Exploring the dynamic changes between pulmonary and cutaneous sarcoidosis based on gene expression

Sarcoidosis is a disease involving the growth of abnormal inflammatory granulomas and affecting multisystems. It has an unknown etiology. The lung and the skin are the most commonly involved organs. Although large amounts of research have focused on the pathogenesis of sarcoidosis, little is known about the link between cutaneous sarcoidosis and pulmonary sarcoidosis. Moreover, the gene expression profiles provide a novel way to find diagnostic or prognostic biomarkers. Therefore, the aim of this study was to analyze the differentially expressed genes (DEGs) in pulmonary sarcoidosis and cutaneous sarcoidosis patients and to compare them to healthy individuals. DEGs and their biological functions are dynamically dysregulated, and several common disease-related genes and mutual disease progression-related genes were identified which linked pulmonary sarcoidosis and cutaneous sarcoidosis together. The biological functional pathways regulated by these DEGs may allow to define the common mechanism shared by different type of sarcoidosis, providing novel insight into the common pathogenesis of sarcoidosis and opening the way to the development of new therapeutic strategies.

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Exploring the Pathogenesis of Psoriasis Complicated With Atherosclerosis via Microarray Data Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.667690 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenxing Su ◽

Ying Zhao ◽

Yuqian Wei ◽

Xiaoyan Zhang ◽

Jiang Ji ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Expression Omnibus ◽

Microarray Data Analysis ◽

Common Mechanism ◽

Hub Genes ◽

Protein Protein Interaction ◽

The Common ◽

Common Pathogenesis

BackgroundAlthough more and more evidence has supported psoriasis is prone to atherosclerosis, the common mechanism of its occurrence is still not fully elucidated. The purpose of this study is to further explore the molecular mechanism of the occurrence of this complication.MethodsThe gene expression profiles of psoriasis (GSE30999) and atherosclerosis (GSE28829) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis and atherosclerosis, three kinds of analyses were performed, namely functional annotation, protein‐protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis.ResultsA total of 94 common DEGs (24 downregulated genes and 70 upregulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. In addition, lipopolysaccharide-mediated signaling pathway is closely related to both. Finally, 16 important hub genes were identified using cytoHubba, including LYN, CSF2RB, IL1RN, RAC2, CCL5, IRF8, C1QB, MMP9, PLEK, PTPRC, FYB, BCL2A1, LCP2, CD53, NCF2 and TLR2.ConclusionsOur study reveals the common pathogenesis of psoriasis and atherosclerosis. These common pathways and hub genes may provide new ideas for further mechanism research.

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Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis

10.1101/2020.08.12.225458 ◽

2020 ◽

Author(s):

Reza Yarani ◽

Oana Palasca ◽

Nadezhda T. Doncheva ◽

Christian Anthon ◽

Bartosz Pilecki ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Mouse Model ◽

High Throughput ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Unknown Etiology ◽

Small Rna Sequencing ◽

Complex Nature

1.AbstractBACKGROUND & AIMSUlcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature, in vivo studies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.METHODSTherefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.RESULTSWe identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.CONCLUSIONGlobal transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.

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Analyzing gene expression profiles with preliminary validations in cardiac hypertrophy induced by pressure overload

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0585 ◽

2018 ◽

Vol 96 (8) ◽

pp. 701-709 ◽

Cited By ~ 1

Author(s):

Jing Gao ◽

Yuhong Li ◽

Tongmei Wang ◽

Zhuo Shi ◽

Yiqi Zhang ◽

...

Keyword(s):

Gene Expression ◽

Cardiac Hypertrophy ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Pressure Overload ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Ontology Term ◽

The Common

The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using the Database for Annotation, Visualization and Integrated Discovery database. Furthermore, the top DEGs were further validated using quantitative PCR in the hypertrophic heart tissue induced by isoprenaline. A total of 113 common DEGs with absolute fold change > 0.5, including 60 significantly upregulated DEGs and 53 downregulated DEGs, were obtained. Gene ontology term enrichment analysis suggested that common upregulated DEG were mainly enriched in neutrophil chemotaxis, extracellular fibril organization, and cell proliferation; and the common downregulated genes were significantly enriched in ion transport, endoplasmic reticulum, and dendritic spine. Kyoto Encyclopedia of Genes and Genomes pathway analysis found that the common DEGs were mainly enriched in extracellular matrix receptor interaction, phagosome, and focal adhesion. Additionally, the expression of Mfap4, Ltbp2, Aspn, Serpina3n, and Cnksr1 were upregulated in the model of CH, while the expression of Anp32a was downregulated. The current study identified the key deregulated genes and pathways involved in the CH, which could shed new light to understand the mechanism of CH.

