PubMed

Environ Sci Pollut Res Int. 2022 Nov 11. doi: 10.1007/s11356-022-23620-6. Online ahead of print.ABSTRACTCadmium (Cd) is a toxic non-essential heavy metal. Chronic low Cd exposure (CLCE) has been associated with distinct pathologies in many organ systems, including liver and kidney damage, osteoporosis, carcinogenicity, or reproductive toxicity. Currently, about 10% of the global population is at risk of CLCE. It is urgent to find robust and effective biomarkers for early diagnosis of Cd exposure and treatment. Metabolomics is a high-throughput method based on mass spectrometry to study the dynamic changes in a series of endogenous small molecular metabolites (typically < 1000 Da) of tissues, cells, or biofluids. It can reflect the rich and complex biochemical changes in the body after exposure to heavy metals, which may be useful in screening biomarkers to monitor exposure to environmental pollutants and/or predict disease risk. Therefore, this review focuses on the changes in metabolic profiles of humans and rodents under long-term Cd exposure from the perspective of metabolomics. Furthermore, the relationship between the disturbance of metabolic pathways and the toxic mechanism of Cd is discussed. All these information will facilitate the development of reliable metabolic biomarkers for early detection and diagnosis of Cd-related diseases.PMID:36367641 | DOI:10.1007/s11356-022-23620-6

Metabolomics. 2022 Nov 11;18(11):91. doi: 10.1007/s11306-022-01952-1.ABSTRACTINTRODUCTION: Advances in metabolomics have significantly improved cancer detection, diagnosis, treatment, and prognosis.OBJECTIVES: To investigate the relationship between metabolic tumor volume (MTV) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) and metabolomics data in patients with colorectal cancer (CRC).METHODS: The metabolome in tumor tissues was analyzed using capillary electrophoresis time-of-flight mass spectrometry in 33 patients with newly diagnosed CRC who underwent FDG PET/CT before treatment and had tumor tissue post-surgery. Based on the FDG PET data, MTV was calculated and was dichotomized according to the median value, and tumors were divided into low-MTV and high-MTV tumors. Metabolomics data were compared between the low-MTV and high-MTV tumors.RESULTS: The levels of most glycolysis-related metabolites were not different between low-MTV and high-MTV tumors. The level of component of the initial part of the tricarboxylic acid (TCA) cycle, citrate, was significantly lower in the high-MTV tumor than in the low-MTV tumor. The TCA intermediate succinate level was significantly higher in the high-MTV tumor than in the low-MTV tumor. In contrast, the TCA intermediate fumarate level was significantly lower in the high-MTV tumor than in the low-MTV tumor. The levels of many amino acids were significantly higher in the high-MTV tumor than in the low-MTV tumor.CONCLUSIONS: Although preliminary, these results suggest that tumors with high FDG metabolism in CRC may obtain more energy by using a reverse reaction of the TCA cycle and amino-acid metabolism. However, further research is required to clarify this relationship.PMID:36367606 | DOI:10.1007/s11306-022-01952-1

Biotechnol Prog. 2022 Nov 11:e3313. doi: 10.1002/btpr.3313. Online ahead of print.ABSTRACTTherapeutic protein productivity and glycosylation pattern highly rely on cell metabolism. Cell culture medium composition and feeding strategy are critical to regulate cell metabolism. In this study, the relationship between toxic metabolic inhibitors and their nutrient precursors was explored to identify the critical medium components toward cellular growth and generation of metabolic by-products. Generic CHO metabolic model was tailored and integrated with CHO fed-batch metabolomic data to obtain a cell line- and process-specific model. Flux balance analysis study was conducted on cytidine monophosphate (CMP), guanosine monophosphate (GMP) and n-acetylputrescine (NAP) - all of which were previously reported to generate from endogenous cellular metabolism - by mapping them to a compartmentalized carbon utilization network. Using this approach, the study projected high level of accumulation across inhibitory metabolites when comparing three industrially relevant fed-batch feeding conditions, from which the results were validated via a dose-dependent amino acids spiking study. Finally, a medium optimization design was employed to lower the amount of supplemented nutrients, of which improvements in critical process performance were realized at 40% increase in peak viable cell density (VCD), 15% increase in integral VCD (IVCD) and 37% increase in growth rate. Tight control of toxic by-products was also achieved, as the study measured decreased inhibitory metabolites accumulation across all conditions. This study successfully presented a digital twin approach to investigate the intertwined relationship between supplemented medium constituents and downstream toxic metabolites generated through host cell metabolism, further elucidating different control strategies capable of improving cellular phenotypes and regulating toxic inhibitors. This article is protected by copyright. All rights reserved.PMID:36367527 | DOI:10.1002/btpr.3313

