scholarly journals Two-Way Impacts Between Macrophages on Vascular Endothelium and Characteristics of TCM Syndromes in Dyslipidemic Mice with the Phlegm-Dampness Retention syndrome and the Spleen and Kidney Yang Deficiency syndrome Using RNA-Seq

2021 ◽  
Author(s):  
Jing Chen ◽  
Chao Ye ◽  
Zheng Yang ◽  
Tieshan Wang ◽  
Bing Xu ◽  
...  
Keyword(s):  
Quality Assessment ◽  
The Body ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Test Model ◽  
Biological Processes ◽  
Rna Seq ◽  
Pathogenic Factors ◽  
Kidney Yang Deficiency ◽  
Protective Processes

Abstract Background: ‘Treating the same disease with different methods’ is a Traditional Chinese Medicine (TCM) therapeutic concept. That means although patients are diagnosed with the same disease, they may have different syndromes that require distinct drug administrations. This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia with the Phlegm-Dampness Retention (PDR) syndrome and the Spleen and Kidney Yang Deficiency (SKYD) syndrome using transcriptomic analysis.Methods: Ten ApoE knockout (ApoE-/-) mice were used for the establishment of dyslipidemic disease-syndrome models via multifactor-hybrid modeling, with 5 in the the PDR group and 5 in the SKYD group. Five C57BL/6J mice were employed as normal controls (NC) group. Test model quality. Aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq.Results: ①The quality assessment of the disease-syndrome model showed that TG, TC, and LDL-C levels significantly increased in the PDR and SKYD groups versus the NC group (P < 0.05). Combined with HE staining of aorta, the disease model was successfully established. ②The quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of the PDR syndrome, and mice in the SKYD group had the related manifestations of the SKYD syndrome, indicating that the syndrome models were successfully constructed. ③After comparing the differentially expressed gene (DEG) expressions in macrophages in dyslipidemia mice with different syndromes, 4142 genes were identified with statistical significance (P < 0.05). The Gene Ontology (GO) analysis for the DEGs showed that biological process of difference between PDR group and SKYD group include both adverse and protective processes were included.Conclusion: The DEGs between the PDR syndrome and the SKYD syndrome indicate different biological mechanisms between the onset of the two syndromes. They have distinctive biological processes, including adverse and protective processes, corresponding to the invasion of pathogenic factors into the body and the fight of healthy qi against pathogenic factors, respectively, in the TCM theory. Our results have demonstrated the biological evidence behind ‘treating the same disease with different treatments’ in TCM.

scholarly journals Study on the Effect of Macrophages on Vascular Endothelium in Mice With Different TCM Syndromes of Dyslipidemia and its Biological Basis Based on RNA-Seq Technology

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Chen ◽  
Chao Ye ◽  
Zheng Yang ◽  
Tieshan Wang ◽  
Bing Xu ◽  
...  
Keyword(s):  
Quality Assessment ◽  
Differentially Expressed Genes ◽  
Normal Control ◽  
Normal Control Group ◽  
Differentially Expressed ◽  
Control Group ◽  
Biological Processes ◽  
Rna Seq ◽  
Pathogenic Factors ◽  
Protective Processes

Background: “Treating the same disease with different methods” is a Traditional Chinese medicine (TCM) therapeutic concept suggesting that, while patients may be diagnosed with the same disease, they may also have different syndromes that require distinct drug administrations.Objective: This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia in relation to phlegm–dampness retention (PDR) syndrome and spleen and kidney Yang deficiency (SKYD) syndrome using transcriptomic analysis.Methods: Ten ApoE−/− mice were used for the establishment of dyslipidemic disease–syndrome models via multifactor-hybrid modeling, with five in the PDR group and five in the SKYD group. Additionally, five C57BL/6J mice were employed as a normal control group. Test model-quality aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq.Results: A quality assessment of the disease–syndrome model showed that levels of lipids significantly increased in the PDR and SKYD groups, compared to the normal control group, p &lt; 0.05. Applying, in addition, hematoxylin and eosin staining of aorta, the disease model was also successfully established. A quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of PDR syndrome, and mice in the SKYD group had related manifestations of SKYD syndrome, indicating that the syndrome models were successfully constructed as well. After comparing the differentially expressed gene expressions in macrophages of the dyslipidemic mice with different syndromes, 4,142 genes were identified with statistical significance, p &lt; 0.05. Gene ontology analysis for the differentially expressed genes showed that the biological process of difference between the PDR group and the SKYD group included both adverse and protective processes.Conclusion: The differentially expressed genes between PDR syndrome and SKYD syndrome indicate different biological mechanisms between the onsets of the two syndromes. They have distinctive biological processes, including adverse and protective processes that correspond to the invasion of pathogenic factors into the body and the fight of healthy Qi against pathogenic factors, respectively, according to TCM theory. Our results provide biological evidence for the TCM principle of “treating the same disease with different treatments.”

