Dietary isothiocyanate sulforaphene induces reactive oxygen species, caspase -9, -8, -3-dependent apoptosis and modulates PTEN/PI3Kinase in human cervical cancer cells

Purpose: To investigate the apoptotic activity, cell proliferation inhibition and different signaling protein expressions after treatment with a new isothiocyanate, sulforaphene, in human cervical cancer (HeLa) cells. Methods: Cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after sulforaphene treatment for 3, 6, 12 and 24 h. Apoptosis assay, cell cycle analysis, intracellular oxygen species (ROS) measurement, mitochondrial membrane depolarization and western blot analysis were performed in four time-intervals to explore sulforaphene activity. Results: HeLa cell viability was reduced by sulforaphene dose and time dependently. ROS plays a causative role in sulforaphene induced cytotoxicity and apoptosis during which stimulation of Bax and blocking of Bcl2 were involved. Mitochondrial membrane potential depletion and cytochrome C, AIF modulation suggest mitochondrial pathway for the apoptosis. Activation of caspase -9, -8 and -3 in treated HeLa cells demonstrated caspase-dependent apoptosis by sulforaphene. Again, sulforaphene induced HeLa cell proliferation inhibition was evidenced by cell cycle arrest and PTEN/PI3Kinase modulation. Conclusion: Dietary sulforaphene induces HeLa cell apoptosis by enhancing intracellular ROS levels, thereby activating multiple apoptotic signal cascades. Therefore, sulforaphene is a potential candidate for anticancer therapy. Keywords: Sulforaphene, HeLa cells, Apoptosis, ROS, Caspase activation, PTEN, PI3Kinas

Anti-oxidant and anti-inflammatory effects of rice bran and green tea fermentation mixture on lipopolysaccharideinduced RAW 264.7 macrophages

Purpose: To investigate the anti-inflammatory and anti-oxidant properties of an enzyme bath of Oryza sativa (rice bran) and Camellia sinensis O. Kuntz (green tea) fermented with Bacillus subtilis (OCB). Methods: The anti-oxidant effects of OCB were assessed by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay and flow cytometry. The anti-inflammatory effects of OCB were assessed by a nitric oxide (NO) assay. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to quantify expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The major compounds of OCB were identified using high performance liquid chromatography (HPLC) analysis. Results: OCB had no cytotoxic effect on LPS-stimulated macrophages or peripheral blood mononuclear cells up to 1 mg/mL. OCB displayed anti-oxidant effects comparable to those of ascorbic acid and reduced reactive oxygen species (ROS) levels in target cells. OCB treatment of LPSstimulated mavrophages decreased nitric oxide (NO), NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and key pro-inflammatory cytokine expressions, suggesting that OCB acts as an anti-oxidant and anti-inflammatory agent by reducing ROS levels and inhibiting pro-inflammatory mediators. The main effector compounds in OCB were epicatechin gallate, cathechin, synigrin acid, epicathechin, epigallocatechin gallate, rutin, and isoquercetin, which are known anti-oxidants. Conclusion: OCB fermentation product may be used as synergistic adjuvant therapy for inflammatory diseases. Keywords: Rice bran, Green tea, Bacillus subtilis, Enzyme bath, Anti-oxidant, Anti-inflammatio

Intra- and inter-hemispheric effective connectivity in the human somatosensory cortex during pressure stimulation

Background: Slow-adapting type I (SA-I) afferents deliver sensory signals to the somatosensory cortex during low-frequency (or static) mechanical stimulation. It has been reported that the somatosensory projection from SA-I afferents is effective and reliable for object grasping and manipulation. Despite a large number of neuroimaging studies on cortical activation responding to tactile stimuli mediated by SA-I afferents, how sensory information of such tactile stimuli flows over the somatosensory cortex remains poorly understood. In this study, we investigated tactile information processing of pressure stimuli between the primary (SI) and secondary (SII) somatosensory cortices by measuring effective connectivity using dynamic causal modeling (DCM). We applied pressure stimuli for 3 s to the right index fingertip of healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. Results: DCM analysis revealed intra-hemispheric effective connectivity between the contralateral SI (cSI) and SII (cSII) characterized by both parallel (signal inputs to both cSI and cSII) and serial (signal transmission from cSI to cSII) pathways during pressure stimulation. DCM analysis also revealed inter-hemispheric effective connectivity among cSI, cSII, and the ipsilateral SII (iSII) characterized by serial (from cSI to cSII) and SII-level (from cSII to iSII) pathways during pressure stimulation. Conclusions: Our results support a hierarchical somatosensory network that underlies processing of low-frequency tactile information. The network consists of parallel inputs to both cSI and cSII (intra-hemispheric), followed by serial pathways from cSI to cSII (intra-hemispheric) and from cSII to iSII (inter-hemispheric). Importantly, our results suggest that both serial and parallel processing take place in tactile information processing of static mechanical stimuli as well as highlighting the contribution of callosal transfer to bilateral neuronal interactions in SII.open1

