• Journal of Medicine and Life Science
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• v.18 no.3
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• pp.41-48
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• 2021

The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopamine-related developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.2
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• pp.49-58
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• 2024

The rapid advancement of generative large language models has revolutionized various real-life domains, emphasizing the importance of exploring their applications in healthcare. This study aims to examine how generative large language models are implemented in the medical domain, with the specific objective of searching for the possibility and potential of integration between generative large language models and East Asian medicine. Through a comprehensive current state analysis, we identified limitations in the deployment of generative large language models within East Asian medicine and proposed directions for future research. Our findings highlight the essential need for accumulating and generating structured data to improve the capabilities of generative large language models in East Asian medicine. Additionally, we tackle the issue of hallucination and the necessity for a robust model evaluation framework. Despite these challenges, the application of generative large language models in East Asian medicine has demonstrated promising results. Techniques such as model augmentation, multimodal structures, and knowledge distillation have the potential to significantly enhance accuracy, efficiency, and accessibility. In conclusion, we expect generative large language models to play a pivotal role in facilitating precise diagnostics, personalized treatment in clinical fields, and fostering innovation in education and research within East Asian medicine.

• Development and Reproduction
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• v.19 no.1
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• pp.53-60
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• 2015

Environmental conditions during early mammalian embryo development are critical and some adaptational phenomena are observed. However, the mechanisms underlying them remain largely masked. Previously, we reported that AQP5 expression is modified by the environmental condition without losing the developmental potency. In this study, AQP11 was examined instead. To compare expression pattern between in vivo and in vitro, we conducted quantitative RT-PCR and analyzed localization of the AQP11 by whole mount immunofluorescence. When the fertilized embryos were developed in the maternal tracts, the level of Aqp11 transcripts was decreased dramatically until 2-cell stage. Its level increased after 2-cell stage and peaked at 4-cell stage, but decreased again dramatically until morula stage. Its transcript level increased again at blastocyst stage. In contrast, the levels of Aqp11 transcript in embryos cultured in vitro were as follows. The patterns of expression were similar but the overall levels were low compared with those of embryos grown in the maternal tracts. AQP11 proteins were localized in submembrane cytoplasm of embryos collected from maternal reproductive tracts. The immune-reactive signals were detected in both trophectoderm and inner cell mass. However, its localization was altered in in vitro culture condition. It was localized mainly in the plasma membrane of the blastocysts contacting with external environment. The present study suggests that early stage embryo can develop successfully by themselves adapting to their environmental condition through modulation of the expression level and localization of specific genes like AQP11.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.8
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• pp.1118-1126
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• 2010

Male reproduction is influenced by a number of intrinsic and extrinsic factors, including environmental endocrine disruptors. Testosterone is a well recognized intrinsic regulator for development and function of the male reproductive tract, and thus male fertility. The testis and semen of many mammalians contain an unusually high concentration of estrogen. Testosterone is converted into estrogen by the enzymatic action of cytochrome P450 aromatase complex (Cyp19a1). Of the male reproductive tract, the efferent ductules (EDs) possess exceptionally elevated levels of estrogen receptors (ERs), ER${\alpha}$ and ER${\beta}$, indicating that estrogen, in addition to testosterone, would have a functional role in regulation of male reproduction. First, this review has focused on description and summary of what is currently known for functions of estrogen in the EDs. The biosynthetic pathway of estrogen occurring in the testis is briefly covered, following by detailed explanation of the morphology and physiology of EDs. In the next section, the sources and targets of estrogen in the male reproductive tract are highlighted, and possible functional roles of estrogen in the EDs are justified from the aspect of physiology, molecular biology, and morphology in adult animal models. Also, this section covers the importance of estrogen and ERs in maintaining normal function and morphology of the EDs during postnatal development. In the last part of this review, the effects of extrinsic factors, especially environmental endocrine-disruptors, on the EDs is summarized. The intent of this review is to emphasize the importance of estrogen for regulation of physiological function of the EDs, and thus male fertility.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.699-705
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• 2015

Vemurafenib has recently been used as drug for treatment of melanomas with $BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant $BRAF^{V600E}$ melanoma cell lines, $A375P^R$, $A375M^R$ and SKMEL-$28^R$, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-$28^R$ cells. Treatment of SKMEL-$28^R$ cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of $BRAF^{V600E}$-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.

