NR4A3 and CCL20 clusters dominate the genetic networks in CD146+ blood cells during acute myocardial infarction in humans

Abstract Background CD146 is a tight junction-associated molecule involved in maintaining endothelial barrier, and balancing immune–inflammation response, in cardiovascular disease. Notably, peripheral CD146+ cells significantly upsurge under vessel dyshomeostasis such as acute myocardial injury (AMI), appearing to be a promising therapeutic target. In this study, with a new view of gene correlation, we aim at deciphering the complex underlying mechanism of CD146+ cells’ impact in the development of AMI. Methods Transcription dataset GSE 66,360 of CD146+ blood cells from clinical subjects was downloaded from NCBI. Pearson networks were constructed and the clustering coefficients were calculated to disclose the differential connectivity genes (DCGs). Analysis of gene connectivity and gene expression were performed to reveal the hub genes and hub gene clusters followed by gene enrichment analysis. Results and conclusions Among the total 23,520 genes, 27 genes out of 126 differential expression genes were identified as DCGs. These DCGs were found in the periphery of the networks under normal condition, but transferred to the functional center after AMI. Moreover, it was revealed that DCGs spontaneously crowded together into two functional models, CCL20 cluster and NR4A3 cluster, influencing the CD146-mediated signaling pathways during the pathology of AMI for the first time.

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NR4A3 and CCL20 Clusters Dominate the Dynamic Gene Network of Peripheral CD146+ Blood Cells in the Early Stage of Acute Myocardial Infarction in Human.

10.21203/rs.3.rs-133154/v1 ◽

2020 ◽

Author(s):

Yanhui Wang ◽

Chenxin Li ◽

Jessica M Stephenson ◽

Sean P Marrelli ◽

Yanming Kou ◽

...

Keyword(s):

Blood Cells ◽

Early Stage ◽

Enrichment Analysis ◽

Central Position ◽

Hub Genes ◽

Functional Models ◽

Differential Expression Genes ◽

Acute Myocardial Injury ◽

Gene Correlation ◽

First Time

Abstract Background: CD146 is a tight junction associated molecule involved in maintaining endothelial barrier and balancing immune-inflammation response in cardiovascular disease. Notably, the peripheral CD146+ cells significantly upsurge under vessel dyshomeostasis like acute myocardial injury (AMI), appearing to be promising therapeutic targets. In this study, in a new view of gene correlation, we aim at deciphering the underlying complex mechanism of CD146+ cells in the development of AMI. Methods: Transcription dataset GSE 66360 of CD146+ blood cells from clinical subjects were downloaded from NCBI. Pearson networks were constructed and the clustering coefficients were calculated to disclose the differential connectivity genes (DCGs). Analysis of gene connectivity and gene expression was performed to reveal the hub genes and hub genes clusters followed by gene enrichment analysis. Results and Conclusions: Among the total 23520 genes, 27 genes out of 126 differential expression genes are identified as DCGs. Those DCGs normally stay in the peripheral of networks while transfer to the functional central position under AMI situation. Moreover, it is revealed that DCGs spontaneously crowd together into two functional models, CCL20 cluster and NR4A3 cluster, influencing the CD146-mediated signaling pathways during the pathology of AMI for the first time.

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The Key Candidate Genes in Tubulointerstitial Injury of Chronic Kidney Diseases (CKD) Patients as Determined by Bioinformatic Analysis

10.21203/rs.2.12859/v1 ◽

2019 ◽

Author(s):

Wanpeng Wang ◽

Jianxiao Shen ◽

Yan Pan ◽

Chaojun Qi ◽

Senlin Liang ◽

...

Keyword(s):

Kidney Diseases ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Expression Data ◽

Tubulointerstitial Injury ◽

Hub Genes ◽

Online Tool ◽

Differential Expression Genes ◽

Gene Correlation ◽

The Relationship

Abstract Background: Tubulointerstitial injury (TIL) is common in chronic kidney disease (CKD), which in turn, leads to loss of renal function. The aims of present study were to screen critical genes with tubulointerstitial lesion in CKD by weighted gene correlation network analysis (WGCNA). Methods: GSE104954 gene expression data downloaded from GEO database were used for analysis for differential expression genes(DEGs); Meanwhile, 90 expression data of tubulointerstitial samples in GSE47185 combined with clinic information were applied to WGCNA. According to the enrichment analysis and relationship with estimated glomerular filtration rate (eGFR), the eGFR-associated modules were defined, and the hub gene is selected according to the average intramodular connectivity (Kwithin); Clinical data from Nephroseq were obtained to further validate the relationship between CKD and hub genes. Results: Totally 294 DEGs were screened. Using the WGCNA, we identified 15 co-expressed modules, the blue, brown and yellow modules exhibited strongly association with eGFR, and were significantly enriched in several signaling pathways that have been reported involved in pathogenesis of CKD. Furthermore, it was found that the 4 genes (PLG, ITGB2, CTSS and CCL5) was one of the DEGs which also be identified as hub genes according to Kwithin. Finally, the Nephroseq online tool showed that the tubulointerstitial expression levels of PLG significantly positively correlated with the eGFR, while ITGB2, CTSS and CCL5 connected negatively to the eGFR. Conclusion: WGCNA is an efficient approach to system biology. By this procedure, the present study improved the understanding of the transcriptome status of renal tubulointerstitial injury in CKD.

