Empty SV40 capsids (VLPs) significantly improve survival and recovery of septic rats
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PROVIDER: PRJNA515732 | ENA |
REPOSITORIES: ENA
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Project description:During the first hours after infection, before SV40 DNA enters the nucleus, empty capsids (VLPs) and the wild-type virus have the same effect on cellular signaling. VLPs were previously found to ameliorate toxic acute kidney injury (AKI) in a mouse model, counteracting apoptosis by inducing the Akt-1 survival pathway. Here we tested their effect on severe sepsis in rats. VLP pre-treatment increased survival and recovery from zero to 75%. RNAseq studies demonstrated that unlike AKI, here the VLPs did not induce survival pathways. Instead they affected thousands of genes and many cellular functions, eliminating deleterious pathways and inducing beneficial ones: immune response, resolution of inflammation, regeneration and cell and system homeostasis. In contrast, only four genes were affected following VLP administration to healthy rats. We propose that SV40 VLPs respond specifically to perturbation in cellular activities. The study suggests that diseases with complex pathophysiology may require treatments affecting wide-spectrum functions.
2020-03-02 | GSE109041 | GEO
Project description:During the first hours after infection, before SV40 DNA enters the nucleus, empty capsids (VLPs) and the wild-type virus have the same effect on cellular signaling. VLPs were previously found to ameliorate toxic acute kidney injury (AKI) in a mouse model, counteracting apoptosis by inducing the Akt-1 survival pathway. Here we tested their effect on severe sepsis in rats. VLP pre-treatment increased survival and recovery from zero to 75%. RNAseq studies demonstrated that unlike AKI, here the VLPs did not induce survival pathways. Instead they affected thousands of genes and many cellular functions, eliminating deleterious pathways and inducing beneficial ones: immune response, resolution of inflammation, regeneration and cell and system homeostasis. In contrast, only four genes were affected following VLP administration to healthy rats. We propose that SV40 VLPs respond specifically to perturbation in cellular activities. The study suggests that diseases with complex pathophysiology may require treatments affecting wide-spectrum functions.
2020-03-02 | GSE125276 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-03-02 | GSE125277 | GEO
Project description:Analysis of pathways elicited by empty SV40 capsids (VLPs) in septic rats 6 hours post 2CLP operation
| PRJNA429471 | ENA
Project description:Analysis of pathways elicited by empty SV40 capsids (VLPs) in septic rats 24 hours post 2CLP operation
| PRJNA515734 | ENA
Project description:Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. It has been established that persistent beta adrenergic stimulation is detrimental in sepsis, and that specific beta 1 blockade mitigates excessive systemic inflammation and improves myocardial function. The aim of this study was to investigate the effects of specific beta 1 blocker esmolol on septic mouse myocardium by genomic and proteomic techniques. We also evaluated survival of septic mice and systemic inflammation under esmolol treatment. C57BL/6 mice were rendered septic by 2 models: cecal ligature and perforation (CLP) and intraperitoneal injection of lipopolysaccharides (LPS). Effects of esmolol on myocardium were assessed by microarray technique. Total RNA were isolated and purified from a 30mg sample of the heart of 6 groups of 8 animals, depending on the sepsis model and the treatment. The labeled cDNA from the treated animals were hybridized against the labeled cDNA from the untreated animals with 2 dye-swaps done for each sepsis model.
2015-08-03 | E-GEOD-31175 | biostudies-arrayexpress
Project description:Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. It has been established that persistent beta adrenergic stimulation is detrimental in sepsis, and that specific beta 1 blockade mitigates excessive systemic inflammation and improves myocardial function. The aim of this study was to investigate the effects of specific beta 1 blocker esmolol on septic mouse myocardium by genomic and proteomic techniques. We also evaluated survival of septic mice and systemic inflammation under esmolol treatment.
2015-08-03 | GSE31175 | GEO
Project description:Analysis of the effect on dendritic cells of the injection in C57BL/6 mice of VLPs or ncRNAVLPs at gene expression level.
2016-06-02 | GSE70557 | GEO
Project description:Severe infections and sepsis is an increasing clinical problem that cause prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of antibiotic resistance is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play a major role in defense against bacterial infections. We have recently shown that a saturated high fat diet decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the dietary fat composition affects survival and neutrophils function after experimental septic infection in mice. We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased septic survival and decreased bacterial load compared with mice fed saturated HFD (HFD/S), and similar to that of mice given low fat diet (LFD). Furthermore, uninfected mice fed HFD/P had increased number of Ly6G+ neutrophils in bone marrow. In addition, mice fed HFD/P had a higher number Ly6G+ neutrophils recruited to the site of inflammation after peritoneal injection of thioglycollate. In conclusion, polyunsaturated dietary fat increased both survival and the efficiency of the bacterial clearance during septic S. aureus infection. Moreover, this diet enhanced the number and chemotaxis of neutrophils, a key component of the immune response to S. aureus infections. Mice (non-infected) fed saturated high fat diet, low fat diet, or polyunsaturated high fat diet
2014-11-24 | E-GEOD-58358 | biostudies-arrayexpress
Project description:TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production. In this dataset, expression data of genes induced by septic peritonitis in spleens from TLR-deficient and wildtype mice are included. 3 groups (septic TLR-deficient mice, septic wildtype mice, and untreated wildtype mice) with 4 replicates each.
2011-06-27 | E-GEOD-24327 | biostudies-arrayexpress