Systemic epigenetic alterations are associated with gastric emptying disturbances in Non-Ulcer Dyspepsia
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ABSTRACT:
PROVIDER: PRJNA578687 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10318200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10318200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10318201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10318201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10318202_1.fastq.gz | Fastqsanger.gz |
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Project description:Background. The mechanisms by which environmental risk factors (eg, stress) predispose to symptoms and gastric emptying (GE) disturbances in non-ulcer dyspepsia (NUD) is unknown. Our aims were to compare the circulating leukocytes’ epigenome between NUD patients with normal versus delayed and normal versus rapid GE. Methods. In 24 NUD patients, we evaluated gastrointestinal symptoms, GE (scintigraphy) and 3 promoter/enhancer-associated histone modifications (H3K4me3, H3K9ac, and H3K27ac) by chromatin immunoprecipitation-sequencing in buffy coats, then compared the genome-wide binding of histone marks between patients with normal versus delayed and normal versus rapid GE. Key results. GE was normal (9 patients), delayed (6 patients), or rapid (9 patients). Compared to normal GE, there was differential binding of H3K4me3, which marks active promoters, at 100 genes in delayed and 233 genes in rapid GE (FDR < 0.05). Delayed GE was associated with increased H3K4me3 binding at several genes that regulate T cell functions (eg, CD247, IL2RA, CD69, CD96, ICOS, ITK, and GRAP2); conversely, binding was reduced at genes that regulate neuronal synapses (ie, SYT6, SYT12, CDH2, CDH11, EFNB3, CAMK2B, and SHISA6) and neuronal nitric oxide synthase (NOS1). In rapid GE, genes related to opioid signaling (OPRD1, MAPK4, CAMK2B, and PDE1C), neuronal development, and synaptic functions bound less H3K4me3. No or few genes were differentially enriched with H3K9ac and H3K27ac. Conclusions. H3K4me3 discriminates among patients with normal, rapid, and delayed GE. Delayed GE is associated with alterations that suggest increased T-cell functions. Rapid GE is associated with changes suggesting reduced opioid signaling.
2021-12-26 | GSE139166 | GEO
Project description:Epigenetic alterations are associated with gastric emptying disturbances in Diabetes Mellitus
| PRJNA596193 | ENA
Project description:Introduction. Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aims were to ascertain if epigenetic alterations in whole blood discriminate among DM patients with normal, delayed and rapid gastric emptying (GE). Methods. Using ChIP-seq (Chromatin immunoprecipitation combined with next generation sequencing) assays, we compared the genome-wide enrichment of three histone modifications (ie, H3K4me3, H3K9ac and H3K27ac) in buffy coats from 20 DM patients with normal (n=6), delayed (n=8), or rapid (n=6) GE. Results. Between DM patients with delayed versus normal GE, there were 108 and 54 genes that were differentially-bound (FDR < 0.05) with H3K27ac and H3K9ac; 100 genes were differentially bound with H3K9ac in patients with rapid versus normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (eg, CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1, PDE4A, CMKLR1). For H3K9ac, the differentially occupied genes were related to T cell development and function (eg, ICOS and CCR3) and innate immunity (RELB, CD300LB, CLEC2D). Compared to normal, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (eg, TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism. The motif analysis disclosed enrichment of binding sites for several transcription factors relevant to the pathogenesis and complications of DM. Conclusions. GE disturbances in DM are associated with epigenetic alterations that may serve as biomarkers and provide clues to the pathogenesis
2021-12-26 | GSE142178 | GEO
Project description:IntroductionEpigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aim was to ascertain whether epigenetic alterations in whole blood discriminate among patients with DM with normal, delayed, and rapid gastric emptying (GE).MethodsUsing the ChIP-seq (chromatin immunoprecipitation combined with next-generation sequencing) assays, we compared the genome-wide enrichment of 3 histone modifications (i.e., H3K4me3, H3K9ac, and H3K27ac) in buffy coats from 20 diabetic patients with gastrointestinal symptoms and normal (n = 6), delayed (n = 8), or rapid (n = 6) GE.ResultsBetween patients with DM with delayed vs normal GE, there were 108 and 54 genes that were differentially bound (false discovery rate < 0.05) with H3K27ac and H3K9ac, respectively; 100 genes were differentially bound with H3K9ac in patients with rapid vs normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (e.g., CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1, PDE4A, and CMKLR1). For H3K9ac, the differentially occupied genes were related to T-cell development and function (e.g., ICOS and CCR3) and innate immunity (RELB, CD300LB, and CLEC2D). Compared with normal GE, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (e.g., TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism. Motif analysis disclosed enrichment of binding sites for transcription factors relevant to the pathogenesis and complications of DM.DiscussionGE disturbances in DM are associated with epigenetic alterations that pertain to dysimmunity, glucose metabolism, and other complications of DM.
| S-EPMC7145053 | biostudies-literature
Project description:Introduction. Hindered by a limited understanding of the molecular mechanisms responsible for diabetic gastroenteropathy (DGE), patients are managed by symptom-based therapies. We investigated the duodenal mucosal expression of protein-coding genes and miRNAs in DGE and related these abnormalities to clinical features. Methods. mRNA and micro RNA (miRNA) expression and ultrastructure of duodenal mucosal biopsies were investigated in 39 DGE patients and 21 healthy controls. Results were analyzed in the context of diabetic phenotype and gastric emptying. Results. There were 3175 differentially-expressed genes (FDR<0.05), especially mitochondrial genes, in DGE versus controls. Several mitochondrial (mt) DNA-encoded genes (12 of 13 protein coding genes mainly involved in oxidative phosphorylation (OXPHOS), both rRNAs and 9 of 22 tRNAs) were downregulated; conversely, nuclear (n) DNA-encoded mitochondrial genes (eg, OXPHOS, TCA cycle) were upregulated in DGE. Motif analysis uncovered binding sites for transcription factors NRF1, GABPA and YY1, which regulate mitochondrial biogenesis, in the promoters of differentially expressed genes. Seventeen of 30 differentially expressed miRNAs in DGE targeted differentially expressed mitochondrial genes. Mitochondrial density was also reduced and correlated with the expression of 9 mt-DNA OXPHOS genes in DGE. Uncovered by a principal component (PC) analysis of OXPHOS genes, PC1 was significantly associated with neuropathy (P = 0.01) and with delayed gastric emptying (P < 0.05). Conclusion. In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased, respectively, associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying, and correlated with cognate miRNA expression. Together, these findings provide substantial evidence for clinically-relevant mitochondrial disturbances in DGE.
