: Different expression of cytokine genes in the body determines the type of immune response (Th1 or Th2), which can play an important role in the pathogenesis of the COVID-19 disease.AIMS: This meta-analysis was conducted to evaluate the probable effect of photobiomodulation (PBMT) therapy on the cytokine's mRNA expression in the lung.METHODS: We systematically searched indexing databases, including PubMed/Medline, ISI web of science, Scopus, EMBASE, and Cochrane central, using standard terms without language, study region or type restrictions. Studies on using PBM in lung injury modeling with samples collected from lung tissue to observe IL-1β, TNF-α, IL-10, and IL-6 mRNA expression were included. RevMan 5.3 software was used for data analysis and standardized mean difference as effect size.RESULTS: Of the 438 studies found through initial searches, 17 met the inclusion criteria. The main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rats (n = 10) and rabbits (n = 3). The analysis revealed that PBMT reduced the mRNA expression of TNFα (SMD: -3.70, 95% CI: -6.29, -1.11, P = .005,I 2 = 71%) and IL-1β (SMD: -5.85, 95% CI: -8.01, -3.69, P < .00001,I 2 = 37%) significantly, but no statistically significant reduction in IL-6 (SMD: -2.89, 95% CI: -5.79, 0.01, P = .05,I 2 = 88%) was observed compared with the model controls. Also, PBMT increased IL-10 mRNA expression significantly compared with the model controls (SMD: 1.04, 95% CI: 0.43, 1.64, P = .0008,I 2 = 17%).CONCLUSION: This meta-analysis revealed that the PBMT utilizes beneficial anti-inflammatory effects and modulation of the immune system on lung damage in animal models and clinical studies. However, animal models and clinical studies appear limited considering the evidence's quality; therefore, large clinical trials are still required.PMID:36938515 | PMC:PMC10014418 | DOI:10.1177/2632010X221127683

Front Plant Sci. 2023 Mar 3;14:1097044. doi: 10.3389/fpls.2023.1097044. eCollection 2023.ABSTRACTINTRODUCTION: Plant pathogens are one of the major constraints on worldwide food production. The antibiotic properties of microbes identified as effective in managing plant pathogens are well documented.METHODS: Here, we used antagonism experiments and untargeted metabolomics to isolate the potentially antifungal molecules produced by KJ-34.RESULTS: KJ-34 is a potential biocontrol bacterium isolated from the rhizosphere soil of rice and can fight multiple fungal pathogens (i.e. Ustilaginoidea virens, Alternaria solani, Fusarium oxysporum, Phytophthora capsica, Corynespora cassiicola). The favoured fermentation conditions are determined and the fermentation broth treatment can significantly inhibit the infection of Magnaporthe oryzae and Botryis cinerea. The fermentation broth suppression ratio is 75% and 82%, respectively. Fermentation broth treatment disrupted the spore germination and led to malformation of hyphae. Additionally, we found that the molecular weight of antifungal products were less than 1000 Da through semipermeable membranes on solid medium assay. To search the potentially antifungal molecules that produce by KJ-34, we used comparative and bioinformatics analyses of fermentation broth before and after optimization by mass spectrometry. Untargeted metabolomics analyses are presumed to have a library of antifungal agents including benzoylstaurosporine, morellin and scopolamine.DISCUSSION: These results suggest that KJ-34 produced various biological control agents to suppress multiple phytopathogenic fungi and showed a strong potential in the ecological technologies of prevention and protection.PMID:36938063 | PMC:PMC10020716 | DOI:10.3389/fpls.2023.1097044

Front Plant Sci. 2023 Mar 3;14:1167513. doi: 10.3389/fpls.2023.1167513. eCollection 2023.NO ABSTRACTPMID:36938031 | PMC:PMC10020689 | DOI:10.3389/fpls.2023.1167513

Front Plant Sci. 2023 Mar 3;14:1111069. doi: 10.3389/fpls.2023.1111069. eCollection 2023.ABSTRACTAgriphotovoltaic (APV) systems allow the simultaneous production of crops and electricity in the same land area. Since the reduction of yield caused by APV systems is important for food security, studies to improve the yield have been conducted steadily. However, there have been limited data on the appearance, quality, and metabolomic changes of crops. Therefore, in this study, we evaluated the visual qualities and metabolites as well as the yield of broccoli grown using an APV system during the fall season. In addition, additional shading treatment was performed, and the same qualities were evaluated. In the spring season, an additional cultivar that does not express anthocyanins was cultivated. Glucosinolate content was more sensitive to the seasonal environment and the type of cultivar than it was to treatment type. The additional shading treatment had a positive effect on the visual qualities of anthocyanin-expressing broccoli cultivar regardless of the season, and we observed that even a cultivar that does not express anthocyanins can be greener. Regardless of cultivar, higher chlorophyll content was detected in broccoli florets with additional shading treatment under the APV system. In addition, reduced anthocyanin content was observed (6.1 mg g-1 DW; about 20% of that obtained on open-field). Aspartic acid content was enhanced upon additional shading treatment. Pathway analysis revealed changes in anthocyanin, alanine, aspartic acid, and glutamic acid metabolism. Overall, our findings suggests that it is possible to produce crops with better visual qualities by utilizing APV systems.PMID:36938023 | PMC:PMC10020647 | DOI:10.3389/fpls.2023.1111069

