PubMed

Redox Biol. 2023 Sep 14;67:102888. doi: 10.1016/j.redox.2023.102888. Online ahead of print.ABSTRACTAlkyl hydroperoxide reductase (Ahp) is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli (E. coli). Ahp-deficient strains have been found to have high reactive oxygen species (ROS) levels, sufficient to cause cell damage. However, the exact role and underlying mechanisms of Ahp deficiency-induced cell damage remain largely unknown. Here, the E. coli MG1655 ΔAhp mutant strain was constructed as a model of deficiency to assess its role. The cells of the ΔAhp strain were found to be significantly longer than those of the wild strain, with elevated ROS and hydrogen peroxide (H2O2) levels. Proteome, redox proteome and metabolome analyses were performed to systematically present a global and quantitative profile and delineate the redox signaling and metabolic alterations at the proteome, metabolome, and cysteine oxidation site levels. The multiomics data revealed that Ahp deficiency disrupted the redox balance, activated the OxyR system, upregulated oxidative defense proteins and inhibited the TCA cycle to some extent. Surprisingly, the mutant strain shifted from aerobic respiration to anaerobic respiration and fermentation during the logarithmic phase in the presence of sufficient O2. The acid resistance system was activated to mitigate the effect of excessive acid produced by fermentation. Taken together, the results of this study demonstrated that Ahp deficiency triggered cellular redox imbalance and regulated metabolic pathways to confer resistance to submicromolar intracellular H2O2 levels in E. coli.PMID:37725887 | DOI:10.1016/j.redox.2023.102888

J Environ Manage. 2023 Sep 17;346:118996. doi: 10.1016/j.jenvman.2023.118996. Online ahead of print.ABSTRACTNitrogen (N) fertilization is crucial to sustain global food security, but fertilizer N production is energy-demanding and subsequent environmental N losses contribute to biodiversity loss and climate change. N losses can be mitigated be interfering with microbial nitrification, and therefore the use of nitrification inhibitors in enhanced efficiency fertilizers (EEFs) is an important N management strategy to increase N use efficiency and reduce N pollution. However, currently applied nitrification inhibitors have limitations and do not target all nitrifying microorganisms. Here, to identify broad-spectrum nitrification inhibitors, we adopted a drug discovery-based approach and screened 45,400 small molecules on different groups of nitrifying microorganisms. Although a high number of potential nitrification inhibitors were identified, none of them targeted all nitrifier groups. Moreover, a high number of new nitrification inhibitors were shown to be highly effective in culture but did not reduce ammonia consumption in soil. One archaea-targeting inhibitor was not only effective in soil, but even reduced - when co-applied with a bacteria-targeting inhibitor - ammonium consumption and greenhouse gas emissions beyond what is achieved with currently applied nitrification inhibitors. This advocates for combining different types of nitrification inhibitors in EEFs to optimize N management practices and make agriculture more sustainable.PMID:37725864 | DOI:10.1016/j.jenvman.2023.118996

EBioMedicine. 2023 Sep 17;96:104802. doi: 10.1016/j.ebiom.2023.104802. Online ahead of print.ABSTRACTBACKGROUND: Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD.METHODS: A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD).FINDINGS: Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE.INTERPRETATION: The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE.FUNDING: INSERM and Sorbonne Université.PMID:37725854 | DOI:10.1016/j.ebiom.2023.104802

