PubMed

Metabolites. 2022 Nov 11;12(11):1098. doi: 10.3390/metabo12111098.ABSTRACTFreezing and thawing plasma samples is known to perturb metabolite stability. However, no study has systematically tested how different freezing and thawing methods affect plasma metabolite levels. The objective of this study was to isolate the effects of freezing from thawing on mouse plasma metabolite levels, by comparing a matrix of freezing and thawing conditions through 10 freeze-thaw cycles. We tested freezing with liquid nitrogen (LN2), at -80 °C, or at -20 °C, and thawing quickly in room temperature water or slowly on ice. Plasma samples were extracted and the relative abundance of 87 metabolites was obtained via liquid chromatography-mass spectrometry (LC-MS). Observed changes in metabolite abundance by treatment group correlated with the amount of time it took for samples to freeze or thaw. Thus, snap-freezing with LN2 and quick-thawing with water led to minimal changes in metabolite levels. Conversely, samples frozen at -20 °C exhibited the most changes in metabolite levels, likely because freezing required about 4 h, versus freezing instantaneously in LN2. Overall, our results show that plasma samples subjected to up to 10 cycles of LN2 snap-freezing with room temperature water quick-thawing exhibit remarkable metabolomic stability.PMID:36422241 | DOI:10.3390/metabo12111098

J Pers Med. 2022 Nov 11;12(11):1889. doi: 10.3390/jpm12111889.ABSTRACTDiabetic nephropathy (DN) is one of the specific complications of diabetes mellitus and one of the leading kidney-related disorders, often requiring renal replacement therapy. Currently, the tests commonly used for the diagnosis of DN, albuminuria (AU) and glomerular filtration rate (GFR), have limited sensitivity and specificity and can usually be noted when typical morphological changes in the kidney have already been manifested. That is why the extreme urgency of the problem of early diagnosis of this disease exists. The untargeted metabolomics analysis of blood plasma samples from 80 patients with type 1 diabetes and early and late stages of DN according to GFR was performed using direct injection mass spectrometry and bioinformatics analysis for diagnosing signatures construction. Among the dysregulated metabolites, combinations of 15 compounds, including amino acids and derivatives, monosaccharides, organic acids, and uremic toxins were selected for signatures for DN diagnosis. The selected metabolite combinations have shown high performance for diagnosing of DN, especially for the late stage (up to 99%). Despite the metabolite signature determined for the early stage of DN being characterized by a diagnostic performance of 81%, these metabolites as potential biomarkers might be useful in the evaluation of treatment of the disease, especially at early stages that may reduce the risk of kidney failure development.PMID:36422065 | DOI:10.3390/jpm12111889

J Fungi (Basel). 2022 Nov 15;8(11):1208. doi: 10.3390/jof8111208.ABSTRACTPepper leaf spot is a common disease of Zanthoxylum schinifolium. When it is serious, it directly affects the growth of Z. schinifolium, making the plant unable to blossom and bear fruit, which seriously restricts the development of the Z. schinifolium industry. Therefore, the pathogenic mechanism of leaf spots should be explored to provide a basis for a comprehensive understanding of the disease. Using liquid chromatography-mass spectrometry (LC-MS) technology combined with the data-dependent acquisition, the full spectrum analysis of pathogen mycelium samples was carried out. Partial least squares discriminant analysis (PLS-DA) was used to reveal the differences in metabolic patterns among different groups. Hierarchical clustering analysis (HCA) and PLS-DA were used to reveal the relationship between samples and metabolites, which reflected the metabolomics changes of Pestalotiopsis kenyana in the logarithmic growth phase of mycelia, the stable growth phase of mycelia, the massive spore stage, the induction culture conditions of PDA and Z. schinifolium leaves, and the possible pathogenic substances were selected for pathogenicity detection. PLS-DA had a strong predictive ability, indicating a clear analysis trend between different groups. The results of the metabolomics analysis showed that the differential metabolites of pathogenic bacteria were abundant at different stages and under different medium conditions, and the content of metabolites changed significantly. There were 3922 differential metabolites in nine groups under positive and negative ion modes, including lipids and lipid molecules, organic acids and their derivatives, organic heterocyclic compounds, organic oxygen compounds, carbohydrate polyketides, nucleosides, nucleotides, and analogs. The results of the pathogenicity test showed that the leaves treated with 3,5-dimethoxy benzoic acid, S-(5-adenosy)-l-homocysteine, 2-(1H-indol-3-yl) acetic acid, l-glutamic acid, and 2-(2-acetyl-3,5-dihydroxy phenyl) acetic acid showed different degrees of yellowish-brown lesions. This indicated that these substances may be related to the pathogenicity of P. kenyana, and the incidence was more serious when treated with 3,5-dimethoxybenzoic acid and S-(5-adenosy)- l -homocysteine. This study provides a basis for further analysis of differential metabolites and provides a theoretical reference for the prevention and treatment of Z. schinifolium leaf spot.PMID:36422029 | DOI:10.3390/jof8111208

