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1.
Free Radic Res ; 58(4): 276-292, 2024.
Article in English | MEDLINE | ID: mdl-38613520

ABSTRACT

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.


Subject(s)
Ginsenosides , Kainic Acid , Mitochondria , STAT3 Transcription Factor , Signal Transduction , Animals , Kainic Acid/toxicity , Mice , Mitochondria/metabolism , Mitochondria/drug effects , STAT3 Transcription Factor/metabolism , Ginsenosides/pharmacology , Signal Transduction/drug effects , Male , Mice, Knockout , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress/drug effects
2.
J Pineal Res ; 76(1): e12921, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37846173

ABSTRACT

Evidence suggests that the neuroprotective effects of melatonin involve both receptor-dependent and -independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post-KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression-like behaviors following KA-induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0.12 µg/µL) in the hippocampus of mice. Ramelteon (3 or 10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) mitigated KA-induced oxidative stress and impairment of glutathione homeostasis and promoted the nuclear translocation and DNA binding activity of Nrf2 in the hippocampus after KA treatment. Ramelteon and melatonin also attenuated microglial activation but did not significantly affect astroglial activation induced by KA, despite the astroglial induction of melatonin receptors after KA treatment. However, ramelteon attenuated KA-induced proinflammatory phenotypic changes in astrocytes. Considering the reciprocal regulation of astroglial and microglial activation, these results suggest ramelteon inhibits microglial activation by regulating astrocyte phenotypic changes. These effects were accompanied by the attenuation of the nuclear translocation and DNA binding activity of nuclear factor κB (NFκB) induced by KA. Consequently, ramelteon attenuated the KA-induced hippocampal neuronal loss, memory impairment, and depression-like behaviors; the effects were comparable to those of melatonin. These results suggest that ramelteon-mediated activation of melatonin receptors provides neuroprotection against KA-induced neurotoxicity in the mouse hippocampus by activating Nrf2 signaling to attenuate oxidative stress and restore glutathione homeostasis and by inhibiting NFκB signaling to attenuate neuroinflammatory changes.


Subject(s)
Indenes , Melatonin , Mice , Animals , Melatonin/pharmacology , Melatonin/metabolism , Receptors, Melatonin/metabolism , Kainic Acid/toxicity , Kainic Acid/metabolism , NF-E2-Related Factor 2/metabolism , Hippocampus , Seizures/chemically induced , Seizures/drug therapy , Seizures/metabolism , Glutathione/metabolism , DNA
3.
Sci Rep ; 13(1): 17728, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853073

ABSTRACT

In this study, to develop soft pressure sensor applicable to wearable robots using stretchable polymers and conductive fillers, 3.25 wt% carbon nanotubes/thermoplastic polyurethane filament with shore 94 A were manufactured. Three infill densities (20%, 50%, and 80%) and patterns (zigzag (ZG), triangle (TR), honeycomb (HN)) were applied to print cubes via fused filament fabrication 3D printing. Most suitable infill conditions were confirmed based on the slicing images, morphologies, compressive properties, electrical properties, and electrical heating properties. For each infill pattern, ZG and TR divided the layers into lines and figures, and the layers were stacked by rotation. For HN, the same layers were stacked in a hexagonal pattern. Consequently, TR divided layer in various directions, showed the strongest compressive properties with toughness 1.99 J for of infill density 80%. Especially, the HN became tougher with increased infill density. Also, the HN laminated with the same layer showed excellent electrical properties, with results greater than 14.7 mA. The electrical heating properties confirmed that ZG and HN had the high layer density, which exhibited excellent heating characteristics. Therefore, it was confirmed that performance varies depending on the 3D printing direction, and it was confirmed that HN is suitable for manufacturing soft sensors.

4.
J Ginseng Res ; 47(4): 561-571, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37397414

ABSTRACT

Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

5.
Food Chem Toxicol ; 178: 113869, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37308051

ABSTRACT

Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.


