PubMed

Sci Rep. 2023 Jun 7;13(1):9254. doi: 10.1038/s41598-023-34866-6.ABSTRACTPrivacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to link SomaScan 1.3K proteomes to genomes for 2812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA). We correctly linked 90-95% of proteomes to their correct genome and for 95-99% we identify the 1% most likely links. The linking accuracy in subjects with African ancestry was lower (~ 60%) unless training included diverse subjects. With larger profiling (SomaScan 5K) in the Atherosclerosis Risk Communities (ARIC) correct identification was > 99% even in mixed ancestry populations. We also linked proteomes-to-proteomes and used the proteome only to determine features such as sex, ancestry, and first-degree relatives. When serial proteomes are available, the linking algorithm can be used to identify and correct mislabeled samples. This work also demonstrates the importance of including diverse populations in omics research and that large proteomic datasets (> 1000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered unidentifiable.PMID:37286633 | DOI:10.1038/s41598-023-34866-6

Atherosclerosis. 2023 May 28:S0021-9150(23)00210-1. doi: 10.1016/j.atherosclerosis.2023.05.016. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Since plasma metabolites can modulate blood pressure (BP) and vary between men and women, we examined sex differences in plasma metabolite profiles associated with BP and sympathicovagal balance. Our secondary aim was to investigate associations between gut microbiota composition and plasma metabolites predictive of BP and heart rate variability (HRV).METHODS: From the HELIUS cohort, we included 196 women and 173 men. Office systolic BP and diastolic BP were recorded, and heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated using finger photoplethysmography. Plasma metabolomics was measured using untargeted LC-MS/MS. Gut microbiota composition was determined using 16S sequencing. We used machine learning models to predict BP and HRV from metabolite profiles, and to predict metabolite levels from gut microbiota composition.RESULTS: In women, best predicting metabolites for systolic BP included dihomo-lineoylcarnitine, 4-hydroxyphenylacetateglutamine and vanillactate. In men, top predictors included sphingomyelins, N-formylmethionine and conjugated bile acids. Best predictors for HRV in men included phenylacetate and gentisate, which were associated with lower HRV in men but not in women. Several of these metabolites were associated with gut microbiota composition, including phenylacetate, multiple sphingomyelins and gentisate.CONCLUSIONS: Plasma metabolite profiles are associated with BP in a sex-specific manner. Catecholamine derivatives were more important predictors for BP in women, while sphingomyelins were more important in men. Several metabolites were associated with gut microbiota composition, providing potential targets for intervention.PMID:37286456 | DOI:10.1016/j.atherosclerosis.2023.05.016

J Ethnopharmacol. 2023 Jun 5:116736. doi: 10.1016/j.jep.2023.116736. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated.AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action.MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions.RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD.CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.PMID:37286117 | DOI:10.1016/j.jep.2023.116736

