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

Relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration

Thu, 18/04/2024 - 12:00
Zhonghua Yi Xue Za Zhi. 2024 Apr 16;104(15):1316-1322. doi: 10.3760/cma.j.cn112137-20230810-00199.ABSTRACTObjective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.PMID:38637168 | DOI:10.3760/cma.j.cn112137-20230810-00199

Correction to: Metabolomic Profiles of Human Glioma Inform Patient Survival, by Scott et al. Antioxid Redox Signal 2023;39(13-15):942-956; doi: 10.1089/ars.2022.0085

Thu, 18/04/2024 - 12:00
Antioxid Redox Signal. 2024 Apr 18. doi: 10.1089/ars.2022.0085.correx. Online ahead of print.NO ABSTRACTPMID:38635956 | DOI:10.1089/ars.2022.0085.correx

Nanomedomics

Thu, 18/04/2024 - 12:00
ACS Nano. 2024 Apr 18. doi: 10.1021/acsnano.3c11154. Online ahead of print.ABSTRACTNanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.PMID:38635910 | DOI:10.1021/acsnano.3c11154

State of open science in cancer research

Thu, 18/04/2024 - 12:00
Clin Transl Oncol. 2024 Apr 18. doi: 10.1007/s12094-024-03468-7. Online ahead of print.ABSTRACTPURPOSE: This study has been focused on assessing the Open Science scenario of cancer research during the period 2011-2021, in terms of the derived scientific publications and raw data dissemination.METHODS: A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion.RESULTS: 50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository.CONCLUSIONS: There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.PMID:38635076 | DOI:10.1007/s12094-024-03468-7

Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor

Thu, 18/04/2024 - 12:00
OMICS. 2024 Apr 17. doi: 10.1089/omi.2023.0278. Online ahead of print.ABSTRACTOver a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.PMID:38634790 | DOI:10.1089/omi.2023.0278

Urinary Metabolomic Profiles Uncover Metabolic Pathways in Children with Asthma

Thu, 18/04/2024 - 12:00
J Asthma. 2024 Apr 18:1-11. doi: 10.1080/02770903.2024.2338865. Online ahead of print.ABSTRACTObjective: The prevalence of asthma has gradually increased worldwide in recent years, which has made asthma a global public health problem. However, due to its complexity and heterogeneity, there are a few academic debates on the pathogenic mechanism of asthma. The study of the pathogenesis of asthma through metabolomics has become a new research direction. We aim to uncover the metabolic pathway of children with asthma.Methods: Liquid chromatography (LC)-mass spectrometry (MS)-based metabolomic analysis was conducted to compare urine metabolic profiles between asthmatic children (n = 30) and healthy controls (n = 10).Results: Orthogonal projections to latent structures-discrimination analysis (OPLS-DA) showed that there were significant differences in metabolism between the asthma group and the control group with three different metabolites screened out, including traumatic acid, dodecanedioic acid and glucobrassicin, and the levels of traumatic acid and dodecanedioic acid in the urine samples of asthmatic children were lower than those of healthy controls therein. Pathway enrichment analysis of differentially abundant metabolites suggested that alpha-linolenic acid metabolism was an asthma-related pathway.Conclusions: This study suggests that there are significant metabolic differences in the urine of asthmatic children and healthy controls, and alpha-linolenic acid metabolic pathways may be involved in the pathogenesis of asthma.PMID:38634666 | DOI:10.1080/02770903.2024.2338865

AtMYB41 acts as a dual-function transcription factor that regulates the formation of lipids in an organ- and development-dependent manner

