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1.
Angew Chem Int Ed Engl ; 63(3): e202312942, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38062619

RESUMEN

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.


Asunto(s)
Clatrina , Micelas , Clatrina/metabolismo , Endocitosis/fisiología , Endosomas/metabolismo , Neuronas/metabolismo
2.
Bioorg Med Chem ; 95: 117513, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37931520

RESUMEN

In this article, the development of fluorescent imaging probes for the detection of Alzheimer's disease (AD)-associated protein aggregates is described. Indane derivatives with a donor-π-acceptor (D-π-A) structure were designed and synthesized. The probes were evaluated for their ability to bind to ß-amyloid (Aß) protein aggregates, which are a key pathological hallmark of AD. The results showed that several probes exhibited significant changes in fluorescence intensity at wavelengths greater than 600 nm when they were bound to Aß aggregates compared to the Aß monomeric form. Among the tested probes, four D-π-A type indane derivatives showed promising binding selectivity to Aß aggregates over non-specific proteins such as bovine serum albumin (BSA). The molecular docking study showed that our compounds were appropriately located along the Aß fibril axis through the hydrophobic tunnel structure. Further analysis revealed that the most active compound having dimethylaminopyridyl group as an election donor and dicyano group as an electron acceptor could effectively stain Aß plaques in brain tissue samples from AD transgenic mice. These findings suggest that our indane-based compounds have the potential to serve as fluorescent probes for the detection and monitoring of Aß aggregation in AD.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Colorantes Fluorescentes/química , Agregado de Proteínas , Simulación del Acoplamiento Molecular , Péptidos beta-Amiloides/metabolismo , Ratones Transgénicos , Encéfalo/metabolismo , Placa Amiloide/química , Placa Amiloide/diagnóstico , Placa Amiloide/patología
3.
Alzheimers Dement ; 19(12): 5482-5497, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37218673

RESUMEN

INTRODUCTION: Hyperphosphorylation and aggregation of the microtubule-associated protein tau cause the development of tauopathies, such as Alzheimer's disease and frontotemporal dementia (FTD). We recently uncovered a causal link between constitutive serotonin receptor 7 (5-HT7R) activity and pathological tau aggregation. Here, we evaluated 5-HT7R inverse agonists as novel drugs in the treatment of tauopathies. METHODS: Based on structural homology, we screened multiple approved drugs for their inverse agonism toward 5-HT7R. Therapeutic potential was validated using biochemical, pharmacological, microscopic, and behavioral approaches in different cellular models including tau aggregation cell line HEK293 tau bimolecular fluorescence complementation, primary mouse neurons, and human induced pluripotent stem cell-derived neurons carrying an FTD-associated tau mutation as well as in two mouse models of tauopathy. RESULTS: Antipsychotic drug amisulpride is a potent 5-HT7R inverse agonist. Amisulpride ameliorated tau hyperphosphorylation and aggregation in vitro. It further reduced tau pathology and abrogated memory impairment in mice. DISCUSSION: Amisulpride may be a disease-modifying drug for tauopathies.


Asunto(s)
Enfermedad de Alzheimer , Demencia Frontotemporal , Células Madre Pluripotentes Inducidas , Tauopatías , Humanos , Ratones , Animales , Agonismo Inverso de Drogas , Amisulprida/uso terapéutico , Demencia Frontotemporal/tratamiento farmacológico , Demencia Frontotemporal/genética , Células HEK293 , Células Madre Pluripotentes Inducidas/metabolismo , Tauopatías/genética , Proteínas tau/metabolismo , Enfermedad de Alzheimer/patología
4.
Int J Med Sci ; 19(7): 1131-1137, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35919819

RESUMEN

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.


