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

Exploring the flavor changes in mung bean flour through lactobacillus fermentation: insights from volatile compounds and non-targeted metabolomics analysis

Tue, 16/04/2024 - 12:00
J Sci Food Agric. 2024 Apr 16. doi: 10.1002/jsfa.13545. Online ahead of print.ABSTRACTBACKGROUND: Mung beans are abundant in nutrition, but their leguminous flavor limits their development. Lactic Acid Bacteria (LAB) fermentation can decrease unwanted bean flavors in legumes and enhance their flavor. This study examined the influence of Lactobacillus fermentation on the flavor characteristics of mung bean flour (MBF) using volatile compounds and non-targeted metabolomics.RESULTS: Lactobacillus plantarum LP90, Lactobacillus casei LC89, and Lactobacillus acidophilus LA85 eliminated 61.37%, 48.29%, and 43.73% of the primary bean odor aldehydes from MBF. The results of relative odor activity values (ROAV) showed that fermented mung bean flour (FMBF) included volatile chemicals that contributed to fruity, flowery, and milky aromas. These compounds included ethyl acetate, hexyl formate, 3-hydroxy-2-butanone, and 2,3-butanedione. The levels of amino acids with a fresh sweet flavor increased significantly by 93.89%, 49.40%, and 35.27% in LP90, LC89, and LA85, respectively. A total of 49 up-regulated and 13 down-regulated significantly differential metabolites were annotated, and 10 metabolic pathways were screened for contributing to the flavor. The correlation between important volatile compounds and non-volatile substances relies on two primary metabolic pathways: the citric acid cycle pathway and the amino acid metabolic system.CONCLUSION: The flavor of MBF was greatly enhanced by the process of Lactobacillus fermentation, with LP90 having the most notable impact. These results serve as a reference for identifying the flavor of FMBF. This article is protected by copyright. All rights reserved.PMID:38625751 | DOI:10.1002/jsfa.13545

The estrogen signaling pathway reprograms prostate cancer cell metabolism and supports proliferation and disease progression

Tue, 16/04/2024 - 12:00
J Clin Invest. 2024 Apr 16:e170809. doi: 10.1172/JCI170809. Online ahead of print.ABSTRACTJust as the androgen receptor (AR), the estrogen receptor α (ERα) is expressed in the prostate and is thought to influence prostate cancer (PCa) biology. Yet, the incomplete understanding of ERα functions in PCa hinders our ability to fully comprehend its clinical relevance and restricts the repurposing of estrogen-targeted therapies for the treatment of this disease. Using two human PCa tissue microarray cohorts, we first demonstrated that nuclear ERα expression was heterogeneous among patients, being only detected in half of tumors. Positive nuclear ERα levels were correlated with disease recurrence, progression to metastatic PCa, and patient survival. Using in vitro and in vivo models of the normal prostate and PCa, bulk and single-cell RNA-Seq analyses revealed that estrogens partially mimic the androgen transcriptional response and induce specific biological pathways linked to proliferation and metabolism. Bioenergetic flux assays and metabolomics confirmed the regulation of cancer metabolism by estrogens, supporting proliferation. Using cancer cell lines and patient-derived organoids, selective estrogen receptor modulators, a pure anti-estrogen, and genetic approaches impaired cancer cell proliferation and growth in an ERα-dependent manner. Overall, our study revealed that, when expressed, ERα functionally reprograms PCa metabolism, is associated with disease progression, and could be targeted for therapeutic purposes.PMID:38625747 | DOI:10.1172/JCI170809

Response and Adaptive Mechanism of Flavonoids in Pigmented Potatoes to Different Altitudes

Tue, 16/04/2024 - 12:00
Plant Cell Physiol. 2024 Apr 16:pcae045. doi: 10.1093/pcp/pcae045. Online ahead of print.ABSTRACTAltitude is an important ecological factor affecting plant physiology and ecology, material metabolism and gene expression. Tuber color changes were observed in purple and red potatoes growing at four different elevations ranging from 1800±50 to 3300±50 meters in the Tiger Leaping Gorge area of Yunnan Province. The results showed that the TPC, TFC, TAC and biological yield of anthocyanin increased with increasing altitude until 2800 ± 50 m, and the highest anthocyanin contents were detected in the purple potato Huaxinyangyu and the red potato Jianchuanhong at the flowering stage and budding stage, respectively. Combined transcriptomic and metabolomic analyses revealed that the content and diversity of flavonoids are associated with gene expression via the promotion of propane metabolism to improve potato adaptation to different altitudes. These results provide a foundation for understanding the coloring mechanism and creating new potato germplasms with high resistance and good quality via genetic manipulation.PMID:38625713 | DOI:10.1093/pcp/pcae045

