Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

There has been increasing interest in the potential applications of gold (III) complexes as anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs. Our previous findings demonstrated that gold (III) porphyrin la preferentially induced apoptosis in a cancer cell line (SUNE1). In this study, we identified differentially expressed proteins related to the drug's cytotoxic action by comparing the protein alterations induced by gold (III) porphyrin la and cisplatin treatments. Several clusters of altered proteins were identified, including cellular structure and stress-related chaperone proteins, proteins involved in reactive oxygen species and enzyme proteins, translation factors, proteins that mediate cell proliferation or differentiation, and proteins participating in the internal degradation systems. Our results indicated that multiple factors leading to apoptosis were involved in drug cytotoxicity in SUNE1 cells. The balance between pro-apoptotic and anti-apoptotic signals determined the final fate of cancer cells. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Circulating fibroblast growth factor 21 Is a sensitive biomarker for severe ischemia/reperfusion injury in patients with liver transplantation

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Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

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Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism

Extensive studies have revealed that berberine, a small molecule derived from Coptidis rhizoma (Huanglian in Chinese) and many other plants, has strong anti-tumor properties. To better understand berberine-induced cell death and its underlying mechanisms in cancer, we examined autophagy and apoptosis in the human hepatic carcinoma cell lines HepG2 and MHCC97-L. The results of this study indicate that berberine can induce both autophagy and apoptosis in hepatocellular carcinoma cells. Berberine-induced cell death in human hepatic carcinoma cells was diminished in the presence of the cell death inhibitor 3-methyladenine, or following interference with the essential autophagy gene Atg5. Mechanistic studies showed that berberine may activate mitochondrial apoptosis in HepG2 and MHCC97-L cells by increasing Bax expression, the formation of permeable transition pores, cytochrome C release to cytosol, and subsequent activation of the caspases 3 and 9 execution pathway. Berberine may also induce autophagic cell death in HepG2 and MHCC97-L cells through activation of Beclin-1 and inhibition of the mTOR-signaling pathway by suppressing the activity of Akt and up-regulating P38 MAPK signaling. This is the first study to describe the role of Beclin-1 activation and mTOR inhibition in berberine-induced autophagic cell death. These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms. © 2010 Wiley-Liss, Inc.postprin

Effect of sex on meat quality characteristics of Qinchuan cattle

A total of 18 Qinchuan cattle, six intact males (IM), six castrated males (CM) and six females (FM), were used to investigate the effect of sex on the physicochemical characteristics (PCC) and fatty acid (FA) composition of the Longissimus dorsi muscle (LDM). Obvious sex differences were found in the PCC of LDM: the IM group had higher shear value, pH, drip and cooking losses, and contents of ash and hydroxyproline (Hyp) than the CM and FM groups, as well as lower ether extract content and lightness. Both the IM and CM groups had lower water content and higher protein content than the FM group. Sex differences were also observed in contents of C14:0, C14:1, C18:1, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and unsaturated fatty acids (UFA) between the IM and both the CM and FM groups but not between the CM and FM groups. The results indicated that sex is an importantsource of differences in meat quality of Qinchuan cattle because the castration and the meat characteristics of the CM group were more similar to the FM than the IM group

Winner-take-all selection in a neural system with delayed feedback

We consider the effects of temporal delay in a neural feedback system with excitation and inhibition. The topology of our model system reflects the anatomy of the avian isthmic circuitry, a feedback structure found in all classes of vertebrates. We show that the system is capable of performing a `winner-take-all' selection rule for certain combinations of excitatory and inhibitory feedback. In particular, we show that when the time delays are sufficiently large a system with local inhibition and global excitation can function as a `winner-take-all' network and exhibit oscillatory dynamics. We demonstrate how the origin of the oscillations can be attributed to the finite delays through a linear stability analysis.Comment: 8 pages, 6 figure

IRE1α inhibition by natural compound genipin on tumour associated macrophages reduces growth of hepatocellular carcinoma

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Proteomic approach to study the cytotoxicity of dioscin (saponin)

Dioscin, extracted from the root of Polygonatum zanlanscianense pamp, exhibits cytotoxicity towards human myeloblast leukemia HL-60 cells. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria are the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by dioscin treatment. Changes in proteome other than mitochondrial related proteins implicate that other mechanisms were also involved in dioscin-induced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alterations of phosphatases in cell signaling, and deregulation of oxidative stress and cell proliferation. Current study of protein alterations in dioscin-treated HL-60 cells suggested that dioscin exerts cytotoxicity through multiple apoptosis-inducing pathways. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin

Open Access JournalThe plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.published_or_final_versio

Pyrite-type ruthenium disulfide with tunable disorder and defects enables ultra-efficient overall water splitting

The exploration of efficient electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is significant for water splitting associated with the storage of clean and renewable energy. Here, we report a simple and scalable low-temperature sulfuration method to achieve simultaneous modulation of disorder and defects in pyrite-type RuS2 nanoparticles to dramatically enhance the HER and OER catalytic activity. The disordered structure can increase the electrochemically active surface area, while defect engineering can effectively regulate the electronic structure and thus improve the intrinsic activity, as revealed by combined experimental and theoretical density functional theory (DFT) investigations. Through controllable disorder and defect engineering, the optimized RuS2-500 catalyst (with a sulfuration temperature of 500 °C) supported on a glassy carbon electrode exhibits ultra-efficient bifunctional electrocatalytic activity with η-10 = 78 mV for the HER and η10 = 282 mV for the OER, superior to various Ru-based and pyrite-type catalysts. Remarkably, when used as both the anode and the cathode in an alkaline water electrolyzer, RuS2-500 delivers 10 mA cm-2 at an ultralow cell voltage of 1.527 V with long-term stability, outperforming the benchmark Pt/C//RuO2 couple and most state-of-the-art overall-water-splitting electrocatalysts ever reported. This work thus provides a new and facile way for improving the catalytic activity through a synergistic modulation strategy