Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Chronic stress dampens Lactobacillus johnsonii-mediated tumor suppression to enhance colorectal cancer progression

Mon, 08/01/2024 - 12:00
Cancer Res. 2024 Jan 8. doi: 10.1158/0008-5472.CAN-22-3705. Online ahead of print.ABSTRACTColorectal cancer (CRC) development and outcome are impacted by modifiable risk factors, including psychological stress. The gut microbiota has also been shown to be linked to psychological factors. Here, we found a marked deteriorative effect of chronic stress in multiple CRC models, including chemically-induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA-seq data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed CRC group by activated β-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on CRC progression. Stressed CRC mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC‒MS/MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced CRC progression by decreasing β-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on CRC. Altogether, these data identify that stress impacts the gut microbiome to support CRC progression.PMID:38190716 | DOI:10.1158/0008-5472.CAN-22-3705

Integrative Metabolomics and Proteomics Allow the Global Intracellular Characterization of <em>Bacillus subtilis</em> Cells and Spores

Mon, 08/01/2024 - 12:00
J Proteome Res. 2024 Jan 8. doi: 10.1021/acs.jproteome.3c00386. Online ahead of print.ABSTRACTReliable and comprehensive multi-omics analysis is essential for researchers to understand and explore complex biological systems more completely. Bacillus subtilis (B. subtilis) is a model organism for Gram-positive spore-forming bacteria, and in-depth insight into the physiology and molecular basis of spore formation and germination in this organism requires advanced multilayer molecular data sets generated from the same sample. In this study, we evaluated two monophasic methods for polar and nonpolar compound extraction (acetonitrile/methanol/water; isopropanol/water, and 60% ethanol) and two biphasic methods (chloroform/methanol/water, and methyl tert-butyl ether/methanol/water) on coefficients of variation of analytes, identified metabolite composition, and the quality of proteomics profiles. The 60% EtOH protocol proved to be the easiest in sample processing and was more amenable to automation. Collectively, we annotated 505 and 484 metabolites and identified 1665 and 1562 proteins in B. subtilis vegetative cells and spores, respectively. We also show differences between vegetative cells and spores from a multi-omics perspective and demonstrate that an integrative multi-omics analysis can be implemented from one sample using the 60% EtOH protocol. The results obtained by the 60% EtOH protocol provide comprehensive insight into differences in the metabolic and protein makeup of B. subtilis vegetative cells and spores.PMID:38190553 | DOI:10.1021/acs.jproteome.3c00386

Occurrence of <em>Alternaria</em> secondary metabolites in milling oats and its de-hulled fractions from harvest years 2017 to 2021

Mon, 08/01/2024 - 12:00
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2024 Jan 8:1-13. doi: 10.1080/19440049.2023.2294003. Online ahead of print.ABSTRACTIn this study, secondary metabolites produced by Alternaria were investigated for their presence in milling oats. For this purpose, pre-cleaned milling oat samples (n = 193), intended for human consumption, out of harvest years 2017 to 2021 originating from different northern European countries were analysed by LC-MS/MS. Alternariol and alternariol methyl ether were positively identified in 38% of the samples with mean values of 2.1 µg/kg and 1.2 µg/kg, respectively. The highest concentrations of 50.5 µg/kg alternariol and 24.2 µg/kg of alternariol methyl ether were detected in a Latvian sample. Tenuazonic acid was found in 45% of all samples, with a mean concentration of 28.9 µg/kg and a maximum concentration of 1430 µg/kg, also in a Latvian sample. Tentoxin was detected in 49% of all samples with a mean value of 1.7 µg/kg. The Alternaria metabolite most frequently detected in 96% of all samples was infectopyrone with a mean concentration of 593 µg/kg and a maximum value reaching up to 3990 µg/kg in a German sample. In addition, eight oat samples were selected to investigate to what extent the Alternaria metabolites are distributed between the oat hulls and the oat kernels. After de-hulling, approximately 23% of Alternaria metabolites were found in the remaining oat kernels. According to the results, alternariol, infectopyrone and altersetin were present in the kernels with the lowest proportion of 10%-20% on average, respectively. The values for tentoxin showed that about 60% of tentoxin was contained in the hulls, while almost 40% remained in the oat kernel. This suggests that potential health risks posed by Alternaria secondary metabolites and metabolites of other fungal genera in milling oats can be reduced by de-hulling.PMID:38190265 | DOI:10.1080/19440049.2023.2294003

Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations

Mon, 08/01/2024 - 12:00
J Neurooncol. 2024 Jan 8. doi: 10.1007/s11060-023-04484-3. Online ahead of print.ABSTRACTPURPOSE: Choroid plexus carcinomas (CPCs) are extremely rare brain tumors and carry a dismal prognosis. Treatment options are limited and there is an urgent need to develop models to further research. In the present study, we established two CPC cell lines and performed multi-omics analyses. These cell lines serve as valuable models to propose new treatments in these rare but deadly brain tumors.METHODS: Multi-omic profiling including, (i) methylation array (EPIC 850 K), (ii) whole genome sequencing (WGS), (iii) CANCERPLEX cancer genome panel testing, (iv) RNA sequencing (RNA-seq), and (v) proteomics analyses were performed in CCHE-45 and NGT131 cell lines.RESULTS: Both cell lines were classified as methylation class B. Both harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. Transcriptome and proteome analysis identified shared and unique signatures, suggesting that variability in choroid plexus carcinoma tumors may exist. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis.CONCLUSION: Multi-omics analyses revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.PMID:38190092 | DOI:10.1007/s11060-023-04484-3

Correction to: Safety assessment, whole genome sequence, and metabolome analysis of Streptococcus thermophilus CICC 20372 for bone cement fermentation

Mon, 08/01/2024 - 12:00
Arch Microbiol. 2024 Jan 8;206(2):56. doi: 10.1007/s00203-023-03822-3.NO ABSTRACTPMID:38189991 | DOI:10.1007/s00203-023-03822-3

Platelet-derived growth factor receptor β-targeted positron emission tomography imaging for the noninvasive monitoring of liver fibrosis

Mon, 08/01/2024 - 12:00
Eur J Nucl Med Mol Imaging. 2024 Jan 8. doi: 10.1007/s00259-023-06577-7. Online ahead of print.ABSTRACTPURPOSE: Noninvasive quantifying activated hepatic stellate cells (aHSCs) by molecular imaging is helpful for assessing disease progression and therapeutic responses of liver fibrosis. Our purpose is to develop platelet-derived growth factor receptor β (PDGFRβ)-targeted radioactive tracer for assessing liver fibrosis by positron emission tomography (PET) imaging of aHSCs.METHODS: Comparative transcriptomics, immunofluorescence staining and flow cytometry were used to evaluate PDGFRβ as biomarker for human aHSCs and determine the correlation of PDGFRβ with the severity of liver fibrosis. The high affinity affibody for PDGFRβ (ZPDGFRβ) was labeled with gallium-68 (68Ga) for PET imaging of mice with carbon tetrachloride (CCl4)-induced liver fibrosis. Binding of the [68Ga]Ga-labeled ZPDGFRβ ([68Ga]Ga-DOTA-ZPDGFRβ) for aHSCs in human liver tissues was measured by autoradiography.RESULTS: PDGFRβ overexpressed in aHSCs was highly correlated with the severity of liver fibrosis in patients and CCl4-treated mice. The 68Ga-labeled ZPDGFRβ affibody ([68Ga]Ga-DOTA-ZPDGFRβ) showed PDGFRβ-dependent binding to aHSCs. According to the PET imaging, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRβ increased with the accumulation of aHSCs and collagens in the fibrotic livers of mice. In contrast, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRβ decreased with spontaneous recovery or treatment of liver fibrosis, indicating that the progression and therapeutic responses of liver fibrosis in mice could be visualized by PDGFRβ-targeted PET imaging. [68Ga]Ga-DOTA-ZPDGFRβ also bound human aHSCs and visualized fibrosis in patient-derived liver tissues.CONCLUSIONS: PDGFRβ is a reliable biomarker for both human and mouse aHSCs. PDGFRβ-targeted PET imaging could be used for noninvasive monitoring of liver fibrosis in mice and has great potential for clinical translation.PMID:38189910 | DOI:10.1007/s00259-023-06577-7

