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1.
Exploration (Beijing) ; 4(1): 20220162, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38854486

ABSTRACT

In the biological nervous system, the integration and cooperation of parallel system of receptors, neurons, and synapses allow efficient detection and processing of intricate and disordered external information. Such systems acquire and process environmental data in real-time, efficiently handling complex tasks with minimal energy consumption. Memristors can mimic typical biological receptors, neurons, and synapses by implementing key features of neuronal signal-processing functions such as selective adaption in receptors, leaky integrate-and-fire in neurons, and synaptic plasticity in synapses. External stimuli are sensitively detected and filtered by "artificial receptors," encoded into spike signals via "artificial neurons," and integrated and stored through "artificial synapses." The high operational speed, low power consumption, and superior scalability of memristive devices make their integration with high-performance sensors a promising approach for creating integrated artificial sensory systems. These integrated systems can extract useful data from a large volume of raw data, facilitating real-time detection and processing of environmental information. This review explores the recent advances in memristor-based artificial sensory systems. The authors begin with the requirements of artificial sensory elements and then present an in-depth review of such elements demonstrated by memristive devices. Finally, the major challenges and opportunities in the development of memristor-based artificial sensory systems are discussed.

2.
J Korean Acad Nurs ; 54(2): 193-210, 2024 May.
Article in Korean | MEDLINE | ID: mdl-38863188

ABSTRACT

PURPOSE: The objective of this study was to develop a predictive model for the sexual experiences of adolescents using the random forest method and to identify the "variable importance." METHODS: The study utilized data from the 2019 to 2021 Korea Youth Risk Behavior Web-based Survey, which included 86,595 man and 80,504 woman participants. The number of independent variables stood at 44. SPSS was used to conduct Rao-Scott χ² tests and complex sample t-tests. Modeling was performed using the random forest algorithm in Python. Performance evaluation of each model included assessments of precision, recall, F1-score, receiver operating characteristics curve, and area under the curve calculations derived from the confusion matrix. RESULTS: The prevalence of sexual experiences initially decreased during the COVID-19 pandemic, but later increased. "Variable importance" for predicting sexual experiences, ranked in the top six, included week and weekday sedentary time and internet usage time, followed by ease of cigarette purchase, age at first alcohol consumption, smoking initiation, breakfast consumption, and difficulty purchasing alcohol. CONCLUSION: Education and support programs for promoting adolescent sexual health, based on the top-ranking important variables, should be integrated with health behavior intervention programs addressing internet usage, smoking, and alcohol consumption. We recommend active utilization of the random forest analysis method to develop high-performance predictive models for effective disease prevention, treatment, and nursing care.


Subject(s)
Risk-Taking , Sexual Behavior , Humans , Adolescent , Female , Male , Surveys and Questionnaires , Republic of Korea , Alcohol Drinking , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/psychology , ROC Curve , Adolescent Behavior/psychology , Internet , Area Under Curve , Secondary Data Analysis , Random Forest
3.
J Am Soc Mass Spectrom ; 35(6): 1301-1309, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38657000

ABSTRACT

Small interfering RNA (siRNA) is known for its ability to silence the expression of specific genes, demonstrating its promising potential as a therapeutic approach. Self-assembled micelle inhibitory RNA (SAMiRNA) is an oligonucleotide duplex developed to overcome the in vivo delivery limitations of siRNA. SAMiRNA has hydrophilic and hydrophobic groups at both ends of a sense strand, forming a spherical nanostructure that enhances the in vivo delivery efficiency. Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the most commonly used method for the analysis of oligonucleotides. Since SAMiRNA is heavily chemically modified, the behavior of SAMiRNA in IP-RPLC combined with mass spectrometry (MS) is anticipated to differ from that of the conventional siRNA drug. The current investigation using IP-RPLC-MS revealed that a distinct duplex peak along with two minor separate strands of antisense and sense was observed at column temperatures below 35 °C in the IP-RPLC system with a 100 mM ammonium bicarbonate buffer system. At column temperatures higher than 35 °C, however, two fully denatured single strands were observed. The mass spectrum from the chromatographic peak of the SAMiRNA duplex contained signals from the duplex, the antisense, and the sense, probably due to duplex denaturation during the MS ionization process. The current comprehensive analysis results will make a substantial contribution to the future application of IP-RPLC-MS in the analysis of SAMiRNA.


