PubMed

AAPS J. 2024 Jun 11;26(4):70. doi: 10.1208/s12248-024-00940-8.ABSTRACTSynthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of β-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption.PMID:38862871 | DOI:10.1208/s12248-024-00940-8

BMC Plant Biol. 2024 Jun 11;24(1):529. doi: 10.1186/s12870-024-05229-8.ABSTRACTBACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear.RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding.CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.PMID:38862926 | DOI:10.1186/s12870-024-05229-8

BMC Plant Biol. 2024 Jun 12;24(1):535. doi: 10.1186/s12870-024-05259-2.ABSTRACTBACKGROUND: Cytoplasmic male sterility (CMS) has greatly improved the utilization of heterosis in crops due to the absence of functional male gametophyte. The newly developed sporophytic D1 type CMS (CMS-D1) rice exhibits unique characteristics compared to the well-known sporophytic CMS-WA line, making it a valuable resource for rice breeding.RESULTS: In this research, a novel CMS-D1 line named Xingye A (XYA) was established, characterized by small, transparent, and shriveled anthers. Histological and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays conducted on anthers from XYA and its maintainer line XYB revealed that male sterility in XYA is a result of delayed degradation of tapetal cells and abnormal programmed cell death (PCD) of microspores. Transcriptome analysis of young panicles revealed that differentially expressed genes (DEGs) in XYA, compared to XYB, were significantly enriched in processes related to chromatin structure and nucleosomes during the microspore mother cell (MMC) stage. Conversely, processes associated with sporopollenin biosynthesis, pollen exine formation, chitinase activity, and pollen wall assembly were enriched during the meiosis stage. Metabolome analysis identified 176 specific differentially accumulated metabolites (DAMs) during the meiosis stage, enriched in pathways such as α-linoleic acid metabolism, flavone and flavonol biosynthesis, and linolenic acid metabolism. Integration of transcriptomic and metabolomic data underscored the jasmonic acid (JA) biosynthesis pathway was significant enriched in XYA during the meiosis stage compared to XYB. Furthermore, levels of JA, MeJA, OPC4, OPDA, and JA-Ile were all higher in XYA than in XYB at the meiosis stage.CONCLUSIONS: These findings emphasize the involvement of the JA biosynthetic pathway in pollen development in the CMS-D1 line, providing a foundation for further exploration of the molecular mechanisms involved in CMS-D1 sterility.PMID:38862889 | DOI:10.1186/s12870-024-05259-2

Nat Commun. 2024 Jun 11;15(1):4923. doi: 10.1038/s41467-024-49212-1.ABSTRACTMissions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.PMID:38862484 | DOI:10.1038/s41467-024-49212-1

Nat Commun. 2024 Jun 11;15(1):4862. doi: 10.1038/s41467-024-48841-w.ABSTRACTAs spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.PMID:38862464 | DOI:10.1038/s41467-024-48841-w

Blood Rev. 2024 Jun 6:101219. doi: 10.1016/j.blre.2024.101219. Online ahead of print.ABSTRACTImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by excessive reticuloendothelial platelet destruction and inadequate compensatory platelet production. However, the pathogenesis of ITP is relatively complex, and its exact mechanisms and etiology have not been definitively established. The gut microbiome, namely a diverse community of symbiotic microorganisms residing in the gastrointestinal system, affects health through involvement in human metabolism, immune modulation, and maintaining physiological balance. Emerging evidence reveals that the gut microbiome composition differs in patients with ITP compared to healthy individuals, which is related with platelet count, disease duration, and response to treatment. These findings suggest that the microbiome and metabolome profiles of individuals could unveil a new pathway for aiding diagnosis, predicting prognosis, assessing treatment response, and formulating personalized therapeutic approaches for ITP. However, due to controversial reports, definitive conclusions cannot be drawn, and further investigations are needed.PMID:38862311 | DOI:10.1016/j.blre.2024.101219

Nature. 2024 Jun 11. doi: 10.1038/s41586-024-07639-y. Online ahead of print.ABSTRACTSpaceflight induces molecular, cellular, and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet, current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools, and protocols. Here, we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular, and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, plus Axiom and Polaris. The SOMA resource represents a >10-fold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation, and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific murine data sets. Leveraging the datasets, tools, and resources in SOMA can help accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation, and countermeasures data for upcoming lunar, Mars, and exploration-class missions.PMID:38862028 | DOI:10.1038/s41586-024-07639-y

