scholarly journals Identifying the Growth Factors for Improving Neointestinal Regeneration in Rats through Transcriptome Analysis Using RNA-Seq Data

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Shyh-Chuan Jwo ◽  
I-Fang Chung ◽  
Hsei-Wei Wang ◽  
Ting-Yu Chang
Keyword(s):  
Growth Factors ◽  
Normal Control ◽  
Intestinal Adaptation ◽  
Regenerative Process ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Control Tissue ◽  
Point Versus ◽  
Potential Applications ◽  
Pathway Analyses

Using our novel surgical model of simultaneous intestinal adaptation “A” and neointestinal regeneration “N” conditions in individual rats to determine feasibility for research and clinical application, we further utilized next generation RNA sequencing (RNA-Seq) here in normal control tissue and both conditions (“A” and “N”) across time to decipher transcriptome changes in neoregeneration and adaptation of intestinal tissue at weeks 1, 4, and 12. We also performed bioinformatics analyses to identify key growth factors for improving intestinal adaptation and neointestinal regeneration. Our analyses indicate several interesting phenomena. First, Gene Ontology and pathway analyses indicate that cell cycle and DNA replication processes are enhanced in week 1 “A”; however, in week 1 “N”, many immune-related processes are involved. Second, we found some growth factors upregulated or downregulated especially in week 1 “N” versus “A”. Third, based on each condition and time point versus normal control tissue, we found in week 1 “N” BMP2, BMP3, and NTF3 are significantly and specifically downregulated, indicating that the regenerative process may be inhibited in the absence of these growth factors. This study reveals complex growth factor regulation in small neointestinal regeneration and intestinal adaptation and provides potential applications in tissue engineering by introducing key growth factors identified here into the injury site.

scholarly journals Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

2021 ◽  
Author(s):  
Mayukh Banerjee ◽  
Ana Ferragut Cardoso ◽  
Laila Al-Eryani ◽  
Jianmin Pan ◽  
Theodore S. Kalbfleisch ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Mrna Expression ◽  
Hacat Cell ◽  
Arsenic Exposure ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Chronic Arsenic Exposure ◽  
Pathway Analyses ◽  
Time Point

AbstractChronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1006-1006
Author(s):  
Leisha A. Emens ◽  
Leonard D Goldstein ◽  
Peter Schmid ◽  
Hope S. Rugo ◽  
Sylvia Adams ◽  
...  
Keyword(s):  
Cox Regression ◽  
Rna Seq ◽  
Phase 3 ◽  
Molecular Subtyping ◽  
Sample Classification ◽  
Damage Repair ◽  
Immune Phenotypes ◽  
Pathway Analyses ◽  
Clinical Trial Information ◽  
Tumor Area

1006 Background: IMpassion130 was the first randomized phase 3 study to show clinical benefit of cancer immunotherapy (CIT) in untreated PD-L1+ mTNBC. Enhanced A + nP efficacy vs placebo (P) + nP was seen in pts with a richer immune TME but was confined to PD-L1 IC+ pts (PD-L1–expressing immune cells on ≥1% of tumor area; Emens JNCI 2021). While TNBC molecular subtyping and CD8 localization are prognostic in early TNBC, it is unknown whether these features are associated with CIT benefit in mTNBC. This exploratory analysis aimed to identify TME components associated with A + nP efficacy in IMpassion130. Methods: IHC was used to assess PD-L1 status (VENTANA SP142) and immune phenotypes (inflamed/excluded/desert per CD8 stromal/intratumoral localization; Mariathasan Nature 2018). RNA-seq was used for molecular subtyping (Burstein CCR 2015) and pathway analyses (MSigDB Hallmark). Cox regression was used to compare PFS/OS between A + nP vs P + nP, adjusted for prior taxanes, liver mets. Results: Sample classification and PD-L1 distribution are shown (Table). Improved PFS with A + nP vs P + nP was seen in PD-L1 IC+ inflamed and excluded tumors, but improved OS was limited to PD-L1 IC+ inflamed tumors. PD-L1 IC+ basal-like immune activated (BLIA) and immune suppressed (BLIS) subgroups derived PFS benefit, but OS benefit was limited to PD-L1 IC+ BLIA subgroups. In PD-L1 IC+ pts, pathway analysis identified proliferation/DNA damage repair (basal-like tumor features) and angiogenesis/ER response (higher in luminal androgen receptor [LAR]/ mesenchymal [MES] tumors) were associated with improved and reduced PFS, respectively. Conclusions: PD-L1 IC+ immune-inflamed tumors and PD-L1 IC+ BLIA tumors show highest CIT sensitivity, and LAR tumors may be resistant to CIT. These data warrant further study and validation. Clinical trial information: NCT02425891 .[Table: see text]