Asunto(s)
Catequina/análogos & derivados , Glicósidos , Melanoma Experimental , Animales , Catequina/farmacología , Línea Celular Tumoral , Glicósidos/farmacología , Melaninas , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Ratones , Monofenol Monooxigenasa/metabolismo , alfa-MSH/farmacología
5.
Molecules ; 27(24)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36557874

RESUMEN

Tomato is a widely distributed, cultivated, and commercialized vegetable crop. It contains antioxidant constituents including lycopene, tocopherols, vitamin C, γ-aminobutyric acid, phenols, and flavonoids. This study determined the contents of the antioxidant components and activities of the pulp with skin of ten regular, six medium-sized, and two small cherry tomato cultivars at red ripe (BR + 10) stage cultivated in Korea. The relationships among the Hunter color coordinates, the content of each component, and antioxidant activities were measured by Pearson's correlation coefficients. As the a* value increased, the carotenoid and vitamin C contents increased, while the L* value, hue angle and tocopherol content decreased. As the b* value increased, the lycopene and total carotenoid contents decreased, and the flavonoid content in the hydrophilic extracts increased. The contents of vitamin C and total carotenoids including lycopene showed high positive correlations with the DPPH radical scavenging activities of both the lipophilic and hydrophilic extracts. Tocopherols and total phenolics in the hydrophilic and lipophilic extracts were not major positive contributors to the antioxidant activity. These findings suggest the quality standards for consumer requirements and inputs for on-going research for the development of better breeds.


Asunto(s)
Antioxidantes , Solanum lycopersicum , Antioxidantes/química , Licopeno , Fitomejoramiento , Carotenoides/química , Ácido Ascórbico , Tocoferoles , Flavonoides/química , Fenoles/análisis , Vitaminas , República de Corea
6.
Molecules ; 27(6)2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35335230

RESUMEN

As part of an ongoing natural product chemical research for the discovery of bioactive secondary metabolites with novel structures, wild fruiting bodies of Daedaleopsis confragosa were collected and subjected to chemical and biological analyses. We subjected the fractions derived from the methanol extract of the fruiting bodies of D. confragosa to bioactivity-guided fractionation because the methanol extract of D. confragosa showed antibacterial activity against Helicobacter pylori strain 51, according to our bioactivity screening. The n-hexane and dichloromethane fractions showed moderate to weak antibacterial activity against H. pylori strain 51, and the active fractions were analyzed for the isolation of antibacterial compounds. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that the n-hexane fraction contains several compounds which are absent in the other fractions, so the fraction was prioritized for further fractionation. Through chemical analysis of the active n-hexane and dichloromethane fractions, we isolated five ergosterol derivatives (1-5), and their chemical structures were determined to be demethylincisterol A3 (1), (20S,22E,24R)-ergosta-7,22-dien-3ß,5α,6ß-triol (2), (24S)-ergosta-7-ene-3ß,5α,6ß-triol (3), 5α,6α-epoxy-(22E,24R)-ergosta-7,22-dien-3ß-ol (4), and 5α,6α-epoxy-(24R)-ergosta-7-en-3ß-ol (5) by NMR spectroscopic analysis. This is the first report on the presence of ergosterol derivatives (1-5) in D. confragosa. Compound 1 showed the most potent anti-H. pylori activity with 33.9% inhibition, rendering it more potent than quercetin, a positive control. Compound 3 showed inhibitory activity comparable to that of quercetin. Distribution analysis of compound 1 revealed a wide presence of compound 1 in the kingdom Fungi. These findings indicate that demethylincisterol A3 (1) is a natural antibiotic that may be used in the development of novel antibiotics against H. pylori.


Asunto(s)
Agaricales , Antibacterianos/farmacología , Cromatografía Liquida , Cromatografía de Gases y Espectrometría de Masas , Polyporaceae , República de Corea , Esteroles/farmacología , Espectrometría de Masas en Tándem
7.
Analyst ; 146(15): 4748-4755, 2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34231563

