PubMed

Adv Exp Med Biol. 2024;1465:55-69. doi: 10.1007/978-3-031-66686-5_4.ABSTRACTRecent studies have identified a critical role of the diverse and dynamic microbiome in modulating various aspects of host physiology and intrinsic processes. However, the altered microbiome has also become a hallmark of cancer, which could influence the tumor microenvironment. Aberrations in epigenetic regulation of tumor suppressors, apoptotic genes, and oncogenes can accentuate breast cancer onset and progression. Interestingly, recent studies have established that the microbiota modulates the epigenetic mechanisms at global and gene-specific levels. While the mechanistic basis is unclear, the cross-talk between the microbiome and epigenetics influences breast cancer trajectory. Here, we review different epigenetic mechanisms of mammalian gene expression and summarize the host-associated microbiota distributed across the human body and their influence on cancer and other disease-related genes. Understanding this complex relationship between epigenetics and the microbiome holds promise for new insights into effective therapeutic strategies for breast cancer patients.PMID:39586993 | DOI:10.1007/978-3-031-66686-5_4

Adv Exp Med Biol. 2024;1465:37-53. doi: 10.1007/978-3-031-66686-5_3.ABSTRACTObesity is a risk factor for developing breast cancer, and significantly increases mortality rates in patients diagnosed with this disease. Drivers of this unfortunate relationships are multifactorial, with obesity-induced changes in the epigenetic state of breast cancer cells being identified as a critical mechanism that impact survival, metastasis, and therapeutic responses. Recent studies have investigated the epigenetic landscape of breast cancer to elucidate the molecular interplay between the breast tissue epigenome and its cellular microenvironment. This chapter highlights studies that demonstrates the impact of obesity on the epigenome and metabolome of breast cancer cells. Furthermore, we discuss how obesity impacts the efficacy of chemotherapy and epigenetic targeting drugs, including the emergence of drug-resistance clonal populations. Delineating the relationships between the obesity and epigenetic changes in breast cancer cells will help identify therapeutic strategies which could improve survival outcomes in the rapidly growing number of patients with obesity and cancer.PMID:39586992 | DOI:10.1007/978-3-031-66686-5_3

Mol Biotechnol. 2024 Nov 26. doi: 10.1007/s12033-024-01304-5. Online ahead of print.ABSTRACTSeed samples of two types of chickpea (Cicer arietinum Linn.), including variety A (NRCGR-4452) and variety B (local varieties), with different seed colors, were collected every five days for a total of four times during the seed development period. Non-targeted metabolome and transcriptome sequencing were conducted to identify differentially expressed genes and metabolites associated with chickpea seed coat color. The results indicated that the relative quercetin, pelargonidin, luteolin, rutin, myricetin, kaempferol, glycitin, and naringin contents were higher in variety A than in variety B, and that carbohydrate and amino acid metabolites had a greater impact on flavonoid metabolites. Quercetin, luteolin, and kaempferol were most significantly associated with seed color differences, the associated enzyme genes were LOC101491583 (callose synthase 5-like), LOC101503703 (flavonoid 3',5'-hydroxylase), LOC101514158 (callose synthase 5), LOC101497872 (UDP-glycosyltransferase 74F1-like), LOC101500232 (callose synthase 7 isoform X1), LOC101511206 (UDP-glycosyltransferase 73C3-like), LOC101502065 (galactoside 2-alpha-L-fucosyltransferase), LOC101492791 (sulfoquinovosyl transferase SQD2), and LOC101509377 (flavonol synthase). Additionally, the gene transcription factor MYB44 may regulate UDP-glycosyltransferase 73C3 to affect seed color differences.PMID:39586901 | DOI:10.1007/s12033-024-01304-5

