PubMed

Microb Pathog. 2023 Nov 11:106445. doi: 10.1016/j.micpath.2023.106445. Online ahead of print.ABSTRACTFoliar fungal blast and bacterial leaf blight have significant impacts on rice production, and their management through host resistance and agrochemicals has proven inadequate. To achieve their sustainable management, innovative approaches like leveraging the foliar microbiome, which collaborates with plants and competes against pathogens, are essential. In our study, we isolated three Pantoea bacterial strains (P. agglomerans Os-Ep-PPA-1b, P. vagans Os-Ep-PPA-3b, and P. deleyi Os-Ep-VPA-9a) from the rice phylloplane. These isolates exhibited antimicrobial action through their metabolome and volatilome, while also promoting rice growth.Our analysis, using Gas Chromatography-Mass Spectrometry (GC-MS), revealed the presence of various antimicrobial compounds such as esters and fatty acids produced by these Pantoea isolates. Inoculating rice seedlings with P. agglomerans and P. vagans led to increased root and shoot growth. Additionally, bacterized seedlings displayed enhanced immunocompetence, as evidenced by upregulated expressions of defense genes (OsEDS1, OsFLS2, OsPDF2.2, ACO4, ICS OsPR1a, OsNPR1.3, OsPAD4, OsCERK1.1), along with heightened activities of defense enzymes like Polyphenol Oxidase and Peroxidase. These plants also exhibited elevated levels of total phenols.In field trials, the Pantoea isolates contributed to improved plant growth, exemplified by increased flag-leaf length, panicle number, and grains per panicle, while simultaneously reducing the incidence of chaffy grains. Hypersensitivity assays performed on a model plant, tobacco, confirmed the non-pathogenic nature of these Pantoea isolates.In summary, our study underscores the potential of Pantoea bacteria in combatting rice foliar diseases. Coupled with their remarkable growth-promoting and biostimulant capabilities, these findings position Pantoea as promising agents for enhancing rice cultivation.PMID:37956936 | DOI:10.1016/j.micpath.2023.106445

Biochem Pharmacol. 2023 Nov 11:115922. doi: 10.1016/j.bcp.2023.115922. Online ahead of print.ABSTRACTInfantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.PMID:37956892 | DOI:10.1016/j.bcp.2023.115922

Neurobiol Dis. 2023 Nov 11:106348. doi: 10.1016/j.nbd.2023.106348. Online ahead of print.ABSTRACT3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported that the gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the stress resilience effects of MDMA in mice subjected to chronic restrain stress (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like behavior and reduced expression of synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in CRS-exposed mice. Analysis of gut microbiome revealed alterations in four measures of α-diversity between the sham + MDMA + CRS group and the SDV + MDMA + CRS group. Moreover, specific microbes differed between the vehicle + CRS group and the MDMA + CRS group, and further differences in microbial composition were observed among all four groups. Untargeted metabolomics analysis showed that SDV prevented the increase in plasma levels of three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] observed in the sham + MDMA + CRS group. Interestingly, positive correlations were found between the plasma levels of two of these compounds and the abundance of several microbes across all groups. In conclusion, our data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the stress resilience of MDMA.PMID:37956855 | DOI:10.1016/j.nbd.2023.106348

Sci Total Environ. 2023 Nov 11:168422. doi: 10.1016/j.scitotenv.2023.168422. Online ahead of print.ABSTRACTSeagrass ecosystems provide crucial ecosystem services for coastal environments and were shown to reduce the abundance of pathogens linked to infections in humans and marine organisms. Among potential drivers, seagrass phenolics released into seawater have been linked to pathogen suppression, but the potential involvement of the seagrass microbiome has not been investigated. We hypothesized that the microbiome of the eelgrass Zostera marina, especially the leaf epiphytes that are at direct interface between the seagrass host and surrounding seawater, inhibit waterborne pathogens thereby contributing to their removal. Using a culture-dependent approach, we isolated 88 bacteria and fungi associated with the surfaces and inner tissues of the eelgrass leaves (healthy and decaying) and the roots. We assessed the antibiotic activity of microbial extracts against a large panel of common aquatic, human (fecal) and plant pathogens, and mined the metabolome of the most active extracts. The healthy leaf epibiotic bacteria, particularly Streptomyces sp. strain 131, displayed broad-spectrum antibiotic activity superior to some control drugs. Gram-negative bacteria abundant on healthy leaf surfaces, and few endosphere-associated bacteria and fungi also displayed remarkable activities. UPLC-MS/MS-based untargeted metabolomics analyses showed rich specialized metabolite repertoires with low annotation rates, indicating the presence of many undescribed antimicrobials in the extracts. This study contributes to our understanding on microbial and chemical ecology of seagrasses, implying potential involvement of the seagrass microbiome in suppression of pathogens in seawater. Such effect is beneficial for the health of ocean and human, especially in the context of climate change that is expected to exacerbate all infectious diseases. It may also assist future seagrass conservation and management strategies.PMID:37956849 | DOI:10.1016/j.scitotenv.2023.168422