scholarly journals Angelman Syndrome and Angelman-like Syndromes Share the Same Calcium-Related Gene Signatures

2021 ◽  
Vol 22 (18) ◽  
pp. 9870
Author(s):  
Julia Panov ◽  
Hanoch Kaphzan
Keyword(s):  
Angelman Syndrome ◽  
Neurodevelopmental Disorders ◽  
Clinical Presentation ◽  
Rna Seq ◽  
Related Gene ◽  
Bioinformatics Analyses ◽  
Gene Signatures ◽  
Signature Genes ◽  
Gene Expression Analyses ◽  
Differential Gene

Angelman-like syndromes are a group of neurodevelopmental disorders that entail clinical presentation similar to Angelman Syndrome (AS). In our previous study, we showed that calcium signaling is disrupted in AS, and we identified calcium-target and calcium-regulating gene signatures that are able to differentiate between AS and their controls in different models. In the herein study, we evaluated these sets of calcium-target and calcium-regulating genes as signatures of AS-like and non-AS-like syndromes. We collected a number of RNA-seq datasets of various AS-like and non-AS-like syndromes and performed Principle Component Analysis (PCA) separately on the two sets of signature genes to visualize the distribution of samples on the PC1–PC2 plane. In addition to the evaluation of calcium signature genes, we performed differential gene expression analyses to identify calcium-related genes dysregulated in each of the studied syndromes. These analyses showed that the calcium-target and calcium-regulating signatures differentiate well between AS-like syndromes and their controls. However, in spite of the fact that many of the non-AS-like syndromes have multiple differentially expressed calcium-related genes, the calcium signatures were not efficient classifiers for non-AS-like neurodevelopmental disorders. These results show that features based on clinical presentation are reflected in signatures derived from bioinformatics analyses and suggest the use of bioinformatics as a tool for classification.

scholarly journals Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

2020 ◽  
Author(s):  
Yijing Chu ◽  
Chongyu Yue ◽  
Wei Peng ◽  
Weiping Chen ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chorionic Villus ◽  
Pcr Analysis ◽  
Rna Seq ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Upstream Regulator ◽  
Pathway Analyses ◽  
Stat3 Signalling

Abstract Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function.Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts.Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment.Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

scholarly journals Identification of RRM2 as a Potential Biomarker for the Diagnosis and Prognosis of Rheumatoid Arthritis

2021 ◽  
Author(s):  
Wu Biao ◽  
Yufeng Chen ◽  
Junlong Zhong ◽  
Shuping Zhong ◽  
Bin Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Clinical Samples ◽  
Healthy Controls ◽  
Rna Seq ◽  
Hub Genes ◽  
Healthy Human ◽  
Bioinformatics Analyses ◽  
Potential Biomarker

