15 research outputs found
Prevention of Prostate Tumor Development by Stimulation of Antitumor Immunity Using a Standardized Herbal Extract (Deep ImmuneÂź) in TRAMP Mice
Low-risk prostate cancer (PCa) does not require immediate treatment, but PCa progression after years of active surveillance will need the treatment. This study was to test the efficacy of immunostimulant Deep Immune (DI) in controlling PCa progression. DI is an extract of eight different medicinal herbs. In vitro activity of DI was determined by phagocytosis activation using flow cytometric analysis of fluorescence-labeled latex bead uptake, expression of immune-modulating 84 genes using PCRarray, and tumor killing using coculturing with immune cells. Anti-PCa activity of DI in vivo was examined in male TRAMP mice. In vitro DI stimulated phagocytosis and expression of a panel of inflammatory mediators (C4b, CXCL3, lymphotoxin, NOS2, TLR1, TNF, and TNFSF14) in cultured macrophages and increased tumor killing of both macrophages and TRAMP mouse splenocytes. Daily intake of this herbal product significantly suppressed the tumor size (P=0.0368) with lower histopathologic scores (P=0.0364) in TRAMP mice, which were associated with an increase in both splenocyte cytotoxicity against tumor cells and numbers of CD8 T cells, macrophages, and dendritic cells in the spleens in vivo. In conclusion, daily intake of DI prevents PCa progression in TRAMP mice, suggesting the possible effectiveness of the immunostimulant herbal products on prevention of PCa progression after diagnosis of low-risk PCa
Correlation between EGFR mutation status and F18âfluorodeoxyglucose positron emission tomographyâcomputed tomography image features in lung adenocarcinoma
Background The purpose of this study was to investigate an association between EGFR mutation status and 18Fâfluorodeoxyglucose positron emission tomographyâcomputed tomography (18FâFDG PETâCT) image features in lung adenocarcinoma. Methods Retrospective analysis of the data of 139 patients with lung adenocarcinoma confirmed by surgical pathology who underwent preoperative 18FâFDG PETâCT was conducted. Correlations between EGFR mutation status, clinical characteristics, and PETâCT parameters, including the maximum standardized uptake value (SUVmax), the mean of the SUV (SUVmean), the peak of the SUV (SUVpeak) of the primary tumor, and the ratio of SUVmax between the primary tumor and the mediastinal blood pool (SUVratio), were statistically analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutation. Receiver operating characteristic curves of statistical quantitative parameters were compared. Results EGFR mutations were detected in 74 (53.2%) of the 139 lung adenocarcinomas and were more frequent in nonâsmoking patients. Univariate analysis showed that the SUVmax, SUVmean, SUVpeak, and SUVratio were lower in EGFRâmutated than in wildâtype tumors. The receiver operating characteristic curves showed no significant differences between their diagnostic efficiencies. Multivariate logistic regression analysis showed that being a never smoker was an independent predictor of EGFR mutation. Conclusion Quantitative parameters based on 18FâFDG PETâCT have modest power to predict the presence of EGFR mutation in lung adenocarcinoma; however, when compared to smoking history, they are not good or significant predictive factors
Tongxinluo attenuates reperfusion injury in diabetic hearts by angiopoietin-like 4-mediated protection of endothelial barrier integrity via PPAR-α pathway
<div><p>Objective</p><p>Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity.</p><p>Methods and results</p><p>I/R injury was created by coronary ligation in ZDF diabetic and non-diabetic control rats. The animals were anesthetized and randomized to sham operation or I/R injury with or without the exposure to insulin, rhAngptl4, TXL, Angptl4 siRNA, and the PPAR-α inhibitor MK886. Tongxinluo, insulin and rhAngptl4 have the similar protective effect on diabetic hearts against I/R injury. In I/R-injured diabetic hearts, TXL treatment remarkably reduced the infarct size, and protected endothelial barrier integrity demonstrated by decreased endothelial cells apoptosis, microvascular permeability, and myocardial hemorrhage, fortified tight junction, and upregulated expression of JAM-A, integrin-α5, and VE-cadherin, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with siRNA interference and inhibition of PPAR-α with MK886 partially diminished these beneficial effects of TXL and rhAngptl4. TXL induced the expression of Angptl4 in I/R-injured diabetic hearts, and was canceled by Angptl4 siRNA and MK886. TXL treatment increased myocardial PPAR-α activity, and was abolished by MK886 but not by Angptl4 siRNA.</p><p>Conclusions</p><p>TXL protects diabetic hearts against I/R injury by activating Angptl4-mediated restoration of endothelial barrier integrity via the PPAR-α pathway.</p></div
Histopathologic assessments of the area at risk and necrosis in the infarcted hearts treated with or without TXL in the presence or absence of signal regulators.
