scholarly journals Comprehensive Analysis of Differentially Expressed lncRNA, circRNA and mRNA and Their ceRNA Networks in Mice With Severe Acute Pancreatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing Wang ◽  
Jun Wu ◽  
Qilin Huang ◽  
Xiaohui Yuan ◽  
Yi Yang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathway ◽  
Severe Acute Pancreatitis ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Control Group ◽  
Calcium Signal ◽  
High Morbidity ◽  
Apoptosis Pathway

Severe acute pancreatitis (SAP) is an acute digestive system disease with high morbidity mortality and hospitalization rate worldwide, due to various causes and unknown pathogenesis. In recent years, a large number of studies have confirmed that non-coding RNAs (ncRNAs) play an important role in many cellular processes and disease occurrence. However, the underlying mechanisms based on the function of ncRNAs, including long noncoding RNA (lncRNA) and circular RNA (circRNA), in SAP remain unclear. In this study, we performed high-throughput sequencing on the pancreatic tissues of three normal mice and three SAP mice for the first time to describe and analyze the expression profiles of ncRNAs, including lncRNA and circRNA. Our results identified that 49 lncRNAs, 56 circRNAs and 1,194 mRNAs were differentially expressed in the SAP group, compared with the control group. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed lncRNAs and circRNAs, and found that the functions of the parental genes are enriched in the calcium-regulated signaling pathway, NF-κB signaling pathway, autophagy and protein digestion and absorption processes, which are closely related to the central events in pathogenesis of SAP. We also constructed lncRNA/circRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in SAP. We found that in the competitive endogenous RNA (ceRNA) networks, differentially expressed lncRNAs and circRNAs are mainly involved in the apoptosis pathway and calcium signal transduction pathway. In conclusion, we found that lncRNAs and circRNAs play an important role in the pathogenesis of SAP, which may provide new insights in further exploring the pathogenesis of SAP and seek new targets for SAP.

scholarly journals Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

2020 ◽  
Author(s):  
Guodong Song ◽  
Jia Zhou ◽  
Ruimei Song ◽  
Dalu Liu ◽  
Weidi Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Severe Acute Pancreatitis ◽  
Long Noncoding Rna ◽  
Therapeutic Efficacy ◽  
Noncoding Rna ◽  
Sodium Taurocholate ◽  
High Morbidity

Abstract Background: Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP.Methods: MSCs transfected with LncRNA H19 overexpression and knock down plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.Results: Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation.Conclusions: In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

Identification of DMSA-Coated Fe3O4 Nanoparticles Induced-Apoptosis Response Genes in Human Monocytes by cDNA Microarrays

2013 ◽  
Vol 749 ◽  
pp. 377-383 ◽  
Author(s):  
Ying Xun Liu ◽  
Jian Yuan Huang ◽  
Dong Liang Wang ◽  
Jin Ke Wang
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Dependent Manner ◽  
Receptor Signaling ◽  
Apoptosis Pathway ◽  
Receptor Signaling Pathway

This study investigated the cell apoptosis and gene expression profiles of human THP-1 monocytes in order to identify the molecular mechanism of cell apoptosis induced by meso-2,-3-dimercaptosuccinnic acid-coated Fe3O4magnetic nanoparticles. Cell apoptosis was visualized with flow cytometry after treated by 50 and 100 μg/ml Fe3O4nanoparticles, and the gene expression profiles were detected with Affymetrix Human Genome U133 Plus 2.0 GeneChips® microarrays. The transmission electron microscopy obserbation revealed that THP-1 cells were effectively labeled by the Fe3O4nanoparticles. The internalized Fe3O4nanoparticles increased cell apoptosis in a dose-dependent manner, but not decreased cell viability significantly. The cDNA microarray results showed that hundreds of genes were significantly regulated at the concentration of 50 and 100 μg/ml, and the level of these genes exhibited a dose response, includingCD14,CD86,CFLAR,IL-1,NFKBIA,NLRC4,NAIPandAIP3. The Fe3O4nanoparticles treatments resulted in significantly altered in Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and Cell apoptosis signaling pathway. Gene ontology analysis of these differentially expressed genes demonstrated that mainly up-regulated genes were related to cytokine production and cell apoptosis. These results showed that the Fe3O4nanoparticles induced THP-1 cells apoptosis and the level of lots of genes involved in extrinsic apoptosis pathway differentially expressed, which further revealed demonstrated the relation between Fe3O4MNPs treatment and cell apoptosis.

