PubMed
Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice
Aging Cell. 2024 Jul 3:e14263. doi: 10.1111/acel.14263. Online ahead of print.ABSTRACTFrailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting.PMID:38961613 | DOI:10.1111/acel.14263
Emerging importance of stool preservation methods in OMICS studies with special focus on cancer biology
Cell Biochem Funct. 2024 Jul;42(5):e4063. doi: 10.1002/cbf.4063.ABSTRACTThe intricate consortium of microorganisms in the human gut plays a crucial role in different physiological functions. The complex known-unknown elements of the gut microbiome are perplexing and the absence of standardized procedures for collecting and preserving samples has hindered continuous research in comprehending it. The technological bias produced because of lack of standard protocols has affected the reproducibility of results. The complex nature of diseases like colorectal cancer, gastric cancer, hepatocellular carcinoma and breast cancer require a thorough understanding of its etiology for an efficient and timely diagnosis. The designated protocols for collection and preservation of stool specimens have great variance, hence generate inconsistencies in OMICS studies. Due to the complications associated to the nature of sample, it is important to preserve the sample to be studied later in a laboratory or to be used in the future research purpose. Stool preservation is gaining importance due to the increased use of treatment options like fecal microbiota transplantation to cure conditions like recurrent Clostridium difficile infections and for OMICS studies including metagenomics, metabolomics and culturomics. This review provides an insight into the importance of omics studies for the identification and development of novel biomarkers for quick and noninvasive diagnosis of various diseases.PMID:38961596 | DOI:10.1002/cbf.4063
Pathophysiology and genomics of bronchiectasis
Eur Respir Rev. 2024 Jul 3;33(173):240055. doi: 10.1183/16000617.0055-2024. Print 2024 Jul.ABSTRACTBronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology. Genomic approaches may help to identify new endotypes, as has been shown in other chronic airway diseases, such as COPD.Different studies have started to work in this direction, and significant contributions to the understanding of the microbiome and proteome diversity have been made in bronchiectasis in recent years. However, the systematic application of omics approaches to identify new molecular insights into the pathophysiology of bronchiectasis (endotypes) is still limited compared with other respiratory diseases.Given the complexity and diversity of these technologies, this review describes the key components of the pathophysiology of bronchiectasis and how genomics can be applied to increase our knowledge, including the study of new techniques such as proteomics, metabolomics and epigenomics. Furthermore, we propose that the novel concept of trained innate immunity, which is driven by microbiome exposures leading to epigenetic modifications, can complement our current understanding of the vicious vortex. Finally, we discuss the challenges, opportunities and implications of genomics application in clinical practice for better patient stratification into new therapies.PMID:38960613 | DOI:10.1183/16000617.0055-2024
Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms
Gut. 2024 Jul 3:gutjnl-2024-332245. doi: 10.1136/gutjnl-2024-332245. Online ahead of print.ABSTRACTOBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome.DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified.RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion.CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.PMID:38960582 | DOI:10.1136/gutjnl-2024-332245
A single-blinded, randomized, parallel intervention to evaluate genetics and omics-based personalized nutrition in general population via an e-commerce tool: The PREVENTOMICS e-commerce study
Am J Clin Nutr. 2024 Jul;120(1):129-144. doi: 10.1016/j.ajcnut.2024.04.004. Epub 2024 May 23.ABSTRACTBACKGROUND: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status.OBJECTIVES: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population.METHODS: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits.RESULTS: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control-3 points; 95% confidence interval [CI]: 2.2, 3.8; PN-2.7 points; 95% CI: 2.0, 3.3; and PP-2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (β: -0.37; 95% CI: -0.56, -0.18), oxidative stress (β: -0.37; 95% CI: -0.60, -0.15), microbiota (β: -0.38; 95% CI: -0.63, -0.15), and inflammation (β: -0.78; 95% CI: -1.24, -0.31) compared with control diet.CONCLUSIONS: Integration of personalized strategies within an e-commerce-like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN. This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).PMID:38960570 | DOI:10.1016/j.ajcnut.2024.04.004