Mitochondrion. 2022 Oct 29;67:59-64. doi: 10.1016/j.mito.2022.10.005. Online ahead of print.ABSTRACTThe low cerebral metabolic rate of oxygen despite the relatively preserved perfusion in Alzheimer's disease (AD) patients' medial temporal lobes suggest histotoxic hypoxia due to mitochondrial dysfunction that is independent of, but could precede, insulin resistance. Neuropathological, metabolomic, and preclinical evidence are consistent with the notion that this mitochondrial dysfunction may be contributed to by oxidative stress and DNA damage, leading to poly-(ADP-ribose)-polymerase-1 (PARP1) activation and consequent AMP accumulation, clogging of mitochondrial adenine nucleotide transporters (ANTs), matrix ADP deprivation, and ATP synthase inhibition. Complementary mechanisms may include mitochondrial-protein poly-ADP-ribosylation and mitochondrial-biogenesis suppression via PARPs outcompeting Sirtuin-1 (SIRT1) for nicotinamide-adenine-dinucleotide (NAD+).PMID:36367519 | DOI:10.1016/j.mito.2022.10.005

J Am Chem Soc. 2022 Nov 11. doi: 10.1021/jacs.2c08238. Online ahead of print.ABSTRACTThe mechanism of action (MoA) of a clickable fatty acid analogue 8-(2-cyclobuten-1-yl)octanoic acid (DA-CB) has been investigated for the first time. Proteomics, metabolomics, and lipidomics were combined with a network analysis to investigate the MoA of DA-CB against Mycobacterium smegmatis (Msm). The metabolomics results showed that DA-CB has a general MoA related to that of ethionamide (ETH), a mycolic acid inhibitor that targets enoyl-ACP reductase (InhA), but DA-CB likely inhibits a step downstream from InhA. Our combined multi-omics approach showed that DA-CB appears to disrupt the pathway leading to the biosynthesis of mycolic acids, an essential mycobacterial fatty acid for both Msm and Mycobacterium tuberculosis (Mtb). DA-CB decreased keto-meromycolic acid biosynthesis. This intermediate is essential in the formation of mature mycolic acid, which is a key component of the mycobacterial cell wall in a process that is catalyzed by the essential polyketide synthase Pks13 and the associated ligase FadD32. The multi-omics analysis revealed further collateral alterations in bacterial metabolism, including the overproduction of shorter carbon chain hydroxy fatty acids and branched chain fatty acids, alterations in pyrimidine metabolism, and a predominate downregulation of proteins involved in fatty acid biosynthesis. Overall, the results with DA-CB suggest the exploration of this and related compounds as a new class of tuberculosis (TB) therapeutics. Furthermore, the clickable nature of DA-CB may be leveraged to trace the cellular fate of the modified fatty acid or any derived metabolite or biosynthetic intermediate.PMID:36367461 | DOI:10.1021/jacs.2c08238

Mol Omics. 2022 Nov 11. doi: 10.1039/d2mo00254j. Online ahead of print.ABSTRACTThe ethyl acetate extract of Caesalpinia sappan L. is a traditional Chinese medicine extract commonly used in the treatment of atherosclerosis. However, the mechanism of its use in the treatment of AS is not yet clear, which seriously affects the wide-scale application of this drug. In this study, a combination of metabolomics and lipidomics was used to analyze cardiac tissue to obtain differential metabolites and differential lipid molecules, bioinformatic analysis was performed on the significantly different metabolites and subclass analysis, cluster analysis, and chain length and chain saturation analyses were performed on screened lipid molecules showing significant differences. A correlation network diagram of the screened differential metabolites and differential lipid molecules was constructed. Hematoxylin and eosin staining of thoracic aorta in rats confirmed its therapeutic effect. This study found that the ethyl acetate extract of C. sappan L. upregulates D-mannose through the lysosome pathway, enhances lysosomal function, mediates autophagy, and indirectly regulates the levels of lipid subtypes such as lysophosphatidylinositol and phosphatidylserine, thereby improving AS.PMID:36367369 | DOI:10.1039/d2mo00254j