Impacts of AlaAT3 transgenic poplar on rhizosphere soil chemical properties, enzyme activity, bacterial community, and metabolites under two nitrogen conditions

Tue, 16/04/2024 - 12:00
GM Crops Food. 2024 Dec 31;15(1):1-15. doi: 10.1080/21645698.2024.2339568. Epub 2024 Apr 16.ABSTRACTPoplar stands as one of the primary afforestation trees globally. We successfully generated transgenic poplar trees characterized by enhanced biomass under identical nutrient conditions, through the overexpression of the pivotal nitrogen assimilation gene, pxAlaAT3. An environmental risk assessment was conducted for investigate the potential changes in rhizosphere soil associated with these overexpressing lines (OL). The results show that acid phosphatase activity was significantly altered under ammonium in OL compared to the wild-type control (WT), and a similar difference was observed for protease under nitrate. 16SrDNA sequencing indicated no significant divergence in rhizosphere soil microbial community diversity between WT and OL. Metabolomics analysis revealed that the OL caused minimal alterations in the metabolites of the rhizosphere soil, posing no potential harm to the environment. With these findings in mind, we anticipate that overexpressed plants will not adversely impact the surrounding soil environment.PMID:38625676 | DOI:10.1080/21645698.2024.2339568

Brain Immune Cell Infiltration and Serum Metabolomic Characteristics Reveal that Lauric Acid Promotes Immune Cell Infiltration in Brain and Streptococcus suis Meningitis in Mice

Tue, 16/04/2024 - 12:00
Mol Neurobiol. 2024 Apr 16. doi: 10.1007/s12035-024-04144-1. Online ahead of print.ABSTRACTAlthough naturally Streptococcus suis serotype 2 (SS2) causes meningitis resulting in death or sequela of neurological symptoms in pigs and humans, severely threatening public health in the world, it has been difficult to build up and confirm experimental meningitis mouse models with obvious neurological syndrome for about two decades, which strongly hampers the in-depth study on the control measures and mechanisms of SS2-induced meningitis. In this study, a typical meningitis mouse model of SS2 was successfully established, as confirmed by the behavioral indicators of balance beam test, suspension test, and gait analysis. With bacteria gathering in the brain, distinguishable unique features including meningeal thickening, vacuolization of the Nissl body, brain barrier damage, glial cell activation, and more infiltration of T cells, macrophages, and DCs are observed in SS2 meningitis mice with typical neurological signs. Some meningitis mice were also accompanied by identical nephritis, ophthalmia, and cochlearitis. Investigation of the metabolic features demonstrated the downregulated cholic acid and upregulated 2-hydroxyvaleric acid, tetrahydrocortisone, nicotinic acid, and lauric acid in blood serum of mice and piglets with meningitis. And feeding trials show that lauric acid can promote meningitis by promoting the infiltration of immune cells into brain. These findings demonstrated that infection of ICR (improved castle road) mice with SS2 was able to induce typical meningitis accompanied by immune cell infiltration and lauric acid upregulation. These data provide a basis for the deep study of SS2 meningitis.PMID:38625620 | DOI:10.1007/s12035-024-04144-1

Exploring Anticancer Properties of Medicinal Plants against Breast Cancer by Downregulating Human Epidermal Growth Factor Receptor 2