Biomed Pharmacother. 2024 Jun 10;176:116888. doi: 10.1016/j.biopha.2024.116888. Online ahead of print.ABSTRACTOBJECTIVES: Co-agonists at the glucagon-like peptide-1 and glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Although most co-agonists to date have been heavily GLP1R-biased, glucagon directly acts on the liver to reduce fat content. The aims of this study were to investigate a GCGR-biased co-agonist as treatment for hepatic steatosis in mice.METHODS: Mice with diet-induced obesity (DIO) were treated with Dicretin, a GLP1/GCGR co-agonist with high potency at the GCGR, Semaglutide (GLP1R monoagonist) or food restriction over 24 days, such that their weight loss was matched. Hepatic steatosis, glucose tolerance, hepatic transcriptomics, metabolomics and lipidomics at the end of the study were compared with Vehicle-treated mice.RESULTS: Dicretin lead to superior reduction of hepatic lipid content when compared to Semaglutide or equivalent weight loss by calorie restriction. Markers of glucose tolerance and insulin resistance improved in all treatment groups. Hepatic transcriptomic and metabolomic profiling demonstrated many changes that were unique to Dicretin-treated mice. These include some known targets of glucagon signaling and others with as yet unclear physiological significance.CONCLUSIONS: Our study supports the development of GCGR-biased GLP1/GCGR co-agonists for treatment of MASLD and related conditions.PMID:38861859 | DOI:10.1016/j.biopha.2024.116888

J Chromatogr A. 2024 Jun 8;1730:465060. doi: 10.1016/j.chroma.2024.465060. Online ahead of print.ABSTRACTHydrophilic interaction (liquid) chromatography (HILIC) has become the first choice LC mode for the separation of hydrophilic analytes. Numerous studies reported the poor retention time repeatability of HILIC. The problem was often ascribed to slow equilibration and insufficient re-equilibration time to establish the sensitive semi-immobilized water layer at the interface of the polar stationary phase and the bulk mobile phase. In this study, we compare retention time repeatability in HILIC for borosilicate glass and PFA (co-polymer of tetrafluoroethylene and perfluoroalkoxyethylene) solvent bottles. During this study, we observed peak patterns shifting towards higher retention times (for metabolites and peptides) and lower retention times (oligonucleotide sample) with ongoing analysis time when standard borosilicate glass bottles were used as solvent reservoirs. It was hypothesized that release of ions (sodium, potassium, borate, etc.) from the borosilicate glass bottles leads to alterations (thickness and electrostatic screening effects) in the semi-immobilized water layer which is adsorbed to the polar stationary phase surface under acetonitrile-rich eluents in HILIC with concomitant shifts in retention. When PFA solvent bottles were employed instead of borosilicate glass, retention time repeatability was greatly improved and changed from average 8.4 % RSD for the tested metabolites with borosilicate glass bottles to 0.14 % RSD for the PFA solvent bottles (30 injections over 12 h). Similar improvements were observed for peptides and oligonucleotides. This simple solution to the retention time repeatability problem in HILIC might contribute to a better acceptance of HILIC, especially in fields like targeted and untargeted metabolomics, peptide and oligonucleotide analysis.PMID:38861823 | DOI:10.1016/j.chroma.2024.465060