Movement Type Prediction before Its Onset Using Signals from Prefrontal Area: An Electrocorticography Study

Power changes in specific frequency bands are typical brain responses during motor planning or preparation. Many studies have demonstrated that, in addition to the premotor, supplementary motor, and primary sensorimotor areas, the prefrontal area contributes to generating such responses. However, most brain-computer interface (BCI) studies have focused on the primary sensorimotor area and have estimated movements using postonset period brain signals. Our aim was to determine whether the prefrontal area could contribute to the prediction of voluntary movement types before movement onset. In our study, electrocorticography (ECoG) was recorded from six epilepsy patients while performing two self-paced tasks: hand grasping and elbow flexion. The prefrontal area was sufficient to allow classification of different movements through the area's premovement signals (-2.0 s to 0 s) in four subjects. The most pronounced power difference frequency band was the beta band (13-30Hz). The movement prediction rate during single trial estimation averaged 74% across the six subjects. Our results suggest that premovement signals in the prefrontal area are useful in distinguishing different movement tasks and that the beta band is the most informative for prediction of movement type before movement onset.open

Cases of Hemolytic Anemia with Periprosthetic Leaks Evaluated by Real-Time 3-Dimensional Transesophageal Echocardiography

Hemolytic anemia is recognized as a rare complication of mitral valve replacement or repair. We report on a 44-year-old man with shortness of breath and hemolytic anemia, 23 years after mitral valve replacement (Hall-Kaster), and a 63-year-old woman diagnosed of hemolytic anemia, 4 years after mitral and tricuspid annuloplasty (Tailor ring, An-core ring). Routine 2-dimensional transthoracic echocardiography revealed paravalvular leakage around the prosthesis. Subsequent real-time 3-dimensional (3D)transesophageal echocardiography helped the perceptional appreciation of the leakage and the measuring of the regurgitant orifice area using the anatomically correct plane. Surgical findings of each case fit those of 3D volumetric images

Analysis of Nociceptive Information Encoded in the Temporal Discharge Patterns of Cutaneous C-Fibers

The generation of pain signals from primary afferent neurons is explained by a labeled-line code. However, this notion cannot apply in a simple way to cutaneous C-fibers, which carry signals from a variety of receptors that respond to various stimuli including agonist chemicals. To represent the discharge patterns of C-fibers according to different agonist chemicals, we have developed a quantitative approach using three consecutive spikes. By using this method, the generation of pain in response to chemical stimuli is shown to be dependent on the temporal aspect of the spike trains. Furthermore, under pathological conditions, gamma-aminobutyric acid resulted in pain behavior without change of spike number but with an altered discharge pattern. Our results suggest that information about the agonist chemicals may be encoded in specific temporal patterns of signals in C-fibers, and nociceptive sensation may be influenced by the extent of temporal summation originating from the temporal patterns.open0

Korean Cardiac Arrest Research Consortium (KoCARC): rationale, development, and implementation

Objective This study aimed to describe the conceptualization, development, and implementation processes of the newly established Korean Cardiac Arrest Resuscitation Consortium (KoCARC) to improve out-of-hospital cardiac arrest (OHCA) outcomes. Methods The KoCARC was established in 2014 by recruiting hospitals willing to participate voluntarily. To enhance professionalism in research, seven research committees, the Epidemiology and Preventive Research Committee, Community Resuscitation Research Committee, Emergency Medical System Resuscitation Research Committee, Hospital Resuscitation Research Committee, Hypothermia and Postresuscitation Care Research Committee, Cardiac Care Resuscitation Committee, and Pediatric Resuscitation Research Committee, were organized under a steering committee. The KoCARC registry was developed with variables incorporated in the currently existing regional OHCA registries and Utstein templates and were collected via a web-based electronic database system. The KoCARC study population comprises patients visiting the participating hospitals who had been treated by the emergency medical system for OHCA presumed to have a cardiac etiology. Results A total of 62 hospitals volunteered to participate in the KoCARC, which captures 33.0% of the study population in Korea. Web-based data collection started in October 2015, and to date (December 2016), there were 3,187 cases compiled in the registry collected from 32 hospitals. Conclusion The KoCARC is a self-funded, voluntary, hospital-based collaborative research network providing high level evidence in the field of OHCA and resuscitation. This paper will serve as a reference for subsequent KoCARC manuscripts and for data elements collected in the study

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong