PubMed

Front Plant Sci. 2023 Feb 27;14:1098280. doi: 10.3389/fpls.2023.1098280. eCollection 2023.ABSTRACTPogostemon cablin is an important aromatic medicinal herb widely used in the pharmaceutical and perfume industries. However, our understanding of the phytochemical compounds and metabolites within P. cablin remains limited. To our knowledge, no integrated studies have hitherto been conducted on the metabolites of the aerial parts of P. cablin. In this study, twenty-three volatile compounds from the aerial parts of P. cablin were identified by GC-MS, predominantly sesquiterpenes. Quantitative analysis showed the highest level of patchouli alcohol in leaves (24.89 mg/g), which was 9.12 and 6.69-fold higher than in stems and flowers. UHPLC-QTOFMS was used to analyze the non-volatile compounds of leaf, stem and flower tissues. The differences in metabolites between flower and leaf tissues were the largest. Based on 112, 77 and 83 differential metabolites between flower-leaf, flower-stem and leaf-stem, three tissue-specific biomarkers of metabolites were identified, and the differential metabolites were enriched in several KEGG pathways. Furthermore, labeling differential metabolites in the primary and secondary metabolic pathways showed that flowers accumulated more lipids and amino acids, including proline, lysine and tryptophan; the leaves accumulated higher levels of terpenoids, vitamins and flavonoids, and stems contained higher levels of carbohydrate compounds. Based on the role of acetyl coenzyme A, the distribution and possible exchange mechanism of metabolites in leaves, stems and flowers of P. cablin were mapped for the first time, laying the groundwork for future research on the metabolites in P. cablin and their regulatory role.PMID:36923120 | PMC:PMC10009150 | DOI:10.3389/fpls.2023.1098280

BMC Microbiol. 2023 Mar 15;23(1):69. doi: 10.1186/s12866-023-02770-8.ABSTRACTBACKGROUND: Bioprospecting of actinobacteria isolated from Kubuqi desert, China for antibacterial, antifungal and cytotoxic metabolites production and their structure elucidation.RESULTS: A total of 100 actinobacteria strains were selectively isolated from Kubuqi desert, Inner Mongolia, China. The taxonomic characterization revealed Streptomyces as the predominant genus comprising 37 different species, along with the rare actinobacterial genus Lentzea. The methanolic extracts of 60.8% of strains exhibited potent antimicrobial activities against Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Salmonella enterica, Saccharomyces cerevisiae and high to mild in vitro cytotoxicity against PC3 (prostate cancer) and A549 (lung carcinoma) cell lines. The metabolomics analysis by TLC, HPLC-UV/vis, HPLC-MS and NMR showed the presence of compounds with molecular weights ranging from 100 to 1000 Da. The scale-up fermentation of the prioritized anti-Gram-negative strain PU-KB10-4 (Streptomyces griseoviridis), yielded three pure compounds including; griseoviridin (1; 42.0 mgL- 1) with 20 fold increased production as compared to previous reports and its crystal structure as monohydrate form is herein reported for the first time, mitomycin C (2; 0.3 mgL- 1) and a new bacterial metabolite 4-hydroxycinnamide (3; 0.59 mgL- 1).CONCLUSIONS: This is the first report of the bioprospecting and exploration of actinobacteria from Kubuqi desert and the metabolite 4-hydroxycinnamide (3) is first time isolated from a bacterial source. This study demonstrated that actinobacteria from Kubuqi desert are a potential source of novel bioactive natural products. Underexplored harsh environments like the Kubuqi desert may harbor a wider diversity of actinobacteria, particularly Streptomyces, which produce unique metabolites and are an intriguing source to develop medicinally valuable natural products.PMID:36922786 | DOI:10.1186/s12866-023-02770-8

