Targeting mitochondrial dynamics proteins for the treatment of doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an extensively used chemotherapeutic agent that can cause severe and frequent cardiotoxicity, which limits its clinical application. Although there have been extensive researches on the cardiotoxicity caused by DOX, there is still a lack of effective treatment. It is necessary to understand the molecular mechanism of DOX-induced cardiotoxicity and search for new therapeutic targets which do not sacrifice their anticancer effects. Mitochondria are considered to be the main target of cardiotoxicity caused by DOX. The imbalance of mitochondrial dynamics characterized by increased mitochondrial fission and inhibited mitochondrial fusion is often reported in DOX-induced cardiotoxicity, which can result in excessive ROS production, energy metabolism disorders, cell apoptosis, and various other problems. Also, mitochondrial dynamics disorder is related to tumorigenesis. Surprisingly, recent studies show that targeting mitochondrial dynamics proteins such as DRP1 and MFN2 can not only defend against DOX-induced cardiotoxicity but also enhance or not impair the anticancer effect. Herein, we summarize mitochondrial dynamics disorder in DOX-induced cardiac injury. Furthermore, we provide an overview of current pharmacological and non-pharmacological interventions targeting proteins involved in mitochondrial dynamics to alleviate cardiac damage caused by DOX.

The transient receptor potential channels in rheumatoid arthritis: Need to pay more attention.

Rheumatoid arthritis (RA) is characterized by the augment of vascular permeability, increased inflammatory cells infiltration, dysregulated immune cells activation, pannus formation and unbearable pain hyperalgesia. Ca2+ affect almost every aspect of cellular functions, involving cell migration, signal transduction, proliferation, and apoptosis. Transient receptor potential channels (TRPs) as a type of non-selective permeable cation channels, can regulate Ca2+ entry and intracellular Ca2+ signal in cells including immune cells and neurons. Researches have demonstrated that TRPs in the mechanisms of inflammatory diseases have achieved rapid progress, while the roles of TRPs in RA pathogenesis and pain hyperalgesia are still not well understood. To solve this problem, this review presents the evidence of TRPs on vascular endothelial cells in joint swelling, neutrophils activation and their trans-endothelial migration, as well as their bridging role in the reactive oxygen species/TRPs/Ca2+/peptidyl arginine deiminases networks in accelerating citrullinated proteins formation. It also points out the distinct functions of TRPs subfamilies expressed in the nervous systems of joints in cold hyperalgesia and neuro-inflammation mutually influenced inflammatory pain in RA. Thus, more attention could be paid on the impact of TRPs in RA and TRPs are useful in researches on the molecular mechanisms of anti-inflammation and analgesic therapeutic strategies.