Thu, 18/04/2024 - 12:00
Plant Biol (Stuttg). 2024 Apr 18. doi: 10.1111/plb.13650. Online ahead of print.ABSTRACTThe plant cuticle controls non-stomatal water loss and can serve as a barrier against biotic agents, whereas the heteropolymer suberin and its associated waxes are deposited constitutively at specific cell wall locations. While several transcription factors controlling cuticle formation have been identified, those involved in the transcriptional regulation of suberin biosynthesis remain poorly characterized. The major goal of this study was to further analyse the function of the R2R3-Myeloblastosis (MYB) transcription factor AtMYB41 in formation of the cuticle, suberin, and suberin-associated waxes throughout plant development. For functional analysis, the organ-specific expression pattern of AtMYB41 was analysed and Atmyb41ge alleles were generated using the CRISPR/Cas9 system. These were investigated for root growth and water permeability upon stress. In addition, the fatty acid, wax, cutin, and suberin monomer composition of different organs was evaluated by gas chromatography. The characterization of Atmyb41ge mutants revealed that AtMYB41 negatively regulates the production of cuticular lipids and fatty acid biosynthesis in leaves and seeds, respectively. Remarkably, biochemical analyses indicate that AtMYB41 also positively regulates the formation of cuticular waxes in stems of Arabidopsis thaliana. Overall, these results suggest that the AtMYB41 acts as a negative regulator of cuticle and fatty acid biosynthesis in leaves and seeds, respectively, but also as a positive regulator of wax production in A. thaliana stems.PMID:38634447 | DOI:10.1111/plb.13650

Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in <em>Botrytis cinerea</em>

Thu, 18/04/2024 - 12:00
J Agric Food Chem. 2024 Apr 18. doi: 10.1021/acs.jafc.4c02409. Online ahead of print.ABSTRACTPlant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.PMID:38634420 | DOI:10.1021/acs.jafc.4c02409

Multiomics Analysis Revealed Colorectal Cancer Pathogenesis

Thu, 18/04/2024 - 12:00
J Proteome Res. 2024 Apr 18. doi: 10.1021/acs.jproteome.3c00894. Online ahead of print.ABSTRACTGut microbiota-derived microbial compounds may link to the pathogenesis of colorectal cancer (CRC). However, the role of the host-microbiome in the incidence and progression of CRC remains elusive. We performed 16S rRNA sequencing, metabolomics, and proteomic studies on samples from 85 CRC patients who underwent colonoscopy examination and found two distinct changed patterns of microbiome in CRC patients. The relative abundances of Catabacter and Mogibacterium continuously increased from intramucosal carcinoma to advanced stages, whereas Clostridium, Anaerostipes, Vibrio, Flavonifractor, Holdemanella, and Hungatella were significantly altered only in intermediate lesions. Fecal metabolomics analysis exhibited consistent increases in bile acids, indoles, and urobilin as well as a decrease in heme. Serum metabolomics uncovered the highest levels of bilin, glycerides, and nucleosides together with the lowest levels of bile acids and amino acids in the stage of intermediate lesions. Three fecal and one serum dipeptides were elevated in the intermediate lesions. Proteomics analysis of colorectal tissues showed that oxidation and autophagy through the PI3K/Akt-mTOR signaling pathway contribute to the development of CRC. Diagnostic analysis showed multiomics features have good predictive capability, with AUC greater than 0.85. Our overall findings revealed new candidate biomarkers for CRC, with potentially significant diagnostic and prognostic capabilities.PMID:38634357 | DOI:10.1021/acs.jproteome.3c00894

Exploring the impact of polyphenolic compounds on the chromatic characteristics in flowers of Rhododendron arboreum Sm. collected from different altitudinal locations

Thu, 18/04/2024 - 12:00
Phytochem Anal. 2024 Apr 18. doi: 10.1002/pca.3354. Online ahead of print.ABSTRACTINTRODUCTION: Rhododendron arboreum Sm. flowers grow in the Himalayan region and have traditionally been used in beverages and food. These wild edible Himalayan flowers are known for their sweet-sour flavor and beautiful scarlet red color. The primary pigments responsible for the scarlet red color of these flowers are anthocyanins.OBJECTIVE: In the present study, we conducted chemo-profiling and elucidated the chromatic characteristics of R. arboreum flower petals growing in the wild in different altitudinal areas.METHODOLOGY: The content of anthocyanins, phenolics, and other flavonoids was determined in R. arboreum flower petals collected from 38 different locations in two provinces in India (Himachal Pradesh and Uttarakhand) to obtain a distinguishable chemical index. A UHPLC method has also been developed and validated for the quantitative analysis. Besides, the color characteristics of each collected floral sample were also analyzed.RESULTS: Chemometric analysis (principal component analysis [PCA] and heatmap analysis) revealed that floral samples collected from different altitudes exhibited similar chemical diversity, whereas statistical analysis (bivariate linear correlation) revealed a positive correlation between the color parameter a*/b* and cyanidin glycosides. Besides, non-targeted metabolomics analysis was carried out, which resulted in the tentative identification of 150 metabolites.CONCLUSION: The results revealed that there is a direct influence of accumulated anthocyanins to color parameter a*/b* values in the floral samples irrespective of altitude.PMID:38634333 | DOI:10.1002/pca.3354