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Serial Gene Expression Studies of Malignant Plasma Cells before Treatment and after Relapse: Identifying Genes Linked to Drug Resistance in Myeloma.

Blood ◽

10.1182/blood.v104.11.784.784 ◽

2004 ◽

Vol 104 (11) ◽

pp. 784-784

Author(s):

Fenghuang Zhan ◽

Sisi Kapp ◽

Y. Huang ◽

Elias J. Anassie ◽

H. Xu ◽

...

Keyword(s):

Gene Expression ◽

Drug Resistance ◽

Plasma Cells ◽

De Novo ◽

Expression Profiles ◽

Gene Expression Profiles ◽

High Dose Chemotherapy ◽

High Dose ◽

Chi Square ◽

The Common

Abstract Virtually all patients with multiple myeloma (MM) eventually develop drug resistance. It is unclear whether drug resistance derives from the emergence of a subclone with de novo, genetically programmed resistance, or whether it develops through accumulation of genetic lesions or epigenetic mechanisms facilitated by microenvironment interactions. We investigated changes in gene expression profiles (GEP) that accompany drug resistance by comparing microarray signatures of purified plasma cells from newly diagnosed MM patients before therapy and after relapse. Paired samples (n=20) were obtained from treated with high-dose chemotherapy and tandem PBSCT. RNA was isolated from plasma cells labeled and hybridized to U133Plus2.0 high-density oligonucleotide microarrays capable of investigating ~33,000 genes. Baseline and relapse samples were grouped together and the GEP of the two groups compared. Only genes with Chi-square >3.84 (P <0.05) or present in >50% of samples were retained. 15,000 genes were analyzed with SAM in R (two-class paired case). The cut-off point was the smallest such that the estimate of the false positives was zero. A total of 234 genes were significant by SAM, with a median FDR of 1% and a 90th percentile FDR of 3%. Of the 234 genes, 199 were down-regulated and 35 were up-regulated at relapse. Thus, with 90% confidence, the FDR among genes found significant was no higher than 3%. Chromosomal translocations involving the immunoglobulin locus are likely to be initiating events in nearly half of all MM cases and we have previously shown that GEP is a robust method for identifying all the common translocations in MM. Because translocations result in the spiked expression of target oncogenes and represent useful tumor-specific landmarks, we also investigated the distribution of the common spikes in both baseline and relapse samples. For the most part, translocations present at baseline were also present at relapse. As expected from our previous work, whereas MMSET spikes were consistently found associated with t(4;14)(p16;q32), FGFR3 spikes could be absent at baseline and lost during progression. A CCND3 spike, not present in the baseline sample, appeared in the relapse sample. This is consistent with this translocation being a secondary event associated with tumor progression. MAF expression was lost in one relapse. This was unexpected and may be due to mislabeling. No MAFB spikes were found in any of the baseline or relapse samples. Interestingly, at the time of this analysis, there were no CCND1 spikes in the relapse cases, consistent with this translocation being a good prognostic marker. Thus, significant and recurrent changes in GEP accompany the development of drug resistance in MM. Surprisingly, the majority of altered genes were down-regulated in relapse. The significance of this finding is not clear, but may reflect loss of chromosome material and/or epigenetic silencing of genes through increased DNA methylation. Validation of our findings may provide important insight into the mechanisms of MM drug resistance.

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Comparative transcriptome analysis reveals distinct gene expression profiles in Brachypodium distachyon infected by two fungal pathogens

BMC Plant Biology ◽

10.1186/s12870-021-03019-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gengrui Zhu ◽

Chengyu Gao ◽

Chenyu Wu ◽

Mu Li ◽

Jin-Rong Xu ◽

...

