Arsenic trioxide is an old drug and has been used for a long time in traditional Chinese and Western medicines. However, the cancer treatment of arsenic trioxide has heart and vascular toxicity. The cytotoxic effects of arsenic trioxide and its molecular mechanism in human umbilical mesenchymal stem cells (HUMSC) and human bone marrow-derived mesenchymal stem cells (HMSC-bm) were investigated in this study. Our results showed that arsenic trioxide significantly reduced the viability of HUMSC and HMSC-bm in a concentration- and time-dependent manner. Arsenic trioxide is able to induce apoptotic cell death in HUMSC and HMSC-bm, as shown from the results of morphological examination, flow cytometric analyses, DAPI staining and comet assay. The appearance of arsenic trioxide also led to an increase of intracellular free calcium (Ca(2+) ) concentration and the disruption of mitochondrial membrane potential (ΔΨm). The caspase-9 and caspase-3 activities were time-dependently increased in arsenic trioxide-treated HUMSC and HMSC-bm. In addition, the proteomic analysis and DNA microarray were carried out to investigate the expression level changes of genes and proteins affected by arsenic trioxide treatment in HUMSC. Our results suggest that arsenic trioxide induces a prompt induction of ER stress and mitochondria-modulated apoptosis in HUMSC and HMSC-bm. A framework was proposed for the effect of arsenic trioxide cytotoxicity by targeting ER stress.

Background: Severely burned patients are at high risk for cardiopulmonary failure. Promising studies have stimulated interest in using extracorporeal membrane oxygenation as a potential therapy for burn patients with refractory cardiac and/or respiratory failure. However, the findings from previous studies vary. Methods: In this study, the authors conducted a systematic review and meta-analysis using standardized mortality ratios to elucidate the benefits associated with the use of extracorporeal membrane oxygenation in patients with burn and/or inhalation injuries. A literature search was performed, and clinical outcomes in the selected studies were compared. Results: The meta-analysis found that the observed mortality was significantly higher than the predicted mortality in patients receiving extracorporeal membrane oxygenation (standardized mortality ratio, 2.07; 95 percent CI, 1.04 to 4.14). However, the subgroup of burn patients with inhalation injuries had lower mortality rates compared to their predicted mortality rates (standardized mortality ratio, 0.95; 95 percent CI, 0.52 to 1.73). Other subgroup analyses reported no benefits from extracorporeal membrane oxygenation; however, these results were not statistically significant. Interestingly, the pooled standardized mortality ratio values decreased as the selected patients’ revised Baux scores increased (R = −0.92), indicating that the potential benefits from the treatment increased as the severity of patients with burns increased. Conclusions: The authors’ meta-analysis revealed that burn patients receiving extracorporeal membrane oxygenation treatment were at a higher risk of death. However, select patients, including those with inhalation injuries and those with revised Baux scores over 90, would benefit from the treatment. The authors suggest that burn patients with inhalation injuries or with revised Baux scores exceeding 90 should be considered for the treatment and early transfer to an extracorporeal membrane oxygenation center.