H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

A late Holocene vegetation and fire record from Ku-ring-gai Chase National Park, New South Wales

Volume: 110Start Page: 317End Page: 32

Asymmetry during load-loss measurement of three-phase three-limb transformers

When the load-loss measurement test is conducted on three-phase transformers, an appreciable asymmetry is observed among the power readings of the three phases. This asymmetry is the result of two causes, viz. asymmetrical disposition of phases in space with respect to each other and unequal stray losses produced by phases. The disposition of phases leads to asymmetrical mutual impedances between phases and this is the principal contributor to the phenomenon. Another factor that may have an important contribution to the phenomenon is the deviation of the phase angle difference between the voltages of the three phase source (used during the test) from 120 degrees. The causes are analyzed using a detailed three-dimensional (3-D) finite-element (FE) simulation of a 31.5 MVA, 132/33 kV transformer. In addition, a six-port network impedance model is deduced from open-circuit 3-D FE simulations. The impedance model is able to reproduce any condition of the transformer (e.g., open-circuit, short-circuit or on-load conditions) since it captures all the transformer electromagnetic phenomena. The six-port network results are discussed in order to elaborately clarify the intriguing problem of asymmetrical load-loss distribution, which is important for both transformer manufacturers and users. The results are further explained through sequence components; of currents

Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling

Ravinder Kodela,1 Niharika Nath,2 Mitali Chattopadhyay,1 Diandra E Nesbitt,1 Carlos A Velázquez-Martínez,3 Khosrow Kashfi11Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 2Department of Life Sciences, New York Institute of Technology, New York, NY, USA; 3Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada Abstract: Colorectal cancer (CRC) is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB) is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs) as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives of NSAIDs. In this study, we examined the growth inhibitory effect of a novel H2S-releasing naproxen (HS-NAP), which has a repertoire as a cardiovascular-safe NSAID, for its effects on cell proliferation, cell cycle phase transitions, and apoptosis using HT-29 human colon cancer cells. We also investigated its effect as a chemopreventive agent in a xenograft mouse model. HS-NAP suppressed the growth of HT-29 cells by induction of G0/G1 arrest and apoptosis and downregulated NF-κB. Tumor xenografts in mice were significantly reduced in volume. The decrease in tumor mass was associated with a reduction of cell proliferation, induction of apoptosis, and decreases in NF-κB levels in vivo. Therefore, HS-NAP demonstrates strong anticancer potential in CRC. Keywords: nonsteroidal anti-inflammatory drugs, cell cycle, apoptosis, xenograft, NF-κB, thioredoxin reductase, chemopreventio