Front Plant Sci. 2023 Mar 1;14:1010669. doi: 10.3389/fpls.2023.1010669. eCollection 2023.ABSTRACTINTRODUCTION: Cycling Dof transcription factors (CDFs) have been involved in different aspects of plant growth and development. In Arabidopsis and tomato, one member of this family (CDF1) has recently been associated with the regulation of primary metabolism and abiotic stress responses, but their roles in crop production under open field conditions remain unknown.METHODS: In this study, we compared the growth, and tuber yield and composition of plants ectopically expressing the CDF1 gene from Arabidopsis under the control of the 35S promoter with wild-type (WT) potato plants cultured in growth chamber and open field conditions.RESULTS: In growth chambers, the 35S::AtCDF1 plants showed a greater tuber yield than the WT by increasing the biomass partition for tuber development. Under field conditions, the ectopic expression of CDF1 also promoted the sink strength of the tubers, since 35S::AtCDF1 plants exhibited significant increases in tuber size and weight resulting in higher tuber yield. A metabolomic analysis revealed that tubers of 35S::AtCDF1 plants cultured under open field conditions accumulated higher levels of glucose, starch and amino acids than WT tubers. A comparative proteomic analysis of tubers of 35S::AtCDF1 and WT plants cultured under open field conditions revealed that these changes can be accounted for changes in the expression of proteins involved in energy production and different aspects of C and N metabolism.DISCUSSION: The results from this study advance our collective understanding of the role of CDFs and are of great interest for the purposes of improving the yield and breeding of crop plants.PMID:36937996 | PMC:PMC10014720 | DOI:10.3389/fpls.2023.1010669

Front Pharmacol. 2023 Mar 3;14:1012716. doi: 10.3389/fphar.2023.1012716. eCollection 2023.ABSTRACTComfrey (Symphytum officinale L.) contains rosmarinic acid which has different pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the medicinal use of comfrey is limited by the hepatotoxic effect of lycopsamine in comfrey, which overshadows the health benefits of rosmarinic acid. Natural deep eutectic solvents (NADES) have a wide range of extraction properties, that provides a new approach to the detoxification of comfrey. In the present study, betaine-based and choline chloride-based NADES were screened for selective extraction of rosmarinic acid over lycopsamine. Ultrasonication was used in conjunction with NADES extraction. The chemical profile of the NADES extracts on antioxidant, anti-inflammatory and hepatotoxic activities were investigated using some chemical reagents. Betaine-urea (1:2 molar ratio, 50% water) obtained the highest content of rosmarinic acid and a low level of lycopsamine (1.934 and 0.018 mg/g, respectively). Betaine-urea was also shown to be more effective to extract rosmarinic acid compared to methanol-UAE under the same conditions, which gave lower rosmarinic acid and higher lycopsamine levels (0.007 and 0.031 mg/g, respectively). Betaine-urea extracts showed higher antioxidant and anti-inflammatory properties as compared with other NADES extracts, however, had lower hepatotoxic profile. This study recommends the use of betaine-urea to detroxify comfrey to open wider opportunities for the development of comfrey for medicinal use.PMID:36937831 | PMC:PMC10020234 | DOI:10.3389/fphar.2023.1012716

Front Oncol. 2023 Mar 3;13:1061083. doi: 10.3389/fonc.2023.1061083. eCollection 2023.ABSTRACTBACKGROUND: Biomarkers of different stages and grades of bladder cancer (BC) are important in clinical work. The objective of our study was to investigate new biomarkers of early-stage BC with liquid chromatography-high resolution mass spectrometry (LC-HRMS) using serum samples.METHODS: A total of 215 cases were included in our study, including 109 healthy adults as the control group and 106 non-muscle invasive bladder cancer (NMIBC) patients as the NMIBC group. Serum samples were collected from BC patients in the early stage, called NMIBC, and healthy people before surgery. We used LC-HRMS to distinguish the NMIBC group from the control group and the low-grade NMIBC group from the control group.RESULTS: An apparent difference between the NMIBC group and the control group was visualized by unsupervised principal component analysis (PCA). Metabolite panels for 16-hydroxy-10-oxohexadecanoic acid, PGF2a ethanolamide, sulfoglycolithocholate, and threoninyl-alanine were used to distinguish the two groups. The area under the curve (AUC) of the panels was 0.985, and the sensitivity and specificity were 98.63% and 98.59%, respectively. To distinguish the low-grade NMIBC group from the control group, serum metabolic profiling differences between the low-grade NMIBC group and control group samples were also analyzed. Metabolite panels of L-octanoylcarnitine, PGF2a ethanolamide, and threoninyl-alanine showed good discrimination performance. The AUC of the panels was 0.999, and the sensitivity and specificity were 97.8% and 100%, respectively.CONCLUSION: Metabolomics analysis of serum samples can distinguish the NMIBC group from the control group, particularly the early-stage low-grade NMIBC group.PMID:36937410 | PMC:PMC10020364 | DOI:10.3389/fonc.2023.1061083