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Nov 11:110896. doi: 10.1016/j.pnpbp.2023.110896. Online ahead of print.ABSTRACTAcid sphingomyelinase deficiency is a neurodegenerative lysosomal storage disorder caused by mutations in the sphingomyelin-degrading enzyme acid sphingomyelinase (ASM) gene. Upregulated neuroinflammation has been well-characterized in an ASM knockout mouse model of acid sphingomyelinase deficiency disease, but lipid mediator pathways involved in 'mediating' inflammation and inflammation-resolution have yet to be characterized. In this study, we 1) measured free (bioactive) and esterified (inactive) lipid mediators involved in inflammation and inflammation resolution in cerebellum and neuronal cultures of ASM knockout (ASMko) mice and wildtype (WT) controls, and 2) tested the incorporation of labeled pro-resolving free d11-14(15)-epoxyeicosatrienoic acid into culture neurons from ASMko and WT mice. We found elevated concentrations of esterified pro-resolving lipid mediators and hydroxyeicosatrienoic acids typically destined for pro-resolving lipid mediator synthesis (e.g. lipoxins) in the cerebellum and neurons of ASMko mice compared to controls. Free d11-14(15)-epoxyeicosatrienoic acid incorporation into neurons of ASMko mice was significantly elevated compared to WT. Our findings show evidence of increased inactivation of free pro-resolving lipid mediators through esterification, suggesting impaired resolution as a new pathway underlying ASM deficiency pathogenesis.PMID:37956788 | DOI:10.1016/j.pnpbp.2023.110896

Toxicology. 2023 Nov 11:153672. doi: 10.1016/j.tox.2023.153672. Online ahead of print.ABSTRACTHuman lifetime exposure to arsenic through drinking water, food supply or industrial pollution leads to its accumulation in many organs such as liver, kidneys, lungs or pancreas but also adipose tissue. Recently, population-based studies revealed the association between arsenic exposure and the development of metabolic diseases such as obesity and type 2 diabetes. To shed light on the molecular bases of such association, we determined the concentration that inhibited 17% of cell viability and investigated the effects of arsenic acute exposure on adipose-derived human mesenchymal stem cells differentiated in vitro into mature adipocytes and treated with sodium arsenite (NaAsO2, 10nM to 10µM). Untargeted metabolomics and gene expression analyses revealed a strong dose-dependent inhibition of lipogenesis and lipolysis induction, reducing the cellular ability to store lipids. These dysregulations were emphasized by the inhibition of the cellular response to insulin, as shown by the perturbation of several genes and metabolites involved in the mentioned biological pathways. Our study highlighted the activation of an adaptive oxidative stress response with the strong induction of metallothioneins and increased glutathione levels in response to arsenic accumulation that could exacerbate the decreased insulin sensitivity of the adipocytes. Arsenic exposure strongly affected the expression of arsenic transporters, responsible for arsenic influx and efflux, and induced a pro-inflammatory state in adipocytes by enhancing the expression of the inflammatory interleukin 6 (IL6). Collectively, our data showed that an acute exposure to low levels of arsenic concentrations alters key adipocyte functions, highlighting its contribution to the development of insulin resistance and the pathogenesis of metabolic disorders.PMID:37956786 | DOI:10.1016/j.tox.2023.153672

