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Adhesion between circulating monocytes and vascular endothelial cells is a key initiator of atherosclerosis. In our previous studies, it was demonstrated that the expression of connexin (Cx)43 in monocytes modulates cell adhesion, however, the effects of the expression of Cx43 in endothelial cells remains to be elucidated. Therefore, the present study investigated the role of the expression of Cx43 in endothelial cells in the process of cell adhesion. A total of four different methods with distinct mechanisms were used to change the function and expression of Cx43 channels in human umbilical vein endothelial cells: Cx43 channel inhibitor (oleamide), enhancer (retinoic acid), overexpression of Cx43 by transfection with pcDNA-Cx43 and knock-down of the expression of Cx43 by small interfering RNA against Cx43. The results indicated that the upregulation of the expression of Cx43 enhanced monocyte-endothelial adhesion and this was markedly decreased by downregulation of Cx43. This mechanism was associated with Cx43-induced expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1. The effects of Cx43 in endothelial cells was independent of Cx37 or Cx40. These experiments suggested that local regulation of endothelial Cx43 expression within the vasculature regulates monocyte-endothelial adhesion, a critical event in the development of atherosclerosis and other inflammatory pathologies, with baseline adhesion set by the expression of Cx43. This balance may be crucial in controlling leukocyte involvement in inflammatory cascades. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication following orthotopic liver transplantation (OLT) that evidently affects prognosis. However, no effective treatment exists for AKI. The aim of the present study was to elucidate whether ulinastatin application during OLT in humans can reduce kidney damage and improve renal function. In addition, the underlying mechanisms of ulinastatin were investigated on a rat autologous OLT (AOLT) model. In total, 60 patients undergoing an OLT were randomly selected to receive ulinastatin (U group; n=30) or saline (C group; n=30) during the OLT surgery. The patient demographics, AKI incidence rate, recovery indicators and renal injury indexes were measured during the perioperative period. In addition to the clinical trials, 40 rats were subjected to an AOLT and were divided into the control (C-R), sham-operation and ulinastatin treatment groups. Pathological renal damage, biomarkers of inflammation and oxidative stress were measured to investigate the effects and possible mechanisms of ulinastatin on AKI. In the clinical trials, ulinastatin application was shown to attenuate the incidence of AKI following OLT (P<0.05) and reduce the serum levels of cystatin C and urinary β2 microglobulin within 24 h of the OLT (P<0.05). Furthermore, ulinastatin was found to significantly improve the recovery of patients by reducing the time spent in the intensive care unit (P<0.01 vs. C group), the ventilation time and the hemodialysis rates (P<0.05 vs. C group). In the rat AOLT model, ulinastatin application was also shown to relieve renal pathological damage by reducing the serum cystatin C and creatinine levels. Notably, the levels of tumor necrosis factor-α, interleukin-6, hydrogen peroxide and reactive oxygen species were evidently reduced, while the level of superoxide dismutase was increased in the ulinastatin groups (P<0.05, vs. C-R group). In conclusion, ulinastatin application was demonstrated to protect against AKI following OLT by inhibiting inflammation and oxidation. [ABSTRACT FROM AUTHOR]

Liver transplantation is known to trigger intestinal injuries. Oxidative damage that is induced by reactive oxygen species (ROS) plays a crucial role in ischemia-reperfusion injuries. NF-E2-related factor-2 (Nrf2) and its modulated antioxidant enzymes form the critical endogenous antioxidant system to scavenge ROS. The present study investigated the dynamic changes of intestinal ROS levels, Nrf2 expression and antioxidant enzyme activity following orthotopic liver autotransplantation (OLAT). Sprague-Dawley rats were randomly divided into five groups consisting of one sham group and four groups with rats that underwent OLAT and were evaluated following 4, 8, 16 and 24 h, respectively. The intestinal specimens were collected for histopathological examination and the detection of hydrogen peroxide (H2O2), hydroxyl radical (*OH), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and the expression of Nrf2. The present study demonstrated that OLAT resulted in severe intestinal injury, which manifested as a significant change in the intestine pathological scores as early as 4 h and peaking at 8 h post-treatment. Oxidative stress was also revealed by the increase of the H2O2, *OH and MDA levels. Significant decreases were observed in the activity of SOD and CAT and a dramatic decrease occurred in the levels of GSH at 4 and 8 h post-treatment. All the parameters were restored gradually at 16 and 24 h post-treatment. The expression of Nrf2 in the intestinal tissues increased significantly at 4, 16 and 24 h following OLAT. The present study shows that an imbalance between oxidants and antioxidants contributes to intestinal oxidative injury, and that the upregulation of Nrf2 is not sufficient to withstand intestinal oxidative injury following OLAT. [ABSTRACT FROM AUTHOR]