PubMed

Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2307981120. doi: 10.1073/pnas.2307981120. Epub 2023 Oct 9.ABSTRACTBenzoxazinoids (BXDs) form a class of indole-derived specialized plant metabolites with broad antimicrobial and antifeedant properties. Unlike most specialized metabolites, which are typically lineage-specific, BXDs occur sporadically in a number of distantly related plant orders. This observation suggests that BXD biosynthesis arose independently numerous times in the plant kingdom. However, although decades of research in the grasses have led to the elucidation of the BXD pathway in the monocots, the biosynthesis of BXDs in eudicots is unknown. Here, we used a metabolomic and transcriptomic-guided approach, in combination with pathway reconstitution in Nicotiana benthamiana, to identify and characterize the BXD biosynthetic pathways from both Aphelandra squarrosa and Lamium galeobdolon, two phylogenetically distant eudicot species. We show that BXD biosynthesis in A. squarrosa and L. galeobdolon utilize a dual-function flavin-containing monooxygenase in place of two distinct cytochrome P450s, as is the case in the grasses. In addition, we identified evolutionarily unrelated cytochrome P450s, a 2-oxoglutarate-dependent dioxygenase, a UDP-glucosyltransferase, and a methyltransferase that were also recruited into these BXD biosynthetic pathways. Our findings constitute the discovery of BXD pathways in eudicots. Moreover, the biosynthetic enzymes of these pathways clearly demonstrate that BXDs independently arose in the plant kingdom at least three times. The heterogeneous pool of identified BXD enzymes represents a remarkable example of metabolic plasticity, in which BXDs are synthesized according to a similar chemical logic, but with an entirely different set of metabolic enzymes.PMID:37812727 | DOI:10.1073/pnas.2307981120

Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2308496120. doi: 10.1073/pnas.2308496120. Epub 2023 Oct 9.ABSTRACTHuman diseases involve metabolic alterations. Metabolomic profiles have served as a vital biomarker for the early identification of high-risk individuals and disease prevention. However, current approaches can only characterize individual key metabolites, without taking into account the reality that complex diseases are multifactorial, dynamic, heterogeneous, and interdependent. Here, we leverage a statistical physics model to combine all metabolites into bidirectional, signed, and weighted interaction networks and trace how the flow of information from one metabolite to the next causes changes in health state. Viewing a disease outcome as the consequence of complex interactions among its interconnected components (metabolites), we integrate concepts from ecosystem theory and evolutionary game theory to model how the health state-dependent alteration of a metabolite is shaped by its intrinsic properties and through extrinsic influences from its conspecifics. We code intrinsic contributions as nodes and extrinsic contributions as edges into quantitative networks and implement GLMY homology theory to analyze and interpret the topological change of health state from symbiosis to dysbiosis and vice versa. The application of this model to real data allows us to identify several hub metabolites and their interaction webs, which play a part in the formation of inflammatory bowel diseases. The findings by our model could provide important information on drug design to treat these diseases and beyond.PMID:37812720 | DOI:10.1073/pnas.2308496120

Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2304668120. doi: 10.1073/pnas.2304668120. Epub 2023 Oct 9.ABSTRACTBacterial natural products have found many important industrial applications. Yet traditional discovery pipelines often prioritize individual natural product families despite the presence of multiple natural product biosynthetic gene clusters in each bacterial genome. Systematic characterization of talented strains is a means to expand the known natural product space. Here, we report genomics, epigenomics, and metabolomics studies of Burkholderia sp. FERM BP-3421, a soil isolate and known producer of antitumor spliceostatins. Its genome is composed of two chromosomes and two plasmids encoding at least 29 natural product families. Metabolomics studies showed that FERM BP-3421 also produces antifungal aminopyrrolnitrin and approved anticancer romidepsin. From the orphan metabolome features, we connected a lipopeptide of 1,928 Da to an 18-module nonribosomal peptide synthetase encoded as a single gene in chromosome 1. Isolation and structure elucidation led to the identification of selethramide which contains a repeating pattern of serine and leucine and is cyclized at the side chain oxygen of the one threonine residue at position 13. A (R)-3-hydroxybutyric acid moiety decorates the N-terminal serine. Initial attempts to obtain deletion mutants to probe the role of selethramide failed. After acquiring epigenome (methylome) data for FERM BP-3421, we employed a mimicry by methylation strategy that improved DNA transfer efficiency. Mutants defective in selethramide biosynthesis showed reduced surfactant activity and impaired swarming motility that could be chemically complemented with selethramide. This work unveils a lipopeptide that promotes surface motility, establishes improved DNA transfer efficiency, and sets the stage for continued natural product identification from a prolific strain.PMID:37812712 | DOI:10.1073/pnas.2304668120

Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2302780120. doi: 10.1073/pnas.2302780120. Epub 2023 Oct 9.ABSTRACTBrain L-serine is critical for neurodevelopment and is thought to be synthesized solely from glucose. In contrast, we found that the influx of L-serine across the blood-brain barrier (BBB) is essential for brain development. We identified the endothelial Slc38a5, previously thought to be a glutamine transporter, as an L-serine transporter expressed at the BBB in early postnatal life. Young Slc38a5 knockout (KO) mice exhibit developmental alterations and a decrease in brain L-serine and D-serine, without changes in serum or liver amino acids. Slc38a5-KO brains exhibit accumulation of neurotoxic deoxysphingolipids, synaptic and mitochondrial abnormalities, and decreased neurogenesis at the dentate gyrus. Slc38a5-KO pups exhibit motor impairments that are affected by the administration of L-serine at concentrations that replenish the serine pool in the brain. Our results highlight a critical role of Slc38a5 in supplying L-serine via the BBB for proper brain development.PMID:37812701 | DOI:10.1073/pnas.2302780120

ACS Nano. 2023 Oct 9. doi: 10.1021/acsnano.3c03066. Online ahead of print.ABSTRACTTo investigate the mechanisms by which g-C3N4 alleviates metal(loid)-induced phytotoxicity, rice seedlings were exposed to 100 and 250 mg/kg graphitic carbon nitride (g-C3N4) with or without coexposure to 10 mg/kg Cd and 50 mg/kg As for 30 days. Treatment with 250 mg/kg g-C3N4 significantly increased shoot and root fresh weight by 22.4-29.9%, reduced Cd and As accumulations in rice tissues by 20.6-26.6%, and elevated the content of essential nutrients (e.g., K, S, Mg, Cu, and Zn) compared to untreated controls. High-throughput sequencing showed that g-C3N4 treatment increased the proportion of plant-growth-promoting endophytic bacteria, including Streptomyces, Saccharimonadales, and Thermosporothrix, by 0.5-3.30-fold; these groups are known to be important to plant nutrient assimilation, as well as metal(loid) resistance and bioremediation. In addition, the population of Deinococcus was decreased by 72.3%; this genus is known to induce biotransformation As(V) to As(III). Metabolomics analyses highlighted differentially expressed metabolites (DEMs) involved in the metabolism of tyrosine metabolism, pyrimidines, and purines, as well as phenylpropanoid biosynthesis related to Cd/As-induced phytotoxicity. In the phenylpropanoid biosynthesis pathway, the increased expression of 4-coumarate (1.13-fold) and sinapyl alcohol (1.26-fold) triggered by g-C3N4 coexposure with Cd or As played a critical role in promoting plant growth and enhancing rice resistance against metal(loid) stresses. Our findings demonstrate the potential of g-C3N4 to enhance plant growth and minimize the Cd/As-induced toxicity in rice and provide a promising nanoenabled strategy for remediating heavy metal(loid)-contaminated soil.PMID:37812587 | DOI:10.1021/acsnano.3c03066

Anal Methods. 2023 Oct 9. doi: 10.1039/d3ay01033c. Online ahead of print.ABSTRACTArchaeological silk undergoes destructive and irreversible changes during the natural process of decay. However, in-depth studies on the influence of this biological factor are still lacking. Here, a combination of proteomics and metabolomics is proposed for the first time to explore the interaction between bacteria and historical silk during biodegradation, which provides information on changes at the molecular level of proteins and bacterial metabolites. Morphological observation revealed biofilms produced by Stenotrophomonas maltophilia and Pseudomonas alcaligenes when cultured in the stationary phase and confirmed severe deterioration of silk. Proteomics showed that S. maltophilia had an unbiased effect on silk fibroin, indicating its ability to disrupt both heavy and light chains, as well as other proteins, while P. alcaligenes showed an affinity for more disordered proteins. Analysis of bacterial metabolites showed that overall activity reduction and significant accumulation of fatty acid and phenol metabolites occurred after silk addition, suggesting that the presence of silk may inhibit the activity of an individual strain. This study provides a new insight into the microbial degradation mechanism of archaeological silk.PMID:37812415 | DOI:10.1039/d3ay01033c