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The Key Candidate Genes in Tubulointerstitial Injury of Chronic Kidney Diseases (CKD) Patients as Determined by Bioinformatic Analysis

10.21203/rs.2.12859/v2 ◽

2019 ◽

Author(s):

Wanpeng Wang ◽

Jianxiao Shen ◽

Yan Pan ◽

Chaojun Qi ◽

Senlin Liang ◽

...

Keyword(s):

Kidney Diseases ◽

Enrichment Analysis ◽

Bioinformatic Analysis ◽

Expression Data ◽

Tubulointerstitial Injury ◽

Hub Genes ◽

Online Tool ◽

Differential Expression Genes ◽

Gene Correlation ◽

The Relationship

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Gene co-expression analyses of health(span) across multiple species

10.1101/2021.04.08.439030 ◽

2021 ◽

Author(s):

Steffen Möller ◽

Nadine Saul ◽

Israel W. Barrantes ◽

András Gézsi ◽

Michael Walter ◽

...

Keyword(s):

Meta Analysis ◽

Enrichment Analysis ◽

Gene Clusters ◽

Hub Genes ◽

Health Span ◽

Network Analyses ◽

Health Related ◽

Gene Correlation ◽

The Cross ◽

Multiple Species

Health(span)-related gene clusters/modules were recently identified based on knowledge about the cross-species genetic basis of health, to interpret transcriptomic datasets describing health-related interventions. However, the cross-species comparison of health-related observations reveals a lot of heterogeneity, not least due to widely varying health(span) definitions and study designs, posing a challenge for the exploration of conserved healthspan modules and, specifically, their transfer across species. To improve the identification and exploration of conserved/transferable healthspan modules, here we apply an established workflow based on gene co-expression network analyses employing GEO/ArrayExpress data for human and animal models, and perform a comprehensive meta-analysis of the resulting modules related to health(span), yielding a small set of health(span) candidate genes, backed by the literature. For each experiment, WGCNA (weighted gene correlation network analysis) was thus used to infer modules of genes which correlate in their expression with a "health phenotype score" and to determine the most-connected (hub) genes for each such module, and their interactions. After mapping these hub genes to their human orthologs, 12 health(span) genes were identified in at least two species (ACTN3, ANK1, MRPL18, MYL1, PAXIP1, PPP1CA, SCN3B, SDCBP, SKIV2L, TUBG1, TYROBP, WIPF1), for which enrichment analysis by g:profiler finds an association with actin filament-based movement and associated organelles as well as muscular structures. We conclude that a meta-study of hub genes from co-expression network analyses for the complex phenotype health(span), across multiple species, can yield molecular-mechanistic insights and can direct experimentalists to further investigate the contribution of individual genes and their interactions to health(span).

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SCANNING ELECTRON MICROSCOPE: POSSIBILITIES FOR STUDYING KIDNEY DISEASES

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-12-176-182 ◽

2020 ◽

pp. 176-182

Author(s):

Mamaeva S.N. ◽

Vinokurov R.R. ◽

Munkhalova Ya.A. ◽

Dyakonova D.P. ◽

Platonova V.A. ◽

...