Lung. 2024 Jun 11. doi: 10.1007/s00408-024-00712-3. Online ahead of print.ABSTRACTBACKGROUND: Fibrotic interstitial lung disease is often identified late due to non-specific symptoms, inadequate access to specialist care, and clinical unawareness precluding proper and timely treatment. Biopsy histological analysis is definitive but rarely performed due to its invasiveness. Diagnosis typically relies on high-resolution computed tomography, while disease progression is evaluated via frequent pulmonary function testing. This study tested the hypothesis that pulmonary fibrosis diagnosis and progression could be non-invasively and accurately evaluated from the hair metabolome, with the longer-term goal to minimize patient discomfort.METHODS: Hair specimens collected from pulmonary fibrosis patients (n = 56) and healthy subjects (n = 14) were processed for metabolite extraction using 2DLC/MS-MS, and data were analyzed via machine learning. Metabolomic data were used to train machine learning classification models tuned via a rigorous combination of cross validation, feature selection, and testing with a hold-out dataset to evaluate classifications of diseased vs. healthy subjects and stable vs. progressed disease.RESULTS: Prediction of pulmonary fibrosis vs. healthy achieved AUROCTRAIN = 0.888 (0.794-0.982) and AUROCTEST = 0.908, while prediction of stable vs. progressed disease achieved AUROCTRAIN = 0.833 (0.784 - 0.882) and AUROCTEST = 0. 799. Top metabolites for diagnosis included ornithine, 4-(methylnitrosamino)-1-3-pyridyl-N-oxide-1-butanol, Thr-Phe, desthiobiotin, and proline. Top metabolites for progression included azelaic acid, Thr-Phe, Ala-Tyr, indoleacetyl glutamic acid, and cytidine.CONCLUSION: This study provides novel evidence that pulmonary fibrosis diagnosis and progression may in principle be evaluated from the hair metabolome. Longer term, this approach may facilitate non-invasive and accurate detection and monitoring of fibrotic lung diseases.PMID:38861171 | DOI:10.1007/s00408-024-00712-3

Methods Mol Biol. 2024;2792:223-240. doi: 10.1007/978-1-0716-3802-6_18.ABSTRACTPlant science has become more and more complex. With the introduction of new experimental techniques and technologies, it is now possible to explore the fine details of plant metabolism. Besides steady-state measurements often applied in gas-exchange or metabolomic analyses, new approaches, e.g., based on 13C labeling, are now available to understand the changes in metabolic concentrations under fluctuating environmental conditions in the field or laboratory. To explore those transient phenomena of metabolite concentrations, kinetic models are a valuable tool. In this chapter, we describe ways to implement and build kinetic models of plant metabolism with the Python software package modelbase. As an example, we use a part of the photorespiratory pathway. Moreover, we show additional functionalities of modelbase that help to explore kinetic models and thus can reveal information about a biological system that is not easily accessible to experiments. In addition, we will point to extra information on the mathematical background of kinetic models to give an impetus for further self-study.PMID:38861091 | DOI:10.1007/978-1-0716-3802-6_18

Microbiol Spectr. 2024 Jun 11:e0352423. doi: 10.1128/spectrum.03524-23. Online ahead of print.ABSTRACTGluten possesses unique properties that render it only partially digestible. Consequently, it exerts detrimental effects on a part of the worldwide population who are afflicted with celiac disease (1%) or related disorders (5%), particularly due to the potential for cross-contamination even when adhering to a gluten-free diet (GFD). Finding solutions to break down gluten during digestion has a high nutritional and social impact. Here, a randomized double-blind placebo-controlled in vivo challenge investigated the gluten-degrading activity of a novel probiotic preparation comprising lactobacilli and their cytoplasmic extracts, Bacillus sp., and bacterial protease. In our clinical trial, we collected feces from 70 healthy volunteers at specific time intervals. Probiotic/placebo administration lasted 32 days, followed by 10 days of wash-out. After preliminary GFD to eliminate residual gluten from feces, increasing amounts of gluten (50 mg-10 g) were administered, each one for 4 consecutive days. Compared to placebo, the feces of volunteers fed with probiotics showed much lower amounts of residual gluten, mainly with increased intakes. Probiotics also regulate the intestinal microbial communities, improving the abundance of genera pivotal to maintaining homeostasis. Quantitative PCR confirmed that all probiotics persisted during the intervention, some also during wash-out. Probiotics promoted a fecal metabolome with potential immunomodulating activity, mainly related to derivatives of branched-chain amino acids and short-chain fatty acids.IMPORTANCE: The untapped potential of gluten-degrading bacteria and their application in addressing the recognized limitations of gluten-related disorder management and the ongoing risk of cross-contamination even when people follow a gluten-free diet (GFD) emphasizes the significance of the work. Because gluten, a common protein found in many cereals, must be strictly avoided to stop autoimmune reactions and related health problems, celiac disease and gluten sensitivity present difficult hurdles. However, because of the hidden presence of gluten in many food products and the constant danger of cross-contamination during food preparation and processing, total avoidance is frequently challenging. Our study presents a novel probiotic preparation suitable for people suffering from gluten-related disorders during GFD and for healthy individuals because it enhances gluten digestion and promotes gut microbiota functionality.PMID:38860826 | DOI:10.1128/spectrum.03524-23

