Blocking autophagy enhances the apoptosis effect of bufalin on human hepatocellular carcinoma cells through endoplasmic reticulum stress and JNK activation.

Bufalin extracts are a part of traditional Chinese medicine, Chansu. In the current study, we investigated the effect of bufalin on the proliferation of the human hepatocellular carcinoma (HCC) cell lines, Huh-7 and HepG-2, and explored the therapeutic potential of the drug. Our results demonstrated that bufalin markedly inhibited cell proliferation and promoted apoptosis in the Huh-7 and HepG-2 cells in vitro. The underlying mechanism of the bufalin-induced apoptosis was the induction of endoplasmic reticulum (ER) stress via the IRE1-JNK pathway. In addition, during the ER stress response, the autophagy pathway, characterized by the conversion of LC3-I to LC3-II, was activated, resulting in increased Beclin-1 protein levels, decreased p62 expression and stimulation of autophagic flux. Our data supported the pro-survival role of bufalin-induced autophagy when the autophagy pathway was blocked with specific chemical inhibitors; the involvement of the IRE1 pathway in the ER stress-induced autophagy was also demonstrated when the expression of IRE1 and CHOP was silenced using siRNA. These data indicate that combining bufalin with a specific autophagy inhibitor could be a promising therapeutic approach for the treatment of HCC.

The integrin-linked kinase gene up-regulated by hypoxia plays its pro-survival role in colorectal cancer cells.

CONTEXT: Colorectal cancer (CRC) is a leading cause of cancer death in recent years. It is believed that there are hypoxic regions in both early and advanced stage of tumor and hypoxia is able to reinforce the aggressiveness of tumor cells and accelerate the progression of cancer. OBJECTIVE: Until now the mechanisms by which hypoxia promotes the progression of CRC are far from well understood. Integrin-linked kinase (ILK) is a crucial mediator and over-expressed in CRC patients. But whether ILK is involved in the process that hypoxia promotes CRC cells growth and silencing the ILK gene results in CRC cells apoptosis is not clear. MATERIALS AND METHODS: Lentivirus transfection, invasion assay, TUNEL assay, Bromodeoxyuridine incorporation and mitochondrial function assay were applied to demonstrate our hypothesis. RESULTS: In this study, we found that hypoxia induced the expression of ILK in a time-dependent manner, and after knocking down ILK expression with ILK shRNA, the cells proliferation promoted by hypoxia was inhibited in HT29 cell line. Moreover, blocking the ILK pathway led to caspase-3 and caspase-9 activations, the decrease of mitochondrial membrane potential, and cells apoptosis. And the inhibitory effects of hypoxia on cells apoptosis were mediated by the ILK pathway. In addition, hypoxia promoted HT29 cells metastasis and invasion through the ILK pathway. CONCLUSIONS: Therefore, we conclude that the CRC cells survival and invasion enhanced by hypoxia are mediated by ILK, and ILK may be an important potential therapeutic target for CRC.

Obtaining help by standing higher: The mediating role of moral reputation.

Drawing on the social cognitive chain of being (SCCB) theory and heuristic perspective, the present study explored whether and how social targets' vertical spatial position influences the help the social targets can get from others. Study 1 demonstrated that individuals would be more likely to help social targets who were presented on a higher vertical spatial position than those who were presented on a lower vertical spatial position. In Study 2, an experimental-causal-chain design was adopted for further testing the mediating role of moral reputation between the social targets' vertical spatial position and the amount of help that the social targets obtain from others. Study 3 cross-validated this mediating process by a measurement-of-mediation design. Those three studies help us comprehend how helping behavior occurs from the characteristics of help recipients as well as extend the influence of vertical spatial metaphor of morality from cognitive connection to action-relevant outcomes.

Kick the Cat: A Serial Crossover Effect of Supervisors' Ego Depletion on Subordinates' Deviant Behavior.

Drawing on the crossover model and conservation of resources theory, we explore the mechanism through which supervisors' ego depletion induces subordinates' deviant behavior. Using the two-wave survey data from 24 supervisors and their 192 respective subordinates, we found supports for our hypotheses that (a) abusive supervision mediated the effect of supervisors' ego depletion on subordinates' ego depletion; (b) subordinates' ego depletion mediated the effect of abusive supervision on subordinates' deviant behavior; and (c) abusive supervision and subordinates' ego depletion serially mediated the effect of supervisors' ego depletion on subordinates' deviant behavior. Our serial crossover model posits that both ego depletion and unethical behavior can be transmitted from supervisors to subordinates, and that these two crossover processes are entwined with each other. Findings are discussed in terms of theoretical contributions and practical implications.

Are Sex Effects on Ethical Decision-Making Fake or Real? A Meta-Analysis on the Contaminating Role of Social Desirability Response Bias.

A meta-analysis of 143 studies was conducted to explore how the social desirability response bias may influence sex effects on ratings on measures of ethical decision-making. Women rated themselves as more ethical than did men; however, this sex effect on ethical decision-making was no longer significant when social desirability response bias was controlled. The indirect questioning approach was compared with the direct measurement approach for effectiveness in controlling social desirability response bias. The indirect questioning approach was found to be more effective.

Biochanin A inhibits lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells.

AIM: Biochanin A, an isoflavone isolated from red clover, cabbage or alfalfa, has been reported to have anti-inflammatory activity. However, the effects of biochanin A on vascular inflammation have not been investigated. In this study, we investigate the anti-inflammatory effects of biochanin A on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVEC cells). MAIN METHODS: The HUVEC cells were treated with biochanin A for 12h before exposure to LPS. The expression of ECAMs, including VCAM-1, ICAM-1, E-selectin, NF-κB and PPAR-γ was detected by Western blotting. The expression of cytokines TNF-α and IL-8 was detected by ELISA. KEY FINDINGS: The results showed that biochanin A inhibited LPS-induced TNF-α and IL-8 production. Meanwhile, biochanin A also suppressed VCAM-1, ICAM-1, and E-selectin expression induced by LPS. We also found that biochanin A inhibited NF-κB activation induced by LPS. Furthermore, biochanin A could activate PPAR-γ and the anti-inflammatory effects of biochanin A can be reversed by GW9662, a specific antagonist for PPAR-γ. SIGNIFICANCE: In conclusion, the anti-inflammatory effect of biochanin A is associated with activating PPAR-γ, thereby attenuating NF-κB activation and LPS-induced inflammatory response. These findings suggest that biochanin A may be a therapeutic agent for inflammatory cardiovascular disease.