Comprehensive transcriptomic and metabolomic insights into simultaneous CO(2) sequestration and nitrate removal by the Chlorella vulgaris and Pseudomonas sp. consortium
Environ Res. 2024 Jul 1:119540. doi: 10.1016/j.envres.2024.119540. Online ahead of print.ABSTRACTSimultaneous CO2 sequestration and nitrate removal can be achieved by co-cultivation of Chlorella vulgaris with Pseudomonas sp. However, a comprehensive understanding of the synergistic mechanism between C. vulgaris and Pseudomonas sp. remains unknown. In this study, transcriptomics and metabolomics analysis were employed to elucidate the synergistic mechanism of C. vulgaris and Pseudomonas sp. Transcriptomic and metabolomic analyses identified 3664 differentially expressed genes and 314 metabolites. Transcriptome analysis revealed that co-culture with Pseudomonas sp. promoted the photosynthesis of C. vulgaris by promoting the synthesis of photosynthetic pigments and photosynthesis-antenna proteins. Furthermore, it stimulated pathways associated with energy metabolism from carbon sources, such as the Calvin cycle, glycolytic pathway, and TCA cycle. Additionally, Pseudomonas sp. reduced nitrate levels in the co-culture system by denitrification, and microalgae regulated nitrate uptake by down-regulating the transcript levels of nitrate transporter genes. Metabolomic analysis indicated that nutrient exchange was conducted between algae and bacteria, and amino acids, phytohormones, and organic heterocyclic compounds secreted by the bacteria promoted the growth metabolism of microalgae. After supplementation with differential metabolites, the carbon fixation rate and nitrate removal rate of the co-culture system reached 0.549 g L-1 d-1 and 135.4 mg L-1 d-1, which were increased by 20% and 8%, respectively. This study provides a theoretical insight into microalgae-bacteria interaction and its practical application, as well as a novel perspective on flue gas treatment management.PMID:38960357 | DOI:10.1016/j.envres.2024.119540
Microbiome-metabolomics-based insight into the protective effects of dietary fiber from sweetpotato residues on the high-fat diet-induced intestinal integrity damage
Int J Biol Macromol. 2024 Jul 1:133620. doi: 10.1016/j.ijbiomac.2024.133620. Online ahead of print.ABSTRACTDietary fibers have attracted much attention due to their multiple benefits on gut health. In this work, the protective mechanism of dietary fiber from sweetpotato residues (SRDF) on the high-fat diet (HFD)-induced intestinal barrier injury was investigated using microbiome-metabolomics-based approach. The physicochemical property analysis demonstrated a thermal stability below 200 °C and porous pectin-polysaccharide structure of SRDF with high in vitro functional activities. The biochemical analysis indicated that SRDF significantly ameliorated intestinal barrier function by improving intestinal morphology and permeability and inhibiting inflammatory response. Microbiome analysis demonstrated that SRDF significantly reversed the HFD-induced dysbacteriosis, decreased the ratio of Firmicutes/Bacteroides and enhanced the relative abundance of probiotics, such as Muribaculaceae and Bifidobacteriaceae. Metabolomics analysis showed that SRDF also significantly altered the metabolic profile in the colon, wherein the differential metabolites were mainly involved in amino acid metabolism (especially tryptophan). Pearson correlation coefficient identified the beneficial relationship between intestinal microbiome and metabolome induced by SRDF. The limitation of this study was that the mouse model may not fully replicate the human intestinal responses due to the difference between the standard environmental conditions and natural world. Generally, our results implied the great potential of SRDF as a functional food ingredient.PMID:38960238 | DOI:10.1016/j.ijbiomac.2024.133620
Marine heatwaves alter competition between the cultured macroalga Gracilariopsis lemaneiformis and the harmful bloom alga Skeletonema costatum