Plant Cell Rep. 2023 Oct 9. doi: 10.1007/s00299-023-03079-6. Online ahead of print.ABSTRACTOsERF096 negatively regulates rice cold tolerance and mediates IAA biosynthesis and signaling under cold stress. The APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors play important roles in regulating plant tolerance to abiotic stress. OsERF096 was previously identified as a direct target of miR1320, and was suggested to negatively regulate rice cold tolerance. In this study, we performed RNA-sequencing and targeted metabolomics assays to reveal the regulatory roles of OsERF096 in cold stress response. GO and KEGG analysis of differentially expressed genes showed that the starch and sucrose metabolism, plant-pathogen interaction, and plant hormone signal transduction pathways were significantly enriched. Quantification analysis confirmed a significant difference in sugar contents among WT and OsERF096 transgenic lines under cold treatment. Targeted metabolomics analysis uncovered that IAA accumulation and signaling were modified by OsERF096 in response to cold stress. Expectedly, qRT-PCR assays confirmed significant OsIAAs and OsARFs expression changes in OsERF096 transgenic lines. Finally, we identified three targets of OsERF096 based on RNA-seq, qRT-PCR, and dual-LUC assays. In summary, these results revealed the multiple regulatory roles of OsERF096 in cold stress response.PMID:37812280 | DOI:10.1007/s00299-023-03079-6

Bioinformatics. 2023 Oct 9:btad618. doi: 10.1093/bioinformatics/btad618. Online ahead of print.ABSTRACTMOTIVATION: Multiple factors can impact accuracy and reproducibility of mass spectrometry data. There is a need to integrate quality assessment and control into data analytic workflows.RESULTS: The MsQuality package calculates 43 low-level quality metrics based on the controlled mzQC vocabulary defined by the HUPO-PSI on a single mass spectrometry-based measurement of a sample. It helps to identify low-quality measurements and track data quality. Its use of community-standard quality metrics facilitates comparability of quality assessment and control (QA/QC) criteria across datasets.AVAILABILITY: The R package MsQuality is available through Bioconductor at https://bioconductor.org/packages/MsQuality.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:37812234 | DOI:10.1093/bioinformatics/btad618

Microbiol Spectr. 2023 Oct 9:e0178623. doi: 10.1128/spectrum.01786-23. Online ahead of print.ABSTRACTMicrobial community imbalance is the main cause of soybean intercropping, but the mechanism of soybean soil fungal community diversity change induced by continuous cropping is still unclear. This study analyzes the fungal community diversity and the change of fungal communities in compartments of different root systems of intercropped soybeans by high-throughput sequencing (endosphere, rhizoplane, and rhizosphere) between continuous cropping and maize-soybean rotation. The results showed that the community composition and the diversity of compartments of different root systems of intercropped soybeans are different, and fungal diversities showed a decreasing trend from rhizosphere to endosphere. Continuous cropping significantly increased fungal community diversities in different root compartments and changed their formation, enrichment, and depletion processes. Continuous cropping brings about the enrichment of soil pathogens, but only partial soil pathogens could colonize from the rhizosphere to the endosphere. All these suggested that root compartments had selective effects on root-associated fungal community diversity. Additionally, metabolomics assay revealed that continuous cropping soybean markedly altered soil metabolic profiling. Correlation analysis results showed that fungal community diversity was significantly correlated with soil metabolites. To sum up, under different planting patterns, the diversity and the functional mode of soybean soil microbial community have changed. Continuous cropping has increased the abundance of pathogenic fungi in soybean soil, resulting in changes in the correlation between soil fungi and metabolites, and then changed the soil metabolic spectrum.IMPORTANCESoybean yield can be affected by soybean soil fungal communities in different tillage patterns. Soybean is an important food crop with great significance worldwide. Continuous cultivation resulted in soil nutrient deficiencies, disordered metabolism of root exudates, fungal pathogen accumulation, and an altered microbial community, which brought a drop in soybean output. In this study, taking the soybean agroecosystem in northeast China, we revealed the microbial ecology and soil metabolites spectrum, especially the diversity and composition of soil fungi and the correlation of pathogenic fungi, and discussed the mechanisms and the measures of alleviating the obstacles.PMID:37811990 | DOI:10.1128/spectrum.01786-23

