Our findings show that transient human matrix metalloproteinase-1 overexpression in the liver effectively attenuates established fibrosis and induces hepatocyte proliferation.

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Breast cancer is the leading cause of cancer and mortality in women worldwide. Recent studies have argued that there is a close relationship between lipid synthesis and cancer progression because some enzymes related to lipid synthesis are overexpressed in breast cancer tissues. However, lipid distribution in breast cancer tissues has not been investigated. We aimed to visualize phosphatidylcholines (PCs) and lysoPCs (LPCs) in human breast cancer tissues by performing matrix assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), which is a novel technique that enables the visualization of molecules comprehensively. Twenty-nine breast tissue samples were obtained during surgery and subjected to MALDI-IMS analysis. We evaluated the heterogeneity of the distribution of PCs and LPCs on the tissues. Three species [PC(32∶1), PC(34∶1), and PC(36∶1)] of PCs with 1 mono-unsaturated fatty acid chain and 1 saturated fatty acid chain (MUFA-PCs) and one [PC(34∶0)] of PCs with 2 saturated fatty acid chains (SFA-PC) were relatively localized in cancerous areas rather than the rest of the sections (named reference area). In addition, the LPCs did not show any biased distribution. The relative amounts of PC(36∶1) compared to PC(36∶0) and that of PC(36∶1) to LPC(18∶0) were significantly higher in the cancerous areas. The protein expression of stearoyl-CoA desaturase-1 (SCD1), which is a synthetic enzyme of MUFA, showed accumulation in the cancerous areas as observed by the results of immunohistochemical staining. The ratios were further analyzed considering the differences in expressions of the estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67. The ratios of the signal intensity of PC(36∶1) to that of PC(36∶0) was higher in the lesions with positive ER expression. The contribution of SCD1 and other enzymes to the formation of the observed phospholipid composition is discussed.

Abstract:In hemodialysis (HD) patients the glycated hemoglobin (HbA1c) level may underestimate glycemic control. The aim of this study is to estimate accurate glycemic control in type 2 diabetic patients on HD. Type 2 diabetes patients (N = 87) who had been receiving maintenance HD for at least one year were enrolled. HbA1c and the percentage of glycated albumin relative to total the serum albumin (%GA) were measured in blood samples and the factors that affected the %GA/HbA1c ratio were examined. There were significant and positive correlations between the plasma glucose and either the HbA1c levels (r = 0.539, P < 0.01) or the %GA level (r = 0.520, P < 0.01). No relationship between the serum albumin levels and %GA levels was observed. A weekly dose of erythropoietin (EPO) was positively correlated with the ratio of %GA/HbA1c and hematocrit (Ht) correlated negatively. There was no significant correlation between the %GA/ HbA1c level and the EPO dose in patients with Ht Ն 30%, although a significant correlation was found between those parameters in the Ht < 30% group. The mean of the %GA/ HbA1c ratios in patients with Ht Ն 30%, with Ht < 30% and treated with EPO < 100 IU/kg/week, and with Ht < 30% and treated with EPO Ն 100 IU/kg/week were 3.41, 3.56 and 4.13, respectively. In HD patients, accurate glycemic control may be estimated as: HbA1c ¥ 1.14 if Ht Ն 30%; HbA1c ¥ 1.19 if Ht < 30% and treated with low dosages of EPO; and HbA1c ¥ 1.38 if Ht < 30% and treated with high dosages of EPO.

We conclude that Rac1 is required in ROS generation and NF-kappaB activation after hepatic I/R in vivo, and that inactivation of NF-kappaB in NPCs and suppression of ROS generation in NPCs and hepatocytes possibly account for the protective effect of N17Rac1 in this study.

Glycated albumin (GA) is considered a more reliable marker than glycated hemoglobin (HbA1c) for monitoring glycemic control, particularly in diabetic hemodialysis patients. We investigated the associations of GA, HbA1c, and random serum glucose levels with survival, and evaluated possible targets for improving survival in diabetic hemodialysis patients. In this prospective, longitudinal, observational study, we enrolled 90 diabetic hemodialysis patients across six dialysis centers in Japan. The median duration of follow-up was 36.0 months (mean follow-up, 29.8 months; range, 3-36 months). There were 11 deaths during the observation period. GA was a significant predictor for mortality (hazard ratio, 1.143 per 1% increase in GA; 95% confidence interval, 1.011-1.292; P = 0.033), whereas HbA1c and random glucose levels were not predictors for mortality. Receiver operating characteristics curve analysis showed that the cutoff value of GA for predicting the risk of mortality was 25%. In the Kaplan-Meier analysis, the cumulative survival rate was significantly greater in patients with GA ≤ 25% than in patients with GA >25%. GA predicted the risk of all-cause and cardiovascular mortality in diabetic hemodialysis patients. Our results suggest that GA ≤ 25% is an appropriate target for improving survival in diabetic hemodialysis patients.

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