Sci Total Environ. 2024 Jul 1:174345. doi: 10.1016/j.scitotenv.2024.174345. Online ahead of print.ABSTRACTSeaweed cultivation can inhibit the occurrence of red tides. However, how seaweed aquaculture interactions with harmful algal blooms will be affected by the increasing occurrence and intensity of marine heatwaves (MHWs) is unknown. In this study, we run both monoculture and coculture systems to investigate the effects of a simulated heatwave on the competition of the economically important macroalga Gracilariopsis lemaneiformis against the harmful bloom diatom Skeletonema costatum. Coculture with G. lemaneiformis led to a growth decrease in S. costatum. Growth and photosynthetic activity (Fv/Fm) of G. lemaneiformis was greatly reduced by the heatwave treatment, and did not recover even after one week. Growth and photosynthetic activity of S. costatum was also reduced by the heatwave in coculture, but returned to normal during the recovery period. S. costatum also responded to the stressful environment by forming aggregates. Metabolomic analysis suggests that the negative effects on S. costatum were related to an allelochemical release from G. lemaneiformis. These findings show that MHWs may enhance the competitive advantages of S. costatum against G. lemaneiformis, leading to more severe harmful algal blooms in future extreme weather scenarios.PMID:38960174 | DOI:10.1016/j.scitotenv.2024.174345
Serum metabolism distribution in individuals exposed to dioxins: A case study of residents near the municipal solid waste incinerators in China
Sci Total Environ. 2024 Jul 1:174431. doi: 10.1016/j.scitotenv.2024.174431. Online ahead of print.ABSTRACTPolychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) have attracted considerable attention owing to their environmental persistence, bioaccumulation, and high toxicity. This study aimed to investigate changes in serum metabolites following exposure to PCDD/Fs and to reveal a novel pathogenesis of PCDD/Fs. Serum samples were collected from 75 residents living near a municipal solid waste incinerator in China to analyse the relationship between PCDD/Fs and serum metabolic components. The serum level in the low-exposure group [19.07 (13.44-23.89) pg-TEQ/L] was significantly lower than that in the high-exposure group [115.60 (52.28-592.65) pg-TEQ/L]. Non-targeted metabolomic studies based on liquid chromatography-high resolution mass spectrometry have been applied to the metabolomic analysis of serum. Thirty-seven metabolites with significant differences among the different groups were identified as biomarkers. Pathway analysis revealed that high dioxin exposure perturbed various biological processes, including glycerol phospholipid metabolism and the interconversion of pentose and glucuronate. The results of a population health survey showed that the serum dioxin concentration in patients with diabetes was significantly higher than that in the control population. These findings suggest that dioxin exposure is associated with several potential adverse health risks, including inflammation, diabetes, and cardiovascular disease, through metabolic changes.PMID:38960151 | DOI:10.1016/j.scitotenv.2024.174431
The nicotine demethylase CYP82E4 is essential for the formation of red dapples on flue-cured leaves of cherry-red tobacco
Plant Sci. 2024 Jul 1:112174. doi: 10.1016/j.plantsci.2024.112174. Online ahead of print.ABSTRACTCommon flue-cured tobacco (Nicotiana tabacum L.) primarily accumulates nicotine, and its flue-cured leaves exhibit a lemon appearance. In contrast, a spontaneous cherry-red variant (CR60) primarily accumulates nornicotine, accompanied by distinctive red dapples on the cured leaves. In this study, suppression of conversion of nicotine to nornicotine by genome editing resulted in decreased nornicotine and N-acyl nornicotines (NacNNs), and the subsequent disappearance of red dapples in CR60. Conversely, overexpression of CYP82E4 increased nornicotine and NacNNs accumulation, inducing a red dapple phenotype in common tobacco. Notably, nicotine conversion triggered significant alterations in leaf total sugars, alkaloids, and nitrogens. Metabolome analyses using 1352 identified compounds indicated nicotine conversion dramatically affected the entire metabolic network and induced unique metabolic responses across diverse genetic backgrounds. Further WGCNA analysis revealed that nicotine conversion caused substantial contents variation of alkaloids, flavonoids and amino acids and derivatives in cured leaves. Overall, this research provides valuable insights into the mechanisms underlying red dapple formation in cherry-red tobacco, elucidating profound influence of nicotine conversion on entire metabolic network.PMID:38960071 | DOI:10.1016/j.plantsci.2024.112174