Plant Mol Biol. 2024 Nov 26;114(6):128. doi: 10.1007/s11103-024-01527-9.ABSTRACTEssential plant nutrients encapsulated or combined with nano-dimensional adsorbents define nano fertilizers (NFs). Nanoformulation of non-essential elements enhancing plant growth and stress tolerance also comes under the umbrella of NFs. NFs have an edge over conventional chemical fertilizers, viz., higher plant biomass and yield using much lesser fertilization, thereby reducing environmental pollution. Foliar and root applications of NFs lead to their successful uptake by the plant, depending on the size, surface charge, and other physicochemical properties of NFs. Smaller NFs can pass through channels on the waxy cuticle depending on the hydrophobicity, while larger NFs pass through the stomatal conduits of leaves. Charge-based adsorption, followed by apoplastic movement and endocytosis, translocates NFs through the root, while the size of NFs influences passage into vascular tissues. Recent transcriptomic, proteomic, and metabolomic studies throw light on the molecular mechanisms of growth promotion by NFs. The expression levels of nutrient transporter genes are regulated by NFs, controlling uptake and minimizing excess nutrient toxicity. Accelerated growth by NFs is brought about by their extensive regulation of cell division, photosynthesis, carbohydrate, and nitrogen metabolism, as well as the phytohormone-dependent signaling pathways related to development, stress response, and plant defense. NFs mimic Ca,2+ eliciting second messengers and associated proteins in signaling cascades, reaching transcription factors and finally orchestrating gene expression to enhance growth and stress tolerance. Developing advanced nano fertilizers of the future must involve exploring molecular interactions with plants to reduce toxicity and improve effectiveness.PMID:39586900 | DOI:10.1007/s11103-024-01527-9

J Ethnopharmacol. 2024 Nov 23:119148. doi: 10.1016/j.jep.2024.119148. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa kwangtungensis Chun (CK) is a traditional herb for the treatment of blood stasis, hemostasis, anti-inflammation, and antidepressant. Previous studies showed that CK extract has significant anti-neuroinflammatory activity. However, the mechanism by which it treats AD is still unclear.AIM OF STUDY: This study aimed to investigate the effects and mechanisms of CK in ameliorating AD pathology using in vivo and in vitro models, supported by a multi-omics analysis approach.MATERIALS AND METHODS: The chemical composition of CK was characterized using UPLC-QE Plus-MS/MS. The effects and mechanisms of CK on AD pathology were then investigated using APP/PS1 mice and BV2 and HT22 cell models, with comprehensive insights provided by network pharmacology, transcriptomics, and metabolomics analyses.RESULTS: This study is the first to report the identification of 146 compounds from CK. CK administration led to significant improvements in cognitive function, reduced amyloid-beta and neurofibrillary tangle formation, and inhibited the activation of microglia and astrocytes in APP/PS1 mice. Comprehensive analyses suggest that CK may modulate the TCA cycle through the PI3K-AKT signaling pathways and inflammation-related MAPK and NF-κB signaling pathways. In vitro studies revealed that CK significantly inhibited LPS-induced inflammation and oxidative stress in BV2 cells, as well as reduced oxidative stress and neuronal apoptosis in HT22 cells.CONCLUSION: These findings underscore the potential of CK as a therapeutic agent in alleviating AD pathology. This study offers new insights into CK's mechanisms, suggesting that its therapeutic effects may be achieved through the coordinated reduction of neuroinflammation, oxidative stress, and neuronal apoptosis across multiple pathways, collectively working to counteract AD pathology.PMID:39586557 | DOI:10.1016/j.jep.2024.119148

Talanta. 2024 Nov 22;284:127273. doi: 10.1016/j.talanta.2024.127273. Online ahead of print.ABSTRACTMetabolomics using mass spectrometry-only (MS) analysis either by continuous or intermittent direct infusion (DIMS) and ambient ionization techniques (AMS) has grown in popularity due to their rapid, high-throughput nature and the advantage of performing fast analysis with minimal or no sample pretreatments. But currently, end-users without programming knowledge do not find applications with Graphical User Interface (GUI) specialized in processing DIMS or AMS data. Specifically, there is a lack of standardized workflow for processing data from limited sample sizes and scans from different total ion chronograms (TIC).To address this gap, we present rIDIMS, a browser-based application that offers a straightforward and fast workflow focusing on high-quality scan selection, grouping of isotopologues and adducts, data alignment, binning, and filtering. We also introduce a novel function for selecting TIC scans that is reproducible and statistically reliable, which is a feature particularly useful for studies with limited sample sizes. After processing in rIDIMS, the result is exported in an HTML report document that presents publication-quality figures, statistical data and tables, ready to be customized and exported. We demonstrate rIDIMS functionality in three cases: (i) Classification of coffee bean species through the chemical profile obtained with Mass Spec Pen; (ii) Public repository DIMS data from lipid profiling in monogenic insulin resistance syndromes, and (iii) Lipids for lung cancer classification. We show that our implementation facilitates the processing of AMS and DIMS data through an easy and intuitive interface, contributing to reproducible and reliable metabolomic investigations. Indeed, rIDIMS function asa user-friendly GUI based Shiny web application for intuitive use by end-users (available at https://github.com/BioinovarLab/rIDIMS).PMID:39586215 | DOI:10.1016/j.talanta.2024.127273