Tue, 16/04/2024 - 12:00
J Agric Food Chem. 2024 Apr 16. doi: 10.1021/acs.jafc.3c07565. Online ahead of print.ABSTRACTPlants have a history of being employed in managing breast cancer. However, no scientific evidence supports the idea that these plants can effectively reduce the level of HER2 expression. In this study, extracts from 10 medicinal plants were evaluated for their anticancer properties against HER2-positive breast cancer cells through various methods, including the SRB assay, comet assay, annexin V-FITC dual staining, and immunoblotting. All extracts exerted antiproliferative activity against HER2-positive breast cancer cells. Furthermore, Terminalia chebula (T. chebula), Berberis aristata (B. aristata), and Mucuna pruriens (M. pruriens) reduced HER2 expression in tested cell lines. In addition, an increased Bax/Bcl-2 ratio was observed after the treatment. A comparative proteomics study showed modulation in the proteome profile of breast cancer cells after treatment with T. chebula, B. aristata, Punica granatum, M. pruriens, and Acorus calamus. Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.PMID:38624258 | DOI:10.1021/acs.jafc.3c07565

Metabolic profiling of peri-implant crevicular fluid in peri-implantitis

Tue, 16/04/2024 - 12:00
Clin Oral Implants Res. 2024 Apr 16. doi: 10.1111/clr.14270. Online ahead of print.ABSTRACTOBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI).MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities.RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus.CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.PMID:38624226 | DOI:10.1111/clr.14270

Machine learning approach to assess the association between anthropometric, metabolic, and nutritional status and semen parameters

Tue, 16/04/2024 - 12:00
Asian J Androl. 2024 Apr 12. doi: 10.4103/aja20247. Online ahead of print.ABSTRACTMany lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.PMID:38624205 | DOI:10.4103/aja20247

Catabolism of phenolics from grape peel and its effects on gut microbiota during in vitro colonic fermentation

Tue, 16/04/2024 - 12:00
J Sci Food Agric. 2024 Apr 16. doi: 10.1002/jsfa.13540. Online ahead of print.ABSTRACTBACKGROUND: Grape peels, the main by-products of wine processing, are rich in bioactive ingredients of phenolics, including proanthocyanidins, flavonoids and anthocyanins. Phenolics have the function of regulating intestinal microbiota and promoting intestinal health. From the perspective of the dietary nutrition of grape peel phenolics (GPP), this study was to investigate the influence of GPP on the composition and metabolism of human gut microbiota during in vitro fermentation.RESULTS: The results indicated that GPP could decrease pH and promote the production of short-chain fatty acids (SCFAs). ACE and Chao1 indices in GPP group were lower than that of the Blank group. GPP enhanced the levels of Lachnospiraceae UCG-004, Bacteroidetes, and Roseburia, but reduced the Firmicutes/Bacteroidetes ratio. KEGG enrichment pathways related to phenolic acid metabolism mainly included flavonoid, anthocyanin, flavone and flavonol biosynthesis. Gut microbiota could accelerate the release and breakdown of phenolic compounds, resulting in a decrease in the content of hesperetin-7-O-glucoside, delphinidin-3-O-glucoside, and cyanidin-3-rutinoside etc. In vitro antibacterial test found that GPP increased the diameters of the inhibition zones of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in a dose-dependent manner.CONCLUSION: The above results revealed that GPP might be a potential prebiotic-like to prevent diseases by improving gut health. This study could provide theoretical basis for potential to exploit GPP as dietary nutrition to maintain intestinal function. This article is protected by copyright. All rights reserved.PMID:38624038 | DOI:10.1002/jsfa.13540

Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L

Tue, 16/04/2024 - 12:00
J Exp Zool A Ecol Integr Physiol. 2024 Apr 16. doi: 10.1002/jez.2812. Online ahead of print.ABSTRACTType 2 diabetes (T2D) is the most common metabolic disorder. The undesirable effects of synthetic drugs demand a search for safe antidiabetic agents. This study aimed to assess the antidiabetic activity of different fractions of Atriplex halimus (petroleum ether 60-80, methylene chloride, ethyl acetate, and n-butanol) using Drosophila melanogaster larvae. Titers of total glucose and trehalose, as well as larval weight, were measured and compared with those of control and diabetic larvae. The expression of Drosophila insulin-like peptides (DILP2 and DILP3) and adipokinetic hormone (AKH) was evaluated. The results revealed a significant increase in total glucose, trehalose, and a decrease in body weight in the larvae fed a high-sugar diet compared with those in the control. When larvae fed diets containing the tested fractions, the total glucose and trehalose decreased to the control level, and the body weight increased. DILP2, DILP3, and AKH exhibited significant decreases upon treatment with A. halimus ethyl acetate. Metabolomic profiling of the ethyl acetate fraction of A. halimus revealed the presence of flavonoids and flavonoid glycosides. After docking screening to predict the most powerful moiety, we discovered that flavonoid glycosides (especially eriodictyol-7-O-neohesperidoside) have a greater affinity for the pocket than the other moieties. The results indicated the therapeutic activity of the A. halimus ethyl acetate fraction against induced T2D in Drosophila larvae. The antidiabetic activity may be attributed to flavonoids, which are the main components of the A. halimus ethyl acetate fraction.PMID:38623920 | DOI:10.1002/jez.2812