PPARγ/NF-κB axis contributes to cold-induced resolution of experimental colitis and preservation of intestinal barrier
Biochim Biophys Acta Mol Basis Dis. 2024 Jul 1:167326. doi: 10.1016/j.bbadis.2024.167326. Online ahead of print.ABSTRACTBACKGROUND: Environmental stress is a significant contributor to the development of inflammatory bowel disease (IBD). The involvement of temperature stimulation in the development of IBD remains uncertain. Our preliminary statistical data suggest that the prevalence of IBD is slightly lower in colder regions compared to non-cold regions. The observation indicates that temperature changes may play a key role in the occurrence and progression of IBD. Here, we hypothesized that cold stress has a protective effect on IBD.METHODS: The cold exposure model for mice was placed in a constant temperature and humidity chamber, maintained at a temperature of 4 °C. Colitis models were induced in the mice using TNBS or DSS. To promote the detection methods more clinically, fluorescence confocal endoscopy was used to observe the mucosal microcirculation status of the colon in the live model. Changes in the colonic wall of the mice were detected using 9.4 T Magnetic Resonance Imaging (MRI) imaging and in vivo fluorescence imaging. Hematoxylin and eosin (H&E) and Immunofluorescence (IF) staining confirmed the pathological alterations in the colons of sacrificed mice. Molecular changes at the protein level were assessed through Western blotting and Enzyme-Linked Immunosorbent Assay (ELISA) assays. RNA sequencing (RNA-seq) and metabolomics (n = 18) were jointly analyzed to investigate the biological changes in the colon of mice treated by cold exposure.RESULTS: Cold exposure decreased the pathologic and disease activity index scores in a mouse model. Endomicroscopy revealed that cold exposure preserved colonic mucosal microcirculation, and 9.4 T MRI imaging revealed alleviation of intestinal wall thickness. In addition, the expression of the TLR4 and PP65 proteins was downregulated and epithelial cell junctions were strengthened after cold exposure. Intriguingly, we found that cold exposure reversed the decrease in ZO-1 and occludin protein levels in dextran sulfate sodium (DSS)- and trinitrobenzenesulfonic acid-induced colitis mouse models. Multi-omics analysis revealed the biological landscape of DSS-induced colitis under cold exposure and identified that the peroxisome proliferator-activated receptor (PPAR) signaling pathway mediates the effects of cold on colitis. Subsequent administration of rosiglitazone (PPAR agonist) enhanced the protective effect of cold exposure on colitis, whereas GW9662 (PPAR antagonist) administration mitigated these protective effects. Overall, cold exposure ameliorated the progression of mouse colitis through the PPARγ/NF-κB signaling axis and preserved the intestinal mucosal barrier.CONCLUSION: Our study provides a mechanistic link between intestinal inflammation and cold exposure, providing a theoretical framework for understanding the differences in the prevalence of IBD between the colder regions and non-cold regions, and offering new insights into IBD therapy.PMID:38960052 | DOI:10.1016/j.bbadis.2024.167326
PANAMA-enabled high-sensitivity dual nanoflow LC-MS metabolomics and proteomics analysis
Cell Rep Methods. 2024 Jun 26:100803. doi: 10.1016/j.crmeth.2024.100803. Online ahead of print.ABSTRACTHigh-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment. Our method, termed proteomic and nanoflow metabolomic analysis (PANAMA), improves compound resolution and detection sensitivity without compromising the depth of coverage as compared with existing widely used analytical procedures. Notably, PANAMA can be applied to a broad array of specimens, including biofluids, cell lines, and tissue samples. It generates high-quality, information-rich metabolite-protein datasets while bypassing the need for specialized instrumentation.PMID:38959888 | DOI:10.1016/j.crmeth.2024.100803
Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids
Cell Rep Med. 2024 Jul 2:101629. doi: 10.1016/j.xcrm.2024.101629. Online ahead of print.ABSTRACTWeight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis.PMID:38959886 | DOI:10.1016/j.xcrm.2024.101629
Selenium-enriched yeast, a selenium supplement, improves the rheological properties and processability of dough: From the view of yeast metabolism and gluten alteration