J Pharm Biomed Anal. 2024 Nov 19;254:116572. doi: 10.1016/j.jpba.2024.116572. Online ahead of print.ABSTRACTThe prevalence of major depressive disorder (MDD) is higher in females than males, emphasizing the need to identify gender-specific biomarkers to improve diagnosis accuracy. In this study, a cross-sectional investigation with 258 samples was conducted to evaluate the discriminative power of potential gender-specific biomarkers for MDD. Eighteen MDD-related differential metabolites have been identified, involving pathways of phospholipids, glycerolipids, fatty acids, sphingolipids, cholesterol, vitamin E, and heme. A potential biomarker combination consisting of palmitelaidic acid, gamma carboxyethyl hydroxychroman (gamma-CEHC), and lysoPE(16:0) was confirmed for predicting depression in women using binary logistic regression analysis. To evaluate the panel's specificity, nine generalized anxiety disorder (GAD) samples, which share highly similar clinical symptoms with MDD, were included in the validation set. The discovery and validation sets yielded an area under the receiver operating characteristic curve of 0.86 and 0.83, respectively. All nine female GAD samples were correctly predicted as non-MDD, demonstrating the panel's specificity in diagnosing female MDD. Remarkably, this composite panel achieved a 75 % prediction accuracy in female samples in both the discovery and validation sets, but it did not reach 60 % prediction accuracy in male samples in either set. Our findings highlight the importance of gender-specific molecular diagnostics in developing practical and accurate diagnostic methods for MDD.PMID:39586142 | DOI:10.1016/j.jpba.2024.116572

Atherosclerosis. 2024 Nov 16;400:119054. doi: 10.1016/j.atherosclerosis.2024.119054. Online ahead of print.ABSTRACTGlobal incidence of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is on the rise while treatments remain elusive. MASLD is a disease of dysregulated systemic and hepatic metabolism. Current understanding of disease pathophysiology as it relates to metabolome changes largely comes from studies on animal models and human plasma. However, human tissue data are crucial for transitioning from mechanisms to clinical therapies. The close relationship between MASLD and comorbidities like obesity, type 2 diabetes and dyslipidemia make it difficult to determine the contribution from liver disease itself. Here, we review recent metabolomics studies in liver tissue from human MASLD patients, which have predominately focused on lipid metabolism, but also include bile acid, tricarboxylic acid (TCA) cycle, and branched chain amino acid (BCAA) metabolism. Several clinical trials are underway to target various of these lipid-related pathways in MASLD. Although only the β-selective thyroid hormone receptor agonist resmetirom has so far been approved for use, many metabolism-targeting pharmaceuticals show promising results for halting disease progression, if not promoting outright reversal. Ultimately, the scarcity of human tissue data and the variability of confounding factors, like obesity, within and between cohorts are impediments to the pathophysiological understanding required for efficient development of metabolic treatments.PMID:39586140 | DOI:10.1016/j.atherosclerosis.2024.119054