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid

Mon, 08/01/2024 - 12:00
Elife. 2024 Jan 8;12:RP88525. doi: 10.7554/eLife.88525.ABSTRACTPhotosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a 'C4-TRAP transporter', and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10-9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.PMID:38189382 | DOI:10.7554/eLife.88525

Inoculation of Newborn Lambs with Ruminal Solids Derived from Adult Goats Reprograms the Development of Gut Microbiota and Serum Metabolome and Favors Growth Performance

Mon, 08/01/2024 - 12:00
J Agric Food Chem. 2024 Jan 8. doi: 10.1021/acs.jafc.3c04632. Online ahead of print.ABSTRACTMicrobial transplantation in early life was a strategy to optimize the health and performance of livestock animals. This study aimed to investigate the effect of active ruminal solids microorganism supplementation on newborn lamb gut microbiota and serum metabolism. Twenty-four Youzhou dark newborn lambs were randomly divided into three groups: (1) newborn lambs fed with sterilized goat milk inoculated with sterilized normal saline (CON), supernatant from ruminal solids (SRS), or autoclaved supernatant from ruminal solids (ASRS). Results showed that SRS increased gut bacterial richness and community, downregulating the Firmicutes/Bacteroidetes ratio, and increased the abundance of some probiotics (Bacteroidetes, Spirochaetota, and Fibrobacterota), while reducing the abundance of Fusobacteriota, compared to the CON group. SRS also improved the plasma metabolic function, such as arachidonic acid metabolism, primary bile acid biosynthesis, and tryptophan metabolism and then actively promoted the levels of ALP and HLD. Our study indicated that inoculation with active ruminal solids significantly affected the intestinal microbial communities and metabolic characteristics, and these changes can improve the growing health of the newborn lamb. These findings provided an experimental and theoretical basis for the application of ruminal solid-attached microorganisms in the nutritional management of lambs reared for human consumption.PMID:38189273 | DOI:10.1021/acs.jafc.3c04632

Metabolomic approaches to explore chemodiversity in seeds of guaraná (<em>Paullinia cupana</em>) using UPLC-QTOF-MS<sup>E</sup> and NMR analysis

Mon, 08/01/2024 - 12:00
Anal Methods. 2024 Jan 8. doi: 10.1039/d3ay01737k. Online ahead of print.ABSTRACTThe growing interest in health and well-being has spurred the evolution of functional foods, which provide enhanced health benefits beyond basic nutrition. Guaraná seeds (Paullinia cupana) have been widely studied and used as a functional food due to their richness in caffeine, phenolic compounds, amino acids, and other nutrients. This has established guaraná as a significant food supplement, with Brazil being the largest producer of the world. This study aims to propose a set of analytical methods to chemically evaluate fifty-six different guaraná clones, from the Guaraná Germplasm Active Bank, to accommodate the diverse requirements of the food industry. Metabolomic approaches were employed, in which a non-target metabolomic analysis via UPLC-QTOF-MSE led to the annotation of nineteen specialized metabolites. Furthermore, targeted metabolomics was also used, leading to the identification and quantification of metabolites by NMR. The extensive data generated were subjected to multivariate analysis, elucidating the similarities and differences between the evaluated guaraná seeds, particularly concerning the varying concentration levels of the metabolites. The metabolomics approach based on the combination of UPLC-QTOF-MSE, NMR and chemometric tools provided sensitivity, precision and accuracy to establish the chemical profiles of guaraná seeds. In conclusion, evaluating and determining the metabolic specificities of different guarana clones allow for their application in the development of products with different levels of specific metabolites, such as caffeine. This caters to various purposes within the food industry. Moreover, the recognized pharmacological properties of the annotated specialized metabolites affirm the use of guarana clones as an excellent nutritional source.PMID:38189175 | DOI:10.1039/d3ay01737k