J Ethnopharmacol. 2023 Jun 5:116698. doi: 10.1016/j.jep.2023.116698. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. mixed with porcine cardiac blood (PCB-DS) is mainly employed for the treatment of brain ischemia-induced mental disturbances, palpitations and phlegm confusion based on the traditional principle of Menghe medical sect. PCB is the guide to DS and enhances the effect of DS. However, the potential mechanism of PCB-DS preventing cerebral ischemia/reperfusion injury (CIRI) from the perspective of oxidative stress induced cell apoptosis remains unknown.AIM OF THE STUDY: To investigate the pharmacological activity and molecular mechanism of PCB-DS against CIRI.MATERIALS AND METHODS: DS samples processed with different methods were prepared and UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the respective processing product. The middle cerebral artery occlusion reperfusion model was then established to investigate the pharmacological activities of PCB-DS. Pathological changes in the rat brain were observed by triphenyl tetrazolium chloride (TTC), hematoxylin-eosin, and TUNEL staining. The levels of IL-6, IL-1β, and TNF-α were detected by ELISA to evaluate the inflammatory damage. Metabolomics of cerebrospinal fluid was further used to explore the potential mechanism of PCB-DS in preventing CIRI. Based on this, the levels of oxidative stress-related lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined. The protein levels of PI3K, AKT, Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 proteins of the cerebral infarct zone were finally measured by western blotting.RESULTS: Forty-seven components were identified in four processing products. Compared to DS, the content of total aqueous components in PCB-DS was significantly increased including salvianolic acid B isomer, salvianolic acid D, salvianolic acid F, and salvianolic acid H/I/J. Among the DS, DS processed with wine, DS processed with pig blood, and DS processed with porcine cardiac blood, PCB-DS best alleviated the CIRI through the neurological score, brain infarct volume, brain histopathology and the levels of inflammatory factors in the brain. Twenty-five significant metabolites in the cerebrospinal fluid were screened out between the sham and I/R groups. They were mainly involved in the beta-alanine metabolism, histidine metabolism, and lysine degradation, which indicated that PCB-DS may inhibit oxidative stress-induced apoptosis to achieve treating ischemic stroke. The results of biomedical examination showed that PCB-DS could alleviate oxidative damage, significantly downregulate the expression of Bax, cleaved caspase-3 and cleaved caspase-9, and upregulate the expression of p-PI3K, p-AKT, and Bcl-2.CONCLUSION: In summary, this study demonstrated that PCB-DS alleviated CIRI and the molecular mechanism may be related to inhibiting the oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway.PMID:37286116 | DOI:10.1016/j.jep.2023.116698

Prog Neurobiol. 2023 Jun 5:102480. doi: 10.1016/j.pneurobio.2023.102480. Online ahead of print.ABSTRACTThe epilepsies are a group of complex neurological disorders characterised by recurrent seizures. Approximately 30% of patients fail to respond to anti-seizure medications, despite the recent introduction of many new drugs. The molecular processes underlying epilepsy development are not well understood and this knowledge gap impedes efforts to identify effective targets and develop novel therapies against epilepsy. Omics studies allow a comprehensive characterisation of a class of molecules. Omics-based biomarkers have led to clinically validated diagnostic and prognostic tests for personalised oncology, and more recently for non-cancer diseases. We believe that, in epilepsy, the full potential of multi-omics research is yet to be realised and we envisage that this review will serve as a guide to researchers planning to undertake omics-based mechanistic studies.PMID:37286031 | DOI:10.1016/j.pneurobio.2023.102480

Sci Total Environ. 2023 Jun 5:164657. doi: 10.1016/j.scitotenv.2023.164657. Online ahead of print.ABSTRACTThe performance of thiosulfate-driven denitrification (TDD) granule reactor and the mechanism of granule sludge bulking were investigated in this study. The results showed that TDD granule bulking occurred under 12 kgNm-3d-1 of nitrogen loading rate (NLR). The higher NLR promoted accumulation of intermediates in the carbon fixation pathway, including citrate, oxaloacetate, oxoglutarate and fumarate. The carbon fixation improved amino acids biosynthesis, which increased proteins (PN) in extracellular polymers (EPS) to 134.6 ± 11.8 mg/gVSS. The excessive PN altered the content, components and chemical groups of EPS, leading to change of granule structure and decline in settling property, permeability and nitrogen removal. By adopting the strategy of intermittently reducing NLR, excess amino acids in sulfur-oxidizing bacteria was consumed through microbial growth-related metabolism instead of EPS synthesis. Therefore, the nitrogen removal rate increased to 10.23 kg-Nm-3d-1 and maintained stable in the long term. The EPS contents decreased from 168.8 ± 13.5 mg/gVSS to 93 ± 11.5 mg/gVSS and the SVI5 decreased from 66 ± 3.5 ml/g to 25 ± 1.5 ml/g. These findings provide an effective strategy to prevent granule bulking and guide practical application of TDD process.PMID:37286004 | DOI:10.1016/j.scitotenv.2023.164657