Liver Int. 2022 Nov 11. doi: 10.1111/liv.15476. Online ahead of print.ABSTRACTPatients with cirrhosis exhibit features of circadian disruption. Hyperammonaemia has been suggested to impair both homeostatic and circadian sleep regulation. Here, we tested if hyperammonaemia directly disrupts circadian rhythm generation in the central pacemaker, the suprachiasmatic nuclei (SCN) of the hypothalamus. Wheel-running activity was recorded from mice fed with a hyperammonaemic or normal diet for ~35 days in a 12:12 light-dark (LD) cycle followed by ~15 days in constant darkness (DD). The expression of the clock protein PERIOD2 (PER2) was recorded from SCN explants before, during and after ammonia exposure, ± glutamate receptor antagonists. In LD, hyperammonaemic mice advanced their daily activity onset time by ~1 hour (16.8±0.3 vs. 18.1±0.04 h, p=0.009) and decreased their total activity, concentrating it during the first half of the night. In DD, hyperammonaemia reduced the amplitude of daily activity (551.5±27.7 vs. 724.9±59 counts, p=0.007), with no changes in circadian period. Ammonia (≥ 0.01 mM) rapidly and significantly reduced PER2 amplitude, and slightly increased circadian period. The decrease in PER2 amplitude correlated with decreased synchrony among circadian cells in the SCN and increased extracellular glutamate, which was rescued by AMPA glutamate receptor antagonists. These data suggest that hyperammonaemia affects circadian regulation of rest-activity behaviour by increasing extracellular glutamate in the SCN.PMID:36367321 | DOI:10.1111/liv.15476

Mol Nutr Food Res. 2022 Nov 11:e2200351. doi: 10.1002/mnfr.202200351. Online ahead of print.ABSTRACTSCOPE: The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non-communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant.METHODS AND RESULTS: Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha-linolenic acid (ALA, 5 percent of energy (E-%)) or a high linoleic acid (LA, 10 E-%) diet during an 8-week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA-derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high-LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high-ALA diet increased the concentration of plasma ALA and its cytochrome P450-derived epoxides and dihydroxys, and cyclooxygenase-derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono- and dihydroxys increased only in TT genotype carriers.CONCLUSIONS: These findings suggest the potential for genotype-based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.PMID:36367234 | DOI:10.1002/mnfr.202200351

Mol Med Rep. 2023 Jan;27(1):9. doi: 10.3892/mmr.2022.12896. Epub 2022 Nov 11.ABSTRACT3,4‑Dihydroxybenzaldehyde (DBD), one of the active components of Gastrodia elata, has a cerebral protective effect and can effectively combat cerebral ischemia/reperfusion (I/R) injury in rats. However, the metabolite profiles and underlying mechanisms associated with DBD remain unclear. To explore the level of energy metabolism and pharmacological targets in brain tissue following DBD treatment of stroke. The right middle cerebral artery of the rats was occluded for 2 h and reperfused for 24 h to simulate brain I/R injury. Pharmacological results showed that DBD reduced cerebral infarct volume, improved neurological function and increased adenosine triphosphate (ATP) content. Mitochondria are the primary sites for ATP generation and cellular energy supply and decreasing mitochondrial dysfunction can alleviate the energy expenditure of ischemic stroke. Through further experiments, it was found that mitochondrial damage was recovered following DBD treatment, which was manifested by the improvement of mitochondrial morphology under an electron microscope and the reduction of oxidative stress damage. The metabolomics of middle cerebral artery occlusion/reperfusion (MCAO/R) rat brain tissue was studied by the liquid chromatography‑tandem mass spectrometry metabolomics method. Significantly different metabolites were screened and the pathways involved included amino sugar and nucleotide sugar metabolism and pentose phosphate pathway. Finally, the present study performed targeted metabolic profiling and validated potential therapeutic targets. Uridine diphosphate N‑acetylglucosamine (UDP‑GlcNAc) levels were decreased in the MCAO/R group but significantly increased in the DBD group. TdT‑mediated dUTP nick end labeling (TUNEL) staining, hematoxylin and eosin staining and western blotting showed that brain cell apoptosis was inhibited and neuronal morphology improved. Among them, the regulatory enzyme O‑GlcNAc transferase (OGT) of UDP‑GlcNAc appeared to be significantly increased and neuronal apoptosis was inhibited following DBD treatment, which was verified by western blotting. Therefore, by analyzing mitochondrial dysfunction following I/R and the characterization of potential markers in mitochondrial energy metabolism, it was shown that OGT could inhibit neuronal apoptosis as a potential therapeutic target for brain I/R injury.PMID:36367170 | DOI:10.3892/mmr.2022.12896

