PubMed

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

Front Cell Dev Biol. 2023 Oct 26;11:1217149. doi: 10.3389/fcell.2023.1217149. eCollection 2023.ABSTRACTWe recently demonstrated that the histone deacetylase inhibitor valproic acid (VPA) reprograms the cisplatin-induced metabolome of triple-negative breast cancer (TNBC) cells, including a shift in hexose levels. Accordingly, here, we tested the hypothesis that VPA alters glucose metabolism in correlation with cisplatin sensitivity. Two TNBC cell lines, MDA-MB-231 (a cisplatin-resistant line) and MDA-MB-436 (a cisplatin-sensitive line), were analyzed. The glycolysis and oxidative metabolism were measured using the Glycolysis Stress Test kit. The expression of aldehyde dehydrogenases (ALDHs), enzymes linked to drug resistance, was investigated by Western blot and real-time PCR analyses. We additionally studied the influence of ALDH inhibition by disulfiram on the viability of MDA-MB-231 cells and on a TNBC patient-derived organoid system. Cisplatin treatment reduced the extracellular acidification rate in MDA-MB-436 cells but not MDA-MB-231 cells, whereas VPA addition increased the extracellular acidification rate in both cell lines. VPA further reduced the oxygen consumption rate of cisplatin-treated MDA-MB-436 cells, which correlated with cell cycle alterations. However, in MDA-MB-231 cells, the cell cycle distribution did not change between cisplatin/VPA-cisplatin treatments. In both cell lines, VPA increased the expression of ALDH isoform and ALDH1A1 expression. However, only in MDA-MB-231 cells, VPA synergized with cisplatin to augment this effect. Disulfiram sensitized the cells to the cytotoxic effects of the VPA-cisplatin combination. Furthermore, the disulfiram-VPA-chemotherapy combination was most effective in TNBC organoids. Our results show that ALDH overexpression may act as one mechanism of cellular resistance to VPA in TNBC and that its inhibition may enhance the therapeutic efficacy of VPA-chemotherapeutic drug combinations.PMID:37954205 | PMC:PMC10639136 | DOI:10.3389/fcell.2023.1217149

Comput Struct Biotechnol J. 2023 Oct 23;21:5273-5284. doi: 10.1016/j.csbj.2023.10.043. eCollection 2023.ABSTRACTCoronarin (COR), an analog of jasmonic acid, has been shown to enhance the tolerance of plants to drought. However, the effects of COR on the interactions among microorganisms associated with plant roots and their implications for enhancing the drought tolerance of plants remain unclear. Here, we studied the effects of applying COR on the microorganisms associated with plant roots and the rhizosphere metabolome. Treatment with COR affected the fungal community of the rhizosphere by inducing changes in the rhizosphere metabolome, which enhanced the drought tolerance of plants. However, treatment with COR had no significant effect on root microorganisms or rhizosphere bacteria. Specifically, the application of COR resulted in a significant reduction in the relative abundance of metabolites, such as mucic acid, 1,4-cyclohexanedione, 4-acetylbutyric acid, Ribonic acid, palmitic acid, and stearic acid, in maize roots under drought conditions; COR application also led to increases in the abundance of drought-resistant fungal microorganisms, including Rhizopus, and the assembly of a highly drought-resistant rhizosphere fungal network, which enhanced the drought tolerance of plants. Overall, the results of our study indicate that COR application positively regulates interactions between plants and microbes and increases the drought tolerance of plants.PMID:37954150 | PMC:PMC10632596 | DOI:10.1016/j.csbj.2023.10.043