J Cardiovasc Surg (Torino). 2024 Jun 11. doi: 10.23736/S0021-9509.24.13062-5. Online ahead of print.ABSTRACTINTRODUCTION: This systematic review aimed to discuss the current knowledge of possibly useful circulatory biomarkers (other than D-dimers) in the diagnosis of patients with an acute aortic dissection (AAD), to distinguish these patients from patients with Acute Myocardial Infarction (AMI).EVIDENCE ACQUISITION: This study followed the PRISMA guidelines. The databases PubMed, EMBASE and Scopus were systematically searched from inception to May 2023. Studies were included if they presented measurements of biomarker(s) in the blood/plasma/serum samples from adult patients with AAD versus AMI. Articles were excluded if aortic dissection was subacute or chronic (>14 days), if they lack a control group (AMI), or if they were animal studies, revisions, or editorials. The main outcome was the identification of biomarkers that exhibited diagnostic potential to differentiate patients with AAD versus AMI.EVIDENCE SYNTHESIS: The research query resulted in 1342 articles after the removal of duplicates, from which seven were included in the systematic review. The biomarkers identified included general blood assessment, metabolomics, products of the degradation of fibrin, extracellular matrix markers and an ischemia-associated molecule. Most studies lack diagnostic validity such as sensitivity and specificity. In six studies, the concentration of a total of six biomarkers showed significative differences between AAD and AMI group.CONCLUSIONS: A great heterogeneity of molecules has been studied as putative diagnostic markers of AAD versus AMI. Studies of better quality are needed, presenting the diagnostic validity of the molecules under analysis and the putative synergic diagnostic value of the molecules identified so far.PMID:38860700 | DOI:10.23736/S0021-9509.24.13062-5

Environ Sci Technol. 2024 Jun 11. doi: 10.1021/acs.est.4c01328. Online ahead of print.ABSTRACTMicrobial organic matter turnover is an important contributor to the terrestrial carbon dioxide (CO2) budget. Partitioning of organic carbons into biomass relative to CO2 efflux, termed carbon-use efficiency (CUE), is widely used to characterize organic carbon cycling by soil microorganisms. Recent studies challenge proposals of CUE dependence on the oxidation state of the substrate carbon and implicate instead metabolic strategies. Still unknown are the metabolic mechanisms underlying variability in CUE. We performed a multiomics investigation of these mechanisms in Pseudomonas putida, a versatile soil bacterium of the Gammaproteobacteria, processing a mixture of plant matter derivatives. Our 13C-metabolomics data captured substrate carbons into different metabolic pathways: cellulose-derived sugar carbons in glycolytic and pentose-phosphate pathways; lignin-related aromatic carbons in the tricarboxylic acid cycle. Subsequent 13C-metabolic flux analysis revealed a 3-fold lower investment of sugar carbons in CO2 efflux compared to aromatic carbons, in agreement with reported substrate-dependent CUE. Proteomics analysis revealed enzyme-level regulation only for substrate uptake and initial catabolism, which dictated downstream fluxes through CO2-producing versus biomass-synthesizing reactions. Metabolic partitioning as shown here explained the substrate-dependent CUE calculated from reported metabolic flux analyses of other bacteria, further supporting a metabolism-guided perspective for predicting the microbial conversion of accessible organic matter to CO2 efflux.PMID:38860668 | DOI:10.1021/acs.est.4c01328