scholarly journals Transcriptional Regulation of lncRNA Genes by Histone Modification in Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Guoqiang Wan ◽  
Wenyang Zhou ◽  
Yang Hu ◽  
Rui Ma ◽  
Shuilin Jin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Histone Modification ◽  
Noncoding Rnas ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Rna Seq ◽  
Wide Range ◽  
And Control ◽  
Histone Modification Data

Increasing studies have revealed that long noncoding RNAs (lncRNAs) are not transcriptional noise but play important roles in the regulation of a wide range of biological processes, and the dysregulation of lncRNA genes is associated with disease development. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. However, little is known about the roles of lncRNA genes in AD and how the lncRNA genes are transcriptionally regulated. Herein, we analyzed RNA-seq data and ChIP-seq histone modification data from CK-p25 AD model and control mice and identified 72 differentially expressed lncRNA genes, 4,917 differential peaks of H3K4me3, and 1,624 differential peaks of H3K27me3 between AD and control samples, respectively. Furthermore, we found 92 differential peaks of histone modification H3K4me3 are located in the promoter of 39 differentially expressed lncRNA genes and 8 differential peaks of histone modification H3K27me3 are located upstream of 7 differentially expressed lncRNA genes, which suggest that the majority of lncRNA genes may be transcriptionally regulated by histone modification in AD.

scholarly journals Identification of novel mRNAs and lncRNAs associated with mouse experimental colitis and human inflammatory bowel disease

2018 ◽  
Vol 315 (5) ◽  
pp. G722-G733 ◽  
Author(s):  
Carl Robert Rankin ◽  
Evangelos Theodorou ◽  
Ivy Ka Man Law ◽  
Lorraine Rowe ◽  
Efi Kokkotou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Models ◽  
High Throughput ◽  
Bowel Disease ◽  
Noncoding Rnas ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Rna Seq ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a complex disorder that is associated with significant morbidity. While many recent advances have been made with new diagnostic and therapeutic tools, a deeper understanding of its basic pathophysiology is needed to continue this trend toward improving treatments. By utilizing an unbiased, high-throughput transcriptomic analysis of two well-established mouse models of colitis, we set out to uncover novel coding and noncoding RNAs that are differentially expressed in the setting of colonic inflammation. RNA-seq analysis was performed using colonic tissue from two mouse models of colitis, a dextran sodium sulfate-induced model and a genetic-induced model in mice lacking IL-10. We identified 81 coding RNAs that were commonly altered in both experimental models. Of these coding RNAs, 12 of the human orthologs were differentially expressed in a transcriptomic analysis of IBD patients. Interestingly, 5 of the 12 of human differentially expressed genes have not been previously identified as IBD-associated genes, including ubiquitin D. Our analysis also identified 15 noncoding RNAs that were differentially expressed in either mouse model. Surprisingly, only three noncoding RNAs were commonly dysregulated in both of these models. The discovery of these new coding and noncoding RNAs expands our transcriptional knowledge of mouse models of IBD and offers additional targets to deepen our understanding of the pathophysiology of IBD. NEW & NOTEWORTHY Much of the genome is transcribed as non-protein-coding RNAs; however, their role in inflammatory bowel disease is largely unknown. This study represents the first of its kind to analyze the expression of long noncoding RNAs in two mouse models of inflammatory bowel disease and correlate them to human clinical samples. Using high-throughput RNA-seq analysis, we identified new coding and noncoding RNAs that were differentially expressed such as ubiquitin D and 5730437C11Rik.