scholarly journals Coding and Noncoding RNA Expression Profiles of Spleen CD4+ T Lymphocytes in Mice With Echinococcosis

2021 ◽  
Author(s):  
Songhao Yang ◽  
Xiancai Du ◽  
Chan Wang ◽  
Tingrui Zhang ◽  
Shimei Xu ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Circular Rnas ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background: Cystic echinococcosis (CE) is a severe and neglected zoonotic disease, which is caused by Echinococcus granulosus sensu lato and poses health and socioeconomic hazards. RNA molecules play important roles in genetic coding, translation, regulation, and gene expression and are classified into noncoding RNAs, such as long noncoding RNAs (lncRNAs), miRNAs, and circular RNAs (circRNAs), and coding RNAs (mRNAs) based on whether they encode proteins.Methods: Peripheral blood serum from E. granulosus-infected and uninfected female BALB/c mice was used to measure IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α levels using the cytometric bead array mouse Th1/Th2/Th17 cytokine kit. mRNA, lncRNA, miRNA, and circRNA profiles were analyzed in spleen CD4+ T cells from the two groups of mice using high-throughput sequencing.Results: The results showed that the levels of serum IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α were significantly higher in the CE mice than in the control group (P < 0. 01). A total of 1,758 known mRNAs, 37 miRNAs, 175 lncRNAs, and 22 circRNAs were differentially expressed between infected and uninfected mice (|fold change| ≥ 0.585, P < 0.05). These differentially expressed molecules were closely related to the JAK/STAT, mitogen-activated protein kinase, p53, and PI3K/Akt signaling pathways, cell cycle, and metabolic pathways.Conclusions: E. granulosus infection caused significant increases in the IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α levels in the peripheral blood of mice, as well as significant changes in the expression levels of a variety of coding and noncoding RNAs. A further study of these trends and pathways may help clarify the pathogenesis of CE and provide new insights into the prevention and treatment of this infection.

scholarly journals Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Jin ◽  
Lei Li ◽  
Yuehan Hao ◽  
Ling Tang ◽  
Yuye Wang ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Network Analysis ◽  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Control Group ◽  
High Morbidity ◽  
Blood Draw

PurposeIntracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA).Materials and MethodsWe collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted.ResultsA total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis.ConclusionWe identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.

scholarly journals Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guodong Song ◽  
Jia Zhou ◽  
Ruimei Song ◽  
Dalu Liu ◽  
Weidi Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Severe Acute Pancreatitis ◽  
Long Noncoding Rna ◽  
Therapeutic Efficacy ◽  
Noncoding Rna ◽  
Sodium Taurocholate ◽  
High Morbidity

Abstract Background Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP. Methods MSCs transfected with LncRNA H19 overexpression and knockdown plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP. Results Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation. Conclusions In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

scholarly journals A Chinese Herbal Decoction, Huoxue Qingyi Decoction, Promotes Rehabilitation of Patients with Severe Acute Pancreatitis: A Retrospective Study

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Chao Hui Ji ◽  
Cheng Wu Tang ◽  
Wen Ming Feng ◽  
Ying Bao ◽  
Li Qin Yao
Keyword(s):  
Acute Pancreatitis ◽  
Retrospective Study ◽  
Severe Acute Pancreatitis ◽  
Control Group ◽  
High Morbidity ◽  
Early Recovery ◽  
Chinese Herbal ◽  
Herbal Decoction ◽  
Standardized Treatment ◽  
Treatment Control Group