Mol Genet Genomic Med. 2024 Jun;12(6):e2472. doi: 10.1002/mgg3.2472.ABSTRACTBACKGROUND: Serine residues in the protein backbone of heavily glycosylated proteoglycans are bound to glycosaminoglycans through a tetrasaccharide linker. UXS1 encodes UDP-glucuronate decarboxylase 1, which catalyzes synthesis of UDP-xylose, the donor of the first building block in the linker. Defects in other enzymes involved in formation of the tetrasaccharide linker cause so-called linkeropathies, characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures, dislocations, and more.METHODS: Whole exome sequencing was performed in a father and son who presented with a mild skeletal dysplasia, as well as the father's unaffected parents. Wild-type and mutant UXS1 were recombinantly expressed in Escherichia coli and purified. Enzyme activity was evaluated by LC-MS/MS. In vivo effects were studied using HeparinRed assay and metabolomics.RESULTS: The son had short long bones, normal epiphysis, and subtle metaphyseal changes especially in his legs. The likely pathogenic heterozygous variant NM_001253875.1(UXS1):c.557T>A p.(Ile186Asn) detected in the son was de novo in the father. Purified Ile186Asn-UXS1, in contrast to the wild-type, was not able to convert UDP-glucuronic acid to UDP-xylose. Plasma glycosaminoglycan levels were decreased in both son and father.CONCLUSION: This is the first report linking UXS1 to short-limbed short stature in humans.PMID:38860481 | DOI:10.1002/mgg3.2472

Front Microbiol. 2024 May 27;15:1391059. doi: 10.3389/fmicb.2024.1391059. eCollection 2024.ABSTRACTPlant-microbe interactions are pivotal for ecosystem dynamics and sustainable agriculture, and are influenced by various factors, such as host characteristics, environmental conditions, and human activities. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have revolutionized our understanding of these interactions. Genomics elucidates key genes, transcriptomics reveals gene expression dynamics, proteomics identifies essential proteins, and metabolomics profiles small molecules, thereby offering a holistic perspective. This review synthesizes diverse microbial-plant interactions, showcasing the application of omics in understanding mechanisms, such as nitrogen fixation, systemic resistance induction, mycorrhizal association, and pathogen-host interactions. Despite the challenges of data integration and ethical considerations, omics approaches promise advancements in precision intervention and resilient agricultural practices. Future research should address data integration challenges, enhance omics technology resolution, explore epigenomics, and understand plant-microbe dynamics under diverse conditions. In conclusion, omics technologies hold immense promise for optimizing agricultural strategies and fortifying resilient plant-microbe alliances, paving the way for sustainable agriculture and environmental stewardship.PMID:38860224 | PMC:PMC11163067 | DOI:10.3389/fmicb.2024.1391059

Front Microbiol. 2024 May 27;15:1416235. doi: 10.3389/fmicb.2024.1416235. eCollection 2024.ABSTRACTOur previous studies have revealed that L. acidophilus possesses inhibitory effects on PCV2 proliferation in vivo, although the underlying mechanisms remain elusive. Probiotics like L. acidophilus are known to exert antiviral through their metabolites. Therefore, in this study, non-targeted metabolomics was used to detect the changes in metabolites of L. acidophilus after 24 h of proliferation. Subsequently, high-throughput molecular docking was utilized to analyze the docking scores of these metabolites with PCV2 Cap and Rep, aiming to identify compounds with potential anti-PCV2 effects. The results demonstrated that 128 compounds such as Dl-lactate were significantly increased. The results of high-throughput molecular docking indicated that compounds such as ergocristine, and telmisartan formed complexes with Cap and Rep, suggesting their potential anti-PCV2 properties. Furthermore, compounds like vitamin C, exhibit pharmacological effects consistent with L. acidophilus adding credence to the idea that L. acidophilus may exert pharmacological effects through its metabolites. These results will provide a foundation for the study of L. acidophilus.PMID:38860222 | PMC:PMC11163031 | DOI:10.3389/fmicb.2024.1416235

