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

Increasing the use of functional and multimodal genetic data in social science research

Mon, 11/09/2023 - 12:00
Behav Brain Sci. 2023 Sep 11;46:e223. doi: 10.1017/S0140525X2200228X.ABSTRACTGenetic studies in the social sciences could be augmented through the additional consideration of functional (transcriptome, methylome, metabolome) and/or multimodal genetic data when attempting to understand the genetics of social phenomena. Understanding the biological pathways linking genetics and the environment will allow scientists to better evaluate the functional importance of polygenic scores.PMID:37695007 | DOI:10.1017/S0140525X2200228X

Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis: A nested case-control study within the ATBC cohort

Mon, 11/09/2023 - 12:00
Int J Cancer. 2023 Sep 11. doi: 10.1002/ijc.34726. Online ahead of print.ABSTRACTIn pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) <0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs) and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation.PMID:37694774 | DOI:10.1002/ijc.34726

Tetracycline inhibit tick host reproduction by modulating bacterial microbiota, gene expression, and metabolism levels

Mon, 11/09/2023 - 12:00
Pest Manag Sci. 2023 Sep 11. doi: 10.1002/ps.7766. Online ahead of print.ABSTRACTBACKGROUND: Ticks are disease vectors that are matters of worldwide concern. Antibiotic treatments have been used to explore the interactions between ticks and their symbiotic microorganisms. In addition to altering the host microbial community, antibiotics can have toxic effects on the host.RESULTS: In the tick Haemaphysalis longicornis, the engorged females showed reproductive disruption after microinjection of tetracycline Multi-omics approaches were implemented to unravel the mechanisms of tick reproductive inhibition in this study. There were no significant changes in bacterial density in the whole ticks on days 2 or 4 after tetracycline treatment, while the bacterial microbial community was significantly altered, especially on day 4. The relative abundances of the bacteria Staphylococcus, Bacillus, and Pseudomonas decreased after tetracycline treatment, while the relative abundances of Coxiella and Rhodococcus increased. Ovarian transcriptional analysis revealed a cumulative effect of tetracycline treatment, as there was a significant increase in the number of differentially expressed genes with treatment time and a higher number of downregulated genes. The tick physiological pathways including lysosome, extracellular matrix (ECM)-receptor interaction, biosynthesis of ubiquinone and other terpenoids-quinones, insect hormone biosynthesis, and focal adhesion were significantly inhibited after 4 days of tetracycline treatment. Metabolite levels were altered after tetracycline treatment, and the differences increased with treatment time. The differential metabolites were involved in a variety of physiological pathways; the downregulated metabolites were significantly enriched in the nicotinate and nicotinamide metabolism, galactose metabolism, and ether lipid metabolism pathways.CONCLUSIONS: These findings indicate that tetracycline inhibits tick reproduction through the regulation of tick bacterial communities, gene expression, and metabolic levels. The results may provide new strategies for tick control. This article is protected by copyright. All rights reserved.PMID:37694307 | DOI:10.1002/ps.7766

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses

Mon, 11/09/2023 - 12:00
iScience. 2023 Aug 12;26(9):107620. doi: 10.1016/j.isci.2023.107620. eCollection 2023 Sep 15.ABSTRACTFetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.PMID:37694157 | PMC:PMC10485038 | DOI:10.1016/j.isci.2023.107620

Peeling back the layers of coral holobiont multi-omics data

Mon, 11/09/2023 - 12:00
iScience. 2023 Aug 14;26(9):107623. doi: 10.1016/j.isci.2023.107623. eCollection 2023 Sep 15.ABSTRACTThe integration of multiple 'omics' datasets is a promising avenue for answering many important and challenging questions in biology, particularly those relating to complex ecological systems. Although multi-omics was developed using data from model organisms with significant prior knowledge and resources, its application to non-model organisms, such as coral holobionts, is less clear-cut. We explore, in the emerging rice coral model Montipora capitata, the intersection of holobiont transcriptomic, proteomic, metabolomic, and microbiome amplicon data and investigate how well they correlate under high temperature treatment. Using a typical thermal stress regime, we show that transcriptomic and proteomic data broadly capture the stress response of the coral, whereas the metabolome and microbiome datasets show patterns that likely reflect stochastic and homeostatic processes associated with each sample. These results provide a framework for interpreting multi-omics data generated from non-model systems, particularly those with complex biotic interactions among microbial partners.PMID:37694134 | PMC:PMC10482995 | DOI:10.1016/j.isci.2023.107623

Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling

Mon, 11/09/2023 - 12:00
Open Med (Wars). 2023 Aug 30;18(1):20230785. doi: 10.1515/med-2023-0785. eCollection 2023.ABSTRACTUlcerative colitis (UC) is an inflammatory bowel disease and associated with metabolic imbalance. Luteolin (LUT) reportedly exhibits anti-inflammatory activity. However, its regulatory effects on metabolites remain indistinct. Here, the effects of LUT on immune response and oxidative stress in UC were determined. Serum metabolomics profiles of UC rats treated with LUT were obtained utilizing liquid chromatography-mass spectrometry. The results revealed that LUT treatment alleviated colon tissue injury, colon shortening, weight loss, and inflammatory response in UC rats. Additionally, the levels of superoxide dismutase and total antioxidant capacity were elevated, but malondialdehyde content was reduced in serum of UC rats, while these changes were abrogated by LUT. Metabolomics analysis unveiled that l-malic acid, creatinine, l-glutamine, and l-lactic acid levels were remarkably decreased, while dimethyl sulfone, 5-methylcytosine, cysteine-S-sulfate, and jasmonic acid levels were notably increased after LUT treatment. Furthermore, differential metabolites primarily participated in d-glutamine and d-glutamate metabolism, glutathione metabolism, and citrate cycle pathways. In summary, these results demonstrated that LUT improved immune response, alleviated oxidative stress, and altered metabolites in UC rats. This study lays the root for further exploring the mechanism of LUT in the treatment of UC.PMID:37693835 | PMC:PMC10487402 | DOI:10.1515/med-2023-0785

Metabolomic profiling of CSF and blood serum elucidates general and sex-specific patterns for mild cognitive impairment and Alzheimer's disease patients

Mon, 11/09/2023 - 12:00
Front Aging Neurosci. 2023 Aug 24;15:1219718. doi: 10.3389/fnagi.2023.1219718. eCollection 2023.ABSTRACTBACKGROUND: Beta-amyloid (Abeta) and tau protein in cerebrospinal fluid (CSF) are established diagnostic biomarkers for Alzheimer's disease (AD). However, these biomarkers may not the only ones existing parameters that reflect Alzheimer's disease neuropathological change. The use of quantitative metabolomics approach could provide novel insights into dementia progression and identify key metabolic alterations in CSF and serum.METHODS: In the present study, we quantified a set of 45 metabolites in CSF (71 patients) and 27 in serum (76 patients) in patients with mild cognitive impairment (MCI), AD, and controls using nuclear magnetic resonance (NMR)-based metabolomics.RESULTS: We found significantly reduced CSF (1.32-fold, p = 0.0195) and serum (1.47-fold, p = 0.0484) levels of the ketone body acetoacetate in AD and MCI patients. Additionally, we found decreased levels (1.20-fold, p = 0.0438) of the branched-chain amino acid (BCAA) valine in the CSF of AD patients with increased valine degradation pathway metabolites (such as 3-hydroxyisobutyrate and α-ketoisovalerate). Moreover, we discovered that CSF 2-hydroxybutyrate is dramatically reduced in the MCI patient group (1.23-fold, p = 0.039). On the other hand, vitamin C (ascorbate) was significantly raised in CSF of these patients (p = 0.008). We also identified altered CSF protein content, 1,5-anhydrosorbitol and fructose as further metabolic shifts distinguishing AD from MCI. Significantly decreased serum levels of the amino acid ornithine were seen in the AD dementia group when compared to healthy controls (1.36-fold, p = 0.011). When investigating the effect of sex, we found for AD males the sign of decreased 2-hydroxybutyrate and acetoacetate in CSF while for AD females increased serum creatinine was identified.CONCLUSION: Quantitative NMR metabolomics of CSF and serum was able to efficiently identify metabolic changes associated with dementia groups of MCI and AD patients. Further, we showed strong correlations between these changes and well-established metabolomic and clinical indicators like Abeta.PMID:37693649 | PMC:PMC10483152 | DOI:10.3389/fnagi.2023.1219718

