B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

This corrects the article DOI: 10.1038/onc.2014.43.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.  In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.

Portable EGG recording system based on a digital voice recorder.

Cutaneous electrogastrogram (EGG) recording offers the benefit of non-invasive gastrointestinal diagnosis. With long-term ambulatory recording of signals, researchers and clinicians could have more opportunities to investigate and analyse paroxysmal or acute symptoms. A portable EGG system based on a digital voice recorder (DVR) is designed for long-term recording of cutaneous EGG signals. The system consists of electrodes, an EGG amplifier, a modulator, and a DVR. Online monitoring and off-line acquisition of EGG are handled by software. A special design employing an integrated timer circuit is used to modulate the EGG frequency to meet the input requirements of the DVR. This approach involves low supply voltage and low power consumption. Software demodulation is used to simplify the complexity of the system, and is helpful in reducing the size of the portable device. By using surface-mount devices (SMD) and a low-power design, the system is robust, compact, and suitable for long-term portable recording. As a result, researchers can record an ambulatory EGG signal by means of the proposed circuits in conjunction with an up-to-date voice-recording device.

Cerebral columnar organization of the first nociceptive component induced by CO2 laser on the tail of the rat.

The somatotopic map of the first nociceptive component in the primary somatosensory cortex (S1) is still unclear. In this study, a CO(2) laser was applied to the tail of the rat to induce nociception without the interference from large myelinated (A(beta)) fibers. Thus, only noxious fibers could be activated. Two-dimensional current-source-density analysis was used to analyze the evoked field potentials. Using this method, the nociceptive responses of A(delta)-fibers in S1 were verified, and the somatotopic map of the first nociceptive component in S1 was identified. We found that whether light touch or laser-induced nociception was applied to the tail of the rat, the responsive topography in S1 was consistent. Discrimination of these two modalities was achieved vertically in the same column; the deeper layer represented the nociceptive response while the superficial layer encoded the response to light touch. This is quite different from that of a primate brain.

Brain nociceptive imaging in rats using (18)f-fluorodeoxyglucose small-animal positron emission tomography.

Preclinical exploration of pain processing in the brain as well as evaluating pain-relief drugs in small animals embodies the potential biophysical effects in humans. However, it is difficult to measure nociception-related cerebral metabolic changes in vivo, especially in unanesthetized animals. The present study used (18)F-fluorodeoxyglucose small-animal positron emission tomography to produce cerebral metabolic maps associated with formalin-induced nociception. Anesthesia was not applied during the uptake period so as to reduce possible confounding effects on pain processing in the brain. The formalin stimulation at the hind paw of rats resulted in significant metabolic increases in the bilateral cingulate cortex, motor cortex, primary somatosensory cortex, secondary somatosensory cortex, insular cortex, visual cortex, caudate putamen, hippocampus, periaqueductal gray, amygdala, thalamus, and hypothalamus. Among the measured areas, clear lateralization was only evident in the primary somatosensory cortex and hypothalamus. In addition, pretreatment with lidocaine (4 mg/kg, i.v.) and morphine (10 mg/kg, i.v.) significantly suppressed formalin-induced cerebral metabolic increases in these areas. The present protocol allowed identification of the brain areas involved in pain processing, and should be useful in further evaluations of the effects of new drugs and preclinical therapies for pain.

High-fidelity evoked potential for mapping the rat tail in thalamus.

The technique of field potentials (FPs) provides a macroscopic view for exploring brain function, and is supplementary to single-unit recording, a microscopic view that investigates each neuron in great detail. Mapping the rat tail in the ventroposterolateral (VPL) nucleus of the thalamus was carried out by analyzing the current source density (CSD) of the evoked FPs. The results showed a clear somatotopic organization of the tail in the VPL nucleus. Also, to obtain high-fidelity FPs, two recording parameters were determined. Based upon cross-correlation coefficient (rho), the cycles of FPs needed to be averaged should not be less than 50 and the distance between the two recording sites should be no longer than 50 mum in each direction (mediolateral, anteroposterior and ventrodorsal). Under these conditions, the representation (or reproducibility) of an FP can be >95%. The procedures used to determine these parameters can serve as a guide to obtain FPs with high signal-to-noise ratio and without spatial aliasing error.

Microcontroller-based wireless recorder for biomedical signals.

A portable multichannel system is described for the recording of biomedical signals wirelessly. Instead of using the conversional time-division analog-modulation method, the technique of digital multiplexing was applied to increase the number of signal channels to 4. Detailed design considerations and functional allocation of the system is discussed. The frontend unit was modularly designed to condition the input signal in an optimal manner. Then, the microcontroller handled the tasks of data conversion, wireless transmission, as well as providing the ability of simple preprocessing such as waveform averaging or rectification. The low-power nature of this microcontroller affords the benefit of battery operation and hence, patient isolation of the system. Finally, a single-chip receiver, which compatible with the RF transmitter of the microcontroller, was used to implement a compact interface with the host computer. An application of this portable recorder for low-back pain studies is shown. This device can simultaneously record one ECG and two surface EMG wirelessly, thus, is helpful in relieving patients' anxiety devising clinical measurement. Such an approach, microcontroller-based wireless measurement, could be an important trend for biomedical instrumentation and we help that this paper could be useful for other colleagues.

Analyzing effects of sodium pentobarbital on hemodynamic responses by using a graphic control system.

The maintenance of adequate anesthesia is very important for animal studies. This goal could be achieved if the pharmacokinetics of the anesthetic is known and a well-controlled instrument system is used. To this end, a graphic control system is developed to study the effects of sodium pentobarbital on anesthesia. Hemodynamic signals such as mean blood pressure, pulse pressure, heart rate were analyzed and used as index for quantitative evaluating the level of anesthesia. Factors that could affect the anesthesia, e.g. body weight (BW) of the rat and the concentration of pentobarbital were used as independent variables to examine the survival time (dependent variable) for an overdosage anesthesia. The relationship among the BW, the drug concentration, and the survival time before death were formulated. As most physiological system have shown, the empirical relationship is exponential in nature. This implies that the mechanism is highly nonlinear and it is complicated by the buffering characteristics of life. Hence, a precision feedback control system seems to be necessary for a well-controlled anesthesia.

Development of wireless blood glucose meter and diabetes self-management system.

Diabetes is a metabolic disorder that is characterized by high blood glucose and either insufficient or ineffective insulin. Blood glucose measurement is crucial to diabetes control, and it is effective in reducing the risk of complications and improving life quality. Unfortunately, both elderly patients and their caregivers find it difficult to monitor glucose levels long term. This study attempts to develop an intelligent maintenance system for home glucose measurement, wireless data transformation, and information analysis. The developed system prompts diabetics to measure their blood glucose regularly at home, and provides remote caregivers with complete patient information for diagnosis and tracking. This aids in the improvement in diabetes control, thereby increasing the social activities and life quality of diabetics.

Dynamic evaluation of [18F]-FDG uptake in the rat brain by microPET imaging.

This study aims to acquire the functional image of the rat brain, small animal positron emission tomography (microPET) with high resolution and sensitivity is adopted to assess the metabolic activity corresponding to the neuronal activity induced by the electrical stimulation of the rat tail using [18F] fluorodeoxyglucose (FDG) as the radiotracer. The microPET imaging technology can provide anatomical and functional information on neuronal activity used to analyze responses in pathway sequence relationships between the thalamus and the cerebral cortex.

Sampling variation caused by A/D cards due to external trigger.

In electrophysiological recording, a microcomputer-based analog-to-digital (A/D) card is an indispensable instrument for signal acquisition and analysis. In our studies, evoked responses sampled by our A/D card showed variation among different cycles. If several cycles had been averaged, the resultant waveform would have a smaller peak amplitude and a longer duration. To explain this phenomenon, a simulated sampling model of compound action potential was proposed. Our experimental data agreed very well with the prediction of the simulated model. The long and varied delay time between the external trigger and the first sampling in each cycle by our A/D card might be the main cause of such variation. This problem could not be solved by any post-sampled programming. Hence, for those electrophysiological laboratories which sampled evoked responses, to buy a new A/D card might be the most straightforward solution to the problem.

Microcomputer-based pulse stimulator.

A low-cost PC-based 2-channel stimulator was designed. This device can generate regular current pulses for many neuroscience experiments. It can also generate irregular pulses for nerve stimulation, thus could possibly avoid the problem of sensitization or habituation in the central nervous system. The stimulation frequency (can be < 0.0005 Hz) and pulse duration (5 microseconds to 65 ms) of this device can be programmed by an interactive user interface. Furthermore, the output current (0-10 mA) can be continuously varied and was optically isolated to minimize stimulus artifact. Moreover, features such as low-power consumption (0.2 mA of a 9 V battery) and high-compliance output (> 120 V) could accommodate the stimulator for widespread applications. A trial of nerve stimulation was illustrated besides the electrical specifications of the stimulator.

Portable current stimulator for transdermal iontophoretic drug delivery.

A pulse stimulator was designed. It is small sized (3 x 2 cm printed circuit board) and battery-powered (185 microA total static current). The current intensity and pulse duration of this device can be continuously varied. Preliminary trials of lidocaine show that this device is usable for transdermal drug delivery and may be valuable for portable applications.

Effect of conduction distance on amplitude and area of compound action potentials of A fiber and C fiber.

We used 24 sacral dorsal roots of the rat to analyze amplitude and area changes of biphasic and monophasic compound action potentials (CAPs) at 4 conduction distances. Both the CAPs of the A-fiber and C-fiber were analyzed. The changes were examined with the paired t test and linear regression. All the variables decreased linearly with increasing conduction distance except area of monophasic CAP, which remained constant throughout. CAP data were also compared between the S1 and S2 roots by using the pooled t test. Only area of monophasic CAP showed good correspondence with the anatomical data. Therefore, area of monophasic CAP is suggested as the best parameter for representing the functional state of a nerve.

Interactive program for spectral and area analysis of compound action potentials of A-fiber and C-fiber.

An interactive program was described to correct the baseline wandering of the compound action potentials (CAPs) of C-fiber, to calculate the area and the peak amplitude of CAPs, and to analyze their spectral distribution. Using this program, we found the optimal bandpass of the filter for recording CAPs to be from 10 Hz to 3 kHz.

A modified "triangular pulse" stimulator for C-fibers stimulation.

A low-cost, battery-powered stimulator is described. This device generates asymmetric current pulse with fast rising phase and slower exponential decay. The current intensity and the time constant of the exponential decay can be independently and continuously varied. An example of using this stimulator to selectively activate C-fibers is demonstrated. In this case the total charge injected in one stimulation is only 67 nanocolumb, which is much smaller than that injected by conventional DC polarization technique. Detailed information about the circuit design is described.