RESUMEN

Since oxidative stress has been recognized as a major factor contributing to the progression of several neurodegenerative disorders, reactive oxygen species (ROS) including superoxide have received great attention as a representative molecular marker for the diagnosis of Alzheimer's disease (AD). Here, superoxide-sensitive fluorogenic molecular probes, benzenesulfonylated resorufin derivatives (BSRs), were newly devised for optical bioimaging of oxidative events in neurodegenerative processes. BSRs, fluorescence-quenched benzenesulfonylated derivatives of resorufin, were designed to recover their fluorescence upon exposure to superoxide through a selective nucleophilic uncaging reaction of the benzenesulfonyl cage. Among BSRs, BSR6 presented the best sensitivity and selectivity to superoxide likely due to the optimal reactivity matching between the nucleophilicity of superoxide and its electrophilicity ascribed to the highly electron-withdrawing pentafluoro-substitution on the benzenesulfonyl cage. Fluorescence imaging of inflammatory cells and animal models presented the potential of BSR6 for optical sensing of superoxide in vitro and in vivo. Furthermore, microglial cell (Bv2) imaging with BSR6 enabled the optical monitoring of intracellular oxidative events upon treatment with an oxidative stimulus (amyloid beta, Aß) or the byproduct of oxidative stress (4-hydroxynonenal, HNE).


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/metabolismo , Animales , Sondas Moleculares , Estrés Oxidativo , Especies Reactivas de Oxígeno , Superóxidos
8.
BMC Microbiol ; 17(1): 154, 2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28693424

RESUMEN

BACKGROUND: Bacillus subtilis is able to utilize at least three inositol stereoisomers as carbon sources, myo-, scyllo-, and D-chiro-inositol (MI, SI, and DCI, respectively). NAD+-dependent SI dehydrogenase responsible for SI catabolism is encoded by iolX. Even in the absence of functional iolX, the presence of SI or MI in the growth medium was found to induce the transcription of iolX through an unknown mechanism. RESULTS: Immediately upstream of iolX, there is an operon that encodes two genes, yisR and iolQ (formerly known as degA), each of which could encode a transcriptional regulator. Here we performed an inactivation analysis of yisR and iolQ and found that iolQ encodes a repressor of the iolX transcription. The coding sequence of iolQ was expressed in Escherichia coli and the gene product was purified as a His-tagged fusion protein, which bound to two sites within the iolX promoter region in vitro. CONCLUSIONS: IolQ is a transcriptional repressor of iolX. Genetic evidences allowed us to speculate that SI and MI might possibly be the intracellular inducers, however they failed to antagonize DNA binding of IolQ in in vitro experiments.


Asunto(s)
Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Enzimológica de la Expresión Génica , Inositol/metabolismo , NAD/metabolismo , Proteínas Represoras/metabolismo , Deshidrogenasas del Alcohol de Azúcar/genética , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Regulación Bacteriana de la Expresión Génica , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Deshidrogenasas del Alcohol de Azúcar/metabolismo
9.
Biosci Biotechnol Biochem ; 81(5): 1026-1032, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28043209

RESUMEN

Bacillus subtilis genes iolG, iolW, iolX, ntdC, yfiI, yrbE, yteT, and yulF belong to the Gfo/Idh/MocA family. The functions of iolG, iolW, iolX, and ntdC are known; however, the functions of the others are unknown. We previously reported the B. subtilis cell factory simultaneously overexpressing iolG and iolW to achieve bioconversion of myo-inositol (MI) into scyllo-inositol (SI). YulF shares a significant similarity with IolW, the NADP+-dependent SI dehydrogenase. Transcriptional abundance of yulF did not correlate to that of iol genes involved in inositol metabolism. However, when yulF was overexpressed instead of iolW in the B. subtilis cell factory, SI was produced from MI, suggesting a similar function to iolW. In addition, we demonstrated that recombinant His6-tagged YulF converted scyllo-inosose into SI in an NADPH-dependent manner. We have thus identified yulF encoding an additional NADP+-dependent SI dehydrogenase, which we propose to rename iolU.