Clin Exp Hypertens. 2023 Dec 31;45(1):2190529. doi: 10.1080/10641963.2023.2190529.ABSTRACTOBJECTIVES: Hypertension is a chronic disease with multiple causative factors that involve metabolic disturbances and can cause various complications. However, the metabolic characteristics of hypertension at different stages are still unclear. This study aimed to explore the metabolic changes induced by hypertension at different ages.METHODS: Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were divided into four groups according to age: 5-week-old SHR (n = 6), 5-week-old WKY rats (n = 6), 32-week-old SHR (n = 6), and 32-week-old WKY rats (n = 6). Metabolites were analyzed in primary tissues (serum, heart, lung, kidney, brain, and brown adipose) using a non-targeted metabolomics approach.RESULTS: Thirty-five metabolites and nine related metabolic pathways were identified in 5-week-old SHR, mainly related to the metabolism of amino acids. Fifty-one metabolites and seven related metabolic pathways were identified in the 32-week-old SHR, involving glycolysis, lipid, and amino acid metabolisms.CONCLUSION: This experiment elucidates the metabolic profile of SHR at different ages and provides a basis for predicting and diagnosing hypertension. It also provides a reference for the pathogenesis of hypertension.PMID:36922753 | DOI:10.1080/10641963.2023.2190529

Commun Biol. 2023 Mar 15;6(1):273. doi: 10.1038/s42003-023-04646-z.ABSTRACTKarenia mikimotoi is a common harmful algal bloom (HAB)-forming dinoflagellate and has caused severe financial loss in aquaculture. There are limited metabolomic studies on dinoflagellate biology. Here, we examined alterations in metabolic profiles over the growth curve of K. mikimotoi under nitrogen or phosphorus deficiency and further explored a key criterion for the diagnosis of late stationary phase to identify when the dinoflagellate cells will enter bloom demise. The results demonstrate the differential expression of metabolites for coping with chronological aging or nutrient deprivation. Furthermore, an increase in the glucose to glycine ratio in the late stationary phase was indicative of dinoflagellate cells entering bloom demise; this was also detected in the cultured diatom, Chaetoceros tenuissimus, indicating that this may be the general criterion for phytoplankton species. Our findings provide insights regarding chronological aging and the criterion for the prediction of phytoplankton bloom demise.PMID:36922623 | DOI:10.1038/s42003-023-04646-z

Nature. 2023 Mar 15. doi: 10.1038/s41586-023-05801-6. Online ahead of print.ABSTRACTArtificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.PMID:36922598 | DOI:10.1038/s41586-023-05801-6

Chembiochem. 2023 Mar 15:e202200766. doi: 10.1002/cbic.202200766. Online ahead of print.ABSTRACTMetastasis poses a major challenge in cancer management, including EML4-ALK-rearranged non-small cell lung cancer (NSCLC). As cell migration is a critical step during metastasis, we assessed the anti-migratory activities of several clinical ALK inhibitors in NSCLC cells and observed differential anti-migratory capabilities despite similar ALK inhibition, with brigatinib displaying superior anti-migratory effects over other ALK inhibitors. Applying an unbiased in-situ mass spectrometry-based chemoproteomics approach, we determined the proteome-wide target profile of brigatinib in EML4-ALK+ NSCLC cells. Dose-dependent and cross-competitive chemoproteomics suggested MARK2 and MARK3 as relevant brigatinib kinase targets. Functional validation showed that combined pharmacological inhibition or genetic modulation of MARK2/3 inhibited cell migration. Consistently, brigatinib treatment induced inhibitory YAP1 phosphorylation downstream of MARK2/3. Collectively, our data suggest that brigatinib exhibits unusual cross-phenotype polypharmacology as, despite similar efficacy for inhibiting EML4-ALK-dependent cell proliferation as other ALK inhibitors, it more effectively prevented migration of NSCLC cells due to co-targeting of MARK2/3.PMID:36922348 | DOI:10.1002/cbic.202200766

Chem Biol Interact. 2023 Mar 13:110449. doi: 10.1016/j.cbi.2023.110449. Online ahead of print.ABSTRACTClerodendranthus spicatus (Thunb.) C. Y. Wu, also known as kidney tea (KT), has been widely employed in kidney protection in Chinese Medicine. It has been reported that KT can lower uric acid (UA) and mitigate gout, while the mechanism remains to be elucidated. Given the close relationship between hyperuricemia (HUA), intestinal flora and host metabolism, this study aimed to explore the mechanism by which KT lowers UA from the perspective of the fecal microbiome and metabolome. Initially, mice were intraperitoneally injected with potassium oxonate to induce the HUA model. The results showed that KT markedly reduced the serum level of UA and impaired renal damage in HUA mice. Subsequently, the result of 16S rRNA gene sequencing analysis indicated that KT administration appeared a significant improvement in the structure of the intestinal flora, especially increased the abundances of Roseburia and Enterorhabdus, while decreased the abundances of Ileibacterium and UBA1819. Moreover, the levels of differential metabolites (including twenty-five in feces and eight in serum) identified by untargeted metabolomics returned to normal after KT intervention. Taken together, the mechanism of KT in alleviating HUA is related to the regulation of the intestinal flora and the remodeling of metabolic disorders, which will lay a theoretical foundation for KT as a UA-lowering drug.PMID:36921834 | DOI:10.1016/j.cbi.2023.110449