J Leukoc Biol. 2023 Oct 9:qiad121. doi: 10.1093/jleuko/qiad121. Online ahead of print.ABSTRACTMacrophages are key immune cells that can adapt their metabolic phenotype in response to different stimuli. Lysine deacetylases (KDAC) are important enzymes regulating inflammatory gene expression and KDAC inhibitors have been shown to exert anti-inflammatory effects in models of chronic obstructive pulmonary disease (COPD). We hypothesized that these anti-inflammatory effects may be associated with metabolic changes in macrophages. To validate this hypothesis, we used an unbiased and a targeted proteomic approach to investigate metabolic enzymes as well as LC- and GC-MS to quantify metabolites in combination with the measurement of functional parameters in primary murine alveolar-like macrophages after lipopolysaccharide (LPS)-induced activation in the presence or absence of KDAC inhibition. We found that KDAC inhibition resulted in reduced production of inflammatory mediators such as TNF-α and IL-1β. However, only minor changes in macrophage metabolism were observed, as only one of the KDAC inhibitors slightly increased mitochondrial respiration while no changes in metabolite levels were seen. However, KDAC inhibition specifically enhanced expression of proteins involved in ubiquitination, which may be a driver of the anti-inflammatory effects of KDAC inhibitors. Our data illustrate that a multi-omics approach provides novel insights into how macrophages interact with cues from their environment. More detailed studies investigating ubiquitination as a potential driver of KDAC inhibition will help developing novel anti-inflammatory drugs for difficult to treat diseases such as COPD.PMID:37811856 | DOI:10.1093/jleuko/qiad121

Physiol Genomics. 2023 Oct 9. doi: 10.1152/physiolgenomics.00072.2023. Online ahead of print.ABSTRACTCardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in chronic stable angina (CSA) and acute coronary syndrome (ACS) patients compared to healthy controls. Bacterial alpha diversity in stool from ACS or CSA patients was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units assigned to commensal taxa differentiating ACS patients from healthy controls at both baseline and follow up. Both CSA and ACS patients had significantly higher levels of trimethylamine N-oxide compared to healthy controls (CSA; 0.032 ± 0.023 mmol/L, p <0.01 vs healthy and ACS; 0.032 ± 0.023 mmol/L, p =0.02 vs healthy respectively). ACS patients had reduced levels of propionate, and butyrate (119 ± 4 vs 139 ± 5.1 µM, p =0.001 and 14 ± 4.3 vs 23.5 ± 8.1 µM, p <0.001 respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs 1834 ± 45.8 ng/mL, p <0.0001) and sCD163 levels (457.3 ± 31.8 vs 326.8 ± 20.7 ng/mL, p =0.001), compared to healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in both CSA and ACS patients compared to healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD.PMID:37811721 | DOI:10.1152/physiolgenomics.00072.2023

Am J Physiol Regul Integr Comp Physiol. 2023 Oct 9. doi: 10.1152/ajpregu.00246.2022. Online ahead of print.ABSTRACTDuchenne muscular dystrophy (DMD), a progressive muscle disease caused by the absence of functional dystrophin protein, is associated with multiple cellular, physiological, and metabolic dysfunctions. As an added complication to the primary insult, obesity/insulin resistance (O/IR) is frequently reported in DMD patients; however, how IR impacts disease severity is unknown. We hypothesized a high-fat, high sucrose diet (HFHSD) would induce O/IR, exacerbate disease severity, and cause metabolic alterations in dystrophic mice. To test this hypothesis, we treated 7-wk old mdx (disease model) and C57 mice with a control diet (CD) or a HFHSD for 15 weeks. The HFHSD induced insulin resistance, glucose intolerance and hyperglycemia in C57 and mdx mice. Of note, mdx mice on CD were also insulin resistant. Additionally, visceral adipose tissue weights were increased with HFHSD in C57 and mdx mice though differed by genotype. Serum creatine kinase activity and histopathological analyses using Masson's trichrome staining in diaphragm indicated muscle damage was driven by dystrophin deficiency but was not augmented by diet. In addition, markers of inflammatory signaling, mitochondrial abundance, and autophagy were impacted by disease but not diet. Despite this, in addition to disease signatures in CD-fed mice, metabolomic and lipidomic analyses demonstrated a HFHSD caused some common changes in C57 and mdx mice and some unique signatures of O/IR within the context of dystrophin deficiency. In total, these data revealed that in mdx mice, 15 weeks of a HFHSD did not overtly exacerbate muscle injury but further impaired the metabolic status of dystrophic muscle.PMID:37811713 | DOI:10.1152/ajpregu.00246.2022