Metabolome-microbiome insights into therapeutic impact of 8-O-acetylharpagide against breast cancer in a murine model

Thu, 18/04/2024 - 12:00
Biomed Chromatogr. 2024 Apr 17:e5880. doi: 10.1002/bmc.5880. Online ahead of print.ABSTRACTIridoid glycosides extract, which is the main active extract of Ajuga decumbens Thunb, has been proved to have anti-breast cancer activity in previous studies. However, it is still unknown whether 8-O-acetylharpagide, a main active compound in the extract, has anti-breast cancer activity. In this study, 4 T1 breast cancer mice model was first successfully established. Then the anti-breast cancer effect of 8-O-acetylharpagide was systematically investigated. Feces were collected for metabolomics and 16S rRNA analysis to assess the potential mechanism. The results showed that 8-O-acetylharpagide was effective in reducing 4 T1 mouse tumor volume and weight compared with the model group. Metabolome analysis revealed 12 potential metabolite biomarkers in feces, mainly involved in primary bile acid biosynthesis and arachidonic acid metabolism. The 16S rRNA sequencing results demonstrated that 8-O-acetylharpagide modulated the abundance of the intestinal flora in 4 T1 mice. Spearman correlation analysis showed that calcitriol and prostaglandin G2 strongly correlated with Akkermansia, Firmicutes and Muribaculum. Overall, the active compound 8-O-acetylharpagide could inhibit significantly breast cancer growth in 4 T1 breast cancer model mice. The mechanism of the anti-breast cancer effect of 8-O-acetylharpagide may be related to the regulation of primary bile acid biosynthesis and arachidonic acid metabolism and modulation of the abundance of Akkermansia and Firmicutes.PMID:38634147 | DOI:10.1002/bmc.5880

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria: Current state of the art

Thu, 18/04/2024 - 12:00
J Pharm Anal. 2024 Apr;14(4):100898. doi: 10.1016/j.jpha.2023.11.005. Epub 2023 Nov 28.ABSTRACTPathogenic microorganisms produce numerous metabolites, including volatile organic compounds (VOCs). Monitoring these metabolites in biological matrices (e.g., urine, blood, or breath) can reveal the presence of specific microorganisms, enabling the early diagnosis of infections and the timely implementation of targeted therapy. However, complex matrices only contain trace levels of VOCs, and their constituent components can hinder determination of these compounds. Therefore, modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed. In this paper, we discuss bacterial VOC analysis under in vitro conditions, in animal models and disease diagnosis in humans, including techniques for offline and online analysis in clinical settings. We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis, in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species interactions, the kinetics of VOC metabolism, and species- and drug-resistance specificity.PMID:38634063 | PMC:PMC11022102 | DOI:10.1016/j.jpha.2023.11.005

Baseline gut microbiome and metabolites are correlated with alcohol consumption in a zonisamide clinical trial of heavy drinking alcoholic civilians