A novel ultrafiltrate extract of propolis exerts anti-inflammatory activity through metabolic rewiring

Mon, 08/01/2024 - 12:00
Chem Biodivers. 2024 Jan 8:e202301315. doi: 10.1002/cbdv.202301315. Online ahead of print.ABSTRACTThousands of years ago humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11β-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.PMID:38189169 | DOI:10.1002/cbdv.202301315

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats

Mon, 08/01/2024 - 12:00
Ren Fail. 2024 Dec;46(1):2300314. doi: 10.1080/0886022X.2023.2300314. Epub 2024 Jan 8.ABSTRACTPURPOSE: To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism.METHODS: Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats.RESULTS: A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation.CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.PMID:38189082 | DOI:10.1080/0886022X.2023.2300314

Phytochemical profile and anti-inflammatory activity of the hull of γ-irradiated wheat mutant lines (<em>Triticum aestivum</em> L.)

Mon, 08/01/2024 - 12:00
Front Nutr. 2023 Dec 22;10:1334344. doi: 10.3389/fnut.2023.1334344. eCollection 2023.ABSTRACTWheat (Triticum aestivum Linn.; Poaceae) is the second most cultivated food crop among all global cereal crop production. The high carbohydrate content of its grains provides energy, multiple nutrients, and dietary fiber. After threshing, a substantial amount of wheat hull is produced, which serves as the non-food component of wheat. For the valorization of these by-products as a new resource from which functional components can be extracted, the hull from the seeds of cultivated wheat mutant lines bred after γ-irradiation were collected. Untargeted metabolite analysis of the hull of the original cultivar (a crossbreeding cultivar., Woori-mil × D-7) and its 983 mutant lines were conducted using ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry technique. A total of 55 molecules were tentatively identified, including 21 compounds found in the Triticum species for the first time and 13 compounds not previously described. Among them, seven flavonolignans with a diastereomeric structure, isolated as a single compound from the hull of T. aestivum in our previous study, were used as the standards in the metabolite analysis. The differences in their collision cross-section values were shown to contribute to the clear distinction between tricine-lignan stereoisomers. To select functionally active agents with anti-inflammatory activity among the identified compounds, the wheat hull samples were evaluated for their inhibitory effect on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. As a result of multivariate analysis based on the results of chemical and biological profiles of the wheat hull samples, 10 metabolites were identified as key markers, contributing to the distinction between active and inactive mutant lines. Considering that one of the four key markers attributed to anti-inflammatory activity has been identified to be a flavonolignan, the wheat hull could be a valuable source of diverse tricin-lignan type compounds and used as a natural health-promoting product in food supplements.PMID:38188878 | PMC:PMC10771830 | DOI:10.3389/fnut.2023.1334344

Microbial composition and metabolic profiles during machine-controlled intra-factory fermentation of cocoa beans harvested in semitropical area of Japan

Mon, 08/01/2024 - 12:00
Biosci Microbiota Food Health. 2024;43(1):29-42. doi: 10.12938/bmfh.2023-036. Epub 2023 Sep 4.ABSTRACTCocoa bean fermentation is typically performed in a spontaneous manner on farms in tropical countries or areas and involves several microbial groups. Metabolism by microbes markedly affects the quality of cocoa beans fermented and the chocolate produced thereof. The present study characterized the microbiota and their metabolic profiles in temperature- and humidity-controlled intra-factory cocoa fermentation in a semitropical area of Japan. Although environmental factors were uniform, the microbiota of cocoa beans subjected to intra-factory fermentation was not stable between tests, particularly in terms of the cell count levels and species observed. Fermentation was sometimes delayed, and fermenting microbes were present at very low levels after 24 hr of fermentation. Due to the unstable microbiota, the profiles of water-soluble compounds differed between tests, indicating the unstable qualities of the fermented cocoa beans. These results suggest the necessity of starter cultures not only in on-farm fermentation but also in machine-controlled intra-factory cocoa fermentation.PMID:38188660 | PMC:PMC10767318 | DOI:10.12938/bmfh.2023-036

