Stable and Highly Efficient Hydrogen Evolution from Seawater Enabled by an Unsaturated Nickel Surface Nitride.

Electrocatalytic production of hydrogen from seawater provides a route to low-cost and clean energy conversion. However, the hydrogen evolution reaction (HER) using seawater is greatly hindered by the lack of active and stable catalysts. Herein, an unsaturated nickel surface nitride (Ni-SN@C) catalyst that is active and stable for the HER in alkaline seawater is prepared. It achieves a low overpotential of 23 mV at a current density of 10 mA cm-2 in alkaline seawater electrolyte, which is superior to Pt/C. Compared to conventional transition metal nitrides or metal/metal nitride heterostructures, the Ni-SN@C has no detectable bulk nickel nitride phase. Instead, unsaturated NiN bonding on the surface is present. In situ Raman measurements show that the Ni-SN@C performs like Pt with the ability to generate hydronium ions in a high-pH electrolyte. The catalyst operation is then demonstrated in a two-electrode electrolyzer system, coupling with hydrazine oxidation at the anode. Using this system, a cell voltage of only 0.7 V is required to achieve a current density of 1 A cm-2 .

Crosstalk between bone marrow-derived myofibroblasts and gastric cancer cells regulates cancer stemness and promotes tumorigenesis.

Bone marrow-derived cells have important roles in cancer development and progression. Our previous studies demonstrated that murine bone marrow-derived myofibroblasts (BMFs) enhanced tumor growth. In this study, we investigated the mechanisms of BMF actions. We found that co-injection of BMFs with gastric cancer cells markedly promoted tumorigenesis. Co-cultured BMFs or BMF-conditioned medium (BMF-CM) induced the formation of spheres, which expressed stem cell signatures and exhibited features of self-renewal, epithelial-to-mesenchymal transition and tumor initiation. Furthermore, CD44+ fractions in spheres were able to initiate tumorigenesis and re-establish tumors in serially passaged xenografts. In co-culture systems, BMFs secreted high levels of murine interleukin-6 (IL-6) and hepatocyte growth factor (HGF), whereas cancer cells produced high level of transformation growth factor-ß1 (TGF-ß1). BMF-CM and IL-6 activated BMFs to produce mHGF, which activated signal transducer and activator of transcription 3 (STAT3) and upregulated TGF-ß1 in human cancer cells. In return, cancer cell-CM stimulated BMFs to produce IL-6, which was inhibited by anti-TGF-ß1 neutralizing antibody. Blockade of HGF/Met, Janus kinase 2 (JAK2)/STAT3 and TGF-ß1 signaling by specific inhibitors inhibited BMF-induced sphere formation. STAT3 knockdown in cancer cells also inhibited BMF-induced sphere formation and tumorigenesis. Moreover, TGF-ß1 overexpression in cancer cells was co-related with IL-6 and HGF overexpression in stromal cells in human gastric cancer tissues. Our results show that BMF-derived IL-6/HGF and cancer cell-derived TGF-ß1 mediate the interactions between BMFs and gastric cancer cells, which regulate cancer stemness and promote tumorigenesis. Targeting inhibition of the interactions between BMFs and cancer cells may be a new strategy for cancer therapy.

NNK-induced DNA methyltransferase 1 in lung tumorigenesis in A/J mice and inhibitory effects of (-)-epigallocatechin-3-gallate.

DNA methyltransferase 1 (DNMT1), a key enzyme mediating DNA methylation, is known to be elevated in various cancers, including the mouse lung tumors induced by the tobacco-specific carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). However, it is not known whether DNMT1 expression is induced right after NNK treatment and how DNMT1 expression varies throughout lung tumorigenesis. In the present study, we found that administration of NNK to A/J mice caused elevation of DNMT1 in bronchial epithelial cells at Days 1, 3, and 14 after NNK treatment. DNMT1 elevation at Day 1 was accompanied by an increase in phospho-histone H2AX (γ-H2AX) and phospho-AKT (p-AKT). At Weeks 5 to 20, NNK-induced DNMT1 in lung tissues was in lower levels than the early stages, but was highly elevated in lung tumors at Week 20. In addition, the early induction of p-AKT and γ-H2AX as well as cleaved caspase-3 in NNK-treated lung tissues was not detected at Weeks 5 to 20 but was elevated in lung tumors. In concordance with DNMT1 elevation, promoter hypermethylation of tumor suppressor genes Cdh13, Prdm2, and Runx3 was observed in lung tissues at Day 3 and in lung tumors. Treatment by EGCG attenuated DNMT1, p-AKT, and γ-H2AX inductions at Days 1 and 3 and inhibited lung tumorigenesis.

