Due to the lack of enough physical or suck central pattern generator (SCPG) development, prematur... more Due to the lack of enough physical or suck central pattern generator (SCPG) development, premature infants require assistance in improving their sucking skills as one of the first coordinated muscular activities in infants. Hence, we need to quantitatively measure their sucking abilities for future studies on their sucking interventions. Here, we present a new device that can measure both intraoral pressure (IP) and expression pressure (EP) as ororhithmic behavior parameters of non-nutritive sucking skills in infants. Our device is low-cost, easy-to-use, and accurate, which makes it appropriate for extensive studies. To showcase one of the applications of our device, we collected weekly data from 137 premature infants from 29 week-old to 36 week-old. Around half of the infants in our study needed intensive care even after they were 36 week-old. We call them full attainment of oral feeding (FAOF) infants. We then used the Non-nutritive sucking (NNS) features of EP and IP signals of infants recorded by our device to predict FAOF infants' sucking conditions. We found that our pipeline can predict FAOF infants several weeks before discharge from the hospital. Thus, this application of our device presents a robust and inexpensive alternative to monitor oral feeding ability in premature infants.
Microwell-generated GBM spheroids are sensitized by AAAPT drugs using targeted, cleavable linkage... more Microwell-generated GBM spheroids are sensitized by AAAPT drugs using targeted, cleavable linkages to reduce off-target toxicity.
Advancing the understanding of the relationship between perinatal nicotine addiction and the rewa... more Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By usi...
Journal of neuroengineering and rehabilitation, Jan 12, 2014
Recent publications highlight differences within the sub-regions of the ventral tegmental area (V... more Recent publications highlight differences within the sub-regions of the ventral tegmental area (VTA) including the parabrachial pigmented nucleus (PBP), parainterfascicular nucleus (PIF) and paranigral nucleus (PN) in the projections to the prefrontal cortex (PFC) and the glutamatergic pathway. In order to characterize the effects of prenatal nicotine exposure on the mesocorticolimbic system of the rat offspring, local field potentials were recorded from 27 sites across the VTA of 9 rats aged 40-55 days. The extracellular VTA neural activities were analyzed using Approximate Entropy (ApEn) method. Approximate entropy values were then grouped according to each anatomic location including the PBP, PIF and PN. Our results have shown that the local field potentials corresponding to the neurons located in the PIF region of the VTA have ApEn values significantly higher (p = 2x10-4) in the maternal nicotine cases when compared to the saline. Therefore, we speculate that the dopamine neuron...
Journal of NeuroEngineering and Rehabilitation, 2011
Background The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicate... more Background The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Methods Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction bet...
Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental ar... more Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental area (VTA) and their projection areas, which include the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, play a primary role in the process of reward-driven behavior induced by the drugs of addiction, including nicotine and alcohol. In our previous study, we developed a novel platform consisting of micro-LED array devices to stimulate a large area of the brain of rats and monkeys with photo-stimulation and a microdialysis probe to estimate the DA release in the PFC. Our results suggested that the platform was able to detect the increased level of dopamine in the PFC in response to the photo-stimulation of both the PFC and VTA. In this study, we used this platform to photo-stimulate the VTA neurons in both ChrimsonR-expressing (non-specific) wild and dopamine transporter (DAT)-Cre (dopamine specific) mice, and measured the dopamine release in the nucleus accumbens shell (NAc...
Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patient... more Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased G...
Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often u... more Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often used simultaneously, and have been linked to significant health hazards. Furthermore, patients diagnosed with dependence on one drug are highly likely to be dependent on the other. Several studies have shown the effects of each drug independently on gene expression within many brain regions, including the ventral tegmental area (VTA). Dopaminergic (DA) neurons of the dopamine reward pathway originate from the VTA, which is believed to be central to the mechanism of addiction and drug reinforcement. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we investigated miRNA and mRNA expression of dopaminergic (DA) neurons of the VTA in rat pups following perinatal alcohol and joint nicotine–alcohol exposure. Microarray analysis was then used to profile the differential expression of both miRNAs and mRNAs from DA neurons of each treatment group to further expl...
Tumor angiogenesis is a promising target for cancer treatment, because severing the supply of oxy... more Tumor angiogenesis is a promising target for cancer treatment, because severing the supply of oxygen and nutrients to tumors halts tumor growth. Unfortunately, many anticancer drugs, including angiogenesis inhibitors, fail in clinical trials, despite showing high efficiency during in vitro and in vivo experiments. This inconsistency from in vitro and in vivo experiments to clinical trials represents a major obstacle in drug development and cancer treatment. Therefore, we set out to demonstrate how our rapid, stable, easy-touse three-dimensional (3D) in vitro angiogenesis model can be used to investigate tumor formation and implement drug screening. In this study, we utilized a 3D in vitro angiogenesis model, based on gelatin methacrylate (GelMA) hydrogel microwells, to mimic the native microenvironment of tumor angiogenesis. Using this model, we were able to quantify the immigration of endothelial cells into a cancer spheroid during the angiogenic process. Next, we tested the antian...