Biomed Pharmacother. 2023 Mar 13;161:114525. doi: 10.1016/j.biopha.2023.114525. Online ahead of print.ABSTRACTMajor depression disorder is more common among adolescents and is a primary reason for suicide in adolescents. Some antidepressants are ineffective and may possess side effects. Therefore, developing an adolescent antidepressant is the need of the hour. We designed the stress model of adolescent male mice induced by chronic unpredictable stress (CUS). The mice were treated using Tongxieyaofang neutral polysaccharide (TXYF-NP), Tongxieyaofang acidic polysaccharide (TXYF-AP), TXYF-AP + TXYF-NP and fructooligosaccharide + galactooligosaccharides to determine their body weight, behavior, and serum hormone levels. RT-qPCR was used to detect the gene expression of Crhr1, Nr3c1, and Nr3c2 in the hypothalamus and hippocampus and the gene expression of glutamic acid and γ-aminobutyric acid-related receptors in the hippocampus. RT-qPCR, Western blot, and ELISA detected tryptophan metabolism in the colon, serum, and hippocampus. 16s rDNA helped sequence colon microflora, and non-targeted metabolomics enabled the collection of metabolic profiles of colon microflora. In adolescent male mice, CUS induced depression-like behavior, hypothalamic-pituitary-adrenal axis hyperactivity, hippocampal tissue damage, abnormal expression of its related receptors, and dysregulation of tryptophan metabolism. The 16s rDNA and non-targeted metabolomics revealed that CUS led to colon microflora disorder and bile acid metabolism abnormality. Tongxieyaofang polysaccharide could improve the bacterial community and bile acid metabolism disorder by upregulating the relative abundance of Lactobacillus gasseri, Lachnospiraceae bacterium 28-4, Bacteroides and Ruminococcaceae UCG-014 while preventing CUS-induced changes. TXYF-P can inhibit depression-like behavior due to CUS by regulating colonic microflora and restoring bile acid metabolism disorder. Thus, based on the different comparisons, TXYF-NP possessed the best effect.PMID:36921537 | DOI:10.1016/j.biopha.2023.114525

J Environ Manage. 2023 Mar 13;336:117730. doi: 10.1016/j.jenvman.2023.117730. Online ahead of print.ABSTRACTSoil and water pollution, rapid industrialization, contaminated irrigation-water, increased waste-production and surge in agricultural land leads to the accumulation of Heavy Metals (HM) with time. HM contamination has raised concern over the past years and new remediation strategies are required to deal with it. HM-contaminated soil is often used for the production of food, which makes a gateway for toxic metals into the food-chain, thereby affecting food security and human health. To avoid HM-toxicity, decontamination of important resources is essential. Therefore, exploring phytoremediation for the removal, decomposition and detoxification of hazardous metals from HM-contaminated sites is of great significance. Hyper-accumulator plants can efficiently remove HMs. However, despite many hyper-accumulator plant species, there is a research gap in the studies of phytotechnology. Hence biotechnological efforts advocating omics studies i.e. genomics, transcriptomics, proteomics, metabolomics and phenomics are in order, the purpose being to select and enhance a plant's potential for the process of phytoremediation to be more effective. There is a need to study newly developed high-efficiency hyper-accumulator plants as HM-decontaminator candidates for phytoremediation and phytomining. Therefore, this review focuses on various strategies and bio-technological methods for the removal of HM contaminants from sites, with emphasis on the advancement of phytoremediation, along with applications in cleaning up various toxic pollutants.PMID:36921476 | DOI:10.1016/j.jenvman.2023.117730