Severe acute pancreatitis (SAP) still remains an important surgical problem with high morbidity and mortality. The utilization of Traditional Chinese Medicine shows good prospects in therapy of SAP since it has advantages of more extensive pharmacological effects and fewer adverse effects. In this retrospective study, 38 patients received standardized treatment (control group) and 37 patients received Chinese herbal decoction, Huoxue Qingyi Decoction (HQD group), in addition to standard treatment for SAP. We found that the HQD group had a shorter hospital stay and lower initial expense than the control group (P<0.05). The duration of hyperamylasemia and systemic inflammatory response syndrome (SIRS) were significantly shorter in HQD group (P<0.05). The percentage of patients having any complication was much lower in HQD group than control group (27/38 versus 17/37,P<0.05), especially pancreatic pseudocyst (10/38 versus 2/37,P<0.05). No adverse effect induced by HQD was found. We concluded that the HQD was effective, safe, and economic for reduction of complication, for early recovery from systemic inflammation, and for promoting earlier rehabilitation from SAP.

scholarly journals Comprehensive circRNA-microRNA-mRNA network analysis revealed the novel regulatory mechanism of Trichosporon asahii infection

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Ming-Wang Zhang ◽  
Zhi-Hong Zhu ◽  
Zhi-Kuan Xia ◽  
Xin Yang ◽  
Wan-Ting Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Rna Seq ◽  
Trichosporon Asahii ◽  
Cerna Network ◽  
Pathway Analyses

Abstract Background Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. Methods RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. Results A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. Conclusions These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii-host interactions.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells (huMSCs) Carrying MicroRNA-342 Relieve Protect Severe Acute Pancreatitis Injury (SAP)

2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He
Keyword(s):  
Stem Cells ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Tissue ◽  
Inflammatory Factors ◽  
Control Group ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation Alleviates Acute Pancreatitis Through Inhibiting Inflammation and Promoting Caspase-8 Apoptosis Pathway

2022 ◽  
Vol 12 (5) ◽  
pp. 1034-1039
Author(s):  
Xiaoxiang Wang ◽  
Lan Yu ◽  
Xing Xiong ◽  
Yao Chen ◽  
Bo Men
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Serum Amylase ◽  
Inflammatory Factors ◽  
Control Group ◽  
Caspase 8 ◽  
Apoptosis Pathway ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) are capable of multipolar differentiation and repairing injured tissues. Herein, we aimed to investigate the mechanism by how BMSCs modulate the apoptotic pathway in the acute pancreatitis (AP). In this study, primary BMSCs were cultured and administrated into 10 AP mice while 10 healthy mice were taken as a blank group and 10 AP mice as a control group. The mouse pancreatic tissues were assessed by HE staining and evaluated by pancreatitis score and serum amylase detection. Level of inflammatory factors CRP and TNF-α was measured by ELISA and PIPK1, PIPK3, MLKL and Caspase-8 expression was detected by RT-qPCR and Western blot. The pancreatitis score (7.29±1.36) and the serum amylase score of (453.66±103.67) mu/ml of BMSCs group was significantly higher than that of control group, indicating increased tissue repair after BMSCs treatment. BMSCs group exhibited a higher level of CRP (711.01±115.31) and TNF-α (132.81±22.13) in serum compared to control group (p < 0.05). PIPK1, PIPK3, and MLKL expression in BMSCs group decreased (p < 0.05) whereas Caspase-8 was increased (p < 0.05). On the other hand, BMSCs group presented upregulated PIPK1, PIPK3, and MLKL (p < 0.05) and downregulated Caspase-8 (p < 0.05). In conclusion, BMSCs regulate cell apoptosis by upregulating Caspase-8 expression, and downregulating PIPK1, PIPK3 and MLKL level, thereby alleviating the inflammation in AP.

scholarly journals MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

2020 ◽  
Author(s):  
Lun Wu ◽  
Ying Wei ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Li-Hua Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Enrichment Analysis ◽  
Gene Chip ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Therapeutic Benefits ◽  
Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

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