IOX1 impedes host inflammation in imiquimod-triggered psoriasis.

Psoriasis is a chronic autoimmune disease with an unknown etiology and highly limited treatment strategies. The drugs currently used in the treatment of psoriasis are rarely recommended for long-term use owing to the serious side effects. Although different targets have been identified for controlling psoriasis, the role of epigenetic modifications as therapeutic targets is yet to be elucidated. Here, we investigated the therapeutic potential of 8-hydroxyquinoline-5-carboxylic acid (IOX1), a novel drug with a genetic target, in psoriasis. The daily topical administration of IOX1 in a mouse model of imiquimod (IMQ)-induced psoriatic inflammation reduced inflammatory reactions in the skin and lowered the PASI score. Furthermore, intraperitoneally injected IOX1 repressed the inflammatory status induced by IMQ in psoriatic mice by reducing the mRNA levels of pro-inflammatory cytokines, restoring splenocyte populations, and regulating macrophage polarization. Our findings indicate the remedial effects of IOX1 on dermatitis psoriasis and the potential of IOX1 as a therapeutic compound in psoriasis.

Myostatin inhibitor YK11 as a preventative health supplement for bacterial sepsis.

Muscle wasting caused by catabolic reactions in skeletal muscle is commonly observed in patients with sepsis. Myostatin, a negative regulator of muscle mass, has been reported to be upregulated in diseases associated with muscle atrophy. However, the behavior of myostatin during sepsis is not well understood. Herein, we sought to investigate the expression and regulation of myostatin in skeletal muscle in mice inoculated with gram-negative bacteria. Interestingly, the protein level of myostatin was found to increase in the muscle of septic mice simultaneously with an increase in the levels of follistatin, NF-κΒ, myogenin, MyoD, p- FOXO3a, and p-Smad2. Furthermore, the inhibition of myostatin by YK11 repressed the levels of pro-inflammatory cytokines and organ damage markers in the bloodstream and in the major organs of mice, which originally increased in sepsis; thus, myostatin inhibition by YK11 decreased the mortality rate due to sepsis. The results of this study suggest that YK11 may help revert muscle wasting during sepsis and subdue the inflammatory environment, thereby highlighting its potential as a preventive agent for sepsis-related muscle wasting.