Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells

AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines,HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological observation,flow cytometry analysis,Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells,as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner,which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition,G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53,pRb,p27,cyclins D1,D2,E,cyclin-dependent kinase (Cdk) 2,Cdk4,and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option,as a potential anticancer agent,in the treatment of hepatoma.

World Economy and the Export Dependence of China's Textile Industry

In this paper,the current status of export dependence of China's textile industry and affecting factors are evaluated.A cointegration test for world economy and China's export of textile and apparel is conducted which suggests that a long-term cointegration relationship exists between the growth rate of the world economy and that of China's export of textiles and apparel.The world economy will enter a period of low-speed growth,and the growth rate of China's textile and apparel exports will slow down accordingly.On the other hand,China's domestic expenditures on textiles and apparel are expected to maintain robust growth.According to the trends of exports and domestic demand,the export dependence of China's textile industry will go down with fluctuations.The conclusion is useful to evaluating the performance of the textile industry and making relevant policies.

Oxidative stress battles neuronal Bcl-xL in a fight to the death

Bcl-xL is a pro-survival protein of the Bcl2 family found in the mitochondrial membrane.Bcl-xL supports growth,development,and maturation of neurons,and it also prevents neuronal death during neurotoxic stimulation.This article reviews the mechanisms and upstream signaling that regulate the activity and abundance of Bcl-xL.Our team and others have reported that oxidative stress is a key regulator of intracellular Bcl-xL balance in neurons.Oxidative stress regulates synthesis,degradation,and activity of Bcl-xL and therefore neuronal function.During apoptosis,pro-apoptotic Bcl2 proteins such as Bax and Bak translocate to and oligomerize in the mitochondrial membrane.Formation of oligomers causes release of cytochrome c and activation of caspases that lead to neuronal death.Bcl-xL binds directly to pro-apoptotic Bcl2 proteins to block apoptotic signaling.Although anti-apoptotic roles of Bcl-xL have been well documented,an increasing number of studies in recent decades show that protein binding partners of Bcl-xL are not limited to Bcl2 proteins.Bcl-xL forms a complex with F1Fo ATP synthase,DJ-1,DRP1,IP3R,and the ryanodine receptor.These proteins support physiological processes in neurons such as growth and development and prevent neuronal damage by regulating mitochondrial ATP production,synapse formation,synaptic vesicle recycling,neurotransmission,and calcium signaling.However,under conditions of oxidative stress,Bcl-xL undergoes proteolytic cleavage thus lowering the abundance of functional Bcl-xL in neurons.Additionally,oxidative stress alters formation of Bcl-xL-mediated multiprotein complexes by regulating post-translational phosphorylation.Finally,oxidative stress regulates transcription factors that target the Bcl-x gene and alter accessibility of microRNA to mRNA influencing mRNA levels of Bcl-xL.In this review,we discussed how Bcl-xL supports the normal physiology of neurons,and how oxidative stress contributes to pathology by manipulating the dynamics of Bcl-xL production,degradation,and activity.

ΔN-Bcl-xL, a therapeutic target for neuroprotection

The B-cell lymphoma-extra large （Bcl-xL） is a mitochondrial anti-apoptotic protein that plays a role in neuroprotection. However, during excitotoxic stimulation, Bcl-xL undergoes caspase-dependent cleavage and produces a fragmented form, △N-Bcl-xL. Accumulation of △N-Bcl-xL is associated with mitochon- drial dysfunction and neuronal death. Therefore, strategies to inhibit the activity or formation of △N-Bcl- xL protect the brain against excitotoxic injuries. Our team found that the pharmacological inhibitor △BT- 737 exerts dose dependent effects in primary neurons. When primary hippocampal neurons were treated with 1 μM ABT-737, glutamate-mediated mitochondrial damage and neuronal death were exacerbated, whereas 10 nM △BT-737, a 100-fold lower concentration, protected mitochondrial function and enhanced neuronal viability against glutamate toxicity. In addition, we suggested acute vs. prolonged formation of △N-Bcl-xL may have different effects on mitochondrial or neuronal functions. Unlike acute production of △N-Bcl-xL by glutamate, overexpression of △N-Bcl-xL did not cause drastic changes in neuronal viability. We predicted that neurons undergo adaptation and may activate altered metabolism to compensate for △N-Bcl-xL-mediated mitochondrial dysfunction. Although the detailed mechanism of ABT-mediated neurotoxicity neuroprotection is still unclear, our study shows that the mitochondrial membrane protein △N-Bcl-xL is a central target for interventions.