Cytogenet Genome Res. 2023 Jun 7. doi: 10.1159/000531444. Online ahead of print.ABSTRACTRadiation-related normal tissue injury sustained during cancer radiotherapy or in a radiological or mass casualty nuclear incident is a major health concern. Reducing the risk and mitigating consequences of radiation injury could have a broad impact on cancer patients and citizens. Efforts to discover biomarkers that can determine radiation dose, predict tissue damage, and aid medical triage are underway. Exposure to ionizing radiation causes changes in gene, protein and metabolite expression that needs to be understood to provide a holistic picture for treating acute and chronic radiation induced toxicities. We present evidence that both RNA (mRNA, miRNA, lncRNA) and metabolomic assays may provide useful biomarkers of radiation injury. RNA markers may provide information on early pathway alterations after radiation injury that can predict damage and implicate downstream targets for mitigation. In contrast, metabolomics is impacted by changes in epigenetics, genetics and proteomics and can be considered a downstream marker that incorporates all these changes to provide an assessment of what is currently happening within an organ. We highlight research from the past 10 years to understand how biomarkers may be used to improve personalized medicine in cancer therapy and medical decision making in mass casualty scenarios.PMID:37285811 | DOI:10.1159/000531444

J Hazard Mater. 2023 Jun 3;457:131760. doi: 10.1016/j.jhazmat.2023.131760. Online ahead of print.ABSTRACT2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100 mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e.g., HSI, ALT, and ARG1), and induced systemic inflammation (e.g., G-CSF, MIP-2, RANTES, and VEGF), dyslipidemia (e.g., TC and TG), and bile acid (BA) synthesis (e.g., CA, GCA, and GDCA). Transcriptomic and metabolomic analyses revealed broad perturbations in gene transcripts and metabolites involved in the representative pathways of liver inflammation (e.g., Hmox1, Spi1, L-methionine, valproic acid, and choline), steatosis (e.g., Nr0b2, Cyp1a1, Cyp1a2, Dusp1, Plin3, arachidonic acid, linoleic acid, and palmitic acid), and cholestasis (e.g., FXR/Nr1h4, Cdkn1a, Cyp7a1, and bilirubin). Microbiome analysis revealed reduced relative abundances of beneficial gut microbial taxa (e.g., Ruminococcaceae and Akkermansia muciniphila), which further contributed to the inflammatory response, lipid accumulation, and BA synthesis in the enterohepatic circulation. The observed effect concentrations here were comparable to the highly contaminated wastewaters, showcasing BDNA's hepatotoxic effects at environmentally relevant concentrations. These results shed light on the biomolecular mechanism and important role of the gut-liver axis underpinning BDNA-induced cholestatic liver disorders in vivo.PMID:37285786 | DOI:10.1016/j.jhazmat.2023.131760

Environ Int. 2023 May 24;177:107979. doi: 10.1016/j.envint.2023.107979. Online ahead of print.ABSTRACTBACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results.AIM: The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease.METHODS: Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45-75 years old, 50.6 % men).RESULTS: After adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS.CONCLUSIONS: Our findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.PMID:37285711 | DOI:10.1016/j.envint.2023.107979