Subject(s)
Ginsenosides , Methamphetamine , Animals , Mice , Antioxidants/pharmacology , Antioxidants/metabolism , Bays , Ginsenosides/pharmacology , Ginsenosides/metabolism , Hippocampus , Methamphetamine/toxicity , Mice, Knockout , Mitochondria , Seizures/chemically induced , Seizures/drug therapy , Seizures/prevention & control , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
6.
Polymers (Basel) ; 15(6)2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36987323

ABSTRACT

The development of waterborne polyurethane (WPU) has been stimulated as an alternative to solvent-based polyurethanes due to low-VOC alternatives and reduced exposure to solvents. However, their relatively low mechanical performance and degradation have presented challenges in their wide application. Here, we developed environmentally-friendly bio polyol-based WPU nanocomposite dispersions and films, and presented the optimal process conditions for their manufacture. Additionally, the condition was established without using harmful catalysts or ethyl methyl ketone (MEK) during the polymerization. Moreover, regenerated cellulose nanoparticles (RCNs) were employed as natural chain-extenders in order to improve the biodegradability and mechanical performances of the nanocomposite films. The RCNs have a lower crystallinity compared to cellulose nanocrystals (CNCs), allowing them to possess high toughness without interfering with the elastomeric properties of polyurethane. The prepared CWPU/RCNs nanocomposite films exhibited high toughness of 58.8 ± 3 kgf∙mm and elongation at break of 240 ± 20%. In addition, depending on the molar ratio of NCO/OH, the polyurethane particle size is variously controlled from 70 to 230 nm, enabling to fabricate their dispersions with various transmittances. We believe that our findings not only open a meaningful path toward green elastomers with biodegradability but provides the design concept for bio-elastomers in order to develop industrial elastomers with mechanical and thermal properties.

7.
Materials (Basel) ; 16(3)2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36770079

ABSTRACT

Bio-based thermoplastic polyurethanes have attracted increasing attention as advanced shape memory materials. Using the prepolymer method, novel fast-responding shape memory thermoplastic polyurethanes (SMTPUs) were prepared from 100% bio-based polyester polyol, poly-propylene succinate derived from corn oil, diphenyl methane diisocyanate, and bio-based 1,3-propanediol as a chain extender. The morphologies of the SMTPUs were investigated by Fourier transform infrared spectroscopy, atomic force microscopy, and X-ray diffraction, which revealed the interdomain spacing between the hard and soft phases, the degree of phase separation, and the intermixing level between the hard and soft phases. The thermal and mechanical properties of the SMTPUs were also investigated, wherein a high hard segment content imparted unique properties that rendered the SMTPUs suitable for shape memory applications at varying temperatures. More specifically, the SMTPUs exhibited a high level of elastic elongation and good mechanical strength. Following compositional optimization, a tensile strength of 24-27 MPa was achieved, in addition to an elongation at break of 358-552% and a hardness of 84-92 Shore A. Moreover, the bio-based SMTPU exhibited a shape recovery of 100%, thereby indicating its potential for use as an advanced temperature-dependent shape memory material with an excellent shape recoverability.

8.
Life Sci ; 319: 121529, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36841471

ABSTRACT

AIMS: We examined the effect of γ-aminobutyric acid (GABA)B receptor activation on astrocyte phenotype changes induced by trimethyltin (TMT) in the dentate gyrus of mice. MAIN METHODS: Male C57BL/6N mice received TMT (2.6 mg/kg, i.p.), and the expression of GABAB receptors was evaluated in the hippocampus. The GABAB receptor agonist baclofen (2.5, 5, or 10 mg/kg, i.p. × 5 at 12-h intervals) was administered 3-5 days after TMT treatment, and the expression of Iba-1, GFAP, and astrocyte phenotype markers was evaluated 6 days after TMT. SL327 (30 mg/kg, i.p.), an extracellular signal-related kinase (ERK) inhibitor, was administered 1 h after each baclofen treatment. KEY FINDINGS: TMT insult significantly induced the astroglial expression of GABAB receptors in the dentate molecular layer. Baclofen significantly promoted the expression of S100A10, EMP1, and CD109, but not that of C3, GGTA1, and MX1 induced by TMT. In addition, baclofen significantly increased the TMT-induced expression of p-ERK in the dentate molecular layer. Interestingly, p-ERK was more colocalized with S100A10 than with C3 after TMT insult, and a significant positive correlation was found between the expression of p-ERK and S100A10. Consistently, SL327 reversed the effect of baclofen on astrocyte phenotype changes. Baclofen also enhanced the TMT-induced astroglial expression of glial cell-derived neurotrophic factor (GDNF), an anti-inflammatory astrocytes-to-microglia mediator, and consequently attenuated Iba-1 expression and delayed apoptotic neuronal death. SIGNIFICANCE: Our results suggest that GABAB receptor activation increases S100A10-positive anti-inflammatory astrocytes and astroglial GDNF expression via ERK signaling after TMT excitotoxicity in the dentate molecular layer of mice.