Food Chem. 2024 Jun 28;458:140256. doi: 10.1016/j.foodchem.2024.140256. Online ahead of print.ABSTRACTThis study investigated the effect mechanism of selenium (Se)-enriched yeast on the rheological properties of dough from the perspective of yeast metabolism and gluten alteration. As the yeast Se content increased, the gas production rate of Se-enriched yeast slowed down, and dough viscoelasticity decreased. The maximum creep of Se-enriched dough increased by 29%, while the final creep increased by 54%, resulting in a softer dough. Non-targeted metabolomics analyses showed that Se inhibited yeast energy metabolism and promoted the synthesis of stress-resistance related components. Glutathione, glycerol, and linoleic acid contributed to the rheological property changes of the dough. The fractions and molecular weight distribution of protein demonstrated that the increase in yeast Se content resulted in the depolymerization of gluten. The intermolecular interactions, fluorescence spectrum and disulfide bond analysis showed that the disruption of intermolecular disulfide bond induced by Se-enriched yeast metabolites played an important role in the depolymerization of gluten.PMID:38959802 | DOI:10.1016/j.foodchem.2024.140256
Identifying ligands directly interacting with target protein in medicinal herbs by metabolomic analysis of T2-filtered HSQC spectra
J Pharm Biomed Anal. 2024 Jun 27;248:116329. doi: 10.1016/j.jpba.2024.116329. Online ahead of print.ABSTRACTA protocol for efficiently identifying ligands directly interacting with a target protein in complex extracts of medicinal herbs was proposed by combining an adapted 2D perfect-echo Carr-Purcell-Meiboom-Gill heteronuclear single quantum correlation (PE-CPMG HSQC) spectrum with metabolomic analysis. PE-CPMG HSQC can suppress the signal interference from the target protein, allowing more accurate peak quantification than conventional HSQC. Inspired from untargeted metabolomics, regions of interest (ROIs) are constructed and quantified for the mixture or complex extract samples with and without a target protein, and then a binding index (BI) of each ROI is determined. ROIs or corresponding peaks significantly perturbed by the presence of the target protein (BI ≥1.5) are detected as differential features, and potential binding ligands identified from the differential features can be equated with bioactive markers associated with the 'treatment' of the target protein. Quantifying ROI can inclusively report the ligand bindings to a target protein in fast, intermediate and slow exchange regimes on nuclear magnetic resonance (NMR) time scale. The approach was successfully implemented and identified Angoroside C, Cinnamic acid and Harpagoside from the extract of Scrophularia ningpoensis Hemsl. as ligands binding to peroxisome proliferator-activated receptor γ. The proposed 2D NMR-based approach saves excess steps for sample processing and has a higher chance of detecting the weaker ligands in the complex extracts of medicinal herbs. We expect that this approach can be applied as an alternative to mining the potential ligands binding to a variety of target proteins from traditional Chinese medicines and herbal extracts.PMID:38959759 | DOI:10.1016/j.jpba.2024.116329
Metabolomics research on treatment of primary liver cancer with Cortex Juglandis Mandshuricae on LC-MS/MS technology
J Pharm Biomed Anal. 2024 Jun 25;248:116320. doi: 10.1016/j.jpba.2024.116320. Online ahead of print.ABSTRACTDiethylnitrosamine (DEN) was applied to create the primary liver cancer (PLC) animal model. In the study, the normal group, model group, cyclophosphamide (CTX) group, Cortex Juglandis Mandshuricae (CJM) extract group, myricetin group and myricitrin group were divided. LC-MS/MS technology was applied to determine the metabolites of liver tissue samples from different locations (nodular and non-nodular parts of liver tissue) in each group of rats. Through metabolomics research, the connection and difference of anti-PLC induced by the CJM extract, myricetin and myricitrin was analyzed. The surface of the liver tissues of rats in the model group was rough, dimly colored, inelastic, on which there were scattered gray white cancer nodules and blood stasis points. The number of cancer nodules was significantly reduced, and the degree of cell malignancy was low, but there were some inflammatory cell infiltrations, necrosis area and karyokinesis in the CJM extract group, myricetin group, myricitrin group and CTX group. The result of metabolic research indicated that 45 potential biomarkers of the PLC were found, as gamma-aminoisobutyrate, taurochenodeoxycholate, xanthurenic acid, etc. There were 22 differential metabolites in the CTX group, 16 differential metabolites in the CJM extract group, 14 differential metabolites in the myricetin group, 14 differential metabolites in the myricitrin group.PMID:38959758 | DOI:10.1016/j.jpba.2024.116320
