Cuproptosis-Inducible Chemotherapeutic/Cascade Catalytic Reactor System for Combating with Breast Cancer.

Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.

Echinatin induces reactive oxygen species-mediated apoptosis via JNK/p38 MAPK signaling pathway in colorectal cancer cells.

Colorectal cancer (CRC) is a very common and deadly cancer worldwide, and oxaliplatin is used as first-line chemotherapy. However, resistance usually develops, limiting treatment. Echinatin (Ech) is the main component of licorice and exhibits various therapeutic effects on inflammation-mediated diseases and cancer, ischemia/reperfusion, and liver injuries. The present study elucidated the underlying molecular mechanism of Ech-induced apoptosis in both oxaliplatin-sensitive (HT116 and HT29) and -resistant (HCT116-OxR and HT29-OxR) CRC cells. To evaluate the antiproliferative activities of Ech, we performed MTT and soft agar assays. Ech reduced viability, colony size, and numbers of CRC cells. The underlying molecular mechanisms were explored by various flow cytometry analyses. Ech-induced annexin-V stained cells, reactive oxygen species (ROS) generation, cell cycle arrest, JNK/p38 MAPK activation, endoplasmic reticulum (ER) stress, mitochondrial membrane potential depolarization, and multi-caspase activity. In addition apoptosis-, cell cycle-, and ER stress-related protein levels were confirmed by western blotting. Moreover, we verified ROS-mediated cell death by treatment with inhibitors such as N-acetyl-L-cysteine, SP600125, and SB203580. Taken together, Ech exhibits anticancer activity in oxaliplatin-sensitive and -resistant CRCs by inducing ROS-mediated apoptosis through the JNK/p38 MAPK signaling pathway. This is the first study to show that Ech has the potential to treat drug-resistant CRC, providing new directions for therapeutic strategies targeting drug-resistant CRC.

Clinical evidence construction of East Asian herbal medicine for inflammatory pain in rheumatoid arthritis based on integrative data mining approach.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to a significant social burden. East Asian herbal medicine (EAHM) has long been used to treat RA. Therefore, a systematic study of how EAHM treatments can be developed into new drugs using specific materials is needed. METHODS: Eleven databases containing literature in English, Korean, Chinese, and Japanese were searched for randomized controlled trials comparing EAHM with conventional medicine (CM). A meta-analysis was performed on the variable data to assess their effects on inflammatory pain. Subsequently, we searched for core materials and combinations of core material-based data mining methods. RESULTS: A total of 186 trials involving 19,716 patients with RA met the inclusion criteria. According to the meta-analysis, EAHM had a significantly superior effect on continuous pain intensity, tender joint count, and response rate. Patients treated with EAHM had a significantly reduced incidence of adverse events compared with those treated with CM. Based on additional analysis of the EAHM formula data included in this meta-analysis, 21 core materials and five core herbal combinations were identified. CONCLUSION: EAHM remedies for RA have the adequate potential for use as candidate materials for treating inflammatory pain in RA. The candidate core herbs evaluated in this study act on multiple pathways and are expected to provide pain relief, sustained inflammation suppression, immune regulation, and prevention of joint destruction. It seems worthwhile to conduct follow-up research on drug development using the core materials derived from this review.

The Post-Translational Regulation of Epithelial-Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis.

Epithelial-mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and down-regulation of specific proteins, both of which are regulated by EMT-inducing transcription factors (EMT-TFs), mainly represented by the families of Snail, Twist, and ZEB proteins. This review highlights the roles of key EMT-TFs and their post-translational regulation in cancer metastasis.