Pre-treatment Amino Acids and Risk of Paclitaxel-induced Peripheral Neuropathy in SWOG S0221

Mon, 11/09/2023 - 12:00
Res Sq. 2023 Sep 1:rs.3.rs-3242513. doi: 10.21203/rs.3.rs-3242513/v1. Preprint.ABSTRACTBackground Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity. Methods Pre-treatment levels of 20 amino acid concentrations were measured via a targeted mass spectrometry assay in banked serum from the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acid levels and CIPN occurrence or severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction for multiple comparisons. The network of metabolic pathways of amino acids was analyzed using over-representation analysis in MetaboAnalyst. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm and Cytoscape. Results In the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In a secondary analysis, no amino acid was associated with CIPN occurrence (all p > 0.0025). Higher concentrations of four amino acids, glutamate (β = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (β = 0.54 [0.19, 0.89], p = 0.002), tyrosine (β = 0.57 [0.23, 0.91], p = 0.001), and valine (β = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality. Conclusions This analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Future prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged.PMID:37693586 | PMC:PMC10491324 | DOI:10.21203/rs.3.rs-3242513/v1

Evolutionarily related host and microbial pathways regulate fat desaturation

Mon, 11/09/2023 - 12:00
bioRxiv. 2023 Aug 31:2023.08.31.555782. doi: 10.1101/2023.08.31.555782. Preprint.ABSTRACTFatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression 1-4 , but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans . Untargeted metabolomics of a β-oxidation mutant, acdh-11 , in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β- cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli . Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, whose activity mimics that of microbiota-dependent becyp#1, but is derived from a methyltransferase, fcmt-1 , that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.PMID:37693574 | PMC:PMC10491262 | DOI:10.1101/2023.08.31.555782

Gut microbiota promoting propionic acid production accompanies diet-induced intentional weight loss in cats

Mon, 11/09/2023 - 12:00
Res Sq. 2023 Aug 28:rs.3.rs-3273531. doi: 10.21203/rs.3.rs-3273531/v1. Preprint.ABSTRACTRodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for seven days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during diet-induced weight loss (adjusted p < 0.05). Spearman correlation revealed the relative abundances of Prevotella 9 copri (ρ = 0.6385, p = 0.0006) and Blautia caecimuris (ρ = 0.5269, p = 0.0068) were significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during diet-induced weight loss.PMID:37693421 | PMC:PMC10491335 | DOI:10.21203/rs.3.rs-3273531/v1

Advancements in ToF-SIMS imaging for life sciences

Mon, 11/09/2023 - 12:00
Front Chem. 2023 Aug 24;11:1237408. doi: 10.3389/fchem.2023.1237408. eCollection 2023.ABSTRACTIn the last 2 decades, Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) has gained significant prominence as a powerful imaging technique in the field of life sciences. This comprehensive review provides an in-depth overview of recent advancements in ToF-SIMS instrument technology and its applications in metabolomics, lipidomics, and single-cell analysis. We highlight the use of ToF-SIMS imaging for studying lipid distribution, composition, and interactions in cells and tissues, and discuss its application in metabolomics, including the analysis of metabolic pathways. Furthermore, we review recent progress in single-cell analysis using ToF-SIMS, focusing on sample preparation techniques, in situ investigation for subcellular distribution of drugs, and interactions between drug molecules and biological targets. The high spatial resolution and potential for multimodal analysis of ToF-SIMS make it a promising tool for unraveling the complex molecular landscape of biological systems. We also discuss future prospects and potential advancements of ToF-SIMS in the research of life sciences, with the expectation of a significant impact in the field.PMID:37693171 | PMC:PMC10483116 | DOI:10.3389/fchem.2023.1237408

Comparative metabolomic profiling of <em>Cupriavidus necator</em> B-4383 revealed production of cupriachelin siderophores, one with activity against <em>Cryptococcus neoformans</em>