Mar Drugs. 2022 Nov 14;20(11):713. doi: 10.3390/md20110713.ABSTRACTNovel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria.PMID:36421991 | DOI:10.3390/md20110713

Genes (Basel). 2022 Nov 17;13(11):2142. doi: 10.3390/genes13112142.ABSTRACTCurrently, metabolic-associated fatty liver disease (MAFLD) is a leading global cause of chronic liver disease, and is expected to become one of the most common indications of liver transplantation. MAFLD is associated with obesity, involving multiple mechanisms such as alterations in lipid metabolism, insulin resistance, hyperinflammation, mitochondrial dysfunction, cell apoptosis, oxidative stress, and extracellular matrix formation. However, the onset and progression of MAFLD is variable among individuals, being influenced by intrinsic (personal) and external environmental factors. In this context, sequence structural variants across the human genome, epigenetic phenomena (i.e., DNA methylation, histone modifications, and long non-coding RNAs) affecting gene expression, gut microbiota dysbiosis, and metabolomics/lipidomic fingerprints may account for differences in MAFLD outcomes through interactions with nutritional features. This knowledge may contribute to gaining a deeper understanding of the molecular and physiological processes underlying MAFLD pathogenesis and phenotype heterogeneity, as well as facilitating the identification of biomarkers of disease progression and therapeutic targets for the implementation of tailored nutritional strategies. This comprehensive literature review highlights the potential of nutrigenetic, nutriepigenetic, nutrimetagenomic, nutritranscriptomics, and nutrimetabolomic approaches for the prevention and management of MAFLD in humans through the lens of precision nutrition.PMID:36421817 | DOI:10.3390/genes13112142

Antioxidants (Basel). 2022 Nov 16;11(11):2261. doi: 10.3390/antiox11112261.ABSTRACTCurcuma is one of the most famous medicinal and tropical aromatic plants. Its health benefits have been appreciated and exploited in traditional Asian medicine since ancient times. Various studies have investigated its complex chemical composition and demonstrated the remarkable therapeutic properties of curcuma's phytoconstituents. Oxidative stress is a decisive driving factor triggering numerous pathologies (neurodegenerative, psychiatric and cardiovascular diseases; diabetes; tumors, etc.). Numerous recent studies have focused on the use of natural compounds and nanomaterials as innovative molecular targeting agents as effective therapeutic strategies. In this study, we report, for the first time, the development of a simple target phytocarrier system that capitalizes on the bioactive properties of curcuma and AgNPs. The complete metabolic profile of curcuma was determined based on gas chromatography-mass spectrometry (GC-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). A total of 80 metabolites were identified under mass spectra (MS)-positive mode from 10 secondary metabolite categories: terpenoids, amino acids, diarylheptanoids, flavonoids, phenolic acids, steroids, fatty acids, coumarins, alkaloids and miscellaneous. In addition, the biological activity of each class of metabolites was discussed. A comprehensive characterization (FT-IR, UV-Vis, DLS, SEM, TEM, EDS, zeta potential and XRD) was performed to study the morphostructural properties of this new phytocarrier system. Antioxidant activity of the new phytocarrier system was evaluated using a combination of in vitro methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and cyclic voltammetric method (Trolox equivalent antioxidant capacity (TEAC) electrochemical assay)). Antioxidants assays showed that the phytocarrier system exhibits superior antioxidant properties to those of its components, i.e., curcuma or citrate-coated-AgNPs. These data confirm the potential to enhance relevant theoretical knowledge in the area of innovative antioxidant agents, with potential application in neurodegenerative therapeutic strategies.PMID:36421447 | DOI:10.3390/antiox11112261