Effect of forest planting patterns on the formation of soil organic carbon during litter lignocellulose degradation from a microbial perspective

Mon, 08/01/2024 - 12:00
Front Microbiol. 2023 Dec 22;14:1327481. doi: 10.3389/fmicb.2023.1327481. eCollection 2023.ABSTRACTLitter decomposition is an important source of soil organic carbon, and it plays a key role in maintaining the stability of forest ecosystems. The microbial mechanism of soil organic carbon (SOC) formation in different urban forest planting patterns during litter lignocellulose degradation is still unclear. The key genes, microbes, and metabolites in the process of lignocellulose degradation and SOC formation were determined by metagenomics and metabolomics in different litter decomposition layers and soil layers in different urban forest planting patterns, including three types of broadleaf forests (BP forests), three types of coniferous forests (CP forests), and two types of mixed coniferous and broadleaf forests (MCBP forests). The results indicated that the cellulose, hemicellulose, and lignin concentrations from the undecomposed layer to the totally decomposed layer decreased by 70.07, 86.83, and 73.04% for CP litter; 74.30, 93.80, and 77.55% for BP litter; and 62.51, 48.58, and 90.61% for MCBP litter, respectively. The soil organic carbon of the BP forests and MCBP forests was higher than that of the CP forests by 38.06 and 94.43% for the 0-10 cm soil layer and by 38.55 and 20.87% for the 10-20 cm soil layer, respectively. Additionally, the gene abundances of glycoside hydrolases (GHs) and polysaccharide lyases (PLs) in the BP forests were higher than those in the MCBP forests and CP forests. Amino acid metabolism, sugar metabolism, TCA metabolism, and cAMP signaling metabolism were mainly between the CP forests and BP forests, while the TCA cycle, pyruvate metabolism, phenylalanine metabolism, and tyrosine metabolism were mainly between the BP forests and MCBP forests during litter decomposition. Additionally, ammonia nitrogen and hemicellulose were key factors driving SOC formation in the CP forests, while ammonia nitrogen, hemicellulose, and lignocellulose-degrading genes were key factors driving SOC formation in the BP forests. For the MCBP forests, cellulose, pH, ammonia nitrogen, and lignin were key factors driving SOC formation. Our findings revealed that the BP forests and MCBP forests had stronger lignocellulose degradation performance in the formation of SOC. This study provided a theoretical basis for the flow and transformation of nutrients in different urban forest management patterns.PMID:38188580 | PMC:PMC10771852 | DOI:10.3389/fmicb.2023.1327481

Metabolites of the gut microbiota may serve as precise diagnostic markers for sarcopenia in the elderly

Mon, 08/01/2024 - 12:00
Front Microbiol. 2023 Dec 21;14:1301805. doi: 10.3389/fmicb.2023.1301805. eCollection 2023.ABSTRACTSarcopenia, a disease recognized by the World Health Organization, has posed a great challenge to the world in the current aging society. The vital role of the gut microbiome through the gut-muscle axis in sarcopenia is increasingly recognized. However, the working mechanisms by which the gut microbiota functions have not been fully explored in the multi-omics field. Here, we designed a cross-sectional study that recruited patients (n = 32) with sarcopenia and healthy old adults (n = 31). Diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia (AWGS) in 2019 criteria. Muscle mass was represented by appendicular skeletal muscle mass measured by using direct segmental multi-frequency bioelectrical impedance and muscle strength was evaluated using the handgrip strength. The Short Physical Performance Battery, the 5-time Chair Stand Test, and the 4-metre Walk Test were used to assess physical performance. Shotgun metagenomic sequencing was used to profile the gut microbiome in order to identify its construction and function. Metabolome based on untargeted metabolomics was applied to describe the features and structure of fecal metabolites. In clinical indexes including triglycerides and high-density lipoprotein cholesterol, we noted a significant decrease in triglycerides (TG) and a significant increase in high-density lipoprotein cholesterol (HDL-C) in patients with sarcopenia. Appendicular skeletal muscle mass of patients with sarcopenia was lower than the health group. Based on intestinal metagenomic and fecal metabolomic profiles, we found that the gut microbiome and metabolome were disturbed in patients with sarcopenia, with significant decreases in bacteria such as Bifidobacterium longum, Bifidobacterium pseudocatenulatum, and Bifidobacterium adolescentis, as well as metabolites such as shikimic acid. Also, we plotted supervised classification models at the species level of gut bacteria (AUC = 70.83-88.33) and metabolites (AUC = 92.23-98.33) based on machine learning, respectively. Based on the gut-muscle axis network, a potential mechanism is proposed along the gut microbiome - key metabolites - clinical index, that Phascolarctobacterium faecium affects appendicular skeletal muscle mass, calf circumference, handgrip strength, and BMI via Shikimic acid metabolites. This study elucidates the potential mechanisms by which the gut microbiome influences the progress of sarcopenia through metabolites and provides a meaningful theoretical foundation for reference in the diagnosis and treatment of sarcopenia.PMID:38188577 | PMC:PMC10768011 | DOI:10.3389/fmicb.2023.1301805