Untargeted Metabolomic to Access Chemical Differences Induced by Dual Endophyte Cultures Isolated from Euphorbia umbellata

Tue, 16/04/2024 - 12:00
Chem Biodivers. 2024 Apr 16:e202400395. doi: 10.1002/cbdv.202400395. Online ahead of print.ABSTRACTEndophytic fungi live asymptomatically inside vegetal tissues, and such uncommon habitat contributes to their exceptional chemical diversity. Isolating natural products from endophytic fungi could fail due to silent biosynthetic gene clusters under ordinary in vitro culture conditions, and co-culturing has been assayed to trigger their metabolism. We carried out single and dual cultures with 13 endophyte strains isolated from Euphorbia umbellata leaves. Multivariate statistics applied to untargeted metabolomics compared the chemical profiles of all endophyte cultures. PCA analysis guided the selection of the Aspergillus pseudonomiae J1 - Porogramme brasiliensis J9 dual culture for its most significant chemical differentiation: Five compounds were putatively annotated in the J1-J9 culture according to UHPLC-HRMS data, kojic acid, haliclonol and its diastereoisomer, caffeic acid, and 2-(3,4-dihydroxyphenyl)acetaldehyde. Analysis by PLS-DA using VIP score showed that kojic acid displayed the most significative importance in discriminating single and dual J1-J9 cultures.PMID:38623912 | DOI:10.1002/cbdv.202400395

Tongue-Coating Microbial and Metabolic Characteristics in Halitosis

Tue, 16/04/2024 - 12:00
J Dent Res. 2024 Apr 16:220345241230067. doi: 10.1177/00220345241230067. Online ahead of print.ABSTRACTHalitosis is a common oral condition, which leads to social embarrassment and affects quality of life. Cumulative evidence has suggested the association of tongue-coating microbiome with the development of intraoral halitosis. The dynamic variations of tongue-coating microbiota and metabolites in halitosis have not been fully elucidated. Therefore, the present study aimed to determine the tongue-coating microbial and metabolic characteristics in halitosis subjects without other oral diseases using metagenomics and metabolomics analysis. The participants underwent oral examination, halitosis assessment, and tongue-coating sample collection for the microbiome and metabolome analysis. It was found that the microbiota richness and diversity were significantly elevated in the halitosis group. Furthermore, species from Actinomyces, Prevotella, Veillonella, and Solobacterium were significantly more abundant in the halitosis group. However, the Rothia and Streptococcus species exhibited opposite tendencies. Eleven Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in the halitosis tongue coatings, including cysteine and methionine metabolism. Functional genes related to sulfur, indole, skatole, and cadaverine metabolic processes (such as serA, metH, metK and dsrAB) were identified to be more abundant in the halitosis samples. The metabolome analysis revealed that indole-3-acetic, ornithine, and L-tryptophan were significantly elevated in the halitosis samples. Furthermore, it was observed that the values of volatile sulfur compounds and indole-3-acetic abundances were positively correlated. The multiomics analysis identified the metagenomic and metabolomic characteristics to differentiate halitosis from healthy individuals using the least absolute shrinkage and selection operator logistic regression and random forest classifier. A total of 19 species and 39 metabolites were identified as features in halitosis patients, which included indole-3-acetic acid, Bacillus altitudinis, Candidatus Saccharibacteria, and Actinomyces species. In conclusion, an evident shift in microbiome and metabolome characteristics was observed in the halitosis tongue coating, which may have a potential etiological significance and provide novel insights into the mechanism for halitosis.PMID:38623900 | DOI:10.1177/00220345241230067

A microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression reveals physiological characteristics similar to depression

Tue, 16/04/2024 - 12:00
Lab Chip. 2024 Apr 16. doi: 10.1039/d3lc01052j. Online ahead of print.ABSTRACTThe diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression. We introduced representative gut microbiota from individuals with depression into our constructed DoGC model, successfully recapitulating the gut microbiota structure of depressed patients. This further led to the manifestation of physiological characteristics resembling depression, such as reduced gut barrier function, chronic low-grade inflammatory responses and decreased neurotransmitter 5-HT levels. Metabolome analysis of substances in the DoGC revealed a significant increase in lipopolysaccharides and tyrosine, while hyodeoxycholic acid, L-proline and L-threonine were significantly reduced, indicating the occurrence of depression. The proposed DoGC can serve as an effective platform for studying the gut microbiota of patients with depression, providing important cues for their roles in the pathology of this condition and acting as a powerful tool for personalized medicine.PMID:38623757 | DOI:10.1039/d3lc01052j

Serum metabolomics improves risk stratification for incident heart failure

Tue, 16/04/2024 - 12:00
Eur J Heart Fail. 2024 Apr 16. doi: 10.1002/ejhf.3226. Online ahead of print.ABSTRACTAIMS: Prediction and early detection of heart failure (HF) is crucial to mitigate its impact on quality of life, survival, and healthcare expenditure. Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance [1H-NMR] spectroscopy) for incident HF.METHODS AND RESULTS: Leveraging data of 68 311 individuals and >0.8 million person-years of follow-up from the UK Biobank cohort, we (i) fitted per-metabolite Cox proportional hazards models to assess individual metabolite associations, and (ii) trained and validated elastic net models to predict incident HF using the serum metabolome. We benchmarked discriminative performance against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF [PCP-HF]). During a median follow-up of ≈12.3 years, several metabolites showed independent association with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈80% feature reduction). Adding metabolomics to PCP-HF improved predictive performance (Harrel's C: 0.768 vs. 0.755, ΔC = 0.013, [95% confidence interval [CI] 0.004-0.022], continuous net reclassification improvement [NRI]: 0.287 [95% CI 0.200-0.367], relative integrated discrimination improvement [IDI]: 17.47% [95% CI 9.463-27.825]). Models including age, sex and metabolomics performed almost as well as PCP-HF (Harrel's C: 0.745 vs. 0.755, ΔC = 0.010 [95% CI -0.004 to 0.027], continuous NRI: 0.097 [95% CI -0.025 to 0.217], relative IDI: 13.445% [95% CI -10.608 to 41.454]). Risk and survival stratification was improved by integrating metabolomics.CONCLUSION: Serum metabolomics improves incident HF risk prediction over PCP-HF. Scores based on age, sex and metabolomics exhibit similar predictive power to clinically-based models, potentially offering a cost-effective, standardizable, and scalable single-domain alternative.PMID:38623713 | DOI:10.1002/ejhf.3226

The synergism of <em>Lactobacillaceae</em>, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

Tue, 16/04/2024 - 12:00
Food Funct. 2024 Apr 16. doi: 10.1039/d3fo04642g. Online ahead of print.ABSTRACTThis study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides, Blautia, Akkermansia, and Faecalibaculum, and significantly decreased the abundance of Proteus. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote β-oxidation by increasing the levels of SCFAs. Faecalibaculum, Blautia, Bacteroides, and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum, Blautia, Bacteroides, and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.PMID:38623620 | DOI:10.1039/d3fo04642g

A comprehensive dataset for assessing the impact of ammonium salts and zeolite on anaerobic digestion performance, microbial dynamics, and metabolomic profiles