Subject(s)
Astrocytes , Baclofen , Animals , Male , Mice , Astrocytes/metabolism , Baclofen/pharmacology , Dentate Gyrus , Extracellular Signal-Regulated MAP Kinases/metabolism , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Hippocampus/metabolism , Mice, Inbred C57BL , Phenotype , Receptors, GABA/metabolism , Receptors, GABA-B
9.
Food Chem Toxicol ; 173: 113627, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36682417

ABSTRACT

Ginsenoside Re (GRe) upregulates anti-aging klotho by mainly upregulating glutathione peroxidase-1 (GPx-1). However, the anti-aging mechanism of GPx-1 remains elusive. Here we investigated whether the GRe-mediated upregulation of GPx-1 modulates oxidative and proinflammatory insults. GPx-1 gene depletion altered redox homeostasis and platelet-activating factor receptor (PAFR) and nuclear factor kappa B (NFκB) expression, whereas the genetic overexpression of GPx-1 or GRe mitigated this phenomenon in aged mice. Importantly, the NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) did not affect PAFR expression, while PAFR inhibition (i.e., PAFR knockout or ginkgolide B) significantly attenuated NFκB nuclear translocation, suggesting that PAFR could be an upstream molecule for NFκB activation. Iba-1-labeled microgliosis was more underlined in aged GPx-1 KO than in aged WT mice. Triple-labeling immunocytochemistry showed that PAFR and NFκB immunoreactivities were co-localized in Iba-1-positive populations in aged mice, indicating that microglia released these proteins. GRe inhibited triple-labeled immunoreactivity. The microglial inhibitor minocycline attenuated aging-related reduction in phospho-ERK. The effect of minocycline was comparable with that of GRe. GRe, ginkgolide B, PDTC, or minocycline also attenuated aging-evoked memory impairments. Therefore, GRe ameliorated aging-associated memory impairments in the absence of GPx-1 by inactivating oxidative insult, PAFR, NFkB, and microgliosis.


Subject(s)
Glutathione Peroxidase GPX1 , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Minocycline/metabolism , Minocycline/pharmacology , Mice, Knockout , Hippocampus
10.
Drug Chem Toxicol ; 46(2): 281-296, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35707918

ABSTRACT

It has been recognized that serotonergic blocker showed serious side effects, and that ginsenoside modulated serotonergic system with the safety. However, the effects of ginsenoside on serotonergic impairments remain to be clarified. Thus, we investigated ginsenoside Re (GRe), a major bioactive component in the mountain-cultivated ginseng on (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. In the present study, we observed that the treatment with GRe resulted in significant inhibition of protein kinase C δ (PKCδ) phosphorylation induced by the 5-HT1A receptor agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) in the hypothalamus of the wild-type (WT) mice. The inhibition of GRe was comparable with that of the PKCδ inhibitor rottlerin or the 5-HT1A receptor antagonist WAY100635 (WAY). 8-OH-DPAT-induced significant reduction in nuclear factor erythroid-2-related factor 2 (Nrf2)-related system (i.e., Nrf2 DNA binding activity, γ-glutamylcysteine ligase modifier (GCLm) and γ-glutamylcysteine ligase catalytic (GCLc) mRNA expression, and glutathione (GSH)/oxidized glutathione (GSSG) ratio) was significantly attenuated by GRe, rottlerin, or WAY in WT mice. However, PKCδ gene knockout significantly protected the Nrf2-dependent system from 8-OH-DPAT insult in mice. Increases in 5-hydroxytryptophan (5-HT) turnover rate, overall serotonergic behavioral score, and hypothermia induced by 8-OH-DPAT were significantly attenuated by GRe, rottlerin, or WAY in WT mice. Consistently, PKCδ gene knockout significantly attenuated these parameters in mice. However, GRe or WAY did not provide any additional positive effects on the serotonergic protective potential mediated by PKCδ gene knockout in mice. Therefore, our results suggest that PKCδ is an important mediator for GRe-mediated protective activity against serotonergic impairments/oxidative burden caused by the 5-HT1A receptor.