Front Nutr. 2023 Sep 22;10:1243503. doi: 10.3389/fnut.2023.1243503. eCollection 2023.ABSTRACTThe study of fermentation and brewing has a long history of pioneering discoveries that continue to influence modern industrial food production. Since then, numerous research endeavors have yielded conventional criteria that guide contemporary brewing practices. However, the intricate open challenges faced today necessitate a more exhaustive understanding of the process at the molecular scale. We have developed an ultra-high-resolution mass spectrometric analysis (FT-ICR-MS) of the brewing process that can rapidly and comprehensively resolve thousands of molecules. This approach allows us to track molecular fluctuation during brewing at the level of chemical compositions. Employing biological triplicates, our investigation of two brewing lines that are otherwise identical except for the malt used revealed over 8,000 molecular descriptors of the brewing process. Metabolite imprints of both the similarities and differences arising from deviating malting temperatures were visualized. Additionally, we translated traditional brewing attributes such as the EBC-value, free amino nitrogen, pH-value, and concentration curves of specific molecules, into highly correlative molecular patterns consisting of hundreds of metabolites. These in-depth molecular imprints provide a better understanding of the molecular circumstances leading to various changes throughout the brewing process. Such chemical maps go beyond the observation of traditional brewing attributes and are of great significance in the investigation strategies of current open challenges in brewing research. The molecular base of knowledge, along with advancements in technological and data integration schemes, can facilitate the efficient monitoring of brewing and other productions processes.PMID:37810931 | PMC:PMC10557258 | DOI:10.3389/fnut.2023.1243503

ACS Omega. 2023 Sep 20;8(39):35555-35570. doi: 10.1021/acsomega.3c00122. eCollection 2023 Oct 3.ABSTRACTFu-Zheng-Qu-Xie (FZQX) decoction is a traditional Chinese herbal prescription for the treatment of lung cancer and exerts proapoptotic and immunomodulatory effects. It has been clinically suggested to be effective in improving the survival of postoperative early-stage lung adenocarcinoma (LUAD), but the mechanism remains unclear. In this study, we used network pharmacology coupled with metabolomics approaches to explore the pharmacological action and effective mechanism of FZQX against the recurrence and metastasis of postoperative early-stage LUAD. Network pharmacology analysis showed that FZQX could prevent the recurrence and metastasis of postoperative early-stage LUAD by regulating a series of targets involving vascular endothelial growth factor receptor 2, estrogen receptor 1, sarcoma gene, epidermal growth factor receptor, and protein kinase B and by influencing the Ras, PI3K-Akt, and mitogen-activated protein kinase signaling pathways. In liquid chromatography-mass spectrometry analysis, 11 differentially expressed metabolites, including PA(12:0/18:4(6Z,9Z,12Z,15Z)), PC(16:0/0:0)[U], LysoPC(18:1(11Z)), and LysoPC(18:0), were discovered in the FZQX-treated group compared to those in the model group before treatment or normal group. They were enriched in cancer metabolism-related signaling pathways such as central carbon metabolism in cancer, choline metabolism, and glycerol phospholipid metabolism. Collectively, our results suggest that the multicomponent and multitarget interaction network of FZQX inhibits the recurrence and metastasis of postoperative early-stage LUAD by activating the receptor signal transduction pathway to inhibit proliferation, induce cell apoptosis, inhibit aerobic glycolysis, and reprogram tumor lipid metabolism.PMID:37810735 | PMC:PMC10552138 | DOI:10.1021/acsomega.3c00122

Front Plant Sci. 2023 Sep 22;14:1111875. doi: 10.3389/fpls.2023.1111875. eCollection 2023.ABSTRACTDrought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition.PMID:37810398 | PMC:PMC10557149 | DOI:10.3389/fpls.2023.1111875

Front Plant Sci. 2023 Sep 21;14:1282465. doi: 10.3389/fpls.2023.1282465. eCollection 2023.NO ABSTRACTPMID:37810395 | PMC:PMC10552640 | DOI:10.3389/fpls.2023.1282465