J Proteome Res. 2023 Mar 15. doi: 10.1021/acs.jproteome.2c00820. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.PMID:36921116 | DOI:10.1021/acs.jproteome.2c00820

J Agric Food Chem. 2023 Mar 15. doi: 10.1021/acs.jafc.2c08647. Online ahead of print.ABSTRACTSmall molecular organic acids (SMOAs) in root exudates are critical for plant-microbe interaction, especially under environmental stresses. However, the dominant organic acids driving the process and promoting the colonization are unclear. Here, using a target metabolomics, 20 main SMOAs of rice root exudates were identified and analyzed in control and 10 mg/L thiamethoxam-treated groups. The composition of these SMOAs differed significantly between the two treatments. Among which, malic acid, citric acid, succinic acid, and proline induced a chemotactic response, swimming ability, and biofilm formation of Enterobacter cloacae TMX-6 in a dose-dependent manner. The maximal chemotactic response of TMX-6 was induced by proline at 10 mg/L, and a strong chemotactic response was even observed at 0.01 mg/L. The recruitment assay confirmed that the addition of these four compounds promoted the colonization of TMX-6. The results provide insight for directional regulation of plant-microbe interactions for beneficial outcomes.PMID:36921065 | DOI:10.1021/acs.jafc.2c08647

Sci Transl Med. 2023 Mar 15;15(687):eabn2110. doi: 10.1126/scitranslmed.abn2110. Epub 2023 Mar 15.ABSTRACTAmong drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.PMID:36921036 | DOI:10.1126/scitranslmed.abn2110

Metabolomics. 2023 Mar 15;19(3):18. doi: 10.1007/s11306-023-01981-4.ABSTRACTINTRODUCTION: Molecular networking (MN) has emerged as a key strategy to organize and annotate untargeted tandem mass spectrometry (MS/MS) data generated using either data independent- or dependent acquisition (DIA or DDA). The latter presents a time-efficient approach where full scan (MS1) and MS2 spectra are obtained with shorter cycle times. However, there are limitations related to DDA parameters, some of which are (i) intensity threshold and (ii) collision energy. The former determines ion prioritization for fragmentation, and the latter defines the fragmentation of selected ions. These DDA parameters inevitably determine the coverage and quality of spectral data, which would affect the outputs of MN methods.OBJECTIVES: This study assessed the extent to which the quality of the tandem spectral data relates to MN topology and subsequent implications in the annotation of metabolites and chemical classification relative to the different DDA parameters employed.METHODS: Herein, characterising the metabolome of Momordica cardiospermoides plants, we employ classical MN performance indicators to investigate the effects of collision energies and intensity thresholds on the topology of generated MN and propagated annotations.RESULTS: We demonstrated that the lowest predefined intensity thresholds and collision energies result in comprehensive molecular networks. Comparatively, higher intensity thresholds and collision energies resulted in fewer MS2 spectra acquisition, subsequently fewer nodes, and a limited exploration of the metabolome through MN.CONCLUSION: Contributing to ongoing efforts and conversations on improving DDA strategies, this study proposes a framework in which multiple DDA parameters are utilized to increase the coverage of ions acquired and improve the global coverage of MN, propagated annotations, and the chemical classification performed.PMID:36920561 | DOI:10.1007/s11306-023-01981-4

