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1.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502229

RESUMO

The two-pore domain K+ (K2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABAAR and GABABR) reduces cellular excitability through Cl- influx and K+ efflux in neurons. Relatively little is known about the link between GABAAR and the K+ channel. The present study was performed to identify the effect of GABAR agonists on K2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABAAR and GABABR agonists. In particular, muscimol, a GABAAR agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABAAR antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl- influx in GABAergic neurons.


Assuntos
Agonistas de Receptores de GABA-A/farmacologia , Neurônios GABAérgicos/metabolismo , Potenciais da Membrana , Muscimol/farmacologia , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Receptores de GABA/química , Animais , Células Cultivadas , Neurônios GABAérgicos/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos , Canais de Potássio de Domínios Poros em Tandem/genética , Ratos
2.
Materials (Basel) ; 14(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34576364

RESUMO

From the viewpoint of the device performance, the fabrication and patterning of oxide-metal-oxide (OMO) multilayers (MLs) as transparent conductive oxide electrodes with a high figure of merit have been extensively investigated for diverse optoelectronic and energy device applications, although the issues of their general concerns about possible shortcomings, such as a more complicated fabrication process with increasing cost, still remain. However, the underlying mechanism by which a thin metal mid-layer affects the overall performance of prepatterned OMO ML electrodes has not been fully elucidated. In this study, indium tin oxide (ITO)/silver (Ag)/ITO MLs are fabricated using an in-line sputtering method for different Ag thicknesses on glass substrates. Subsequently, a Q-switched diode-pumped neodymium-doped yttrium vanadate (Nd:YVO4, λ = 1064 nm) laser is employed for the direct ablation of the ITO/Ag/ITO ML films to pattern ITO/Ag/ITO ML electrodes. Analysis of the laser-patterned results indicate that the ITO/Ag/ITO ML films exhibit wider ablation widths and lower ablation thresholds than ITO single layer (SL) films. However, the dependence of Ag thickness on the laser patterning results of the ITO/Ag/ITO MLs is not observed, despite the difference in their absorption coefficients. The results show that the laser direct patterning of ITO/Ag/ITO MLs is primarily affected by rapid thermal heating, melting, and vaporization of the inserted Ag mid-layer, which has considerably higher thermal conductivity and absorption coefficients than the ITO layers. Simulation reveals the importance of the Ag mid-layer in the effective absorption and focusing of photothermal energy, thereby supporting the experimental observations. The laser-patterned ITO/Ag/ITO ML electrodes indicate a comparable optical transmittance, a higher electrical current density, and a lower resistance compared with the ITO SL electrode.

3.
Plants (Basel) ; 10(5)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919440

RESUMO

BACKGROUND: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism. METHODS: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons. Mice were fed a normal or high-fat diet for 12 weeks, then received PNE for the last 2 weeks to measure the following physiological indices: Body weight, food intake, fat/lean mass, glucose metabolism, and plasma leptin levels. In addition, changes of thermogenic, lipolytic, and lipogenetic markers were evaluated in brown adipose tissue (BAT) and white adipose tissue (WAT) by western blotting, respectively. RESULTS: PNE increased hypothalamic POMC neuronal activity, and the effect was abolished by blockade of melanocortin 3/4 receptors (MC3/4Rs). PNE decreased body weight, fat mass, plasma leptin levels, and improved glucose metabolism after high-fat-induced obesity. However, PNE did not change the expression of thermogenic markers of the BAT in HFD fed groups, but decreased only the lipogenetic markers of WAT. This study suggests that PNE has a potent anti-obesity effect, inhibiting lipogenesis in WAT, even though HFD-induced leptin resistance-mediated disruption of POMC neuronal activity.

4.
Int J Mol Sci ; 21(23)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256222

RESUMO

TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TGTRESK). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (p < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TGTRESK SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TGTRESK mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1ß concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TGTRESK SCI mice compared to WT-SCI mice (p < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.


Assuntos
Neurônios Motores/patologia , Canais de Potássio/genética , Recuperação de Função Fisiológica , Células Receptoras Sensoriais/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Regulação para Cima/genética , Animais , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Camundongos Endogâmicos C57BL , Neurônios Motores/metabolismo , Canais de Potássio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo
5.
Mar Drugs ; 18(10)2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33050644

RESUMO

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.


