• Mass Spectrometry Letters
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• v.10 no.1
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• pp.38-42
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• 2019

Damaurone D belongs to the genus Rosa and is a traditional medicinal product used for the treatment of depression, inflammation, and infectious diseases. The purpose of this study was to develop a simple liquid chromatography-tandem mass spectrometry method for the detection of damaurone D in rat plasma and to demonstrate its application in pharmacokinetic studies. Damaurone D and berberine (internal standard) were extracted with acetonitrile using a protein precipitation method. Mass transition was monitored in multiple reaction monitoring mode at m/z $323.2{\rightarrow}267.0$ for damaurone D and m/z $336.1{\rightarrow}320.0$ for berberine in positive ion mode. Analytical validation was conducted by evaluating the specificity, linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The calibration curves were linear over 2-1000 ng/mL. The intra- and inter-day precision and accuracy of quality control samples were 4.79-13.33% and 86.23-102.75%, respectively. The matrix effect and extraction recovery were 96.11-98.47% and 96.11-102.25%, respectively. In the pharmacokinetic study after intravenous administration of damaurone D at a dose of 3 mg/kg in rats, the area under the curve and clearance of damaurone D in rat plasma were $16750.26{\pm}2676.10min{\cdot}ng/mL$ and $182.44{\pm}31.36mL/min/kg$, respectively.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.232-238
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• 2018

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

• Herbal Formula Science
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• v.29 no.1
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• pp.45-55
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• 2021

Objectives : This study was conducted to evaluate the anti-atrophic effect of polycan in dexamethasone-induced skeletal muscle atrophy in vitro model. Methods : C2C12 myoblast were differentiated into myotube by 2% horese serum medium for 6 days, and then treated polycan extract at different concentrations for 24h. The effect of dexamethasone on the induction of muscle atrophy and expression of atrophy-related genes in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : The results showed that Treatment with polycan (100 and 200 ㎍/㎖) noncytotoxic levels on both myoblast and myotube. Polycan decreased the ROS level overproduced with dexamethasone and improved the depletion of GSH level. Dexamethasone showed a decrease in myotube diameter, which was associated with up-regulation muscle-specific ubiquitin ligases markers, such as atrogin-1, FoxO3, myostatin and muscle RING finger-1 (MuRF1), and down-regulation of myogenin, MEF2, Myogenic regulatory factor 5, 6 and MyoD. The results showed that polycan treatment significantly dose-dependently inhibited it. Furthermore, decreased expressions of PI3K/Akt signal pathway by dexamethasone were reversed by treatment with polycan. Conclusions : Thus, polycan suppresses dexamethasone induced muscle atrophy in C2C12 myotube in vitro model through activation of PI3K/Akt pathway and protective effect of improve skeletal muscle function.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.291-297
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• 2022

Dry age-related macular degeneration (AMD) is a type of progressive blindness that is primarily due to dysfunction and the loss of retinal pigment epithelium (RPE). The accumulation of N-retinylidene-N-retinylethanolamine (A2E), a by-product of the visual cycle, causes RPE and photoreceptor degeneration that impairs vision. Genes associated with dry AMD have been identified using a blue light model of A2E accumulation in the retinal pigment epithelium and transcriptomic studies of retinal tissue from patients with AMD. However, dry macular degeneration progresses slowly, and current approaches cannot reveal changes in gene transcription according to stages of AMD progression. Thus, they are limited in terms of identifying genes responsible for pathogenesis. Here, we created a model of long-term exposure to identify temporally-dependent changes in gene expression induced in human retinal pigment epithelial cells (ARPE-19) exposed to blue light and a non-cytotoxic dose of A2E for 120 days. We identified stage-specific genes at 40, 100, and 120 days, respectively. The expression of genes corresponding to epithelial-mesenchymal transition (EMT) during the early stage, glycolysis and angiogenesis during the middle stage, and apoptosis and inflammation pathways during the late stage was significantly altered by A2E and blue light. Changes in the expression of genes at the late stages of the EMT were similar to those found in human eyes with late-stage AMD. Our results provide further insight into the pathogenesis of dry AMD induced by blue light and a novel model in vitro with which relevant genes can be identified in the future.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.1
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• pp.27-33
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• 2022

Functional dyspepsia (FD) is a gastrointestinal disorder with diverse symptoms but no structural or organic manifestations. Benachio-F^® (herein named 'BF-1') is an over-the-counter liquid digestive formulated with multiple herbal extracts, which has been reported to improve symptoms of FD. A total two experiments were conducted. First, we examined whether BF-1 can modulate the progression of FD through two experimental rat models. A total of three doses (0.3x, 1x, 3x of the human equivalent dose) were used. In the gastric emptying model, both 1x (standard) or 3x (3-fold-concentrated) BF-1 enhanced gastric emptying was compared with that of vehicle-treated animals. In a feeding inhibition model induced by acute restraint stress, treatment with 1x or 3x BF-1 led to a similar degree of restoration in food intake that was comparable to that of acotiamide-treated animals. Among the constituents of BF, fennel is known for its choleretic effect. Thus, we next investigated whether a novel BF-based formula (named 'BF-2') that contains an increased amount of fennel extract (3.5-fold over BF-1), has greater potency in increasing bile flow. BF-2 showed a superior choleretic effect compared to BF-1. Furthermore, the postprandial concentration of serum secretin was higher in animals pretreated with BF-2 than in those pretreated with BF-1, suggesting that the increased choleretic effect of BF-2 is related to secretin production. Our results demonstrate that BF-1 can modulate the pathophysiological mechanisms of FD by exerting prokinetic and stress-relieving effects, and that BF-2 has a better choleretic effect than BF-1.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.3
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• pp.275-285
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• 2022