Anti-Cancer Effects of Glaucarubinone in the Hepatocellular Carcinoma Cell Line Huh7 via Regulation of the Epithelial-To-Mesenchymal Transition-Associated Transcription Factor Twist1.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths. As HCC has a high mortality rate and its incidence is increasing worldwide, understanding and treating HCC are crucial for resolving major public health concerns. In the present study, wound healing screening assays were performed using natural product libraries to identify natural chemicals that can inhibit cancer cell migration. Glaucarubinone (GCB) showed a high potential for inhibiting cell migration. The anti-cancer effects of GCB were evaluated using the HCC cell line, Huh7. GCB showed anti-cancer effects, as verified by wound healing, cell migration, invasion, colony formation, and three-dimensional spheroid invasion assays. In addition, cells treated with GCB showed suppressed matrix metalloproteinase activities. Immunoblotting analyses of intracellular signaling pathways revealed that GCB regulated the levels of Twist1, a crucial transcription factor associated with epithelial-to-mesenchymal transition, and mitogen-activated protein kinase. The invasive ability of cancer cells was found to be decreased by the regulation of Twist1 protein levels. Furthermore, GCB downregulated phosphorylation of extracellular signal-regulated kinase. These results indicate that GCB exhibits anti-metastatic properties in Huh7 cells, suggesting that it could be used to treat HCC.

Dual inhibition of EGFR and MET by Echinatin retards cell growth and induces apoptosis of lung cancer cells sensitive or resistant to gefitinib.

Patients with non-small-cell lung cancer (NSCLC) containing epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to tyrosine kinase inhibitor gefitinib; however, the treatment is less effective over time. Gefitinib resistance mechanisms include MET gene amplification. A therapeutic strategy targeting MET as well as EGFR can overcome resistance to gefitinib. In the present study we identified Echinatin (Ecn), a characteristic chalcone in licorice, which inhibited both EGFR and MET and strongly altered NSCLC cell growth. The antitumor efficacy of Ecn against gefitinib-sensitive or -resistant NSCLC cells with EGFR mutations and MET amplification was confirmed by suppressing cell proliferation and anchorage-independent colony growth. During the targeting of EGFR and MET, Ecn significantly blocked the kinase activity, which was validated with competitive ATP binding. Inhibition of EGFR and MET by Ecn decreases the phosphorylation of downstream target proteins ERBB3, AKT and ERK compared with total protein expression or control. Ecn induced the G2/M cell cycle arrest, and apoptosis via the intrinsic pathway of caspase-dependent activation. Ecn induced ROS production and GRP78, CHOP, DR5 and DR4 expression as well as depolarized the mitochondria membrane potential. Therefore, our results suggest that Ecn is a promising therapeutic agent in NSCLC therapy.

Licochalcone D directly targets JAK2 to induced apoptosis in human oral squamous cell carcinoma.

Licochalcone (LC) families have been reported to have a wide range of biological function such as antioxidant, antibacterial, antiviral, and anticancer effects. Although various beneficial effects of LCD were revealed, its anticancer effect in human oral squamous cancer has not been identified. To examine the signaling pathway of LCD's anticancer effect, we determined whether LCD has physical interaction with Janus kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) signaling, which is critical in promoting cancer cell survival and proliferation. Our results demonstrated that LCD inhibited the kinase activity of JAK2, soft agar colony formation, and the proliferation of HN22 and HSC4 cells. LCD also induced mitochondrial apoptotic events such as altered mitochondrial membrane potential and reactive oxygen species production. LCD increased the expression of apoptosis-associated proteins in oral squamous cell carcinoma (OSCC) cells. Finally, the xenograft study showed that LCD significantly inhibited HN22 tumor growth. Immunohistochemical data supported that LCD suppressed p-JAK2 and p-STAT3 expression and induced cleaved-caspase-3 expression. These results indicate that the anticancer effect of LCD is due to the direct targeting of JAK2 kinase. Therefore, LCD can be used for therapeutic application against OSCC.

Phosphorylation Dynamics of JNK Signaling: Effects of Dual-Specificity Phosphatases (DUSPs) on the JNK Pathway.