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease that can occur at any age. If treatment is delayed, RA can seriously affect the patients’ quality of life. However, there is no diagnostic criteria for RA and the positive predictive value of the current biomarkers is moderate. Objective: to identify RA-associated susceptibility genes and explore their potential as a novel biomarker for diagnosis and evaluation of the prognosis of RA.Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy human donors and RA patients. RNA-seq analyses were performed to identify the differentially expressed genes (DEGs) between RA and control samples. The PBMCs-mRNA in DEGs were further subjected to enrichment analysis. Furthermore, the hub genes and key modules associated with RA were screened by bioinformatics analyses. Then, the expression of hub genes in RA were assessed in mRNA expression profiles. Next, real time-quantitative PCR (RT-qPCR) analyses were performed to further confirm the expression of the hub genes from the PBMCs that collected from 47 patients with RA and 40 healthy controls. Finally, we evaluated the clinical characters for the candidate mRNAs.Results: RNA-seq analyses revealed the expression of 178 mRNAs from PBMCs were disregulated between the healthy controls and the RA patients. Bioinformatics analyses revealed 10 hub mRNAs. The top 3 significant functional modules screened from PPI network functionally were involved in DNA replication origin binding, chemokine activity, etc. After validating the 10 hub mRNAs in GSE93272 dataset and clinical samples, we identified 3 candidate mRNAs, including ASPM, DTL and RRM2. Among which, RRM2 showed great capacity in discriminating between remissive RA and active RA. Significant correlations were observed between DTL and IL-8, TNF-α, between RRM2 and CDAI, DAS-28, tender joints and swollen joints, respectively. The AUC values of ASPM, DTL and RRM2 were 0.654, 0.995 and 0.990, respectively.Conclusion: We successfully identified multiple candidate mRNAs associated with RA. RRM2 showed high diagnosis efficiency with the AUC of 0.990 (sensitivity=100%, specificity=97.5%). And RRM2 severed as an additional biomarker for evaluating disease activity. The findings provided a novel candidate biomarker for diagnosis and evaluation of the prognosis of RA.

scholarly journals RNA-Sequencing Analyses of Small Bacterial RNAs and their Emergence as Virulence Factors in Host-Pathogen Interactions

2020 ◽  
Vol 21 (5) ◽  
pp. 1627 ◽  
Author(s):  
Idrissa Diallo ◽  
Patrick Provost
Keyword(s):  
Rna Sequencing ◽  
Virulence Factors ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Rna Seq ◽  
Host Pathogen Interactions ◽  
Bioinformatics Analyses ◽  
Additional Layer ◽  
Host Pathogen

Proteins have long been considered to be the most prominent factors regulating so-called invasive genes involved in host-pathogen interactions. The possible role of small non-coding RNAs (sRNAs), either intracellular, secreted or packaged in outer membrane vesicles (OMVs), remained unclear until recently. The advent of high-throughput RNA-sequencing (RNA-seq) techniques has accelerated sRNA discovery. RNA-seq radically changed the paradigm on bacterial virulence and pathogenicity to the point that sRNAs are emerging as an important, distinct class of virulence factors in both gram-positive and gram-negative bacteria. The potential of OMVs, as protectors and carriers of these functional, gene regulatory sRNAs between cells, has also provided an additional layer of complexity to the dynamic host-pathogen relationship. Using a non-exhaustive approach and through examples, this review aims to discuss the involvement of sRNAs, either free or loaded in OMVs, in the mechanisms of virulence and pathogenicity during bacterial infection. We provide a brief overview of sRNA origin and importance and describe the classical and more recent methods of identification that have enabled their discovery, with an emphasis on the theoretical lower limit of RNA sizes considered for RNA sequencing and bioinformatics analyses.

scholarly journals Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles

2019 ◽  
Vol 20 (20) ◽  
pp. 4999 ◽  
Author(s):  
Jennifer R. King ◽  
Melissa L. Wilson ◽  
Szabolcs Hetey ◽  
Peter Kiraly ◽  
Koji Matsuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
First Trimester ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Immune Genes ◽  
Molecular Features ◽  
Immune Pathways ◽  
And Control ◽  
Hydatidiform Moles

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10−6), and immune genes (OR = 1.82, p = 7.34 × 10−18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. “Cytokine–cytokine receptor interaction” was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.

scholarly journals Electroacupuncture Alleviates Experimental Chronic Inflammatory Pain by Inhibiting Calcium Voltage-Gated Channel-Mediated Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Zhou ◽  
Ying Jin ◽  
Ruijie Ma ◽  
Hongyun Song ◽  
Qin Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Expression Profiles ◽  
Arachidonic Acid Metabolism ◽  
Receptor Interaction ◽  
Bioinformatics Analyses ◽  
Protein Coding ◽  
Chronic Inflammatory Pain ◽  
Gated Channel ◽  
Pathway Analyses