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Electron Microscope ◽

Scanning Electron Microscope ◽

Red Blood Cells ◽

Blood Cells ◽

Filtration Rate ◽

Kidney Diseases ◽

First Time ◽

Scanning Electron

Currently, due to the intensive development of high-tech science-intensive medical and research devices, more and more attention is paid to the development of diagnostics of rare and difficult to diagnose diseases. It is known that among numerous nephropathies, hematuria may be the only symptom of kidney and urinary tract diseases, which complicates their diagnosis and treatment. In order to develop new approaches for the diagnosis of nephropathies, the authors have been studying the morphology of red blood cells in the blood and urine of children and adults using a scanning electron microscope for several years. The paper presents the results of studies of children with various kidney diseases, including IgA-nephropathy, and chronic glomerulonephritis. Scanning electron microscopy was used for the first time to detect nanoparticles on the surface of red blood cells, the size of which is comparable to the size of viruses, which became the basis for one of the authors ' assumptions, namely, the possible transport of certain types of viruses by red blood cells. Thus, some kidney diseases could be considered virus-associated. This paper presents for the first time the results of determining the glomerular filtration rate of both kidneys separately in the study of separate kidney function and of the study of urine smears obtained during catheterization of the ureters in patients with hydronephrosis of one of the kidneys by scanning electron microscopy. As in previous studies, nanoparticles were found on the surface of red blood cells, which leads to the conclusion about the possible viral nature of the disease of the considered patient. In addition, smear images obtained using a microscope showed a significant difference in the elements of the right and left kidneys urine, which did not contradict the data on the study of glomerular filtration rate. According to the authors, the capabilities of the scanning electron microscope can be applied in fundamental research of kidney diseases at the cellular and molecular levels, forming new ideas about their origin, as well as on the basis of which new methods of non-invasive diagnostics can be built.

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Biosynthetic strategies for tetramic acid formation

Natural Product Reports ◽

10.1039/d0np00099j ◽

2021 ◽

Author(s):

Xuhua Mo ◽

Tobias A. M. Gulder

Keyword(s):

Molecular Mechanism ◽

Gene Clusters ◽

Acid Formation ◽

Biosynthetic Gene ◽

Tetramic Acid ◽

Biosynthetic Gene Clusters ◽

The Individual ◽

First Time ◽

Acid Unit

Over 30 biosynthetic gene clusters for natural tetramate have been identified. This highlight reviews the biosynthetic strategies for formation of tetramic acid unit for the first time, discussing the individual molecular mechanism in detail.

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Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01878-x ◽

2021 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Weiqiang Huang ◽

Longshan Zhang ◽

Mi Yang ◽

Xixi Wu ◽

Xiaoqing Wang ◽

...

Keyword(s):

Dna Damage ◽

Nasopharyngeal Carcinoma ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Gene Set Enrichment Analysis ◽

Cancer Associated Fibroblasts ◽

Western Blot Assay ◽

Damage Level ◽

Radiation Resistant

Abstract Background Irradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy. Methods Fibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA and FAP. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay and γ-H2AX foci assay were used to measure DNA damage level. Protein expression was detected by western blot assay. In vivo experiment was performed subcutaneously. Results We found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties. Conclusions Together, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.

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lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22031407 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1407

Author(s):

Hongxia Liu ◽

Wang Zheng ◽

Qianping Chen ◽

Yuchuan Zhou ◽

Yan Pan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Malignant Tumors ◽

Underlying Mechanism ◽

Mtor Pathway ◽

Rna Seq ◽

Cellular Autophagy ◽

First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

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Uncovering Statistical Links Between Gene Expression and Structural Connectivity Patterns in the Mouse Brain

Neuroinformatics ◽

10.1007/s12021-021-09511-0 ◽

2021 ◽

Author(s):

Nestor Timonidis ◽

Alberto Llera ◽

Paul H. E. Tiesinga

Keyword(s):

Gene Expression ◽

Mouse Brain ◽

Structural Connectivity ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Synaptic Function ◽

Reticular Nucleus ◽

Sources Of Information ◽

Independent Components ◽

Brain Connectome

AbstractFinding links between genes and structural connectivity is of the utmost importance for unravelling the underlying mechanism of the brain connectome. In this study we identify links between the gene expression and the axonal projection density in the mouse brain, by applying a modified version of the Linked ICA method to volumetric data from the Allen Institute for Brain Science for identifying independent sources of information that link both modalities at the voxel level. We performed separate analyses on sets of projections from the visual cortex, the caudoputamen and the midbrain reticular nucleus, and we determined those brain areas, injections and genes that were most involved in independent components that link both gene expression and projection density data, while we validated their biological context through enrichment analysis. We identified representative and literature-validated cortico-midbrain and cortico-striatal projections, whose gene subsets were enriched with annotations for neuronal and synaptic function and related developmental and metabolic processes. The results were highly reproducible when including all available projections, as well as consistent with factorisations obtained using the Dictionary Learning and Sparse Coding technique. Hence, Linked ICA yielded reproducible independent components that were preserved under increasing data variance. Taken together, we have developed and validated a novel paradigm for linking gene expression and structural projection patterns in the mouse mesoconnectome, which can power future studies aiming to relate genes to brain function.

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Network Pharmacology-Based Strategy for the Investigation of the Anti-Osteoporosis Effects and Underlying Mechanism of Zhuangguguanjie Formulation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.727808 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wang Gong ◽

Xingren Chen ◽

Tianshu Shi ◽

Xiaoyan Shao ◽

Xueying An ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Mass ◽

Signaling Pathway ◽

Osteoclast Differentiation ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Network Pharmacology ◽

Biological Processes

As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug–disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified in vitro. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug–disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments in vitro validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.

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