Arch Oral Biol. 2023 May 8;153:105720. doi: 10.1016/j.archoralbio.2023.105720. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to explore the key genes, metabolites, and pathways that influence periodontitis pathogenesis by integrating transcriptomic and metabolomic studies.DESIGN: Gingival crevicular fluid samples from periodontitis patients and healthy controls were collected for liquid chromatography/tandem mass-based metabolomics. RNA-seq data for periodontitis and control samples were obtained from the GSE16134 dataset. Differential metabolites and differentially expressed genes (DEGs) between the two groups were then compared. Based on the protein-protein interaction (PPI) network module analysis, key module genes were selected from immune-related DEGs. Correlation and pathway enrichment analyses were performed for differential metabolites and key module genes. A multi-omics integrative analysis was performed using bioinformatic methods to construct a gene-metabolite-pathway network.RESULTS: From the metabolomics study, 146 differential metabolites were identified, which were mainly enriched in the pathways of purine metabolism and Adenosine triphosphate binding cassette transporters (ABC transporters). The GSE16134 dataset revealed 102 immune-related DEGs (458 upregulated and 264 downregulated genes), 33 of which may play core roles in the key modules of the PPI network and are involved in cytokine-related regulatory pathways. Through a multi-omics integrative analysis, a gene-metabolite-pathway network was constructed, including 28 genes (such as platelet derived growth factor D (PDGFD), neurturin (NRTN), and interleukin 2 receptor, gamma (IL2RG)); 47 metabolites (such as deoxyinosine); and 8 pathways (such as ABC transporters).CONCLUSION: PDGFD, NRTN, and IL2RG may be potential biomarkers of periodontitis and may affect disease progression by regulating deoxyinosine to participate in the ABC transporter pathway.PMID:37285682 | DOI:10.1016/j.archoralbio.2023.105720

Plant J. 2023 Jun 7. doi: 10.1111/tpj.16329. Online ahead of print.ABSTRACTLegumes represent an important component of human and livestock diets; they are rich in macro- and micronutrients such as proteins, dietary fibers and polyunsaturated fatty acids. Whilst, several health-promoting and anti-nutritious properties have been associated with grain content, in-depth metabolomics characterization of major legume species remains elusive. In this article, we used both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to assess the metabolic diversity in the five legume species commonly grown in Europe, including common bean, chickpea, lentil, white and pearl lupin at the tissue-specific level. We were able to detect and quantify over 3,430 metabolites covering major nutritional and anti-nutritional compounds. Specifically, the metabolomics atlas includes 224 derivatized metabolites, 2283 specialized metabolites, and 923 lipids. The data generated here will serve the community as a basis for future integration to metabolomics-assisted crop breeding and facilitate the metabolite-based genome-wide association study (mGWAS) to dissect the genetic and biochemical bases of metabolism in legume species.PMID:37285370 | DOI:10.1111/tpj.16329

Environ Sci Technol. 2023 Jun 7. doi: 10.1021/acs.est.3c02071. Online ahead of print.ABSTRACTThe effects and mechanisms of zinc oxide nanoparticles (ZnO NPs) and their aging products, sulfidized (s-) ZnO NPs, on the carbon cycling in the legume rhizosphere are still unclear. We observed that, after 30 days of cultivation, in the rhizosphere soil of Medicago truncatula, under ZnO NP and s-ZnO NP treatments, the dissolved organic carbon (DOC) concentrations were significantly increased by 1.8- to 2.4-fold compared to Zn2+ treatments, although the soil organic matter (SOM) contents did not change significantly. Compared to Zn2+ additions, the additions of NPs significantly induced the production of root metabolites such as carboxylic acids and amino acids and also stimulated the growth of microbes involved in the degradations of plant-derived and recalcitrant SOM, such as bacteria genera RB41 and Bryobacter, and fungi genus Conocybe. The bacterial co-occurrence networks indicated that microbes associated with SOM formation and decomposition were significantly increased under NP treatments. The adsorption of NPs by roots, the generation of root metabolites (e.g., carboxylic acid and amino acid), and enrichment of key taxa (e.g., RB41 and Gaiella) were the major mechanisms by which ZnO NPs and s-ZnO NPs drove DOC release and SOM decomposition in the rhizosphere. These results provide new perspectives on the effect of ZnO NPs on agroecosystem functions in soil-plant systems.PMID:37285309 | DOI:10.1021/acs.est.3c02071