Front Microbiol. 2023 Mar 1;14:1129904. doi: 10.3389/fmicb.2023.1129904. eCollection 2023.ABSTRACTEmerging evidences about gut-microbial modulation have been accumulated in the treatment of nonalcoholic fatty liver disease (NAFLD). We evaluated the effect of Bifidobacterium breve and Bifidobacterium longum on the NAFLD pathology and explore the molecular mechanisms based on multi-omics approaches. Human stool analysis [healthy subjects (n = 25) and NAFLD patients (n = 32)] was performed to select NAFLD-associated microbiota. Six-week-old male C57BL/6 J mice were fed a normal chow diet (NC), Western diet (WD), and WD with B. breve (BB) or B. longum (BL; 109 CFU/g) for 8 weeks. Liver/body weight ratio, histopathology, serum/tool analysis, 16S rRNA-sequencing, and metabolites were examined and compared. The BB and BL groups showed improved liver histology and function based on liver/body ratios (WD 7.07 ± 0.75, BB 5.27 ± 0.47, and BL 4.86 ± 0.57) and NAFLD activity scores (WD 5.00 ± 0.10, BB 1.89 ± 1.45, and BL 1.90 ± 0.99; p < 0.05). Strain treatment showed ameliorative effects on gut barrier function. Metagenomic analysis showed treatment-specific changes in taxonomic composition. The community was mainly characterized by the significantly higher composition of the Bacteroidetes phylum among the NC and probiotic-feeding groups. Similarly, the gut metabolome was modulated by probiotics treatment. In particular, short-chain fatty acids and tryptophan metabolites were reverted to normal levels by probiotics, whereas bile acids were partially normalized to those of the NC group. The analysis of gene expression related to lipid and glucose metabolism as well as the immune response indicated the coordinative regulation of β-oxidation, lipogenesis, and systemic inflammation by probiotic treatment. BB and BL attenuate NAFLD by improving microbiome-associated factors of the gut-liver axis.PMID:36937300 | PMC:PMC10014915 | DOI:10.3389/fmicb.2023.1129904

Front Microbiol. 2023 Mar 2;14:1132866. doi: 10.3389/fmicb.2023.1132866. eCollection 2023.ABSTRACTBACKGROUND: Feather pecking (FP) is a maladaptive behavior in laying hens that is associated with numerous physiological traits, including those involving the central neurotransmitter system and the immune system, which have been identified in many species as being regulated by the gut microbiota via the "microbiota-gut-brain" (MGB) axis. Yet, it is unknown whether and how gut microbiota influences FP by regulating multiple central neurotransmission systems and immune system.METHODS: This study was measured the prevalence of severe FP (SFP) in the commercial layer farm. The chicken flock with the highest frequency of SFP were selected for FP phenotype identification. Nontargeted metabolomics was performed to investigated the differences in the peripheral and central metabolites and 16S rDNA sequencing was performed to investigated the differences in gut microbiome of laying hens with different FP phenotypes. Correlation analysis was performed to determine the potential mechanism by which the disturbed gut microbiota may modulate host physiology and behavior.RESULTS: The results showed that pullets (12 weeks of age) showed significantly higher SFP frequencies than chicks (6 weeks of age) and adults (22 weeks of age; p < 0.05). Compared to neutrals (N), peckers (P) exhibited the stress-induced immunosuppression with the increased plasma levels of corticosterone and norepinephrine, and the decreased plasma levels of IgA, IL-1, IL-6 and tumor necrosis factor α (p < 0.05). In the cecum, the relative abundances of Bacteroides and Gemmiger were higher in the P group, while Roseburia, Ruminococcus2, Anaerostipes, Lachnospiracea_incertae_sedis and Methanobrevibacter were more enriched in the N group. Moreover, increased plasma levels of L-tryptophan, beta-tyrosine and L-histidine were found in the P group (p < 0.05). Notably, in the P group, hippocampal levels of L-tryptophan, xanthurenic acid, L-histidine and histamine were improved and showed a positive association with L-glutamic acid levels. Plasma levels of L-tryptophan, beta-tyrosine and L-histidine were both positively correlated with Bacteroides abundance but negatively correlated with Methanobrevibacter abundance.CONCLUSION: Overall, these findings suggest that the development of FP may be affected by the gut microbiota, which regulates the central glutamatergic nerve system by altering the metabolism of tryptophan, histidine and tyrosine.PMID:36937288 | PMC:PMC10017472 | DOI:10.3389/fmicb.2023.1132866