Anal Chem. 2023 Sep 19. doi: 10.1021/acs.analchem.3c02923. Online ahead of print.ABSTRACTThe multiplicity-edited heteronuclear single quantum correlation (ME-HSQC) NMR method is widely used for the structural characterization of marine dissolved organic matter (DOM), which is a complex molecular mixture comprising millions of individual compounds. However, the standard ME-HSQC suffers from significant signal cancellation and subsequent loss of crucial structural information due to the overlap between CH3/CH (positive) and CH2 (negative) cross-peaks in overcrowded regions. This study introduces nonuniform sampling in frequency-reversed ME-HSQC (NUS FR-ME-HSQC), highlighting its remarkable potential for the comprehensive structural characterization of marine DOM. By reversing the frequency of CH2 cross-peaks into an empty region, the FR-ME-HSQC method effectively simplifies the spectra and eliminates signal cancellation. We demonstrate that nonuniform sampling enables the acquisition of comparable spectra in half the time or significantly enhances the sensitivity in time-equivalent spectra. Comparative analysis also identifies vulnerable CH2 cross-peaks in the standard ME-HSQC that coincide with CH3 and CH cross-peaks, resulting in the loss of critical structural details. In contrast, the NUS FR-ME-HSQC retains these missing correlations, enabling in-depth characterization of marine DOM. These findings highlight the potential of NUS FR-ME-HSQC as an advanced NMR technique that effectively addresses challenges such as signal overcrowding and prolonged experimental times, enabling the thorough investigation of complex mixtures with implications in several fields, including chemistry, metabolomics, and environmental sciences. The advantages of NUS FR-ME-HSQC are experimentally demonstrated on two solid-phase-extracted DOM (SPE-DOM) samples from the surface and deep ocean. With this new technology, differences in the composition of DOM from various aquatic environments can be assigned to individual molecules.PMID:37725656 | DOI:10.1021/acs.analchem.3c02923

J Am Soc Nephrol. 2023 Aug 7. doi: 10.1681/ASN.0000000000000195. Online ahead of print.ABSTRACTBACKGROUND: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear.METHODS: Mice with an erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 (eEnt1-/-) and a global deficiency in AMP deaminase 3 (Ampd3-/-) were generated to define their function in two independent CKD models, including angiotensin II (Ang II) infusion and unilateral ureteral obstruction (UUO). Unbiased metabolomics, isotopic adenosine flux, and various biochemical and cell culture analyses coupled with genetic studies were performed. Translational studies in patients with CKD and cultured human erythrocytes examined the role of ENT1 and AMPD3 in erythrocyte function and metabolism.RESULTS: eEnt1-/- mice display severe renal hypoxia, kidney damage, and fibrosis in both CKD models. The loss of eENT1-mediated adenosine uptake reduces intracellular AMP and thus abolishes the activation of AMPKα and bisphosphoglycerate mutase (BPGM). This results in reduced 2,3-bisphosphoglycerate and glutathione, leading to overwhelming oxidative stress in eEnt1-/- mice. Excess reactive oxygen species (ROS) activates AMPD3, resulting in metabolic reprogramming and reduced O2 delivery, leading to severe renal hypoxia in eEnt1-/- mice. By contrast, genetic ablation of AMPD3 preserves the erythrocyte adenine nucleotide pool, inducing AMPK-BPGM activation, O2 delivery, and antioxidative stress capacity, which protect against Ang II-induced renal hypoxia, damage, and CKD progression. Translational studies recapitulated the findings in mice.CONCLUSION: eENT1-AMPD3, two highly enriched erythrocyte purinergic components that sense hypoxia, promote eAMPK-BPGM-dependent metabolic reprogramming, O2 delivery, energy supply, and antioxidative stress capacity, which mitigates renal hypoxia and CKD progression.PMID:37725437 | DOI:10.1681/ASN.0000000000000195

J Physiol. 2023 Sep 19. doi: 10.1113/JP285170. Online ahead of print.ABSTRACTSmall extracellular vesicles (EV) are membrane-encapsulated particles that carry bioactive cargoes, are released by all cell types and are present in all human biofluids. Changes in EV profiles and abundance occur in response to acute exercise, but this study investigated whether individuals with divergent histories of exercise training (recreationally active controls - CON; endurance-trained - END; strength-trained - STR) presented with varied abundances of small EVs in resting samples and whether the abundance of small EVs differed within each group across two measurement days. Participants (n = 38, all male; CON n = 12, END n = 13, STR n = 13) arrived at the lab on two separate occasions in a rested, overnight fasted state, with standardisation of time of day of sampling, recent dietary intake, time since last meal and time since last exercise training session (∼40 h). Whole blood samples were collected and separated into plasma from which small EVs were separated using size exclusion chromatography and identified in accordance with the Minimal Information For Studies of Extracellular Vesicles (MISEV) guidelines. No differences in the abundance of small EVs were observed within or between groups across multiple methods of small EV identification (nanoparticle tracking analysis, flow cytometry, immunoblot of specific EV markers). Targeted metabolomics of the small EV preparations identified 96 metabolites that were associated with the structure and function of small EVs, with no statistically significant differences in concentrations observed across groups. The results of the current study suggest that the abundance and metabolomic profile of small EVs derived from men with divergent histories of exercise training are similar to those in resting blood samples. KEY POINTS: Extracellular vesicles (EV) are membrane-encapsulated particles that are present in circulation and carry bioactive materials as 'cargo'. The abundance and profile of small EVs are responsive to acute exercise, but little is known about the relationship between small EVs and exercise training. This study examined the abundance, and a targeted metabolomic profile, of small EVs separated from the blood of endurance athletes, strength athletes and recreationally active controls at rest (∼40 h after the most recent exercise session) on two separate but identical lab visits. No differences were observed in the abundance or metabolomic profile of small EV preparations between the groups or between the lab visits within each group. Further research should determine whether the bioactive cargoes (e.g. RNA, protein and additional metabolites) carried within EVs are altered in individuals with divergent histories of exercise training or in response to exercise training interventions.PMID:37725436 | DOI:10.1113/JP285170