Front Pharmacol. 2024 May 27;15:1284752. doi: 10.3389/fphar.2024.1284752. eCollection 2024.ABSTRACTBACKGROUND: Both Sophora flavescens (SF) and Astragalus mongholicus (AM) are known for their anti-inflammatory, antifibrotic, and anticancer activities. However, the efficacy, multi-target mechanisms, and therapeutic substances of SF-AM herb pair on the progression of hepatitis-cirrhosis-hepatocellular carcinoma hepatocellular carcinoma (HCC) remain unclear.PURPOSE: To investigate the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the progression of hepatitis-cirrhosis-HCC.METHODS: Firstly, diethylnitrosamine was used to establish the hepatitis-cirrhosis-HCC model. HE staining and non-targeted metabolomics were used to evaluate the efficacy of SF-AM herb pair. Subsequently, the absorbed components of SF-AM herb pair in the plasma of rats were determined through HPLC-Q-TOF-MS/MS analysis. Flow cytometry, Western blot, and qRT-PCR were then employed to assess CD4+ and CD8+ T lymphocytes, PI3K/Akt signaling pathway-related proteins, and their corresponding mRNAs. Simultaneously, the efficacy and mechanism of SF-AM herb pair on HCC were confirmed by in vitro experiments. Finally, Pearson correlation analysis was performed between pharmacodynamic indicators and in vivo components to identify the potential therapeutic substances of SF-AM herb pair.RESULTS: SF-AM herb pair can alleviate the pathological damage and reverse metabolic abnormalities in hepatitis, cirrhosis, and HCC rats, particularly during the hepatitis and cirrhosis stages. Pharmacological researches have demonstrated that SF-AM herb pair can increase the proportion of CD8+ T lymphocytes, inhibit the expression of PI3K, Akt, p-Akt, NF-κB p65, NF-κB pp65, and Bcl-2, as well as increase the expression of IκBα, Bax, and cleaved caspase-3. These findings suggest that SF-AM herb pair has the ability to enhance immunity, anti-inflammation and promote apoptosis. Cell experiments have shown that SF-AM herb pair can inhibit the proliferation of HepG2 cell and regulate the PI3K/Akt signaling pathway. Moreover, 23 absorbed prototypical components and 53 metabolites of SF-AM herb pair were identified at different stages of HCC rats. Pearson correlation analysis revealed that matrine, cytisine, wogonoside, and isoastragaloside are potential therapeutic substances in SF-AM herb pair for the prevention and treatment of hepatitis, cirrhosis, and HCC.CONCLUSION: In summary, this study revealed the efficacy, mechanisms, and potential therapeutic substances of SF-AM herb pair in the hepatitis-cirrhosis-HCC axis and provided a reference for its clinical application.PMID:38860166 | PMC:PMC11163057 | DOI:10.3389/fphar.2024.1284752

Front Physiol. 2024 May 27;15:1396212. doi: 10.3389/fphys.2024.1396212. eCollection 2024.ABSTRACTIntroduction: European mistletoe (Viscum album L.) has been gaining increasing interest in the field of oncology as a clinically relevant adjunctive treatment in many forms of cancer. In the field of phytopharmacology, harvesting time is pivotal. In the last century, a form of metabolomic fingerprinting based on pattern formation was proposed as a way to determine optimal harvesting times to ensure high quality of mistletoe as raw material for pharmaceutical use. In order to further evaluate the information obtained with this metabolomic fingerprinting method, we analysed a large time series of previously undigitised daily mistletoe chromatograms dating back to the 1950s. Methods: These chromatograms were scanned and evaluated using computerized image analysis, resulting in 12 descriptors for each individual chromatogram. We performed a statistical analysis of the data obtained, investigating statistical distributions, cross-correlations and time self-correlations. Results: The analysed dataset spanning about 27 years, contains 19,037 evaluable chromatograms in daily resolution. Based on the distribution and cross-correlation analyses, the 12 descriptors could be clustered into six independent groups describing different aspects of the chromatograms. One descriptor was found to mirror the annual rhythm being well correlated with temperature and a phase shift of 10 days. The time self-correlation analysis showed that most other descriptors had a characteristic self-correlation of ∼50 days, which points to further infradian rhythms (i.e., more than 24 h). Discussion: To our knowledge, this dataset is the largest of its type. The combination of this form of metabolomic fingerprinting with the proposed computer analysis seems to be a promising tool to characterise biological variations of mistletoe. Additional research is underway to further analyse the different rhythms present in this dataset.PMID:38860114 | PMC:PMC11163206 | DOI:10.3389/fphys.2024.1396212

Clin Kidney J. 2024 Apr 24;17(6):sfae108. doi: 10.1093/ckj/sfae108. eCollection 2024 Jun.ABSTRACTBACKGROUND: There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation.METHODS: We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < -0.5), we assessed additional variation by age (height in children), sex, race and body mass index (BMI).RESULTS: A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates and nucleotides were more often negatively correlated with mGFR compared with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry platform and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r < -0.5), 27 were consistently not associated with age (height in children), sex or race.CONCLUSIONS: The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.PMID:38859934 | PMC:PMC11163224 | DOI:10.1093/ckj/sfae108