Tue, 16/04/2024 - 12:00
Data Brief. 2024 Mar 26;54:110357. doi: 10.1016/j.dib.2024.110357. eCollection 2024 Jun.ABSTRACTThis article presents comprehensive data derived from lab-scale batch anaerobic digesters that were subjected to inhibition by various sources of ammonia. To counter this inhibition, zeolite was introduced into selected digesters. The provided dataset offers a detailed depiction of degradation performance dynamics over time, as well as insights into both microbial and metabolic changes during the inhibition. In detail, 10 conditions were tested in triplicate. In a first series of 15 bioreactors ammonia was introduced to achieve a TAN concentration of 8 g/L, utilizing NH3 solution, NH4Cl salt, (NH4)2CO3 salt, or (NH4)2PO4 salt as inhibitors. A control condition without ammonia was also set up. A second series of 15 bioreactors was set up exactly as the first one, with the addition of zeolite at a concentration of 15 g/L. The data provided includes information on operational conditions, degradation performance measurements throughout the entire process (using biogas production and composition, dissolved organic and inorganic carbon, volatile fatty acids, pH, free and total ammonia nitrogen, apparent isotopic fractionation of biogas as indicators), microbial community analysis using 16S rRNA gene sequencing (50 samples analysed), and metabolomic analysis through liquid chromatography-mass spectrometry (LC-MS) (108 samples analysed). Sequencing data were generated by using IonTorrent PGM sequencer. The sequencing data have been deposited with links to project PRJEB52324, in ENA database from EBI (https://www.ebi.ac.uk/ena/browser/view/PRJEB52324). Sample accession numbers go from SAMEA14277573 to SAMEA14277621. The metabolomic data were generated using an LTQ Orbitrap XL mass spectrometer (Thermo Fisher Scientific, MA, US). The metabolomic data have been deposited to the EMBL-EBI MetaboLights database with the identifier MTBLS7859 (https://www.ebi.ac.uk/metabolights/MTBLS7859). This data can be used as a source for comparisons with other studies focusing on the inhibition of anaerobic digestion by ammonia, particularly in the context of exploring microbial or metabolomic dynamics during inhibition. Additionally it provides a multi-omic dataset (metataxonomic and metabolomic) with detailed associated metadata describing anaerobic digesters. The dataset is directly is associated to the research article titled "Inhibition of anaerobic digestion by various ammonia sources resulted in subtle differences in metabolite dynamics." [1].PMID:38623544 | PMC:PMC11017268 | DOI:10.1016/j.dib.2024.110357

Optimized combination of Cervus nippon (Sika deer), Angelica (Dangui), and Rehmannia (Suk-jihwang) mitigates LPS-induced inflammation: exploring signaling pathways through plasma metabolomics

Tue, 16/04/2024 - 12:00
Food Sci Biotechnol. 2024 Jan 17;33(7):1671-1683. doi: 10.1007/s10068-023-01476-x. eCollection 2024 Jun.ABSTRACTThis study aimed to determine the optimal combination of three anti-inflammatory materials [i.e., Cervus nippon Temminck (CT), Angelica gigas Nakai (AN), and Rehmannia glutinosa (RG)] for the strongest anti-inflammatory potential. Eighteen combinations of the three materials were tested in LPS-stimulated RAW264.7 cells via assessing nitric oxide (NO). The best combination from in vitro studies was administered to LPS-treated C57BL/6J mice for five days. Subsequently, plasma metabolites were profiled by bioinformatics analyses and validations. As results, 2, 20, and 50 µg/mL of CT, AN, and RG (TM) were the most effective combination suppressing inflammation. In mice, TM mitigated hepatic inflammatory markers. Similarly, the metabolomics indicated that TM may suppress NF-κB signaling pathway, thereby alleviating hepatic inflammation. TM also decreased systemic and hepatic pro-inflammatory cytokines. Collectively, we found the optimal combination of TM for mitigating inflammation; thus further studies on safety, mechanisms, and clinical models are warranted for human applications.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-023-01476-x.PMID:38623429 | PMC:PMC11016027 | DOI:10.1007/s10068-023-01476-x

Drought stress in <em>Lens culinaris</em>: effects, tolerance mechanism, and its smart reprogramming by using modern biotechnological approaches