Background. Both experimental and clinical studies have shown that electroacupuncture (EA) administration ameliorates chronic inflammatory pain (CIP). However, the multifaceted mechanism underlying the effects of EA on CIP is poorly understood. In this study, the mRNA transcriptome was used to study various therapeutic targets of EA. Methods. Using RNA-sequencing, protein-coding mRNA expression profiles of the L4-L5 dorsal root ganglion (DRG) were examined in the control (CN), complete Freund’s adjuvant- (CFA-) induced CIP, and EA-treated CIP groups. A series of bioinformatics analyses was performed; “EA-reversed upregulated genes with CIP” (up-DEGs) and “EA-reversed downregulated genes with CIP” (down-DEGs) were identified. Thereafter, based on up-DEGs and down-DEGs, biological functions and signaling pathways were enriched using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. Results. In total, 189 DEGs were identified, including 134 up- and 55 down-DEGs, which were enriched in arachidonic acid metabolism (rno00590), glutamatergic synapse (rno04724), serotonergic synapse (rno04726), FoxO signaling pathway (rno04068), insulin signaling pathway (rno04910), amyotrophic lateral sclerosis (rno05014), cholinergic synapse (rno04725), ECM-receptor interaction (rno04512), and choline metabolism in cancer (rno05231). Conclusion. We identified a few GOs, pathways, and genes that could play key roles in the amelioration of CIP by EA. Hence, this study may provide a theoretical basis for CIP amelioration by EA.

scholarly journals Liver Regeneration: Analysis of the Main Relevant Signaling Molecules

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yachao Tao ◽  
Menglan Wang ◽  
Enqiang Chen ◽  
Hong Tang
Keyword(s):  
Growth Factors ◽  
Liver Regeneration ◽  
Normal Liver ◽  
Initial Step ◽  
Signaling Molecules ◽  
Regenerative Process ◽  
Liver Mass ◽  
Termination Phase ◽  
And Function ◽  
Stimulation Of

Liver regeneration is a highly organized tissue regrowth process and is the most important reaction of the liver to injury. The overall process of liver regeneration includes three phases: priming stage, proliferative phase, and termination phase. The initial step aims to induce hepatocytes to be sensitive to growth factors with the aid of some cytokines, including TNF-α and IL-6. The proliferation phase promotes hepatocytes to re-enter G1 with the stimulation of growth factors. While during the termination stage, hepatocytes will discontinue to proliferate to maintain normal liver mass and function. Except for cytokine- and growth factor-mediated pathways involved in regulating liver regeneration, new substances and technologies emerge to influence the regenerative process. Here, we reviewed novel and important signaling molecules involved in the process of liver regeneration to provide a cue for further research.

scholarly journals PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3065
Author(s):  
Shreya Udawant ◽  
Carl Litif ◽  
Alma Lopez ◽  
Bonnie Gunn ◽  
Erin Schuenzel ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Enrichment Analysis ◽  
Pi3k Pathway ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
Clinical Samples ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Dual Inhibitor ◽  
The Impact

Glioblastoma (GBM) is the most lethal primary brain cancer that lacks effective molecular targeted therapies. The PI3K/AKT/mTOR pathway is activated in 90% of all Glioblastoma multiforme (GBM) tumors. To gain insight into the impact of the PI3K pathway on GBM metabolism, we treated U87MG GBM cells with NVP-BEZ235 (PI3K and mTOR a dual inhibitor) and identified differentially expressed genes with RNA-seq analysis. RNA-seq identified 7803 differentially regulated genes in response to NVP-BEZ235. Gene Set Enrichment Analysis (GSEA) identified two glycolysis-related gene sets that were significantly enriched (p < 0.05) in control samples compared to NVP-BEZ235-treated samples. We validated the inhibition of glycolytic genes by NVP-BEZ235 and examined the impact of the FOXO1 inhibitor (AS1842856) on these genes in a set of GBM cell lines. FOXO1 inhibition alone was associated with reduced LDHA expression, but not ENO1 or PKM2. Bioinformatics analyses revealed that PI3K-impacted glycolytic genes were over-expressed and co-expressed in GBM clinical samples. The elevated expression of PI3K-impacted glycolytic genes was associated with poor prognosis in GBM based on Kaplan–Meier survival analyses. Our results suggest novel insights into hallmark metabolic reprogramming associated with the PI3K-mTOR dual inhibition.

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