We investigated the influence of 2-APB (2-aminoethoxy-diphenylborate) acute exposure on hippocamp... more We investigated the influence of 2-APB (2-aminoethoxy-diphenylborate) acute exposure on hippocampal oscillations using time-frequency analysis methods including continuous wavelet transform and short-time Fourier transform. We hypothesized that acute exposure to 2-APB drastically reduced the hippocampal gamma oscillations. We estimated the hippocampal oscillations' time-frequency representations from 24 hippocampal slices in five rats. Our results indicated that it took at least 100 ms to see any hippocampal activities in response to the 100 Hz stimulus. The hippocampal oscillations' spectral energies dominated in the 31-60 Hz and 61-90 Hz frequency bands in the early time (100-200 ms) segment post-stimulus and in the 31-60 Hz and 61-90 Hz frequency bands after 200 ms until 400 ms post-stimulus. They were noticeably reduced in the late time segment (above 400 ms). The hippocampal oscillations' spectral energies in the 31-60 and 61-90 Hz frequency bands still dominated the early time segment after the acute 2-APB exposure. The 2-APB exposure never changed the energy content in all three frequency bands in the early time segment (p > 0.01). The exposure significantly reduced the energy content in both the mid-time segment and in the 31-60 Hz frequency band (p < 0.001) and in both the second time segment and in the 61-90 Hz frequency band (p…
Medical & biological engineering & computing, Jan 2, 2016
Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbir... more Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbirth, conduct disorder, attention-deficit/hyperactivity disorder and neurocognitive deficits. Ventral tegmental area dopamine (DA) neurons in the mesocorticolimbic pathway were suggested to play a critical role in these pathological mechanisms induced by nicotine. Nicotine-mediated changes in genetic expression during pregnancy are of great interest for current researchers. We used patch clamp methods to identify and harvest DA and non-DA neurons separately and assayed them using oligonucleotide arrays to elucidate the alterations in gene expressions in these cells upon gestational nicotine exposure. Microarray analysis identified a set of 135 genes as significantly differentially expressed between DA and non-DA neurons. Some of the genes were found to be related to neurological disease pathways, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Signifi...
Due to the lack of enough physical or suck central pattern generator (SCPG) development, prematur... more Due to the lack of enough physical or suck central pattern generator (SCPG) development, premature infants require assistance in improving their sucking skills as one of the first coordinated muscular activities in infants. Hence, we need to quantitatively measure their sucking abilities for future studies on their sucking interventions. Here, we present a new device that can measure both intraoral pressure (IP) and expression pressure (EP) as ororhithmic behavior parameters of non-nutritive sucking skills in infants. Our device is low-cost, easy-to-use, and accurate, which makes it appropriate for extensive studies. To showcase one of the applications of our device, we collected weekly data from 137 premature infants from 29 week-old to 36 week-old. Around half of the infants in our study needed intensive care even after they were 36 week-old. We call them full attainment of oral feeding (FAOF) infants. We then used the Non-nutritive sucking (NNS) features of EP and IP signals of infants recorded by our device to predict FAOF infants' sucking conditions. We found that our pipeline can predict FAOF infants several weeks before discharge from the hospital. Thus, this application of our device presents a robust and inexpensive alternative to monitor oral feeding ability in premature infants.
Microwell-generated GBM spheroids are sensitized by AAAPT drugs using targeted, cleavable linkage... more Microwell-generated GBM spheroids are sensitized by AAAPT drugs using targeted, cleavable linkages to reduce off-target toxicity.
Advancing the understanding of the relationship between perinatal nicotine addiction and the rewa... more Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By usi...
Journal of neuroengineering and rehabilitation, Jan 12, 2014
Recent publications highlight differences within the sub-regions of the ventral tegmental area (V... more Recent publications highlight differences within the sub-regions of the ventral tegmental area (VTA) including the parabrachial pigmented nucleus (PBP), parainterfascicular nucleus (PIF) and paranigral nucleus (PN) in the projections to the prefrontal cortex (PFC) and the glutamatergic pathway. In order to characterize the effects of prenatal nicotine exposure on the mesocorticolimbic system of the rat offspring, local field potentials were recorded from 27 sites across the VTA of 9 rats aged 40-55 days. The extracellular VTA neural activities were analyzed using Approximate Entropy (ApEn) method. Approximate entropy values were then grouped according to each anatomic location including the PBP, PIF and PN. Our results have shown that the local field potentials corresponding to the neurons located in the PIF region of the VTA have ApEn values significantly higher (p = 2x10-4) in the maternal nicotine cases when compared to the saline. Therefore, we speculate that the dopamine neuron...