Clin Cancer Res. 2023 Sep 19. doi: 10.1158/1078-0432.CCR-23-0088. Online ahead of print.ABSTRACTPURPOSE: Lynch Syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacological intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.EXPERIMENTAL DESIGN: To address this, we enrolled 21 LS patients onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes thrice weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNAseq, and spatial transcriptomics by NanoString GeoMx.RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (Prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of NK and CD8+ T cells in the exercise group that were further confirmed by immunohistochemical studies.CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.PMID:37724990 | DOI:10.1158/1078-0432.CCR-23-0088

Eur J Immunol. 2023 Sep 19:e2350536. doi: 10.1002/eji.202350536. Online ahead of print.ABSTRACTViral infections can result in metabolism rewiring of host cells, which in turn affects the viral lifecycle. Phosphoenolpyruvate (PEP), a metabolic intermediate in the glycolytic pathway, plays important roles in several biological processes including anti-tumor T cell immunity. However, whether PEP might participate in modulating viral infection remains largely unknown. Here, we demonstrate that PEP generally inhibits viral replication via upregulation of AATK expression. Targeted metabolomic analyses shown that intracellular level of PEP was increased upon viral infection. PEP treatment significantly restricted viral infection and hence declined subsequent inflammatory response both in vitro and in vivo. Besides, PEP took inhibitory effect on the stage of viral replication and also decreased the mortality of mice with viral infection. Mechanistically, PEP significantly promoted the expression of apoptosis-associated tyrosine kinase (AATK). Knockdown of AATK led to enhanced viral replication and consequent increased levels of cytokines. Moreover, AATK deficiency disabled the antiviral effect of PEP. Together, our study reveals a previously unknown role of PEP in broadly inhibiting viral replication by promoting AATK expression, highlighting the potential application of activation or upregulation of PEP-AATK axis in controlling viral infections. This article is protected by copyright. All rights reserved.PMID:37724936 | DOI:10.1002/eji.202350536

Rep Biochem Mol Biol. 2023 Apr;12(1):127-135. doi: 10.52547/rbmb.12.1.127.ABSTRACTBACKGROUND: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.METHODS: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.RESULTS: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.CONCLUSION: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.PMID:37724146 | PMC:PMC10505474 | DOI:10.52547/rbmb.12.1.127

Anal Bioanal Chem. 2023 Sep 18. doi: 10.1007/s00216-023-04928-9. Online ahead of print.ABSTRACTThe National Institute of Standards and Technology (NIST) has prepared four seafood reference materials (RMs) for use in food safety and nutrition studies: wild-caught and aquacultured salmon (RM 8256 and RM 8257) and wild-caught and aquacultured shrimp (RM 8258 and RM 8259). These materials were characterized using genetic, metabolomic (1H-NMR, nuclear magnetic resonance and LC-HRMS/MS, liquid chromatography high-resolution tandem mass spectrometry), lipidomic, and proteomic methods to explore their use as matrix-matched, multi-omic differential materials for method development towards identifying product source and/or as quality control in untargeted omics studies. The results from experimental replicates were reproducible for each reference material and analytical method, with the most abundant features reported. Additionally, differences between the materials could be detected, where wild-caught and aquacultured seafood could be distinguished using untargeted metabolite, lipid, and protein analyses. Further processing of the fresh-frozen RMs by freeze-drying revealed the freeze-dried seafoods could still be reliably discerned. These results demonstrate the usefulness of these reference materials as tools for omics instrument validation and measurement harmonization in seafood-related studies. Furthermore, their use as differential quality control (QC) materials, regardless of preparation method, may also provide a tool for laboratories to demonstrate proficiency at discriminating between products based on source/species.PMID:37723254 | DOI:10.1007/s00216-023-04928-9