Antioxidants (Basel). 2022 Nov 16;11(11):2258. doi: 10.3390/antiox11112258.ABSTRACTWounds adversely affect people's quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.05). Histological analysis revealed a considerable rise in the number of fibroblasts, the amount of collagen, and its cross-linking in LP-treated wounds. Gene expression patterns showed significant elevation of TGF-β levels (2.1-fold change after 7 days treatment and 2.7-fold change in 14 days treatment) and downregulation of the inflammatory TNF-α and IL-1β levels in LP-treated wounds. Regarding in vitro antioxidant activity, LP extract significantly diminished the formation of H2O2 radical (IC50 = 171.6 μg/mL) and scavenged the superoxide radical (IC50 of 286.7 µg/mL), indicating antioxidant potential in a dose-dependent manner. Dereplication of the secondary metabolites using LC-HRMS resulted in the annotation of 16 metabolites. The identified compounds were docked against important wound-healing targets, including vascular endothelial growth factor (VEGF), collagen α-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β). Among dereplicated compounds, luteolin 8-C-glucoside (orientin) demonstrated binding potential to four investigated targets (VEGF, interleukin 1β, TNF-α, and collagen α-1). To conclude, Launaea procumbens extract could be regarded as a promising topical therapy to promote wound healing in excisional wounds, and luteolin 8-C-glucoside (orientin), one of its constituents, is a potential wound-healing drug lead.PMID:36421445 | DOI:10.3390/antiox11112258

Biology (Basel). 2022 Nov 18;11(11):1679. doi: 10.3390/biology11111679.ABSTRACTMobilization and repartition of nutrients and energy are prerequisites for the normal sexual maturity of broodstock. However, there are few studies on the mechanisms of hepatic nutrients and energy metabolism during sexual maturation in female rainbow trout (Oncorhynchus mykiss). This study investigated hepatic metabolite changes and explored the potential nutritional regulation mechanism between mature and immature female rainbow trout by combining UPLC-QTOF/MS metabolomics and biochemical assays. It was observed that hepatic biochemical assays differed considerably between the two groups, such as glucose, triglycerides, hexokinase, lipase, and aspartate aminotransferase. Liver metabolomics showed that various differential metabolites involved in amino acid and lipid metabolism markedly increased, suggesting the enhancement of lipid metabolism and amino acid anabolism in the liver provides the necessary material basis for ovarian development. Meanwhile, glycogen catabolism and glycolysis hold the key to maintaining organismal energy homeostasis with normal sexual maturation of female rainbow trout. Overall, the results from this study suggested that the liver undergoes drastic reprogramming of the metabolic profile in response to mobilization and repartition of nutrients and energy during the sexual maturation of female rainbow trout. This study further deepened the understanding of the reproductive biology of rainbow trout, and provided the theoretical basis and practical ramifications for nutritional requirements of breeding high-quality broodstock in the artificial propagation of rainbow trout.PMID:36421392 | DOI:10.3390/biology11111679

Antibiotics (Basel). 2022 Nov 19;11(11):1658. doi: 10.3390/antibiotics11111658.ABSTRACTApicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against Toxoplasma gondii, the etiological agent of toxoplasmosis, are highly toxic and lack efficacy in eradicating tissue cysts, promoting the establishment of latent infection and acute relapsing disease. Cryptosporidiosis has been recognized as the most frequent waterborne parasitosis in US outbreaks; anti-cryptosporidium drug discovery still faces a major obstacle: drugs that can act on the epicellular parasite. Severe malaria is most commonly caused by the progression of infection with Plasmodium falciparum. In recent years, great progress has been made in the field of antimalarial drugs and vaccines, although the resistance of P. falciparum to artemisinin has recently gained a foothold in Africa. As seen, the search for new drugs against these parasites remains a challenge. Peptide-based drugs seem to be attractive alternative therapeutic agents recently recognized by the pharmaceutical industry, as they can kill different infectious agents and modulate the immune response. A review of the experimental effects of bioactive peptides on these parasites follows, along with comments. In addition, some biological and metabolomic generalities of the parasites are reviewed to elucidate peptide mechanisms of action on Apicomplexan targets.PMID:36421302 | DOI:10.3390/antibiotics11111658