Multi-omics combined to explore the purging mechanism of Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jun 28;1243:124218. doi: 10.1016/j.jchromb.2024.124218. Online ahead of print.ABSTRACTRhei Radix et Rhizoma and Magnoliae Officinalis Cortex have been used together to treat constipation in the clinical practices for more than 2000 years. Nonetheless, their compatibility mechanism is still unclear. In this study, the amelioration of Rhei Radix et Rhizoma combined with Magnoliae Officinalis Cortex on constipation was systematically and comprehensively evaluated. The results showed that their compatibility could markedly shorten gastrointestinal transport time, increase fecal water content and frequency of defecation, improve gastrointestinal hormone disorders and protect colon tissue of constipation rats compared with the single drug. Furthermore, according to 16S rRNA sequencing in conjunction with UPLC-Q-TOF/MS, the combination of two herbal medications could greatly raise the number of salutary bacteria (Lachnospiraceae, Romboutsia and Subdoligranulum) while decreasing the abundance of pathogenic bacteria (Erysipelatoclostridiaceae). And two herb drugs could markedly improve the disorder of fecal metabolic profiles. A total of 7 different metabolites associated with constipation were remarkably shifted by the compatibility of two herbs, which were mainly related to arachidonic acid metabolism, alpha-linolenic acid metabolism, unsaturated fatty acid biosynthesis and other metabolic ways. Thus, the regulation of intestinal microbiome and its metabolism could be a potential target for Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex herb pair to treat constipation. Furthermore, the multi-omics approach utilized in this study, which integrated the microbiome and metabolome, had potential for investigating the mechanism of traditional Chinese medicines.PMID:38959707 | DOI:10.1016/j.jchromb.2024.124218
Investigation of non-volatile metabolite variations during round green tea processing and effect of pan-frying degree using untargeted metabolomics and objective quantification
Food Chem. 2024 Jun 13;457:140067. doi: 10.1016/j.foodchem.2024.140067. Online ahead of print.ABSTRACTRound green tea (RGT) presents unique properties and is widely distributed in China, and during processing, it undergoes dynamic changes in non-volatile metabolites (NVMs), which are poorly understood. Utilizing UHPLC-Q-Exactive/MS analysis, this study comprehensively characterized 216 NVMs during RGT processing and identified fixation and pan-frying as key processes influencing NVMs. Additionally, 23 key differential NVMs were screened, with amino acid and flavonoid metabolism highlighted as key metabolic pathways for RGT taste and color quality. The impact of pan-frying degree on shape, color, and taste was also explored. Moderate pan-frying led to optimal results, including a tight and round shape, green and bright color, mellow and umami taste, and reduced astringent and bitter taste NVMs, including epigallocatechin gallate, procyanidin B2, myricetin 3-O-galactoside, quinic acid, strictinin, phenylalanine, and theobromine. This study addresses the NVM research gap in RGT processing, thus providing a technical foundation for the precision-oriented processing of high-quality tea.PMID:38959681 | DOI:10.1016/j.foodchem.2024.140067
Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics
Poult Sci. 2024 Jun 8;103(8):103968. doi: 10.1016/j.psj.2024.103968. Online ahead of print.ABSTRACTBerberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.PMID:38959643 | DOI:10.1016/j.psj.2024.103968
Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis
Diabetes Metab Syndr. 2024 Jun 28;18(6):103068. doi: 10.1016/j.dsx.2024.103068. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics.METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis.RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered.CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.PMID:38959546 | DOI:10.1016/j.dsx.2024.103068