Subject(s)
Ginsenosides , Mice , Animals , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Ginsenosides/pharmacology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Receptor, Serotonin, 5-HT1A/genetics , Glutathione , Glutathione Disulfide , Serotonin Antagonists , Ligases
11.
Polymers (Basel) ; 14(20)2022 Oct 12.
Article in English | MEDLINE | ID: mdl-36297847

ABSTRACT

In this study, a series of bio-based thermoplastic polyurethane (TPU) was synthesized via the solvent-free one-shot method using 100% bio-based polyether polyol, prepared from fermented corn, and 1,4-butanediol (BDO) as a chain extender. The average molecular weight, degree of phase separation, thermal and mechanical properties of the TPU-based aromatic (4,4-methylene diphenyl diisocyanate: MDI), and aliphatic (bis(4-isocyanatocyclohexyl) methane: H12MDI) isocyanates were investigated by gel permeation chromatography, Fourier transform infrared spectroscopy, atomic force microscopy, X-ray Diffraction, differential scanning calorimetry, dynamic mechanical thermal analysis, and thermogravimetric analysis. Four types of micro-phase separation forms of a hard segment (HS) and soft segment (SS) were suggested according to the [NCO]/[OH] molar ratio and isocyanate type. The results showed (a) phase-mixed disassociated structure between HS and SS, (b) hydrogen-bonded structure of phase-separated between HS and SS forming one-sided hard domains, (c) hydrogen-bonded structure of phase-mixed between HS, and SS and (d) hydrogen-bonded structure of phase-separated between HS and SS forming dispersed hard domains. These phase micro-structure models could be matched with each bio-based TPU sample. Accordingly, H-BDO-2.0, M-BDO-2.0, H-BDO-2.5, and M-BDO-3.0 could be related to the (a)-form, (b)-form, (c)-form, and (d)-form, respectively.

12.
Free Radic Biol Med ; 189: 2-19, 2022 08 20.
Article in English | MEDLINE | ID: mdl-35840016

ABSTRACT

Ginseng is known to possess anti-aging potential. Klotho mutant mice exhibit phenotypes that resemble the phenotype of the human aging process. Similar to Klotho deficient mice, patients with chronic kidney disease (CKD) suffer vascular damage and cognitive impairment, which might upregulate the angiotensin II AT1 receptor. Since AT1 receptor expression was more pronounced than endothelin ET-1 expression in the hippocampus of aged Klotho deficient (±) mice, we focused on the AT1 receptor in this study. Ginsenoside Re (GRe), but not ginsenoside Rb1 (GRb1), significantly attenuated the increase in AT1 receptor expression in aged Klotho deficient mice. Both GRe and the AT1 receptor antagonist losartan failed to attenuate the decrease in phosphorylation of JAK2/STAT3 in aged Klotho deficient (±) mice but significantly activated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling. Both GRe and losartan attenuated the increased NADPH oxidase (NOX) activity and reactive oxygen species (ROS) in aged Klotho deficient mice. Furthermore, of all the antioxidant enzymes, GRe significantly increased glutathione peroxidase (GPx) activity. GRe significantly attenuated the reduced phosphorylation of ERK and CREB in GPx-1 knockout mice; however, genetic overexpression of GPx-1 did not significantly affect them in aged mice. Klotho-, Nrf2-, and GPx-1-immunoreactivities were co-localized in the same cells of the hippocampus in aged Klotho wild-type mice. Both the GPx inhibitor mercaptosuccinate and Nrf2 inhibitor brusatol counteracted the effects of GRe on all neurobehavioral impairments in aged Klotho deficient (±) mice. Our results suggest that GRe attenuates all alterations, such as AT1 receptor expression, NOX-, ROS-, and GPx-levels, and cognitive dysfunction in aged Klotho deficient (±) mice via upregulation of Nrf2/GPx-1/ERK/CREB signaling.