Antibiotics (Basel). 2022 Nov 15;11(11):1631. doi: 10.3390/antibiotics11111631.ABSTRACTMalaria is a persistent illness with a great public health concern. To combat this fatal disease, developing effective antimalarial medications has become a necessity. In the present study, we described the actinomycetes associated with the Red Sea soft coral Nephthea sp. and isolated a strain that was sub-cultured in three different media (M1, ISP2, and OLIGO). Actinomycete isolate's phylogenetic analysis of the 16S rRNA gene revealed that it belongs to the genus Rhodococcus. In vitro screening of the antimalarial activity for three extracts against Plasmodium falciparum was carried out. Non-targeted metabolomics for the chemical characterization of the isolated actinomycete species UA111 derived extracts were employed using high-resolution liquid chromatography-mass spectrometry (LC-HR-MS) for dereplication purposes. Additionally, statistical analysis of the vast LC-MS data was performed using MetaboAnalyst 5.0. Finally, an in silico analysis was conducted to investigate the potential chemical compounds that could be the source of the antimalarial potential. The results revealed that ISP2 media extract is the most effective against Plasmodium falciparum, according to antimalarial screening (IC50 8.5 µg/mL), in contrast, OLIGO media extract was inactive. LC-HRMS-based metabolomics identified a range of metabolites, mainly alkaloids, from the genus Rhodococcus. On the other hand, multivariate analysis showed chemical diversity between the analyzed samples, with ISP2 extract being optimal. The docking analysis was able to anticipate the various patterns of interaction of the annotated compounds with three malarial protein targets (P. falciparum kinase, P. falciparum cytochrome bc1 complex, and P. falciparum lysyl-tRNA synthetase). Among all of the test compounds, perlolyrine (11) and 3097-B2 (12) displayed the best docking profiles. In conclusion, this work demonstrated the value of the established method for the metabolic profiling of marine actinomycetes using the data from liquid chromatography-mass spectrometry (LC-MS), which helps to streamline the difficult isolation stages required for their chemical characterization. In addition, the antimalarial efficacy of this strain has intriguing implications for future pharmaceutical development.PMID:36421275 | DOI:10.3390/antibiotics11111631

Antibiotics (Basel). 2022 Nov 11;11(11):1595. doi: 10.3390/antibiotics11111595.ABSTRACTInvasive plants efficiently colonize non-native territories, suggesting a great production of bioactive metabolites which could be effective antibiofilm weapons. Our study aimed to look for original molecules able to inhibit bispecies biofilm formed by S. aureus and C. albicans. Extracts from five invasive macrophytes (Ludwigia peploides, Ludwigia grandiflora, Myriophyllum aquaticum, Lagarosiphon major and Egeria densa) were prepared and tested in vitro against 24 h old bispecies biofilms using a crystal violet staining (CVS) assay. The activities of the extracts reducing the biofilm total biomass by 50% or more were comparatively analyzed against each microbial species forming the biofilm by flow cytometry (FCM) and scanning electron microscopy. Extracts active against both species were fractionated. Obtained fractions were analyzed by UHPLC-MS/MS and evaluated by the CVS assay. Chemical and biological data were combined into a bioactivity-based molecular networking (BBMN) to identify active compounds. The aerial stem extract of L. grandiflora showed the highest antibiofilm activity (>50% inhibition at 50 µg∙mL-1). The biological, chemical and BBMN investigations of its fractions highlighted nine ions correlated with the antibiofilm activity. The most correlated compound, identified as betulinic acid (BA), inhibited bispecies biofilms regardless of the three tested couples of strains (ATCC strains: >40% inhibition, clinical isolates: ≈27% inhibition), confirming its antibiofilm interest.PMID:36421241 | DOI:10.3390/antibiotics11111595

