A unique 3D nitrogen-doped carbon composite as high-performance oxygen reduction catalyst

The synthesis and properties of an oxygen reduction catalyst based on a unique 3-dimensional (3D) nitrogen doped (N-doped) carbon composite are described. The composite material is synthesised via a two-step hydrothermal and pyrolysis method using bio-source low-cost materials of galactose and melamine. Firstly, the use of iron salts and galactose to hydrothermally produceiron oxide (Fe₂O₃) magnetic nanoparticle clusters embedded carbon spheres. Secondly, magnetic nanoparticles diffused out of the carbon sphere when pyrolysed in the presence of melamine as nitrogen precursor. Interestingly, many of these nanoparticles, as catalyst-grown carbon nanotubes (CNTs), resulted in the formation of N-doped CNTs and N-doped carbon spheres under the decomposition of carbon and a nitrogen environment. The composite material consists of integrated N-doped carbon microspheres and CNTs show high ORR activity through a predominantly four-electron pathway.Ramesh Karunagaran, Tran Thanh Tung, Cameron Shearer, Diana Tran, Campbell Coghlan, Christian Doonan, and Dusan Losi

A unique synthesis of macroporous N-doped carbon composite catalyst for oxygen reduction reaction

Macroporous carbon materials (MCMs) are used extensively for many electrocatalytic applications, particularly as catalysts for oxygen reduction reactions (ORRs)—for example, in fuel cells. However, complex processes are currently required for synthesis of MCMs. We present a rapid and facile synthetic approach to produce tailored MCMs efficiently via pyrolysis of sulfonated aniline oligomers (SAOs). Thermal decomposition of SAO releases SO2 gas which acts as a blowing agent to form the macroporous structures. This process was used to synthesise three specifically tailored nitrogen (N)-doped MCM catalysts: N-SAO, N-SAO (phenol formaldehyde) (PF) and N-SAO-reduced graphene oxide (rGO). Analysis using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the formation of macropores (100–350 µm). Investigation of ORR efficacy showed that N-SAOPF performed with the highest onset potential of 0.98 V (vs. RHE) and N-SAOrGO showed the highest limiting current density of 7.89 mAcm−2. The macroporous structure and ORR efficacy of the MCM catalysts synthesised using this novel process suggest that this method can be used to streamline MCM production while enabling the formation of composite materials that can be tailored for greater efficiency in many applications.Ramesh Karunagaran, Diana Tran, Tran Thanh Tung, Cameron Shearer and Dusan Losi

Green synthesis of three-dimensional hybrid N-doped ORR electro-catalysts derived from apricot sap

Rapid depletion of fossil fuel and increased energy demand has initiated a need for an alternative energy source to cater for the growing energy demand. Fuel cells are an enabling technology for the conversion of sustainable energy carriers (e.g., renewable hydrogen or bio-gas) into electrical power and heat. However, the hazardous raw materials and complicated experimental procedures used to produce electro-catalysts for the oxygen reduction reaction (ORR) in fuel cells has been a concern for the effective implementation of these catalysts. Therefore, environmentally friendly and low-cost oxygen reduction electro-catalysts synthesised from natural products are considered as an attractive alternative to currently used synthetic materials involving hazardous chemicals and waste. Herein, we describe a unique integrated oxygen reduction three-dimensional composite catalyst containing both nitrogen-doped carbon fibers (N-CF) and carbon microspheres (N-CMS) synthesised from apricot sap from an apricot tree. The synthesis was carried out via three-step process, including apricot sap resin preparation, hydrothermal treatment, and pyrolysis with a nitrogen precursor. The nitrogen-doped electro-catalysts synthesised were characterised by SEM, TEM, XRD, Raman, and BET techniques followed by electro-chemical testing for ORR catalysis activity. The obtained catalyst material shows high catalytic activity for ORR in the basic medium by facilitating the reaction via a four-electron transfer mechanism.Ramesh Karunagaran, Campbell Coghlan, Cameron Shearer, Diana Tran, Karan Gulati, Tran Thanh Tung, Christian Doonan, and Dusan Losi

Influence of pristine graphene particle sizes on physicochemical, microstructural and mechanical properties of Portland cement mortars

This paper aims to study the effect of the size of pristine graphene (PRG) particles on the compressive and tensile strengths of cement-based mortars and to gain better understandings of the mechanism behind the enhancement of these properties. PRG industrially manufactured by the electrochemical process with a variety of particle sizes including 5 µm, 43 µm, 56 µm, and 73 µm was used at the optimal dosage of 0.07% by weight of cement binder. The results indicate that mechanical strengths of cement mortars at 7 and 28 days considerably depend on the size of PRG. The mixes with size 56 µm and 73 µm show significant influence on both compressive and tensile strengths of cement mortars, which increase approximately 34.3% and 30.1% at 28-day compressive strengths, and 26.9% and 38.6% at 28-day tensile strengths, respectively. On the other hand, the mix with size 43 µm of PRG addition exhibits a significant increase only in tensile strength, and there are no significant effects on either compressive strengths or tensile strengths of the mix containing 5 µm particles. The observed enhancement in the mechanical properties of cement mortars by large PRG sizes is attributed to the improvement of cement hydration level, the reduction of cement particles’ distance in cement gels because of the effect of van der Waals forces between PRG sheets, and the mechanical adhesion forces between PRG sheets and cement gels. The results from this study indicate that PRG is not only a promising additive in practical application for building materials to improve the current drawbacks of cement composites, but also a feasible option to support the reduction of cement mass used in cement composites, which could reduce the CO₂ footprint and amount of CO₂ emission into the atmosphere.Van Dac Ho, Ching-Tai Ng, Togay Ozbakkaloglu, Andy Goodwin, Craig McGuckin, Ramesh U. Karunagaran, Dusan Losi

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins

ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

<p>Abstract</p> <p>Background</p> <p>Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of <it>Curcuma longa</it>. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.</p> <p>Methods</p> <p>Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an <it>in vitro </it>APC activity assay.</p> <p>Results</p> <p>We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells.</p> <p>Conclusions</p> <p>We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin.</p

Alpha-Tomatine Induces Apoptosis and Inhibits Nuclear Factor-Kappa B Activation on Human Prostatic Adenocarcinoma PC-3 Cells

BACKGROUND: Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of highly aggressive human prostate cancer PC-3 cells with α-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC(50)) value of 1.67±0.3 µM. It is also less cytotoxic to normal human liver WRL-68 cells and normal human prostate RWPE-1 cells. Assessment of real-time growth kinetics by cell impedance-based Real-Time Cell Analyzer (RTCA) showed that α-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of α-tomatine on PC-3 cancer cell growth was mainly due to induction of apoptosis as evidenced by positive Annexin V staining and decreased in mitochondrial membrane potential but increased in nuclear condensation, polarization of F-actin, cell membrane permeability and cytochrome c expressions. Results also showed that α-tomatine induced activation of caspase-3, -8 and -9, suggesting that both intrinsic and extrinsic apoptosis pathways are involved. Furthermore, nuclear factor-kappa B (NF-κB) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-κB/p50 and NF-κB/p65 in the nuclear fraction of the treated cells compared to the control untreated cells. These results provide further insights into the molecular mechanism of the anti-proliferative actions of α-tomatine. CONCLUSION/SIGNIFICANCE: α-tomatine induces apoptosis and inhibits NF-κB activation on prostate cancer cells. These results suggest that α-tomatine may be beneficial for protection against prostate cancer development and progression

Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases

ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors