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"Kim, In-Su"
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Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols in the Treatment of Age-Linked Neurodegenerative Diseases: Focus on TLR4 Signaling
Neuronal dysfunction initiates several intracellular signaling cascades to release different proinflammatory cytokines and chemokines, as well as various reactive oxygen species. In addition to neurons, microglia, and astrocytes are also affected by this signaling cascade. This release can either be helpful, neutral or detrimental for cell survival. Toll-like receptors (TLRs) activate and signal their downstream pathway to activate NF-κB and pro-IL-1β, both of which are responsible for neuroinflammation and linked to the pathogenesis of different age-related neurological conditions. However, herein, recent aspects of polyphenols in the treatment of neurodegenerative diseases are assessed, with a focus on TLR regulation by polyphenols. Different polyphenol classes, including flavonoids, phenolic acids, phenolic alcohols, stilbenes, and lignans can potentially target TLR signaling in a distinct pathway. Further, some polyphenols can suppress overexpression of inflammatory mediators through TLR4/NF-κB/STAT signaling intervention, while others can reduce neuronal apoptosis via modulating the TLR4/MyD88/NF-κB-pathway in microglia/macrophages. Indeed, neurodegeneration etiology is complex and yet to be completely understood, it may be that targeting TLRs could reveal a number of molecular and pharmacological aspects related to neurodegenerative diseases. Thus, activating TLR signaling modulation via natural resources could provide new therapeutic potentiality in the treatment of neurodegeneration.
Journal Article
A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study
,
we describe a novel microtubule inhibitor, 5-(
N
-methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Treatment with SPC-160002 arrested the cell cycle at the M phase, as evidenced using fluorescence-activated cell sorting analysis, and increased the levels of mitotic marker proteins, including cyclin B, pS10-H3, and chromosomal passenger complex. This mitotic arrest by SPC-160002 was mediated by promoting and stabilizing microtubule polymerization, similar to the mechanism observed in case of taxane-based drugs. Furthermore, SPC-160002 suppressed the growth and sphere-forming activity of cancer stem cells. Our data herein strongly suggest that SPC-160002, a novel microtubule inhibitor, can be used to overcome MDR and can serve as an attractive candidate for anticancer drugs.
Journal Article
Molecular Quantification of Total and Toxigenic Microcystis Using Digital-Droplet-Polymerase-Chain-Reaction-Based Multiplex Assay
The proliferation of harmful cyanobacteria, particularly Microcystis, poses significant risks to drinking and recreational water resources, especially under the influence of climate change. Conventional monitoring methods based on microscopy for harmful cyanobacteria management systems are limited in detecting toxigenic genotypes, hindering accurate risk assessment. In this study, we developed a digital droplet PCR (ddPCR)-based method for the simultaneous quantification of total and toxigenic Microcystis in freshwater environments. We targeted the secA gene, specific to the Microcystis genus, and the mcyA gene, associated with microcystin biosynthesis. Custom-designed primers and probes showed high specificity and sensitivity, enabling accurate detection without cross-reactivity. The multiplex ddPCR assay allowed for concurrent quantification of both targets in a single reaction, reducing the analysis time and cost. Application to field samples demonstrated good agreement with microscopic counts and revealed seasonal shifts in toxigenic genotype abundance. Notably, ddPCR detected Microcystis at very low densities—down to 7 cells/mL in the mixed cyanobacterial communities of field samples—even when microscopy failed, highlighting its utility for early bloom detection. This approach provides a reliable and efficient tool for monitoring Microcystis dynamics and assessing toxin production potential, offering significant advantages for the early warning and proactive management of harmful cyanobacterial blooms.
Journal Article
Climate Risk, Stock Crash Risk, and Greenhouse Gas Emission Trading Scheme: Evidence From Korea
This study examines the relationship between climate risk and stock crash risk and the moderating effect of greenhouse gas emission trading scheme (ETS). Numerous studies have tested stock price crash risk measured by the negative skewness of return distributions in the areas of internal governance mechanism. While interest in environmental performance for sustainable growth of firms has increased, there are no studies on the effect of climate risk on stock crash risk. Thus, we find that climate risk (a firm’s greenhouse gas emissions and energy consumption) increases stock crash risk, and the positive effect of climate risk on stock crash risk is weakened after introduction of the emission trading scheme. This study theoretically extends the literature on the empirical determinants of stock crash risk, and practically provides investors with proven information about whether climate risk is worth considering during investment decisions. Furthermore, at the level of government policy, we can suggest that a monitoring system is needed to mitigate potential information asymmetry problems in firm with high climate risk.
Journal Article
Mito-TEMPO improves development competence by reducing superoxide in preimplantation porcine embryos
Mito-TEMPO is a well-known mitochondria-specific superoxide scavenger. However, the effect of Mito-TEMPO on porcine embryo development, to our knowledge, has not been studied yet. In the present study, porcine embryos were classified into two groups (G1 and G2) based on the cytoplasm lipid contents at the zygote stage. The development of blastocysts derived from G2 zygotes was reduced (G2:16.2 ± 7.9% vs G1: 26.5 ± 5.9%; 1.6-fold, p < 0.05) compared to those from G1 zygotes. In G2 embryos, the proportion of TUNEL-positive cells was also higher than that of G1 embryos. Superoxide in G2 embryos was significantly increased compared to that in G1 embryos. Mitochondrial membrane potential and ATP production were lower in G2 embryos than in G1 embryos. Phosphorylation of Drp1 at Ser 616 increased in G1 embryos during the cleavage stages compared to that in the zygote but was not significantly different in G2 embryos. Then, the effects of Mito-TEMPO were investigated in G2 embryos. Blastocyst formation rate (G2: 19.1 ± 5.1% vs G2 + Mito-TEMPO: 28.8 ± 4.0%; 1.5-fold, p < 0.05) and mitochondrial aggregation were recovered after superoxide reduction by Mito-TEMPO treatment. Thus, we showed that Mito-TEMPO improves blastocyst development by superoxide reduction in porcine embryos
in vitro
.
Journal Article
Melatonin Improves Oocyte Maturation and Mitochondrial Functions by Reducing Bisphenol A-Derived Superoxide in Porcine Oocytes In Vitro
Bisphenol A (BPA) is synthetic organic compound that exhibits estrogen-like properties and it induces mitochondrial superoxide production. Melatonin (Mela) protects against BPA-mediated cell damage and apoptosis. However, the antioxidative effects of Mela against BPA-induced superoxide production in porcine oocytes are still not known. In this study, we investigated the antioxidative effects of Mela against BPA-derived superoxide on oocyte maturation in pigs. To investigate the effects of the superoxide specific scavenger, Mito-TEMPO, on porcine oocyte maturation in response to BPA exposure apoptosis proteins, we treated the oocytes with Mito-TEMPO (0.1 µM) after pre-treating them with BPA (75 µM) for 22 h. As expected, the reduction in meiotic maturation and cumulus cell expansion of cumulus-oocyte-complexes (COCs) in the BPA (75 µM) treated group was recovered (p < 0.01) by treatment with Mito-TEMPO (0.1 µM). An increase in the levels of mitochondrial apoptotic proteins (AIF, cleaved Cas 3 and cleaved Parp1) in response to BPA-induced damage was also reduced by Mito-TEMPO treatment in porcine COCs. Interestingly, we confirmed the positive effects of Mela with respect to superoxide production upon BPA exposure during oocyte maturation and also confirmed the reduction in mitochondrial apoptosis in Mela (0.1 µM)-treated porcine COCs. These results provide evidence for the first time that antioxidative effects of Mela on BPA-derived superoxide improve porcine oocyte maturation.