J Water Health. 2022 Feb;20(2):314-328. doi: 10.2166/wh.2022.218.ABSTRACTWastewater-based epidemiology (WBE) is an effective approach for tracking information on spatial distribution and temporal trends of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level. Herein, the development, implementation, and operation of the wastewater monitoring program serving Tyrol - a federal province of Austria - are described. The development of this program was initiated by Tyrolean health authorities at the end of the first phase of the Coronavirus disease 2019 (COVID-19) pandemic (May 2020). In close co-operation with the water sector and academic institutions, efficient and effective workflows and processes for wastewater surveillance were established. The monitoring program went into operation in November 2020. By the end of July 2021, a total of 5,270 wastewater influent samples collected at 43 sites were analyzed. The monitoring program provided valuable insights into the development of the pandemic situation in Tyrol and fulfilled several tasks that are of importance in different phases of the pandemic. It represented an early-warning system, provided independent confirmation of temporal trends in COVID-19 prevalence, enabled the assessment of the effectiveness of measures, alerted about bursts of disease activity, and provided evidence for the absence of COVID-19. These findings underline the importance of establishing national wastewater monitoring programs as a complementary source of information for efficient and effective pandemic management.PMID:36366989 | DOI:10.2166/wh.2022.218

Vaccines (Basel). 2022 Nov 9;10(11):1890. doi: 10.3390/vaccines10111890.ABSTRACTBACKGROUND: Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination.METHODS: 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2-4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis.RESULTS: The level of anti-RBD antibody 14-28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine.CONCLUSION: We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.PMID:36366398 | DOI:10.3390/vaccines10111890

Sensors (Basel). 2022 Nov 4;22(21):8496. doi: 10.3390/s22218496.ABSTRACTCurrently, antibiotics are often prescribed to children without reason due to the inability to quickly establish the presence of a bacterial etiology of the disease. One way to obtain additional diagnostic information quickly is to study the volatile metabolome of biosamples using arrays of sensors. The goal of this work was to assess the possibility of using an array of chemical sensors with various sensitive coatings to determine the presence of a bacterial infection in children by analyzing the equilibrium gas phase (EGP) of urine samples. The EGP of 90 urine samples from children with and without a bacterial infection (urinary tract infection, soft tissue infection) was studied on the "MAG-8" device with seven piezoelectric sensors in a hospital. General urine analysis with sediment microscopy was performed using a Uriscan Pro analyzer and using an Olympus CX31 microscope. After surgical removal of the source of inflammation, the microbiological studies of the biomaterial were performed to determine the presence and type of the pathogen. The most informative output data of an array of sensors have been established for diagnosing bacterial pathology. Regression models were built to predict the presence of a bacterial infection in children with an error of no more than 15%. An indicator of infection is proposed to predict the presence of a bacterial infection in children with a high sensitivity of 96%.PMID:36366200 | DOI:10.3390/s22218496