Subject(s)
NF-E2-Related Factor 2 , Receptor, Angiotensin, Type 1 , Animals , Mice , Angiotensin II , Antioxidants/pharmacology , Ginsenosides , Glutathione Peroxidase , Glutathione Peroxidase GPX1 , Klotho Proteins , Losartan/pharmacology , Memory Disorders , Mice, Knockout , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species
13.
J Neuroinflammation ; 19(1): 142, 2022 Jun 11.
Article in English | MEDLINE | ID: mdl-35690821

ABSTRACT

BACKGROUND: It has been demonstrated that reactive astrocytes can be polarized into pro-inflammatory A1 phenotype or anti-inflammatory A2 phenotype under neurotoxic and neurodegenerative conditions. Microglia have been suggested to play a critical role in astrocyte phenotype polarization by releasing pro- and anti-inflammatory mediators. In this study, we examined whether trimethyltin (TMT) insult can induce astrocyte polarization in the dentate gyrus of mice, and whether protein kinase Cδ (PKCδ) plays a role in TMT-induced astrocyte phenotype polarization. METHODS: Male C57BL/6 N mice received TMT (2.6 mg/kg, i.p.), and temporal changes in the mRNA expression of A1 and A2 phenotype markers were evaluated in the hippocampus. In addition, temporal and spatial changes in the protein expression of C3, S100A10, Iba-1, and p-PKCδ were examined in the dentate gyrus. Rottlerin (5 mg/kg, i.p. × 5 at 12-h intervals) was administered 3-5 days after TMT treatment, and the expression of A1 and A2 transcripts, p-PKCδ, Iba-1, C3, S100A10, and C1q was evaluated 6 days after TMT treatment. RESULTS: TMT treatment significantly increased the mRNA expression of A1 and A2 phenotype markers, and the increased expression of A1 markers remained longer than that of A2 markers. The immunoreactivity of the representative A1 phenotype marker, C3 and A2 phenotype marker, S100A10 peaked 6 days after TMT insult in the dentate gyrus. While C3 was expressed evenly throughout the dentate gyrus, S100A10 was highly expressed in the hilus and inner molecular layer. In addition, TMT insult induced microglial p-PKCδ expression. Treatment with rottlerin, a PKCδ inhibitor, decreased Iba-1 and C3 expression, but did not affect S100A10 expression, suggesting that PKCδ inhibition attenuates microglial activation and A1 astrocyte phenotype polarization. Consistently, rottlerin significantly reduced the expression of C1q and tumor necrosis factor-α (TNFα), which has been suggested to be released by activated microglia and induce A1 astrocyte polarization. CONCLUSION: We demonstrated the temporal and spatial profiles of astrocyte polarization after TMT insult in the dentate gyrus of mice. Taken together, our results suggest that PKCδ plays a role in inducing A1 astrocyte polarization by promoting microglial activation and consequently increasing the expression of pro-inflammatory mediators after TMT insult.


Subject(s)
Astrocytes , Complement C1q , Acetophenones , Animals , Astrocytes/metabolism , Benzopyrans , Complement C1q/metabolism , Dentate Gyrus/pathology , Male , Mice , Mice, Inbred C57BL , Microglia/metabolism , Phenotype , RNA, Messenger/metabolism , Trimethyltin Compounds
14.
Sci Rep ; 12(1): 7780, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35546596

ABSTRACT

A strain sensor characterized by elasticity has recently been studied in various ways to be applied to monitoring humans or robots. Here, 4 types of 3D-printed auxetic lattice structures using thermoplastic polyurethane as raw material were characterized: truss and honeycomb with positive Poisson's ratio and chiral truss and re-entrant with negative Poisson's ratio. Each structure was fabricated as a flexible and stable strain sensor by coating graphene through a dip-coating process. The fabricated auxetic structures have excellent strength, flexibility, and electrical conductivity desirable for a strain sensor and detect a constant change in resistance at a given strain. The 3D-printed auxetic lattice 4 type structures coated with CWPU/Graphene suggest potential applications of multifunctional strain sensors under deformation.


Subject(s)
Graphite , Elasticity , Electric Conductivity , Humans , Polyurethanes , Printing, Three-Dimensional
15.
Pharmacol Res ; 179: 106226, 2022 05.
Article in English | MEDLINE | ID: mdl-35460881