Thu, 18/04/2024 - 12:00
medRxiv [Preprint]. 2024 Apr 3:2024.04.02.24305199. doi: 10.1101/2024.04.02.24305199.ABSTRACTDevelopment and severity of alcohol use disorder (AUD) has been linked to variations in gut microbiota and their associated metabolites in both animal and human studies. However, the involvement of the gut microbiome in alcohol consumption of individuals with AUD undergoing treatment remains unclear. To address this, stool samples (n=48) were collected at screening (baseline) and trial completion from a single site of a multi-site double-blind, placebo-controlled trial of Zonisamide in individuals with AUD. Alcohol consumption, gamma-glutamyl transferase (GGT), and phosphatidylethanol (PEth)levels were measured both at baseline and endpoint of 16-week trial period. Fecal microbiome was analyzed via 16S rRNA sequencing and metabolome via untargeted LC-MS. Both sex (p = 0.003) and psychotropic medication usage (p = 0.025) are associated with baseline microbiome composition. The relative abundance of 12 genera at baseline was correlated with percent drinking reduction, baseline and endpoint alcohol consumption, and changes in GGT and PeTH over the course of treatment (p.adj < 0.05). Overall microbiome community structure at baseline differed between high and low responders (67-100% and 0-33% drinking reduction, respectively; p = 0.03). A positive relationship between baseline fecal GABA levels and percent drinking reduction (R=0.43, p < 0.05) was identified by microbiome function prediction and confirmed by ELISA and metabolomics. Predicted microbiome function and metabolomics analysis have found that tryptophan metabolic pathways are over-represented in low responders. These findings highlight importance of baseline microbiome and metabolites in alcohol consumption in AUD patients undergoing zonisamide treatment.PMID:38633809 | PMC:PMC11023652 | DOI:10.1101/2024.04.02.24305199

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases

Thu, 18/04/2024 - 12:00
medRxiv [Preprint]. 2024 Apr 5:2024.04.04.24305284. doi: 10.1101/2024.04.04.24305284.ABSTRACTBACKGROUND: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type-2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to provide a deeper insight into the metabolic changes associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and explore their link to disease.METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3×10 -3 ). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type-2 diabetes (r = 0.77, p = 3×10 -27 ), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1×10 -18 ). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 :< r :< 0.9, p < 3.2×10 -4 ). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.PMID:38633796 | PMC:PMC11023671 | DOI:10.1101/2024.04.04.24305284

Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder

Thu, 18/04/2024 - 12:00
medRxiv [Preprint]. 2024 Apr 3:2024.04.02.24304677. doi: 10.1101/2024.04.02.24304677.ABSTRACTMetabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA 14 ]) were evaluated, both at baseline and after 12 weeks of treatment. Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.PMID:38633777 | PMC:PMC11023644 | DOI:10.1101/2024.04.02.24304677

Classification of grape seed residues from distillation industries in Europe according to the polyphenol composition highlights the influence of variety, geographical origin and color

Thu, 18/04/2024 - 12:00
Food Chem X. 2024 Apr 7;22:101362. doi: 10.1016/j.fochx.2024.101362. eCollection 2024 Jun 30.ABSTRACTGrape seed residues represent the raw material to produce several value-added products including polyphenol-rich extracts with nutritional and health attributes. Although the impact of variety and environmental conditions on the polyphenol composition in fresh berries is recognized, no data are available regarding grape seed residues. The chemical composition of grape seed residues from wine distilleries in France, Spain and Italy was characterized by mass spectrometry. Forty-two metabolites were identified belonging to non-galloylated and galloylated procyanidins as well as amino acids. Polyphenol concentrations in the red varieties originated from Champagne or Veneto were twice higher than in white varieties from the Loire Valley. The chemical profiles of grape seed residues were mainly classified according to the color variety with galloylated procyanidins as biomarkers of white varieties and non-galloylated procyanidins as biomarkers of red ones. The present approach might assist the selection of grape seed residues as quality raw materials for the production of polyphenol-rich extracts.PMID:38633739 | PMC:PMC11021364 | DOI:10.1016/j.fochx.2024.101362

Aptly chosen, effectively emphasizing the action and mechanism of antimycin A<sub>1</sub>