In this study, we prepared two extracts using 1,3-butylene glycol (DBG) and ethanol (DET), with Diospyros kaki and determined the anti-oxidant, anti-aging, and whitening effects in vitro. Anti-oxidant activity was measured by DPPH and superoxide dismutase (SOD) method, and as a result, both DBG and DET extracts confirmed their anti-oxidant properties by exhibiting significant DPPH scavenging and SOD-like activities. For anti-aging activity, we measured elastase and hyaluronidase inhibition, and the inhibition of MMP-1 expression. Both DBG and DET significantly inhibited elastase and hyaluronidase activities dose-dependently, and MMP-1 expression was also reduced in both extracts. We also measured the whitening effects with tyrosinase activity and melanin production, but only DBG showed a decrease in tyrosinase. In summary, D. kaki extract has strong antioxidant, anti-aging, and whitening functions, and it is believed that it can be used as a cosmetic material in the future.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.25-30
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• 2015

Objectives : Laver (Porphyra tenera), a red algae species, is one of the most widely consumed edible seaweed in Korea. Laver contains various substances such as essential amino acid, fiber, minerals and polyphenols that benefit human health. In the present study, we prepared ethanol extracts from commercially processed product of Porphyra tenera, and evaluated the growth inhibitory effect against human oral squamous carcinoma YD-10B cells. Methods : Cell viability was measured by MTT assay. Apoptosis was confirmed by TUNEL assay and flow cytometry with the green fluorescent dye FITC annexin V entering apoptotic cells and the red fluorescent dye PI not entering. The expression of the relevant proteins was detected using Western blot. Results : Ethanol extracts of Porphyra tenera (PTE, $50-200{\mu}g/m{\ell}$) caused a significant decrease of cell viability in a dose dependant manner. The cell death occurred as a result of apoptotic process as determined by TUNEL assay and flow cytometric analysis. In line with this observation, decrease in procaspase proteins and increase in cytosolic cytochrome c were observed in cells treated with PTE. In addition, exposure to PTE decreased the expression levels of Bcl-2, and induced PARP cleavage and AIF translocation from mitochondria to nucleus. Conclusions : In conclusion, PTE exerts anti-cancer effects by inducing apoptosis via caspase activation and AIF nuclear translocation in YD-10B cells. These results provide evidence for the possible therapeutic effect of Porphyra tenera in oral cancer cells.

• The Korea Journal of Herbology
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• v.38 no.2
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• pp.27-34
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• 2023

Objectives : Currently, the benign prostatic hyperplasia (BPH) is one of the most common urogenital disorder in old men. We were performed to determine the effects of abietic acid (AC), component of pine resin, in benign prostatic hyperplastic Sprague-Dawley rat (SD rat) induced by testosterone injection (IP). Methods : We monitored body weights in SD rat at start and end date of experiment. After end of experiment, the prostate weights were measured in SD rats. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels was performed in serum. And we determined the 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels in prostate tissue and serum using ELISA kit. Results : As results, the prostate wights were increased in BPH group compared to normal group and were decreased in fina, AC30, and AC 50 groups, respectively. Serum GOT levels were decreased in AC50 group compared to BPH group. And Serum GPT levels of AC30 and AC50 groups were lower than BPH group. In addition, the 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels were decreased the fina, AC10, AC30, and AC 50 groups contrast to the BPH group. Furthermore, 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels were decreased dose dependent in AC groups compared to BPH group. Conclusion : These results suggest that AC could be used as a potential material for the treatment of BPH by decreasing the androgen levels in benign prostatic hyperplasia model rats.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.493-511
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• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• Journal of Radiation Protection and Research
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• v.48 no.1
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• pp.9-14
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• 2023

Background: The detectors of both computed radiography (CR) and direct digital radiography (DR) have a wide dynamic range that could tolerate high values of exposure factors without an adverse effect on image quality. Therefore, this study aims to assess patient radiation dose and proposes institutional diagnostic reference levels (DRLs) for two teaching hospitals in Ghana. Materials and Methods: CR and DR systems were utilized in this study from two teaching hospitals. The CR system was manufactured by Philips Medical Systems DMC GmbH, while the DR system was manufactured by General Electric. The entrance skin doses (ESDs) were calculated using the standard equation and the tube output measurements. Free-in-air kerma (µGy) was measured using a calibrated radiation dosimeter. The proposed institutional DRLs were estimated using 75^th percentiles values of the estimated ESDs for nine radiographic projections. Results and Discussion: The calculated DRLs were 0.4, 1.6, 3.4, 0.5, 0.4, 1.1, 1.0, 1.2, and 1.7 mGy for chest posteroanterior (PA), lumbar spine anteroposterior (AP), lumbar spine lateral (LAT), cervical spine AP, cervical spine LAT, skull PA, pelvis AP, and abdomen AP, respectively in CR system. In the DR system, the values were 0.3, 1.6, 3.1, 0.4, 0.3, 0.7, 0.6, 0.9, and 1.3 for chest PA, lumbar spine AP, lumbar spine LAT, cervical spine AP, cervical spine LAT, skull PA, pelvis AP, and abdomen AP, respectively. Conclusion: Institutional DRLs in nine radiographic projections have been proposed for two teaching hospitals in Ghana for the first time. The proposed DRLs will serve as baseline data for establishing local DRLs in the hospitals and will be a valuable tool in optimizing patient doses.