Assuntos
Crassostrea/química , Dipeptídeos/farmacologia , Etanol/metabolismo , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Animais , Dipeptídeos/química , Etanol/administração & dosagem , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidrólise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
6.
Micromachines (Basel) ; 11(9)2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32872492

RESUMO

Demand for the fabrication of high-performance, transparent electronic devices with improved electronic and mechanical properties is significantly increasing for various applications. In this context, it is essential to develop highly transparent and conductive electrodes for the realization of such devices. To this end, in this work, a chemical vapor deposition (CVD)-grown graphene was transferred to both glass and polyethylene terephthalate (PET) substrates that had been pre-coated with an indium tin oxide (ITO) layer and then subsequently patterned by using a laser-ablation method for a low-cost, simple, and high-throughput process. A comparison of the results of the laser ablation of such a graphene/ITO double layer with those of the ITO single-layered films reveals that a larger amount of effective thermal energy of the laser used is transferred in the lateral direction along the graphene upper layer in the graphene/ITO double-layered structure, attributable to the high thermal conductivity of graphene. The transferred thermal energy is expected to melt and evaporate the lower ITO layer at a relatively lower threshold energy of laser ablation. The transient analysis of the temperature profiles indicates that the graphene layers can act as both an effective thermal diffuser and converter for the planar heat transfer. Raman spectroscopy was used to investigate the graphite peak on the ITO layer where the graphene upper layer was selectively removed because of the incomplete heating and removal process for the ITO layer by the laterally transferred effective thermal energy of the laser beam. Our approach could have broad implications for designing highly transparent and conductive electrodes as well as a new way of nanoscale patterning for other optoelectronic-device applications using laser-ablation methods.

7.
Cancers (Basel) ; 12(3)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204484

RESUMO

Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1ß in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH's effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy.

8.
Nano Lett ; 20(2): 812-819, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31670525

RESUMO

Nanolenses of alkali metal halides can be a unique optical element due to their hygroscopicity, optical transparency, and high mobility of constituent ions. It has been challenging, however, to form and place such lenses in a controlled manner. Here, we report micro/nanolenses of various alkali metal halides arranged as a one-dimensional (1D) array, using the exterior of single-walled carbon nanotubes (SWNTs) as a template for forming the lenses. Applying an electrical bias to an aqueous solution of alkali metal halides placed at the end of an SWNT array causes ionic transport along the exterior of SWNTs and the subsequent formation of salt micro/nanocrystals. The crystals serve as micro/nanolenses that optically visualize individual SWNTs and amplify their Raman scattering by orders of magnitude. Molecules dissolved in the ionic solution can be electrokinetically transported along the nanotubes, captured within the lenses, and analyzed by Raman spectroscopy, which we demonstrate by detecting ∼12 attomoles of glucose and 2 femtomoles of urea. The hygroscopic salt nanolenses are robust under various ambient conditions indefinitely, by transitioning to liquid droplets above their deliquescence relative humidity, yet can be removed nondestructively by water. Our approach could have broad implications in the optical visualization of 1D nanostructures, molecular transport or chemical reactions in 1D space, and molecular spectroscopy in salty environments.

9.
Cells ; 8(5)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091801

RESUMO

Lipid emulsion (LE) therapy has been used to reduce overdose of bupivacaine (BPV)-induced cardiotoxicity. The TWIK-related potassium channel-1 (TREK-1) is inhibited by BPV and activated by polyunsaturated fatty acids, which are the main component in LE. These pharmacological properties inspired us to investigate whether the TREK-1 channel is associated with cell viability of H9c2 cardiomyoblasts affected by BPV and LE. Consistent with previous studies, BPV-induced cell death was reduced by LE treatment. The reduction in the TREK-1 expression level by BPV was alleviated by LE. The BPV cytotoxicity highly decreased in TREK-1 overexpressed cells but was the opposite in TREK-1 knocked-down cells. TREK-1 channel activators and inhibitors increased and decreased cell viability, respectively. BPV-induced depolarization of the plasma and mitochondrial membrane potential and increase in intracellular Ca2+ level were blocked by LE treatment. BPV-induced depolarization of membrane potential was reduced in TREK-1 overexpressed cells, indicating that TREK-1 channels mediate setting the resting membrane potentials as a background K+ channel in H9c2 cells. These results show that TREK-1 activity is involved in the BPV cytotoxicity and the antagonistic effect of LE in H9c2 cells and suggest that TREK-1 could be a target for action of BPV and LE.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Lipídeos/farmacologia , Mioblastos Cardíacos/efeitos dos fármacos , Canais de Potássio de Domínios Poros em Tandem/fisiologia , Animais , Bupivacaína/química , Cardiotoxicidade/tratamento farmacológico , Linhagem Celular , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mioblastos Cardíacos/citologia
10.
Micromachines (Basel) ; 10(1)2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30621033