Protein phosphorylation affects conformational change, interaction, catalytic activity, and subcellular localization of proteins. Because the post-modification of proteins regulates diverse cellular signaling pathways, the precise control of phosphorylation states is essential for maintaining cellular homeostasis. Kinases function as phosphorylating enzymes, and phosphatases dephosphorylate their target substrates, typically in a much shorter time. The c-Jun N-terminal kinase (JNK) signaling pathway, a mitogen-activated protein kinase pathway, is regulated by a cascade of kinases and in turn regulates other physiological processes, such as cell differentiation, apoptosis, neuronal functions, and embryonic development. However, the activation of the JNK pathway is also implicated in human pathologies such as cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, the proper balance between activation and inactivation of the JNK pathway needs to be tightly regulated. Dual specificity phosphatases (DUSPs) regulate the magnitude and duration of signal transduction of the JNK pathway by dephosphorylating their substrates. In this review, we will discuss the dynamics of phosphorylation/dephosphorylation, the mechanism of JNK pathway regulation by DUSPs, and the new possibilities of targeting DUSPs in JNK-related diseases elucidated in recent studies.

Licochalcone C induced apoptosis in human oral squamous cell carcinoma cells by regulation of the JAK2/STAT3 signaling pathway.

Oral cancer is of an aggressive malignancy that arises on oral cavity and lip, 90% of cancers histologically originated in the squamous cells. Licochalcone (LC)C has been known as natural phenolic chalconoid substances, and its origin is the root of Glycyrrhiza glabra or Glycyrrhiza inflata. LCC inhibited oral squamous cell carcinoma (OSCC) cell viability, mitochondrial function, and anchorage-independent growth in a dose-dependent manner. To investigate the ability of LCC to target Janus kinase 2 (JAK2), we performed pull-down binding assay, kinase assay, and docking simulation. The molecular docking studies were performed between JAK2 and the potent inhibitor LCC. It was shown that LCC tightly interacted with ATP-binding site of JAK2. In addition, LCC inhibited the JAK2/signal transducer and activator of transcription 3 pathway, upregulated p21, and downregulated Bcl-2, Mcl-1, and Survivin, while it disrupted mitochondrial membrane potential and subsequently caused cytochrome c release with activation of multi-caspase, eventually leading to apoptosis in HN22 and HSC4 cells. LCC elevated the protein levels of Bax, cleaved Bid and PARP, and increased Apaf-1, and this effect was reversed by LCC treatment. Our results demonstrated that treatment of OSCC cells with LCC induced the death receptor (DR)4 and DR5 expression level with the generation of reactive oxygen species and the upregulation of CHOP protein expression. Taken together, these results could provide the basis for clinical application as a new therapeutic strategy in the treatment of oral cancer.

Determination of Osmium Concentration and Isotope Composition at Ultra-low Level in Polar Ice and Snow.

Here we use two chemical separation procedures to determine exceptionally low Os concentrations (∼10-15 g g-1) and Os isotopic composition in polar snow/ice. Approximately 50 g of meltwater is spiked with 190Os tracer solution and frozen at -20 °C in quartz-glass ampules. A mixture of H2O2 and HNO3 is then added, and the sample is heated to 300 °C at 100 bar. This allows tracer Os to be equilibrated with the sample as all Os species are oxidized to OsO4. The resulting OsO4 is separated using either distillation (Method-I) or solvent-extraction (Method-II), purified, and measured using negative thermal ionization mass spectrometry (N-TIMS). A new technique is presented that minimizes Re and Os blanks of the Pt filaments used in N-TIMS. We analyze snow collected from Summit, Greenland during 2009, 2014, and 2017. We find that the average Os concentration of the snow is 0.459 ± 0.018 (95% C.I.) fg g-1 corresponding to an Os flux of 0.0579 ± 0.0023 (95% C.I.) fmol cm-2 yr-1. The average R(187Os/188Os) ratio of the Summit snow is 0.264 ± 0.026 (95% C.I.). Assuming that the volcanic source is negligible, the average ratio indicates that about 0.0518 ± 0.0040 (95% C.I.) fmol cm-2 yr-1 of Os is of cosmic derivation, corresponding to an accretion rate of extra-terrestrial Os to the Earth of 264 ± 21 mol yr-1.