Clin Chim Acta. 2023 Sep 16:117561. doi: 10.1016/j.cca.2023.117561. Online ahead of print.ABSTRACTBACKGROUND: We investigated alterations in the serum metabolomic profile of IgA nephropathy (IgAN) patients and screen biomarkers of IgA nephropathy based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).METHODS: Serum samples from 65 IgAN patients and 31 healthy controls were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Univariate and multivariate analysis were performed to screen the differential metabolites. Differential metabolites should meet both the following two criteria: adjusted P < 0.05 in the univariate analysis and VIP value > 1 in the multivariate model. Pathway analysis was performed to reveal the metabolic pathways that were significantly influenced in IgAN. Spearman correlation analysis was applied to explore the correlation between metabolites and between the metabolites and clinicopathological features of IgAN. A random forest model and Logistics regression analysis were conducted to evaluate the predictive ability of the metabolites.RESULTS: The metabolic profile was significantly altered in IgAN patients compared with healthy controls. Thirty-nine metabolites were identified, including glycerophospholipids, sphingolipids, vitamin K1, vitamin K2, bile acids and amino acids. Sphingolipid metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and glycerophospholipid metabolism were found to be significantly disturbed in the pathway analysis. Differential metabolites were found to be associated with the clinical and pathological features of IgAN patients. Lanosterol, vitamin K1, vitamin K2, and β-elemonic acid were found to have promising predictive ability for IgAN.CONCLUSIONS: We confirmed the differences in the metabolic profiles of IgAN patients and healthy controls and identified the differential metabolites of IgAN, which may help with the further exploration of the pathogenesis and treatment of IgAN.PMID:37722576 | DOI:10.1016/j.cca.2023.117561

Bioresour Technol. 2023 Sep 16:129769. doi: 10.1016/j.biortech.2023.129769. Online ahead of print.ABSTRACTThe study investigated the effectiveness of magnetite and potassium ions (K+) in enhancing anaerobic digestion of high salinity food waste. Results indicated that both magnetite and K+ improved anaerobic digestion in high-salt environments, and their combination yielded even better results. The combination of magnetite and K+ promoted microorganism activity, and resulted in increased abundance of DMER64, Halobacteria and Methanosaeta. Metabolomic analysis revealed that magnetite mainly influenced quorum sensing, while K+ mainly stimulated the synthesis of compatible solutes, aiding in maintaining osmotic balance. The combined additives regulated pathways such as ATP binding cassette transport, methane metabolism, and inhibitory substance metabolism, enabling cells to resist environmental stress and maintain normal metabolic activity. Overall, this study demonstrated the potential of magnetite and K+ to enhance food waste anaerobic digestion in high salt conditions and provided valuable insights into the molecular mechanism.PMID:37722541 | DOI:10.1016/j.biortech.2023.129769

Gerontology. 2023 Sep 18. doi: 10.1159/000533789. Online ahead of print.ABSTRACTDelirium, an acute change in cognition, is common, morbid, and costly, particularly among hospitalized older adults. Despite growing knowledge of its epidemiology, far less is known about delirium pathophysiology. Initial work understanding delirium pathogenesis has focused on assaying single or a limited subset of molecules or genetic loci. Recent technological advances at the forefront of biomarker and drug target discovery have facilitated application of multiple "omics" approaches aimed to provide a more complete understanding of complex disease processes such as delirium. At its basic level, "omics" involves comparison of genes (genomics, epigenomics), transcripts (transcriptomics), proteins (proteomics), metabolites (metabolomics), or lipids (lipidomics) in biological fluids or tissues obtained from patients who have a certain condition (i.e., delirium), and those who do not. Multi-omics analyses of these various types of molecules combined with machine learning and systems biology enables the discovery of biomarkers, biological pathways, and predictors of delirium, thus elucidating its pathophysiology. This review provides an overview of the most recent omics techniques, their current impact on identifying delirium biomarkers, and future potential in enhancing our understanding of delirium pathogenesis. We summarize challenges in identification of specific biomarkers of delirium, and more importantly, in discovering the mechanisms underlying delirium pathophysiology. Based on mounting evidence, we highlight a heightened inflammatory response as one common pathway in delirium risk and progression, and we suggest other promising biological mechanisms that have recently emerged. Advanced multiple omics approaches coupled with bioinformatics methodologies have great promise to yield important discoveries that will advance delirium research.PMID:37722373 | DOI:10.1159/000533789