Front Plant Sci. 2023 Sep 22;14:1292878. doi: 10.3389/fpls.2023.1292878. eCollection 2023.NO ABSTRACTPMID:37810378 | PMC:PMC10556855 | DOI:10.3389/fpls.2023.1292878

iScience. 2023 Sep 19;26(10):107948. doi: 10.1016/j.isci.2023.107948. eCollection 2023 Oct 20.ABSTRACTThe metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.PMID:37810253 | PMC:PMC10551651 | DOI:10.1016/j.isci.2023.107948

Heliyon. 2023 Sep 14;9(9):e19949. doi: 10.1016/j.heliyon.2023.e19949. eCollection 2023 Sep.ABSTRACTQijiao Shengbai capsule (QJSB) is formulated according to the traditional Chinese medicine formula, its function is to nourish Qi and blood, improve the body's immunity. Leukopenia has been treated with it in clinical settings. However, the mechanism of leukopenia from the perspective of intestinal tract has not been reported. This study combined metabolomics and 16S rRNA sequencing technologies to investigate the mechanism of QJSB on leukopenia from the intestine. As a result of cyclophosphamide induction in mice, the results demonstrated that QJSB may greatly increase the quantity of peripheral leukocytes (including neutrophils). Meanwhile, QJSB had a restorative effect on the colon of leukopenic mice; it also increased the level of IL-2, IL-6 and G-CSF in the intestine, further enhancing the immunity and hematopoietic function of mice. Metabolic studies showed that QJSB altered 27 metabolites, most notably amino acid metabolism. In addition, QJSB had a positive regulatory effect on the intestinal microbiota, and could alter community composition by improving the diversity and abundance of the intestinal microbial, which mainly involved 6 related bacterial groups, and primarily regulates three associated SCFAs (acetic acid, butyrate acid and valeric acid). Therefore, this study suggests that QJSB can improve hematopoietic function, enhance the immune system, relieve leucopenia and improve the gut in leucopenic mice by modulating metabolic response pathways, fecal metabolites and intestinal microbiota.PMID:37810141 | PMC:PMC10559567 | DOI:10.1016/j.heliyon.2023.e19949

Heliyon. 2023 Sep 9;9(9):e20034. doi: 10.1016/j.heliyon.2023.e20034. eCollection 2023 Sep.ABSTRACTPodocarpus is the most dominant genus of Podocarpaceae, with higher taxonomical proximity to the Taxaceae, having numerous pharmaceutical applications, however, scarce studies dealing with the physiological and metabolic criteria of Podocarpus in Egypt were reported. Thus, the objective of this work was to assess the physiological and metabolical patterns of the different species of Podocarpus; P. gracilior, P. elongates, P. macrophyllus and P. neriifolius. The highest terpenoids contents were reported in P. neriifolius, followed by P. elongatus, and P. macrophyllus. P. gracilior had the highest antioxidants amount, followed by P. macrophyllus, P. neriifolius and P. elongatus. From the GC/MS metabolic profiling, caryophyllene, β-cadinene, β-cuvebene, vitispirane, β-cadinene and amorphene were the most dominant metabolites in P. gracilior. β-Caryophyllene was the common in P. gracilior, P. elongatus, P. macrophyllus and P. neriifolius with an obvious fluctuation. The plant methanolic extracts have an obvious activity against the multidrug resistant bacteria; E. coli, P. aeruginosa, S. pyogenes and S. aureus, and fungi; A. fumigatus, A. flavus, A. niger and C. albicans in a concentration-dependent manner. The highest Taxol yield was assessed in the extracts of P. elongatus (16.4 μg/gdw), followed by P. macrophyllus, and P. neriifolius. The chemical identity of Taxol derived from P. elongatus was resolved by LC/MS, with molecular mass 854.6 m/z, and similar structural fragmentation pattern of the authentic one. The highest antitumor activity of P. elongatus extracted Taxol was assessed towards HCT-116 (30.2 μg/ml), HepG-2 (53.7 μg/ml) and MCF-7 (71.8 μg/ml). The ITS sequence of P. elongatus "as potent Taxol producer" was deposited on Genbank with accession #ON540734.1, that is the first record of Podocarpus species on Genbank.PMID:37810029 | PMC:PMC10559778 | DOI:10.1016/j.heliyon.2023.e20034