Cardiovascular Risk After SARS-CoV-2 Infection Is Mediated by IL18/IL18R1/HIF-1 Signaling Pathway Axis

ObjectivesCurrently, cardiovascular risk associated with COVID-19 has been brought to people’s attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data.MethodologyWeighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm.ResultsHIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation.ConclusionsThe IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection

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CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-9-21-25 ◽

2020 ◽

pp. 21-25

Author(s):

Tupitsyn V.V. ◽

Bataev Kh.M. ◽

Men’shikova A.N. ◽

Godina Z.N.

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Heart Disease ◽

Cardiovascular Risk ◽

Digestive System ◽

Control Group ◽

Study Group ◽

Type I ◽

Internal Organs ◽

History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

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Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus

Current Proteomics ◽

10.2174/1570164617999200728192812 ◽

2020 ◽

Vol 17 ◽

Author(s):

Qian Lu ◽

Hai-Zhu Xing ◽

Nian-Yun Yang

Keyword(s):

Insulin Resistance ◽

Liver Injury ◽

Protein Expression ◽

Signaling Pathway ◽

Proteomic Analysis ◽

Acute Liver Injury ◽

Liver Cells ◽

Differentially Expressed ◽

Liver Protein ◽

Differentially Expressed Proteins

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage

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Identification of key mRNAs and lncRNAs involved in the effects of anti-TWEAK on Osteosarcoma

Current Bioinformatics ◽

10.2174/1574893615999200626191405 ◽

2020 ◽

Vol 15 ◽

Author(s):

Mingxuan Yang ◽

Liangtao Zhao ◽

Xuchang Hu ◽

Haijun Feng ◽

Xuewen Kang

Keyword(s):

Dna Replication ◽

Signaling Pathway ◽

Bioinformatics Analysis ◽

Mapk Signaling ◽

Migration And Invasion ◽

Type I ◽

Interferon Signaling ◽

Nf Kappa B ◽

Ppi Networks ◽

Coexpression Networks

Background: Osteosarcoma (OS) is one of the most common primary malignant bone tumors in teenagers. Emerging studies demonstrated TWEAK and Fn14 were involved in regulating cancer cell differentiation, proliferation, apoptosis, migration and invasion. Objective: The present study identified differently expressed mRNAs and lncRNAs after anti-TWEAK treatment in OS cells using GSE41828. Methods: We identified 922 up-regulated mRNAs, 863 downregulated mRNAs, 29 up-regulated lncRNAs, and 58 down-regulated lncRNAs after anti-TWEAK treatment in OS cells. By constructing PPI networks, we identified several key proteins involved in anti-TWEAK treatment in OS cells, including MYC, IL6, CD44, ITGAM, STAT1, CCL5, FN1, PTEN, SPP1, TOP2A, and NCAM1. By constructing lncRNAs coexpression networks, we identified several key lncRNAs, including LINC00623, LINC00944, PSMB8-AS1, LOC101929787. Result: Bioinformatics analysis revealed DEGs after anti-TWEAK treatment in OS were involved in regulating type I interferon signaling pathway, immune response related pathways, telomere organization, chromatin silencing at rDNA, and DNA replication. Bioinformatics analysis revealed differently expressed lncRNAs after antiTWEAK treatment in OS were related to telomere organization, protein heterotetramerization, DNA replication, response to hypoxia, TNF signaling pathway, PI3K-Akt signaling pathway, Focal adhesion, Apoptosis, NF-kappa B signaling pathway, MAPK signaling pathway, FoxO signaling pathway. Conclusion: : This study provided useful information for understanding the mechanisms of TWEAK underlying OS progression and identifying novel therapeutic markers for OS.

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Genetic and Epigenetic Changes of Intercellular Communication Genes During Multistage Carcinogenesis

Cancer Detection and Prevention ◽

10.1046/j.1525-1500.1999.99037.x ◽

1999 ◽

Vol 23 (4) ◽

pp. 273-279 ◽

Cited By ~ 42

Author(s):

Hiroshi Yamasaki ◽

Yasufumi Omori ◽

Maria-Lucia Zaidan-Dagli ◽

Nikolai Mironov ◽

Marc Mesnil ◽

...