Atherosclerosis. 2023 Sep 2;382:117265. doi: 10.1016/j.atherosclerosis.2023.117265. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Dyslipidemia is an independent risk factor for atherosclerosis and atherosclerotic cardiovascular disease (ASCVD). To date, a comprehensive assessment of individual lipid species associated with atherosclerosis is lacking in large-scale epidemiological studies, especially in a longitudinal setting. We investigated the association of circulating lipid species and its longitudinal changes with carotid atherosclerosis.METHODS: Using liquid chromatograph-mass spectrometry, we repeatedly measured 1542 lipid species in 3687 plasma samples from 1918 unique American Indians attending two visits (mean ∼5 years apart) in the Strong Heart Family Study. Carotid atherosclerotic plaques were assessed by ultrasonography at each visit. We identified lipids associated with prevalence or progression of carotid plaques, adjusting age, sex, BMI, smoking, hypertension, diabetes, and eGFR. Then we examined whether longitudinal changes in lipids were associated with changes in cardiovascular risk factors. Multiple testing was controlled at false discovery rate (FDR) < 0.05.RESULTS: Higher levels of sphingomyelins, ether-phosphatidylcholines, and triacylglycerols were significantly associated with prevalence or progression of carotid plaques (odds ratios ranged from 1.15 to 1.34). Longitudinal changes in multiple lipid species (e.g., acylcarnitines, phosphatidylcholines, triacylglycerols) were associated with changes in cardiometabolic traits (e.g., BMI, blood pressure, fasting glucose, eGFR). Network analysis identified differential lipid networks associated with plaque progression.CONCLUSIONS: Baseline and longitudinal changes in multiple lipid species were significantly associated with carotid atherosclerosis and its progression in American Indians. Some plaque-related lipid species were also associated with risk for CVD events.PMID:37722315 | DOI:10.1016/j.atherosclerosis.2023.117265

Plant Physiol Biochem. 2023 Sep 12;203:108029. doi: 10.1016/j.plaphy.2023.108029. Online ahead of print.ABSTRACTPine seedling leaf characteristics show a distinct transition from primary to secondary needles, known as heteroblastic change. However, the underlying regulatory mechanism is poorly understood. The molecular mechanism of sugar metabolism involved in regulating heteroblastic changes in Pinus massoniana seedlings was investigated via transcriptomics and targeted metabolomics. The results identified 12 kinds of sugar metabolites in the foliage. Three types of sugar accumulated at the highest levels: sucrose, glucose and fructose. Compared to seedlings with only primary needles (PN), the contents of these soluble sugars were lower in seedlings with developing secondary needle buds (SNB). RNA-seq analysis highlighted 1086 DEGs between PN and SNB seedlings, revealing significant enrichment in KEGG pathways including starch and sucrose metabolism, plant hormone signal transduction and amino sugar and nucleic acid sugar metabolism. Combined transcriptomic and metabolomic analysis revealed that HK, MDH, and ATPase could potentially enhance sugar availability by stimulating the glycolytic/TCA cycle and oxidative phosphorylation. These processes may lead to a reduced sugar content in the foliage of SNB seedlings. We also identified 72 transcription factors, among which the expression levels of MYB, WRKY, NAC and C2H2 family genes were closely related to those of DEGs in the sugar metabolism pathway. In addition, we identified alternative splicing (AS) events in one NAC gene leading to two isoforms, PmNAC5L and PmNAC5S. PmNAC5L was significantly upregulated, while PmNAC5S was significantly downregulated in SNB seedlings. Overall, our results provide new insights into how sugar metabolism is involved in regulating heteroblastic changes in pine seedlings.PMID:37722284 | DOI:10.1016/j.plaphy.2023.108029