• Journal of Veterinary Science
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• v.22 no.5
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• pp.47.1-47.10
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• 2021

Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.1
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• pp.42-50
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• 2001

The activity of immobilized cell-support particle aggregates is influenced by physical and biochemical elements, mass transfer, and physiology. Accordingly, the mathematical model discussed in this study is capable of predicting the steady state and transient concentration profiles of the cell mass and substrate, plus the effects of the substrate and product inhibition in an immobilized cell-support aggregate. The overall mathematical model is comprised of material balance equations for the cell mass, major carbon source, dissolved oxygen, and non-biomass products in a bulk suspension along with a single particle model. A smaller bead size and higher substrate concentration at the surface of the particle, resulted in a higher supply of the substrate into the aggregate and consequently a higher biocatalyst activity.

• Journal of Preventive Medicine and Public Health
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• v.27 no.4 s.48
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• pp.763-776
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• 1994

Recent studies reveal that grip forces during the hand-arm vibration are most significant for the genesis of vibration-induced white linger syndrome. Therefore, exerted grip forces and skin temperatures of fingers were regarded as dependent variables in experiments and the effects of grip temperature, noise, pushing force, vibration and the combined effect of vibration and pushing force were studied. The objectives of the present study were, first, to varify and compare the changes of grip force affected by grip temperature, noise, pushing force, vibration and the combined effect of vibration and pushing force and, second, to observe the reaction of finger skin temperature affected by above factors. Forty-six healthy male students ($25.07{\pm}2.85$) participated in five systematically permuted trials, which endured 4 minutes each other. Experiments were executed in a special chamber with an air temperature of 21C. In each experiments, the subjects were exposed to five experiment types: (1) grip force of 25N only, (2) pushing force of 50N, (3) acceleration of vibration $7.1m/sec^2(z-direction)$, (4) pink noise of 95 dB (A) and (5) combination of pushing force 50N and acceleration of vibration $7.1m/sec^2$. A repeated-measures analysis of variance (ANOVA) was performed on the grip force to test whether it was affected by noise, pushing force, vibration and pushing force. The present results show that vibration was significantly related to the increase of grip force, but the other factors, such as pushing force, noise and grip temperature had no signigicant influence on the increase of grip force, and that the reaction of finger skin temperature were significantly affected by the skin temperature at start of experiment and grip temperature, not grip force and other experimental conditions. Therefore, we suggest that the management for decreasing the grip force is meaningful to prevent the occurrence of Hand-arm vibration syndrome (HAVS).

• Journal of Mushroom
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• v.22 no.1
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• pp.8-16
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• 2024

Paecilomyces tenuipes (P. tenuipes) is a fungus cultivated artificially by South Korean researchers, utilizing rice bran as its substrate. The increased demand for this fungus has not been met with successful cultivation methods for fruiting body production in natural environments. Therefore, we tested the effect on the growth of P. tenuipes using a Solid media based on pests. In this results, the Solid media based on M.alternatus was effective in increasing the growth of P. tenuipes and the content of cordycepin. Moreover, we confirmed the conditions for manufacturing a Solid media based on M.alternatus for P. tenuipes growth. We suggested that the growth-promoting compounds offers valuable insights for optimizing fungal cultivation conditions, thereby enhancing productivity and contributing to a broader understanding of fungal physiology in varying nutritional environments.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.155-155
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• 2001

Acute cadmium exposure has been shown to increase sodium reabsorption in kidney through increase in aldosterone secretion in human and rodents. However, the antinatriuresis is not completely explained by hyperaldosteronism. Moreover, it is still controversial that the increase in plasma aldosterone concentration is mediated by the renin-angiotensin-aldosterone system(RAAS).(omitted)