scholarly journals Transcriptomic analyses suggest a dominant role of insulin in the coordinated control of energy metabolism and ureagenesis in goat liver

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhongyan Lu ◽  
Zhihui Xu ◽  
Zanming Shen ◽  
Hong Shen ◽  
Jörg R. Aschenbach
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Signaling Pathway ◽  
Dominant Role ◽  
Coordinated Control ◽  
The Body ◽  
Differentially Expressed ◽  
Acid Oxidation ◽  
Rna Seq

Abstract Background The ureagenesis plays a central role in the homeostatic control of nitrogen metabolism. This process occurs in the liver, the key metabolic organ in the maintenance of energy homeostasis in the body. To date, the understanding of the influencing factors and regulators of ureagenesis in ruminants is still poor. The aim of this study was to investigate the relationship between energy metabolism and ureagenesis and detect the direct regulators of ureagenesis in the liver by using RNA-seq technology. Results Eighteen four-month-old male goats were divided into two groups randomly and received a diet containing 10% (LNFC group, n = 9) or 30% non-fiber carbohydrate (MNFC group, n = 9), respectively, for four weeks. The global gene expression analysis of liver samples showed that, compared with a LNFC diet, the MNFC diet promoted the expression of genes required for synthesis of fatty acid and glycerol, whereas it suppressed those related to fatty acid oxidation, gluconeogenesis from amino acids and ureagenesis. Additionally, gene expression for rate-limiting enzymes of ureagenesis were highly correlated to the gene expression of key enzymes of both fatty acid synthesis and glycerol synthesis (Spearman correlation coefficient > 0.8 and p < 0.05). In the differentially expressed signaling pathways related to the endocrine system, the MNFC diet activated the insulin and PPAR signaling pathway, whereas it suppressed the leptin-JAK/STAT signaling pathway, compared with the LNFC diet. Reverse transcription quantitative PCR analyses of 40 differentially expressed genes confirmed the RNA-seq results (R2 = 0.78). Conclusion Our study indicated that a dietary NFC-induced increase of energy supply promoted lipid anabolism and decreased ureagenesis in the caprine liver. By combining our results with previously published reports, insulin signaling can be suggested to play the dominant role in the coordinated control of hepatic energy metabolism and ureagenesis.

Transcriptome Analysis Reveals Candidate Genes During the Prepupal-pupal Transition in the Oriental Armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

2020 ◽  
Author(s):  
Peirong Li ◽  
Xinru Li ◽  
Wei Wang ◽  
Xiaoling Tan ◽  
Xiaoqi Wang ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Transcriptome Assembly ◽  
Insect Pest ◽  
Pupal Stage ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Rna Seq ◽  
Mythimna Separata ◽  
Expression Levels ◽  
Lepidoptera Noctuidae

Abstract Background Metamorphosis ensures the transformation of a larva of the holometabolous insects into a reproductive adult through a transitory pupal stage. Understanding how changes in expression levels of genes during the prepupal-pupal transition will inform us of how the metamorphosis arises. Results In this study, mature larvae (ML), wandering (W), 1 day (P1), 5 days (P5), and 10 days (P10) after pupation of the Mythimna separata (Walker), a notorious migratory pest of agricultural crops, were selected, forming five groups. RNA-Seq revealed that the draft transcriptome assembly contained 140562 contigs, and more than half (74,059) were similar to sequence at NCBI (e value < e− 3), including 22884, 23534, 26643, and 33238 differentially expressed genes (DEGs) in ML vs W, W vs P1, P1 vs P5, and P5-vs-P10, respectively. Comparative transcriptomics revealed the enrichment of biological processes related to the membrane and integral component of membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, enabled us to delineate and partially validate the metabolic pathway in M. separata. Of these DEGs, 33 CP, 18 20E, and 7 JH genes were differentially expressed across the developmental stages. Correlation analysis uncovered that the relative expression levels of 10 selected CP, 20E, and JH-related genes obtained by real-time PCR quantitative (RT-qPCR) matched well with their FPKM values derived from RNA-seq. Conclusions The data gave here represent an important first step to uncover the molecular mechanism of metamorphosis in M. separata, which also provide valuable information for manipulation of insect development and metamorphosis using the obtained DEGs as targets and broaden the applications of available tools for insect pest control.