Combined microbiome and metabolomics analysis of Taorong-type baijiu high-temperature Daqu and medium-temperature Daqu

Mon, 08/01/2024 - 12:00
PeerJ. 2024 Jan 3;12:e16621. doi: 10.7717/peerj.16621. eCollection 2024.ABSTRACTBACKGROUND: Daqu is an essential starter for baijiu brewing in China. However, the microbial enrichment and metabolic characteristics of Daqu formed at different fermentation temperatures are still unclear.METHODS: High-throughput sequencing technology and the non-targeted metabolomics were used to compare the microbial communities and metabolites of Taorong-type high-temperature Daqu and middle-temperature Daqu. In this study, the relationship between microorganisms and metabolites was established.RESULTS: The study found that the composition and metabolites of the microbial community differed due to the difference in Daqu-making temperature. The bacterial diversity of Taorong-type high-temperature Daqu was higher than that of middle-temperature Daqu, while the fungal community diversity of Taorong-type middle-temperature Daqu was higher than that of high temperature Daqu. A total of 1,034 differential metabolites were screened from the two types of Daqu, and 76 metabolites with significant differences were detected (P < 0.001 and variable importance in projection (VIP) > 1.15). Tetraacetylethylenediamine is the metabolite with the largest differential fold among the 76 differential metabolites, which can be used as a potential marker metabolite of high-temperature Daqu.CONCLUSION: This study helps elucidate the microbial assembly mechanisms and functional expression under different processing conditions through a further understanding of the composition and metabolic profile differences of different types of Daqu microflora in Taorong-type baijiu.PMID:38188181 | PMC:PMC10771096 | DOI:10.7717/peerj.16621

Multi-omics reveals changed energy metabolism of liver and muscle by caffeine after mice swimming

Mon, 08/01/2024 - 12:00
PeerJ. 2024 Jan 3;12:e16677. doi: 10.7717/peerj.16677. eCollection 2024.ABSTRACTIn recent years, numerous studies have investigated the effects of caffeine on exercise, and provide convincing evidence for its ergogenic effects on exercise performance. However, the precise mechanisms underlying these ergogenic effects remain unclear. In this study, an exercise swimming model was conducted to investigate the effects of orally administered with caffeine before swimming on the alterations of proteome and energy metabolome of liver and muscle after swimming. We found proteins in liver, such as S100a8, S100a9, Gabpa, Igfbp1 and Sdc4, were significantly up-regulated, while Rbp4 and Tf decreased after swimming were further down-regulated in caffeine group. The glycolysis and pentose phosphate pathways in liver and muscle were both significantly down-regulated in caffeine group. The pyruvate carboxylase and amino acid levels in liver, including cysteine, serine and tyrosine, were markedly up-regulated in caffeine group, exhibiting a strong correlation with the increased pyruvic acid and oxaloacetate levels in muscle. Moreover, caffeine significantly decreased the lactate levels in both liver and muscle after swimming, potentially benefiting exercise performance.PMID:38188177 | PMC:PMC10771084 | DOI:10.7717/peerj.16677