Food Chem. 2023 Nov 7;437(Pt 2):137934. doi: 10.1016/j.foodchem.2023.137934. Online ahead of print.ABSTRACTSunki is an unsalted lactic fermented pickle made from red turnip leaves in the Kiso district, Japan. Accidental insufficient decrease in pH during sunki fermentation seriously reduces the product quality. To obtain insights into how the insufficient decrease occurs, we comprehensively analyzed differences in the microbiological and chemical properties of sunki made from three different turnip harvests and found a significant difference in their final pH. Microbiota and metabolome analyses revealed that the insufficient pH decrease showed strong relationships with the chemical composition (low lactic acid and high ammonia levels) and bacterial community structure (low Lactobacillus and high Limosilactobacillus). In vitro sunki fermentation experiments demonstrated that accumulated ammonia was associated with a decrease in glutamine and an increase in glutamic acid. Limosilactobacillus reuteri, a species of lactic acid bacteria possessing heterolactic metabolism, was suggested to be mainly responsible for insufficient decrease in pH related to accumulated ammonia during sunki fermentation.PMID:37956596 | DOI:10.1016/j.foodchem.2023.137934

Neoplasia. 2023 Nov 11;46:100949. doi: 10.1016/j.neo.2023.100949. Online ahead of print.ABSTRACTTriple negative breast cancer (TNBC) is an aggressive malignancy for which chemotherapy remains the standard treatment. However, between 3 and 5 years after chemotherapy, about half patients will relapse and it is essential to identify vulnerabilities of cancer cells surviving neoadujuvant therapy. In this study, we established persistent TNBC cell models after treating MDA-MB-231 and SUM159-PT TNBC cell lines with epirubicin and cyclophosphamide, and then with paclitaxel, for a total of 18 weeks. The resulting chemo-persistent cell lines were more proliferative, both in vitro and in xenografted mice. Interestingly, MDA-MB-231 persistent cells became less sensitive to chemotherapeutic drugs, whereas SUM159-PT persistent cells kept similar sensitivity compared to control cells. The reduced sensitivity to chemotherapy in MDA-MB-231 persistent cells was found to be associated with an increased oxidative phosphorylation (OXPHOS) and modified levels of tricarboxylic acid cycle (TCA) intermediates. Integration of data from proteomics and metabolomics demonstrated TCA cycle among the most upregulated pathways in MDA-MB-231 persistent cells. The absence of glucose and pyruvate impeded OXPHOS in persistent cells, while the absence of glutamine did not. In contrast, OXPHOS was not modified in control cells independently of TCA substrates, indicating that MDA-MB-231 persistent cells evolved towards a more pyruvate dependent profile. Finally, the inhibition of pyruvate entry into mitochondria with UK-5099 reduced OXPHOS and re-sensitized persistent cells to therapeutic agents. Together, these findings suggest that targeting mitochondrial pyruvate metabolism may help to overcome mitochondrial adaptation of chemo-persistent TNBC.PMID:37956532 | DOI:10.1016/j.neo.2023.100949

Hepatol Int. 2023 Nov 13. doi: 10.1007/s12072-023-10604-y. Online ahead of print.ABSTRACTIntrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease. It is characterized by pruritus, abnormal liver function and elevated total bile acid (TBA) levels, increasing the risk of maternal and fetal adverse outcomes. Its etiology remains poorly elucidated. Over the years, various omics techniques, including metabolomics, microbiome, genomics, etc., have emerged with the advancement of bioinformatics, providing a new direction for exploring the pathogenesis, diagnosis and treatment of ICP. In this review, we first summarize the role of bile acids and related components in the pathogenesis of ICP and then further illustrate the results of omics studies.PMID:37957532 | DOI:10.1007/s12072-023-10604-y