[Application of silk fibroin in biomedical areas].

For a long period of time, silk fibroin has been applied in biomedical areas. Along with the development of biotechnology, new functions of silk fibroin are being found and developed. From the suture of surgery to the therapeutic drug and the ordinary tissue engineering frame to high grade frame with drug buffer system, exploitation of silk fibroin is constantly introduced with something new from the old ones. In our review, we summarize the applications of silk fibroin in tissue engineering, drug buffer system and medical care.

Bone marrow-derived myofibroblasts promote colon tumorigenesis through the IL-6/JAK2/STAT3 pathway.

Bone marrow-derived myofibroblasts (BMFs) have been shown to promote tumor growth. Here, we found that BMFs or BMF conditioned medium (BMF-CM) induced cancer stem cell-like sphere formation of colon cancer cells. The co-cultured BMFs, but not co-cultured cancer cells, expressed higher levels of IL-6 than BMFs or cancer cells cultured alone. Anti-mouse IL-6 neutralizing antibody, JAK2 inhibitors and STAT3 knockdown in mouse cancer cells reduced BMF- and BMF-CM-induced sphere formation of colon cancer cells. When co-injected, BMFs significantly enhanced tumorigenesis of colon cancer cells in mice. Our results demonstrate that BMFs promote tumorigenesis via the activation of the IL-6/JAK2/STAT3 pathway.

Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth.

Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumors and contribute to tumor growth, angiogenesis, and progression. In this study, we examined the effects of curcumin on the activation and differentiation of MDSCs, their interaction with human cancer cells, and related tumor growth. Treatment with curcumin in the diet or by intraperitoneal injection significantly inhibited tumorigenicity and tumor growth, decreased the percentages of MDSCs in the spleen, blood, and tumor tissues, reduced interleukin (IL)-6 levels in the serum and tumor tissues in a human gastric cancer xenograft model and a mouse colon cancer allograft model. Curcumin treatment significantly inhibited cell proliferation and colony formation of cancer cells and decreased the secretion of murine IL-6 by MDSCs in a coculture system. Curcumin treatment inhibited the expansion of MDSCs, the activation of Stat3 and NF-κB in MDSCs, and the secretion of IL-6 by MDSCs, when MDSCs were cultured in the presence of IL-1ß, or with cancer cell- or myofibroblast-conditioned medium. Furthermore, curcumin treatment polarized MDSCs toward a M1-like phenotype with an increased expression of CCR7 and decreased expression of dectin 1 in vivo and in vitro. Our results show that curcumin inhibits the accumulation of MDSCs and their interaction with cancer cells and induces the differentiation of MDSCs. The induction of MDSC differentiation and inhibition of the interaction of MDSCs with cancer cells are potential strategies for cancer prevention and therapy.

Cancer prevention by tea: Evidence from laboratory studies.

The cancer preventive activities of tea (Camellia sinensis Theaceae) have been studied extensively. Inhibition of tumorigenesis by green tea extracts and tea polyphenols has been demonstrated in different animal models, including those for cancers of the skin, lung, oral cavity, esophagus, stomach, small intestine, colon, bladder, liver, pancreas, prostate, and mammary glands. Many studies in cell lines have demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events can result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, the molecular mechanisms of inhibition of carcinogenesis in animals and humans remain to be further investigated. Future research directions in this area are discussed.

Pro-oxidative activities and dose-response relationship of (-)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: a comparative study in vivo and in vitro.

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to inhibit tumorigenesis and cancer cell growth in animal models. Nevertheless, the dose-response relationship of the inhibitory activity in vivo has not been systematically characterized. The present studies were conducted to address these issues, as well as the involvement of reactive oxygen species (ROS), in the inhibitory action of EGCG in vivo and in vitro. We characterized the inhibitory actions of EGCG against human lung cancer H1299 cells in culture and in xenograft tumors. The growth of tumors was dose dependently inhibited by EGCG at doses of 0.1, 0.3 and 0.5% in the diet. Tumor cell apoptosis and oxidative DNA damage, assessed by the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and phosphorylated histone 2A variant X (gamma-H2AX), were dose dependently increased by EGCG treatment. However, the levels of 8-OHdG and gamma-H2AX were not changed by the EGCG treatment in host organs. In culture, the growth of viable H1299 cells was dose dependently reduced by EGCG; the estimated concentration that causes 50% inhibition (IC(50)) (20 microM) was much higher than the IC(50) (0.15 microM) observed in vivo. The action of EGCG was mostly abolished by the presence of superoxide dismutase (SOD) and catalase, which decompose the ROS formed in the culture medium. Treatment with EGCG also caused the generation of intracellular ROS and mitochondrial ROS. Although EGCG is generally considered to be an antioxidant, the present study demonstrates the pro-oxidative activities of EGCG in vivo and in vitro in the described experimental system.