ABSTRACT

BKM120 is an inhibitor of class I phosphoinositide 3-kinases and its anti-cancer effects have been demonstrated in various solid cancer models. BKM120 is highly brain permeable and has been reported to induce mood disturbances in clinical trials. Therefore, we examined whether BKM120 produces anxiety- and depression-like behaviors in mice, as with patients receiving BKM120 in clinical trials. In this study, repeated BKM120 treatment (2.0 or 5.0 mg/kg, i.p., five times at 12-h interval) significantly induced anxiety- and depression-like behaviors in mice. Although abnormal changes in hippocampal neurogenesis have been suggested to, at least in part, associated with the pathogenesis of depression and anxiety, BKM120 did not affect the incorporation of 5-bromo-2'-deoxyuridine or the expression of doublecortin (DCX); however, it significantly enhanced the radial migration of DCX-positive cells in the dentate gyrus. BKM120-induced changes in migration were not accompanied by obvious neuronal damage in the hippocampus. Importantly, BKM120-induced anxiety- and depression-like behaviors were positively correlated with the extent of DCX-positive cell migration. Concomitantly, p-Akt expression was significantly decreased in the dentate gyrus. Moreover, the expression of p-c-Jun N-terminal kinase (JNK), p-DCX, and Ras homolog family member A (RhoA)-GTP decreased significantly, particularly in aberrantly migrated DCX-positive cells. Together, the results suggest that repeated BKM120 treatment enhances the radial migration of DCX-positive cells and induces anxiety- and depression-like behaviors by regulating the activity of Akt, JNK, DCX, and RhoA in the dentate gyrus. It also suggests that the altered migration of adult-born neurons in the dentate gyrus plays a role in mood disturbances.


Subject(s)
Dentate Gyrus , Neuropeptides , Aminopyridines , Animals , Dentate Gyrus/metabolism , Doublecortin Domain Proteins , Doublecortin Protein , Hippocampus/metabolism , Humans , Mice , Microtubule-Associated Proteins/metabolism , Morpholines , Neuropeptides/metabolism , Proto-Oncogene Proteins c-akt/metabolism
16.
Nanomaterials (Basel) ; 12(7)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35407261

ABSTRACT

In this study, a series of castor oil-based anionic waterborne polyurethane (CWPU) systems, which it has been suggested may be suitable for use as green elastomers with diverse applications in films and coatings, was prepared by modified with O-carboxymethyl chitosan (CS) as not only a reinforcing filler, but a chain-extender of polyurethane prepolymer to enhance the properties of polyurethanes. Moreover, not only was the system obtained with castor oil-based polyol in the absence of a catalyst, but it was maintained with low viscosity by using acetone instead of toxic methyl ethyl ketone (MEK) during the synthesis process. The sizes, zeta potential, chemical formation, and morphology of the CWPU-CS composites had been investigated by dynamic light scattering (DLS), infrared spectroscopy (IR), and scanning electron microscopy (SEM). Moreover, the results show that the modification allows to enhance storage/loss modulus, tensile properties, thermal stability at high temperature, and biocompatibility of CWPU and CWPU/CS nanocomposites according to various contents of CS.

17.
Polymers (Basel) ; 14(6)2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35335411

ABSTRACT

The sharp increase in the use of cellulose seems to be in increasing demand in wood; much more research related to sustainable or alternative materials is necessary as a lot of the arable land and natural resources use is unsustainable. In accordance, attention has focused on bacterial cellulose as a new functional material. It possesses a three-dimensional, gelatinous structure consisting of cellulose with mechanical and thermal properties. Moreover, while a plant-originated cellulose is composed of cellulose, hemi-cellulose, and lignin, bacterial cellulose attributable to the composition of a pure cellulose nanofiber mesh spun is not necessary in the elimination of other components. Moreover, due to its hydrophilic nature caused by binding water, consequently being a hydrogel as well as biocompatibility, it has only not only used in medical fields including artificial skin, cartilage, vessel, and wound dressing, but also in delivery; some products have even been commercialized. In addition, it is widely used in various technologies including food, paper, textile, electronic and electrical applications, and is being considered as a highly versatile green material with tremendous potential. However, many efforts have been conducted for the evolution of novel and sophisticated materials with environmental affinity, which accompany the empowerment and enhancement of specific properties. In this review article, we summarized only industry and research status regarding BC and contemplated its potential in the use of BC.

