Histological Assessment of Respiratory Tract and Liver of BALB/c Mice Nebulized with Tocilizumab.

Pulmonary drug delivery offers a minimally invasive and efficient method for treating lung conditions, leveraging the lungs' extensive surface area and blood flow for rapid drug absorption. Nebulized therapies aim to deliver drugs directly to the lung tissue. This study investigates the histological impact of nebulized tocilizumab-a monoclonal antibody targeting IL-6, traditionally administered intravenously for rheumatoid arthritis and severe COVID-19-on a murine model. Thirty BALB/c mice were nebulized with tocilizumab (10 mg, 5 mg, and 2.5 mg) and six controls were nebulized with saline solution. They were euthanized 48 h later, and their organs (lungs, nasal mucosa, and liver) were analyzed by a microscopic histological evaluation. The results indicate that all the mice survived the 48 h post-nebulization period without systemic compromise. The macroscopic examination showed no abnormalities, and the histopathological analysis revealed greater lung vascular changes in the control group than in the nebulized animals, which is attributable to the euthanasia with carbon dioxide. Additionally, increased alveolar macrophages were observed in the nebulized groups compared to controls. No significant histological changes were observed in the liver, indicating the safety of nebulized tocilizumab. In conclusion, these findings suggest the potential of nebulized tocilizumab for treating pulmonary inflammation, warranting further research to establish its efficacy and safety in clinical settings.

Tick salivary proteome and lipidome with low glycan content correlate with allergic type reactions in the zebrafish model.

Ticks, as hematophagous ectoparasites, can manipulate host immune and metabolic processes, causing tick-borne allergies such as α-Gal syndrome (AGS). Glycolipids with bound galactose-alpha-1-3-galactose (α-Gal) are potential allergenic molecules associated with AGS. Nevertheless, proteins and lipids lacking α-Gal modifications may contribute to tick salivary allergies and be linked to AGS. In this study, we characterized the effect of deglycosylated tick salivary proteins without lipids on treated zebrafish fed with dog food formulated with mammalian (beef, lamb, pork) meat by quantitative proteomics analysis of intestinal samples. The characterization and functional annotations of tick salivary lipids with low representation of glycolipids was conducted using a lipidomics approach. Results showed a significant effect of treatment with saliva and saliva deglycosylated protein fraction on zebrafish abnormal or no feeding (p < 0.005). Treatment with this fraction affected multiple metabolic pathways, defense responses to pathogens and protein metabolism, which correlated with abnormal or no feeding. Lipidomics analysis identified 23 lipid classes with low representation of glycolipids (0.70% of identified lipids). The lipid class with highest representation was phosphatidylcholine (PC; 26.66%) and for glycolipids it corresponded to diacylglycerol (DG; 0.48%). Qualitative analysis of PC antibodies revealed that individuals bitten by ticks were more likely to produce PC-IgG antibodies (p < 0.001). DG levels were significantly higher in tick salivary glands (p < 0.05) compared with tick saliva and salivary fractions. The α-Gal content was higher in tick saliva than in deglycosylated saliva and lipid fractions. These results support a possible role for tick salivary proteins and lipids without α-Gal modifications in AGS.

Zebrafish gut microbiota composition in response to tick saliva biomolecules correlates with allergic reactions to mammalian meat consumption.

The α-Gal syndrome (AGS) is an IgE-mediated tick borne-allergy that results in delayed anaphylaxis to the consumption of mammalian meat and products containing α-Gal. Considering that α-Gal-containing microbiota modulates natural antibody production to this glycan, this study aimed to evaluate the influence on tick salivary compounds on the gut microbiota composition in the zebrafish (Danio rerio) animal model. Sequencing of 16 S rDNA was performed in a total of 75 zebrafish intestine samples, representing different treatment groups: PBS control, Ixodes ricinus tick saliva, tick saliva non-protein fraction (NPF), tick saliva protein fraction (PF), and tick saliva protein fractions 1-5 with NPF (F1-5). The results revealed that treatment with tick saliva and different tick salivary fractions, combined with α-Gal-positive dog food feeding, resulted in specific variations in zebrafish gut microbiota composition at various taxonomic levels and affected commensal microbial alpha and beta diversities. Metagenomics results were corroborated by qPCR, supporting the overrepresentation of phylum Firmicutes in the tick saliva group, phylum Fusobacteriota in group F1, and phylum Cyanobacteria in F2 and F5 compared to the PBS-control. qPCRs results at genus level sustained significant enrichment of Plesiomonas spp. in groups F3 and F5, Rhizobium spp. in NPF and F4, and Cloacibacterium spp. dominance in the PBS control group. This study provides new results on the role of gut microbiota in allergic reactions to tick saliva components using a zebrafish model of AGS. Overall, gut microbiota composition in response to tick saliva biomolecules may be associated with allergic reactions to mammalian meat consumption in AGS.

A comprehensive examination of small-bowel capsule endoscopy in Spanish centers to meet European Society of Gastrointestinal Endoscopy standards.

Background and study aims In 2019, the European Society of Gastrointestinal Endoscopy (ESGE) created a working group to develop technical and quality standards for small-bowel capsule endoscopy (SBCE) to improve the daily practice of endoscopy services. They developed 10 quality parameters, which have yet to be tested in a real-life setting. Our study aimed to evaluate the accomplishment of the quality standards in SBCE established by the ESGE in several Spanish centers. Materials and methods An online survey of 11 multiple-choice questions related to the ESGE performance measures was sent to Spanish centers with experience in SBCE. In order to participate and obtain reliable data, at least 100 questionnaires had to be answered per center because that is the minimum number established by ESGE. Results 20 centers participated in the study, compiling 2049 SBCEs for the analysis. Only one of 10 performance measures (cecal visualization) reached the minimum standard established by the ESGE. In five of 10 performance measures (Indication, lesion detection rate, terminology, and retention rate) the minimum standard was nearly achieved. Conclusions Our study is the first multicenter study regarding SBCE quality performance measures in a real setting. Our results show that the minimum standard is hardly reached in most procedures, which calls into question their clinical applicability in real life. We suggest performing similar studies in other countries to evaluate whether there is a need for quality improvement programs or a need to reevaluate the minimum and target values published so far.

RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.

Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.