Mon, 11/09/2023 - 12:00
Front Chem. 2023 Aug 24;11:1256962. doi: 10.3389/fchem.2023.1256962. eCollection 2023.ABSTRACTCupriavidus necator H16 is known to be a rich source of linear lipopeptide siderophores when grown under iron-depleted conditions; prior literature termed these compounds cupriachelins. These small molecules bear β-hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as ferric cupriachelin. Here, we present structural assignment of cupriachelins from C. necator B-4383 grown under iron limitation. The characterization of B-4383 cupriachelins is based on MS/MS fragmentation analysis, which was confirmed by 1D- and 2D-NMR for the most abundant analog (1). The cupriachelin congeners distinguish these two strains with differences in the preferred lipid tail; however, our rigorous metabolomic investigation also revealed minor analogs with changes in the peptide core, hinting at a potential mechanism by which these siderophores may reduce biologically unavailable ferric iron (4-6). Antifungal screening of the C. necator B-4383 supernatant extract and the isolated cupriachelin analog (1) revealed inhibitory activity against Cryptococcus neoformans, with IC50 values of 16.6 and 3.2 μg/mL, respectively. This antifungal activity could be explained by the critical role of the iron acquisition pathway in the growth and pathogenesis of the C. neoformans fungal pathogen.PMID:37693169 | PMC:PMC10484230 | DOI:10.3389/fchem.2023.1256962

Copper boosts the biostimulant activity of a vegetal-derived protein hydrolysate in basil: morpho-physiological and metabolomics insights

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 24;14:1235686. doi: 10.3389/fpls.2023.1235686. eCollection 2023.ABSTRACTIn addition to be used as a plant protection agent, copper (Cu) is also an essential micronutrient for plant growth and development. The bioavailability of Cu in agricultural systems can be limited due to its specific physical-chemical characteristics, leading to imbalances in plant production. To address this issue, an experimental trial was conducted on Genovese basil (Ocimum basilicum L.) in protected conditions to comparatively evaluate the effects of a vegetable protein hydrolysate (VPH), free Cu and Cu complexed with peptides and amino acids of vegetal origin (Cu and Cu-VPH, respectively), and a combination of VPH and Cu-VPH (VPH+Cu-VPH). The study showed that the combined application of VPH+Cu-VPH led to a significant average increase of 16.3% in fresh yield compared to the untreated Control and Cu treatment. This finding was supported by an improved photosynthetic performance in ACO2 (+29%) and Fv/Fm (+7%). Furthermore, mineral analysis using ICP OES demonstrated that Cu and Cu-VPH treatments determined, on average, a 15.1-, 16.9-, and 1.9-fold increase in Cu in plant tissues compared to control, VPH, and VPH+Cu-VPH treatments, respectively. However, the VPH+Cu-VPH treatment induced the highest contents of the other analyzed ions, except for P. In particular, Mg, Mn, Ca, and Fe, which take part in the constitution of chlorophylls, water splitting system, and photosynthetic electron transport chain, increased by 23%, 21%, 25%, and 32% compared to respective controls. Indeed, this improved the photosynthetic efficiency and the carboxylation capacity of the plants, and consequently, the physiological and productive performance of Genovese basil, compared to all other treatments and control. Consistently, the untargeted metabolomics also pointed out a distinctive modulation of phytochemical signatures as a function of the treatment. An accumulation of alkaloids, terpenoids, and phenylpropanoids was observed following Cu treatment, suggesting an oxidative imbalance upon metal exposure. In contrast, a mitigation of oxidative stress was highlighted in Cu-VPH and VPH+Cu-VPH, where the treatments reduced stress-related metabolites. Overall, these results highlight an interaction between Cu and VPH, hence paving the way towards the combined use of Cu and biostimulants to optimize agronomic interventions.PMID:37692443 | PMC:PMC10484225 | DOI:10.3389/fpls.2023.1235686

<em>Trichoderma</em> spp.-mediated mitigation of heat, drought, and their combination on the Arabidopsis thaliana holobiont: a metabolomics and metabarcoding approach