Asunto(s)
Bacillus subtilis/enzimología , Bacillus subtilis/genética , Inositol/metabolismo , NADP/metabolismo , Deshidrogenasas del Alcohol de Azúcar/genética , Deshidrogenasas del Alcohol de Azúcar/metabolismo , Activación Enzimática
10.
Plants (Basel) ; 13(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38475547

RESUMEN

Salix chaenomeloides Kimura, commonly known as pussy willow, is a deciduous shrub and tree belonging to the Salicaceae family. The genus Salix spp. has been known as a healing herb for the treatment of fever, inflammation, and pain relief. The current study aimed to investigate the potential bioactive natural products from S. chaenomeloides leaves and evaluate their antibacterial activity against Helicobacter pylori. A phytochemical investigation of the ethanol (EtOH) extract of S. chaenomeloides leaves led to the isolation of 13 phenolic compounds (1-13) from the ethyl acetate (EtOAc) fraction, which showed antibacterial activity against H. pylori strain 51. The chemical structure of a new phenolic glycoside, chaenomelin (1), was established by a detailed analysis of 1D and 2D (1H-1H correlation spectroscopy (COSY), heteronuclear single-quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC)) nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), and chemical reactions. The other known compounds were identified as 5-O-trans-p-coumaroyl quinic acid methyl ester (2), tremulacin (3), citrusin C (4), benzyl 3-O-ß-d-glucopyranosyl-7-hydroxybenzoate (5), tremuloidin (6), 1-[O-ß-d-glucopyranosyl(1→2)-ß-d-glucopyranosyl]oxy-2-phenol (7), arbutin cinnamate (8), tremulacinol (9), catechol (10), 4-hydroxybenzaldehyde (11), kaempferol 3-rutinoside (12), and narcissin (13), based on the comparison of their NMR spectra with the reported data and liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds were evaluated for antibacterial activity against H. pylori strain 51. Among the isolates, 1-[O-ß-d-glucopyranosyl(1→2)-ß-d-glucopyranosyl]oxy-2-phenol (7) and arbutin cinnamate (8) exhibited antibacterial activity against H. pylori strain 51, with inhibitions of 31.4% and 33.9%, respectively, at a final concentration of 100 µM. These results were comparable to that of quercetin (38.4% inhibition), which served as a positive control. Generally, these findings highlight the potential of the active compounds 7 and 8 as antibacterial agents against H. pylori.

11.
Micromachines (Basel) ; 14(6)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37374812

RESUMEN

In this paper, we compared the characteristics of normally-on/off AlGaN/GaN MISHEMTs passivated by an in situ/ex situ SiN layer. The devices passivated by the in situ SiN layer revealed enhanced DC characteristics, such as the drain current of 595 mA/mm (normally-on) and 175 mA/mm (normally-off) with the high on/off current ratio of ~107, respectively, compared with those of the devices passivated by the ex situ SiN layer. The MISHEMTs passivated by the in situ SiN layer also exhibited a much lower increase of dynamic on-resistance (RON) of 4.1% for the normally-on device and 12.8% for the normally-off device, respectively. Furthermore, the breakdown characteristics are greatly improved by employing the in situ SiN passivation layer, suggesting that the in situ SiN passivation layer can remarkably not only suppress the surface-trapping effects, but also decrease the off-state leakage current in the GaN-based power devices.

12.
Micromachines (Basel) ; 14(6)2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-37374686

RESUMEN

This study investigates the operating characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) by applying HfO2 as the passivation layer. Before analyzing HEMTs with various passivation structures, modeling parameters were derived from the measured data of fabricated HEMT with Si3N4 passivation to ensure the reliability of the simulation. Subsequently, we proposed new structures by dividing the single Si3N4 passivation into a bilayer (first and second) and applying HfO2 to the bilayer and first passivation layer only. Ultimately, we analyzed and compared the operational characteristics of the HEMTs considering the basic Si3N4, only HfO2, and HfO2/Si3N4 (hybrid) as passivation layers. The breakdown voltage of the AlGaN/GaN HEMT having only HfO2 passivation was improved by up to 19%, compared to the basic Si3N4 passivation structure, but the frequency characteristics deteriorated. In order to compensate for the degraded RF characteristics, we modified the second Si3N4 passivation thickness of the hybrid passivation structure from 150 nm to 450 nm. We confirmed that the hybrid passivation structure with 350-nm-thick second Si3N4 passivation not only improves the breakdown voltage by 15% but also secures RF performance. Consequently, Johnson's figure-of-merit, which is commonly used to judge RF performance, was improved by up to 5% compared to the basic Si3N4 passivation structure.