Subject(s)
Chromatography, Reverse-Phase , Micelles , RNA, Small Interfering , Chromatography, Reverse-Phase/methods , RNA, Small Interfering/chemistry , RNA, Small Interfering/analysis , RNA, Small Interfering/genetics , Mass Spectrometry/methods
4.
Nano Converg ; 10(1): 55, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38038784

ABSTRACT

HfO2 shows promise for emerging ferroelectric and resistive switching (RS) memory devices owing to its excellent electrical properties and compatibility with complementary metal oxide semiconductor technology based on mature fabrication processes such as atomic layer deposition. Oxygen vacancy (Vo), which is the most frequently observed intrinsic defect in HfO2-based films, determines the physical/electrical properties and device performance. Vo influences the polymorphism and the resulting ferroelectric properties of HfO2. Moreover, the switching speed and endurance of ferroelectric memories are strongly correlated to the Vo concentration and redistribution. They also strongly influence the device-to-device and cycle-to-cycle variability of integrated circuits based on ferroelectric memories. The concentration, migration, and agglomeration of Vo form the main mechanism behind the RS behavior observed in HfO2, suggesting that the device performance and reliability in terms of the operating voltage, switching speed, on/off ratio, analog conductance modulation, endurance, and retention are sensitive to Vo. Therefore, the mechanism of Vo formation and its effects on the chemical, physical, and electrical properties in ferroelectric and RS HfO2 should be understood. This study comprehensively reviews the literature on Vo in HfO2 from the formation and influencing mechanism to material properties and device performance. This review contributes to the synergetic advances of current knowledge and technology in emerging HfO2-based semiconductor devices.

5.
Biomimetics (Basel) ; 8(8)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38132547

ABSTRACT

A living lab is a valuable method for designing tangible and intangible service elements, ensuring a comprehensive user experience. Developing a digital companion service, which users may be unfamiliar with, requires observing user behavior in real-world environments and analyzing living and behavioral patterns. A living lab starts with understanding user characteristics and behaviors. Living lab methods have an impact on the accuracy and precision of service design. The number of seniors in South Korea is rapidly increasing, leading to a rise in social issues like solitary deaths and suicide. Addressing these problems has led to a growing demand for companion robots. To design effective companion services, understanding seniors' living environments and their cognitive and behavioral traits is essential. This opinion piece, based on a national R&D project, presents the development of a digital companion for seniors. It offers insights, providing a comprehensive overview of living lab-based service interaction design and proposing methodologies about living lab environment construction and experimentation and considerations when designing robot interaction functions and appearance. The living lab environment includes real living spaces, laboratories, virtual reality settings, and senior welfare centers. Using the research findings, we created service scenarios, analyzed senior language characteristics, and developed the concept and facial expressions of the digital companion. To successfully introduce a novel service, it is crucial to analyze users' real-life behavior and adjust the service accordingly.

6.
Nano Lett ; 23(14): 6360-6368, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37409775

ABSTRACT

Vertical two-terminal synaptic devices based on resistive switching have shown great potential for emulating biological signal processing and implementing artificial intelligence learning circuitries. To mimic heterosynaptic behaviors in vertical two-terminal synaptic devices, an additional terminal is required for neuromodulator activity. However, adding an extra terminal, such as a gate of the field-effect transistor, may lead to low scalability. In this study, a vertical two-terminal Pt/bilayer Sr1.8Ag0.2Nb3O10 (SANO) nanosheet/Nb:SrTiO3 (Nb:STO) device emulates heterosynaptic plasticity by controlling the number of trap sites in the SANO nanosheet via modulation of the tunneling current. Similar to biological neuromodulation, we modulated the synaptic plasticity, pulsed pair facilitation, and cutoff frequency of a simple two-terminal device. Therefore, our synaptic device can add high-level learning such as associative learning to a neuromorphic system with a simple cross-bar array structure.

7.
Adv Mater ; 35(35): e2302219, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37116944

ABSTRACT

Technologies based on the fusion of gas sensors and neuromorphic computing to mimic the olfactory system have immense potential. However, the implementation of neuromorphic olfactory systems remains in a state of infancy because conventional gas sensors lack the necessary functions. Therefore, this study proposes a hysteretic "chemi-memristive gas sensor" based on oxygen vacancy chemi-memristive dynamics that differ from that of conventional gas sensors. After the memristive switching operation, the redox reaction with the external gas molecules is enhanced, resulting in the generation and elimination of oxygen vacancies that induce rapid current changes. In addition, the pre-generated oxygen vacancies enhance the post-sensing properties. Therefore, fast responses, short recovery times, and hysteretic gas response are achieved by the proposed sensor at room temperature. Based on the advantageous functionality of the sensor, device-level olfactory systems that can monitor the history of input gas stimuli are experimentally demonstrated as a potential application. Moreover, analog conductance modulation induced by oxidizing and reducing gases enables the conversion of external gas stimuli into synaptic weights and hence the realization of typical synaptic functionalities without an additional device or circuit. The proposed chemi-memristive device represents an advance in the bioinspired technology adopted in creating artificial intelligence systems.