Plants (Basel). 2022 Nov 7;11(21):2998. doi: 10.3390/plants11212998.ABSTRACTSilicon (Si) is a beneficial element for the growth of various crops, but its effect on plant metabolism is still not completely elucidated. Even if Si is not classified as an essential element for plants, the literature has reported its beneficial effects in a variety of species. In this work, the influence of Si foliar application on berry composition was evaluated on four grapevine cultivars. The berries of Teroldego and Oseleta (red grapes) and Garganega and Chardonnay (white grapes) were analyzed after foliar application of silicon by comparing the treated and control groups. A targeted metabolomic approach was used that focused on secondary metabolites, amino acids, sugars, and tartaric acid. Measurements were performed using liquid chromatography coupled with a diode array detector and mass spectrometry (LC-DAD-MSn), a LC-evaporative light scattering detector (ELDS), and LC-MS/MS methods specific for the analysis of each class of constituents. After the data collection, multivariate models, PCA, PLS-DA, OPLS-DA, were elaborated to evaluate the effect of Si application in the treated vs. control samples. Results were different for each grape cultivar. A significant increase in anthocyanins was observed in the Oseleta cultivar, with 0.48 mg g-1 FW in the untreated samples vs. 1.25 mg g-1 FW in the Si-treated samples. In Garganega, Si treatment was correlated with increased proline levels. In Chardonnay, the Si application was related to decreased tartaric acid. The results of this work show for the first time that Si induces cultivar specific changes in the berry composition in plants cultivated without an evident abiotic or biotic stress.PMID:36365453 | DOI:10.3390/plants11212998

Plants (Basel). 2022 Oct 31;11(21):2931. doi: 10.3390/plants11212931.ABSTRACTCadmium is one of the most toxic heavy metal pollutants, and its accumulation in the soil is harmful to agriculture. Plants have a higher cadmium tolerance than animals, and some species can be used for phytoremediation. Flax (Linum usitatissimum L.) can accumulate high amounts of cadmium, but the molecular mechanism behind its tolerance is unknown. Here, we employed four genotypes representing two fiber cultivars, an oilseed breeding line, and a transgenic line overexpressing the metallothionein domain for improved cadmium tolerance. We analyzed the proteome of suspensions and the proteome and metabolome of seedling roots in response to cadmium. We identified more than 1400 differentially abundant proteins representing putative mechanisms in cadmium tolerance, including metal-binding proteins and transporters, enzymes of flavonoid, jasmonate, polyamine, glutathione metabolism, and HSP70 proteins. Our data indicated the role of the phytohormone cytokinin in the observed responses. The metabolome profiling found that pipecolinic acid could be a part of the cadmium accumulation mechanism, and the observed accumulation of putrescine, coumaric acid, cinnamic acid, and coutaric acid confirmed the role of polyamines and flavonoids in tolerance to cadmium. In conclusion, our data provide new insight into cadmium tolerance and prospective targets for improving cadmium tolerance in other plants.PMID:36365383 | DOI:10.3390/plants11212931

Plants (Basel). 2022 Oct 27;11(21):2861. doi: 10.3390/plants11212861.ABSTRACTThe extensive use of Embelia ribes Burm. f. (Embelia) in tribal medicine proclaimed global attention as a promising candidate in complementary and alternative medicine. The knowledge of chemical blends is a prerequisite for the selection of raw materials for herbal medicine formulations; however, the influence of geographical distance and genetic diversity on the metabolome of Embelia fruits is unknown. Therefore, we collected Embelia fruits from four locations across the Western Ghats of India and analyzed the metabolic profile and genotypic diversity of Embelia fruits by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inter simple sequence repeats (ISSR), respectively. LC-MS/MS analysis yielded 583 compounds; however, the trimmed data resulted in 149 compounds. Further, MS/MS analysis identified 36 compounds, among which we reported 30 compounds for the first time from Embelia. These compounds belong to 11 compound classes that suggest location-specific chemical blends of Embelia fruits. Multivariate analysis showed 94% compound diversity across the accessions. ISSR analysis suggests 95% polymorphism across the accessions. A significant positive correlation (80%) between metabolomics and genotypic data matrices validates the genotype's influence in tuning Embelia's metabolic profiles. We conclude that the chemical profiles of Embelia are location-specific, which can be explored for the selection of herbal trade sustainably.PMID:36365314 | DOI:10.3390/plants11212861