ACS Chem Biol. 2023 Mar 15. doi: 10.1021/acschembio.2c00958. Online ahead of print.ABSTRACTStreptomycetes are bacteria known for their extraordinary biosynthetic capabilities. Herein, we describe the genome and metabolome of a particularly talented strain, Streptomyces ID71268. Its 8.4-Mbp genome harbors 32 bioinformatically predicted biosynthetic gene clusters (BGCs), out of which 10 are expressed under a single experimental condition. In addition to five families of known metabolites with previously assigned BGCs (nigericin, azalomycin F, ectoine, SF2766, and piericidin), we were able to predict BGCs for three additional metabolites: streptochlorin, serpetene, and marinomycin. The strain also produced two families of presumably novel metabolites, one of which was associated with growth inhibitory activity against the human opportunistic pathogen Acinetobacter baumannii in an iron-dependent manner. Bioassay-guided fractionation, followed by extensive liquid chromatography-mass spectrometry (LC-MS) and NMR analyses, established that the molecule responsible for the observed antibacterial activity is an unusual tridecapeptide siderophore with a ring-and-tail structure: the heptapeptide ring is formed through a C-C bond between a 2,3-dihydroxybenzoate (DHB) cap on Gly1 and the imidazole moiety of His7, while the hexapeptide tail is sufficient for binding iron. This molecule, named megalochelin, is the largest known siderophore. The megalochelin BGC encodes a 13-module nonribosomal peptide synthetase for the synthesis of the tridecapeptide, and a copper-dependent oxidase, likely responsible for the DHB-imidazole cross-link, whereas the genes for synthesis of the DHB starter unit are apparently specified in trans by a different BGC. Our results suggest that prolific producers of specialized metabolites may conceal hidden treasures within a background of known compounds.PMID:36920304 | DOI:10.1021/acschembio.2c00958

Brief Bioinform. 2023 Mar 15:bbad096. doi: 10.1093/bib/bbad096. Online ahead of print.ABSTRACTGaussian graphical model is a strong tool for identifying interactions from metabolomics data based on conditional correlation. However, data may be collected from different stages or subgroups of subjects with heterogeneity or hierarchical structure. There are different integrating strategies of graphical models for multi-group data proposed by data scientists. It is challenging to select the methods for metabolism data analysis. This study aimed to evaluate the performance of several different integrating graphical models for multi-group data and provide support for the choice of strategy for similar characteristic data. We compared the performance of seven methods in estimating graph structures through simulation study. We also applied all the methods in breast cancer metabolomics data grouped by stages to illustrate the real data application. The method of Shaddox et al. achieved the highest average area under the receiver operating characteristic curve and area under the precision-recall curve across most scenarios, and it was the only approach with all indicators ranked at the top. Nevertheless, it also cost the most time in all settings. Stochastic search structure learning tends to result in estimates that focus on the precision of identified edges, while BEAM, hierarchical Bayesian approach and birth-death Markov chain Monte Carlo may identify more potential edges. In the real metabolomics data analysis from three stages of breast cancer patients, results were in line with that in simulation study.PMID:36920069 | DOI:10.1093/bib/bbad096

Environ Toxicol Chem. 2023 Mar 15. doi: 10.1002/etc.5608. Online ahead of print.ABSTRACTEarly vertebrate development is partially regulated by thyroid hormones (THs). Environmental pollutants that interact with the TH system (TH system disrupting chemicals; THSDCs) can have massively disrupting effects on this essential phase. Eye development of fish is directly regulated by THs and can, therefore, be used as a thyroid-related endpoint in endocrine disruptor testing. To evaluate the effects of THSDC-induced eye malformations during early development, zebrafish (Danio rerio) embryos were exposed for 5 days post fertilization (dpf) to either propylthiouracil, a TH synthesis inhibitor, or tetrabromobisphenol A, which interacts with TH receptors. Subsequently, one half of the embryos were exposed further to the THSDCs until 8 dpf, while the other half of the embryos was raised in clean water for 3 days to check for reversibility of effects. Continued THSDC exposure altered eye size and pigmentation and induced changes in the cellular structure of the retina. This correlated with morphological alterations of thyroid follicles as revealed by use of a transgenic zebrafish line. Interestingly, effects were partly reversible after a recovery period as short as 3 days. Results are consistent with changes in TH levels measured in different tissues of the embryos, e.g., in the eyes. Results show that eye development in zebrafish embryos is very sensitive to THSDC treatment, but able to recover quickly from early exposure by effective repair mechanisms. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2023;00:0-0. © 2023 SETAC.PMID:36920003 | DOI:10.1002/etc.5608