8.
Environ Res ; 214(Pt 1): 113830, 2022 11.
Article in English | MEDLINE | ID: mdl-35820655

ABSTRACT

Soil contaminated with diesel fuel is a hazard to the environment and people; therefore, it needs to be remediated. Soil washing enhanced with Tween 80 (TW80), non-toxic and non-ionic surfactant, can effectively remove diesel from contaminated soils. In this study, the effects of 0.01%, 0.1%, 0.5%, 1%, and 1.5% (v/v) [TW80] concentrations; 0%, 5%, and 15% (w/w) bentonite; and variation in pH on washing efficiency were examined in a batch test. The prepared samples were physiochemically characterized on the basis of particle size, zeta potential, cation exchange capacity (CEC), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) analysis. When the bentonite content in soil was 5% or 15%, 1.5% [TW80] solution exhibited the highest washing efficiency. The diesel removal efficiencies in soil with 0% bentonite were slightly higher than those in soils with 5% and 15% bentonite because of the increase in adsorption sites by bentonite; consequently, diesel could not be easily washed out. The extracted n-alkanes showed that the percentage of carbon number 20 was higher than that of the other even-numbered carbons in the retained washed samples analyzed by gas chromatography-mass spectrometry (GC-MS). In all the washing tests, the diesel removal efficiencies in soil with 15% bentonite and 0.1% [TW80] were lower than those in soil with 15% bentonite and water because of adsorption. The bentonite samples washed with TW80 have different morphologies, with a voluminous structure composed of the fusion of all layered structures, as supported by SEM results. Changes in the diesel content and residual TW80 content in the soil before and after washing were shown by the carbon content in the EDS results. The mechanism of the washing effect was investigated by CEC and zeta potential measurements. This study may aid in selecting appropriate conditions for improving washing efficiencies in future field applications.


Subject(s)
Polysorbates , Soil Pollutants , Bentonite , Carbon , Humans , Hydrogen-Ion Concentration , Soil , Surface-Active Agents
9.
Sensors (Basel) ; 22(6)2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35336253

ABSTRACT

Photoplethysmography (PPG) is a simple and cost-efficient technique that effectively measures cardiovascular response by detecting blood volume changes in a noninvasive manner. A practical challenge in the use of PPGs in real-world applications is noise reduction. PPG signals are likely to be compromised by various types of noise, such as scattering or motion artifacts, and removing such compounding noises using a monotonous method is not easy. To this end, this paper proposes a neural PPG denoiser that can robustly remove multiple types of noise from a PPG signal. By casting the noise reduction problem into a signal restoration approach, we aim to achieve a solid performance in the reduction of different noise types using a single neural denoiser built upon transformer-based deep generative models. Using this proposed method, we conducted the experiments on the noise reduction of a PPG signal synthetically contaminated with five types of noise. Following this, we performed a comparative study using six different noise reduction algorithms, each of which is known to be the best model for each noise. Evaluation results of the peak signal-to-noise ratio (PSNR) show that the neural PPG denoiser is superior in three out of five noise types to the performance of conventional noise reduction algorithms. The salt-and-pepper noise type showed the best performance, with the PSNR of the neural PPG denoiser being 36.6080, and the PSNRs of the other methods were 19.8160 and 32.8234. The Poisson noise type performed the worst, showing a PSNR of 33.0090; the PSNRs of other methods were 35.1822 and 33.4795, respectively. Thereafter, an experiment to recover a signal synthesized with two or more of the five noise types was conducted. When the number of mixed noises was two, three, four, and five, the PSNRs were 29.2759, 27.8759, 26.5608, and 25.9402, respectively. Finally, an experiment to recover motion artifacts was also conducted. The synthesized motion artifact signal was created by synthesizing only a certain ratio of the total signal length. As a result of the motion artifact signal restoration, the PSNRs were 25.2872, 22.8240, 21.2901, and 19.9577 at 30%, 50%, 70%, and 90% motion artifact ratios, respectively. In the three experiments conducted, the neural PPG denoiser showed that various types of noise were effectively removed. This proposal contributes to the universal denoising of continuous PPG signals and can be further expanded to denoise continuous signals in the general domain.