Commun Biol. 2023 Nov 13;6(1):1155. doi: 10.1038/s42003-023-05543-1.ABSTRACTBeyond motor neuron degeneration, homozygous mutations in the survival motor neuron 1 (SMN1) gene cause multiorgan and metabolic defects in patients with spinal muscular atrophy (SMA). However, the precise biochemical features of these alterations and the age of onset in the brain and peripheral organs remain unclear. Using untargeted NMR-based metabolomics in SMA mice, we identify cerebral and hepatic abnormalities related to energy homeostasis pathways and amino acid metabolism, emerging already at postnatal day 3 (P3) in the liver. Through HPLC, we find that SMN deficiency induces a drop in cerebral norepinephrine levels in overt symptomatic SMA mice at P11, affecting the mRNA and protein expression of key genes regulating monoamine metabolism, including aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DβH) and monoamine oxidase A (MAO-A). In support of the translational value of our preclinical observations, we also discovered that SMN upregulation increases cerebrospinal fluid norepinephrine concentration in Nusinersen-treated SMA1 patients. Our findings highlight a previously unrecognized harmful influence of low SMN levels on the expression of critical enzymes involved in monoamine metabolism, suggesting that SMN-inducing therapies may modulate catecholamine neurotransmission. These results may also be relevant for setting therapeutic approaches to counteract peripheral metabolic defects in SMA.PMID:37957344 | DOI:10.1038/s42003-023-05543-1

J Microbiol Biotechnol. 2023 Sep 22;34(1):1-13. doi: 10.4014/jmb.2305.05016. Online ahead of print.ABSTRACTTeat cleaning pre- and post-milking is important for the overall health and hygiene of dairy cows. The purpose of this research was to evaluate the effectiveness of a teat detergents based on lactic acid bacteria according to changes in somatic cell count and cow-milk metabolites. Sixty-nine raw milk samples were collected from 11 Holstein-Friesian cows in China during 12 days of teat cleaning. An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry-based untargeted metabolomic approach was applied to detect metabolomic differences after treatment with lactic acid bacteria and chemical teat detergents in cows with subclinical mastitis. The results suggest that the lactobacilli-based teat detergents could reduce somatic cell count and improve microhabitat of cow teat apex by adjusting the composition of metabolites. Furthermore, the somatic cell count could be decreased significantly within 10 days following the cleaning protocol. Lactic acid bacteria have the potential to be applied as a substitution to teat chemical detergents before and after milking for maintenance of healthy teats and breasts. Further, larger scale validation work is required to support the findings of the current study.PMID:37957117 | DOI:10.4014/jmb.2305.05016

Plant Cell. 2023 Nov 13:koad286. doi: 10.1093/plcell/koad286. Online ahead of print.ABSTRACTThe importance of metabolite modification and species-specific metabolic pathways has long been recognized. However, linking the chemical structure of metabolites to gene function in order to explore the genetic and biochemical basis of metabolism has not yet been reported in wheat (Triticum aestivum). Here, we profiled metabolic fragment enrichment in wheat leaves and consequently applied chemical-tag-based semi-annotated metabolomics in a genome-wide association study in accessions of wheat. The studies revealed that all 1,483 quantified metabolites have at least one known functional group whose modification is tailored in an enzyme-catalyzed manner and eventually allows efficient candidate gene mining. A Triticeae crop-specific flavonoid pathway and its underlying metabolic gene cluster were elucidated in further functional studies. Additionally, upon overexpressing the major effect gene of the cluster TraesCS2B01G460000 (TaOMT24), the pathway was reconstructed in rice (Oryza sativa), which lacks this pathway. The reported workflow represents an efficient and unbiased approach for gene mining using forward genetics in hexaploid wheat. The resultant candidate gene list contains vast molecular resources for decoding the genetic architecture of complex traits and identifying valuable breeding targets, and will ultimately aid in achieving wheat crop improvement.PMID:37956052 | DOI:10.1093/plcell/koad286