Thu, 18/04/2024 - 12:00
Front Microbiol. 2024 Apr 3;15:1371850. doi: 10.3389/fmicb.2024.1371850. eCollection 2024.ABSTRACTRhizoctonia solani Kühn, a plant pathogenic fungus that can cause diseases in multiple plant species is considered one of the common and destructive pathogens in many crops. This study investigated the action of antimycin A1, which was isolated from Streptomyces AHF-20 found in the rhizosphere soil of an ancient banyan tree, on Rhizoctonia solani and its mechanism. The inhibitory effect of antimycin A1 on R. solani was assessed using the comparative growth rate method. The results revealed that antimycin A1 exhibited a 92.55% inhibition rate against R. solani at a concentration of 26.66 μg/mL, with an EC50 value of 1.25 μg/mL. To observe the impact of antimycin A1 on mycelial morphology and ultrastructure, the fungal mycelium was treated with 6.66 μg/mL antimycin A1, and scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed. SEM analysis demonstrated that antimycin A1 caused mycelial morphology to become stripped, rough, and folded. The mycelium experienced severe distortion and breakage, with incomplete or locally enlarged ends, shortened branches, and reduced numbers. TEM observation revealed thickened cell walls, indistinct organelle boundaries, swollen mitochondria, exosmotic substances in vesicles, slow vesicle fusion, and cavitation. Real-time quantitative PCR and enzyme activity assays were conducted to further investigate the impact of antimycin A1 on mitochondria. The physiological and biochemical results indicated that antimycin A1 inhibited complexes III and IV of the mitochondrial electron transport chain. RT-PCR analysis demonstrated that antimycin A1 controlled the synthesis of relevant enzymes by suppressing the transcription levels of ATP6, ATP8, COX3, QCR6, CytB, ND1, and ND3 genes in mitochondria. Additionally, a metabolomic analysis revealed that antimycin A1 significantly impacted 12 metabolic pathways. These pathways likely experienced alterations in their metabolite profiles due to the inhibitory effects of antimycin A1. Consequently, the findings of this research contribute to the potential development of novel fungicides.PMID:38633707 | PMC:PMC11021728 | DOI:10.3389/fmicb.2024.1371850

Impact of <em>Pediococcus acidilactici</em> GLP06 supplementation on gut microbes and metabolites in adult beagles: a comparative analysis

Thu, 18/04/2024 - 12:00
Front Microbiol. 2024 Apr 3;15:1369402. doi: 10.3389/fmicb.2024.1369402. eCollection 2024.ABSTRACTThere is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals.PMID:38633690 | PMC:PMC11021720 | DOI:10.3389/fmicb.2024.1369402

Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture

Thu, 18/04/2024 - 12:00
Int J Endocrinol. 2024 Apr 10;2024:5568337. doi: 10.1155/2024/5568337. eCollection 2024.ABSTRACTINTRODUCTION: To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics.METHODS: Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD.RESULTS: After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress.CONCLUSION: Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.PMID:38633528 | PMC:PMC11023731 | DOI:10.1155/2024/5568337

Silicon nanoparticles <em>vs</em> trace elements toxicity: <em>Modus operandi</em> and its omics bases

Thu, 18/04/2024 - 12:00
Front Plant Sci. 2024 Apr 3;15:1377964. doi: 10.3389/fpls.2024.1377964. eCollection 2024.ABSTRACTPhytotoxicity of trace elements (commonly misunderstood as 'heavy metals') includes impairment of functional groups of enzymes, photo-assembly, redox homeostasis, and nutrient status in higher plants. Silicon nanoparticles (SiNPs) can ameliorate trace element toxicity. We discuss SiNPs response against several essential (such as Cu, Ni, Mn, Mo, and Zn) and non-essential (including Cd, Pb, Hg, Al, Cr, Sb, Se, and As) trace elements. SiNPs hinder root uptake and transport of trace elements as the first line of defence. SiNPs charge plant antioxidant defence against trace elements-induced oxidative stress. The enrolment of SiNPs in gene expressions was also noticed on many occasions. These genes are associated with several anatomical and physiological phenomena, such as cell wall composition, photosynthesis, and metal uptake and transport. On this note, we dedicate the later sections of this review to support an enhanced understanding of SiNPs influence on the metabolomic, proteomic, and genomic profile of plants under trace elements toxicity.PMID:38633451 | PMC:PMC11021597 | DOI:10.3389/fpls.2024.1377964

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