Tue, 16/04/2024 - 12:00
Physiol Mol Biol Plants. 2024 Feb;30(2):227-247. doi: 10.1007/s12298-024-01417-w. Epub 2024 Feb 27.ABSTRACTAmong legumes, lentil serves as an imperative source of dietary proteins and are considered an important pillar of global food and nutritional security. The crop is majorly cultivated in arid and semi-arid regions and exposed to different abiotic stresses. Drought stress is a polygenic stress that poses a major threat to the crop productivity of lentils. It negatively influenced the seed emergence, water relations traits, photosynthetic machinery, metabolites, seed development, quality, and yield in lentil. Plants develop several complex physiological and molecular protective mechanisms for tolerance against drought stress. These complicated networks are enabled to enhance the cellular potential to survive under extreme water-scarce conditions. As a result, proper drought stress-mitigating novel and modern approaches are required to improve lentil productivity. The currently existing biotechnological techniques such as transcriptomics, genomics, proteomics, metabolomics, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/cas9), and detection of QTLs (quantitative trait loci), proteins, and genes responsible for drought tolerance have gained appreciation among plant breeders for developing climate-resilient lentil varieties. In this review, we critically elaborate the impact of drought on lentil, mechanisms employed by plants to tolerate drought, and the contribution of omics approaches in lentils for dealing with drought, providing deep insights to enhance lentil productivity and improve resistance against abiotic stresses. We hope this updated review will directly help the lentil breeders to develop resistance against drought stress.PMID:38623164 | PMC:PMC11016033 | DOI:10.1007/s12298-024-01417-w

The impact of lipidome on breast cancer: a Mendelian randomization study

Mon, 15/04/2024 - 12:00
Lipids Health Dis. 2024 Apr 15;23(1):109. doi: 10.1186/s12944-024-02103-2.ABSTRACTOBJECTIVE: This study aims to investigate the association between specific lipidomes and the risk of breast cancer (BC) using the Two-Sample Mendelian Randomization (TSMR) approach and Bayesian Model Averaging Mendelian Randomization (BMA-MR) method.METHOD: The study analyzed data from large-scale GWAS datasets of 179 lipidomes to assess the relationship between lipidomes and BC risk across different molecular subtypes. TSMR was employed to explore causal relationships, while the BMA-MR method was carried out to validate the results. The study assessed heterogeneity and horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, and MR-PRESSO. Moreover, a leave-one-out sensitivity analysis was performed to evaluate the impact of individual single nucleotide polymorphisms on the MR study.RESULTS: By examining 179 lipidome traits as exposures and BC as the outcome, the study revealed significant causal effects of glycerophospholipids, sphingolipids, and glycerolipids on BC risk. Specifically, for estrogen receptor-positive BC (ER+ BC), phosphatidylcholine (P < 0.05) and phosphatidylinositol (OR: 0.916-0.966, P < 0.05) within glycerophospholipids play significant roles, along with the importance of glycerolipids (diacylglycerol (OR = 0.923, P < 0.001) and triacylglycerol, OR: 0.894-0.960, P < 0.05)). However, the study did not observe a noteworthy impact of sphingolipids on ER+BC. In the case of estrogen receptor-negative BC (ER- BC), not only glycerophospholipids, sphingolipids (OR = 1.085, P = 0.008), and glycerolipids (OR = 0.909, P = 0.002) exerted an influence, but the protective effect of sterols (OR: 1.034-1.056, P < 0.05) was also discovered. The prominence of glycerolipids was minimal in ER-BC. Phosphatidylethanolamine (OR: 1.091-1.119, P < 0.05) was an important causal effect in ER-BC.CONCLUSIONS: The findings reveal that phosphatidylinositol and triglycerides levels decreased the risk of BC, indicating a potential protective role of these lipid molecules. Moreover, the study elucidates BC's intricate lipid metabolic pathways, highlighting diverse lipidome structural variations that may have varying effects in different molecular subtypes.PMID:38622701 | DOI:10.1186/s12944-024-02103-2

Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods

Mon, 15/04/2024 - 12:00
Zhongguo Zhong Yao Za Zhi. 2024 Mar;49(5):1225-1239. doi: 10.19540/j.cnki.cjcmm.20231113.301.ABSTRACTUltra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P&lt;0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P&lt;0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P&lt;0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P&lt;0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.PMID:38621969 | DOI:10.19540/j.cnki.cjcmm.20231113.301

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