Artif Organs. 2022 Nov 24. doi: 10.1111/aor.14466. Online ahead of print.ABSTRACTBACKGROUND: Haemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800TM , with HD with 2 MCO dialysers: Theranova 500® and the new Elisio21 HXTM dialyser.METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800TM were randomised to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HXTM .The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000 , detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified.RESULTS: Lower RRs were found for molecules around 20,000 with Elisio 21HXTM compared to OL- HDF (RR prolactin 58.5% versus 66.7%, P=0.034; RR Kappa light chain 63.1% versus 71.8%, P=0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HXTM (2249.9±714.1 mg, 815.2 ±474.0 mg, 442.9±135.9 mg, P<0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HXTM , and then Theranova 500®.CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio21HXTM resulted in lower removal of molecules around 20,000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.PMID:36420938 | DOI:10.1111/aor.14466

Nucleic Acids Res. 2022 Nov 24:gkac1083. doi: 10.1093/nar/gkac1083. Online ahead of print.ABSTRACTThe Bioinformation and DNA Data Bank of Japan (DDBJ) Center (https://www.ddbj.nig.ac.jp) maintains database archives that cover a wide range of fields in life sciences. As a founding member of the International Nucleotide Sequence Database Collaboration (INSDC), our primary mission is to collect and distribute nucleotide sequence data, as well as their study and sample information, in collaboration with the National Center for Biotechnology Information in the United States and the European Bioinformatics Institute. In addition to INSDC resources, the Center operates databases for functional genomics (GEA: Genomic Expression Archive), metabolomics (MetaboBank), and human genetic and phenotypic data (JGA: Japanese Genotype-Phenotype Archive). These databases are built on the supercomputer of the National Institute of Genetics, whose remaining computational capacity is actively utilized by domestic researchers for large-scale biological data analyses. Here, we report our recent updates and the activities of our services.PMID:36420889 | DOI:10.1093/nar/gkac1083

Crit Rev Clin Lab Sci. 2022 Nov 24:1-18. doi: 10.1080/10408363.2022.2140329. Online ahead of print.ABSTRACTThe two common progressive lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are the leading causes of morbidity and mortality worldwide. Asthma-COPD overlap, referred to as ACO, is another complex pulmonary disease that manifests itself with features of both asthma and COPD. The disease has no clear diagnostic or therapeutic guidelines, thereby making both diagnosis and treatment challenging. Though a number of studies on ACO have been documented, gaps in knowledge regarding the pathophysiologic mechanism of this disorder exist. Addressing this issue is an urgent need for improved diagnostic and therapeutic management of the disease. Metabolomics, an increasingly popular technique, reveals the pathogenesis of complex diseases and holds promise in biomarker discovery. This comprehensive narrative review, comprising 99 original research articles in the last five years (2017-2022), summarizes the scientific advances in terms of metabolic alterations in patients with asthma, COPD, and ACO. The analytical tools, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), commonly used to study the expression of the metabolome, are discussed. Challenges frequently encountered during metabolite identification and quality assessment are highlighted. Bridging the gap between phenotype and metabotype is envisioned in the future.PMID:36420874 | DOI:10.1080/10408363.2022.2140329

Comput Struct Biotechnol J. 2022 Nov 8;20:6149-6162. doi: 10.1016/j.csbj.2022.11.008. eCollection 2022.ABSTRACTThe etiology of neuropsychiatric disorders involves complex biological processes at different omics layers, such as genomics, transcriptomics, epigenetics, proteomics, and metabolomics. The advent of high-throughput technology, as well as the availability of large open-source datasets, has ushered in a new era in system biology, necessitating the integration of various types of omics data. The complexity of biological mechanisms, the limitations of integrative strategies, and the heterogeneity of multi-omics data have all presented significant challenges to computational scientists. In comparison to early and late integration, intermediate integration may transform each data type into appropriate intermediate representations using various data transformation techniques, allowing it to capture more complementary information contained in each omics and highlight new interactions across omics layers. Here, we reviewed multi-modal intermediate integrative techniques based on component analysis, matrix factorization, similarity network, multiple kernel learning, Bayesian network, artificial neural networks, and graph transformation, as well as their applications in neuropsychiatric domains. We depicted advancements in these approaches and compared the strengths and weaknesses of each method examined. We believe that our findings will aid researchers in their understanding of the transformation and integration of multi-omics data in neuropsychiatric disorders.PMID:36420153 | PMC:PMC9674886 | DOI:10.1016/j.csbj.2022.11.008

Comput Struct Biotechnol J. 2022 Nov 7;20:6067-6077. doi: 10.1016/j.csbj.2022.10.041. eCollection 2022.ABSTRACTThere is a dearth of studies focused on understanding pharmacokinetics, pharmacodynamics and toxicodynamics of polymyxins following direct administration to the central nervous system (CNS). In this study, for the first time, untargeted metabolomics were employed to ascertain the perturbations of brain metabolism in the rat cerebral cortex following direct brain injection of 0.75 mg/kg polymyxin B (1 and 4 h) through the right lateral ventricle. In the right cortex metabolome, ICV polymyxin B induced a greater perturbation at 1 h compared to negligible effect at 4 h. Pathway enrichment analysis showed that sphingolipid, arginine, and histidine metabolism, together with aminoacyl-tRNA biosynthesis were significantly affected in the right cortex metabolome. Furthermore, intracerebroventricular (ICV) polymyxin B dysregulated the two arms (CDP-choline and CDP-ethanolamine) of the Kennedy pathway that governs the de novo biosynthesis of neuronal phospholipids. Importantly, the key intermediates of metabolic pathways that maintain cellular redox balance (e.g., glutathione metabolism) and mitochondrial function (e.g., electron transport chain) were markedly depleted. The abundance of key metabolites (e.g., N-acetyl-l-glutamate) associated with diverse CNS disorders (e.g., neurodegenerative disease) were also significantly perturbed. The biological significance of these metabolic perturbations on the CNS includes impaired oxidant-antioxidant balance, impaired neuronal lipid homeostasis and mitochondrial dysfunction. Furthermore, ICV polymyxin B caused a significant alteration in the abundance of several metabolic biomarkers associated with cerebral ischemia, oxidative stress as well as certain neurological disorders. These findings may facilitate the development of new pharmacokinetic/pharmacodynamic strategies to attenuate polymyxins ICV related CNS toxicities and stimulate the discovery of safer next-generation polymyxin-like lipopeptide antibiotics.PMID:36420146 | PMC:PMC9667150 | DOI:10.1016/j.csbj.2022.10.041

PeerJ. 2022 Nov 18;10:e14404. doi: 10.7717/peerj.14404. eCollection 2022.ABSTRACTBACKGROUND: The banana-growing rhizosphere soil ecosystem is very complex and consists of an entangled network of interactions between banana plants, microbes and soil, so identifying key components in banana production is difficult. Most of the previous studies on these interactions ignore the role of the banana plant. At present, there is no research on the the micro-ecological environment of the banana planting growth cycle.METHODS: Based on high-throughput sequencing technology and metabolomics technology, this study analyzed the rhizosphere soil microbial community and metabolic dynamics of healthy banana plants during one growth cycle.RESULTS: Assessing the microbial community composition of healthy banana rhizosphere soil, we found that the bacteria with the highest levels were Proteobacteria, Chloroflexi, and Acidobacteria, and the dominant fungi were Ascomycota, Basidiomycota, and Mortierellomycota. The metabolite profile of healthy banana rhizosphere soil showed that sugars, lipids and organic acids were the most abundant, accounting for about 50% of the total metabolites. The correlation network between fungi and metabolites was more complex than that of bacteria and metabolites. In a soil environment with acidic pH, bacterial genera showed a significant negative correlation with pH value, while fungal genera showed no significant negative correlation with pH value. The network interactions between bacteria, between fungi, and between bacteria and fungi were all positively correlated.CONCLUSIONS: Healthy banana rhizosphere soil not only has a stable micro-ecology, but also has stable metabolic characteristics. The microorganisms in healthy banana rhizosphere soil have mutually beneficial rather than competitive relationships.PMID:36420134 | PMC:PMC9677880 | DOI:10.7717/peerj.14404

