ABSTRACT
Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research.
ABSTRACT
In the present study, we synthesized and evaluated the anti-inflammatory effects of the two component hybrids, caffeic acid (CA)-ferulic acid (FA), FA-Tryptamine (Trm), CA-Piperonyl Triazol (PT) and FA-PT. Of these five hybrids, CA-FA had the most potent inhibitory effect on butyrylcholinesterase (BuChE) activity. The CA containing hybrids, CA-FA, CA-Trm, and CA-PT, dose-dependently inhibited LPS-induced nitric oxide (NO) generation in BV2 cells, whereas FA-PT, FA-Trm, CA, FA, Trm, and PT did not. Although CA-FA, CA-Trm and CA-PT had similar inhibitory effects on LPS-induced NO generation, CA-FA best protected BV2 cells from LPS-induced cell death. CA-FA, but not CA or FA, dose-dependently inhibited LPS-induced up-regulations of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in BV2 and RAW264.7â¯cells. Furthermore, CA-FA inhibited LPS-induced iNOS, COX-2, interleukin-6, and interleukin-1ß mRNA expressions in BV2 cells. CA-FA also inhibited the LPS-induced phosphorylations of STAT3, Akt, and IκB and selectively inhibited LPS-induced NF-κB activation. Overall, our data suggest that CA-FA has BuChE inhibitory effects and down-regulates inflammatory responses by inhibiting NF-κB, which indicates CA-FA be viewed as a potential therapeutic agent for the treatment of inflammatory diseases of the peripheral system and central nervous systems.