Phytomedicine. 2024 Nov 10;136:156247. doi: 10.1016/j.phymed.2024.156247. Online ahead of print.ABSTRACTBACKGROUND: The KITENIN/ErbB4 complex has been reported to participate in metastasis, which is the principal reason of death in most colorectal cancer patients.PURPOSE: New therapeutics need to be developed to suppress the malignant effects of the KITENIN/ErbB4 complex, which is related to drug resistance. The present study aimed to evaluate changes in cancer cell invasion capacity, transcriptional regulators, and cellular bioenergetics after targeting the KITENIN/ErbB4 complex with emodin. Moreover, we aimed to reveal the mechanistic effects of emodin and observe the dual blockade effects of ErbB4-targeted therapy with KH-type splicing regulatory protein (KSRP) and search for new alternative blockade pathways.METHODS: Using in vitro, in vivo, molecular-docking, and metabolomics studies, we evaluated the anticancer effect of emodin alone or in combination with DKCC14S.RESULTS: Emodin treatment decreased KITENIN and ErbB4 protein levels. The dysfunctional KITENIN/ErbB4 complex suppressed KITENIN-mediated cell invasion and downregulated AP-1 activity, aerobic glycolysis, and the levels of transcriptional regulators associated with cell metabolism. We conclude that emodin targets the KITENIN/ErbB4 complex and offering a novel mechanism by which it disrupts KITENIN-mediated signaling. Furthermore, we were demonstrated that the dual blocking effect of emodin and DKC-C14S on the KITENIN complex showed synergistic effects in suppressing colorectal cancer progression under in cell-based and animal assay.CONCLUSION: The results suggest that co-treatment with ErbB4 and KSRP-binding compounds could constitute a potential strategy for controlling colorectal cancer progression by disrupting the KITENIN complex.PMID:39586126 | DOI:10.1016/j.phymed.2024.156247

Hum Reprod. 2024 Nov 25:deae248. doi: 10.1093/humrep/deae248. Online ahead of print.ABSTRACTSTUDY QUESTION: What is the composition of currently available commercial human embryo culture media provided by seven suppliers, for each stage of human preimplantation embryo development?SUMMARY ANSWER: While common trends existed across brands, distinct differences in composition underlined the absence of a clear standard for human embryo culture medium formulation.WHAT IS KNOWN ALREADY: The reluctance of manufacturers to fully disclose the composition of their human embryo culture media generates uncertainty regarding the culture conditions that are used for human preimplantation embryo culture. The critical role of the embryo culture environment is well-recognized, with proven effects on IVF success rates and child outcomes, such as birth weight. The lack of comprehensive composition details restricts research efforts crucial for enhancing our understanding of its impacts on these outcomes. The ongoing demand for greater transparency remains unmet, highlighting a significant barrier in embryo culture medium optimization.STUDY DESIGN, SIZE, DURATION: For this study, 47 different human embryo culture media and protein supplements were purchased between December 2019 and June 2020; they comprise complete media (n = 23), unsupplemented media (n = 14), and supplements (n = 10). Unsupplemented media were supplemented with each available supplement from the same brand (n = 33 combinations). All samples were directly frozen in liquid nitrogen and stored at -80°C until composition analysis.PARTICIPANTS/MATERIALS, SETTING, METHODS: We determined the concentrations of 40 components in all samples collected (n = 80). Seven electrolytes (calcium, chloride, iron, magnesium, phosphate, potassium, sodium), glucose, immunoglobulins A, G, and M (IgA, IgG, IgM), uric acid, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), and albumin, as well as the total protein concentration, were determined in each sample using a Cobas 8000 Analyser (Roche Diagnostics). Analysis of pyruvate, lactate, carnitine, and 21 amino acids was achieved with Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS).MAIN RESULTS AND THE ROLE OF CHANCE: Our analysis showed that generally, the concentrations of components of ready-to-use human embryo culture media align with established assumptions about the changing needs of an embryo during early development. For instance, glucose concentrations displayed a high-low-high pattern in sequential media systems from all brands: 2.5-3 mM in most fertilization media, 0.5 mM or below in all cleavage stage media, and 2.5-3.3 mM in most blastocyst stage media. Continuous media generally resembled glucose concentrations of cleavage stage media. However, for other components, such as lactate, glycine, and potassium, we observed clear differences in medium composition across different brands. No two embryo culture media compositions were the same. Remarkably, even embryo culture media from brands that belong to the same parent company differed in composition. Additionally, the scientific backing for the specific concentrations used and the differences in the composition of sequential media is quite limited and often based on minimal in vivo studies of limited sample size or studies using animal models.LARGE SCALE DATA: N/A.LIMITATIONS, REASONS FOR CAUTION: We used a targeted approach and performed a selection of tests which limit the composition analysis to this set of analytes.WIDER IMPLICATIONS OF THE FINDINGS: Comprehensive disclosure and complete transparency concerning the composition of human embryo culture media, including the exact concentration of each component, are crucial for evidence-based improvements of culture media for human preimplantation embryos.STUDY FUNDING/COMPETING INTEREST(S): This research was supported by ZonMw (https://www.zonmw.nl/en), Programme Translational Research 2 (project number 446002003). M.G. declares an unrestricted research grant from Ferring not related to the presented work, paid to the institution VU Medical Center. The remaining authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBER: N/A.PMID:39585967 | DOI:10.1093/humrep/deae248

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):51. doi: 10.1167/iovs.65.13.51.ABSTRACTPURPOSE: Myopia development is closely associated with scleral tissue loss in both human and animal models. This research aimed to investigate the metabolic changes in the sclera of lens-induced myopic guinea pigs and explore the underlying mechanisms.METHODS: Myopia was induced in 2-week-old pigmented guinea pigs by having them wear -20-diopter lenses for 10 days, with one eye designated as the lens-induced myopic eye and the other as the control. Dual-platform untargeted metabolomics was performed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolic changes in the sclera. Validation of amino acid levels in the sclera was conducted via targeted metabolomics. Glycine intervention was carried out in both scleral fibroblasts and the lens-induced myopia guinea pig model to evaluate its effects on COL1A1 synthesis and myopia progression.RESULTS: After 10 days of lens-induced myopia, GC-MS and LC-MS analyses identified significant changes in 29 and 85 metabolites in the myopic sclera, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the downregulation of amino acid and pyrimidine metabolism pathways was crucial in myopia development. Targeted amino acid metabolomics confirmed that multiple amino acids were significantly reduced in the myopic sclera. Glycine deficiency reduced COL1A1 levels in scleral fibroblasts, and glycine supplementation significantly increased its content. Animal studies demonstrated that glycine gavage significantly inhibited axial elongation and refractive error increase in lens-induced myopic guinea pigs, increased COL1A1 content, and reversed the reduction of ferroptosis-related proteins GPX4 and FTH1.CONCLUSIONS: Several amino acids, including glycine, l-isoleucine, l-serine, and l-valine, were significantly reduced in the myopic sclera, along with a marked downregulation of amino acid and pyrimidine metabolism pathways. Glycine supplementation can increase COL1A1 content and inhibit myopia progression by reducing ferroptosis within the sclera, suggesting that glycine could serve as a potential therapeutic intervention for myopia.PMID:39585677 | DOI:10.1167/iovs.65.13.51

Curr Microbiol. 2024 Nov 25;82(1):9. doi: 10.1007/s00284-024-03982-5.ABSTRACTThe emergence of pathogenic bacteria resistant to conventional antibiotics is becoming increasingly challenging. Plant-derived flavonoids are potential alternatives to antibiotics, owing to their antimicrobial properties. However, the molecular mechanisms through which they inhibit the growth of pathogenic microorganisms remain unclear. Therefore, Klebsiella pneumoniae ATCC700603 was separately incubated in two flavonoids to elucidate their inhibitory mechanism. Metabolomic and transcriptomic analyses were performed after 4-h incubation. In total, 5483 genes and 882 metabolites were identified. Compared to the untreated control, rutin and luteolin activated 507 and 374 differentially expressed genes (DEGs), respectively. However, the number of differential abundant metabolites (DAMs) remained the same. The top 10 correlated DEGs and DAMs were identified within each comparative group after a correlation analysis. Rutin induced the accumulation of unique metabolites and suppressed gene expression whereas luteolin did not. Our results explain the disparate effects of these two flavonoids and demonstrate the inhibitory mechanism of rutin on strain growth.PMID:39585437 | DOI:10.1007/s00284-024-03982-5

