As effective non-viral vectors of gene therapy, cationic lipids still have the problem of toxicity, which has become one of the main bottlenecks for their applications. The toxicity of cationic lipids is strongly connected to the headgroup structures. In this article, we studied the cytotoxicity of two cationic lipids with a quaternary ammonium headgroup (CDA14) and a tri-peptide headgroup (CDO14), respectively, and with the same linker bond and hydrophobic domain. The IC values of CDA14 and CDO14 against NCI-H460 cells were 109.4 μg mL and 340.5 μg mL, respectively. To determine the effects of headgroup structures of cationic lipids on cytotoxicity, apoptosis related pathways were investigated. As the lipids with a quaternary ammonium headgroup could induce more apoptotic cells than the ones with a peptide headgroup, the enzymatic activity of caspase-9 and caspase-3 increased obviously, whereas the mitochondrial membrane potential (MMP) decreased. At the same time, the reactive oxygen species (ROS) levels also increased and the cell cycle was arrested at the S phase. The results showed that the toxicity of the cationic lipid had a close relationship with its headgroup structures, and the cytotoxic mechanism was mainly the caspase activation dependent signaling pathway and mitochondrial dysfunction. Through this study, we hope to provide the scientific basis for exploiting safer and more efficient cationic lipids for gene delivery.

Background Individuals with mild cognitive impairment and dementia have impaired physical and cognitive functions, leading to a reduced quality of life compared with those without such impairment. Exergaming, which is defined as a combination of exercise and gaming, is an innovative, fun, and relatively safe way to exercise in a virtual reality or gaming environment. Therefore, exergaming may help people living with mild cognitive impairment or dementia to overcome obstacles that they may experience regarding regular exercise and activities. Objective The aim of this systematic review was to review studies on exergaming interventions administered to elderly individuals with mild cognitive impairment and dementia, and to summarize the results related to physical and cognitive functions such as balance, gait, executive function, and episodic memory. Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, PsycINFO, Amed, and Nursing Database for articles published from the inception of the respective databases to January 2019. We included all clinical trials of exergaming interventions in individuals with mild cognitive impairment and dementia for review. The risk of bias was independently evaluated by two reviewers using the Cochrane Collaboration and Risk of Bias in Non-randomized Studies of Interventions tools. Results Ten studies involving 702 participants were included for review. There was consistent evidence from 7 studies with a low risk of bias showing statistically significant effects of exergaming on cognitive functioning in people with mild cognitive impairment and dementia. With respect to physical function, 3 of 5 full-scale studies found positive results, and the intensity of most games was classified as moderate. Conclusions Overall, exergaming is an innovative tool for improving physical and cognitive function in people with mild cognitive impairment or dementia, although there is high heterogeneity among studies in terms of the duration, frequency, and gaming platform used. The quality of the included articles was moderate to high. More high-quality studies with more accurate outcome indicators are needed for further exploration and validation of the benefits of exergaming for this population.