J Clin Endocrinol Metab. 2023 Nov 13:dgad663. doi: 10.1210/clinem/dgad663. Online ahead of print.ABSTRACTCONTEXT: Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a non-invasive manner. We have recently demonstrated that [18F]FDG-PET can be used to analyze renal glucose uptake rates (GU), and that the renal cortex is an insulin sensitive tissue.OBJECTIVE: To confirm that renal GU is decreased in people with obesity, and to test whether circulating metabolites are related to renal GU.DESIGN, SETTING AND PARTICIPANTS: 18 people with obesity and 18 non-obese controls were studied with [18F]FDG-PET during insulin clamp. Renal scans were obtained ∼60 min after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton NMR metabolomics.RESULTS: Cortical GU was higher in healthy non-obese controls compared to people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], p = 0.004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, p = 0.01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, p = 0.009), acetoacetate (r = -0.48, p = 0.008), citrate (r = -0.44, p = 0.01) and free fatty acids (FFA) (r = -0.68, p < 0.0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters.CONCLUSIONS: These data confirm differences in renal cortical GU between people with obesity and healthy non-obese controls. Moreover, the negative correlations between renal cortex GU and FFA, ketone bodies and citrate are suggestive of substrate competition in the renal cortex.PMID:37955868 | DOI:10.1210/clinem/dgad663

Environ Sci Technol. 2023 Nov 13. doi: 10.1021/acs.est.3c05228. Online ahead of print.ABSTRACTDecades of research have established the toxicity of soot particles resulting from incomplete combustion. However, the unique chemical compounds responsible for adverse health effects have remained uncertain. This study utilized mass spectrometry to analyze the chemical composition of extracted soot organics at three oxidation states, aiming to establish quantitative relationships between potentially toxic chemicals and their impact on human alveolar basal epithelial cells (A549) through metabolomics-based evaluations. Targeted analysis using MS/MS indicated that particles with a medium oxidation state contained the highest total abundance of compounds, particularly oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) composed of fused benzene rings and unsaturated carbonyls, which may cause oxidative stress, characterized by the upregulation of three specific metabolites. Further investigation focused on three specific OPAH standards: 1,4-naphthoquinone, 9-fluorenone, and anthranone. Pathway analysis indicated that exposure to these compounds affected transcriptional functions, the tricarboxylic acid cycle, cell proliferation, and the oxidative stress response. Biodiesel combustion emissions had higher concentrations of PAHs, OPAHs, and nitrogen-containing PAHs (NPAHs) compared with other fuels. Quinones and 9,10-anthraquinone were identified as the dominant compounds within the OPAH category. This knowledge enhances our understanding of the compounds contributing to adverse health effects observed in epidemiological studies and highlights the role of aerosol composition in toxicity.PMID:37955649 | DOI:10.1021/acs.est.3c05228

J Am Chem Soc. 2023 Nov 13. doi: 10.1021/jacs.3c07861. Online ahead of print.ABSTRACTAmino compounds are widely present in complex mixtures in chemistry, biology, medicine, food, and environmental sciences involving drug impurities and metabolisms of proteins, biogenic amines, neurotransmitters, and pyrimidine in biological systems. Nuclear magnetic resonance (NMR) spectroscopy is an excellent tool for simultaneously identifying and quantifying these in-mixture compounds but has a limit-of-detection (LOD) over several micromolarities (>5 μM). To break such a sensitivity barrier, we developed a sensitive and rapid method by combining the probe-induced sensitivity enhancement and nonuniform-sampling-based 1H-13C HSQC 2D-NMR (PRISE-NUS-HSQC). We introduced two 13CH3 tags for each analyte to respectively increase the 1H and 13C abundances for up to 6 and 200 fold. This enabled high-resolution detection of 0.4-0.8 μM analytes in mixtures in 5 mm tubes with a 5 min acquisition on 600 MHz spectrometers. The method is much more sensitive and faster than traditional 1H-13C HSQC methods (∼50 μM, >10 h). Using sulfanilic acid as a single reference, furthermore, we established a database covering chemical shifts and relative-response factors for >100 compounds, enabling reliable identification and quantification. The method showed good quantitation linearity, accuracy, precision, and applicability in multiple biological matrices, offering a rapid and sensitive approach for quantitative analysis of large cohorts of chemical, medicinal, metabolomic, food, and other mixtures.PMID:37955622 | DOI:10.1021/jacs.3c07861