Plant Physiol Biochem. 2023 Sep 7;203:108025. doi: 10.1016/j.plaphy.2023.108025. Online ahead of print.ABSTRACTThe wild Atractylodes lancea rhizomes have been traditionally used as herbal medicine. As the increasingly exhaustion of wild A. lancea, the artificial cultivation mainly contributed to the medicinal material production. However, besides the phenotypic variation of rhizome phenotypic trait alteration, the qualities of cultivated A. lancea decrease compared with the wild counterpart. To unveil the physiological and molecular mechanism beneath the phenotypic variation, GC-MS-based volatile organic compounds (VOCs) profiling and RNAseq-based transcriptome analysis were conducted. The volatile metabolomics profiling revealed 65 differentially accumulated metabolites (DAMs) while the transcriptomic profiling identified 12 009 differentially expressed unigenes (DEGs) post-cultivation. The volatile active compounds including atractylone, and eudesmol accumulated more in wild rhizome than in the cultivated counterpart, and several unigenes in terpene synthesis were downregulated under cultivated condition. Compared with the wild A. lancea rhizome, the contents of bioactive Jasmonic Acid (JAs) in cultivated A. lancea rhizome were higher, and evidences that JAs negatively regulate the terpenes biosynthesis in the cultivated A. lancea rhizome were also provided. The combinational omics analysis further indicated the high correlation between the ten cultivation-suppressed VOCs and the cultivation-altered genes for sesquiterpenoids biosynthesis in A. lancea. The network of the cultivation-altered transcription factors (TFs) and the ten VOCs suggested TFs (e.g. Arabidopsis ERF13 homologs and WRKY50) are involved in the regulation of terpenes biosynthesis. These results laid a theoretical basis for developing geo-herbalism medicinal plants with "high quality and optimal shape".PMID:37722282 | DOI:10.1016/j.plaphy.2023.108025

Phytomedicine. 2023 Sep 12;121:155084. doi: 10.1016/j.phymed.2023.155084. Online ahead of print.ABSTRACTBACKGROUND: Cinnamomi cortex called as Rougui (RG) in Chinese was a widely used food-medicine homology. RG has the potential to treat chronic atrophic gastritis (CAG), a disease with widespread impact in the Chinese population.PURPOSE: This study aimed to explore its mechanism against CAG based on amalgamated strategies.METHODS: Network pharmacology was used to predict the potential effective components and the core targets of RG against CAG based on the comprehensive chemical characterization using UHPLC-Q/TOF MS (ultra high performance liquid chromatogramphy-quadrupole/time-of-flight mass spectrometry). The CAG animals model were further used to validate its pharmacodynamics, of which gut microbiota of caecal contents were analyzed by integrating metabolomics, 16S rRNA sequencing, Metorigin metabolite traceability analysis and molecular docking to explore its action mechanism.RESULTS: Network pharmacology firstly predicted the efficacy of RG was attributed to four effective components and seven targets. Metabolomics of caecal contents in CAG rats revealed primary bile acid biosynthesis was its targeted metabolic pathway associated with the metabolism of gut microbiota coupled with Metorigin traceability analysis. 16S rRNA sequencing showed that RG treated CAG by regulating the imbalance of gut microbiota. Molecular docking further confirmed that the effective components of RG could intervene with potential targets, metorigin analysis pathway, and key enzymes of gut microbiota metabolic pathways.CONCLUSION: Our results proved that RG exerted favorable effect on CAG. The four active ingredients (quercetin, kaempferol, oleic acid, and (-)-epicatechin) of RG were the key to exert drug effect, which could targeted the core target of CAG, primary bile acid biosynthesis and intestinal flora metabolic pathways.PMID:37722245 | DOI:10.1016/j.phymed.2023.155084