Cell Rep. 2023 Jun 6;42(6):112620. doi: 10.1016/j.celrep.2023.112620. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer that typically demonstrates resistance to chemotherapy. Tumor-associated macrophages (TAMs) are essential in tumor microenvironment (TME) regulation, including promoting chemoresistance. However, the specific TAM subset and mechanisms behind this promotion remain unclear. We employ multi-omics strategies, including single-cell RNA sequencing (scRNA-seq), transcriptomics, multicolor immunohistochemistry (mIHC), flow cytometry, and metabolomics, to analyze chemotherapy-treated samples from both humans and mice. We identify four major TAM subsets within PDAC, among which proliferating resident macrophages (proliferating rMφs) are strongly associated with poor clinical outcomes. These macrophages are able to survive chemotherapy by producing more deoxycytidine (dC) and fewer dC kinases (dCKs) to decrease the absorption of gemcitabine. Moreover, proliferating rMφs promote fibrosis and immunosuppression in PDAC. Eliminating them in the transgenic mouse model alleviates fibrosis and immunosuppression, thereby re-sensitizing PDAC to chemotherapy. Consequently, targeting proliferating rMφs may become a potential treatment strategy for PDAC to enhance chemotherapy.PMID:37285267 | DOI:10.1016/j.celrep.2023.112620

Environ Sci Pollut Res Int. 2023 Jun 7. doi: 10.1007/s11356-023-27990-3. Online ahead of print.ABSTRACTNowadays, people are interested to use plants, especially air-purifying plants, in residential and other indoor settings to purify indoor air and increase the green area in the building. In this study, we investigated the effect of water deficit and low light intensity on the physiology and biochemistry of popular ornamental plants, including Sansevieria trifasciata, Episcia cupreata and Epipremnum aureum. Plants were grown under low light intensity in the range of 10-15 μmol quantum m-2 s-1 and 3 days of water deficit. The results showed that these three ornamental plants responded to water deficit with different pathways. Metabolomic analysis indicated that water deficit affected Episcia cupreata and Epipremnum aureum by inducing a 1.5- to 3-fold increase of proline and a 1.1- to 1.6-fold increase in abscisic acid compared to well-watered conditions, which led to hydrogen peroxide accumulation. This resulted in a reduction of stomatal conductance, photosynthesis rate and transpiration. Sansevieria trifasciata responded to water deficit by significantly increasing gibberellin by around 2.8-fold compared to well-watered plants and proline contents by around 4-fold, while stomatal conductance, photosynthesis rate and transpiration were maintained. Notably, proline accumulation under water deficit stress could be attributed to both gibberellic acid and abscisic acid, depending on plant species. Therefore, the enhancement of proline accumulation in ornamental plants under water deficit could be detected early from day 3 after water deficit conditions, and this compound can be used as a key compound for real-time biosensor development in detecting plant stress under water deficit in a future study.PMID:37284956 | DOI:10.1007/s11356-023-27990-3

Metabolomics. 2023 Jun 7;19(6):55. doi: 10.1007/s11306-023-02017-7.ABSTRACTINTRODUCTION: Various studies have identified TB-induced metabolome variations. However, in most of these studies, a large degree of variation exists between individual patients.OBJECTIVES: To identify differential metabolites for TB, independent of patients' sex or HIV status.METHODS: Untargeted GCxGC/TOF-MS analyses were applied to the sputum of 31 TB + and 197 TB- individuals. Univariate statistics were used to identify metabolites which are significantly different between TB + and TB- individuals (a) irrespective of HIV status, and (b) with a HIV + status. Comparisons a and b were repeated for (i) all participants, (ii) males only and (iii) females only.RESULTS: Twenty-one compounds were significantly different between the TB + and TB- individuals within the female subgroup (11% lipids; 10% carbohydrates; 1% amino acids, 5% other and 73% unannotated), and 6 within the male subgroup (20% lipids; 40% carbohydrates; 6% amino acids, 7% other and 27% unannotated). For the HIV + patients (TB + vs. TB-), a total of 125 compounds were significant within the female subgroup (16% lipids; 8% carbohydrates; 12% amino acids, 6% organic acids, 8% other and 50% unannotated), and 44 within the male subgroup (17% lipids; 2% carbohydrates; 14% amino acids related, 8% organic acids, 9% other and 50% unannotated). Only one annotated compound, 1-oleoyl lysophosphaditic acid, was consistently identified as a differential metabolite for TB, irrespective of sex or HIV status. The potential clinical application of this compound should be evaluated further.CONCLUSIONS: Our findings highlight the importance of considering confounders in metabolomics studies in order to identify unambiguous disease biomarkers.PMID:37284915 | DOI:10.1007/s11306-023-02017-7