Simultaneous extraction and quantitative analysis of <em>S</em>-Methyl-l-Cysteine Sulfoxide, sulforaphane and glucosinolates in cruciferous vegetables by liquid chromatography mass spectrometry

Mon, 08/01/2024 - 12:00
Food Chem X. 2023 Dec 14;21:101065. doi: 10.1016/j.fochx.2023.101065. eCollection 2024 Mar 30.ABSTRACTSulfur containing compounds including glucosinolates (GLS), sulforaphane (SFN) and S-methyl-l-cysteine sulfoxide (SMCSO) have been proposed to be partly responsible for the beneficial health effects of cruciferous vegetables. As such, greater understanding of their measurements within foods is important to estimate intake in humans and to inform dietary intervention studies. Herein is described a simple and sensitive method for simultaneous analysis of 20 GLS, SFN and SMCSO by liquid chromatography mass spectrometry. Analytes were effectively retained and resolved on an Xbridge C18 column. Detection can be achieved using high resolution or unit resolution mass spectrometry; the latter making the method more applicable to large studies. Quantitative analysis using calibration standards was demonstrated for 10 GLS, SFN and SMCSO. A further 10 GLS were tentatively identified using high resolution mass spectrometry. The use of surrogate GLS standards was shown to be unreliable, with closely related GLS displaying significantly different ionisation efficiencies.PMID:38187949 | PMC:PMC10767375 | DOI:10.1016/j.fochx.2023.101065

Chemical component of differences in the endosperm of <em>Gleditsia</em> species seeds revealed based on comparative metabolomics

Mon, 08/01/2024 - 12:00
Food Chem X. 2023 Dec 12;21:101060. doi: 10.1016/j.fochx.2023.101060. eCollection 2024 Mar 30.ABSTRACTTo investigate the chemical composition and interfunctional differences among the endosperm of Gleditsia species seeds (EGS), this study was conducted to determine the metabolic profiles in three EGSs based on the metabolomics approach of UPLC-ESI-MS/MS. A total of 505 metabolites were identified, of which 156 metabolites of EGS were annotated as pharmaceutical ingredients for six human diseases. A total of 110, 146, and 104 metabolites showed different accumulation patterns in the three control groups, LEGS vs. MEGS, LEGS vs. SEGS, and MEGS vs. SEGS, respectively. The metabolic profiles of EGSs differed significantly, and KEGG annotation and enrichment analyses indicated aminoacyl-tRNA biosynthesis as the key metabolic pathway of EGSs. This study enriches the understanding of the chemical composition of EGSs and provides theoretical support for the development and application of EGSs.PMID:38187947 | PMC:PMC10767367 | DOI:10.1016/j.fochx.2023.101060

Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions

Mon, 08/01/2024 - 12:00
bioRxiv. 2023 Dec 20:2023.12.20.572584. doi: 10.1101/2023.12.20.572584. Preprint.ABSTRACTNormal hematopoiesis requires constant prolific production of different blood cell lineages by multipotent hematopoietic stem cells (HSC). Stem- and progenitor- cells need to balance dormancy with proliferation. How genetic alterations impact frequency, lineage potential, and metabolism of HSC is largely unknown. Here, we compared induced expression of KRAS G12D or RasGRP1 to normal hematopoiesis. At low-resolution, both Ras pathway lesions result in skewing towards myeloid lineages. Single-cell resolution CyTOF proteomics unmasked an expansion of HSC- and progenitor- compartments for RasGRP1, contrasted by a depletion for KRAS G12D . SCENITH™ quantitates protein synthesis with single-cell precision and corroborated that immature cells display low metabolic SCENITH™ rates. Both RasGRP1 and KRAS G12D elevated mean SCENITH™ signals in immature cells. However, RasGRP1-overexpressing stem cells retain a metabolically quiescent cell-fraction, whereas this fraction diminishes for KRAS G12D . Our temporal single cell proteomics and metabolomics datasets provide a resource of mechanistic insights into altered hematopoiesis at single cell resolution.PMID:38187679 | PMC:PMC10769276 | DOI:10.1101/2023.12.20.572584

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