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 21;14:1190304. doi: 10.3389/fpls.2023.1190304. eCollection 2023.ABSTRACTINTRODUCTION: The use of substances to increase productivity and resource use efficiency is now essential to face the challenge of feeding the rising global population with the less environmental impact on the ecosystems. Trichoderma-based products have been used as biopesticides, to inhibit pathogenic microorganisms, and as biostimulants for crop growth, nutrient uptake promotion, and resistance to abiotic stresses.METHODS: In this work, plant metabolomics combined with roots and rhizosphere bacterial metabarcoding were exploited to inspect the performance of Trichoderma spp. biostimulants on Arabidopsis thaliana under drought, heat and their combination and its impact on plant holobiont.RESULTS AND DISCUSSION: An overall modulation of N-containing compounds, phenylpropanoids, terpenes and hormones could be pointed out by metabolomics. Moreover, metabarcoding outlined an impact on alpha and beta-diversity with an abundance of Proteobacteria, Pseudomonadales, Burkholderiales, Enterobacteriales and Azospirillales. A holobiont approach was applied as an integrated analytical strategy to resolve the coordinated and complex dynamic interactions between the plant and its rhizosphere bacteria using Arabidopsis thaliana as a model host species.PMID:37692426 | PMC:PMC10484583 | DOI:10.3389/fpls.2023.1190304

Editorial: Metabolomics: a tool to understand plant protection against biotic and abiotic stresses

Mon, 11/09/2023 - 12:00
Front Plant Sci. 2023 Aug 24;14:1274405. doi: 10.3389/fpls.2023.1274405. eCollection 2023.NO ABSTRACTPMID:37692415 | PMC:PMC10484605 | DOI:10.3389/fpls.2023.1274405

Intestinal acetic acid regulates the synthesis of sex pheromones in captive giant pandas

Mon, 11/09/2023 - 12:00
Front Microbiol. 2023 Aug 25;14:1234676. doi: 10.3389/fmicb.2023.1234676. eCollection 2023.ABSTRACTAs a typical solitary animal, adult giant pandas rely on chemical signals (sex pheromones) to transmit reproductive information during oestrous. Although researchers have confirmed that the gut microbiota is related to the emission and reception of sex pheromones, there is no clear correlation between the gut microbes and the synthesis of sex pheromone of giant pandas, that is, which gut microbes and microbial metabolites are participate in the synthesis of giant panda's sex pheromone. As a mirror of gut microbiota, fecal microbiota can reflect the composition of gut microbiota and its interaction with host to some extent. The purpose of this study is to explore how the gut microbes affect the synthesis of sex pheromones in captive giant pandas by combining analysis of the fecal microbiome and metabolomics. The results of correlation and microbial function analysis show that intestinal microorganisms such as Veillonellaceae and Lactobacillilaceae are associated with the synthesis of short chain fatty acid (acetic acid) and volatile ester metabolites, such as 1-butanol, 3-methyl, acetate, acetic acid, hexyl ester and 3-hexen-1-ol, acetate, (Z). In summary, based on this study, we believe that volatile metabolites such as fecal acetate participate in the process of mate preference of captive giant pandas and affect their expression of natural mating behavior. The possible mechanism is that the gut microbes can promote the synthesis of key chemical signaling substances in perianal glands through mediated intermediate fecal metabolites, thus affecting the normal information exchange between giant pandas individuals. The results of this study have greatly enriched our understanding of gut microbes regulating the synthesis of sex pheromones in giant pandas.PMID:37692393 | PMC:PMC10485365 | DOI:10.3389/fmicb.2023.1234676

Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics

Mon, 11/09/2023 - 12:00
Front Microbiol. 2023 Aug 24;14:1256142. doi: 10.3389/fmicb.2023.1256142. eCollection 2023.ABSTRACTINTRODUCTION: Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear.METHODS: In this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS.RESULTS: The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman's correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α).DISCUSSION: In conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.PMID:37692389 | PMC:PMC10483239 | DOI:10.3389/fmicb.2023.1256142

Angiotensin II modulates THP-1-like macrophage phenotype and inflammatory signatures via angiotensin II type 1 receptor

