scholarly journals Re-analysis of SARS-CoV-2 infected host cell proteomics time-course data by impact pathway analysis and network analysis. A potential link with inflammatory response

2020 ◽  
Author(s):  
Ignacio Ortea ◽  
Jens-Ole Bock
Keyword(s):  
Network Analysis ◽  
Inflammatory Response ◽  
Host Cell ◽  
Time Course ◽  
Treatment Options ◽  
Proteomics Data ◽  
Impact Pathways ◽  
Pathways Analysis ◽  
Potential Link

AbstractThe disease known as coronavirus disease 19 (COVID-19), potentially caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has hit the world hard, and has led to an unprecedent health and economic crisis. In order to develop treatment options able to stop or ameliorate SARS-CoV-2 effects, we need to understand the biology of the virus inside cells, but this kind of studies are still scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. In the present study, we use the publicly available proteomics data from this study to re-analyze the mechanisms altered by the virus infection by impact pathways analysis and network analysis. Proteins linked to inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be regulated. The up-regulation of the inflammatory-related proteins observed could be linked to the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients.

scholarly journals Down Regulation of Macrophage Activation in Brugia pahangi-Infected Jirds (Meriones unguiculatus)

1998 ◽  
Vol 66 (3) ◽  
pp. 1063-1069 ◽  
Author(s):  
C. Nasarre ◽  
J. L. Krahenbuhl ◽  
T. R. Klei
Keyword(s):  
Inflammatory Response ◽  
Macrophage Activation ◽  
Time Course ◽  
Meriones Unguiculatus ◽  
No Production ◽  
Mongolian Gerbils ◽  
Down Regulation ◽  
Brugia Pahangi ◽  
Mouse System

ABSTRACT The macrophage is a major component of the inflammatory response induced by lymphatic tissue-dwelling filariae. Intraperitoneal (i.p.) infections with Brugia pahangi in Mongolian gerbils, or jirds (Meriones unguiculatus), induce a peritoneal inflammatory response characterized by accumulation of numerous macrophages and fewer eosinophils. This inflammatory response is associated with the release of microfilariae by female worms. The aim of this study was to investigate the activation state of the peritoneal macrophages during the course of i.p. infections with either male or female worms. Activation was determined by a toxoplasmacidal assay and assays which measured the production of tumor necrosis factor (TNF)-like activity and nitric oxide (NO) production. The development of these assays with jirds was initially conducted in parallel with the mouse system, which served as a positive control. Jird macrophages became activated to kill Toxoplasma gondii by in vivo immunization with Mycobacterium bovis BCG in a pattern similar to that of mouse macrophages. However, unlike the mouse system, supernatants from purified protein derivative- or concanavalin A-stimulated jird splenocytes plus lipopolysaccharide failed to activate jird macrophages in vitro or induce NO production. These results indicate that factors involved in jird macrophage activation may differ from those demonstrated in the mouse system and other systems. i.p. infections of 15 days in duration with either male or female worms induced macrophage activation as measured byToxoplasma killing and TNF production. These responses decreased as the infection progressed to the chronic period on a time course that parallels the down regulation of experimentalB. pahangi granulomas. There was no evidence of NO production by activated jird macrophages. These data indicate that macrophage function is down modulated during filarial infection and suggest that mechanisms involved in macrophage deactivation are related to those that induce down modulation of the systemic granulomatous inflammatory response in the jird. This response is not dependent on the microfilarial stage of the parasite and is also independent of mechanisms which induce peritoneal accumulations of macrophages.

Hemolytic phospholipaseRv0183of Mycobacterium tuberculosis induces inflammatory response and apoptosis in alveolar macrophage RAW264.7 cells

2010 ◽  
Vol 56 (11) ◽  
pp. 916-924 ◽  
Author(s):  
Guangxian Xu ◽  
Hao Jia ◽  
Yong Li ◽  
Xiaoming Liu ◽  
Min Li ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Alveolar Macrophage ◽  
Cell Apoptosis ◽  
Time Course ◽  
Ectopic Expression ◽  
Host Cells ◽  
Raw264.7 Cells ◽  
Raw264.7 Cell

The metabolic pathway of phospholipids is one of the most important physiologic pathways in Mycobacterium tuberculosis , a typical intracellular bacterium. The hemolytic phospholipase lip gene (Rv0183) is one of 24 phospholipase genes that have been demonstrated to play critical roles in the metabolism of phospholipids in M. tuberculosis. Quantitative RT–PCR and flow cytometry were used to elucidate the immunological and pathogenic implications of the Rv0183 gene on the inflammatory response following persistent expression of Rv0183 in mouse alveolar macrophage RAW264.7 cells. Our results demonstrate that a time-course-dependent ectopic expression of Rv0183 significantly elevated the expression of IL-6, NF-κB, TLR-2, TLR-6, TNFα, and MyD88 in these alveolar macrophage cells. Furthermore, the persistent expression of Rv0183 induced RAW264.7 cell apoptosis in vitro. These findings demonstrate that the expression of Rv0183 induces an inflammatory response and cell apoptosis in the host cells, suggesting that Rv0183 may play an important role in the virulence and pathogenesis of M. tuberculosis infection.

scholarly journals Akt Inhibitor MK2206 Prevents Influenza pH1N1 Virus InfectionIn Vitro