Licochalcone A Suppresses Specificity Protein 1 as a Novel Target in Human Breast Cancer Cells.

Licochalcone A (LCA), isolated from the root of Glycyrrhiza inflata, are known to have medicinal effect such as anti-oxidant, anti-bacterial, anti-viral, and anti-cancer. Though, as a pharmacological mechanism regulator, anti-cancer studies on LCA were not investigated in human breast cancer. We investigated the anti-proliferative and apoptotic effect of LCA in human breast cancer cells MCF-7 and MDA-MB-231 through MTS assay, PI staining, Annexin-V/7-AAD assay, mitochondrial membrane potential assay, multi-caspase assay, RT-PCR, Western blot analysis, and anchorage-independent cell transformation assay. Our results showed the little difference between two cells, as MCF-7 cell is both estrogen/progesterone receptor positive, there were only effect on Sp1 protein level, but not in mRNA level. Adversely, estrogen/progesterone/human epidermal growth factor receptor 2 triple negative, MDA-MB-231 showed decreased Sp1 mRNA, and protein levels. To confirm the participation of Sp1 in breast cancer cell viability, siRNA techniques were introduced. Both cells showed dysfunction of mitochondrial membrane potential and mitochondrial ROS production, which reflects it passed intracellular mitochondrial apoptosis pathway. Additionally, LCA showed the anti-proliferative and apoptotic effect in breast cancer cells through regulating Sp1 and apoptosis-related proteins in a dose- and a time-dependent manner. Consequently, LCA might be a potential anti-breast cancer drug substitute. J. Cell. Biochem. 118: 4652-4663, 2017. © 2017 Wiley Periodicals, Inc.

Correlation between headaches and affective symptoms in patients with epilepsy.

Headaches are a neglected entity in patients with epilepsy (PWE), although PWE have a high chance of suffering from seizure-related as well as seizure-unrelated headaches. We aimed to identify the prevalence and characteristics of headaches and investigate the correlation between headaches and affective symptoms in PWE. Consecutive PWE who visited our tertiary outpatient clinic were interviewed about headaches and epilepsy. Affective symptoms were evaluated using the Korean version of the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and suicidality portion of the Mini-International Neuropsychiatric Interview. We classified headaches as interictal or seizure-related headaches (SRHs; pre- and postictal). Tension-type headache and migraine were defined based on International Classification of Headache Disorders criteria. From the initial cohort of 177 patients (92 men, mean age: 37.1years), 73 (41.2%) reported suffering from interictal (N=34, 19.2%), preictal (N=3, 1.7%), and postictal (N=48, 27.1%) headaches. Univariate analysis revealed significantly higher BDI and BAI scores in the headache group. Tension-type headaches were the most frequent, and half of the interictal headaches and most of the SRHs were untreated. Spearman's partial correlation analyses showed that headaches overall were significantly related with depression and anxiety. Interictal headaches were correlated with depression only, and postictal headaches were correlated with depression as well as suicidality, separately. These results show that investigating and controlling headaches may relieve affective symptoms and ultimately improve the quality of life of PWE.

HPLC Analysis, Optimization of Extraction Conditions and Biological Evaluation of Corylopsis coreana Uyeki Flos.

A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, quercetin, quercitrin and isosalipurposide were used as calibration standards. In the present study, an excellent linearity was obtained with an r² higher than 0.999. The chromatographic peaks showed good resolution. In combination with other validation data, including precision, specificity, and accuracy, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of bergenin, quercetin, quercitrin and isosalipurposide in the crude ethanolic extract of C. coreana Uyeki flos. Furthermore, the plant extracts were analyzed with HPLC to determine the four constituents and compositional differences in the extracts obtained under different extraction conditions. Several extracts of them which was dependent on the ethanol percentage of solvent were also analyzed for their antimicrobial and antioxidant activities. One hundred % ethanolic extract from C. coreana Uyeki flos showed the best antimicrobial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain. Eighty % ethanolic extract showed the best antioxidant activity and phenolic content. Taken of all, these results suggest that the flower of C. coreana Uyeki flos may be a useful source for the cure and/or prevention of septic arthritis, and the validated method was useful for the quality control of C. coreana Uyeki.

