The Network Regulation of Yiqi Jiedu Formulae Against Cerebral Ischemia Based on Central-periphery Inflammation System

Abstract Background:Connections between inflammation and gene-network regulation are suggested important in understanding the therapeutic target of stroke and in illuminating underlying mechanism. However, studies on the establishment of network relating with inflammation during stroke process are still in their early stages. Results:Herein, Message RNA chips were used to scan whole genome of stroke-model rats. We selected the inflammation genes from the whole mRNA expression results. And after a series of analysis, we tried to establish a central-peripheral inflammation network on MCAO rice which then be used as disease background network for our further study. As for the background network, we found and verified some key node genes (also named as hub-genes), which are joint in several inflammation and immune related pathways. While mapping genes from treatment group to the background network, we found the promising target genes of Yiqi Jiedu formulae, a traditional chinese prescription used in clinic for stroke, which might give an explanation to the common characteristic about TCM treatment called PK-PD inconsistent. Conclusions:The mRNA network-based analysis provides a foundation for elucidating inflammation-disease associations, a rather promising insight into the inflammation progress during stroke and a novel strategy to reveal the underlying mechanism of TCM.

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Network using Michaelis–Menten kinetics: constructing an algorithm to find target genes from expression data

Journal of Complex Networks ◽

10.1093/comnet/cnz016 ◽

2019 ◽

Author(s):

Mythreye Krishnan ◽

Michael Small ◽

Anthony Bosco ◽

Thomas Stemler

Keyword(s):

Gene Network ◽

Target Genes ◽

Underlying Mechanism ◽

Relevant Information ◽

Complex Data ◽

Expression Data ◽

Gene Expression Data Analysis ◽

Biologically Relevant ◽

Cell Responses ◽

Network Patterns

Abstract The most challenging aspect of gene expression data analysis is to process the large and complex data using mathematical models and find biologically relevant information that gives insight to the underlying mechanism. We derived a simple ordinary differential equation-based model using Michaelis–Menten Kinetics to process the microarray data. Different biological systems of experimental rhinovirus infection in humans, atopic CD4 T cell responses in allergens and responses to cancer immunotherapy in mice have been studied. The resulting analysis extracts highly linked target genes, the changes in which might cause changes in the other genes, in other words, potential targets for modulating gene network patterns and emergent biological phenotypes. We illustrate the application of the algorithm to identify novel targets in addition to previously identified targets in different experimental contexts.

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Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth

Molecular Cancer ◽

10.1186/s12943-019-1075-2 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 11

Author(s):

Liang-qi Cao ◽

Xue-wei Yang ◽

Yu-bin Chen ◽

Da-wei Zhang ◽

Xiao-Feng Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Target Genes ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Reporter Assays ◽

Important Means ◽

And Migration ◽

Insight Into ◽

Hcc Cells

Abstract Background As an important means of communication, exosomes play an important role in the development of hepatocellular carcinoma (HCC). Methods Bioinformatics analysis, dual-luciferase reporter assays, methylation-specific quantitative PCR, and ChIP-PCR analysis were used to gain insight into the underlying mechanism of miR-21 in HCC. Results The detection of miRNAs in exosomes of HCC showed that miR-21 expression in exosomes was positively correlated with the expression level of miR-21 in cells and negatively correlated with the expression of its target genes PTEN, PTENp1 and TETs. HCC cell-derived exosomes could increase miR-21 and p-Akt expression in HCC cells and downregulate the expression of PTEN, PTENp1 and TETs. MiR-21 inhibitors or PTENp1 overexpression vectors could weaken the effect of the abovementioned exosomes and simultaneously weaken their role in promoting cell proliferation and migration and inhibiting apoptosis. Further studies showed that miR-21 not only directly regulated the expression of PTEN, PTENp1 and TETs but also increased the methylation level of the PTENp1 promoter by regulating the expression of TETs, thereby inhibiting the expression of PTENp1 and further downregulating the expression of PTEN. Conclusions Exosomal miR-21 can regulate the expression of the tumor suppressor genes PTEN and PTENp1 in various ways and affect the growth of HCC cells.

