Systemically interfering with immune response by a fluorescent cationic dendrimer delivered gene suppression

2014 ◽  
Vol 2 (29) ◽  
pp. 4653-4659 ◽  
Author(s):  
Dongxu Shen ◽  
Fan Zhou ◽  
Zejun Xu ◽  
Bicheng He ◽  
Miao Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Insect Cells ◽  
Water Soluble ◽  
Immune Gene ◽  
Gene Suppression

A water-soluble, fluorescent, cationic dendrimer systemically delivers dsRNA into insect cells and tissues, resulting in the suppression of the immune gene.

scholarly journals Multicompartmental Lipopolyplex as Vehicle for Antigens and Genes Delivery in Vaccine Formulations

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 281
Author(s):  
Isaías Sanmartín ◽  
Luis Sendra ◽  
Inés Moret ◽  
María José Herrero ◽  
Salvador F. Aliño
Keyword(s):  
Immune Response ◽  
Humoral Response ◽  
Water Soluble ◽  
Vaccine Research ◽  
Current Vaccine ◽  
Humoral Antibodies ◽  
Melanoma Model ◽  
Gd3 Ganglioside ◽  
Lipid Antigen ◽  
Simultaneous Delivery

Vector design and its characterization is an area of great interest in current vaccine research. In this article, we have formulated and characterized a multicompartmental lipopolyplex, which associates multiple liposomes and polyplexes in the same complex. These particles allow the simultaneous delivery of lipid or water-soluble antigens associated with genes to the same cell, in much higher amounts than conventional lipopolyplexes. The vector characterization and optimization were carried out using liposomes with entrapped carboxyfluorescein and adapted electrophoretic assays. Two types of lipopolyplexes (containing hydrophilic or lipophilic antigens) were employed to evaluate their interest in vaccination. The lipopolyplex loaded with an extract of water-soluble melanoma proteins proved to efficiently induce humoral response in murine melanoma model, increasing the levels of IgM and IgG. The specificity of the immune response induced by the lipopolyplex was demonstrated in mice with the lipopolyplex containing the GD3 ganglioside lipid antigen, abundant in melanoma cells. The levels of anti-GD3 IgG increased markedly without modifying the expression of humoral antibodies against other gangliosides.

scholarly journals A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

2021 ◽  
Author(s):  
Alberto Gomez-Carballa ◽  
Irene Rivero-Calle ◽  
Jacobo Pardo-Seco ◽  
Jose Gomez-Rial ◽  
Carmen Rivero-Velasco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Local Level ◽  
Antiviral Response ◽  
Innate Immune ◽  
Nasal Epithelium ◽  
Severe Illness ◽  
Immune Gene ◽  
Innate Antiviral Response ◽  
Immune Related Genes

Background: COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. Methods and findings: We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Conclusions: We found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

scholarly journals IFN-I Independent Antiviral Immune Response to Vesicular Stomatitis Virus Challenge in Mouse Brain

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 326
Author(s):  
Anurag R. Mishra ◽  
Siddappa N. Byrareddy ◽  
Debasis Nayak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vesicular Stomatitis Virus ◽  
Antiviral Response ◽  
Type I ◽  
Immune Gene ◽  
Antiviral Immune Response ◽  
Virus Challenge ◽  
Vesicular Stomatitis ◽  
Ifn Γ

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role of IFN-I in the CNS against viral encephalitis is not entirely clear. Here we have implemented the combination of global differential gene expression profiling followed by bioinformatics analysis to decipher the CNS immune response in the presence and absence of the IFN-I signaling. We observed that vesicular stomatitis virus (VSV) infection induced 281 gene changes in wild-type (WT) mice primarily associated with IFN-I signaling. This was accompanied by an increase in antiviral response through leukocyte vascular patrolling and leukocyte influx along with the expression of potent antiviral factors. Surprisingly, in the absence of the IFN-I signaling (IFNAR−/− mice), a significantly higher (1357) number of genes showed differential expression compared to the WT mice. Critical candidates such as IFN-γ, CCL5, CXCL10, and IRF1, which are responsible for the recruitment of the patrolling leukocytes, are also upregulated in the absence of IFN-I signaling. The computational network analysis suggests the presence of the IFN-I independent pathway that compensates for the lack of IFN-I signaling in the brain. The analysis shows that TNF-α is connected maximally to the networked candidates, thus emerging as a key regulator of gene expression and recruitment of myeloid cells to mount antiviral action. This pathway could potentiate IFN-γ release; thereby, synergistically activating IRF1-dependent ISG expression and antiviral response.

Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

2020 ◽  
pp. 1-13
Author(s):  
Chenglin Li ◽  
Yanfei Zhou ◽  
Hanshun Deng ◽  
Yuanshen Ye ◽  
Shuizhen Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Web Applications ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Immune Gene ◽  
Nf Kappa B ◽  
Signal Transducers ◽  
Pathways Analysis

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

scholarly journals Supplementation of a water-soluble zinc–AA complex to reduce stress in broilers, pullets, and layers1

2020 ◽  
Vol 98 (1) ◽  
Author(s):  
Jill R Nelson ◽  
Eric B Sobotik ◽  
Marco A Rebollo ◽  
Gregory S Archer
Keyword(s):  
Immune Response ◽  
Uric Acid ◽  
Plasma Chemistry ◽  
Water Soluble ◽  
Water Withdrawal ◽  
White Leghorn ◽  
Time Intervals ◽  
Humoral Immune ◽  
Eden Prairie ◽  
Soluble Zinc

Abstract This study consisted of three 5-wk experiments to test the effects of administering Zinpro-LQ (Zinpro-LQ, Zinpro Corporation, Eden Prairie, MN) for different time intervals in stressed broilers, pullets, and layers. Treatments included: nonstressed control (NC), stressed control (SC), stressed and supplemented Zinpro-LQ for 14 d prior to stressor (S1), 10 d prior (S2), 7 d prior to and 7 d during stressor (S3), and 5 d prior (S4). Birds included 1-d-old Cobb 500 male broilers (Experiment 1), 7-wk-old white Leghorn pullets (Experiment 2), and 50-wk-old white Leghorn layers (Experiment 3). All stressed birds were vaccinated against Newcastle Disease Virus (NDV) on day 28 and exposed to random feed and water withdrawal days 28 to 35 for 6 h/d. Pullets were beak trimmed on day 21, and layers were heat stressed days 28 to 35. Blood was sampled on day 35 to determine plasma chemistry, corticosterone (CORT), anti-NDV antibody titer, and heterophil/lymphocyte (H/L) ratio. Mortality, feed and water consumption, and BW were also recorded. In Experiment 1, CORT and H/L ratio were highest in SC (P < 0.05). In Experiment 2, CORT was higher in SC than S4 (P < 0.05) while all other treatments were statistically intermediate. NDV titer was lower in SC than S4 while all other treatments were statistically intermediate. Treatment differences were also observed for H/L ratio, and plasma uric acid and cholesterol in Experiment 2. In Experiment 3, treatment differences were observed for H/L ratio, plasma glucose, sodium, and chloride. H/L ratio was lower in NC, S1, and S4 compared with SC (P < 0.05); and NC and S1 were lower than S2 (P < 0.05). In conclusion, dietary inclusion of zinc AA complex for any length of time prior to a stressor helped reduce measures of stress in broilers. The S1 and S4 treatments helped reduce stress and improve humoral immune response in pullets and layers.

A functionalized fluorescent dendrimer as a pesticide nanocarrier: application in pest control

Nanoscale ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 445-449 ◽  
Author(s):  
Xiaoxia Liu ◽  
Bicheng He ◽  
Zejun Xu ◽  
Meizhen Yin ◽  
Wantai Yang ◽  
...  
Keyword(s):  
Pest Control ◽  
Insect Cells ◽  
Water Soluble

A water-soluble fluorescent cationic dendrimer can efficiently deliver a pesticide into the insect cells and largely increase the cytotoxicity of the drug.

scholarly journals SUMOylation of Jun fine-tunes the Drosophila gut immune response

2021 ◽  
Author(s):  
Amarendranath Soory ◽  
Girish S Ratnaparkhi
Keyword(s):  
Immune Response ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Antimicrobial Agents ◽  
Immune Gene ◽  
Post Translational Modification ◽  
Sumo Conjugation ◽  
Core Elements ◽  
Gene Regulatory ◽  
Kinetics Of

Post-translational modification by the small ubiquitin-like modifier, SUMO can modulate the activity of its conjugated proteins. The transcriptional regulator Jun, a member of the AP-1 complex is one such SUMO target. We find that Jra, the Drosophila Jun ortholog, is a regulator of the Pseudomonas entomophila induced gut immune gene regulatory network, modulating the expression of a few thousand genes, as measured by quantitative RNA sequencing. Decrease in Jra in gut enterocytes is protective, suggesting that reduction of Jra signaling favors the host over the pathogen. In Jra, lysines 29 and 190 are SUMO conjugation targets, with the JraK29R+K190R double mutant being SUMO conjugation resistant (SCR). Interestingly, a JraSCR fly line, generated by CRISPR/Cas9 based genome editing, is more sensitive to infection, with adults showing a weakened host response and increased proliferation of Pseudomonas. Transcriptome analysis of the guts of JraSCR and JraWT flies suggests that lack of SUMOylation of Jra significantly changes core elements of the immune gene regulatory network, that include antimicrobial agents, secreted ligands, feedback regulators, and transcription factors. SUMOylation attenuates Jra activity, with the master immune regulator Relish being an important transcriptional target. Our study implicates Jra as a major immune regulator, with dynamic SUMO conjugation/deconjugation modulating the kinetics of the gut transcriptional immune response.

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