Ferrostatin­1 alleviates liver injury via decreasing ferroptosis following ricin toxin poisoning in rat.

Ricin is a highly toxic plant toxin that can cause multi-organ failure, especially liver dysfunction, and is a potential bioterrorism agent. Despite the serious public health challenge posed by ricin, effective therapeutic for ricin-induced poisoning is currently unavailable. Therefore, it is important to explore the mechanism of ricin poisoning and develop appropriate treatment protocols accordingly. Previous studies have shown that lipid peroxidation and iron accumulation are associated with ricin poisoning. Ferroptosis is an iron-dependent form of cell death caused by excessive accumulation of lipid peroxide. The role and mechanism of ferroptosis in ricin poisoning are unclear and require further study. We investigated the effect of ferroptosis on ricin-induced liver injury and further elucidated the mechanism. The results showed that ferroptosis occurred in the liver of ricin-intoxicated rats, and Ferrostatin­1 could ameliorate hepatic ferroptosis and thus liver injury. Ricin induced liver injury by decreasing hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, increasing iron, malondialdehyde and reactive oxygen species, and mitochondrial damage, whereas Ferrostatin­1 pretreatment increased hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, decreased iron, malondialdehyde, and reactive oxygen species, and ameliorated mitochondrial damage, thereby alleviated liver injury. These results suggested that ferroptosis exacerbated liver injury after ricin poisoning and that inhibition of ferroptosis may be a novel strategy for the treatment of ricin poisoning.

A genome-wide landscape of mRNAs, miRNAs, lncRNAs, and circRNAs of skeletal muscles during dietary restriction in Mongolian horses.

The proportion of different muscle fibers is essential for the horse breed's aptitude for athletic activities. Adaptation of locomotor muscle is correlated with altered physiologic conditions. To investigate the adaptive changes of muscle fiber phenotype and transcriptome in horse skeletal muscle during dietary restriction (DR). The muscle fiber type distribution and deep RNA-seq analysis of detecting differentially expressed mRNAs (DEGs), miRNA (DEMIRs), lncRNAs (DELs), circRNAs (DECs), and their function analysis were investigated in gluteus medius muscle of Mongolian horses during DR. A total of 1433 DEGs, 5 DEMIRs, 329 DELs, and 53 DECs were identified. Differing from non-uniform muscle fiber type changing, functional enrichment analysis showed that most downregulated DEGs were associated in muscle contraction, fuel energy metabolism, and protein balance. Linkages between non-coding RNA and mRNA landscape were detected from their functional changes. Our study provides new insights into the expressional changes of mRNA and non-coding RNA in horse skeletal muscles during DR, which might improve our understanding of the molecular mechanisms regulating muscle adaption during DR for racing horses.

Fast and slow myofiber-specific expression profiles are affected by noncoding RNAs in Mongolian horses.

The heterogeneity and plasticity of muscle fibers are essential for the athletic performance of horses, mainly at the adaption of exercises and the effect on muscle diseases. Skeletal muscle fibers can be generally distinguished by their characteristics of contraction as slow and fast type myofibers. The diversity of contractile properties and metabolism enable skeletal muscles to respond to the variable functional requirements. We investigated the muscle fiber composition and metabolic enzyme activities of splenius muscle and gluteus medius muscle from Mongolian horses. The deep RNA-seq analysis of detecting differentially expressed mRNAs, lncRNAs, circRNAs and their correlation analysis from two muscles were performed. Splenius muscle and gluteus medius muscle from Mongolian horses showed a high divergence of myofiber compositions and metabolic enzyme activities. Corresponding to their phenotypic characteristics, 57 differentially expressed long noncoding RNAs and 12 differentially expressed circle RNAs were found between two muscles. The analysis results indicate multiple binding sites were detected in lncRNAs and circRNAs with myofiber-specific expressed miRNAs. Among which we found significant correlations between the above noncoding RNAs, miRNAs, their target genes, myofiber-specific developmental transcript factors, and sarcomere genes. We suggest that the ceRNA mechanism of differentially expressed noncoding RNAs by acting as miRNA sponges could be fine tuners in regulating skeletal muscle fiber composition and transition in horses, which will operate new protective measures of muscle disease and locomotor adaption for racehorses.

The distinct transcriptomes of fast-twitch and slow-twitch muscles in Mongolian horses.

Skeletal muscle is the largest organ system in the mammalian body and plays a key role in locomotion of horses. Fast and slow muscle fibers have different abilities and functions to adapt to exercises. To investigate the RNA and miRNA expression profiles in the muscles with different muscle fiber compositions on Mongolian horses. We examined the muscle fiber type population and produced deep RNA sequencing for different parts of skeletal muscles. And chose two of them with the highest difference in fast and slow muscle fiber population (splenius and gluteus medius) for comparing the gene expression profile of slow and fast muscle fiber types. We identified a total of 275 differentially expressed genes (DEGs), and 11 differentially expressed miRNAs (DEmiRs). In addition, target gene prediction and alternative splicing analysis were also performed. Significant correlations were found between the differentially expressed gene, miRNAs, and alternative splicing events. The result indicated that differentially expressed muscle-specific genes and target genes of miRNAs might co-regulating the performance of slow and fast muscle fiber types in Mongolian horses.