Keyword(s):

Gene Expression ◽

Fungal Pathogens ◽

Time Course ◽

Expression Profiles ◽

Brachypodium Distachyon ◽

Gene Expression Profiles ◽

Cereal Crops ◽

Valuable Insight ◽

Crop Resistance ◽

The Common

Abstract Background The production of cereal crops is frequently affected by diseases caused by Fusarium graminearum and Magnaporthe oryzae, two devastating fungal pathogens. To improve crop resistance, many studies have focused on understanding the mechanisms of host defense against these two fungi individually. However, our knowledge of the common and different host defenses against these pathogens is very limited. Results In this study, we employed Brachypodium distachyon as a model for cereal crops and performed comparative transcriptomics to study the dynamics of host gene expression at different infection stages. We found that infection with either F. graminearum or M. oryzae triggered massive transcriptomic reprogramming in the diseased tissues. Numerous defense-related genes were induced with dynamic changes during the time course of infection, including genes that function in pattern detection, MAPK cascade, phytohormone signaling, transcription, protein degradation, and secondary metabolism. In particular, the expression of jasmonic acid signaling genes and proteasome component genes were likely specifically inhibited or manipulated upon infection by F. graminearum. Conclusions Our analysis showed that, although the affected host pathways are similar, their expression programs and regulations are distinct during infection by F. graminearum and M. oryzae. The results provide valuable insight into the interactions between B. distachyon and two important cereal pathogens.

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Gene Expression in Peripheral Blood Differs after Cardioembolic Compared with Large-Vessel Atherosclerotic Stroke: Biomarkers for the Etiology of Ischemic Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.22 ◽

2008 ◽

Vol 28 (7) ◽

pp. 1320-1328 ◽

Cited By ~ 55

Author(s):

Huichun Xu ◽

Yang Tang ◽

Da-Zhi Liu ◽

Ruiqiong Ran ◽

Bradley P Ander ◽

...

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Peripheral Blood ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Large Vessel ◽

Cardioembolic Stroke ◽

Unknown Etiology ◽

Stroke Patients ◽

Clinical Criteria

There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and ~30% of strokes and transient ischemic attacks have undetermined etiologies using current clinical criteria. We aimed to define gene expression profiles in blood that differentiate cardioembolic from large-vessel atherosclerotic stroke. Peripheral blood samples were obtained from healthy controls and acute ischemic stroke patients (< 3, 5, and 24 h). RNA was purified, labeled, and applied to Affymetrix Human U133 Plus 2.0 Arrays. Expression profiles in the blood of cardioembolic stroke patients are distinctive from those of large-vessel atherosclerotic stroke patients. Seventy-seven genes differ at least 1.5-fold between them, and a minimum number of 23 genes differentiate the two types of stroke with at least 95.2% specificity and 95.2% sensitivity for each. Genes regulated in large-vessel atherosclerotic stroke are expressed in platelets and monocytes and modulate hemostasis. Genes regulated in cardioembolic stroke are expressed in neutrophils and modulate immune responses to infectious stimuli. This new method can be used to predict whether a stroke of unknown etiology was because of cardioembolism or large-vessel atherosclerosis that would lead to different therapy. These results have wide ranging implications for similar disorders.

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Genome-wide targets of selection: female response to experimental removal of sexual selection inDrosophila melanogaster

10.1101/000240 ◽

2013 ◽

Author(s):

Paolo Innocenti ◽

Ilona Flis ◽

Edward H Morrow

Keyword(s):

Gene Expression ◽

Sexual Selection ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mating Strategies ◽

Female Fecundity ◽

Common Assumption ◽

Female Response ◽

Genome Wide ◽

The Common

Despite the common assumption that promiscuity should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the mating system in replicate populations ofDrosophila melanogasterby removing sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies. We show that monogamous females suffer decreased fecundity, a decrease that was partially recovered by experimentally reversing the selection pressure back to the ancestral promiscuous state. The post-mating gene expression profiles of monogamous females differ significantly from promiscuous females, involving 9% of the genes tested. These transcripts are active in several tissues, mainly ovaries, neural tissues and midgut, and are involved in metabolic processes, reproduction and signaling pathways. Our results demonstrate how the female post-mating response can evolve under different mating systems, and provide novel insights into the genes targeted by sexual selection in females, by identifying a list of candidate genes responsible for the decrease in female fecundity in the absence of promiscuity.

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