RESUMO

In this work, a study on a semi-floating-gate synaptic transistor (SFGST) is performed to verify its feasibility in the more energy-efficient hardware-driven neuromorphic system. To realize short- and long-term potentiation (STP/LTP) in the SFGST, a poly-Si semi-floating gate (SFG) and a SiN charge-trap layer are utilized, respectively. When an adequate number of holes are accumulated in the SFG, they are injected into the nitride charge-trap layer by the Fowler⁻Nordheim tunneling mechanism. Moreover, since the SFG is charged by an embedded tunneling field-effect transistor existing between the channel and the drain junction when the post-synaptic spike occurs after the pre-synaptic spike, and vice versa, the SFG is discharged by the diode when the post-synaptic spike takes place before the pre-synaptic spike. This indicates that the SFGST can attain STP/LTP and spike-timing-dependent plasticity behaviors. These characteristics of the SFGST in the highly miniaturized transistor structure can contribute to the neuromorphic chip such that the total system may operate as fast as the human brain with low power consumption and high integration density.

11.
Cancers (Basel) ; 11(1)2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30634506

RESUMO

Depression is more common in women with breast cancer than the general population. Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are widely used for the treatment of patients with depression and a range of anxiety-related disorders. The association between the use of antidepressant medication and breast cancer is controversial. In this study, we investigated whether and how SSRIs induce the death of human breast cancer MCF-7 cells. Of the antidepressants tested in this study (amitriptyline, bupropion, fluoxetine, paroxetine, and tianeptine), paroxetine most reduced the viability of MCF-7 cells in a time-and dose-dependent manner. The exposure of MCF-7 cells to paroxetine resulted in mitochondrion-mediated apoptosis, which is assessed by increase in the number of cells with sub-G1 DNA content, caspase-8/9 activation, poly (ADP-ribose) polymerase cleavage, and Bax/Bcl-2 ratio and a reduction in the mitochondrial membrane potential. Paroxetine increased a generation of reactive oxygen species (ROS), intracellular Ca2+ levels, and p38 MAPK activation. The paroxetine-induced apoptotic events were reduced by ROS scavengers and p38 MAPK inhibitor, and the paroxetine's effect was dependent on extracellular Ca2+ level. Paroxetine also showed a synergistic effect on cell death induced by chemotherapeutic drugs in MCF-7 and MDA-MB-231 cells. Our results showed that paroxetine induced apoptosis of human breast cancer MCF-7 cells through extracellular Ca2+-and p38 MAPK-dependent ROS generation. These results suggest that paroxetine may serve as an anticancer adjuvant to current cancer therapies for breast cancer patients with or without depression.

12.
Micromachines (Basel) ; 9(11)2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30405029

RESUMO

These days, the demand on electronic systems operating at high temperature is increasing owing to bursting interest in applications adaptable to harsh environments on earth, as well as in the unpaved spaces in the universe. However, research on memory technologies suitable to high-temperature conditions have been seldom reported yet. In this work, a novel one-transistor dynamic random-access memory (1T DRAM) featuring the device channel with partially inserted wide-bandgap semiconductor material toward the high-temperature application is proposed and designed, and its device performances are investigated with an emphasis at 500 K. The possibilities of the program operation by impact ionization and the erase operation via drift conduction by a properly high drain voltage have been verified through a series of technology computer-aided design (TCAD) device simulations at 500 K. Analyses of the energy-band structures in the hold state reveals that the electrons stored in the channel can be effectively confined and retained by the surrounding thin wide-bandgap semiconductor barriers. Additionally, for more realistic and practical claims, transient characteristics of the proposed volatile memory device have been closely investigated quantifying the programming window and retention time. Although there is an inevitable degradation in state-1/state-0 current ratio compared with the case of room-temperature operation, the high-temperature operation capabilities of the proposed memory device at 500 K have been confirmed to fall into the regime permissible for practical use.

