• Journal of the Korean Electrochemical Society
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• v.26 no.4
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• pp.43-55
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• 2023

Mass transport through nanoporous structures such as nanopores or nanochannels has fundamental electrochemical implications and many potential applications as well. These structures can be particularly useful for water treatment, energy conversion, biosensing, and controlled delivery of substances. Earlier research focused on creating nanopores with diameters ranging from tens to hundreds of nanometers that can selectively transport cationic or anionic charged species. However, recent studies have shown that nanopores with diameters of a few nanometers or even less can achieve more complex and versatile transport control. For example, nanopores that mimic biological channels can be functionalized with specific receptors to detect viruses, small molecules, and even ions, or can be made hydrophobic and responsive to external stimuli, such as light and electric field, to act as efficient valves. This review summarizes the latest developments in nanopore-based systems that can control mass transport based on the size of the nanopores (e.g., length, diameter, and shape) and the physical/chemical properties of their inner surfaces. It also provides some examples of practical applications of these systems.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Korean Journal of Radiology
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• v.21 no.4
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• pp.471-482
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• 2020

Objective: We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Materials and Methods: A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed. Results: Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria. Conclusion: Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.34.1-34.16
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• 2021

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• Animal Bioscience
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• v.37 no.1
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• pp.28-38
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• 2024

Objective: Tibetan chickens, which have unique adaptations to extreme high-altitude environments, exhibit phenotypic and physiological characteristics that are distinct from those of lowland chickens. However, the mechanisms underlying hypoxic adaptation in the liver of chickens remain unknown. Methods: RNA-sequencing (RNA-Seq) technology was used to assess the differentially expressed genes (DEGs) involved in hypoxia adaptation in highland chickens (native Tibetan chicken [HT]) and lowland chickens (Langshan chicken [LS], Beijing You chicken [BJ], Qingyuan Partridge chicken [QY], and Chahua chicken [CH]). Results: A total of 352 co-DEGs were specifically screened between HT and four native lowland chicken breeds. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses indicated that these co-DEGs were widely involved in lipid metabolism processes, such as the peroxisome proliferator-activated receptors (PPAR) signaling pathway, fatty acid degradation, fatty acid metabolism and fatty acid biosynthesis. To further determine the relationship from the 352 co-DEGs, protein-protein interaction network was carried out and identified eight genes (ACSL1, CPT1A, ACOX1, PPARC1A, SCD, ACSBG2, ACACA, and FASN) as the potential regulating genes that are responsible for the altitude difference between the HT and other four lowland chicken breeds. Conclusion: This study provides novel insights into the molecular mechanisms regulating hypoxia adaptation via lipid metabolism in Tibetan chickens and other highland animals.

• Journal of Soil and Groundwater Environment
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• v.12 no.4
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• pp.25-31
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• 2007

Characterizing the risk posed by a mixture of chemicals is a challenging task due to the chemical interactions of individual components that may affect their physical behavior and hence alter their exposure to receptors. In this study, cell tests that represent subsurface environment were carried out using benz[a]anthracene (BaA) and p-xylene focusing on phasetransforming interaction to verify increased mobility and risk of highly sorbed pollutants in the presence of less sorbed, mobile liquid pollutants. A transport model was also developed to interpret results and to simulate the same process on a field scale. The experimental results showed that BaA had far greater mobility in the presence of p-xylene than in the absence of that. The main transport mechanisms in the vadose zone were by dissolution to p-xylene or water. The transport model utilizing Defined Time Steps (DTS) was developed and tested with the experimental results. The predicted and observed values showed similar tendency, but the more work is needed in the future study for more precise modeling. The field-scale simulation results showed that transport of BaA to groundwater table was significantly faster in the presence of NAPL, and the oral carcinogenic risk of BaA calculated with the concentration in groundwater was 15${\sim}$87 times larger when mixed with NAPL than when solely contaminated. Since transport rate of PAHs is very slow in the subsurface without NAPL and no degradation of PAHs was considered in this simulation during the transport, the increase of risk in the presence of NAPL is expected to be greater for the actual contaminated site.

