Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization

Scope: Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed “browning,” may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. Methods and Results: 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/ sirtuin1/ peroxisome proliferator-activated receptor gamma coactivator 1 alpha signaling. SFN enhanced uncoupling protein 1 expression, a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Conclusion: SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and the application of SFN is a promising strategy to combat obesity and obesity-related metabolic disorder

Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

On the performance of densified DVB-H single frequency networks

The broadcasting of TV programmes to mobile phones can be enabled by the newly developed technology called Digital Video Broadcasting-Handheld (DVB-H). Because of the scarcity and cost of frequency resources, frequency reuse needs to be considered when rolling out DVB-H networks. By simulcasting the same content from several transmitters, a Single Frequency Network (SFN) can provide good coverage and good frequency efficiency. In this paper, the performance of densified DVB-H SFN networks is analysed in terms of the coverage probability under different coverage requirements with and without frequency reuse. A dichotomy searching approach is used to determine the optimal cell radius for a cell in a densified DVB-H SFN for a given network topology. Based on the optimal cell radius map and a SFN gain map generated from the simulation results, guidelines are proposed on how to avoid the potential pitfalls in configuring the parameters of a densified DVB-H SFN network and optimise its parameters in terms of minimising the cost of the network for a range of predefined network parameters

Soliton solutions in an effective action for SU(2) Yang-Mills theory: including effects of higher-derivative term

The Skyrme-Faddeev-Niemi (SFN) model which is an O(3) $\sigma$ model in three dimensional space upto fourth-order in the first derivative is regarded as a low-energy effective theory of SU(2) Yang-Mills theory. One can show from the Wilsonian renormalization group argument that the effective action of Yang-Mills theory recovers the SFN in the infrared region. However, the thoery contains an additional fourth-order term which destabilizes the soliton solution. In this paper, we derive the second derivative term perturbatively and show that the SFN model with the second derivative term possesses soliton solutions.Comment: 7 pages, 3 figure

Extended Soliton Solutions in an Effective Action for SU(2) Yang-Mills Theory

The Skyrme-Faddeev-Niemi (SFN) model which is an O(3) $\sigma$ model in three dimensional space up to fourth-order in the first derivative is regarded as a low-energy effective theory of SU(2) Yang-Mills theory. One can show from the Wilsonian renormalization group argument that the effective action of Yang-Mills theory recovers the SFN in the infrared region. However, the theory contains an additional fourth-order term which destabilizes the soliton solution. We apply the perturbative treatment to the second derivative term in order to exclude (or reduce) the ill behavior of the original action and show that the SFN model with the second derivative term possesses soliton solutions.Comment: Published in SIGMA (Symmetry, Integrability and Geometry: Methods and Applications) at http://www.emis.de/journals/SIGMA

Brain awareness week and beyond: encouraging the next generation.

The field of neuroscience is generating increased public appetite for information about exciting brain research and discoveries. As stewards of the discipline, together with FUN and others, the Society for Neuroscience (SfN) embraces public outreach and education as essential to its mission of promoting understanding of the brain and nervous system. The Society looks to its members, particularly the younger generation of neuroscientists, to inspire, inform and engage citizens of all ages, and most importantly our youth, in this important endeavor. Here we review SfN programs and resources that support public outreach efforts to inform, educate and tell the story of neuroscience. We describe the important role the Brain Awareness campaign has played in achieving this goal and highlight opportunities for FUN members and students to contribute to this growing effort. We discuss specific programs that provide additional opportunities for neuroscientists to get involved with K-12 teachers and students in ways that inspire youth to pursue further studies and possible careers in science. We draw attention to SfN resources that support outreach to broader audiences. Through ongoing partnerships such as that between SfN and FUN, the neuroscience community is well positioned to pursue novel approaches and resources, including harnessing the power of the Internet. These efforts will increase science literacy among our citizens and garner more robust support for scientific research

Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential

Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells

Sulforaphane (SFN) is a naturally occurring compound which is known to induce the phase II antioxidant genes via Nrf2 activation, although the underlying mechanism has not been fully elucidated. In this study, we investigated Nrf2 induction in response to SFN in human bronchial epithelial BEAS-2B cells and determined the signaling pathways involved in this process. SFN treatment reduced cell viability. Prior to cell death, intracellular reactive oxygen species (ROS) were generated at a high rate within a minute of commencing SFN treatment. Pretreatment with antioxidant N-acetylcysteine (NAC) blocked SFN-induced decrease in cell growth. Erk1/2 was activated within 30 min of SFN addition, whereas Akt phosphorylation did not significantly change until the first 8 hr after SFN treatment but then became substantially low until 48 hr. Inhibition of Erk1/2 phosphorylation attenuated SFN-induced loss of cell viability. Nrf2 protein levels in both nuclear and whole cell lysates were increased by SFN treatment, which was dependent on ROS production. Knockdown of Nrf2 with siRNA attenuated SFN-induced heme oxygenase-1 (HO-1) up-regulation. Induction of the Nrf2/HO-1 after SFN treatment was potently suppressed by pretreatment with NAC. Overall, our results indicate that SFN mediates antioxidative and antiproliferative responses by generating ROS in BEAS-2B cells

The diagnostic accuracy of the small fiber neuropathy symptoms inventory questionnaire (SFN-SIQ) for identifying pure small fiber neuropathy

A definite diagnosis of pure small fiber neuropathy (SFN) relies on specific diagnostic testing, such as skin biopsy, quantitative sensory testing (QST), and nociceptive evoked potentials, which require considerable resources that may not be widely available. Accordingly, diagnostic tools with easy implementation in non-specialist centers are warranted to identify patients who require second-level diagnostic tests. In this study, we aimed to test the accuracy of the Small Fiber Neuropathy Symptoms Inventory Questionnaire (SFN-SIQ) in diagnosing pure SFN. We enrolled 86 patients with suspected pure SFN. In these patients, we calculated the diagnostic accuracy of the SFN-SIQ using a combination of clinical examination, QST, and skin biopsy as a reference standard. We found that the SFN-SIQ showed an excellent ability to discriminate between patients with and without pure SFN, with 86% sensitivity and 70% specificity in the diagnosis of pure SFN. Our study providing the diagnostic yield of the SFN-SIQ for pure SFN diagnosis suggests that this questionnaire might be used to screen patients with suspected SFN and identify those requiring second-level diagnostic tests such as QST, skin biopsy, or nociceptive evoked potentials