PubMed

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

Brain. 2023 Sep 18:awad306. doi: 10.1093/brain/awad306. Online ahead of print.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood, but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation, and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma metabolite correlations, which could identify robust disease biomarkers and potentially shed mechanistic insight. Here, gut microbiome changes were longitudinally profiled in ALS, and correlated to plasma metabolome. Gut microbial structure at the phylum level differed in ALS versus control participants, with differential abundance of several distinct genera. Unsupervised clustering of microbe and metabolite levels identified modules, which differed significantly in ALS versus control participants. Network analysis found several prominent amplicon sequence variants strongly linked to a group of metabolites, primarily lipids. Similarly, identifying the features that contributed most to case versus control separation pinpointed several bacteria correlated to metabolites, predominantly lipids. Mendelian randomization indicated possible causality from specific lipids related to fatty acid and acylcarnitine metabolism. Overall, the results suggest ALS cases and controls differ in their gut microbiome, which correlates with plasma metabolites, particularly lipids, through specific genera. These findings have the potential to identify robust disease biomarkers and shed mechanistic insight into ALS.PMID:37721161 | DOI:10.1093/brain/awad306

Radiat Prot Dosimetry. 2023 Sep 18;199(14):1526-1532. doi: 10.1093/rpd/ncad035.ABSTRACTThreats of radiological or nuclear disasters are of serious concern and a top priority for government agencies involved in domestic security and public health preparedness. There is a need for sensitive bioassays for biodosimetric assessments of radiation exposures originating from unanticipated nuclear/radiological events. The Food and Drug Administration Animal Rule approval pathway requires an in-depth understanding of the mechanisms of radiation injury, drug efficacy and biomarkers for radiation medical countermeasure approval. Biomarkers can be helpful for extrapolating the efficacious countermeasure dose in animals to humans. We summarised here our studies to identify candidate biomarkers for the acute radiation injury using various omic platforms (metabolomics/lipidomics, proteomics, microbiome and transcriptomics/microRNA) using murine and non-human primate models conducted in our laboratory. Multi-omic platforms appear to be highly useful in assessing radiation exposure levels and for identifying biomarkers of radiation injury and countermeasure efficacy, which can expedite the regulatory approval of countermeasures.PMID:37721071 | DOI:10.1093/rpd/ncad035

Food Funct. 2023 Sep 18. doi: 10.1039/d3fo90080k. Online ahead of print.ABSTRACTCorrection for 'Muscle characteristics comparison and targeted metabolome analysis reveal differences in carcass traits and meat quality of three pig breeds' by Bo Song et al., Food Funct., 2023, 14, 7603-7614, https://doi.org/10.1039/D2FO03709B.PMID:37720984 | DOI:10.1039/d3fo90080k

ACS Omega. 2023 Aug 30;8(36):32352-32364. doi: 10.1021/acsomega.3c01381. eCollection 2023 Sep 12.ABSTRACTLimited knowledge regarding the susceptibility of grape varieties to ochratoxin A (OTA)-producing fungi is available to date. This study aimed to investigate the susceptibility of different grape varieties to Aspergillus carbonarius concerning OTA contamination and modulation at the metabolome level. Six grape varieties were selected, sampled at early veraison and ripening, artificially inoculated with A. carbonarius, and incubated at two temperature regimes. Significant differences were observed across cultivars, with Barbera showing the highest incidence of moldy berries (around 30%), while Malvasia and Ortrugo showed the lowest incidence (about 2%). OTA contamination was the lowest in Ortrugo and Malvasia, and the highest in Croatina, although it was not significantly different from Barbera, Merlot, and Sauvignon Blanc. Fungal development and mycotoxin production changed with grape variety; the sugar content in berries could also have played a role. Unsupervised multivariate statistical analysis from metabolomic fingerprints highlighted cultivar-specific responses, although a more generalized response was observed by supervised OPLS-DA modeling. An accumulation of nitrogen-containing compounds (alkaloids and glucosinolates), phenylpropanoids, and terpenoids, in addition to phytoalexins, was observed in all samples. A broader modulation of the metabolome was observed in white grapes, which were less contaminated by OTA. Jasmonates and oxylipins were identified as critical upstream modulators in metabolomic profiles. A direct correlation between the plant defense machinery and OTA was not observed, but the information was acquired and can contribute to optimizing preventive actions.PMID:37720731 | PMC:PMC10500680 | DOI:10.1021/acsomega.3c01381

Front Immunol. 2023 Sep 1;14:1253913. doi: 10.3389/fimmu.2023.1253913. eCollection 2023.ABSTRACTOBJECTIVE: There is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA.METHODS: We applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel.RESULTS: Significant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA.CONCLUSION: A metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA.PMID:37720214 | PMC:PMC10502709 | DOI:10.3389/fimmu.2023.1253913

Front Microbiol. 2023 Aug 31;14:1255971. doi: 10.3389/fmicb.2023.1255971. eCollection 2023.ABSTRACTINTRODUCTION: Heart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated.METHODS: In this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1-/-) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF.RESULTS: Compared with the WT-ISO group, Sigmar1-/- aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1-/- exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar-/--ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues.CONCLUSION: Taken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.PMID:37720144 | PMC:PMC10501138 | DOI:10.3389/fmicb.2023.1255971

iScience. 2023 Aug 25;26(10):107710. doi: 10.1016/j.isci.2023.107710. eCollection 2023 Oct 20.ABSTRACTMice lacking caveolin-1 (Cav1), a key protein of plasma membrane, exhibit brain aging at an early adult stage. Here, integrative analyses of metabolomics, transcriptomics, epigenetics, and single-cell data were performed to test the hypothesis that metabolic deregulation of fetal brain due to the ablation of Cav1 is linked to brain aging in these mice. The results of this study show that lack of Cav1 caused deregulation in the lipid and amino acid metabolism in the fetal brain, and genes associated with these deregulated metabolites were significantly altered in the brain upon aging. Moreover, ablation of Cav1 deregulated several metabolic genes in specific cell types of the fetal brain and impacted DNA methylation of those genes in coordination with mouse epigenetic clock. The findings of this study suggest that the aging program of brain is confounded by metabolic abnormalities in the fetal stage due to the absence of Cav1.PMID:37720105 | PMC:PMC10500482 | DOI:10.1016/j.isci.2023.107710

iScience. 2023 Aug 31;26(10):107802. doi: 10.1016/j.isci.2023.107802. eCollection 2023 Oct 20.ABSTRACTAdoptive cell therapy using allogeneic γδ-T cells is a promising option for off-the-shelf T cell products with a low risk of graft-versus-host disease (GVHD). Long-term persistence may boost the clinical development of γδ-T cell products. In this study, we found that genetically modified Vγ9+Vδ2+ T cells expressing a tumor antigen-specific αβ-TCR and CD8 coreceptor (GMC) showed target-specific killing and excellent persistence. To determine the mechanisms underlying these promising effects, we investigated metabolic characteristics. Cytokine secretion by γδ-TCR-stimulated nongene-modified γδ-T cells (NGMCs) and αβ-TCR-stimulated GMCs was equally suppressed by a glycolysis inhibitor, although the cytokine secretion of αβ-TCR-stimulated GMCs was more strongly inhibited by ATP synthase inhibitors than that of γδ-TCR-stimulated NGMCs. Metabolomic and transcriptomic analyses, flow cytometry analysis using mitochondria-labeling dyes and extracellular flux analysis consistently suggest that αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function. In conclusion, αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function with promising persistence.PMID:37720098 | PMC:PMC10502403 | DOI:10.1016/j.isci.2023.107802

Res Sq. 2023 Sep 6:rs.3.rs-3306891. doi: 10.21203/rs.3.rs-3306891/v1. Preprint.ABSTRACTIn this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilized whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalized models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.PMID:37720019 | PMC:PMC10503865 | DOI:10.21203/rs.3.rs-3306891/v1

Front Aging Neurosci. 2023 Aug 30;15:1214932. doi: 10.3389/fnagi.2023.1214932. eCollection 2023.ABSTRACTINTRODUCTION: Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer's disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease.METHODS: The relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer's Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer's Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study.RESULTS: Metabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein.DISCUSSION: This study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.PMID:37719875 | PMC:PMC10499619 | DOI:10.3389/fnagi.2023.1214932

PNAS Nexus. 2023 Sep 5;2(9):pgad287. doi: 10.1093/pnasnexus/pgad287. eCollection 2023 Sep.ABSTRACTAs coral reef ecosystems experience unprecedented change, effective monitoring of reef features supports management, conservation, and intervention efforts. Omic techniques show promise in quantifying key components of reef ecosystems including dissolved metabolites and microorganisms that may serve as invisible sensors for reef ecosystem dynamics. Dissolved metabolites are released by reef organisms and transferred among microorganisms, acting as chemical currencies and contributing to nutrient cycling and signaling on reefs. Here, we applied four omic techniques (taxonomic microbiome via amplicon sequencing, functional microbiome via shotgun metagenomics, targeted metabolomics, and untargeted metabolomics) to waters overlying Florida's Coral Reef, as well as microbiome profiling on individual coral colonies from these reefs to understand how microbes and dissolved metabolites reflect biogeographical, benthic, and nutrient properties of this 500-km barrier reef. We show that the microbial and metabolite omic approaches each differentiated reef habitats based on geographic zone. Further, seawater microbiome profiling and targeted metabolomics were significantly related to more reef habitat characteristics, such as amount of hard and soft coral, compared to metagenomic sequencing and untargeted metabolomics. Across five coral species, microbiomes were also significantly related to reef zone, followed by species and disease status, suggesting that the geographic water circulation patterns in Florida also impact the microbiomes of reef builders. A combination of differential abundance and indicator species analyses revealed metabolite and microbial signatures of specific reef zones, which demonstrates the utility of these techniques to provide new insights into reef microbial and metabolite features that reflect broader ecosystem processes.PMID:37719750 | PMC:PMC10504872 | DOI:10.1093/pnasnexus/pgad287

Infect Drug Resist. 2023 Sep 12;16:6121-6138. doi: 10.2147/IDR.S422363. eCollection 2023.ABSTRACTPURPOSE: Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis.PATIENTS AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI.RESULTS: A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests.CONCLUSION: This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientific evidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.PMID:37719654 | PMC:PMC10505020 | DOI:10.2147/IDR.S422363

Infect Drug Resist. 2023 Sep 11;16:6061-6077. doi: 10.2147/IDR.S420898. eCollection 2023.ABSTRACTPURPOSE: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI.PATIENTS AND METHODS: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI.RESULTS: FEP/AVI (MIC50/MIC90 0.5/4-64/4 μg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC50/MIC90 4/4-128/4 μg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP.CONCLUSION: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.PMID:37719649 | PMC:PMC10503517 | DOI:10.2147/IDR.S420898

Acta Pharm Sin B. 2023 Sep;13(9):3802-3816. doi: 10.1016/j.apsb.2023.06.002. Epub 2023 Jun 8.ABSTRACTThe chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.PMID:37719385 | PMC:PMC10502289 | DOI:10.1016/j.apsb.2023.06.002

Front Mol Biosci. 2023 Aug 30;10:1268001. doi: 10.3389/fmolb.2023.1268001. eCollection 2023.NO ABSTRACTPMID:37719265 | PMC:PMC10502714 | DOI:10.3389/fmolb.2023.1268001

Front Mol Biosci. 2023 Aug 31;10:1228771. doi: 10.3389/fmolb.2023.1228771. eCollection 2023.ABSTRACTBackground: Cold exposure (CE) can effectively modulate adipose tissue metabolism and improve metabolic health. Although previous metabolomics studies have primarily focused on analyzing one or two samples from serum, brown adipose tissue (BAT), white adipose tissue (WAT), and liver samples, there is a significant lack of simultaneous analysis of multiple tissues regarding the metabolic changes induced by CE in mice. Therefore, our study aims to investigate the metabolic profiles of the major tissues involved. Methods: A total of 14 male C57BL/6J mice were randomly assigned to two groups: the control group (n = 7) and the CE group (n = 7). Metabolite determination was carried out using gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to identify metabolites exhibiting differential expression between the two groups. Results: In our study, we identified 32 discriminant metabolites in BAT, 17 in WAT, 21 in serum, 7 in the liver, 16 in the spleen, and 26 in the kidney, respectively. Among these metabolites, amino acids, fatty acids, and nucleotides emerged as the most significantly altered compounds. These metabolites were found to be associated with 12 differential metabolic pathways closely related to amino acids, fatty acids, and energy metabolism. Conclusion: Our study may provide valuable insights into the metabolic effects induced by CE, and they have the potential to inspire novel approaches for treating metabolic diseases.PMID:37719264 | PMC:PMC10500074 | DOI:10.3389/fmolb.2023.1228771

Front Plant Sci. 2023 Sep 1;14:1211162. doi: 10.3389/fpls.2023.1211162. eCollection 2023.ABSTRACTAs a multifunctional tree species, Cyclocarya paliurus leaves are rich in bioactive substances with precious healthy values. To meet the huge requirement of C. paliurus leaf production, sites with some environmental stresses would be potential land for developing its plantations due to the limitation of land resources in China. Nitric oxide (NO) and hydrogen sulfide (H2S) are common gas messengers used to alleviate abiotic stress damage, whereas the mechanism of these messengers in regulating salt resistance of C. paliurus still remains unclear. We performed a comprehensive study to reveal the physiological response and molecular regulatory mechanism of C. paliurus seedlings to the application of exogenous NO and H2S under salt stress. The results showed that the application of sodium hydrosulfide (NaHS) and sodium nitroprusside (SNP) not only maintained the photosynthetic capacity and reduced the loss of leaf biomass, but also promoted endogenous NO synthesis and reduced oxidative damage by activating antioxidant enzyme activity and increasing the content of soluble protein and flavonoids. Moreover, transcriptome and metabolome analysis indicated the expression of genes encoding phenylalanine ammonia lyase (PAL), cytochromeP450 (CYP), chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS) in flavonoid biosynthesis pathway was all up-regulated by the application of NO and H2S. Meanwhile, 15 transcriptional factors (TFs) such as WRKY, ERF, bHLH and HY5 induced by NO were found to regulated the activities of several key enzymes in flavonoid biosynthesis pathway under salt stress, via the constructed co-expression network. Our findings revealed the underlying mechanism of NO and H2S to alleviate salt stress and regulate flavonoid biosynthesis, which provides a theoretical basis for establishing C. paliurus plantations in the salt stress areas.PMID:37719222 | PMC:PMC10502730 | DOI:10.3389/fpls.2023.1211162