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The use of cyclosporine A as monotherapy was reported in 137 patients and provided an ORR of 83.2% (95% CI, 72.3-94.1, I 2 , 58%), whereas 124 patients were reported to receive cyclosporine combined with corticosteroids, providing an ORR of 77.3% (95% CI, 69.9-84.7, I 2 , 0%)
It is now accepted that this overoxidation leads to the transient inactivation of the peroxidase activity allowing the local accumulation of H 2 O 2 which can then promote appropriate signaling pathways ( 2 H are mostly irreversible oxidation forms, an enzyme called sulfiredoxin (Srx) is able to catalyze the ATP-dependent reduction of the SO 2 H formed on these sensitive 2-Cys Prxs ( 2 H formed on 2-Cys Prxs but also on plant PrxII or mammalian PrxV ( 2 H reduction proceeds via the formation of a phosphoryl intermediate on the sulfinyl moiety, attacked by the catalytic cysteine of Srx finally forming a thiosulfinate intermediate between Prx and Srx ( To further illustrate cysteine-based signaling mechanisms in response to peroxides, it is worth mentioning that the DNA binding activity of numerous transcription factors in microbes (bacteria or fungi), such as OxyR, OhrR, AP1, or CrtJ is regulated by the primary formation of a sulfenic acid which is often transformed into a disulfide bond ( The biochemical characterization of recombinant proteins coupled to redox proteome studies often led to the observation that a single protein, either a metabolic enzyme or a signaling protein can undergo a plethora of redox PTMs
On the other hand, various risk factors such as unhealthy dietary regimens, physical inactivity, smoking, and alcohol abuse play a major role in the development and acceleration of cardiovascular diseases (80)