PLoS Negl Trop Dis. 2023 Sep 18;17(9):e0011604. doi: 10.1371/journal.pntd.0011604. Online ahead of print.ABSTRACTSynthetic insecticides are the primary vector control method used globally. However, the widespread use of insecticides is a major cause of insecticide-resistance in mosquitoes. Hence, this study aimed at elucidating permethrin and temephos-resistant protein expression profiles in Ae. aegypti using quantitative proteomics. In this study, we evaluated the susceptibility of Ae. aegypti from Penang Island dengue hotspot and non-hotspot against 0.75% permethrin and 31.25 mg/l temephos using WHO bioassay method. Protein extracts from the mosquitoes were then analysed using LC-ESI-MS/MS for protein identification and quantification via label-free quantitative proteomics (LFQ). Next, Perseus 1.6.14.0 statistical software was used to perform differential protein expression analysis using ANOVA and Student's t-test. The t-test selected proteins with≥2.0-fold change (FC) and ≥2 unique peptides for gene expression validation via qPCR. Finally, STRING software was used for functional ontology enrichment and protein-protein interactions (PPI). The WHO bioassay showed resistance with 28% and 53% mortalities in adult mosquitoes exposed to permethrin from the hotspot and non-hotspot areas. Meanwhile, the susceptibility of Ae. aegypti larvae revealed high resistance to temephos in hotspot and non-hotspot regions with 80% and 91% mortalities. The LFQ analyses revealed 501 and 557 (q-value <0.05) differentially expressed proteins in adults and larvae Ae. aegypti. The t-test showed 114 upregulated and 74 downregulated proteins in adult resistant versus laboratory strains exposed to permethrin. Meanwhile, 13 upregulated and 105 downregulated proteins were observed in larvae resistant versus laboratory strains exposed to temephos. The t-test revealed the upregulation of sodium/potassium-dependent ATPase β2 in adult permethrin resistant strain, H15 domain-containing protein, 60S ribosomal protein, and PB protein in larvae temephos resistant strain. The downregulation of troponin I, enolase phosphatase E1, glucosidase 2β was observed in adult permethrin resistant strain and tubulin β chain in larvae temephos resistant strain. Furthermore, the gene expression by qPCR revealed similar gene expression patterns in the above eight differentially expressed proteins. The PPI of differentially expressed proteins showed a p-value at <1.0 x 10-16 in permethrin and temephos resistant Ae. aegypti. Significantly enriched pathways in differentially expressed proteins revealed metabolic pathways, oxidative phosphorylation, carbon metabolism, biosynthesis of amino acids, glycolysis, and citrate cycle. In conclusion, this study has shown differentially expressed proteins and highlighted upregulated and downregulated proteins associated with insecticide resistance in Ae. aegypti. The validated differentially expressed proteins merit further investigation as a potential protein marker to monitor and predict insecticide resistance in field Ae. aegypti. The LC-MS/MS data were submitted into the MASSIVE database with identifier no: MSV000089259.PMID:37721966 | DOI:10.1371/journal.pntd.0011604

Sci China Life Sci. 2023 Sep 15. doi: 10.1007/s11427-022-2379-x. Online ahead of print.ABSTRACTSARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination. The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences. Molecular markers for evaluating the pathogenicity of new variants are therefore needed. By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels, six key molecules on the polyamine biosynthesis pathway including putrescine, SAM, dc-SAM, ODC1, SAMS, and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants. To validate our discovery, human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients. Using ODC1 as a proof-of-concept, differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system (RAS) and positively associated with ACE2 activity. Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern (VOCs) and was found to be correlated with each VOCs' pathogenic properties. Particularly, the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models. Our work, therefore, presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.PMID:37721637 | DOI:10.1007/s11427-022-2379-x

Chem Biodivers. 2023 Sep 18:e202300829. doi: 10.1002/cbdv.202300829. Online ahead of print.ABSTRACTMicrobial mats are microbial communities capable of recycling the essential elements of life and considered to be the oldest evidence of microbial communities on Earth. Due to their uniqueness and limited sampling material, analyzing their metabolomic profile in different seasons or conditions is challenging. In this study, microbial mats from a small pond in the Cuatro Cienegas Basin in Coahuila, Mexico, were collected in wet and dry seasons. In addition to these samples, mesocosm experiments from the wet samples were set. These mats are elastic and rise after heavy rainfall by forming gas domes structures known as "Archean domes", by the outgassing of methanogenic bacteria, archaea, and sulfur bacteria. Extracts from all mats and mesocosms were subjected to untargeted mass spectrometry-based metabolomics and molecular networking analysis. Interestingly, each mat showed high chemical diversity that may be explained by the temporal dynamic processes in which they were sampled.PMID:37721179 | DOI:10.1002/cbdv.202300829