Ac-SDKP increases α-TAT 1 and promotes the apoptosis in lung fibroblasts and epithelial cells double-stimulated with TGF-ß1 and silica.

Crystalline silica (SiO2) particles have very strong toxicity to the lungs, and silicosis is an excessive pulmonary interstitial remodeling disease that follows persistent SiO2 injury. We showed here that DNA double strand breaks (DSBs) and apoptosis were aggravated during rat silicosis induced by SiO2 exposure. Ac-SDKP attenuates lung parenchymal distortion and collagen deposition, and decreases the expression of γH2AX, p21, and cleaved caspase-3, as well as improves the reduction of pulmonary function caused by silicosis. In vitro, we found an evolution of smooth muscle actin α (α-SMA), collagen type I (Col I) in both A549 and MRC-5 cells in response to transforming growth factor-beta 1 (TGF-ß1) + SiO2. Only A549 cells showed any reduction in the rate of apoptosis induced by the double stimulation, because of the anti-apoptotic effects of TGF-ß1. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an anti-fibrotic tetrapeptide. It also has the ability to promote the apoptosis of leukemia cells. However its role in promoting cell apoptosis in silicosis is still unknown. We here found that Ac-SDKP could induce cell apoptosis and inhibit fibrotic response in A549 and MRC-5 cells treated with TGF-ß1 + SiO2, and these effects depended on regulation of α-tubulin acetyltransferase 1 (α-TAT1). These findings suggest that Ac-SDKP may have therapeutic value in the treatment of silicotic fibrosis.

Positron emission tomography/magnetic resonance imaging for the diagnosis and differentiation of pancreatic tumors.

OBJECTIVE: This retrospective study aimed to evaluate the diagnostic efficiency of simultaneous positron emission tomography/magnetic resonance imaging (PET/MR) in differentiating the benign and malignant of pancreatic tumors as well as the differentiation of pancreatic cancer. METHODS: A total of 62 patients with suspected pancreatic tumors, diagnosed by PET/MR examinations, were collected in this study. These patients were divided into benign group and malignant group. The characteristics of the morphological MR, apparent diffusion coefficient (ADC), the mean of standardized uptake value (SUVmean), maximum values of standardized uptake value (SUVmax), in lesions were measured, and the novel parameters SUVpeak/ADC and SUVmax/ADC were constructed. The diagnostic efficiency for differentiating the benign and malignant lesions was analyzed by receiver operating characteristic (ROC) curve, and the diagnosis efficiency for the differentiation of pancreatic cancer was analyzed by Spearman correlation analysis. RESULTS: In differentiating the benign and malignant of pancreatic tumors, the diagnostic efficiency increased in the order of SUVpeak (AUROC: 0.760), SUVmax (AUROC: 0.774), T1T2 (AUROC: 0.789), ADC (AUROC: 0.817), SUVpeak/ADC (AUROC: 0.836), SUVmax/ADC (AUROC: 0.847). There was no significant correlation for SUVmax, SUVpeak, ADC, SUVpeak/ADC, and SUVmax/ADC with the differentiation of pancreatic cancer (P > 0.05). Besides, T1T2 was not significantly correlated to the differentiation of pancreatic cancer (P = 0.026, r = -0.406). CONCLUSION: The integration of PET/MR imaging could be used to efficiently diagnose whether the pancreatic tumor was benign or malignant. The SUVmax/ADC was the most efficient metric, while it could not help in the differentiation of pancreatic cancer.

Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica.

Silicosis is the most serious occupational disease in China. The objective of this study was to screen various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) using proteomic profile analysis. We also aimed to explore a potential mechanism of acetylated α-tubulin (α-Ac-Tub) regulation by Ac-SDKP. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to assess the different protein expression profiles between control and silicosis rats treated with or without Ac-SDKP. Twenty-nine proteins were identified to be potentially involved in the progression of silicosis and the anti-fibrotic effect of Ac-SDKP. Our current study finds that 1) the lost expression of Ac-Tub-α may be a new mechanism in rat silicosis; 2) treatment of silicotic rats with N-acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits myofibroblast differentiation and collagen deposition accompanied by stabilizing the expression of α-Ac-Tub in vivo and in vitro, which is related with deacetylase family member 6 (HDAC6) and α-tubulin acetyl transferase (α-TAT1). Our data suggest that α-Ac-Tub regulation by Ac-SDKP may potentially be a new anti-fibrosis mechanism.