Front Microbiol. 2023 Mar 2;14:1080851. doi: 10.3389/fmicb.2023.1080851. eCollection 2023.ABSTRACTMacrophages can participate in immune responses by altering their metabolism, and play important roles in controlling bacterial infections. However, Salmonella Enteritidis can survive and proliferate in macrophages. After the deletion of DNA adenine methylase (Dam), the proliferation of Salmonella Enteritidis in macrophages decreased, the molecular mechanism is still unclear. After infecting macrophages with Salmonella Enteritidis wild type and dam gene deletion strains, intracellular metabolites were extracted and detected by non-targeted metabolomics and fatty acid targeted metabolomics. We found Dam had significant effects on arachidonic acid and related metabolic pathways in macrophages. The dam gene can promote the proliferation of Salmonella Enteritidis in macrophages by inhibiting the metabolic pathway of cytosolic phospholipase A2-mediated arachidonic acid production and conversion to prostaglandin E2 in macrophages, reducing the secretion of the pro-inflammatory factors IL-1β and IL-6. In addition, inhibition of arachidonic acid-related pathways in macrophages by Arachidonyl trifluoromethyl ketone could restore the proliferation of dam gene deletion strains in macrophages. This study explored the role of Dam in the process of Salmonella Enteritidis invading host cells from the perspective of host cell metabolism, and provides new insights into the immune escape mechanism of Salmonella Enteritidis.PMID:36937256 | PMC:PMC10018194 | DOI:10.3389/fmicb.2023.1080851

Front Plant Sci. 2023 Mar 2;13:910895. doi: 10.3389/fpls.2022.910895. eCollection 2022.ABSTRACTTo investigate differences in fresh leaves of tea plants at different ages in gene expression, metabolism, and dried tea quality, and to provide references to a deep exploration on metabolite differential accumulation of fresh leaves of tea plants at different ages as well as the regulation mechanism, two groups of fresh leaves from tea plants at different ages (group JP: 20-, 200-, and 1,200-year tea plants; group YX: 50-, 100-, and 400-year tea plants) were chosen as materials, and their differences in gene expression, metabolites, and metabolic regulatory network were investigated by transcriptomics and metabolomics. A total of 12,706 differentially expressed genes (DEGs) were screened from the fresh tea leaves in the JP group, of which tea-20 vs. tea-200 had the largest number of DEGs, up to 9,041 (4,459 down-regulated genes, 4,582 up-regulated genes). A total of 644 common genes in the fresh leaves of three different ages of tea plants in the JP group were differentially expressed. A total of 8,971 DEGs were screened from the fresh leaf samples of tea plants in the YX group, of which the number of DEGs obtained in the tea-50 vs. tea-400 comparison combination was the largest with a total of 3,723 (1,722 up-regulated genes and 2,001 down-regulated genes). A total of 147 common genes were differentially expressed in the fresh leaves of three different tree ages in the YX group. The pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two groups, and that the metabolic pathways of common significant enrichment included flavonoid biosynthesis, phenylpropane biosynthesis, carbon metabolism, amino acid biosynthesis, and plant pathogen interaction. The metabolomics results showed that 72 and 117 different metabolites were screened from the JP and YX groups, respectively. Most of the different metabolites in the two groups were flavonoids, phenolic acids, amino acids, and their derivatives. Among them, the number of down-regulated flavonoids in older tea plants is generally higher than the number of up-regulated flavonoids. Moreover, according to the sensory evaluation results of dried tea of fresh leaves from tea plants of different ages, tea-1200 and tea-400 showed the highest sensory evaluation scores in their groups. With increase in plant age, the fragrance of the tea was more elegant, and it changed from a dense scent to a faint scent; the tea tasted sweet and its freshness increased, while the sense of astringency was weakened and the concentration declined. Therefore, the quality difference of tea of different tree ages is mainly related to secondary metabolic pathways such as the flavonoid biosynthesis pathway. With increase in tea age, a large number of gene expression in the flavonoid biosynthesis pathway is down-regulated, which reduces the content of bitter flavonoid substances in fresh leaves and makes tea soup more mellow.PMID:36937142 | PMC:PMC10019279 | DOI:10.3389/fpls.2022.910895

Front Mol Biosci. 2023 Mar 3;10:1100486. doi: 10.3389/fmolb.2023.1100486. eCollection 2023.ABSTRACTIntroduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.PMID:36936993 | PMC:PMC10022496 | DOI:10.3389/fmolb.2023.1100486