Can an exercise bicycle be safely used in the epilepsy monitoring unit?: An exercise method to provoke epileptic seizures and the related safety issues.

BACKGROUND AND PURPOSE: Long-term videoelectroencephalogram (video-EEG) monitoring is performed to diagnose an epileptic seizure and to investigate the differential diagnosis of paroxysmal events. To provoke an epileptic seizure, an exercise method is performed in some cases during long-term video-EEG recording in the epilepsy monitoring unit (EMU). The purpose of this study was two-fold: to assess the frequency and severity of adverse events associated with the use of an exercise bicycle and to find a way to safely use it in the EMU. METHODS: A retrospective survey was performed on all epileptic seizure videos recorded in the EMU from January 2012 to December 2013. Three hundred and fifty patients were included in this study. RESULTS: Eleven patients experienced an epileptic seizure while riding the exercise bicycle in the EMU. One patient's foot got stuck between the cycling pedal and its strap, and one patient fell off the exercise bicycle during the epileptic seizure. However, there were no serious adverse events over two years. CONCLUSION: Epileptic seizures were not frequent while riding the exercise bicycle, and serious injuries did not occur. But, there is a need to improve the safety in the EMU to control the potentially dangerous factors associated with the use of the exercise bicycle and to continuously monitor the patients with help from the staff.

P2Y2 R activation by nucleotides promotes skin wound-healing process.

P2Y2 R has been shown to be upregulated in a variety of tissues in response to stress or injury and to mediate tissue regeneration through its ability to activate multiple signalling pathways. This study aimed to investigate the role of P2Y2 R in the wound-healing process and the mechanisms by which P2Y2 R activation promotes wound healing in fibroblasts. The role of P2Y2 R in skin wound healing was examined using a full-thickness skin wound model in wildtype (WT) and P2Y2 R(-/-) mice and an in vitro scratch wound model in control or P2Y2 R siRNA-transfected fibroblasts. WT mice showed significantly decreased wound size compared with P2Y2 R(-/-) mice at day 14 post-wounding, and immunohistochemical analysis showed that a proliferation marker Ki67 and extracellular matrix (ECM)-related proteins VEGF, collagen I, fibronectin and α-SMA were overexpressed in WT mice, which were reduced in P2Y2 R(-/-) mice. Scratch-wounded fibroblasts increased ATP release, which peaked at 5 min. In addition, scratch wounding increased the level of P2Y2 R mRNA. Activation of P2Y2 R by ATP or UTP enhanced proliferation and migration of fibroblasts in in vitro scratch wound assays and were blocked by P2Y2 R siRNA. Finally, ATP or UTP also increased the levels of ECM-related proteins through the activation of P2Y2 R in fibroblasts. This study suggests that P2Y2 R may be a potential therapeutic target to promote wound healing in chronic wound diseases.

Integrative medicine using East Asian herbal medicine for inflammatory pain in patients with rheumatoid arthritis: A protocol for systematic review and meta-analysis integrated with multiple data mining for core candidate discovery.

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by a wide range of clinical symptoms affecting various bodily functions, including skeletal, vascular, metabolic, and cognitive functions. This review aimed to evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used for the treatment of inflammatory pain in rheumatoid arthritis and to identify key candidate drugs based on the data. METHODS: A comprehensive literature search will be conducted in 4 core databases (PubMed, Excerpta Medica database, Cochrane Library, and Cumulative Index to Nursing & Allied Health Literature) 4 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from December 13, 2022. Statistical analysis will be performed using R version 4.1.2 and R Studio program. The American College of Rheumatology 20/50/70 score and rate of adverse events will be the primary outcomes. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. Sensitivity, meta-regression, and subgroup analyses will be used to identify the sources of any heterogeneity in the study. The revised tool for assessing the risk of bias in randomized trials, version 2.0, will be used to evaluate methodological quality. The overall quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation Pro Framework. ETHICS AND DISSEMINATION: There are no ethical issues, as no primary data will be collected directly from the participants. The results of this review will be reported in a peer-reviewed scientific journal. TRIAL REGISTRATION: PROSPERO registration number: CRD42023412385.

