Preoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis
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PROVIDER: PRJNA1226112 | ENA |
REPOSITORIES: ENA
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Project description:We have employed single-cell RNA sequencing using the 10x Genomics platform to investigate the immune cell distribution in the liver of Sedentary (Sed) and preoperative exercise (PEx) mice following surgical stress-promoted colorectal cancer liver metastasis model. The liver immune microenvironment plays a critical role in tumor progression and response to PEx. This study provides a comprehensive immune landscape at single-cell resolution, offering novel insights into how PEx modulates hepatic immune cell populations to mitigate surgical stress-induced tumor progression.
2025-02-27 | GSE290055 | GEO
Project description:Preoperative exercise therapy triggers anti-inflammatory trained immunity of Kupffer cells through metabolic reprogramming
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Project description:Single-cell transcriptomics revealed that transcriptomic profile is shifted towards anti-inflammatory in Kupffer cells after pre-operative exercise therapy in mice.
2021-04-28 | GSE173429 | GEO
Project description:Extracellular vesicles (EVs) transport biomolecules that mediate intercellular communication. We previously showed that EVs contain DNA (EV-DNA) representing the entire genome. However, the mechanism of EV-DNA packaging and its role in cancer remains elusive. Here, we demonstrate that the majority of DNA is localized on the vesicle surface and associated with uniquely modified and cleaved histones. We conducted a genome-wide CRISPR knockout screen, which revealed that immune developmental pathways and genes, including APAF1 and NCF1, regulated EV-DNA packaging. We further demonstrated in colorectal cancer models that uptake of EVs and EV-DNA by Kupffer cells (KC) activated DNA damage responses. This activation re-wired KC cytokine production and generated tertiary lymphoid structures in pre-metastatic livers, thereby suppressing metastasis. Conversely, loss of APAF1 decreased EV-DNA packaging and promoted liver metastasis. Quantifying EV-DNA in colorectal cancer biopsies revealed that EV-DNA could possibly serve as a predictive biomarker for metastatic risk.
2024-09-23 | PXD056104 | Pride
Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.
2023-09-09 | GSE242736 | GEO
Project description:RNAseq of Kupffer cells treated with IL2 and purifed Kupffer cells sub-populations (Kupffer Cell 1 and Kupffer Cell 2)
| PRJNA638642 | ENA
Project description:Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity. Expression profiling of livers from mice fed control, low-fat diet diet or high-fat diet for 20weeks with or without knockdown of Kupffer cells.
2011-10-17 | E-GEOD-33044 | biostudies-arrayexpress
Project description:To reveal the transcriptomes associated with M1 or M2-polarized Kupffer cells, the primary Kupffer cells isolated from mouse liver were treated with lipopolysaccharides or IL-4 and the gene expression patterns were analyzed by microarray. To study the role of RORα in Kupffer cell polarization, Kupffer cells were treated with RORα ligands and transcriptions were compared with those of the M1/M2 polarized Kupffer cells.
2016-09-03 | GSE86397 | GEO
Project description:LPC-promoted Th1 differentiation
| PRJNA702059 | ENA
Project description:Permanent synthetic meshes are a prized option to promote soft-tissue support and repair in several surgical procedures. Contrariwise, the risk to develop biomaterial-associated infection (BAI) has not been solved. Intrinsically antibacterial materials, such as those that include metals with antimicrobial activity as part of their composition, are an advanced approach to be further explored for BAI prevention. In this study, a panel of in vitro, ex vivo and in vivo assays was used to compare a novel polypropylene-based surgical mesh modified with silver-containing microparticles with a commercially available similar device normally used for hernia repair. To comprehensively identify specific mechanisms of how the new silver-containing meshes influence the full host-tissue response in the presence and absence of infection, prostheses were screened for cytotoxicity, biological integration and transcriptomic responses, and additional antibiofilm production behaviour. Silver-modified polypropylene meshes exhibited good properties in terms of mechanical and cytotoxic values, as well as a modest prevention of biofilm formation. Moreover, they promoted connective tissue deposition and angiogenesis and, outstandingly, induced “immunomodulating” effects that may be potentially useful in the clinical context. Overall, the results substantiate the potential use of polypropylene surgical meshes modified with silver-containing microparticles as a means to prevent BAI in soft tissue repair.
2016-10-03 | GSE85139 | GEO