Renal Mast Cell-Specific Proteases in the Pathogenesis of Tubulointerstitial Fibrosis.

Chronic kidney disease is detected in 8-15% of the world's population. Along with fibrotic changes, it can lead to a complete loss of organ function. Therefore, a better understanding of the onset of the pathological process is required. To address this issue, we examined the interaction between mast cells (MCs) and cells in fibrous and intact regions, focusing on the role of MC proteases such as tryptase, chymase, and carboxypeptidase A3 (CPA3). MCs appear to be involved in the development of inflammatory and fibrotic changes through the targeted secretion of tryptase, chymase, and CPA3 to the vascular endothelium, nephron epithelium, interstitial cells, and components of intercellular substances. Protease-based phenotyping of renal MCs showed that tryptase-positive MCs were the most common phenotype at all anatomic sites. The infiltration of MC in different anatomic sites of the kidney with an associated release of protease content was accompanied by a loss of contact between the epithelium and the basement membrane, indicating the active participation of MCs in the formation and development of fibrogenic niches in the kidney. These findings may contribute to the development of novel strategies for the treatment of tubulointerstitial fibrosis.

Enzymatic Activity and Microbial Diversity of Sod-Podzolic Soil Microbiota Using 16S rRNA Amplicon Sequencing following Antibiotic Exposure.

Antibiotic contamination of the environment negatively affects soil fertility by disrupting natural microbial communities. Currently, the study of the effect of antibacterial drugs on soils typical in Russia, which are of great importance for agriculture, is insufficient. Despite a rapid increase in the number of metagenomic studies, this article is the first publication devoted to the microbial diversity of sod-podzolic soil and its relationship with enzymatic activity. In the present study, we use 16S rRNA metagenomic sequencing to analyze microbiota dynamics and to examine soil enzymatic activities after antibiotic treatment with benzylpenicillin, oxytetracycline, and tylosin. We found that, following treatment, urease activity was reduced regardless of the antibiotic used while nitrification activity showed no statistically significant changes (p > 0.05). Oxytetracycline and tylosin produced no effect on catalase activity but benzylpenicillin caused an increase. Benzylpenicillin and oxytetracycline increased cellulolytic activity whereas tylosin had no significant effect (p > 0.05). Microbiome profiling through 16S rRNA gene sequencing demonstrated antibiotic administration and exhibited no significant impact on bacterial abundance and species diversity (p > 0.05), thus pointing to the resilience of the soil microbial community. Oxytetracycline, benzylpenicillin, and tylosin are likely to negatively affect the enzymatic profiles in sod-podzolic soil but with a negligible influence on the bacterial composition.