• Journal of the Korean Society for Marine Environment & Energy
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• v.12 no.4
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• pp.307-319
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• 2009

Carbon dioxide capture and storage (CCS) technology has been regarded as one of the most possible and practical option to reduce the emission of carbon dioxide ($CO_2$) and consequently to mitigate the climate change. Korean government also have started a 10-year R&D project on $CO_2$ storage in sea-bed geological structure including gas field and deep saline aquifer since 2005. Various relevant researches are carried out to cover the initial survey of suitable geological structure storage site, monitoring of the stored $CO_2$ behavior, basic design of $CO_2$ transport and storage process and the risk assessment and management related to $CO_2$ leakage from engineered and geological processes. Leakage of $CO_2$ to the marine environment can change the chemistry of seawater including the pH and carbonate composition and also influence adversely on the diverse living organisms in ecosystems. Recently, IMO (International Maritime Organization) have developed the risk assessment and management framework for the $CO_2$ sequestration in sub-seabed geological structures (CS-SSGS) and considered the sequestration as a waste management option to mitigate greenhouse gas emissions. This framework for CS-SSGS aims to provide generic guidance to the Contracting Parties to the London Convention and Protocol, in order to characterize the risks to the marine environment from CS-SSGS on a site-specific basis and also to collect the necessary information to develop a management strategy to address uncertainties and any residual risks. The environmental risk assessment (ERA) plan for $CO_2$ storage work should include site selection and characterization, exposure assessment with probable leak scenario, risk assessment from direct and in-direct impact to the living organisms and risk management strategy. Domestic trial of the $CO_2$ capture and sequestration in to the marine geologic formation also should be accomplished through risk management with specified ERA approaches based on the IMO framework. The risk assessment procedure for $CO_2$ marine storage should contain the following components; 1) prediction of leakage probabilities with the reliable leakage scenarios from both engineered and geological part, 2) understanding on physio-chemical fate of $CO_2$ in marine environment especially for the candidate sites, 3) exposure assessment methods for various receptors in marine environments, 4) database production on the toxic effect of $CO_2$ to the ecologically and economically important species, and finally 5) development of surveillance procedures on the environmental changes with adequate monitoring techniques.

• Journal of Life Science
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• v.30 no.1
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• pp.10-17
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• 2020

Kinesin-1 is microtubule-dependent plus-end direct molecular motor protein essential for intracellular transport. It is a member of the kinesin superfamily proteins (KIFs) which transport cargo, including organelles, vesicles, neurotransmitter receptors, cell-signaling molecules, and protein complexes through interaction between its light chain subunit and the cargo. Kinesin light chain 1 (KLC1) is a non-motor subunit that associates with the kinesin heavy chain (KHC). Although KLC1 interacts with many different adaptor proteins and scaffolding proteins, its binding proteins have not yet been fully identified. We used the yeast two-hybrid assay to identify proteins that interact with the tetratricopeptide repeat (TPR) domain of KLC1, and found an interaction between KLC1 and EH domain-binding protein 1 like 1 (EHBP1L1). EHBP1L1 bound to the region containing all six TPR repeats of KLC1 and did not interact with KIF5B (a motor protein of kinesin 1) or KIF3A (a motor protein of kinesin 2) in the yeast two-hybrid assay. The carboxyl-terminus of the coiled-coil domain of EHBP1L1 is essential for interaction with KLC1. However, another EHBP1L1 isoform, EHBP1, did not interact with KLC1 in the yeast two-hybrid assay. KLC1 interacted with GST-EHBP1L1 and its coiled-coil domain but not with GST only. When co-expressed in HEK-293T cells, EHBP1L1 co-localized with KLC1 and co-immunoprecipitated with KLC1 and KIF5B but not KIF3A. These results suggest that kinesin 1 motor protein may transport EHBP1L1-associated cargo in cells.

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.