Journal of NeuroEngineering and Rehabilitation, 2011
Background The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicate... more Background The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Methods Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction bet...
Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental ar... more Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental area (VTA) and their projection areas, which include the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, play a primary role in the process of reward-driven behavior induced by the drugs of addiction, including nicotine and alcohol. In our previous study, we developed a novel platform consisting of micro-LED array devices to stimulate a large area of the brain of rats and monkeys with photo-stimulation and a microdialysis probe to estimate the DA release in the PFC. Our results suggested that the platform was able to detect the increased level of dopamine in the PFC in response to the photo-stimulation of both the PFC and VTA. In this study, we used this platform to photo-stimulate the VTA neurons in both ChrimsonR-expressing (non-specific) wild and dopamine transporter (DAT)-Cre (dopamine specific) mice, and measured the dopamine release in the nucleus accumbens shell (NAc...
Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patient... more Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased G...
Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often u... more Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often used simultaneously, and have been linked to significant health hazards. Furthermore, patients diagnosed with dependence on one drug are highly likely to be dependent on the other. Several studies have shown the effects of each drug independently on gene expression within many brain regions, including the ventral tegmental area (VTA). Dopaminergic (DA) neurons of the dopamine reward pathway originate from the VTA, which is believed to be central to the mechanism of addiction and drug reinforcement. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we investigated miRNA and mRNA expression of dopaminergic (DA) neurons of the VTA in rat pups following perinatal alcohol and joint nicotine–alcohol exposure. Microarray analysis was then used to profile the differential expression of both miRNAs and mRNAs from DA neurons of each treatment group to further expl...
Tumor angiogenesis is a promising target for cancer treatment, because severing the supply of oxy... more Tumor angiogenesis is a promising target for cancer treatment, because severing the supply of oxygen and nutrients to tumors halts tumor growth. Unfortunately, many anticancer drugs, including angiogenesis inhibitors, fail in clinical trials, despite showing high efficiency during in vitro and in vivo experiments. This inconsistency from in vitro and in vivo experiments to clinical trials represents a major obstacle in drug development and cancer treatment. Therefore, we set out to demonstrate how our rapid, stable, easy-touse three-dimensional (3D) in vitro angiogenesis model can be used to investigate tumor formation and implement drug screening. In this study, we utilized a 3D in vitro angiogenesis model, based on gelatin methacrylate (GelMA) hydrogel microwells, to mimic the native microenvironment of tumor angiogenesis. Using this model, we were able to quantify the immigration of endothelial cells into a cancer spheroid during the angiogenic process. Next, we tested the antian...
We investigated the influence of 2-APB (2-aminoethoxy-diphenylborate) acute exposure on hippocamp... more We investigated the influence of 2-APB (2-aminoethoxy-diphenylborate) acute exposure on hippocampal oscillations using time-frequency analysis methods including continuous wavelet transform and short-time Fourier transform. We hypothesized that acute exposure to 2-APB drastically reduced the hippocampal gamma oscillations. We estimated the hippocampal oscillations' time-frequency representations from 24 hippocampal slices in five rats. Our results indicated that it took at least 100 ms to see any hippocampal activities in response to the 100 Hz stimulus. The hippocampal oscillations' spectral energies dominated in the 31-60 Hz and 61-90 Hz frequency bands in the early time (100-200 ms) segment post-stimulus and in the 31-60 Hz and 61-90 Hz frequency bands after 200 ms until 400 ms post-stimulus. They were noticeably reduced in the late time segment (above 400 ms). The hippocampal oscillations' spectral energies in the 31-60 and 61-90 Hz frequency bands still dominated the early time segment after the acute 2-APB exposure. The 2-APB exposure never changed the energy content in all three frequency bands in the early time segment (p > 0.01). The exposure significantly reduced the energy content in both the mid-time segment and in the 31-60 Hz frequency band (p < 0.001) and in both the second time segment and in the 61-90 Hz frequency band (p…
Medical & biological engineering & computing, Jan 2, 2016
Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbir... more Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbirth, conduct disorder, attention-deficit/hyperactivity disorder and neurocognitive deficits. Ventral tegmental area dopamine (DA) neurons in the mesocorticolimbic pathway were suggested to play a critical role in these pathological mechanisms induced by nicotine. Nicotine-mediated changes in genetic expression during pregnancy are of great interest for current researchers. We used patch clamp methods to identify and harvest DA and non-DA neurons separately and assayed them using oligonucleotide arrays to elucidate the alterations in gene expressions in these cells upon gestational nicotine exposure. Microarray analysis identified a set of 135 genes as significantly differentially expressed between DA and non-DA neurons. Some of the genes were found to be related to neurological disease pathways, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Signifi...
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