Synergistic actions of atorvastatin with gamma-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells.

The synergistic actions of atorvastatin (ATST) with gamma-tocotrienol (gamma-TT) and celecoxib (CXIB) were studied in human colon cancer cell lines HT29 and HCT116. The synergistic inhibition of cell growth by ATST and gamma-TT was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and isobologram analysis. delta-TT exhibited a similar inhibitory action when combined with ATST. Mevalonate and geranylgeranyl pyrophosphate eliminated most of the growth inhibitory effect of ATST, but only marginally decreased that of gamma-TT; whereas farnesyl pyrophosphate and squalene exhibited little effect on the inhibitory action of ATST and gamma-TT, indicating protein geranylgeranylation, but not farnesylation are involved in the inhibition of colon cancer cell growth. Both mevalonate and squalene restored the cellular cholesterol level that was reduced by ATST treatment, but only mevalonate eliminated the cell growth inhibitory effect, suggesting that the cholesterol level in cells does not play an essential role in inhibiting cancer cell growth. Protein level of HMG-CoA reductase increased after ATST treatment, and the presence of gamma-TT attenuated the elevated level of HMG-CoA reductase. ATST also decreased membrane-bound RhoA, possibly due to a reduced level of protein geranylgeranylation; addition of gamma-TT enhanced this effect. The mediation of HMG-CoA reductase and RhoA provides a possible mechanism for the synergistic action of ATST and gamma-TT. The triple combination of ATST, gamma-TT and CXIB showed a synergistic inhibition of cancer cell growth in MTT assays. The synergistic action of these three compounds was also illustrated by their induction of G(0)/G(1) phase cell cycle arrest and apoptosis.

Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis.

Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3',4'-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/G1 phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention.

Synergistic inhibition of lung tumorigenesis by a combination of green tea polyphenols and atorvastatin.

PURPOSE: The present study investigated the possible synergistic inhibitory effect of a novel combination of polyphenon E (PPE, a standardized green tea polyphenol preparation) and atorvastatin (trade name Lipitor) in a mouse tumorigenesis model and in human lung cancer H1299 and H460 cell lines. EXPERIMENTAL DESIGN: Female A/J mice were given two weekly i.p. injections of 4-(methylnitrosaminao)-1-(3-pyridyl)-1-butanone (150 mg/kg total dose); 1 week later, mice were treated with PPE (0.25% or 0.5% in drinking fluid), atorvastatin (200 or 400 ppm in diet), or PPE (0.25%) plus atorvastatin (200 ppm) for 16 weeks. The interaction of these two agents was also studied in human lung cancer H1299 and H460 cells. RESULTS: The individual agents, PPE or atorvastatin, were not effective in inhibiting lung tumorigenesis. The low-dose combination of PPE and atorvastatin, however, significantly reduced both the tumor multiplicity and tumor burden (by 56% and 55%, respectively, P < 0.05). Isobologram analysis of the interaction of the two agents indicated that the combination synergistically decreased tumor multiplicity (P = 0.0006) and tumor burden (P = 0.0009). The inhibition was associated with enhanced apoptosis and suppressed myeloid cell leukemia 1 (Mcl-1) level in adenoma as determined by immunohistochemistry and Western blots. Treatment with combinations of PPE and atorvastatin also synergistically decreased the number of viable H1299 and H460 cells as determined by isobologram analysis. This synergistic effect was associated with increased apoptosis as determined by the terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. The combination of PPE and atorvastatin was more efficient in reducing the antiapoptotic protein Mcl-1 level and increasing the cleaved caspase-3 and cleaved poly(ADP)-ribose polymerase level than the single-agent treatment. CONCLUSIONS: The present work showed that PPE and atorvastatin synergistically inhibited 4-(methylnitrosaminao)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in mice and the growth of lung cancer H1299 and H460 cells, possibly through enhanced apoptosis. The results provide leads for future research on the application of this combination for the prevention and treatment of lung cancer.