Subject(s)
Photoplethysmography , Signal Processing, Computer-Assisted , Algorithms , Artifacts , Photoplethysmography/methods , Signal-To-Noise Ratio
10.
Brain Behav ; 12(1): e2459, 2022 01.
Article in English | MEDLINE | ID: mdl-34904796

ABSTRACT

BACKGROUND: The present study investigated the joint impact of adolescent sport experience and dopamine-related genes (i.e., DRD2 and COMT genes) on sport participation in adulthood. METHODS: Using the National Longitudinal Study of Adolescent Health (Add Health) data, the hierarchical multivariable logistic regression models for predicting sport participation in wave 3 (around 20 years of age) and wave 4 (around 30 years of age) were conducted separately by gender (male and female) and gene (DRD2 and COMT genes). RESULTS: Adolescent sport experience significantly interacted with the number of DRD2 A1 alleles and COMT Met alleles in affecting wave 3 sport participation among male adults. The interaction between adolescent sport experience and DRD2 gene significantly affected wave 4 sport participation in opposite direction to that affected wave 3 sport participation among male participants. Among female participants, there were no significant interaction effects between dopamine-related genes and adolescent sport experience on sport participation in both wave 3 and 4. CONCLUSIONS: Since adult sport participation is most likely to be influenced by the joint impact of environmental and genetic factors, it is important to consider gene-by-environment interactions when designing policies or programs to promote adult sport participation.


Subject(s)
Catechol O-Methyltransferase , Receptors, Dopamine D2 , Sports , Youth Sports , Adolescent , Adult , Alleles , Catechol O-Methyltransferase/genetics , Female , Humans , Longitudinal Studies , Male , Receptors, Dopamine D2/genetics
11.
AMB Express ; 9(1): 122, 2019 Jul 30.
Article in English | MEDLINE | ID: mdl-31363941

ABSTRACT

Rates of microbial drug resistance are increasing worldwide; therefore, antimicrobial peptides (AMPs) are considered promising alternative therapeutic agents to antibiotics. AMPs are essential components of the innate immune system and exhibit broad-spectrum antimicrobial activity. P5 is a Cecropin A-Magainin 2 hybrid analog peptide with antimicrobial activity against Gram-negative and Gram-positive bacteria. In the present study, truncated peptides were designed to reduction length, retainment their antimicrobial activity and low toxicity at high concentrations compared with that of the parent peptide P5. The truncated peptides P5-CT1 and P5-NT1 exhibited antibacterial activities against both Gram-negative and Gram-positive bacteria. In contrast, P5-CT2, P5-CT3, P5-NT2, and P5-NT3 showed higher antibacterial activities against gram-positive bacteria compared to Gram-negative bacteria at low concentration of peptides. The truncated peptides showed lower hemolytic activity and toxic effects against mammalian cells compared with those of the parent peptide P5. The levels of several truncated peptides were maintained in the presence of physiological concentrations of salts, indicating their high stability. The results of flow cytometry, propidium iodide uptake, n-phenyl-1-naphthylamine uptake, and 3,3'-dipropylthiadicarbocyanine iodide assays showed that these truncated peptides killed microbial cells by increasing membrane permeability, thereby causing membrane damage. The results suggested that truncated peptides of P5 have good potential for use as novel antimicrobial agents.

12.
Transl Oncol ; 9(1): 79-88, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26947885

ABSTRACT

The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs) and normal colonic fibroblasts (NCFs) and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D) scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α) by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

