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Aim To explore the effects of cinnamaldehyde on the proliferation and stemness of pancreatic cancer PANC-1 cells, and its possible mechanism of action.Methods CCK8 assay was used to detect the effect of cinnamaldehyde treatment on cell viability at different concentrations(0, 5, 15, 20, 30, 50, 70, 100, 150 μmol·L-1)and different intervention time(24, 48, 72 h).CFSE proliferation assay was used to detect the inhibitory effects of cinnamaldehyde on PANC-1 cells.Colony formation assay was employed to determine the colony-forming ability of PANC-1 cells after cinnamaldehyde treatment.The sphere formation assay was employed to detect the effects of cinnamaldehyde on sphere-forming ability in PANC-1 cells.Western blot analysis and qRT-PCR analysis were applied to determine the expression levels of Nanog, Sox-2 and Oct-4.Flow cytometry was used to detect the percentage of CD44+CD24+ cells and ALDH+ cells in cinnamaldehyde treated and untreated PANC-1 cells.Western blot analysis was used to detect the effects of cinnamaldehyde on the expression of CD44s, p-STAT3 and STAT3 in PANC-1 cells.Results Cinnamaldehyde suppressed cell viability in a dose- and time-dependent manner, and inhibited tumor-cell proliferation and colony forming ability significantly in a dose-dependent manner in PANC-1 cells.Sphere-forming assay showed that cinnamaldehyde could significantly inhibit sphere-forming ability in suspension culture of PANC-1 cells.The mRNA and protein expression levels of three stemness-related genes were down-regulated after cinnamaldehyde treatment.In addition, cinnamaldehyde treatment significantly decreased the proportion of CD44+CD24+ cells and ALDH+ cells.Western blotting showed that cinnamaldehyde inhibited the expression of CD44s and p-STAT3, while it had no effect on the expression of STAT3.With the addition of STAT3 activator(Colivelin TFA), the inhibition of cinnamaldehyde on proliferation and tumor-cell stemness in PANC-1 cells was partially rescued.Conclusions Cinnamaldehyde significantly inhibits the proliferation and tumor-cell stemness of pancreatic cancer PANC-1 cells, and the mechanism could be related to the modulation of CD44s/STAT3 signaling pathway.
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Objective:To observe the changes in oxidative stress and transforming growth factor-<italic>β</italic><sub>1</sub> （TGF-<italic>β</italic><sub>1</sub>）/Smad signaling pathway in hippocampal tissue of senile depressed mice after chronic unpredictable mild stress and to explore the possible anti-depression mechanism of Bushen Shugan prescription. Method:Ninety five-month-old mice were randomly divided into six groups， namely the normal group， senile depression model group， high-， medium-， and low-dose Bushen Shugan prescription groups， and fluoxetine group， with 15 in each group. Mice in all groups， except for the normal group， were exposed to chronic unpredictable mild stress （CUMS） for inducing the senile depression. Since the first day of modeling， the mice in the high-， medium- and low-dose Bushen Shugan prescription groups were gavaged with 19.5， 9.75， 4.87 g·kg<sup>-1</sup> Bushen Shugan prescription， the ones in the fluoxetine group with 0.033 g·kg<sup>-1 </sup>fluoxetine， and those in the normal and senile depression model groups with an equal volume of normal saline for 21 successive days. The behavioral responses of mice in each group were evaluated in the open field test （OFT）， and the hippocampal tissues of mice were collected for testing the relevant indexes. The superoxide dismutase （SOD） content was determined by WST-1 method， malondialdehyde （MDA） content by TBA method， glutathione （GSH） content by micro enzyme-linked immunosorbent assay （ELISA）， and mRNA expression of TGF-<italic>β</italic><sub>1</sub>， Smad2， Smad3， and Smad7 by Real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the senile depression model group exhibited significantly lowered horizontal and vertical scores in OFT， decreased SOD and GSH contents in hippocampal tissues， elevated MDA （<italic>P</italic><0.05）， up-regulated TGF-<italic>β</italic><sub>1</sub>， Smad2， and Smad3 mRNA expression， and down-regulated Smad7 （<italic>P</italic><0.05）. Compared with the senile depression model group， Bushen Shugan prescription at the high， medium， and low doses and fluoxetine all increased SOD and GSH contents in mouse hippocampal tissues， decreased the MDA content （<italic>P</italic><0.05）， down-regulated the mRNA expression of TGF-<italic>β</italic><sub>1</sub>， Smad2， and Smad3 in hippocampal tissues， and up-regulated the Smad7 mRNA expression （<italic>P</italic><0.05）. The comparison with the high-dose Bushen Shugan prescription group showed that the SOD and GSH contents in hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups declined significantly， while the MDA contents rose significantly （<italic>P</italic><0.05）. Besides， the mRNA expression levels of TGF-<italic>β</italic><sub>1</sub>， Smad2 and Smad3 in the hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups were significantly up-regulated， and those of Smad7 were significantly down-regulated （<italic>P</italic><0.05）. Conclusion:Bushen Shugan prescription alleviates the depression symptoms in aged SAPM8 mice possibly by regulating the hippocampal oxidative stress and TGF-<italic>β</italic><sub>1</sub>/Smad signaling pathway.
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<p><b>BACKGROUND</b>Although the results of surgical treatment in cardiac valve disease continue to improve, the postoperative mortality rate and the rate of complications in patients with advanced valvular heart disease (AVHD) are still very high. We did this retrospective study to summarize the surgical experience of heart valve replacement for patients with AVHD and discuss effective ways to improve the surgical outcome.</p><p><b>METHODS</b>From January 1994 to October 2003, surgical procedures of heart valve replacement were performed on 227 (136 men and 91 women) patients with AVHD in our Department of Cardiothoracic Surgery. The clinical data of all patients were collected and analysed. Patients' age ranged from 10 years to 77 years. In preoperative cardiac function grading, 157 cases were NYHA III and 70 cases NYHA IV. Fifty-one patients had had cardiac operations. The ultrasonic cardiac graphs showed that 145 patients suffered from moderate or severe pulmonary hypertension and 73 had combined giant left ventricle. Mitral valve replacement was performed in 32 cases, aortic valve replacement in 90, tricuspid valve replacement in 1, combined mitral and aortic replacement in 103 and combined mitral and tricuspid replacement in 1. Nineteen patients also received surgical corrections for other minor abnormalities during the operations. A logistic model was established to evaluate the influence of perioperative factors on the mortality rate.</p><p><b>RESULTS</b>The operative mortality rate was 13.2% (30/227). The main causes of death included multiple organ dysfunction syndrome (MODS), low cardiac output syndrome and ventricular fibrillation. From the results of the binary noncounterpart multivariate logistic regression, the following statistically significant factors were found to influence the operative mortality rate: redo operation, age >/= 55 years, preoperative NYHA cardiac function grading, extracorporeal circulation time >/= 120 minutes and postoperative usage of GIK (glucose, insulin and potassium) solution. All factors were risk ones except postoperative application of GIK. The Hosmer-Lemeshow goodness of fit coefficient of this model was 0.976.</p><p><b>CONCLUSIONS</b>The risk factors associated with postoperative mortality rate in the patients with AVHD were redo operation, age >/= 55 years, preoperative NYHA cardiac function grading and extracorporeal circulation time >/= 120 minutes. Postoperative usage of GIK acted as a kind of metabolic therapy and will improve the recovery for patients with AVHD. Active perioperative management and care will play a very important role in reducing the operative risk and improving the short term outcome of surgical treatment for the patients with AVHD.</p>