Plants (Basel). 2022 Oct 26;11(21):2859. doi: 10.3390/plants11212859.ABSTRACTWater avens (Geum rivale L.) is a common Rosaceae plant widely spread in Europe and North America. It is rich in biologically active natural products, some of which are promising as prospective pharmaceuticals. The extracts of water avens are well known for their triterpenoid metabolites and associated anti-inflammatory, antimicrobial and antioxidant activities. However, the polyphenolic profiles of G. rivale L. are still awaiting complete characterization. Accordingly, the contribution of its individual components to the antioxidant, antibacterial and neuroprotective activity of the extracts is still unknown. As this plant can be available on an industrial scale, a better knowledge of its properly-relevant constituents might give access to new highly-efficient pharmaceutical substances and functional products. Therefore, herein we comprehensively characterize the secondary metabolome of G. rivale by ESI-HR-MS, ESI-HR-MSn and NMR spectroscopy with a special emphasis on the polyphenolic composition of its aerial parts. Furthermore, a multilateral evaluation of the antioxidant, neuroprotective and antibacterial properties of the aqueous and ethyl acetate fractions of the total aqueous alcoholic extract as well as individual isolated polyphenols was accomplished. Altogether four phenolic acid derivatives (trigalloyl hexose, caffeoyl-hexoside malate, ellagic acid and ellagic acid pentoside), six flavonoids (three quercetin derivatives, kaempferol and three its derivatives and two isorhamnetin derivatives) and four tannins (HHDP-hexoside, proantocyanidin dimer, pedunculagin I and galloyl-bis-HHDP-hexose) were identified in this plant for the first time. The obtained aqueous and ethyl acetate fractions of the total extract as well as the isolated individual compounds showed pronounced antioxidant activity. In addition, a pronounced antibacterial activity against several strains was proved for the studied fractions (for ethyl acetate fraction the highest activity against E. coli АТСС 25922 and S. aureus strains ATCC 27853 and SG-511 (MIC 15.6 μg/mL) was observed; for aqueous fraction-against Staphylococcus aureus SG-511 (MIC 31.2 μg/mL)). However, the anti-neurodegenerative (neuroprotective) properties could not be found with the employed methods. However, the antibacterial activity of the fractions could not be associated with any of the isolated individual major phenolics (excepting 3-O-methylellagic acid). Thus, the aerial parts of water avens represent a promising source of polyphenolic compounds with antioxidant activity and therefrom derived human health benefits, although the single constituents isolated so far lack a dominant selectively bioactive constituent in the bioassays performed.PMID:36365312 | DOI:10.3390/plants11212859

Plants (Basel). 2022 Oct 26;11(21):2849. doi: 10.3390/plants11212849.ABSTRACTPine wood nematode, Bursaphelenchus xylophilus, is a worldwide pest of pine trees, spreading at an alarming rate and with great ecological adaptability. In the process of causing disease, the nematode causes metabolic disorders and changes in the endophytic microbial community of the pine tree. However, the changes at the pine nidus during early nematode invasion have not been well studied, especially the differential metabolites, in Pinus massoniana, the main host of B. xylophilus in China. In this study, we analyzed the endophytic bacterial and fungal communities associated with healthy and B. xylophilus-caused wilted pine trees. The results show that 1333 bacterial OTUs and 502 fungal OTUs were annotated from P. massoniana stem samples. The abundance of bacterial communities in pine trees varies more following infection by B. xylophilus, but the abundance changes of fungal communities are less visible. There were significant differences in endophytic microbial diversity between wilted and healthy P. massoniana. In wilted pine trees, Actinobacteria and Bacteroidia were differential indicators of bacterial communities, whereas, in healthy pine trees, Rhizobiales in the Proteobacteria phylum were the major markers of bacterial communities. Meanwhile, the differential markers of fungal communities in healthy pines are Malasseziales, Tremellales, Sordariales, and Fusarium, whereas Pleosporaceae is the key marker of fungal communities in wilted pines. Our study examines the effect of changes in the endophytic microbial community on the health of pine trees that may be caused by B. xylophilus infection. In parallel, a non-targeted metabolomic study based on liquid mass spectrometry (LC-MS) technology was conducted on pine trees inoculated with pine nematodes and healthy pine trees with a view to identifying key compounds affecting early pine lesions. Ultimately, 307 distinctly different metabolites were identified. Among them, the riboflavin metabolic pathway in pine trees may play a key role in the early pathogenesis of pine wood nematode disease.PMID:36365304 | DOI:10.3390/plants11212849

