Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma, displays marked heterogeneity. Although it is usually curable, 30-40% of patients die within 1-2 years due to refractory treatment or cancer relapse. In different types of cancer in humans, inorganic pyrophosphatase (PPA1) is deregulated, thereby contributing to tumorigenesis by supplying the tumor with an enormous energy source. However, the role of PPA1 in DLBCL is still unclear. Here, we analized PPA1 in 65 patients with DLBCL and 20 patients with reactive hyperplasia of the lymph nodes (control). The PPA1 level was significantly higher in patients with DLBCL than in control subjects (p < 0.05), and it is closely associated with B symptoms (i.e., fever, night sweats, and weight loss) and the IPI score (p < 0.05). Furthermore, PPA1 mRNA and protein levels were higher in most DLBCL cell lines than in the control HMy2.CIR cell line. Lastly, we investigated the effects of PPA1 knockdown on the proliferation and survival of the DLBCL cell line. We found that p53 and p21 expression decreased in PPA1-silenced DLBCL cells. In addition, cell proliferation decreased and cell apoptosis increased. In conclusion, PPA1 is a novel molecule that may be useful in the development and prognosis of DLBCL in the future.

-Patients with diabetes mellitus, particularly those with cardiovascular complications, have increased risk of mortality when subject to anesthetics and surgery, compared with non-diabetic patients. Anesthetics may exert pressure on the cardiovascular system of diabetic patients, directly or by aggravating pre-existing cardiovascular complications. Advanced glycation end products (AGEs) are extremely accumulated in diabetes mellitus, and are confirmed to play an important role in the pathogenesis of diabetic microvascular and macrovascular complications. The purpose of the present study was to investigate the regulatory role of etomidate, which is widely used as intravenous general anesthetics, on the viability and apoptosis of human endothelial Eahy926 cells, in the presence of AGEs. The results demonstrated that etomidate and Glu-BSA (one type of AGE) synergistically reduced the human endothelial Eahy926 cell viability and induced cell apoptosis. In addition, western blot assay of apoptosis-associated molecules indicated that both agents synergistically upregulated the cytochrome c release, activated the apoptosis executor, caspase 3, and promoted the poly-ADP-ribose polymerase (PARP) lysis. Further results confirmed that the two agents synergistically promoted oxidative stress by decreasing mitochondrial respiratory chain complex IV and mitochondrial membrane potential (MMP), while upregulating reactive oxygen species (ROS) and mitochondrial superoxide. In conclusion, the results presented in this study offer a novel insight into the mechanisms of endothelial cell apoptosis in response to etomidate in the presence of AGEs. These results suggest that oxidative stress has important role in the synergistic promotion of apoptosis by etomidate and AGEs in endothelial Eahy926 cells.

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