scholarly journals Nanosilver in Biomedicine: Advantages and Restrictions

2021 ◽  
Author(s):  
Olga V. Morozova ◽  
Dmitry V. Klinov
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Surface Layer ◽  
Drug Efficacy ◽  
Multidrug Resistant ◽  
Deionized Water ◽  
Sensitivity Threshold ◽  
Specific Interactions ◽  
Anti Cancer ◽  
Potential Formation

Nanosilver (in a range 1–100 nm) binds with thyol-, amino- and carboxy-groups of aminoacid residues of proteins and nucleic acids, thus providing inactivation of pathogenic multidrug-resistant microorganisms. Besides antibacterial, antiviral, antifungal and anti-cancer properties Ag-based nanomaterials possess anti-inflammatory, anti-angiogenesis and antiplatelet features. Drug efficacy depends on their stability, toxicity and host immune response. Citrate coated Ag nanoparticles (NPs) remain stable colloid solutions in deionized water but not in the presence of ions due to replacement of Ag+ by electrolyte ions, potential formation of insoluble AgCl, subsequent catalyzed oxidative corrosion of Ag and further dissolution of surface layer of Ag2O. Protein shells protect core of AgNPs from oxidation, dissolution, aggregation and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics but the sensitivity threshold does not exceed 10 pg Cytotoxicity of AgNPs conjugated with proteins is associated with the rate of intracellular Ag+ release, a ‘Trojan horse’ effect, and exceeds one of Ag+ because of endocytosis uptake of NPs but not ions. Relatively toxic nanosilver causes immunosuppression of the majority of cytokines with a few exceptions (IL-1β, G-CSF, MCP-1) whereas AgNO3 additionally activate TNFα and IL8 gene expression.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals Protein citrullination as a source of cancer neoantigens

2021 ◽  
Vol 9 (6) ◽  
pp. e002549
Author(s):  
Hiroyuki Katayama ◽  
Makoto Kobayashi ◽  
Ehsan Irajizad ◽  
Alejandro Sevillarno ◽  
Nikul Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Family Members ◽  
Immunohistochemical Analysis ◽  
Cancer Cell Lines ◽  
Mhc Ii

BackgroundCitrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.MethodsProtein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.ResultsProteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p<0.0001); PADI2 protein expression was positively correlated (p<0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen–antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012).ConclusionsAn immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.

scholarly journals H-Ras gene takes part to the host immune response to COVID-19

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Salvatore Sciacchitano ◽  
Andrea Sacconi ◽  
Claudia De Vitis ◽  
Giovanni Blandino ◽  
Giulia Piaggio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Severe Disease ◽  
Host Immune Response ◽  
Severe Form ◽  
Ras Gene ◽  
Peripheral Blood Mononuclear ◽  
Ras Genes

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

scholarly journals Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Barrier Function ◽  
Nutrient Transport ◽  
Gene Expression Pattern ◽  
Vaccine Dose ◽  
Special Focus ◽  
Intestinal Health ◽  
Barrier Failure ◽  
Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

scholarly journals A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
The Novel ◽  
The Central Nervous System ◽  
Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

scholarly journals The Sex Differences in Uveal Melanoma: Potential Roles of EIF1AX, Immune Response and Redox Regulation

2021 ◽  
Vol 28 (4) ◽  
pp. 2801-2811
Author(s):  
Feng Liu-Smith ◽  
Chi-Yang Chiu ◽  
Daniel L. Johnson ◽  
Phillip Winston Miller ◽  
Evan S. Glazer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Sex Difference ◽  
Uveal Melanoma ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Men And Women ◽  
Copy Numbers ◽  
Differential Gene

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM.

scholarly journals SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marta Ferreira-Gomes ◽  
Andrey Kruglov ◽  
Pawel Durek ◽  
Frederik Heinrich ◽  
Caroline Tizian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Reaction ◽  
Adaptive Immune Response ◽  
Gene Expression Signature ◽  
Spike Protein ◽  
Single Cell Level ◽  
Cell Level ◽  
Adaptive Immune

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

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