Plants (Basel). 2022 Oct 25;11(21):2838. doi: 10.3390/plants11212838.ABSTRACTThe head milled rice rate (HMRR) is the most important trait of milling quality, which affects the final yield and quality of rice. However, few genes related to HMRR have been identified and the regulatory mechanism of HMRR remains elusive. In this study, we performed a comparative analysis integrating the transcriptome sequencing of developing seeds at the grain-filling stage and a metabolome analysis of brown rice between two groups of accessions with contrasting performances in HMRR. A total of 768 differentially expressed genes (DEGs) were identified between the transcriptome profiles of low-HMRR and high-HMRR accessions. In comparison to the high-HMRR accessions, 655 DEGs were up-regulated in the low-HMRR accessions, which was 4.79 folds higher than the number of down-regulated genes. These up-regulated DEGs were enriched in various metabolic and biosynthetic processes, oxidation reduction, phosphorylation, ion transport and ATP-related processes. However, the 113 down-regulated DEGs in the low-HMRR accessions were concentrated in carbohydrate metabolic processes, cell-death-related processes and defense response. Among the 30 differential metabolites, 20 and 10 metabolites were down-/up-regulated, respectively, in the accessions with low HMRR. In addition, 10 differential metabolites, including five metabolites of the shikimate pathway and five metabolites of the pyruvate pathway, were integrated into two separate pathways, starting from sucrose. Our global analysis of HMRR provides an invaluable resource for a better understanding of the molecular mechanism underlying the genetic regulation of HMRR.PMID:36365290 | DOI:10.3390/plants11212838

Pathogens. 2022 Oct 29;11(11):1257. doi: 10.3390/pathogens11111257.ABSTRACTSalmonella enterica serovar Typhimurium incites salmonellosis in many different species including chickens and human beings. Acute salmonellosis was studied in neonatal broiler chicks by orally inoculating 2-day-old chicks with S. Typhimurium DT104. The temporal impact of disease (1, 2, and 4 days post-inoculation) on the structure and function of the enteric microbiota, on the bird's immune response in the ileum, cecum, and colon, and on the metabolome of digesta, breast muscle, liver, serum, and hippocampus were examined. Substantive histopathologic changes were observed in the small and large intestine, including the colon of chicks inoculated with S. Typhimurium, and increased in magnitude over the experimental time period. A variety of inflammatory genes (IFNγ, IL8, IL10, INOS, MIP1β, TGFβ2, TLR4, and TLR15) were temporally regulated. In addition, the metabolome of ileal digesta, breast muscle, liver, serum, and hippocampus was temporally altered in infected chicks. Although the structure of bacterial communities in digesta was not affected by S. Typhimurium infection, metabolomic analysis indicated that the function of the microbiota was changed. Collectively, the study findings demonstrate that infection of neonatal chicks by S. Typhimurium imparts a temporal and systemic impact on the host, affecting the immune system, the metabolome, and the function of the enteric microbiota.PMID:36365008 | DOI:10.3390/pathogens11111257

Pathogens. 2022 Oct 27;11(11):1244. doi: 10.3390/pathogens11111244.ABSTRACTThe microbial ecosystem of the female urogenital tract is composed of many niche microenvironments across multiple organ systems in the urinary and reproductive tract. It is complex and contains a variety of bacteria, archaea, viruses, yeast, and protozoa-Many of which are still unidentified or whose functionality is unknown. Unlike the gut microbiome, whose composition is relatively stable in the absence of external perturbations, the urogenital microbiome is constantly shifting in response to biological cycles such as hormonal fluctuations during menstruation. Microbial composition differs between women but the dominance of some microbial families, such as Lactobacillaceae and other lactic acid-producing bacteria, are shared. Research suggests that it is difficult to define a universal healthy urogenital microbiome and consequently map a path to recovery from disease due to dysbiosis. Due to its temporal shifts, the female urogenital microbiome offers a unique opportunity to examine the biological mechanisms that work to restore a microbiome to its baseline. Common functional disorders in women's health are often difficult to diagnose and treat, are prone to recurrence, and can lead to subfertility or infertility. Knowledge of the interconnected microorganism communities along the continuum of the female reproductive tract could revolutionize the quality of women's healthcare.PMID:36364994 | DOI:10.3390/pathogens11111244