Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad­spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti­inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation­induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase­3, B­cell lymphoma­2 (Bcl­2) family proteins, total­Akt and phospho­Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase­3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl­2, Bcl­extra large and Bcl­associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI­induced anti­apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.

[Prognostic value of extra-vascular lung water index and pulmonary vascular permeability index in patients with ARDS].

OBJECTIVE: To investigate the correlation of the extra-vascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) with disease severity and their prognostic value in patients with acute respiratory distress syndrome (ARDS). METHODS: A total of 44 patients with ARDS from October 2012 to June 2014 admitted in the Second Affiliated Hospital of Wenzhou Medical University were recruited in this study. According to the severity, patients were divided into three groups (Mild group, Moderate group and Severe group); the acute physiology and chronic health evaluation system II score (APACHE II), the lung injury score (LIS), the pulse contour curve continuous cardiac output (PiCCO) and other clinical indicators were respectively monitored in the period of 24, 48, 72 hrs after admission; then the correlation of EVLWI, PVPI and oxygenation index (OI) among groups were analyzed; According to the prognosis, patients were divided into the survival group and the death group, both given the univariate and multivariate Logistic regression analysis; EVLWI, PVPI, APACHE II score, LIS and lactic acid were admitted into the receiver operating characteristic (ROC) curve analysis, and the prognosis was evaluated respectively. RESULTS: With the increase of disease severity, LIS and lactic acid gradually increased, the difference was significant among the three groups of Mild, Moderate and Severe (P<0.05). And the APACHE II score also increased gradually with the severity, but the difference was statistically significant only between the Mild group and the Severe group (P<0.01). And likewise, mild, moderate, severe ARDS patients had 1, 6, 9 cases of death, respectively. The 28-day mortality rate increased gradually after admission, with a significant difference between the Mild group and the Severe group (P<0.05). When all the 44 patients of three severities (during the 24 hrs period and during the 72 hrs period) were compared, the OI gradually decreased with the increase of severity of ARDS, while EVLWI and PVPI ascended, and differences between any two groups were statistically significant (P<0.05). In addition, there was a significant negative correlation between EVLWI and OI or between PVPI and OI (r=-0.666, -0.763, all P<0.01), and a significant positive correlation between EVLWI and PVPI, the APACHE II score or LIS (r=0.929, 0.895, 0.661, all P<0.01). Besides, OI was a predictive protection factor of ARDS, whereas lactic acid, EVLWI and PVPI were risk factors. Multivariate Logistic regression analysis showed that EVLWI and lactic acid were risk factors for ARDS death (all P<0.05). ROC curve analysis results suggested EVLWI and lactic acid were risk factors, (odd ratio (OR)> 1, and 95%CI: 1.071-5.201, 5.201-99.852, all P<0.05). CONCLUSION: EVLWI, PVPI were positively correlated with the severity of ARDS illness; EVLWI can be used as an independent risk factor for forecasting ARDS death, jointing EVLWI with PVPI could improve the accuracy of ARDS death forecasting.