scholarly journals Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1793
Author(s):  
Ho-Su Lee ◽  
Maaike Vancamelbeke ◽  
Sare Verstockt ◽  
Tom Wilms ◽  
Bram Verstockt ◽  
...  

Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis patients were related to immune functions. The ileal changes in the inactive ulcerative colitis subjects converged into the maintenance of the intestinal barrier through increased mitochondrial function and dampened immune functions. In conclusion, we identified molecular changes in the non-inflamed ileum of ulcerative colitis that are dependent on colonic inflammation.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Nelly F Mostajo ◽  
Marie Lataretu ◽  
Sebastian Krautwurst ◽  
Florian Mock ◽  
Daniel Desirò ◽  
...  

Abstract Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.


2021 ◽  
Author(s):  
Michihito Deguchi ◽  
Shobha Potlakayala ◽  
Zachary Spuhler ◽  
Hannah George ◽  
Vijay Sheri ◽  
...  

Abstract Industrial hemp (Cannabis sativa L.) is a dioecious crop widely known for its production of phytocannabinoids, flavonoids, and terpenes. In the past two years since its legalization, there has been significant interest in researching this important crop for pharmaceutical applications. Although many scientific reports have demonstrated gene expression analysis of hemp through OMICs approaches, accurate validation of omics data cannot be performed because of lack of reliable reference genes for normalization of qRT-PCR data. The differential gene expression patterns of 13 candidate reference genes under osmotic, heavy metal, hormonal, and UV stress were evaluated through four software packages: geNorm, NormFinder, BestKeeper, and RefFinder. The EF-1a ranked as the most stable reference gene across all stresses, TUB was the most stable under osmotic stress, and TATA was the most stable under both heavy metal and hormonal stress. The expression profiles of two cannabinoid pathway genes, AAE1 and THCAS, using the two most stable and single least stable reference genes confirmed that two most stables genes were apt for normalization of gene expression data. This work will contribute to the future studies on the expression analysis of hemp genes regulating the synthesis, transport and accumulation of secondary metabolites.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Mbaye Tine

The present work examines the induction of theband 3 anion transport protein,mitogen-activated protein kinase, andlactate dehydrogenase, respectively related to osmolyte transport, cell volume regulation, and energy production in the gills of two tilapia strains exposed to either freshwater or hypersaline water. Overall, genes showed similar expression patterns between strains. However, a wild population survey across a range of natural habitats and salinities did not reveal the expected patterns. Although significant, the correlations between gene expression and salinity were slightly ambiguous and did not show any link with phenotypic differences in life history traits previously reported between the same populations. The differential expression was also not associated with the population genetic structure inferred from neutral markers. The results suggest that the differential expression observed is not the result of evolutionary forces such as genetic drift or adaptation by natural selection. Instead, it can be speculated that genes responded to various abiotic and biotic stressors, including factors intrinsic to animals. This study provides clear evidence of the complexity of gene expression analysis in wild populations and shows that more attention needs to be paid when selecting candidates as potential biomarkers for monitoring adaptive responses to a specific environmental perturbation.


2022 ◽  
Vol 8 ◽  
Author(s):  
Ziqi Dai ◽  
Lijun Shang ◽  
Fengming Wang ◽  
Xiangfang Zeng ◽  
Haitao Yu ◽  
...  

Microcin C7 is an antimicrobial peptide produced by Escherichia coli, composed of a heptapeptide with a modified adenosine monophosphate. This study was performed to evaluate the effects of Microcin C7 as a potential substrate to traditional antibiotics on growth performance, immune functions, intestinal barrier, and cecal microbiota of broilers. In the current study, 300 healthy Arbor Acres broiler chicks were randomly assigned to one of five treatments including a corn–soybean basal diet and basal diet supplemented with antibiotic or 2, 4, and 6 mg/kg Microcin C7. Results showed that Microcin C7 significantly decreased the F/G ratio of broilers; significantly increased the levels of serum cytokine IL-10, immunoglobulins IgG and IgM, and ileal sIgA secretion; significantly decreased the level of serum cytokine TNF-α. Microcin C7 significantly increased villus height and V/C ratio and significantly decreased crypt depth in small intestine of broilers. Microcin C7 significantly increased gene expression of tight junction protein Occludin and ZO-1 and significantly decreased gene expression of pro-inflammatory and chemokine TNF-α, IL-8, IFN-γ, Toll-like receptors TLR2 and TLR4, and downstream molecular MyD88 in the jejunum of broilers. Microcin C7 significantly increased the number of Lactobacillus and decreased the number of total bacteria and Escherichia coli in the cecum of broilers. Microcin C7 also significantly increased short-chain fatty acid (SCFA) and lactic acid levels in the ileum and cecum of broilers. In conclusion, diet supplemented with Microcin C7 significantly improved growth performance, strengthened immune functions, enhanced intestinal barrier, and regulated cecal microbiota of broilers. Therefore, the antimicrobial peptide Microcin C7 may have the potential to be an ideal alternative to antibiotic.