Clin Chem Lab Med. 2023 Nov 14. doi: 10.1515/cclm-2023-1017. Online ahead of print.ABSTRACTOBJECTIVES: The stratification of individuals suffering from acute and post-acute SARS-CoV-2 infection remains a critical challenge. Notably, biomarkers able to specifically monitor viral progression, providing details about patient clinical status, are still not available. Herein, quantitative metabolomics is progressively recognized as a useful tool to describe the consequences of virus-host interactions considering also clinical metadata.METHODS: The present study characterized the urinary metabolic profile of 243 infected individuals by quantitative nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography mass spectrometry (LC-MS). Results were compared with a historical cohort of noninfected subjects. Moreover, we assessed the concentration of recently identified antiviral nucleosides and their association with other metabolites and clinical data.RESULTS: Urinary metabolomics can stratify patients into classes of disease severity, with a discrimination ability comparable to that of clinical biomarkers. Kynurenines showed the highest fold change in clinically-deteriorated patients and higher-risk subjects. Unique metabolite clusters were also generated based on age, sex, and body mass index (BMI). Changes in the concentration of antiviral nucleosides were associated with either other metabolites or clinical variables. Increased kynurenines and reduced trigonelline excretion indicated a disrupted nicotinamide adenine nucleotide (NAD+) and sirtuin 1 (SIRT1) pathway.CONCLUSIONS: Our results confirm the potential of urinary metabolomics for noninvasive diagnostic/prognostic screening and show that the antiviral nucleosides could represent novel biomarkers linking viral load, immune response, and metabolism. Moreover, we established for the first time a casual link between kynurenine accumulation and deranged NAD+/SIRT1, offering a novel mechanism through which SARS-CoV-2 manipulates host physiology.PMID:37955280 | DOI:10.1515/cclm-2023-1017

Evid Based Complement Alternat Med. 2023 Nov 4;2023:6684263. doi: 10.1155/2023/6684263. eCollection 2023.ABSTRACTBACKGROUND: In Thai traditional medicine (TTM), the dominant body element called "Dhat Chao Ruean" (DCR) is an integral part in the diagnostic process of Thai traditional medicine. TTM practitioners usually use Thai herbal Benjakul formula (BKF) for adjusting and balancing the body elements. However, the effects of BKF on metabolism and individual response to it have not been studied yet.METHODS: This study proposed to investigate the metabolic profiling in 24 volunteers categorized by their types of birth month DCR (bDCR) after the administration of BKF (450 mg, three tablets three times a day before meals) for seven days. Differences in metabolic profiling between bDCR groups were investigated by using liquid chromatography coupled with mass spectrometry for untargeted analysis, and in addition, the safety was assessed by testing the plasma biochemical level.RESULTS: This study identified 57 biomarkers in positive ESI and 12 in negative ESI. Piperine was found in varying amount among the participants but it was the highest in the earth group. In addition, this study found that elemicin, phenylpropionic acid, ricinoleic acid, and β-sitosterol are important substances in a single herb of BKF. Regarding biochemical tests, the results indicated that BKF can decrease the lipid profile and it has no toxic effects on liver and kidney functions.CONCLUSION: The findings indicated that it is safe to use BKF which can help to improve health in chronic diseases by adjusting abnormality of the elements of the body. In addition, the information gathered from this study is valuable for further study in the field of Thai traditional medicine.PMID:37954926 | PMC:PMC10640159 | DOI:10.1155/2023/6684263

MicroPubl Biol. 2023 Oct 27;2023. doi: 10.17912/micropub.biology.000905. eCollection 2023.ABSTRACTGlycerol Monolaurate (GML) is a naturally occurring fatty acid monoester with antimicrobial properties. Francisella tularensis is an agent of bioterrorism known for its unique lipopolysaccharide structure and low immunogenicity. Here we assessed whether exogenous GML would inhibit the growth of Francisella novicida . GML potently impeded Francisella growth and survival in vitro . To appraise the metabolic response to infection, we used GC-MS to survey the metabolome, and surprisingly, observed intracellular GML production following Francisella infection. Notably, the ubiquitin-like protein ISG15 was necessary for increased GML levels induced by bacterial infection, and enhanced ISG15 conjugation correlated with GML levels following serum starvation.PMID:37954520 | PMC:PMC10638595 | DOI:10.17912/micropub.biology.000905