Keyword(s):

Intercellular Communication ◽

Epigenetic Changes ◽

Multistage Carcinogenesis

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Type I Interferon as cardiovascular risk factor in systemic and cutaneous lupus erytheematosus: A systematic review

Autoimmunity Reviews ◽

10.1016/j.autrev.2021.102794 ◽

2021 ◽

pp. 102794

Author(s):

Chiara Kirchler ◽

Emma Husar-Memmer ◽

Klemens Rappersberger ◽

Kylie Thaler ◽

Ruth Fritsch-Stork

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factor ◽

Type I Interferon ◽

Type I ◽

Cutaneous Lupus

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Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

Human Genomics ◽

10.1186/s40246-020-00293-1 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Fatemeh Khodabandehloo ◽

Sara Taleahmad ◽

Reza Aflatoonian ◽

Farzad Rajaei ◽

Zahra Zandieh ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Signaling Pathway ◽

Expression Profiles ◽

Wnt Signaling Pathway ◽

Hub Genes ◽

Gene Expressions ◽

Cell Based Therapy ◽

Wnt Pathways ◽

Key Pathways

Abstract Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

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African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway

Veterinary Microbiology ◽

10.1016/j.vetmic.2021.109265 ◽

2021 ◽

pp. 109265

Author(s):

Kaidian Yang ◽

Quntao Huang ◽

Ruyu Wang ◽

Yan Zeng ◽

Mingyang Cheng ◽

...

Keyword(s):

Signaling Pathway ◽

Type I Interferon ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Type I ◽

Interferon Production

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187 Glucocorticoid regulation of the type I interferon-JAK/STAT signaling pathway

Cytokine ◽

10.1016/j.cyto.2008.07.249 ◽

2008 ◽

Vol 43 (3) ◽

pp. 283-284

Author(s):

Jamie R. Flammer ◽

Megan A. Kennedy ◽

Yurii Chinenov ◽

Lionel B. Ivashkiv ◽

Inez Rogatsky

Keyword(s):

Signaling Pathway ◽

Type I Interferon ◽

Type I ◽

Stat Signaling

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Modulation of TGF-β signaling by endoglin in murine hemangioblast development and primitive hematopoiesis

Blood ◽

10.1182/blood-2010-12-325019 ◽

2011 ◽

Vol 118 (1) ◽

pp. 88-97 ◽

Cited By ~ 31

Author(s):

Liying Zhang ◽

Alessandro Magli ◽

Jacquelyn Catanese ◽

Zhaohui Xu ◽

Michael Kyba ◽

...

Keyword(s):

Signaling Pathway ◽

Transforming Growth Factor ◽

Es Cells ◽

Transforming Growth Factor Β ◽

Early Developmental Stage ◽

Type I ◽

Hematopoietic Development ◽

Downstream Target ◽

Primitive Hematopoiesis ◽

Alk 5

Abstract Endoglin (Eng), an accessory receptor for the transforming growth factor β (TGF-β) superfamily, is required for proper hemangioblast and primitive hematopoietic development. However the mechanism by which endoglin functions at this early developmental stage is currently unknown. Transcriptional analyses of differentiating eng−/− and eng+/+ ES cells revealed that lack of endoglin leads to profound reductions in the levels of key hematopoietic regulators, including Scl, Lmo2, and Gata2. We also detected lower levels of phosphorylated Smad1 (pSmad1), a downstream target signaling molecule associated with the TGF-β pathway. Using doxycycline-inducible ES cell lines, we interrogated the TGF-β signaling pathway by expressing activated forms of ALK-1 and ALK-5, type I receptors for TGF-β. Our results indicate that ALK-1 signaling promotes hemangioblast development and hematopoiesis, as evidenced by colony assays, gene expression and FACS analyses, whereas signaling by ALK-5 leads to the opposite effect, inhibition of hemangioblast and hematopoietic development. In Eng−/− ES cells, ALK-1 rescued both the defective hemangioblast development, and primitive erythropoiesis, indicating that ALK-1 signaling can compensate for the absence of endoglin. We propose that endoglin regulates primitive hematopoiesis by modulating the activity of the Smad1/5 signaling pathway in early stages of development.

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