Food Funct. 2023 Nov 13. doi: 10.1039/d3fo03867j. Online ahead of print.ABSTRACTThe wide application of immune checkpoint blockade (ICB) therapy is impeded by the development of ICB-induced colitis, a condition intricately linked to alterations in the gut microbiota. In our previous study, Ligilactobacillus salivarius CCFM 1266 and Bacteroides fragilis HCK-B3 exhibited anti-inflammatory properties. In this research, treatment with both L. salivarius CCFM 1266 and B. fragilis HCK-B3 significantly ameliorated body weight loss and colonic inflammation in murine colitis models induced by intravenous ipilimumab injection, with L. salivarius CCFM 1266 demonstrating superior effectiveness. This amelioration was characterized by an augmented ratio of Treg cells and M2 macrophages, a diminishment in pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-23), and an elevation in the anti-inflammatory cytokine IL-10. The ingestion of L. salivarius CCFM 1266 exerted a discernible influence on the composition of the gut microbiota. Untargeted metabolomics revealed an increase in colonic nicotinic acid levels following the administration of L. salivarius CCFM 1266, potentially initiating the activation of the colonic GPR109a pathway. This mechanism likely serves as the fundamental basis for the protective capacity of L. salivarius CCFM 1266 against ICB-induced colitis. Importantly, L. salivarius CCFM 1266 did not interfere with the anti-tumor immune response elicited by ipilimumab. Probiotic intervention thus emerges as a promising approach for alleviating ICB-induced colitis.PMID:37953676 | DOI:10.1039/d3fo03867j

Nucleic Acids Res. 2023 Nov 11:gkad980. doi: 10.1093/nar/gkad980. Online ahead of print.ABSTRACTPlants are unique with tremendous chemical diversity and metabolic complexity, which is highlighted by estimates that green plants collectively produce metabolites numbering in the millions. Plant metabolites play crucial roles in all aspects of plant biology, like growth, development, stress responses, etc. However, the lack of a reference metabolome for plants, and paucity of high-quality standard compound spectral libraries and related analytical tools, have hindered the discovery and functional study of phytochemicals in plants. Here, by leveraging an advanced LC-MS platform, we generated untargeted mass spectral data from >150 plant species collected across the five major phyla. Using a self-developed computation protocol, we constructed reference metabolome for 153 plant species. A 'Reference Metabolome Database for Plants' (RefMetaPlant) was built to encompass the reference metabolome, integrated standard compound mass spectral libraries for annotation, and related query and analytical tools like 'LC-MS/MS Query', 'RefMetaBlast' and 'CompoundLibBlast' for searches and profiling of plant metabolome and metabolite identification. Analogous to a reference genome in genomic research, RefMetaPlant provides a powerful platform to support plant genome-scale metabolite analysis to promote knowledge/data sharing and collaboration in the field of metabolomics. RefMetaPlant is freely available at https://www.biosino.org/RefMetaDB/.PMID:37953341 | DOI:10.1093/nar/gkad980

Mol Hortic. 2023 Nov 13;3(1):24. doi: 10.1186/s43897-023-00073-0.ABSTRACTStorage or transportation temperature is very important for preserving the quality of fruit. However, low temperature in sensitive fruit such as peach can induce loss of quality. Fruit exposed to a specific range of temperatures and for a longer period can show chilling injury (CI) symptoms. The susceptibility to CI at low temperature varies among cultivars and genetic backgrounds. Along with agronomic management, appropriate postharvest management can limit quality losses. The importance of correct temperature management during postharvest handling has been widely demonstrated. Nowadays, due to long-distance markets and complex logistics that require multiple actors, the management of storage/transportation conditions is crucial for the quality of products reaching the consumer.Peach fruit exposed to low temperatures activate a suite of physiological, metabolomic, and molecular changes that attempt to counteract the negative effects of chilling stress. In this review an overview of the factors involved, and plant responses is presented and critically discussed. Physiological disorders associated with CI generally only appear after the storage/transportation, hence early detection methods are needed to monitor quality and detect internal changes which will lead to CI development. CI detection tools are assessed: they need to be easy to use, and preferably non-destructive to avoid loss of products.PMID:37953307 | DOI:10.1186/s43897-023-00073-0

Nucleic Acids Res. 2023 Nov 11:gkad976. doi: 10.1093/nar/gkad976. Online ahead of print.ABSTRACTFirst released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.PMID:37953279 | DOI:10.1093/nar/gkad976