13.
Nanomaterials (Basel) ; 13(5)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36903774

RESUMEN

Recently, we reported that device performance degradation mechanisms, which are generated by the γ-ray irradiation in GaN-based metal-insulator-semiconductor high electron mobility transistors (MIS-HEMTs), use extremely thin gate insulators. When the γ-ray was radiated, the total ionizing dose (TID) effects were generated and the device performance deteriorated. In this work, we investigated the device property alteration and its mechanisms, which were caused by the proton irradiation in GaN-based MIS-HEMTs for the 5 nm-thick Si3N4 and HfO2 gate insulator. The device property, such as threshold voltage, drain current, and transconductance varied by the proton irradiation. When the 5 nm-thick HfO2 layer was employed for the gate insulator, the threshold voltage shift was larger than that of the 5 nm-thick Si3N4 gate insulator, despite the HfO2 gate insulator exhibiting better radiation resistance compared to the Si3N4 gate insulator. On the other hand, the drain current and transconductance degradation were less for the 5 nm-thick HfO2 gate insulator. Unlike the γ-ray irradiation, our systematic research included pulse-mode stress measurements and carrier mobility extraction and revealed that the TID and displacement damage (DD) effects were simultaneously generated by the proton irradiation in GaN-based MIS-HEMTs. The degree of the device property alteration was determined by the competition or superposition of the TID and DD effects for the threshold voltage shift and drain current and transconductance deterioration, respectively. The device property alteration was diminished due to the reduction of the linear energy transfer with increasing irradiated proton energy. We also studied the frequency performance degradation that corresponded to the irradiated proton energy in GaN-based MIS-HEMTs using an extremely thin gate insulator.

14.
ACS Omega ; 8(45): 42548-42554, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38024697

RESUMEN

Gastric problems are often caused by the well-known Helicobacter pylori (H. pylori) bacterium. One of the biggest obstacles to the treatment of H. pylori infections is increasing the antibiotic resistance. During our search for naturally derived anti-H. pylori compounds, six major compounds were isolated from the methylene chloride (CH2Cl2) and ethyl acetate (EtOAc) fractions of Rumex acetosa that showed anti-H. pylori activity. Three anthraquinones and three anthraquinone glucosides were identified as the major chemical constituents of the CH2Cl2 and EtOAc fractions, respectively. The chemical structures were identified to be emodin (1), chrysophanol (2), physcion (3), emodin-8-O-ß-d-glucoside (4), chrysophanol-8-O-ß-d-glucoside (5), and physcion-8-O-ß-d-glucoside (6) by UV, 1H NMR, 13C NMR, and mass spectrometry. Anti-H. pylori activity, including the minimum inhibitory concentration (MIC) value of each compound, was evaluated against two H. pylori strains. All isolates exhibited anti-H. pylori activity with different potencies, with an MIC value ranging between 3.13 and 25 µM. However, some variations were found between the two strains. While compound 5 displayed the most potent antibacterial activity with an MIC50 value of 8.60 µM and an MIC90 value of 15.7 µM against H. pylori strain 51, compound 1 exhibited the most potent inhibitory activity against H. pylori strain 43504. The two compounds also showed moderate urease inhibitory activity, with compound 1 demonstrating activity higher than that of compound 5. Furthermore, a molecular docking study revealed the high binding ability of compounds 1 and 5 to the active site of H. pylori urease. The present study suggests that the six anthraquinones isolated from R. acetosa with the whole parts of this plant may be natural candidates for the treatment of H. pylori infection. Further studies are required to determine the exact mechanism of action and to evaluate safety issues in the human body.

15.
Micromachines (Basel) ; 15(1)2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38258177

RESUMEN

In this study, we propose an optimized AlGaN/GaN high-electron-mobility transistor (HEMT) with a considerably improved breakdown voltage. First, we matched the simulated data obtained from a basic T-gate HEMT with the measured data obtained from the fabricated device to ensure the reliability of the simulation. Thereafter, to improve the breakdown voltage, we suggested applying a gate-head extended structure. The gate-head-top and gate-head-bottom lengths of the basic T-gate HEMT were symmetrically extended by 0.2 µm steps up to 1.0 µm. The breakdown voltage of the 1.0 µm extended structure was 52% higher than that of the basic T-gate HEMT. However, the cutoff frequency (fT) and maximum frequency (fmax) degraded. To minimize the degradation of fT and fmax, we additionally introduced a gate-recessed structure to the 1.0 µm gate-head extended HEMT. The thickness of the 25 nm AlGaN barrier layer was thinned down to 13 nm in 3 nm steps, and the highest fT and fmax were obtained at a 6 nm recessed structure. The fT and fmax of the gate-recessed structure improved by 9% and 28%, respectively, with respect to those of the non-gate-recessed structure, and further improvement of the breakdown voltage by 35% was observed. Consequently, considering the trade-off relationship between the DC and RF characteristics, the 1.0 µm gate-head extended HEMT with the 6 nm gate-recessed structure was found to be the optimized AlGaN/GaN HEMT for high-power operations.

16.
Exp Mol Med ; 55(3): 612-627, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36914856

RESUMEN

Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer's disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. 14C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan disassembles tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents methylene blue and LMTM failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued cognitive declines induced by tauopathy in the TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.


Asunto(s)
Enfermedad de Alzheimer , Tauopatías , Ratones , Animales , Proteínas tau/metabolismo , Simendán/farmacología , Simendán/uso terapéutico , Simendán/metabolismo , Tauopatías/tratamiento farmacológico , Tauopatías/metabolismo , Tauopatías/patología , Enfermedad de Alzheimer/metabolismo , Neuronas/metabolismo , Modelos Animales de Enfermedad , Ratones Transgénicos
17.
J Belg Soc Radiol ; 106(1): 24, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35581984

RESUMEN

Teaching Point: Radiologists need to be familiar with that ovarian vein thrombosis can occur as a complication of urinary tract infection. Ovarian vein thrombosis is a rare disease in which a majority of cases occur during the postpartum period. There are few case reports for ovarian vein thrombosis associated with urinary tract infection in non-postpartum women. We report a case of ovarian vein thrombosis incidentally diagnosed on computed tomography in a patient with symptoms of urinary tract infection.

18.
J Belg Soc Radiol ; 106(1): 70, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35974891

RESUMEN

A vas deferens abscess is a very rare complication of acute vasitis and lower urinary tract infection. A case of vas deferens rupture due to an abscess with severe pelvic inflammation requiring surgical drainage is reported. Teaching Point: Vas deferens abscess rupture is an example of a very rare complication of severe inflammation of the vas deferens.

19.
Antioxidants (Basel) ; 11(2)2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35204303

RESUMEN

The nuclear factor erythroid-derived 2-related factor 2 (NRF2) plays a pivotal role in the regulation of genes involved in oxidative stress and drug detoxification. Therefore, it is important to find NRF2 inducers to protect cells from excessive oxidative damage. Here, we investigated the effect of medicarpin isolated from the root of Robinia pseudoacacia L. on the activity of NRF2 in HeLa cells. Medicarpin significantly induced the antioxidant response elements (ARE)-luciferase activity in a concentration-dependent manner. Furthermore, medicarpin not only induced HO-1, GCLC, and NQO1 mRNA by translocating NRF2 to the nucleus but also induced the mRNA level of NRF2. To verify the NRF2 induction mechanism by medicarpin, ~2 kb of NRF2 promoter-luciferase assay was executed. As a result, medicarpin significantly induced NRF2-luciferase activity. Moreover, medicarpin strongly inhibited the ubiquitin-dependent proteasomal degradation of NRF2. Thus, medicarpin might protect cells by promoting the NRF2 transcriptional activity.

20.
Taehan Yongsang Uihakhoe Chi ; 83(1): 168-172, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36237347

RESUMEN

Tailgut cysts are known to originate from the remnants of the embryonic hindgut. They occur exclusively in the retrorectal and presacral spaces. There have been limited reports of tailgut cysts occurring in the left perirenal space. The present case features a huge tailgut cyst extending from the right perirenal to the perivesical space. We believe that this case report will help to further elucidate the characteristics of perirenal and perivesical tailgut cysts.

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