Search results for "Toxic"

Insufficient Antigen Presentation Due to Viral Immune Evasion Explains Lethal Cytomegalovirus Organ Disease After Allogeneic Hematopoietic Cell Trans…

2020

Reactivation of latent cytomegalovirus (CMV) poses a clinical problem in transiently immunocompromised recipients of hematopoietic cell (HC) transplantation (HCT) by viral histopathology that results in multiple organ manifestations. Compared to autologous HCT and to syngeneic HCT performed with identical twins as HC donor and recipient, lethal outcome of CMV infection is more frequent in allogeneic HCT with MHC/HLA or minor histocompatibility loci mismatch between donor and recipient. It is an open question if a graft-versus-host (GvH) reaction exacerbates CMV disease, or if CMV exacerbates GvH disease (GvHD), or if interference is mutual. Here we have used a mouse model of experimental HC…

Phage Therapy in Livestock and Companion Animals

2021

The irrational use of antibiotics has led to a high emergence of multi-drug resistant (MDR) bacteria. The traditional overuse of antibiotics in the animal feed industry plays a crucial role in the emergence of these pathogens that pose both economic and health problems. In addition, antibiotics have also recently experienced an increase to treat companion animal infections, promoting the emergence of MDR bacteria in pets, which can reach humans. Phages have been proposed as an alternative for antibiotics for the treatment of livestock and companion animal infections due to their multiple advantages as adaptative drugs, such as their ability to evolve, to multiply at the site of infections, …

Directed evolution of a Mycobacteriophage

2019

This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond.

Evaluation of cytocompatibility of calcium silicate-based endodontic sealers and their effects on the biological responses of mesenchymal dental stem…

2015

Aim To investigate in vitro the cytocompatibility of the calcium silicate-containing endodontic sealers MTA Fillapex and TotalFill BC Sealer on human periodontal ligament stem cells (hPDLSCs) by assaying their biological responses and compare them with that observed when using an epoxy resin-based sealer (AH Plus). Methodology Specimens from the three different endodontic sealers were eluated with culture medium for 24 h. The cytotoxicity of these eluates was evaluated using the MTT assay. In addition, an in vitro scratch wound healing model was used to determine their effects on cell migration. Cell adhesion to collagen type I after treatment with the different sealer eluates was also meas…

Cellular Responses in Human Dental Pulp Stem Cells Treated with Three Endodontic Materials

2017

Human dental pulp stem cells (HDPSCs) are of special relevance in future regenerative dental therapies. Characterizing cytotoxicity and genotoxicity produced by endodontic materials is required to evaluate the potential for regeneration of injured tissues in future strategies combining regenerative and root canal therapies. This study explores the cytotoxicity and genotoxicity mediated by oxidative stress of three endodontic materials that are widely used on HDPSCs: a mineral trioxide aggregate (MTA-Angelus white), an epoxy resin sealant (AH-Plus cement), and an MTA-based cement sealer (MTA-Fillapex). Cell viability and cell death rate were assessed by flow cytometry. Oxidative stress was m…

2016

AbstractGenetic manipulations in nutrient-sensing pathways are known to both extend lifespan and modify responses to environmental stressors (e.g., starvation, oxidative and thermal stresses), suggesting that similar mechanisms regulate lifespan and stress resistance. However, despite being a key factor reducing female lifespan and affecting female fitness, male-induced harm has rarely been considered as a stressor mediated by nutrient sensing pathways. We explored whether a lifespan-extending manipulation also modifies female resistance to male-induced harm. To do so, we used long-lived female Drosophila melanogaster that had their insulin signalling pathway downregulated by genetically ab…

2018

The murine Friend virus (FV) retrovirus model has been widely used to study anti-viral immune responses, and virus-induced cancer. Here we analyzed FV immune evasion mechanisms on the level of dendritic cells (DC) essential for the induction of primary adaptive immune responses. Comparative quantitative proteome analysis of FV-infected DC (FV-DC) of different genotypes (BALB/c, C57BL/6) and non-infected DC revealed numerous genotype-independently regulated proteins rergulating metabolic activity, cytoskeletal rearrangements, and antigen processing/presentation. These alterations may promote virion production in FV-DC. Stimulation of FV-DC with LPS resulted in strongly enhanced IL-10 product…

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

2016

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…

Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim

2021

24 páginas, 3 figuras, 1 tabla. The sequence data generated by this study has been deposited on SRA (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA670836. Extended data is available here: https://github.com/fmenardo/MTBC_L1_L3. DOI: https://doi.org/10.5281/zenodo.4609804 (Menardo, 2021).

Myeloid cell-synthesized coagulation Factor X dampens anti-tumor immunity

2019

Immune evasion in the tumor microenvironment (TME) is a crucial barrier for effective cancer therapy, and plasticity of innate immune cells may contribute to failures of targeted immunotherapies. Here, we show that rivaroxaban, a direct inhibitor of activated coagulation factor X (FX), promotes antitumor immunity by enhancing infiltration of dendritic cells and cytotoxic T cells at the tumor site. Profiling FX expression in the TME identifies monocytes and macrophages as crucial sources of extravascular FX. By generating mice with immune cells lacking the ability to produce FX, we show that myeloid cell-derived FX plays a pivotal role in promoting tumor immune evasion. In mouse models of ca…