13.
Anticancer Res ; 35(7): 3925-31, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26124339

ABSTRACT

AIM: To investigate whether differential expression of Yes-associated protein (YAP) and ß-catenin is important in gastric carcinogenesis. MATERIALS AND METHODS: A total of 284 paraffin-embedded samples collected from 232 patients with gastric adenocarcinoma were used to evaluate YAP and ß-catenin expression by immunohistochemistry, and the experimental findings were compared against those for gastric adenocarcinoma cell lines. RESULTS: Nuclear YAP expression gradually increased from non-neoplastic epithelia to tubular or papillary adenocarcinomas (TPADs) and decreased in signet-ring cell carcinoma (SRCC). Cytoplasmic ß-catenin expression increased from non-neoplastic epithelia to high-grade dysplasia and was decreased in TPAD and SRCC. YAP-overexpressing cell lines exhibited marked tumor cell invasion, whereas YAP-depleted cells showed reduced invasion. CONCLUSION: Nuclear YAP and cytoplasmic ß-catenin play important roles in carcinogenesis, and the differential patterns YAP and ß-catenin expression between TPAD and SRCC imply the existence of different carcinogenic pathways in these conditions.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Phosphoproteins/genetics , Stomach Neoplasms/genetics , beta Catenin/genetics , Adenocarcinoma/genetics , Adult , Aged , Aged, 80 and over , Carcinogenesis/genetics , Carcinoma, Signet Ring Cell/genetics , Cell Line, Tumor , Cell Nucleus/genetics , Cytoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Middle Aged , Neoplasm Invasiveness/genetics , Transcription Factors , YAP-Signaling Proteins
14.
Histol Histopathol ; 28(11): 1483-90, 2013 11.
Article in English | MEDLINE | ID: mdl-23673988

ABSTRACT

Yes-associated protein (YAP) is a transcriptional co-activator and functions as a nuclear downstream effector of the Hippo pathway. Differential expression of YAP and phosphorylated Yes-associated protein (pYAP), which are involved in the expression of Ki-67 and phosphorylated extracellular signal-regulated kinase (pERK) in colorectal adenocarcinoma (CRAC), is not clear. Herein, we hypothesized that nuclear expression of YAP could predict cell proliferation and poor prognosis, while cytoplasmic expression of pYAP would show a reverse correlation with cell proliferation. Paraffin-embedded samples from 144 CRAC patients were studied using immunohistochemistry for YAP, pYAP, Ki-67 and pERK. Frozen samples from 20 CRAC patients were examined for YAP mRNA in tumor and non-tumor tissues, using quantitative real-time PCR. High nuclear YAP expression coincided with high Ki-67 expression (P=0.002). The high nuclear YAP expression group tended to display a poor overall and disease-free survival (P=0.089 and P=0.089, respectively), but YAP mRNA levels in the 20 CRAC tissues were not significantly different in comparison with the 20 non-tumor tissues (P=0.929). We observed an inverse correlation between high cytoplasmic pYAP expression and high Ki-67 expression (P=0.001). Nuclear pERK expression was positively correlated with nuclear YAP expression, but negatively correlated with cytoplasmic pYAP expression (P=0.017 and P=0.020, respectively). Activated nuclear YAP and inactivated cytoplasmic pYAP in CRAC showed a positive correlation with Ki-67 and nuclear pERK expression, suggesting that the expression of YAP and pYAP is a possible predictor of tumor cell proliferation and prognosis in CRAC.


Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Ki-67 Antigen/biosynthesis , Nuclear Proteins/biosynthesis , Transcription Factors/biosynthesis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Cell Cycle Proteins , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Phosphorylation , Prognosis , Proportional Hazards Models , Real-Time Polymerase Chain Reaction
15.
Article in English | MEDLINE | ID: mdl-21096245

ABSTRACT

Ultrasound (US) images are degraded by speckle noise that reduces the contrast and details of images. But the effective method for speckle noise reduction with keeping edge has been still a challenging point. Coherence measurement has been used to distinguish homogeneous region and coherence regions, e.g. edges, and the edge map obtained from coherence measurement has limitation such as noisy or discontinued edge detection. In this paper, to overcome these problems, the enhanced edge map generation using multi-resolutional coherence measurement is proposed and adaptive wavelet based-speckle noise reduction is performed using the enhanced edge map. The experimental results showed that the enhanced edge map by proposed method contains the robust and linked edge information. Moreover, the results show that the proposed method outperforms the conventional method in preserving edge details.


Subject(s)
Algorithms , Artifacts , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Ultrasonography/methods , Humans , Reproducibility of Results , Sensitivity and Specificity
16.
J Korean Med Sci ; 25(11): 1676-9, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21060762

ABSTRACT

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-α. The patient developed progressive, severe anemia after the use of erythropoietin-α. As the anemia did not improve after the administration of either other erythropoietin-α products or erythropoietin-ß, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-α at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-α can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.