13.
Int J Mol Sci ; 19(7)2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973548

RESUMO

Tandem pore domain weak inward rectifier potassium channel (TWIK)-related spinal cord K⁺ (TRESK; K2P18.1) channel is the only member of the two-pore domain K⁺ (K2P) channel family that is activated by an increase in intracellular Ca2+ concentration ([Ca2+]i) and linked to migraines. This study was performed to identify the effect of verapamil, which is an L-type Ca2+ channel blocker and a prophylaxis for migraines, on the TRESK channel in trigeminal ganglion (TG) neurons, as well as in a heterologous system. Single-channel and whole-cell currents were recorded in TG neurons and HEK-293 cells transfected with mTRESK using patch-clamping techniques. In TG neurons, changes in [Ca2+]i were measured using the fluo-3-AM Ca2+ indicator. Verapamil, nifedipine, and NiCl2 inhibited the whole-cell currents in HEK-293 cells overexpressing mTRESK with IC50 values of 5.2, 54.3, and >100 µM, respectively. The inhibitory effect of verapamil on TRESK channel was also observed in excised patches. In TG neurons, verapamil (10 µM) inhibited TRESK channel activity by approximately 76%. The TRESK channel activity was not dependent on the presence of extracellular Ca2+. In addition, the inhibitory effect of verapamil on the TRESK channel remained despite the absence of extracellular Ca2+. These findings show that verapamil inhibits the TRESK current independently of the blockade of Ca2+ influx in TG neurons. Verapamil will be able to exert its pharmacological effects by modulating TRESK, as well as Ca2+ influx, in TG neurons in vitro. We suggest that verapamil could be used as an inhibitor for identifying TRESK channel in TG neurons.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Neurônios/metabolismo , Canais de Potássio/metabolismo , Gânglio Trigeminal/metabolismo , Verapamil/farmacologia , Animais , Cálcio/metabolismo , Células HEK293 , Humanos , Concentração Inibidora 50 , Camundongos , Níquel/farmacologia , Nifedipino/farmacologia , Técnicas de Patch-Clamp , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Pflugers Arch ; 470(10): 1449-1458, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29931651

RESUMO

Transient receptor-potential, cation channel, subfamily M, member 4 (TRPM4) channels regulate a variety of physiological and pathological processes; however, their roles as functional channels under diverse conditions remain unclear. In this study, cytosolic protein tyrosine phosphatase non-receptor type 6 (PTPN6) interacted with TRPM4 channels. We confirmed their interaction by performing co-immunoprecipitation (Co-IP) assays following heterologous PTPN6 and TRPM4 channel expression in HEK293 cells. Furthermore, biomolecular fluorescence complementation (BiFC) image analysis confirmed TRPM4-PTPN6 binding. In addition, immunoblotting and Co-IP analyses revealed that TRPM4 expression significantly decreased in the membrane fraction of cells after PTPN6 was silenced with a specific short-hairpin RNA (shRNA-PTPN6). In agreement, TRPM4-induced changes in whole-cell currents were not detected in PTPN6-silenced HEK cells, in contrast to cells transfected with a scrambled RNA (scRNA) or in naïve HEK cells. These data suggest that PTPN6 inhibits TRPM4 channel activity by disrupting TRPM4 expression. Furthermore, TRPM4 channels were expressed in the membrane of naïve cells and scRNA transfectants, but not in those of PTPN6-silenced cells. These results indicated that PTPN6 is critically associated with TRPM4 trafficking. This role of PTPN6 in TRPM4 membrane localization was also demonstrated in HeLa cells. TRPM4 overexpression significantly enhanced cell proliferation in untreated HeLa cells, but not in HeLa cells with silenced PTPN6 expression. These findings indicate that PTPN6-dependent TRPM4 expression and trafficking to the plasma membrane is critical for cell proliferation in both HEK293 and HeLa cells. Therefore, PTPN6 is a novel therapeutic target for treating pathologic diseases involving TRPM4.


Assuntos
Membrana Celular/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Canais de Cátion TRPM/metabolismo , Células HEK293 , Células HeLa , Humanos , Ligação Proteica , Transporte Proteico
15.
J Nanosci Nanotechnol ; 18(9): 6257-6264, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29677777

RESUMO

As direct formation of p-type two-dimensional transition metal dichalcogenides (TMDC) films on substrates, tungsten disulfide (WS2) thin films were deposited onto sapphire glass substrate through shadow mask patterns by radio-frequency (RF) sputtering at different sputtering powers ranging from 60 W to 150 W and annealed by rapid thermal processing (RTP) at various high temperatures ranging from 500 °C to 800 °C. Based on scanning electron microscope (SEM) images and Raman spectra, better surface roughness and mode dominant E12g and A1g peaks were found for WS2 thin films prepared at higher RF sputtering powers. It was also possible to obtain high mobilities and carrier densities for all WS2 thin films based on results of Hall measurements. Process conditions for these WS2 thin films on sapphire substrate were optimized to low RF sputtering power and high temperature annealing.