2021-03-10 | GSE151496 | GEO
Project description:Introduction. Hindered by a limited understanding of the molecular mechanisms responsible for diabetic gastroenteropathy (DGE), patients are managed by symptom-based therapies. We investigated the duodenal mucosal expression of protein-coding genes and miRNAs in DGE and related these abnormalities to clinical features. Methods. mRNA and micro RNA (miRNA) expression and ultrastructure of duodenal mucosal biopsies were investigated in 39 DGE patients and 21 healthy controls. Results were analyzed in the context of diabetic phenotype and gastric emptying. Results. There were 3175 differentially-expressed genes (FDR<0.05), especially mitochondrial genes, in DGE versus controls. Several mitochondrial (mt) DNA-encoded genes (12 of 13 protein coding genes mainly involved in oxidative phosphorylation (OXPHOS), both rRNAs and 9 of 22 tRNAs) were downregulated; conversely, nuclear (n) DNA-encoded mitochondrial genes (eg, OXPHOS, TCA cycle) were upregulated in DGE. Motif analysis uncovered binding sites for transcription factors NRF1, GABPA and YY1, which regulate mitochondrial biogenesis, in the promoters of differentially expressed genes. Seventeen of 30 differentially expressed miRNAs in DGE targeted differentially expressed mitochondrial genes. Mitochondrial density was also reduced and correlated with the expression of 9 mt-DNA OXPHOS genes in DGE. Uncovered by a principal component (PC) analysis of OXPHOS genes, PC1 was significantly associated with neuropathy (P = 0.01) and with delayed gastric emptying (P < 0.05). Conclusion. In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased, respectively, associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying, and correlated with cognate miRNA expression. Together, these findings provide substantial evidence for clinically-relevant mitochondrial disturbances in DGE.
2021-03-10 | GSE151495 | GEO
Project description:The mechanisms of 'idiopathic' rapid gastric emptying, which are associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying.Fasting and postprandial (300kcal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; seven had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying.While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (P=0.002) body mass index than normal gastric emptying. MRI visualized propagating contractions at ?3cpm in healthy people and patients. Compared with controls (0.32±0.04, Mean±SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2-14.0) in patients with rapid (0.48±0.06), but not normal gastric emptying (0.20±0.06). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls.MRI provides a non-invasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia.
| S-EPMC3117921 | biostudies-literature
Project description:Marjolin’s Ulcer is an aggressive cutaneous malignancy that typically ensues over a period of time in the post-burned lesions and scars or any other chronic wound. Marjolin’s Ulcer makes up 1.2% of all skin cancers, it is reported that 2% of squamous cell carcinoma and 0.03% of basal cell carcinoma originate in burn scars. Recent studies have shown that long non-coding (lncRNA) plays critical roles in a myriad of biological processes and human diseases,Since the roles of lncRNA in Marjolin’s Ulcer remain unknown,they were investigated in the study.Our findings indicate that the expression profiles of lncRNAs has changed in Marjolin’s Ulcer as compared with normal skin and para-cancerous scar, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for Marjolin’s Ulcer.
2018-12-11 | GSE110138 | GEO
Project description:Background & Aims: Spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) is known to emerge following parietal cell loss and during Helicobacter pylori infection, however its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods: Acetic acid ulcers were induced in young (2-3 months) C57BL/6 mice to determine the quality of ulcer repair. Gastric tissue was collected and analyzed to determine the expression of SPEM within the regenerating epithelium. As a comparison to native tissue the expression of SPEM was also identified within cultured gastric mouse-derived organoids. Results: Wound healing in the mice coincided with the emergence of SPEM expressing CD44v within the ulcerated region. The emergence of SPEM was also observed in cultured gastric organoids. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration. 4 samples were used for ulcerated and uninjured tissue. 1 sample was used for intact tissue and organoid-derived RNA. The 'Ulcerated' samples represent C57BL/6 mice with ulcers and the 'Uninjured' samples represent the healthy controls (for "ulcerated" samples). The "Intact stomach tissue" and "Gastric organoids" samples are other types of samples that compared separately. "Gastric organoids" in this comparison are derived from "Intact stomach tissue".
2015-09-23 | E-GEOD-73336 | biostudies-arrayexpress
Project description:Background & Aims: Spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) is known to emerge following parietal cell loss and during Helicobacter pylori infection, however its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods: Acetic acid ulcers were induced in young (2-3 months) C57BL/6 mice to determine the quality of ulcer repair. Gastric tissue was collected and analyzed to determine the expression of SPEM within the regenerating epithelium. As a comparison to native tissue the expression of SPEM was also identified within cultured gastric mouse-derived organoids. Results: Wound healing in the mice coincided with the emergence of SPEM expressing CD44v within the ulcerated region. The emergence of SPEM was also observed in cultured gastric organoids. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration.
2015-09-23 | GSE73336 | GEO