2021 ◽  
Author(s):  
Ying-xue Zhang ◽  
Feng-xia Sun ◽  
Xiao-ling Li ◽  
Qing-hua Liu ◽  
Zi-meng Chen ◽  
...  

Abstract Background: Cirrhosis is a common clinical chronic progressive liver disease and has become one of the main causes of death worldwide. The condition of liver cirrhosis is complex and there is also clinical heterogeneity. Identifying liver cirrhosis based on molecular characteristics has become a challenge.Methods: To reveal the potential molecular characteristics of different types of cirrhosis, we divided 79 patients with cirrhosis into 4 subgroups based on gene expression profiles. These gene expression profiles were retrieved from the mprehensive gene expression database. In addition, these subgroups showed different expression patterns. To reveal the differences between subgroups, we used weighted gene co-expression analysis and identified six subgroup-specific gene co-expression analysis modules.Results: The characteristics ofWCGNAmodules indicate that TGF - β signaling pathway,viral protein interaction with cytokines and cytokine receptors, including a variety of chemokines and inflammatory factors, are upregulated in subgroup I, indicating that subjects in subgroup I may show inflammatory characteristics; fatty acid metabolism, biosynthesis of cofactors, carbon metabolism and protein processing pathway in endoplasmic reticulum were significantly enriched in subgroup II, which indicated that the subjects in subgroup II might have the characteristics of active metabolism; arrhythmogenic right ventricular cardiomyopathy and Neuroactive ligand−receptor interaction are significantly enriched in subgroup IV; we did not find a significant upregulation pathway in the third subgroup.Conclusion: The subgroups classification of liver cirrhosis cases shows that patients from different subgroups may have unique gene expression patterns, which indicates that patients in each subgroup should receive more personalized treatment.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 285-285
Author(s):  
Hui-Li Wong ◽  
Martin Jones ◽  
Peter Eirew ◽  
Joanna Karasinska ◽  
Kasmintan A Schrader ◽  
...  

285 Background: In the absence of defined tumor molecular subtypes and validated predictive markers, PDAC has been largely treated as a single disease. Recent studies of molecular subtyping in PDAC reveal a complex mutational landscape with data suggesting the presence of genomic and gene expression signatures that may have prognostic and therapeutic significance. These studies predominantly focused on resected PDAC and lack data on metastatic tumors. We aim to explore the clinical utility of whole genome sequencing (WGS) and transcriptome analysis from metastatic biopsy samples in patients (pts) with advanced PDAC. Methods: Pts with incurable advanced cancers undergo tumor biopsy for in-depth WGS and RNA sequencing (RNASeq) as part of an ongoing prospective study (NCT02155621). Comprehensive bioinformatics analysis is performed to identify somatic cancer aberrations, gene expression changes and cellular pathway abnormalities. Here we describe clinical and molecular data on the subset of pts with advanced PDAC. Results: Sixteen PDAC pts have been enrolled; median age 59 years, 8 males (50%), 10 with de novo metastases (63%). Full WGS and RNASeq were completed in 11 pts (1 failed biopsy, 4 had insufficient tumor). KRAS codon 12 and TP53 mutations were present in all but one pt. CDKN2A and SMAD4 were also frequently altered (7 and 4 pts respectively). Gene expression analysis for classical and basal subtypes similar to those recently described (PMID 26343385) identified 3 and 6 pts with classical and basal expression patterns respectively, and 2 pts with mixed expression. Overall survival (OS) was significantly worse for the basal subtype vs all others (median OS 7 vs. 13.9 months (ms), p = 0.017). When separated into 3 subtypes a significant difference was still noted (median OS 7 ms in basal, 19.2 ms in classical and 11.8 ms in mixed subtype, p = 0.032). Conclusions: WGS analysis demonstrated a similar mutation pattern to that described in resectable PDAC, with no novel actionable mutations identified. Gene expression analysis demonstrated the presence of distinct gene expression signatures significantly associated with outcome, despite small pt numbers. These results need to be validated prospectively in larger cohorts. Clinical trial information: NCT02155621.


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