18.
Int J Mol Sci ; 23(4)2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35216059

ABSTRACT

The purpose of this review article is to outline the extended applications of polyurethane (PU)-based nanocomposites incorporated with conductive polymeric particles as well as to condense an outline on the chemistry and fabrication of polyurethanes (PUs). Additionally, we discuss related research trends of PU-based conducting materials for EMI shielding, sensors, coating, films, and foams, in particular those from the past 10 years. PU is generally an electrical insulator and behaves as a dielectric material. The electrical conductivity of PU is imparted by the addition of metal nanoparticles, and increases with the enhancing aspect ratio and ordering in structure, as happens in the case of conducting polymer fibrils or reduced graphene oxide (rGO). Nanocomposites with good electrical conductivity exhibit noticeable changes based on the remarkable electric properties of nanomaterials such as graphene, RGO, and multi-walled carbon nanotubes (MWCNTs). Recently, conducting polymers, including PANI, PPY, PTh, and their derivatives, have been popularly engaged as incorporated fillers into PU substrates. This review also discusses additional challenges and future-oriented perspectives combined with here-and-now practicableness.


Subject(s)
Nanocomposites/chemistry , Polyurethanes/chemistry , Electric Conductivity , Graphite/chemistry , Nanotubes, Carbon/chemistry , Polymers/chemistry
19.
Food Chem Toxicol ; 158: 112657, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34740715

ABSTRACT

Dextromethorphan (DM) abuse produces mania-like symptoms in humans. ERK/Akt signaling activation involved in manic potential can be attenuated by the inhibition of ouabain-like cardiac steroids. In this study, increased phosphorylations of ERK/Akt and hyperlocomotion induced by DM (30 mg/kg, i.p./day × 7) were significantly protected by the ouabain inhibitor rostafuroxin (ROSTA), suggesting that DM induces the manic potential. ROSTA significantly attenuated DM-induced protein kinase C δ (PKCδ) phosphorylation, GluN2B (i.e., MDA receptor subunit) expression, and phospho-PKCδ/GluN2B interaction. DM instantly upregulated the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent system. However, DM reduced Nrf2 nuclear translocation, Nrf2 DNA binding activity, γ-glutamylcysteine mRNA expression, and subsequent GSH/GSSG level and enhanced oxidative parameters following 1-h of administration. ROSTA, PKCδ inhibitor rottlerin, and GluN2B inhibitor traxoprodil significantly attenuated DM-induced alterations in Nrf2-related redox parameters and locomotor activity induced by DM in wild-type mice. Importantly, in PKCδ knockout mice, DM failed to alter the above parameters. Further, ROSTA and traxoprodil also failed to enhance PKCδ depletion effect, suggesting that PKCδ is a critical target for the anti-manic potential of ROSTA or GluN2B antagonism. Our results suggest that ROSTA inhibits DM-induced manic potential by attenuating ERK/Akt activation, GluN2B/PKCδ signalings, and Nrf2-dependent system.


Subject(s)
Androstanols/pharmacology , Bipolar Disorder , Dextromethorphan/adverse effects , Ouabain/antagonists & inhibitors , Animals , Bipolar Disorder/chemically induced , Bipolar Disorder/metabolism , Disease Models, Animal , Locomotion/drug effects , Male , Mice , Signal Transduction/drug effects
20.
Sci Rep ; 11(1): 22317, 2021 11 16.
Article in English | MEDLINE | ID: mdl-34785741

ABSTRACT

Direct energy deposition (DED) is a newly developed 3D metal printing technique that can be utilized on a porous surface coating of joint implants, however there is still a lack of studies on what advantages DED has over conventional techniques. We conducted a systematic mechanical and biological comparative study of porous coatings prepared using the DED method and other commercially available technologies including titanium plasma spray (TPS), and powder bed fusion (PBF). DED showed higher porosity surface (48.54%) than TPS (21.4%) and PBF (35.91%) with comparable fatigue cycle. At initial cell adhesion, cells on DED and PBF surface appeared to spread well with distinct actin stress fibers through immunofluorescence study. It means that the osteoblasts bind more strongly to the DED and PBF surface. Also, DED surface showed higher cell proliferation (1.27 times higher than TPS and PBF) and osteoblast cell activity (1.28 times higher than PBF) for 2 weeks culture in vitro test. In addition, DED surface showed better bone to implant contact and new bone formation than TPS in in vivo study. DED surface also showed consistently good osseointegration performance throughout the early and late period of osseointegration. Collectively, these results show that the DED coating method is an innovative technology that can be utilized to make cementless joint implants.


Subject(s)
Coated Materials, Biocompatible/chemistry , Implants, Experimental , Osseointegration , Osteoblasts/metabolism , Titanium/chemistry , Cell Line, Tumor , Humans , Porosity , Surface Properties
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