Mon, 11/09/2023 - 12:00
Front Cardiovasc Med. 2023 Aug 25;10:1129704. doi: 10.3389/fcvm.2023.1129704. eCollection 2023.ABSTRACTAngiotensin II (Ang II) is a major component of the renin-angiotensin or renin-angiotensin-aldosterone system, which is the main element found to be involved in cardiopathology. Recently, long-term metabolomics studies have linked high levels of angiotensin plasma to inflammatory conditions such as coronary heart disease, obesity, and type 2 diabetes. Monocyte/macrophage cellular function and phenotype orchestrate the inflammatory response in various pathological conditions, most notably cardiometabolic disease. An activation of the Ang II system is usually associated with inflammation and cardiovascular disease; however, the direct effect on monocyte/macrophages has still not been well elucidated. Herein, we have evaluated the cellular effects of Ang II on THP-1-derived macrophages. Ang II stimulated the expression of markers involved in monocyte/macrophage cell differentiation (e.g., CD116), as well as adhesion, cell-cell interaction, chemotaxis, and phagocytosis (CD15, CD44, CD33, and CD49F). Yet, Ang II increased the expression of proinflammatory markers (HLA-DR, TNF-α, CD64, CD11c, and CD38) and decreased CD206 (mannose receptor), an M2 marker. Moreover, Ang II induced cytosolic calcium overload, increased reactive oxygen species, and arrested cells in the G1 phase. Most of these effects were induced via the angiotensin II type 1 receptor (AT1R). Collectively, our results provide new evidence in support of the effect of Ang II in inflammation associated with cardiometabolic diseases.PMID:37692050 | PMC:PMC10485254 | DOI:10.3389/fcvm.2023.1129704

The role of the symbiotic microecosystem in cancer: gut microbiota, metabolome, and host immunome

Mon, 11/09/2023 - 12:00
Front Immunol. 2023 Aug 24;14:1235827. doi: 10.3389/fimmu.2023.1235827. eCollection 2023.ABSTRACTThe gut microbiota is not just a simple nutritional symbiosis that parasitizes the host; it is a complex and dynamic ecosystem that coevolves actively with the host and is involved in a variety of biological activities such as circadian rhythm regulation, energy metabolism, and immune response. The development of the immune system and immunological functions are significantly influenced by the interaction between the host and the microbiota. The interactions between gut microbiota and cancer are of a complex nature. The critical role that the gut microbiota plays in tumor occurrence, progression, and treatment is not clear despite the already done research. The development of precision medicine and cancer immunotherapy further emphasizes the importance and significance of the question of how the microbiota takes part in cancer development, progression, and treatment. This review summarizes recent literature on the relationship between the gut microbiome and cancer immunology. The findings suggest the existence of a "symbiotic microecosystem" formed by gut microbiota, metabolome, and host immunome that is fundamental for the pathogenesis analysis and the development of therapeutic strategies for cancer.PMID:37691931 | PMC:PMC10484231 | DOI:10.3389/fimmu.2023.1235827

Inceptor facilitates acrosomal vesicle formation in spermatids and is required for male fertility

Mon, 11/09/2023 - 12:00
Front Cell Dev Biol. 2023 Aug 24;11:1240039. doi: 10.3389/fcell.2023.1240039. eCollection 2023.ABSTRACTSpermatogenesis is a crucial biological process that enables the production of functional sperm, allowing for successful reproduction. Proper germ cell differentiation and maturation require tight regulation of hormonal signals, cellular signaling pathways, and cell biological processes. The acrosome is a lysosome-related organelle at the anterior of the sperm head that contains enzymes and receptors essential for egg-sperm recognition and fusion. Even though several factors crucial for acrosome biogenesis have been discovered, the precise molecular mechanism of pro-acrosomal vesicle formation and fusion is not yet known. In this study, we investigated the role of the insulin inhibitory receptor (inceptor) in acrosome formation. Inceptor is a single-pass transmembrane protein with similarities to mannose-6-phosphate receptors (M6PR). Inceptor knockout male mice are infertile due to malformations in the acrosome and defects in the nuclear shape of spermatozoa. We show that inceptor is expressed in early spermatids and mainly localizes to vesicles between the Golgi apparatus and acrosome. Here we show that inceptor is an essential factor in the intracellular transport of trans-Golgi network-derived vesicles which deliver acrosomal cargo in maturing spermatids. The absence of inceptor results in vesicle-fusion defects, acrosomal malformation, and male infertility. These findings support our hypothesis of inceptor as a universal lysosomal or lysosome-related organelle sorting receptor expressed in several secretory tissues.PMID:37691832 | PMC:PMC10483240 | DOI:10.3389/fcell.2023.1240039

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