Front Plant Sci. 2022 Nov 7;13:1005711. doi: 10.3389/fpls.2022.1005711. eCollection 2022.ABSTRACTAngelica sinensis is a medicinal plant widely used to treat multiple diseases in Asia and Europe, which contains numerous active components with therapeutic value. The interaction between root and rhizosphere microorganisms is crucial for the growth and quality formation of medicinal plants. But the micro-plant-metabolite regulation patterns for A. sinensis remain largely undetermined. Here, we collected roots and rhizosphere soils from A. sinensis in seedling stage (M) and picking stage (G), respectively cultivated for one year and two years, generated metabolite for roots, microbiota data for rhizospheres, and conducted a comprehensive analysis. Changes in metabolic and microbial communities of A.sinensis over growth were distinct. The composition of rhizosphere microbes in G was dominated by proteobacteria, which had a strong correlation with the synthesis of organic acids, while in M was dominated by Actinobacteria, which had a strong correlation with the synthesis of phthalide and other organoheterocyclic compounds, flavonoids, amines, and fatty acid. Additionally, co-occurrence network analysis identified that Arthrobacter was found to be strongly correlated with the accumulation of senkyunolide A and n-butylidenephthalide. JGI 0001001.H03 was found to be strongly correlated with the accumulation of chlorogenic acid. Based on rhizosphere microorganisms, this study investigated the correlation between root metabolism and rhizosphere microbiota of A. sinensis at different growth stages in traditional geoherb region, which could provide references for exploring the quality formation mechanism of A. sinensis in the future.PMID:36420035 | PMC:PMC9676459 | DOI:10.3389/fpls.2022.1005711

iScience. 2022 Nov 4;25(12):105508. doi: 10.1016/j.isci.2022.105508. eCollection 2022 Dec 22.ABSTRACTAdenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition.PMID:36419846 | PMC:PMC9676393 | DOI:10.1016/j.isci.2022.105508

Front Cardiovasc Med. 2022 Nov 7;9:1019598. doi: 10.3389/fcvm.2022.1019598. eCollection 2022.ABSTRACTOBJECTIVES: Most patients with acute aortic dissection (AAD) have a history of hypertension. Diagnosis of AAD in patients with hypertension at an early stage is complicated and challenging. This study aimed to explore the distinctive metabolic changes in plasma samples of AAD patients with hypertension and patients with hypertension only and provide early identification and diagnosis of AAD in patients with hypertension.MATERIALS AND METHODS: We collected blood samples from 20 patients with type A AAD and hypertension admitted to the emergency department and physically examined other 20 patients with hypertension as controls. The plasma metabolomic profiles of these patients were determined using untargeted metabolomics with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.RESULTS: A total of 38 metabolites that differed between the AAD and hypertension groups were screened. In the positive ion mode, 12 metabolites were different between the two groups, and in the negative ion mode, 26 metabolites were different. Among the 26 different metabolites detected by the negative ion mode, 21 were significantly upregulated and five were downregulated in patients with AAD compared to patients with hypertension. Moreover, five metabolites were upregulated and seven were significantly downregulated in patients with AAD compared to those with hypertension, as detected by the positive ion mode. The metabolites differentially expressed in AAD were mainly involved in lipid metabolism (fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism), carbohydrate metabolism (galactose, fructose, and mannose metabolisms), and membrane transport (ATP-binding cassette transporters). Interestingly, plasma hydrocortisone and dimethylglycine concentrations were significantly increased in patients with type A AAD, with the highest area under the curve value (AUC = 0.9325 or 0.9200, respectively) tested by the receiver operating characteristic curve analysis.CONCLUSION: This study provides possible metabolic markers for the early clinical diagnosis of AAD in patients with hypertension.PMID:36419495 | PMC:PMC9676262 | DOI:10.3389/fcvm.2022.1019598