Radiation dermatitis (RD) is a common side effect in patients receiving radiotherapy. Currently, clinical skincare approaches for acute RD vary widely among institutions and lack consensus. Hydrogen molecules, acting as radioprotective agents by selectively scavenging free radicals, have the potential to protect against RD. In this study, we demonstrate that hydrogen reduces double-strand breaks, mitochondrial depolarization, and inflammatory cytokines induced by irradiation damage in HaCaT cells. Furthermore, in vivo experiments reveal that exposing irradiated skin areas to a hydrogen gas environment alleviates RD. Assessment of skin appearance grade and histology staining revealed that direct transdermal application of hydrogen can prevent radiation-induced follicle damage, dermal thickening, and leukocyte infiltration, thereby reducing the severity of RD. In addition, hydrogen enhances the skin’s antioxidant capacity, leading to a reduction in the Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio, the number of apoptotic cells, and the expression of pro-inflammatory cytokines. Our data demonstrate that hydrogen possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, and could be a preventive strategy for RD.

In-stent restenosis is a serious concern for patients treated through the stenting procedure, although this can be solved using drug-eluting stents and/or drug-eluting balloon catheters. However, the chemical agents released from the drug-eluting layer for inhibiting smooth muscle cell (SMC) migration are inevitably associated with damage to vascular endothelial cell (ECs). The present in vitro study used a distinct strategy, in which a smart gene (phEGR1-PKCδ, an engineered plasmid consists of an SMC-specific promoter (human early growth response 1, hEGR1 promoter) ligated with a gene encoding apoptosis-inducing protein (protein kinase C-delta, PKCδ) was incorporated into a novel gene vehicle (Au cluster-incorporated polyethylenimine/carboxymethyl hexanoyl chitosan, PEI-Au/CHC) to form the PEI-Au/CHC/phEGR1-PKCδ complex, which was proposed for the selective inhibition of SMC proliferation. It was found that the cell viability of SMCs receiving the PEI-Au/CHC/phEGR1-PKCδ complex under simulated inflammation conditions was significantly lower than that of the ECs receiving the same treatment. In addition, the PEI-Au/CHC/phEGR1-PKCδ complex did not demonstrate an inhibitory effect on EC proliferation and migration under simulated inflammation conditions. Finally, the PEI-Au/CHC/phEGR1-PKCδ complexes coated onto a balloon catheter used in percutaneous transluminal coronary angioplasty (PTCA) could be transferred to both the ECs and the SMC layer of Sprague Dawley (SD) rat aortas ex vivo. These preliminary in vitro results suggest that the newly developed approach proposed in the present study might be a potential treatment for reducing the incidence rate of in-stent restenosis and late thrombosis in the future.