Food Funct. 2023 Mar 15. doi: 10.1039/d2fo02939a. Online ahead of print.ABSTRACTParkinson's disease (PD) is the second most prevalent neurodegenerative disorder with limited therapeutic agents. Rhynchophylline (RIN), a tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla, has multiple neuropharmacological activities, including anti-inflammatory, anti-depression, anti-neurodegenerative disease, and anti-drug addiction. Though it is reported that RIN exerts a neuroprotective effect against PD, the underlying protective mechanism remains obscure. In this study, a mass spectrometry-based metabolomic strategy combined with neurobehavioral tests, serum biochemical assays, and immunohistochemistry were employed to decipher the protective mechanism of RIN against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced subacute PD in mice. Our results indicated that RIN significantly improved the MPTP-induced behavioral abnormalities, reduced the loss of dopaminergic neurons, and reversed the secretion of inflammatory cytokines and oxidative stress indicators. Further studies showed that RIN significantly suppressed the expression of toll-like receptor 4, NOD-like receptor protein 3, and cyclooxygenase 2 in the mouse striatum. The results of serum metabolomics showed that RIN could ameliorate metabolic disorders in PD mainly through the regulation of retinol metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism. These pieces of evidence revealed that RIN is a promising drug candidate for PD by alleviating neuroinflammation and maintaining metabolic homeostasis.PMID:36919954 | DOI:10.1039/d2fo02939a

Chem Biodivers. 2023 Mar 15:e202201087. doi: 10.1002/cbdv.202201087. Online ahead of print.ABSTRACTEndophytic fungi possess a versatile metabolism which is related to their ability to live in diverse ecological niches. While culturing under laboratory conditions, their metabolism is mainly influenced by the culture media, time of incubation and other physicochemical factors. In this study, we focused on the production of 3 thiodiketopiperazines (TDKPs) botryosulfuranols A-C produced by an endophytic strain of Cophinforma mamane isolated from the leaves of Bixa orellana L collected in the Peruvian Amazon. We studied the time-course production of botryosulfuranols A-C during 28 days and evaluated the variations in the production of secondary metabolites, including the TDKPs, produced by C. mamane in response to different culture media, light versus dark conditions and different incubation times. We observed a short time-frame production of botryosulfuranol C while its production was significantly affected by the light conditions and nutrients of the culture media. Botryosulfuranols A and B showed a similar production pattern and a similar response to culturing conditions. Molecular networking allowed us to detect three compounds related to TDKPs that will be the focus of future experiments.PMID:36919620 | DOI:10.1002/cbdv.202201087

Biomed Chromatogr. 2023 Mar 15:e5625. doi: 10.1002/bmc.5625. Online ahead of print.ABSTRACTLiver cirrhosis is currently the twelfth leading cause of death globally and the sixth leading cause of death in China. Its treatment is expensive. Changes in the composition of the serum bile acid pool are sensitive indicators of the severity of liver cirrhosis. In this study, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and used to simultaneously determine 15 bile acids in human serum in patients with decompensated cirrhosis. Sample preparation involved spiking with isotope internal standards (ISs) followed by protein precipitation and the analytical run time was 5 min. The LC-MS/MS method was fully validated according to CLSI C62A and the Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories. The method achieved an acceptable coefficient of variation for precision (0.83-14.80%) and accuracy (89.39-107.62%). Finally, as proof of applicability, the method was applied to patients with decompensated cirrhosis in routine clinical sample analysis. The degree of variation of different bile acids was clearly shown. These results indicated that abnormal metabolic pathways might play important roles in decompensated cirrhosis.PMID:36919355 | DOI:10.1002/bmc.5625

Mol Plant. 2023 Mar 14:S1674-2052(23)00071-0. doi: 10.1016/j.molp.2023.03.007. Online ahead of print.ABSTRACTIn the post-GWAS era, multi-omics techniques have shown great power and potential for candidate gene mining and functional genomics research. However, due to the lack of effective data integration and multi-omics analysis platforms, such techniques have not still been applied widely in rapeseed, an important oil crop worldwide. Here, we constructed a rapeseed multi-omics database (BnIR; http://yanglab.hzau.edu.cn/BnIR), which provides datasets of six omics including genomics, transcriptomics, variomics, epigenetics, phenomics and metabolomics, as well as numerous "variation-gene expression-phenotype" associations by using multiple statistical methods. In addition, a series of multi-omics search and analysis tools are integrated to facilitate the browsing and application of these datasets. BnIR is the most comprehensive multi-omics database for rapeseed so far, and two case studies demonstrated its power to mine candidate genes associated with specific traits and analyze their potential regulatory mechanisms.PMID:36919242 | DOI:10.1016/j.molp.2023.03.007