Front Plant Sci. 2023 May 22;14:1122621. doi: 10.3389/fpls.2023.1122621. eCollection 2023.ABSTRACTINTRODUCTION: Humic substances (HSs), components of plant biostimulants, are known to influence plant physiological processes, nutrient uptake and plant growth, thereby increasing crop yield. However, few studies have focused on the impact of HS on overall plant metabolism, and there is still debate over the connection between HS' structural characteristics and their stimulatory actions.METHODS: In this study, two different HSs (AHA, Aojia humic acid and SHA, Shandong humic acid) screened in a previous experiment were chosen for foliar spraying, and plant samples were collected on the tenth day after spraying (62 days after germination) to investigate the effects of different HSs on photosynthesis, dry matter accumulation, carbon and nitrogen metabolism and overall metabolism in maize leaf.RESULTS AND DISCUSSION: The results showed different molecular compositions for AHA and SHA and a total of 510 small molecules with significant differences were screened using an ESI-OPLC-MS techno. AHA and SHA exerted different effects on maize growth, with the AHA inducing more effective stimulation than the SHA doing. Untargeted metabolomic analysis revealed that the phospholipid components of maize leaves treated by SHA generally increased significantly than that in the AHA and control treatments. Additionally, both HS-treated maize leaves exhibited different levels of accumulation of trans-zeatin, but SHA treatment significantly decreased the accumulation of zeatin riboside. Compared to CK treatment, AHA treatment resulted in the reorganization of four metabolic pathways: starch and sucrose metabolism, TCA cycle, stilbenes, diarylheptanes, and curcumin biosynthesis, and ABC transport, SHA treatment modified starch and sucrose metabolism and unsaturated fatty acid biosynthesis. These results demonstrate that HSs exert their function through a multifaceted mechanism of action, partially connected to their hormone-like activity but also involving hormoneindependent signaling pathways.PMID:37284724 | PMC:PMC10239833 | DOI:10.3389/fpls.2023.1122621

Front Plant Sci. 2023 May 22;14:1101994. doi: 10.3389/fpls.2023.1101994. eCollection 2023.ABSTRACTPeanut growth, development, and eventual production are constrained by biotic and abiotic stresses resulting in serious economic losses. To understand the response and tolerance mechanism of peanut to biotic and abiotic stresses, high-throughput Omics approaches have been applied in peanut research. Integrated Omics approaches are essential for elucidating the temporal and spatial changes that occur in peanut facing different stresses. The integration of functional genomics with other Omics highlights the relationships between peanut genomes and phenotypes under specific stress conditions. In this review, we focus on research on peanut biotic stresses. Here we review the primary types of biotic stresses that threaten sustainable peanut production, the multi-Omics technologies for peanut research and breeding, and the recent advances in various peanut Omics under biotic stresses, including genomics, transcriptomics, proteomics, metabolomics, miRNAomics, epigenomics and phenomics, for identification of biotic stress-related genes, proteins, metabolites and their networks as well as the development of potential traits. We also discuss the challenges, opportunities, and future directions for peanut Omics under biotic stresses, aiming sustainable food production. The Omics knowledge is instrumental for improving peanut tolerance to cope with various biotic stresses and for meeting the food demands of the exponentially growing global population.PMID:37284721 | PMC:PMC10239885 | DOI:10.3389/fpls.2023.1101994