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Analysis of key genes and pathways associated with the pathogenesis of intervertebral disc degeneration

10.21203/rs.3.rs-32769/v2 ◽

2020 ◽

Author(s):

Shiyu Hu ◽

Yucheng Fu ◽

Bin Yan ◽

Zhe Shen ◽

Tao Lan

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Target Genes ◽

Underlying Mechanism ◽

Hub Genes ◽

Protein Protein Interaction ◽

Matrix Organization ◽

Underlying Mechanisms ◽

Upregulated Genes

Abstract Background: Intervertebral disc degeneration (IDD) is widely known as a main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. This study aims to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD.Material/Methods: The gene expression data of GSE23130 was downloaded and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. Also, Protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module.Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs mainly enriched in regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most of DEGs were primarily enriched in PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1.Conclusions: In summary, key candidate genes and pathway were identified by using integrated bioinformatics analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

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Analysis of key genes and pathways associated with pathogenesis of intervertebral disc degeneration

10.21203/rs.3.rs-32769/v1 ◽

2020 ◽

Author(s):

Shiyu Hu ◽

Yucheng Fu ◽

Bin Yan ◽

Zhe Shen ◽

Tao Lan

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Target Genes ◽

Underlying Mechanism ◽

Hub Genes ◽

Protein Protein Interaction ◽

Matrix Organization ◽

Underlying Mechanisms ◽

Upregulated Genes

Abstract Background: Intervertebral disc degeneration (IDD) is widely known as a main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. The aim of this study is to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD. Material/Methods: The gene expression data of GSE23130 was downloaded and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. In addition, Protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module. Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs mainly enriched in regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most of DEGs were primarily enriched in PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1. Conclusions: In summary, key candidate genes and pathway were identified by using integrated bioinformatics analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

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Identification of differentially expressed genes in asthma by bioinformatics analysis

Medical Research ◽

10.6913/mrhk.202106_3(2).0004 ◽

2021 ◽

Vol 3 (2) ◽

pp. 28-36

Author(s):

Zhaojun Wang ◽

Zhifeng Mo ◽

Hongsen Liang ◽

Qiwei Zhang ◽

Wei Li ◽

...

Keyword(s):

Regulatory Networks ◽

Target Genes ◽

Microarray Dataset ◽

Underlying Mechanism ◽

Gene Expression Omnibus ◽

The Novel ◽

Hub Genes ◽

Protein Protein Interaction ◽

Healthy Donors

Objective Asthma is a common inflammatory disease of the airway, and its underlying mechanism is complex. The role of microRNAs (miRNAs) in asthma is unclear. The present study aimed to investigate miRNA-mRNA regulatory networks underlying asthma. Methods One microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differential expression of miRNAs (DEMs) was identified in bronchial epithelial cells (BECs) isolated from healthy donors and patients with asthma. MiRTarBase, mirDIP, and miRDB were used to predict target genes, followed by protein-protein interaction (PPI) network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Ontology (GO) analysis; cytoHubba was used to predict the important nodes in the network. The miRNA-hub genes sub-network of interest was determined. Results This study constructed an asthma-associated miRNA-mRNA network, in which seven key miRNAs and 10 hub genes were identified. Conclusions The novel miRNAs and hub genes identified in the present study could be potential diagnostic and treatment biomarkers for asthma.

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What Can Economists Contribute to the Common Good Tradition?

10.1093/oso/9780190670054.003.0003 ◽

2017 ◽

Cited By ~ 1

Author(s):

Andrew M. Yuengert

Keyword(s):

Common Good ◽

Common Pool Resources ◽

Economic Approach ◽

Public And Private ◽

Private Provision ◽

The Public ◽

The Common Good ◽

The Common ◽

The Individual ◽

Insight Into

Although most economists are skeptical of or puzzled by the Catholic concept of the common good, a rejection of the economic approach as inimical to the common good would be hasty and counterproductive. Economic analysis can enrich the common good tradition in four ways. First, economics embodies a deep respect for economic agency and for the effects of policy and institutions on individual agents. Second, economics offers a rich literature on the nature of unplanned order and how it might be shaped by policy. Third, economics offers insight into the public and private provision of various kinds of goods (private, public, common pool resources). Fourth, recent work on the development and logic of institutions and norms emphasizes sustainability rooted in the good of the individual.

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TUP1, CPH1 and EFG1 Make Independent Contributions to Filamentation in Candida albicans

Genetics ◽

10.1093/genetics/155.1.57 ◽

2000 ◽

Vol 155 (1) ◽

pp. 57-67 ◽

Cited By ~ 4

Author(s):

Burkhard R Braun ◽

Alexander D Johnson

Keyword(s):