2014 ◽  
Vol 58 (7) ◽  
pp. 3689-3696 ◽  
Author(s):  
Oxana V. Denisova ◽  
Sandra Söderholm ◽  
Salla Virtanen ◽  
Carina Von Schantz ◽  
Dmitrii Bychkov ◽  
...  
Keyword(s):  
Virus Infection ◽  
Host Cell ◽  
Treatment Options ◽  
Cell Interaction ◽  
Akt Signaling ◽  
Akt Inhibitor ◽  
Prevention And Treatment ◽  
Host Cell Interaction

ABSTRACTThe influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infectionin vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.

scholarly journals Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Haixia Luo ◽  
Yuanxing Li ◽  
Yueyang Zhao ◽  
Jingjing Chang ◽  
Xiu Zhang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Time Course ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cervical Squamous Cell Carcinoma ◽  
Circular Rnas ◽  
Cervical Carcinogenesis ◽  
Molecular Events ◽  
Highly Correlated

Circular RNAs (circRNAs) are regulatory molecules that participate in the occurrence, development and progression of tumors. To obtain a complete blueprint of cervical carcinogenesis, we analyzed the temporal transcriptomic landscapes of mRNAs and circRNAs. Microarrays were performed to identify the circRNA and mRNA expression profiles of cervical squamous cell carcinoma (CSCC) and high-grade squamous intraepithelial lesion (HSIL) patients compared with normal controls (NC). Short time-series expression miner (STEM) was utilized to characterize the time-course expression patterns of circRNAs and mRNAs from NC to HSIL and CSCC. A total of 3 circRNA profiles and 3 mRNA profiles with continuous upregulated patterns were identified and selected for further analysis. Furthermore, functional annotation showed that the mRNAs were associated with DNA repair and cell division. The protein-protein interaction (PPI) network analysis revealed that the ten highest-degree genes were considered to be hub genes. Subsequently, a competing endogenous RNA (ceRNA) network analysis and real-time PCR validation indicated that hsa_circ_0001955/hsa-miR-6719-3p/CDK1, hsa_circ_0001955/hsa-miR-1277-5p/NEDD4L and hsa_circ_0003954/hsa-miR-15a-3p/SYCP2 were highly correlated with cervical carcinogenesis. Silencing of hsa_circ_0003954 inhibited SiHa cell proliferation and perturb the cell cycle in vitro. This study provides insight into the molecular events regulating cervical carcinogenesis, identifies functional circRNAs in CSCC, and improves the understanding of the pathogenesis and molecular biomarkers of CSCC and HSIL.

scholarly journals Functional Network Profiles in ARSACS Disclosed by Aptamer-Based Proteomic Technology

2021 ◽  
Vol 11 ◽  
Author(s):  
Federica Morani ◽  
Stefano Doccini ◽  
Giovanna Chiorino ◽  
Fabiana Fattori ◽  
Daniele Galatolo ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Model ◽  
Treatment Options ◽  
Neuroblastoma Cell ◽  
Rare Condition ◽  
Proteomics Data ◽  
Diagnostic Strategies ◽  
Modifying Factors ◽  
Functional Pathways

Although the genetic basis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has been uncovered, our poor understanding of disease mechanisms requires new light on functional pathways and modifying factors to improve early diagnostic strategies and offer alternative treatment options in a rare condition with no cure. Investigation of the pathologic state combining disease models and quantitative omic approach might improve biomarkers discovery with possible implications in patients' diagnoses. In this study, we analyzed proteomics data obtained using the SomaLogic technology, comparing cell lysates from ARSACS patients and from a SACS KO SH-SY5Y neuroblastoma cell model. Single-stranded deoxyoligonucleotides, selected in vitro from large random libraries, bound and quantified molecular targets related to the neuroinflammation signaling pathway and to neuronal development. Changes in protein levels were further analyzed by bioinformatics and network approaches to identify biomarkers of ARSACS and functional pathways impaired in the disease. We identified novel significantly dysregulated biological processes related to neuroinflammation, synaptogenesis, and engulfment of cells in patients and in KO cells compared with controls. Among the differential expressed proteins found in this work, we identified several proteins encoded by genes already known to be mutated in other forms of neurodegeneration. This finding suggests that common dysfunctional networks could be therapeutic targets for future investigations.

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

The Effect of Heparin vs. Citrate on the Interaction of Platelets with Vascular Graft Materials

1985 ◽  
Vol 54 (04) ◽  
pp. 842-848 ◽  
Author(s):  
Kandice Kottke-Marchant ◽  
James M Anderson ◽  
Albert Rabinovitch ◽  
Richard A Huskey ◽  
Roger Herzig
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Vascular Graft ◽  
Time Course ◽  
Platelet Reactivity ◽  
Polymer Surfaces ◽  
In Vitro Perfusion ◽  
Citrate Anticoagulation ◽  
Platelet Release

SummaryHeparin is known to affect platelet function in vitro, but little is known about the effect of heparin on the interaction of platelets with polymer surfaces in general, and vascular graft materials in particular. For this reason, the effect of heparin vs. citrate anticoagulation on the interaction of platelets with the vascular graft materials expanded polytetrafluoroethylene (ePTFE), Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC) was studied in a recirculating, in vitro perfusion system. Platelet activation, as shown by a decrease in platelet count, an increase in platelet release and a decrease in platelet aggregation, was observed for all vascular graft materials tested using heparin and was greater for Dacron and preclotted Dacron than for ePTFE. Significant differences between heparin and citrate anticoagulation were seen for platelet release, platelet aggregation and the relative ranking of material platelet-reactivity. However, the trends and time course of platelet activation were similar with both heparin and citrate for the materials tested.

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