J Infect Dis. 2024 Nov 25:jiae529. doi: 10.1093/infdis/jiae529. Online ahead of print.ABSTRACTBACKGROUND: Acquired immunity to Plasmodium falciparum malaria is mainly mediated by immunoglobulin G (IgG) targeting erythrocyte membrane protein 1 (PfEMP1). These adhesins mediate infected erythrocyte (IE) sequestration, protecting IEs from splenic destruction. PfEMP1-specific IgG is therefore thought to protect mainly by inhibiting IE sequestration. VAR2CSA-type PfEMP1 mediates placental IE sequestration, putting pregnant women exposed to P falciparum parasites at risk of placental malaria (PM).METHODS: Levels and Fc-afucosylation of VAR2CSA-specific plasma IgG were measured by a modified enzyme-linked immunosorbent assay (FEASI). We also measured the ability of the IgG to inhibit IE adhesion and to induce natural killer (NK) cell degranulation. The results were related to parity and clinical pregnancy outcomes.RESULTS: Parity was positively correlated with levels and Fc-afucosylation of VAR2CSA-specific IgG, and with birth weight and plasma IgG inhibition of IE adhesion in vitro. Fc-afucosylation of VAR2CSA-specific IgG increased NK-cell degranulation. Women with Fc-afucosylated VAR2CSA-specific IgG had a reduced risk of delivering a low birth weight (LBW) baby, but not of PM or anemia.CONCLUSIONS: Fc-afucosylated VAR2CSA-specific IgG effectively induced NK-cell degranulation and was associated with protection against LBW, independent of IgG levels. Our study has implications for the development of VAR2CSA-based subunit vaccines, which exclusively induce Fc-fucosylated IgG.PMID:39585195 | DOI:10.1093/infdis/jiae529

Oncoimmunology. 2024 Dec 31;13(1):2421028. doi: 10.1080/2162402X.2024.2421028. Epub 2024 Oct 26.ABSTRACTA recent in vitro study showed that pharmacological inhibition of the nuclear export receptor XPO1 suppresses oxaliplatin-induced nuclear release of HMGB1 and HMGB2, as well as the translocation of CALR to the plasma membrane. Moreover, cell-targeted-HMGB2 protein potently induced CALR exposure, even in the absence of oxaliplatin.PMID:39585160 | DOI:10.1080/2162402X.2024.2421028

Oncoimmunology. 2024 Dec 31;13(1):2425465. doi: 10.1080/2162402X.2024.2425465. Epub 2024 Nov 4.ABSTRACTApoptosis, necroptosis and pro-inflammatory NF-κB-dependent signaling are repressed by receptor-interacting serine/threonine-protein kinase 1 (RIPK1). A recent paper in Immunity describes a small molecule inducing the proteolytic degradation of RIPK1. In preclinical experiments, this RIPK1 inhibitor improved the anticancer efficacy of radiotherapy, immunotherapy (with PD-1 blockade) and radioimmunotherapy (with CTLA-4 blockade).PMID:39585102 | DOI:10.1080/2162402X.2024.2425465

mBio. 2024 Nov 25:e0167924. doi: 10.1128/mbio.01679-24. Online ahead of print.ABSTRACTTamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug. Here, using gnotobiotic- and antibiotics-treated mice, we show that tamoxifen pharmacokinetics are heavily influenced by gut bacteria and prolonged exposure to tamoxifen. Interestingly, 16S rRNA gene sequencing shows tamoxifen does not affect overall microbiota composition and abundance. Metabolomics, however, reveals differential metabolic profiles across the microbiomes of different donors cultured with tamoxifen, suggesting an enzymatic diversity within the gut microbiome that influences response to tamoxifen. Consistent with this notion, we found that β-glucuronidase (GUS) enzymes vary in their hydrolysis activity of glucuronidated tamoxifen metabolites across the gut microbiomes of people. Together, these findings highlight the importance of the gut microbiome in tamoxifen's pharmacokinetics.IMPORTANCEOne in eight women will develop breast cancer in their lifetime, and tamoxifen is used to suppress breast cancer recurrence, but nearly 50% of patients are not effectively treated with this drug. Given that tamoxifen is orally administered and, thus, reaches the intestine, this variable patient response to the drug is likely related to the gut microbiota composed of trillions of bacteria, which are remarkably different among individuals. This study aims to understand the impact of the gut microbiome on tamoxifen absorption, metabolism, and recycling. The significance of our research is in defining the role that gut microbes play in tamoxifen pharmacokinetics, thus paving the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.PMID:39584836 | DOI:10.1128/mbio.01679-24

