Integrated microbiome and metabolome analysis of milk of lactational mastitis women in remission period
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ABSTRACT:
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase
PROVIDER: MTBLS14200 | MetaboLights | 2026-04-01
REPOSITORIES: MetaboLights
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Project description:Breast cancer treatment has significantly improved, achieving a five-year survival rate of 90%. However, 30% to 50% of survivors continue to suffer from persistent pain, a common long-term side effect. Tramadol, an analgesic often prescribed for postsurgical pain, has recently been shown to have anticancer effects on breast cancer cells. The use of tramadol in postoperative care has been associated with reduced recurrence and improved survival rates, but the mechanisms involved in its anticancer activity are not fully understood. This study explored how tramadol induces paraptosis, a form of nonapoptotic cell death, by focusing on endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) pathways in breast cancer cells. The findings revealed that tramadol treatment increased ROS levels, triggering ER stress and activating the p-eIF2α/ATF4/CHOP signaling axis. This stress response led to cytoplasmic vacuolization and mitochondrial dysfunction, both of which are key features of paraptosis. Inhibiting ROS production or blocking the ATF4 pathway reduced tramadol-induced paraptosis, confirming the critical role of these mechanisms in breast cancer cells. In summary, tramadol induces paraptosis in breast cancer cells by activating ROS and ER stress, offering potential insight into its anticancer effects. These findings could have implications for improving both pain management and cancer treatment outcomes in breast cancer patients.
2025-11-15 | GSE282008 | GEO
Project description:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring.
Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants.
Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings.
Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.
| MSV000095983 | MassIVE
Project description:Despite the use of current antiretroviral therapy (ART) in HIV-1 infected mothers, approximately 5% of new HIV-1 infections still occur in breastfed infants annually. Human Milk (HM) exosomes are highly enriched in maternal microRNAs (miRNAs) and after ingestion and subsequent absorption play an important role in neonatal innate and adaptive immunity. Although, HM exosomes derived from healthy donors are known to inhibit HIV-1 transmission; the effect of HIV-1 on HM exosomal miRNA signatures remains unknown. In the present study, for the first time HM derived exosomal miRNA profiles were determined in HIV-1 infected women.
2020-01-04 | GSE143039 | GEO
Project description:Background: Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. In maternal obesity, miRNAs in bEVs are deregulated, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of obese mothers and their potential impact on breastfed infants. Methods: We recruited healthy nursing mothers who were either obese (BMI≥30) or lean (BMI<25) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior six months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find deregulated miRNAs in bEVs of obese mothers compared to lean mothers. Results: We included 65 nursing mothers: 47 lean and 18 obese mothers based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of general EV markers. Out of 37 EV markers, CD326 was the most highly expressed marker in bEVs. From miRNA analysis using NanoString, we found that the most abundant miRNAs include miR-30b-5p, miR-494-3p, and let-7 families, and the list of top 10 miRNAs was not different between lean and obese mothers. Target genes of the top 10 miRNAs were associated with the EGFR, ErbB, and FoxO signaling pathway. Nineteen miRNAs were deregulated in bEVs of obese mothers (adjusted p < 0.05 cut-off), including miR-575, miR-548g-3p, miR-582-3p, and miR-652-5p. The target genes of these miRNAs are associated with lipid metabolism, inflammatory diseases, and nervous/cardiovascular system development. Conclusion: In this study, we demonstrated altered miRNAs in bEVs of obese mothers and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.
2022-09-09 | GSE212951 | GEO
Project description:Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life, 4 from high frequency and 4 from low frequency mothers. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained transcription profiles by hybridizing cDNA to microarrays. Each profile was generated in duplicate.
2011-03-09 | E-GEOD-20717 | biostudies-arrayexpress
Project description:Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained DNA methylation and H3K9 acetylation profiles by ChIP-on-chip. Each profile was generated in triplicate, each type of profile from 3 high frequency and 3 low frequency mothers.
2011-03-09 | E-GEOD-20714 | biostudies-arrayexpress
Project description:By successfully tracking individual maternal food intake and milk investment, we show that offspring gain more milk from their own mother, particularly when partner mothers are unrelated and when offspring born second experience strong competition from older pups. Unrelated partner mothers are less efficient, requiring more energy than sisters to rear communal broods of equivalent mass. Further, while unrelated partners provide more equal (but not proportional) investment in the brood, individual fitness gains from investment are much greater and more equal between sisters. Our results show that cryptic kin discrimination in maternal investment provides a strong selective advantage for the choice of close relatives as communal rearing partners, reducing costs and potential exploitation of effort when partners were closely matched.
2023-06-27 | PXD019586 | Pride
Project description:Remission has become both the gold standard for clinical care and the end point for clinical trials for children with juvenile idiopathic arthritis (JIA). Using gene expression microarrays, we found that when remission induced by methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX+Et) was compared with healthy controls, there were notable differences in gene expression patterns, demonstrating that remission is not a restoration of immunologic normalcy. Differences were detected in PBMC as well as in granulocytes. Total RNA was extracted from isolated PBMC and granulocytes from patients with polyarticular JIA and from healthy controls. Patients had achieved remission (clinical remission on medicine as defined by Wallace et al, Arthritis Rheum. 2005;52(11):3354-3562) using either MTX or MTX+Et.
2013-10-24 | E-GEOD-41831 | biostudies-arrayexpress
Project description:Trigeminal neuralgia (TN) is a type of neuropathic pain caused by injury to sensory nerves, manifesting as severe paroxysmal pain of the head and face. Trigeminal neuralgia brings a huge burden to patients, without long-term effective treatment. Changes in the expression of pain-related genes in the whole blood samples of patients play an important role in the pathogenesis, diagnosis, and evaluation of treatment effects of trigeminal neuralgia. To better understand the mechanism of trigeminal neuralgia, we collect the whole blood samples from the trigeminal neuralgia patients and the pain-free healthy comparisons. RNA-seq was conducted between the two groups to find the transcriptome changes in patients with trigeminal neuralgia.
2021-10-28 | GSE186505 | GEO
Project description:Background: Human milk extracellular vesicles (EVs) affect various cell types in the gastrointestinal tract, including T cells, and play a role in the development of the newborn’s immune system by delivering specific molecular cargo to target cells. Although maternal allergic sensitization alters the composition of milk, it is unknown whether this impacts the function of milk EVs. Therefore, we analyzed the T cell modulatory capacity and compared the protein and miRNA cargo of EVs from milk of allergic and non-allergic mothers. Methods: EVs were isolated from human milk from allergic and non-allergic donors by differential centrifugation, density gradient floatation and size exclusion chromatography. Functional modulation of primary human CD4+ T cells by EVs was assessed in vitro. Proteomic analysis and small RNA sequencing was performed on milk EVs to evaluate protein and miRNA abundance and to identify cellular targets of this EV cargo in relevant T cell signaling pathways. Results: T cell proliferation, activation and cytokine production were suppressed in the presence of milk EVs. Remarkably, milk EVs from allergic mothers modulated T cell activation to a lesser extent than EVs from non-allergic mothers. Integrative multi-omics analysis identified EV cargo of which the cellular targets could be linked to T cell activation-associated processes. Conclusions: Milk EVs from non-allergic mothers are stronger inhibitors of T cell activation compared to milk EVs from allergic mothers. This altered functionality might be linked to small changes in modulation of certain T cell signaling pathways.
2022-10-30 | GSE216498 | GEO