Oncoimmunology. 2023 Jun 3;12(1):2219591. doi: 10.1080/2162402X.2023.2219591. eCollection 2023.ABSTRACTImmunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.PMID:37284695 | PMC:PMC10240992 | DOI:10.1080/2162402X.2023.2219591

Kidney Int Rep. 2023 Mar 23;8(6):1239-1254. doi: 10.1016/j.ekir.2023.03.015. eCollection 2023 Jun.ABSTRACTINTRODUCTION: Nephrotic syndrome (NS) occurs commonly in children with glomerular disease and glucocorticoids (GCs) are the mainstay treatment. Steroid resistant NS (SRNS) develops in 15% to 20% of children, increasing the risk of chronic kidney disease compared to steroid sensitive NS (SSNS). NS pathogenesis is unclear in most children, and no biomarkers exist that predict the development of pediatric SRNS.METHODS: We studied a unique patient cohort with plasma specimens collected before GC treatment, yielding a disease-only sample not confounded by steroid-induced gene expression changes (SSNS n = 8; SRNS n = 7). A novel "patient-specific" bioinformatic approach merged paired pretreatment and posttreatment proteomic and metabolomic data and identified candidate SRNS biomarkers and altered molecular pathways in SRNS versus SSNS.RESULTS: Joint pathway analyses revealed perturbations in nicotinate or nicotinamide and butanoate metabolic pathways in patients with SRNS. Patients with SSNS had perturbations of lysine degradation, mucin type O-glycan biosynthesis, and glycolysis or gluconeogenesis pathways. Molecular analyses revealed frequent alteration of molecules within these pathways that had not been observed by separate proteomic and metabolomic studies. We observed upregulation of NAMPT, NMNAT1, and SETMAR in patients with SRNS, in contrast to upregulation of ALDH1B1, ACAT1, AASS, ENPP1, and pyruvate in patients with SSNS. Pyruvate regulation was the change seen in our previous analysis; all other targets were novel. Immunoblotting confirmed increased NAMPT expression in SRNS and increased ALDH1B1 and ACAT1 expression in SSNS, following GC treatment.CONCLUSION: These studies confirmed that a novel "patient-specific" bioinformatic approach can integrate disparate omics datasets and identify candidate SRNS biomarkers not observed by separate proteomic or metabolomic analysis.PMID:37284673 | PMC:PMC10239920 | DOI:10.1016/j.ekir.2023.03.015

Plant Environ Interact. 2023 Feb 9;4(1):36-54. doi: 10.1002/pei3.10101. eCollection 2023 Feb.ABSTRACTThrough crosstalk, FLAGELLIN SENSITIVE 2 (FLS2) and RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) are involved in regulating the homeostasis of cellular reactive oxygen species (ROS) and are linked to the metabolic response of plants toward both biotic and abiotic stress. In the present study, we examined the metabolome of Arabidopsis seedlings under drought and salt conditions to better understand the potential role of FLS2 and RBOHD-dependent signaling in the regulation of abiotic stress response. We identified common metabolites and genes that are regulated by FLS2 and RBOHD, and are involved in the response to drought and salt stress. Under drought conditions, D-aspartic acid and the expression of associated genes, such as ASPARAGINE SYNTHASE 2 (ASN2), increased in both fls2 and robed/f double mutants. The accumulation of amino acids, carbohydrates, and hormones, such as L-proline, D-ribose, and indoleacetaldehyde increased in both fls2 and rbohd/f double mutants under salt conditions, as did the expression of related genes, such as PROLINE IMINOPEPTIDASE, PHOSPHORIBOSYL PYROPHOSPHATE SYNTHASE 5, and NITRILASE 3. Collectively, these results indicate that the FLS2-RBOHD module regulates plant response to drought and salt stress through ROS signaling by adjusting the accumulation of metabolites and expression of genes related to metabolite synthesis.PMID:37284598 | PMC:PMC10168046 | DOI:10.1002/pei3.10101