Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1308318 | ENA |
REPOSITORIES: ENA
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Project description:The molecular basis underlying the known anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. We investigated the microRNA (miRNA)-modulatory effects of cranberry proanthocyanidin (PAC) and two of its main gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), in intestinal cells at homeostasis and in inflammatory conditions. Differentiated Caco-2BBe1 cells were pre-treated with PAC, DHPAA, or HPPA then stimulated with IL-1ß or not. Total RNA was used to profile the expression of 799 miRNAs. PAC, DHPAA, and HPPA generated subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not by PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, pre-treatment with PAC and DHPAA, but not HPPA, reversed the expression of 16 and two IL-1ß-induced miRNAs, targeting genes enriched in inflammatory and cancer pathways. These data suggest that in the absence of inflammation, PAC may be reliant on its transformation by the gut microbiota for its miRNA-modulatory effects, while in an inflammatory environment, both PAC and DHPAA counter inflammatory miRNA responses. This work provides a novel mechanism to characterize the bioactivity of cranberry and will inform cranberry utilization in nutritional strategies for the maintenance of intestinal homeostasis.
2024-03-27 | GSE237078 | GEO
Project description:The proton-activated chloride (PAC) channel (also known as acid-sensitive outwardly rectifying anion channel, ASOR) plays a critical role in acid-induced cell death and endocytosis. However, little is known about the regulatory factors and binding partners of PAC. In this study, we discovered that transfer RNA (tRNA) interacts directly with PAC as an unexpected binding partner. Using cryo-electron microscopy, we determined that two PAC trimers and one co-purified tRNA molecule form a stable complex via a highly conserved KR motif, representing the closed conformation. tRNA is located on the intracellular side of PAC, blocking the channel pores. Furthermore, electrophysiological data showed that tRNA modulates chloride currents and channel open probability of PAC, thus protecting against acid-induced cell death. Our study provides insight into the regulation of PAC activity by cytosolic tRNA and extends the role of tRNAs in pathological and physiological events.
2024-06-28 | GSE216637 | GEO
Project description:Effect of GA on PAC and PAO1 treated Arabidopsis seeds. Seeds were treated during 20h with paclobutrazol (PAC) or with lyophilized extracts of Pseudomonas aeruginosa liquid culture medium (PAO1). Experiments were also performed with exogenous application of gibberellic acid.
2018-06-05 | GSE115272 | GEO
Project description:S2 cells transfected with pAc-Clk or empty vector Experiment Overall Design: S2 cells transfected with pAc-Clk or empty vector. Cells were transfected and RNA collected after 48hs
2008-06-15 | E-GEOD-7653 | biostudies-arrayexpress
Project description:Bone marrow-derived mast cells were differentiated over 4-6 weeks using bone marrow from Pac-1+/+ and Pac1-/- littermate mice. Cell purity was 99% c-kit and Fc epsilon receptor positive as assessed by flow cytometry. Cells were stimulated by Fc epsilon receptor crosslinking using IgE-DNP/HSA for sensitization for 18 hours and DNP-HSA antigen for crosslinking for 2 hours. Gene transcript abundance was determined and scaled to 150 using alogorithms in MicroArray Analysis Suite Software 5.0 (Affymetrix). Keywords: Cpmparison of Pac-1+/+ and Pac-1-/- activated BMMCs
2006-01-10 | GSE3994 | GEO
Project description:The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague Dawley rats, with or without reflux-induction received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis, and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory and immune-implicated proteins and genes including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1β, Lbp, Lcn2, Myd88, Nfkb1, Tlr2 and Tlr4 aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation and cellular damage.
2024-02-08 | GSE254633 | GEO
Project description:We introduce poly-adenine CRISPR gRNA-based single cell RNA-sequencing (pAC-Seq), a method enabling simultaneous observation of mutagenic guide RNAs (gRNAs) and their transcriptional consequences in single cell RNA sequencing (scRNA-seq) data. We have made gRNAs robustly visible in scRNA-seq data while maintaining full activity by modifying them with a hardcoded poly-adenine tract. We apply pAC-Seq to study the transcriptomic effects of non-coding CRISPR/Cas9-induced mutations in a pooled screening format. pAC-Seq is a simple, robust, and broadly applicable method of measuring the global effects of genomic mutation.
2021-02-24 | GSE117053 | GEO
Project description:Right ventricular (RV) failure plays a critical role in any type of heart failure. However, there is no specific therapy developed for RV failure. To understand RV failure, we focused on the RV specific genes. Global gene expression analysis showed that alternative complement pathway-related genes including C3 and Cfd were significantly upregulated in right ventricle in murine heart. We generated the RV failure by right ventricle-specific pressure overload model mice, pulmonary artery constriction (PAC), which induces RV failure around 14 days. In C3 knockout (C3KO) mice, PAC-induced RV dysfunction and fibrosis were significantly attenuated. C3a is produced from C3 by C3 convertase complex including Cfd. Cfd knockout mice also attenuated PAC-induced RV failure. Moreover, C3a receptor (C3aR) antagonist dramatically improved PAC-induced RV dysfunction in wild type mice. Here we revealed the crucial role of C3-Cfd-C3a-C3aR axis in RV failure and highlight the potential therapeutic target for RV failure with no pharmacologic option.
2021-09-07 | GSE183504 | GEO
Project description:Genomic DNA from sporadic breast tumours was isolated and analysed using array CGH. The NKI 1MB BAC/PAC micro array was used to identify chromosomal aberrations of all tumours. Keywords: sporadic breast tumour, CGH
2010-07-05 | GSE9114 | GEO
Project description:S2 cells transfected with pAc-Clk or empty vector Keywords: S2 cells Clk
2007-07-09 | GSE7653 | GEO