Subject(s)
Antibodies/blood , Erythropoietin/analogs & derivatives , Erythropoietin/immunology , Hematinics/therapeutic use , Red-Cell Aplasia, Pure/drug therapy , Adult , Anemia/drug therapy , Anemia/etiology , Antibodies/immunology , Bone Marrow Cells/pathology , Darbepoetin alfa , Drug Hypersensitivity/immunology , Erythropoietin/adverse effects , Erythropoietin/therapeutic use , Female , Glomerulonephritis, IGA/complications , Hematinics/adverse effects , Hematinics/immunology , Humans , Kidney Failure, Chronic/complications , Oxymetholone/therapeutic use , Recombinant Proteins , Red-Cell Aplasia, Pure/chemically induced , Red-Cell Aplasia, Pure/immunology
17.
Int J Mol Med ; 19(1): 157-63, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17143560

ABSTRACT

A 36 kDa extracellular metalloprotease (designated to as vEP-MO6) was purified and characterized from Vibrio vulnificus sp. strain MO6 24/0. vEP-MO6 cleaved azocasein and a few other proteins such as prothrombin, plasminogen, fibrinogen and Factor Xa, which are associated with the blood coagulation pathway. The enzyme activity of vEP-MO6 was inhibited by EDTA, which was reversed by the addition of excess divalent cations. vEP-MO6 showed little or no activity toward various chromogenic substrates that are specific for other proteases. The cleavage of prothrombin by vEP-MO6 produced active thrombin, as revealed by an activity assay with thrombin-specific chromogenic substrate and Western blot analysis with anti-thrombin antibody. The enzyme also actively hydrolyzed fibrin polymer as well as the cross-linked fibrin. These results suggest that vEP-MO6 is a prothrombin-activating and cross-linked fibrin-degrading enzyme belonging to the metalloprotease family.


Subject(s)
Fibrinolysis , Metalloproteases/physiology , Prothrombin/metabolism , Vibrio vulnificus/enzymology , Amino Acid Sequence , Chelating Agents/pharmacology , Enzyme Activation , Fibrin/metabolism , Metalloproteases/antagonists & inhibitors , Metalloproteases/genetics , Metalloproteases/isolation & purification , Metals/pharmacology , Molecular Sequence Data , Protease Inhibitors/pharmacology , Sequence Homology, Amino Acid , Vibrio vulnificus/genetics
18.
Eur J Pharmacol ; 528(1-3): 37-42, 2005 Dec 28.
Article in English | MEDLINE | ID: mdl-16324698

ABSTRACT

Cdc25B is a dual specific phosphatase, which plays a pivotal role in the activation of cell-cycle-dependent kinase 1 (Cdk1). A novel Cdc25B inhibitor, EK-6136, was identified by high throughput screening (HTS) using compounds from Korea Chemical Bank and examined for its biological effects. EK-6136 inhibited Cdc25B with an IC50 of 6.4+/-1.5 microM. EK-6136 showed selectivity against several phosphatases including PTP-1B, CD45, Cdc25A, PP1, VHR and Yop. In the inhibition kinetic study, EK-6136 displayed a mixed inhibition pattern with a Ki value of 7.8+/-1.2 microM. Consistent with in vitro results, EK-6136 inhibited the proliferation of MCF-7 (human breast carcinoma), HT-29 (human colorectal adenocarcinoma) and A549 (lung carcinoma) cells with increased Cdk-1 phosphorylation. Herein, we propose that EK-6136 is an active HTS hit as a Cdc25B inhibitor with antiproliferative activity, and can be used for the design of more potent and selective antiproliferative agents.


Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Pyrazolones/pharmacology , cdc25 Phosphatases/antagonists & inhibitors , CDC2 Protein Kinase/metabolism , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , HT29 Cells , Humans , Inhibitory Concentration 50 , Kinetics , Phosphorylation , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases/antagonists & inhibitors
19.
Bioorg Med Chem ; 10(1): 185-8, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11738620

ABSTRACT

5-Demethylovalicin was isolated from the fermentation broth Chrysosporium lucknowense and the structure was identified by spectroscopic methods. 5-Demethylovalicin inhibited the recombinant human MetAP-2 (IC(50)=17.7 nM) and the growth of human umbilical vein endothelial cells (HUVEC; IC(50)=100 nM) in cell proliferation assay without cytotoxicity on the transformed and cancer cell lines.


Subject(s)
Aminopeptidases/antagonists & inhibitors , Chrysosporium/metabolism , Enzyme Inhibitors/pharmacology , Metalloendopeptidases/antagonists & inhibitors , Sesquiterpenes/pharmacology , Cells, Cultured , Humans , Recombinant Proteins/antagonists & inhibitors
20.
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