Candida Albicans ◽

Environmental Conditions ◽

Target Genes ◽

Single Cells ◽

Filamentous Growth ◽

Surface Proteins ◽

Pathway Expression ◽

Separate Pathway ◽

The Common ◽

Growth Pathway

Abstract The common fungal pathogen, Candida albicans, can grow either as single cells or as filaments (hyphae), depending on environmental conditions. Several transcriptional regulators have been identified as having key roles in controlling filamentous growth, including the products of the TUP1, CPH1, and EFG1 genes. We show, through a set of single, double, and triple mutants, that these genes act in an additive fashion to control filamentous growth, suggesting that each gene represents a separate pathway of control. We also show that environmentally induced filamentous growth can occur even in the absence of all three of these genes, providing evidence for a fourth regulatory pathway. Expression of a collection of structural genes associated with filamentous growth, including HYR1, ECE1, HWP1, ALS1, and CHS2, was monitored in strains lacking each combination of TUP1, EFG1, and CPH1. Different patterns of expression were observed among these target genes, supporting the hypothesis that these three regulatory proteins engage in a network of individual connections to downstream genes and arguing against a model whereby the target genes are regulated through a central filamentous growth pathway. The results suggest the existence of several distinct types of filamentous forms of C. albicans, each dependent on a particular set of environmental conditions and each expressing a unique set of surface proteins.

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EGCG modulates PKD1 and ferroptosis to promote recovery in ST rats

Translational Neuroscience ◽

10.1515/tnsci-2020-0119 ◽

2020 ◽

Vol 11 (1) ◽

pp. 173-181 ◽

Cited By ~ 1

Author(s):

Jianjun Wang ◽

Ying Chen ◽

Long Chen ◽

Yanzhi Duan ◽

Xuejun Kuang ◽

...

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Antioxidant Properties ◽

Underlying Mechanism ◽

Maximal Effect ◽

Loss Of Function ◽

Protein Kinase D1 ◽

Erk Phosphorylation ◽

Cord Injury ◽

Novel Strategy

AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.

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ATRT-03. IDENTIFICATION OF microRNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR

Neuro-Oncology ◽

10.1093/neuonc/noaa222.003 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii275-iii276

Author(s):

Yang Zhang ◽

Jianguo Xu

Keyword(s):

Target Genes ◽

Kinase Inhibitor ◽

Therapeutic Agents ◽

Rhabdoid Tumor ◽

Janus Kinase ◽

Prognostic Biomarkers ◽

Atypical Teratoid Rhabdoid Tumor ◽

Overlapping Genes ◽

Hub Genes ◽

Atypical Teratoid

Abstract BACKGROUND MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. METHODS Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. RESULTS A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). CONCLUSION In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.

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Reducing the metabolic energy of walking and running using an unpowered hip exoskeleton

Journal of NeuroEngineering and Rehabilitation ◽

10.1186/s12984-021-00893-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Tiancheng Zhou ◽

Caihua Xiong ◽

Juanjuan Zhang ◽

Di Hu ◽

Wenbin Chen ◽

...

Keyword(s):

Energy Consumption ◽

Design Method ◽

Metabolic Cost ◽

Metabolic Energy ◽

Spring Stiffness ◽

Spatiotemporal Parameters ◽

The Common ◽

Hip Flexion ◽

Optimal Stiffness ◽

Insight Into

Abstract Background Walking and running are the most common means of locomotion in human daily life. People have made advances in developing separate exoskeletons to reduce the metabolic rate of walking or running. However, the combined requirements of overcoming the fundamental biomechanical differences between the two gaits and minimizing the metabolic penalty of the exoskeleton mass make it challenging to develop an exoskeleton that can reduce the metabolic energy during both gaits. Here we show that the metabolic energy of both walking and running can be reduced by regulating the metabolic energy of hip flexion during the common energy consumption period of the two gaits using an unpowered hip exoskeleton. Methods We analyzed the metabolic rates, muscle activities and spatiotemporal parameters of 9 healthy subjects (mean ± s.t.d; 24.9 ± 3.7 years, 66.9 ± 8.7 kg, 1.76 ± 0.05 m) walking on a treadmill at a speed of 1.5 m s−1 and running at a speed of 2.5 m s−1 with different spring stiffnesses. After obtaining the optimal spring stiffness, we recruited the participants to walk and run with the assistance from a spring with optimal stiffness at different speeds to demonstrate the generality of the proposed approach. Results We found that the common optimal exoskeleton spring stiffness for walking and running was 83 Nm Rad−1, corresponding to 7.2% ± 1.2% (mean ± s.e.m, paired t-test p < 0.01) and 6.8% ± 1.0% (p < 0.01) metabolic reductions compared to walking and running without exoskeleton. The metabolic energy within the tested speed range can be reduced with the assistance except for low-speed walking (1.0 m s−1). Participants showed different changes in muscle activities with the assistance of the proposed exoskeleton. Conclusions This paper first demonstrates that the metabolic cost of walking and running can be reduced using an unpowered hip exoskeleton to regulate the metabolic energy of hip flexion. The design method based on analyzing the common energy consumption characteristics between gaits may inspire future exoskeletons that assist multiple gaits. The results of different changes in muscle activities provide new insight into human response to the same assistive principle for different gaits (walking and running).

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