Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics

Cross-education does not accelerate the rehabilitation of neuromuscular functions after ACL reconstruction: a randomized controlled clinical trial

Purpose: Cross-education reduces quadriceps weakness 8 weeks after anterior cruciate ligament (ACL) surgery, but the long-term effects are unknown. We investigated whether cross-education, as an adjuvant to the standard rehabilitation, would accelerate recovery of quadriceps strength and neuromuscular function up to 26 weeks post-surgery. Methods: Group allocation was randomized. The experimental (n = 22) and control (n = 21) group received standard rehabilitation. In addition, the experimental group strength trained the quadriceps of the non-injured leg in weeks 1–12 post-surgery (i.e., cross-education). Primary and secondary outcomes were measured in both legs 29 ± 23 days prior to surgery and at 5, 12, and 26 weeks post-surgery. Results: The primary outcome showed time and cross-education effects. Maximal quadriceps strength in the reconstructed leg decreased 35% and 12% at, respectively, 5 and 12 weeks post-surgery and improved 11% at 26 weeks post-surgery, where strength of the non-injured leg showed a gradual increase post-surgery up to 14% (all p ≤ 0.015). Limb symmetry deteriorated 9–10% more for the experimental than control group at 5 and 12 weeks post-surgery (both p ≤ 0.030). One of 34 secondary outcomes revealed a cross-education effect: Voluntary quadriceps activation of the reconstructed leg was 6% reduced for the experimental vs. control group at 12 weeks post-surgery (p = 0.023). Both legs improved force control (22–34%) and dynamic balance (6–7%) at 26 weeks post-surgery (all p ≤ 0.043). Knee joint proprioception and static balance remained unchanged. Conclusion: Standard rehabilitation improved maximal quadriceps strength, force control, and dynamic balance in both legs relative to pre-surgery but adding cross-education did not accelerate recovery following ACL reconstruction