J Vis Exp. 2024 Nov 8;(213). doi: 10.3791/66849.ABSTRACTOne challenge in studies using tissue collected from multiple cohorts is avoiding batch effects when preparing for large-scale multi-omic experiments, such as combined single-cell RNA sequencing and metabolomics. The method in the current study utilizes flash-frozen pancreatic islets from fetal non-human primates collected over a span of two years for input into single-nucleus RNA sequencing and ATAC sequencing assays. The cytosolic fraction generated during nuclear extraction was retained for downstream capillary electrophoresis-mass spectrometry and subsequent metabolite quantification. This method allows for bulk analysis of metabolites that contribute to the changing transcriptomic and epigenomic landscapes within experimental conditions. It is applicable to many tissue types and maximizes the amount of information that can be extracted from samples that are not readily available. As the contribution of metabolism to the establishment of cellular identity via epigenetic modifications becomes more appreciated, techniques that allow for identifying the contribution of metabolites in specific cell types are timely and necessary.PMID:39584693 | DOI:10.3791/66849

J Vis Exp. 2024 Nov 8;(213). doi: 10.3791/67175.ABSTRACTClimate change increases drought risk to agriculture and impacts both food nutrient content and overall food security. Metabolomics is one way to observe and quantify the impacts of drought on grain and other agricultural products. The identified metabolites may allow for the identification of the biochemical response that allows the plant to tolerate stressful environments. The methodology presented herein allowed for the total metabolomic analysis of barley flour using gas chromatography/mass spectrometry (GC/MS). Barley flour metabolite extracts were fractionated into four fractions based on polarity. To allow for analysis by GC/MS, metabolites were derivatized to increase volatility and metabolite separation: fatty acids esters were derivatized into fatty acid methyl esters; sugars were oximated into their straight chain form; and metabolites with hydroxyl groups were converted to their corresponding silyl ethers. The derivatized samples were injected into the GC/MS and the generated mass spectra were used for metabolite identification by comparing the generated spectra to the National Institute of Standards and Technology (NIST) Tandem Mass Spectra library. The method described here can also be used to examine the total metabolome for other plants, furthering our understanding of the biochemical responses of stressed plants.PMID:39584676 | DOI:10.3791/67175

Infect Drug Resist. 2024 Nov 20;17:5097-5110. doi: 10.2147/IDR.S490547. eCollection 2024.ABSTRACTBACKGROUND: Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases.METHODS: A total of 25 children were included in the study, comprising 15 pneumonia patients and 10 healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids.RESULTS: The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0).DISCUSSION: Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.PMID:39584178 | PMC:PMC11585984 | DOI:10.2147/IDR.S490547

MedComm (2020). 2024 Nov 24;5(12):e70018. doi: 10.1002/mco2.70018. eCollection 2024 Dec.ABSTRACTLung cancer (LC) continues to pose the highest mortality and exhibits a common prevalence among all types of cancer. The genetic interaction between human eukaryotes and microbial cells plays a vital role in orchestrating every physiological activity of the host. The dynamic crosstalk between gut and lung microbiomes and the gut-lung axis communication network has been widely accepted as promising factors influencing LC progression. The advent of the 16s rDNA sequencing technique has opened new horizons for elucidating the lung microbiome and its potential pathophysiological role in LC and other infectious lung diseases using a molecular approach. Numerous studies have reported the direct involvement of the host microbiome in lung tumorigenesis processes and their impact on current treatment strategies such as radiotherapy, chemotherapy, or immunotherapy. The genetic and metabolomic cross-interaction, microbiome-dependent host immune modulation, and the close association between microbiota composition and treatment outcomes strongly suggest that designing microbiome-based treatment strategies and investigating new molecules targeting the common holobiome could offer potential alternatives to develop effective therapeutic principles for LC treatment. This review aims to highlight the interaction between the host and microbiome in LC progression and the possibility of manipulating altered microbiome ecology as therapeutic targets.PMID:39584048 | PMC:PMC11586092 | DOI:10.1002/mco2.70018