scholarly journals Differentially expressed lncRNAs in liver tissues of TX mice with hepatolenticular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Zhang ◽  
Ying Ma ◽  
Daojun Xie ◽  
Yuancheng Bao ◽  
Wenming Yang ◽  
...  
Keyword(s):  
Expression Profiles ◽  
The Body ◽  
Signalling Pathway ◽  
Differentially Expressed ◽  
Inherited Disease ◽  
Rna Seq ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling ◽  
Regulation Network ◽  
Almost All

AbstractWilson's Disease (WD), an ATP7B-mutated inherited disease that affects copper transport, is characterised by liver and nervous system manifestations. Long non-coding (ln-c) RNAs are widely involved in almost all physiological and pathological processes in the body, and are associated with numerous diseases. The present study aimed to elucidate the lncRNA-mRNA regulation network in a TX WD mouse model using RNA sequencing (RNA-seq). lncRNA expression profiles were screened using RNA-seq and real-time polymerase chain reaction, and differentially expressed lncRNAs and mRNAs were identified. To analyse the biological functions and pathways for the differentially expressed mRNAs, gene ontology and pathway enrichment analyses were performed. A significantly correlated lncRNA-mRNA relationship pair was calculated by CNC analysis to construct differential lncRNA and mRNA co-expression networks. A total of 2564 significantly up-regulated and 1052 down-regulated lncRNAs, and 1576 up-regulated and 297 down-regulated mRNAs, were identified. These genes were found to be associated with key processes such as apoptosis, and KEGG analysis revealed enrichment in the drug metabolism-cytochrome P450 pathway, PPAR signalling pathway, Notch signalling pathway, and MAPK signalling pathway. The identified differential lncRNAs may be involved in the pathogenesis and development of WD liver injury.

scholarly journals Transcriptome Profile Alterations with Carbon Nanotubes, Quantum Dots, and Silver Nanoparticles: A Review

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 794
Author(s):  
Cullen Horstmann ◽  
Victoria Davenport ◽  
Min Zhang ◽  
Alyse Peters ◽  
Kyoungtae Kim
Keyword(s):  
Carbon Nanotubes ◽  
Quantum Dots ◽  
High Throughput Sequencing ◽  
The Body ◽  
Rna Seq ◽  
Mechanisms Of Toxicity ◽  
Promising Tool ◽  
Engineered Nanomaterial ◽  
Next Generation Sequencing Ngs ◽  
Transcriptomic Changes

Next-generation sequencing (NGS) technology has revolutionized sequence-based research. In recent years, high-throughput sequencing has become the method of choice in studying the toxicity of chemical agents through observing and measuring changes in transcript levels. Engineered nanomaterial (ENM)-toxicity has become a major field of research and has adopted microarray and newer RNA-Seq methods. Recently, nanotechnology has become a promising tool in the diagnosis and treatment of several diseases in humans. However, due to their high stability, they are likely capable of remaining in the body and environment for long periods of time. Their mechanisms of toxicity and long-lasting effects on our health is still poorly understood. This review explores the effects of three ENMs including carbon nanotubes (CNTs), quantum dots (QDs), and Ag nanoparticles (AgNPs) by cross examining publications on transcriptomic changes induced by these nanomaterials.

scholarly journals OP0021 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN EARLY RHEUMATOID ARTHRITIS PATIENTS RESPONDING TO TOCILIZUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Gene Ontology ◽  
Regulatory T Cells ◽  
Early Rheumatoid Arthritis ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Double Blind

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared

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