Fibroblast-targeting polymeric nanovehicles to enhance topical wound healing through promotion of PAR-2 receptor-mediated endocytosis.

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy. In this study, we propose a smart drug delivery system using polymeric nanovehicles (PNVs), in which the periphery is conjugated with a fibroblast-targeting collagen-derived peptide, KTTKS (Lys-Thr-Thr-Lys-Ser). We showed that surface engineering of PNVs with simultaneous PEGylation and peptide patching improved the dispersibility of PNVs, while promoting selective cellular uptake to fibroblasts via PAR-2 receptor-mediated endocytosis. In vitro collagen production and in vivo wound healing assays revealed that curcumin-loaded fibroblast-targeting PNVs significantly enhanced collagen production and wound healing activities, thus promising effective skin tissue regeneration.

Role of Transition Metals in Metal-Organic Frameworks as Nanoporous Ion Emitters for Thermal Ionization Mass Spectrometry.

Thermal ionization mass spectrometry is a powerful analytical technique that allows for precise determination of isotopic ratios. Analysis of low abundance samples, however, can be limited by the ionization efficiency. Following an investigation into a new type of metal-organic hybrid material, nanoporous ion emitters (nano-PIEs), devised to promote the emission of analyte ions and reduce traditional sample loading challenges, this work evaluates the impact that changing the metal in the material has on the ionization of uranium (U). Being derived from metal-organic frameworks (MOFs), nano-PIEs inherit the tunability of their parent MOFs. The MOF-74 series has been well studied for probing the impact various framework metals (i.e., Mg, Mn, Co, Ni, Cu, Zn, and Cd) have on material properties, and thus, a series of nano-PIEs with different metals were derived from this isoreticular MOF series. Trends in ionization efficiency were studied as a function of ionization potential, volatility, and work function of the framework metals to gain a better understanding of the mechanism of analyte ionization. This study finds a correlation between the analyte ionization efficiency and nano-PIE framework metal volatility that is attributed to its tunable thermal stability and degradation behavior.

Neuroprotective Effects of Licochalcone D in Oxidative-Stress-Induced Primitive Neural Stem Cells from Parkinson's Disease Patient-Derived iPSCs.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.

Characteristics of site-specific response using the measured data from seismic accelerometers in Pohang Yeongil New Port under 9.12 and Pohang earthquakes.

Recently, medium-sized earthquakes such as the Gyeongju 9.12 earthquake (September 12, 2016, ML = 5.8) and the Pohang earthquake (November 15, 2017, ML = 5.4) occurred in Korea, thereby increasing social concern about earthquakes. Because Korea is not located near the Circum-Pacific Belt, also referred to as the "Ring of Fire", people in Korea are not used to earthquake disasters. Coastal areas in Korea are lined with multiple mega-cities and major industrial facilities. Most of them constructed on landfill, they have a high threat level to the damage to populations and structures leading to complex disasters in the event of an earthquake. However, studies of seismic hazards in ports is incomplete compared with those of onshore sites. Improving the understanding of seismic hazards and characterizing them catching up with related research from various perspectives being actively conducted. In this study, the site-specific response characteristics of the Pohang International Container Terminal in Pohang Yeongil New Port were analyzed using the S-wave energy of 10 sets of ground motions recorded by seismic accelerometers operated by the Ministry of Oceans and Fisheries based on the horizontal-to-vertical spectral ratio (H/V ratio) method. As a result of analysis, the H/V ratio curves show that the peak frequency values for the target site averages 9 Hz, and the natural period values of the site were preliminarily predicted to average 0.11 s. In addition, site amplification characteristics are different based on the seismic wave calculation method. The result can be used as data for identifying ground dynamic characteristics and verifying the site amplification coefficients and design spectrum in the seismic design.