16.
J Nanosci Nanotechnol ; 18(9): 6265-6269, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29677778

RESUMO

In this work, the UV-Vis-NIR absorption spectrum of liquid-phase exfoliated two-dimensional (2D) MoS2 nanosheets, revealed two prominent peaks at 608 nm (2.04 eV) and 668 nm (1.86 eV). These peaks were blue-shifted compared to the reported literature values and are attributed to the quantum confinement effect. Interestingly, the WS2 nanosheets exhibited the same characteristic absorption peak at ~624 nm (1.99 eV). Raman spectroscopy analysis revealed that both nanosheets displayed distinctive peaks [377.8 cm-1 and 405.6 cm-1 for MoS2, 348.3 cm-1 and 417.9 cm-1 for WS2] that originate from optical phonon modes (E12g and A1g). These peaks are shifted toward higher wavenumbers (i.e., blue-shift or phonon-stiffening) compared to bulk MoS2 and WS2, probably due to enhanced Stokes Raman scattering. Subsequently, surface functionalization of the nanosheets with 2-Mercaptoethanol was successfully performed and confirmed using optical characterization techniques, including FT-IR spectroscopy. In addition, we determined the spectral broadening after functionalization, which would be attributed to photon confinement of the nano-sized layer structure, or to inhomogeneous broadening.

17.
Micromachines (Basel) ; 10(1)2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30597929

RESUMO

The triboelectric generator (TEG) is a strong candidate for low-power sensors utilized in the Internet of Things (IoT) technology. Within IoT technologies, advanced driver assistance system (ADAS) technology is included within autonomous driving technology. Development of an energy source for sensors necessary for operation becomes an important issue, since a lot of sensors are embedded in vehicles and require more electrical energy. Although saving energy and enhancing energy efficiency is one of the most important issues, the application approach to harvesting wasted energy without compromising the reliability of existing mechanical systems is still in very early stages. Here, we report of a new type of TEG, a suspension-type free-standing mode TEG (STEG) inspired from a shock absorber in a suspension system. We discovered that the optimum width of electrode output voltage was 131.9 V and current was 0.060 µA/cm² in root mean square (RMS) value while the optimized output power was 4.90 µW/cm² at 66 MΩ. In addition, output power was found to be proportional to frictional force due to the contact area between two frictional surfaces. It was found that the STEG was made of perfluoroalkoxy film and showed good mechanical durability with no degradation of output performance after sliding 11,000 times. In addition, we successfully demonstrated charging a capacitor of 330 µF in 6 min.

18.
Int J Mol Sci ; 18(11)2017 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-29156592

RESUMO

Earlier studies have demonstrated that the tandem pore domain weak inward rectifying K⁺ channel (TWIK)-related K⁺ (TREK)-1 channel is inhibited by antidepressants and is associated with major depression. However, little is known about the effect of mood stabilizers that are commonly used for treatment of bipolar disorder on TREK channels, members of the two-pore domain K⁺ (K2P) channel family. This study sought to investigate the effect of mood stabilizers on TREK-1 and TREK-2 channels. HEK-293A cells were transfected with human TREK-1 or TREK-2 DNA. The effect of mood stabilizers on TREK-1 and TREK-2 was studied using the patch clamp technique. Changes in TREK protein expression by mood stabilizers were studied in the HT-22 mouse hippocampal neuronal cells using western blot analysis. Lithium chloride (LiCl, 1 mM), gabapentin (100 µM), valproate (100 µM), and carbamazepine (100 µM) increased TREK-1 currents by 31 ± 14%, 25 ± 11%, 28 ± 12%, and 72 ± 12%, respectively, whereas they had no effect on TREK-2 channel activity. In addition, western blot analysis showed LiCl and carbamazepine slightly upregulated TREK-1 expression, but not TREK-2 in the HT-22 cells. These results suggest that TREK-1 could be a potential therapeutic target for treatment of bipolar disorders as well as depression, while TREK-2 is a target well suited for treatment of major depression.


Assuntos
Antimaníacos/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Antidepressivos/farmacologia , Antipsicóticos/farmacologia , Células HEK293 , Hipocampo/metabolismo , Humanos , Cloreto de Lítio/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ácido Valproico/farmacologia
19.
Korean J Physiol Pharmacol ; 20(4): 379-85, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27382354

RESUMO

TWIK-related K(+) channel-2 (TREK-2) and TWIK-related spinal cord K(+) (TRESK) channel are members of two-pore domain K(+) channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specifi c activators of TREK-2 and TRESK may be benefi cial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently.

20.
Molecules ; 21(4): 430, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27043510

RESUMO

Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE2, NO, IL-6, IL-1ß, LTD4, and LTE4 production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS.


Assuntos
Anti-Inflamatórios/química , Alho/química , Inflamação/tratamento farmacológico , Extratos Vegetais/química , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/química , Linhagem Celular , Humanos , Peróxido de Hidrogênio/toxicidade , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Camundongos , Extratos Vegetais/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo
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