Journal Article
Ameliorative potential of desalted Salicornia europaea L. extract in multifaceted Alzheimer’s-like scopolamine-induced amnesic mice model
The
Salicornia europaea L
. (SE) plant is a halophyte that has been widely consumed as a seasoned vegetable, and it has been recently reported to counteract chronic diseases related to oxidative and inflammatory stress. In this study, we performed an initial phytochemical analysis with
in vitro
biochemical tests and chromatographic profiling of desalted and enzyme-digested SE ethanol extract (SE-EE). Subsequently, we evaluated the anti-neuroinflammatory and ameliorative potential of SE-EE in LPS-inflicted BV-2 microglial cells and scopolamine-induced amnesic C57/BL6N mice, respectively. SE-EE possess considerable polyphenols and flavonoids that are supposedly responsible to improve its bio-efficacy. SE-EE dose-dependently attenuated LPS-induced inflammation in BV-2 cells, significantly repressed behavioural/cognitive impairment, dose-dependently regulated the cholinergic function, suppressed oxidative stress markers, regulated inflammatory cytokines/associated proteins expression and effectively ameliorated
p
-CREB/BDNF levels, neurogenesis (DCX stain), neuron proliferation (Ki67 stain) in scopolamine-administered mice. Thus, SE-EE extract shows promising multifactorial disease modifying activities and can be further developed as an effective functional food, drug candidate, or supplemental therapy to treat neuroinflammatory mediated disorders.
Journal Article
Recent Developments in (K, Na)NbO3-Based Lead-Free Piezoceramics
(K0.5Na0.5)NbO3 (KNN)-based ceramics have been extensively investigated as replacements for Pb(Zr, Ti)O3-based ceramics. KNN-based ceramics exhibit an orthorhombic structure at room temperature and a rhombohedral–orthorhombic (R–O) phase transition temperature (TR–O), orthorhombic–tetragonal (O–T) phase transition temperature (TO–T), and Curie temperature of −110, 190, and 420 °C, respectively. Forming KNN-based ceramics with a multistructure that can assist in domain rotation is one technique for enhancing their piezoelectric properties. This review investigates and introduces KNN-based ceramics with various multistructures. A reactive-templated grain growth method that aligns the grains of piezoceramics in a specific orientation is another approach for improving the piezoelectric properties of KNN-modified ceramics. The piezoelectric properties of the [001]-textured KNN-based ceramics are improved because their microstructures are similar to those of the [001]-oriented single crystals. The improvement in the piezoelectric properties after [001] texturing is largely influenced by the crystal structure of the textured ceramics. In this review, [001]-textured KNN-based ceramics with different crystal structures are investigated and systematically summarized.
Journal Article
Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders
Neurological disorders are important causes of morbidity and mortality around the world. The increasing prevalence of neurological disorders, associated with an aging population, has intensified the societal burden associated with these diseases, for which no effective treatment strategies currently exist. Therefore, the identification and development of novel therapeutic approaches, able to halt or reverse neuronal loss by targeting the underlying causal factors that lead to neurodegeneration and neuronal cell death, are urgently necessary. Plants and other natural products have been explored as sources of safe, naturally occurring secondary metabolites with potential neuroprotective properties. The secondary metabolites α- and β-asarone can be found in high levels in the rhizomes of the medicinal plant Acorus calamus (L.). α- and β-asarone exhibit multiple pharmacological properties including antioxidant, anti-inflammatory, antiapoptotic, anticancer, and neuroprotective effects. This paper aims to provide an overview of the current research on the therapeutic potential of α- and β-asarone in the treatment of neurological disorders, particularly neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), as well as cerebral ischemic disease, and epilepsy. Current research indicates that α- and β-asarone exert neuroprotective effects by mitigating oxidative stress, abnormal protein accumulation, neuroinflammation, neurotrophic factor deficit, and promoting neuronal cell survival, as well as activating various neuroprotective signalling pathways. Although the beneficial effects exerted by α- and β-asarone have been demonstrated through in vitro and in vivo animal studies, additional research is required to translate laboratory results into safe and effective therapies for patients with AD, PD, and other neurological and neurodegenerative diseases.
Journal Article