<p>The area at risk and necrosis was respectively examined by Evans blue and triphenyltetrazolium chloride (TTC) staining (n = 8 in each group). The health myocardium was stained blue by Evans blue, the area at risk (AAR) was not stained by Evans blue. TTC-unstained white myocardium was identified as the area of necrosis (AN). Abbreviations: DB-sham = Diabetic sham; DB-MI = Diabetic MI control; non-DB-MI = non-diabetic MI control; rhAngptl4 = recombinant human Angptl4; rhAngptl4+siCtrl = rhAngptl4+control siRNA; TXL+siCtrl = TXL+control siRNA; rhAngptl4+siR = rhAngptl4+Angptl4 siRNA; TXL+siR = TXL+Angptl4 siRNA.</p
Evaluation of intramyocardiac hemorrhage in the infarcted hearts treated with or without TXL.
<p>Sections of the hearts were stained with hematoxylin-eosin (n = 8 in each group). DB-sham group has no obvious extravasation of red blood cells in the interstitial space (A). I/R injury induced apparent extravasation of red blood cells into the interstitial space in both DB-MI (B) and non-DB-MI (C) groups. Treatment with insulin (D), rhAngptl4 (E) or TXL (F) greatly decreased extravasation of red blood cells. Combination with angptl4 siRNA canceled the effects of rhAngptl4 (I) and TXL (J). However, combination with MK886 abolished the effect of TXL (L) but not rhAngptl4 (K). Images were taken under a Leica microscope with 40Ăobjective. Black arrows indicate intra-myocardiac hemorrhage. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198403#pone.0198403.g001" target="_blank">Fig 1</a>.</p
Expression levels of Angptl4 and analysis of PPAR-α activity in the I/R-injured diabetic hearts treated with or without TXL in the presence or absence of signal regulators.
<p>(A) Angptl4 expression was decreased by I/R injury, and pre-treatment with insulin, rhAngptl4, or TXL reverted this effect. Whereas, Angptl4 siRNA and MK886 abolished the TXL-induced upregulation of Angptl4. (B) I/R injury decreased the PPAR-α activity in the I/R-injured myocardium, and even worse in diabetic hearts. Pre-treatment of insulin, rhAngptl4 and TXL increased the PPAR-α activity. Addition of MK886 but not Angptl4 siRNA abolished the TXL-stimulated PPAR-α activation. Compared with the DB-sham group, *<i>P</i><0.05, **<i>P</i><0.01; Compared with the DB-MI group, <sup>â </sup><i>P</i><0.05, <sup>â â </sup><i>P</i><0.01; Compared with the TXL group, <sup>âĄ</sup><i>P</i><0.05, <sup>âĄâĄ</sup><i>P</i><0.01; Compared with the rhAngptl4+siR group, <sup>§§</sup><i>P</i><0.01. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198403#pone.0198403.g001" target="_blank">Fig 1</a>.</p
Identification of endothelial cell apoptosis in the I/R-injured hearts treated with or without TXL by confocal microscopy.
<p>Endothelial cells were identified by red fluorescence (CD34), total cell number was detected by blue fluorescence (DAPI DNA staining), and apoptosis was detected by green fluorescence (TUNEL). Apoptotic endothelial cells were detected and counted by colocalized red and green (displayed as yellow). I/R injury induced significant ECs apoptosis in both MI control and diabetic MI rats (n = 8 in each group). Treatment with insulin, rhAngptl4 or TXL ameliorated ECs apoptosis compared with the diabetic MI controls. Whereas, co-treatment with Angptl4 siRNA partially blocked the beneficial effect of TXL. Administration of the PPARα inhibitor MK886 also reversed the inhibition effect of TXL on ECs apoptosis, but not reduce ECs apoptosis in the rhAngptl4-treated animals. Red arrows indicate endothelial cells and white arrows show apoptotic cells. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198403#pone.0198403.g001" target="_blank">Fig 1</a>.</p
Expression levels of JAM-A, VE-cadherin, and integrin-α5 in the I/R-injured hearts with or without TXL treatment.
<p>I/R injury decreased the expression levels of JAM-A (A), VE-cadherin (B), and Integrin-α5 (C). Pre-treatment with insulin, rhAngptl4, or TXL up-regulated expression levels of JAM-A (A), VE-cadherin (B), and Integrin-α5 (C). Addition of Angptl4 siRNA canceled the effects of TXL-induced up-regulation of JAM-A (A) and VE-cadherin (B), but not Integrin-α5 (C). Co-treatment with MK886 abolished the TXL-upregulated expression of JAM-A (A), VE-cadherin (B), and Integrin-α5 (C). Compared with DB-sham group, *<i>P</i><0.05, ** <i>P</i><0.01; Compared with the DB-MI group, <sup>â </sup><i>P</i><0.05, <sup>â â </sup><i>P</i><0.01; Compared with the TXL group, <sup>âĄ</sup><i>P</i><0.05, <sup>âĄâĄ</sup><i>P</i><0.01; Compared with the rhAngptl4+siR group, <sup>§§</sup><i>P</i><0.01. Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198403#pone.0198403.g001" target="_blank">Fig 1</a>.</p