Drug Des Devel Ther. 2023 Nov 7;17:3269-3280. doi: 10.2147/DDDT.S428783. eCollection 2023.ABSTRACTOBJECTIVE: Chronic non-atrophic gastritis (CNAG) is a common clinical gastrointestinal disease with a long and recurrent course. In China, Wuzhuyu decoction (WZYD) has been used for centuries to treat gastrointestinal disorders. To unravel the efficacy and mechanism of WZYD for CNAG, a clinical study was conducted. And metabolomics was used to explore the mechanism of WZYD for CNAG patients.METHODS: Twenty patients in total were recruited in this study (Nos. ChiCTR2200062296) and the protocol was approved by the Ethics Committee (Approval number: KY-2022-2-6-1) and complied with the Declaration of Helsinki. The formula granule of WZYD were assessed by UHPLC-QQQ-TOF to discern the main potential active compounds. The endoscopy evaluation and histopathological changes were detected as effective indicators. Serum samples from patients were used for metabolomics. Inflammatory factors in patients' serum were determined by ELISA. Metabolomics revealed a series of differential metabolites and signaling pathways.RESULTS: WZYD was capable to prevent CNAG by ameliorating score of endoscopy evaluation including erosion, hemorrhage, as well as chronic inflammation and active chronic inflammation score after treatment were decreased. The results indicated that 10 core metabolic components were associated with the treatment of WZYD. Moreover, these metabolic components proved that pyrimidine metabolism and thiamine metabolism were critically responsible for CNAG. In addition, WZYD treatment effectively reduced serum levels of TNF-α, IL-10, and COX-2.CONCLUSION: Altogether, WZYD can effectively alleviate CNAG by inhibiting inflammation and regulating related metabolic processes, which might be the molecular mechanism of WZYD treatment of CNAG. More studies are warranted to be conducted in this area.TRIAL REGISTRATION: ChiCTR, ChiCTR2200062296. Registered 1 August 2022, https://www.chictr.org.cn/com/25/showprojen.aspx?proj=174027.PMID:37954485 | PMC:PMC10638898 | DOI:10.2147/DDDT.S428783

Front Microbiol. 2023 Oct 25;14:1278271. doi: 10.3389/fmicb.2023.1278271. eCollection 2023.ABSTRACTThe gut microbiota, a complex ecosystem integral to host wellbeing, is modulated by environmental triggers, including exposure to heavy metals such as chromium. This study aims to comprehensively explore chromium-induced gut microbiota and metabolomic shifts in the quintessential lepidopteran model organism, the silkworm (Bombyx mori). The research deployed 16S rDNA sequence analysis and LC/MS metabolomics in its experimental design, encompassing a control group alongside low (12 g/kg) and high (24 g/kg) feeding chromium dosing regimens. Considerable heterogeneity in microbial diversity resulted between groups. Weissella emerged as potentially resilient to chromium stress, while elevated Propionibacterium was noted in the high chromium treatment group. Differential analysis tools LEfSe and random forest estimation identified key species like like Cupriavidus and unspecified Myxococcales, offering potential avenues for bioremediation. An examination of gut functionality revealed alterations in the KEGG pathways correlated with biosynthesis and degradation, suggesting an adaptive metabolic response to chromium-mediated stress. Further results indicated consequential fallout in the context of metabolomic alterations. These included an uptick in histidine and dihydropyrimidine levels under moderate-dose exposure and a surge of gentisic acid with high-dose chromium exposure. These are critical players in diverse biological processes ranging from energy metabolism and stress response to immune regulation and antioxidative mechanisms. Correlative analyses between bacterial abundance and metabolites mapped noteworthy relationships between marker bacterial species, such as Weissella and Pelomonas, and specific metabolites, emphasizing their roles in enzyme regulation, synaptic processes, and lipid metabolism. Probiotic bacteria showed robust correlations with metabolites implicated in stress response, lipid metabolism, and antioxidant processes. Our study reaffirms the intricate ties between gut microbiota and metabolite profiles and decodes some systemic adaptations under heavy-metal stress. It provides valuable insights into ecological and toxicological aspects of chromium exposure that can potentially influence silkworm resilience.PMID:37954243 | PMC:PMC10635416 | DOI:10.3389/fmicb.2023.1278271