• The Korea Journal of Herbology
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• v.37 no.3
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• pp.9-19
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• 2022

Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

• Journal of Life Science
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• v.33 no.3
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• pp.234-241
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• 2023

At present, many countries around the world are legalizing cannabis and its products, and research on various treatments using cannabis is being actively conducted. However, the cannabis plant contains other compounds whose biological effects have not yet been established. We investigated the effect of cannabidiol (CBD) on hair growth in human dermal papilla cells (HDPCs). 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of CBD. The HDPCs viability of CBD was examined via water-soluble tetrazolium salt (WST-1) assay. The expression of hair-loss-related markers in HDPCs by CBD treatment was analyzed by real-time PCR and western blotting. The DPPH, ABTS radical scavenging activity assay showed that CBD had superior antioxidant activities. In HDPCs, CBD increased cellular proliferation at concentrations without cytotoxicity. It also increased the expressions of fibroblast growth factor 1 (FGF1), fibroblast growth factor 7 (FGF7), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF). These results correlated with a decrease in the expression of inhibition-related factors, such as androgen receptor (AR) and transforming growth factor beta 1 (TGF-B1). Moreover, CBD resulted in a significant increase in the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). Therefore, it is suggested that CBD may be a potential remedy for the treatment of alopecia.

• The Journal of the Institute of Internet, Broadcasting and Communication
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• v.23 no.2
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• pp.119-129
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• 2023

Sleep apnea causes various secondary disease such as hypertension, stroke, myocardial infarction, depression and cognitive impairment. Early detection and continuous management of sleep apnea are urgently needed since it causes cardio-cerebrovascular diseases. In this study, wearable device for monitoring respiration during sleep using PVDF film was developed to detect vibration through trachea caused by breathing, which determines normal breathing and sleep apnea. Variables such as respiration rate and apnea were extracted based on the detected breathing sound data, and a noise reduction algorithm was established to minimize the effect even when there is a noise signal. In addition, it was confirmed that irregular breathing patterns can be analyzed by establishing a moving threshold algorithm. The results show that the accuracy of the respiratory rate from the developed device was 98.7% comparing with the polysomnogrphy result. Accuracy of detection for sleep apnea event was 92.6% and that of the sleep apnea duration was 94.0%. The results of this study will be of great help to the management of sleep disorders and confirmation of treatment by commercialization of wearable devices that can monitor sleep information easily and accurately at home during daily life and confirm the progress of treatment.

• Journal of Life Science
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• v.33 no.1
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• pp.64-72
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• 2023

Despite several advances in identification of cardiac transcription factors, there are still needs to find new bioactive molecules that promote cardiomyogenesis from stem cells to highly efficient myocardial differentiation. We analyzed Illumina expression microarray data of mouse embryonic stem cells (mESCs)-derived cardiomyocytes. 276 genes were upregulated (≥ 4fold) in mESCs-derived cardiomyocytes compared undifferentiated ESCs. Secreted phosphoprotein 2 (Spp2) is one of candidates and is known to inhibit bone morphogenetic protein 2 (BMP2) signal transduction as a pseudoreceptor for BMP2. However, its function in cardiomyogenesis is unknown. We confirmed that Spp2 expression increased during the differentiation into functional cardiomyocytes using mESCs, TC-1/Kh2 and E14. Interestingly, Spp2 secretion transiently increased 3 days after formation of embryoid bodies (EBs), indicating that the extracellular secretion of Spp2 is involved in the differentiation of ESCs into cardiomyocytes. To characterize Spp2, we performed experiments using the C2C12 mouse myoblast cell line, which has the property of shifting the differentiation pathway from myoblastic to osteoblastic by treatment with BMP2. Similar to the differentiation of ESCs, transcription of Spp2 increased as C2C12 myoblasts differentiated into myotubes. In particular, Spp2 secretion increased dramatically in the early stage of differentiation. Furthermore, treatment with Spp2-Flag recombinant protein promoted the differentiation of C2C12 myoblasts into myotubes. Taken together, we suggest a novel bioactive protein Spp2 that differentiates ESCs into cardiomyocytes. This may be useful for understanding the molecular pathways of cardiomyogenesis and for experimental or clinical promotion of stem cell therapy for ischemic heart diseases.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.458-468
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• 2023

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

• Korean Journal of Radiology
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• v.22 no.9
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• pp.1451-1461
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• 2021

Objective: Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. Materials and Methods: We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017-2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: 'AND,' if both showed CR; 'OR,' if any one showed CR; and 'conditional OR,' if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. Results: Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. Conclusion: AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.

• Korean Journal of Radiology
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• v.24 no.3
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• pp.235-246
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• 2023

Objective: It is difficult to predict the treatment response of tissue after stereotactic radiosurgery (SRS) because radiation necrosis (RN) and tumor recurrence can coexist. Our study aimed to predict tumor recurrence, including the recurrence site, after SRS of brain metastasis by performing a longitudinal tumor habitat analysis. Materials and Methods: Two consecutive multiparametric MRI examinations were performed for 83 adults (mean age, 59.0 years; range, 27-82 years; 44 male and 39 female) with 103 SRS-treated brain metastases. Tumor habitats based on contrast-enhanced T1- and T2-weighted images (structural habitats) and those based on the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) images (physiological habitats) were defined using k-means voxel-wise clustering. The reference standard was based on the pathology or Response Assessment in Neuro-Oncologycriteria for brain metastases (RANO-BM). The association between parameters of single-time or longitudinal tumor habitat and the time to recurrence and the site of recurrence were evaluated using the Cox proportional hazards regression analysis and Dice similarity coefficient, respectively. Results: The mean interval between the two MRI examinations was 99 days. The longitudinal analysis showed that an increase in the hypovascular cellular habitat (low ADC and low CBV) was associated with the risk of recurrence (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.46-4.91; P = 0.001). During the single-time analysis, a solid low-enhancing habitat (low T2 and low contrast-enhanced T1 signal) was associated with the risk of recurrence (HR, 1.54; 95% CI, 1.01-2.35; P = 0.045). A hypovascular cellular habitat was indicative of the future recurrence site (Dice similarity coefficient = 0.423). Conclusion: After SRS of brain metastases, an increased hypovascular cellular habitat observed using a longitudinal MRI analysis was associated with the risk of recurrence (i.e., treatment resistance) and was indicative of recurrence site. A tumor habitat analysis may help guide future treatments for patients with brain metastases.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.84-93
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• 2024

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.297-303
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• 2014

Purpose : The purpose of this study is reproducibility evaluation of deep inspiration breath-hold(DIBH) technique by respiration data and heart position analysis in radiation therapy for Left Breast cancer patients. Materials and Methods : Free breathing(FB) Computed Tomography(CT) images and DIBH CT images of three left breast cancer patients were used to evaluate the heart volume and dose during treatment planing system( Eclipse version 10.0, Varian, USA ). The signal of RPM (Real-time Position Management) Respiratory Gating System (version 1.7.5, Varian, USA) was used to evaluate respiration stability of DIBH during breast radiation therapy. The images for measurement of heart position were acquired by the Electronic portal imaging device(EPID) cine acquisition mode. The distance of heart at the three measuring points(A, B, C) on each image was measured by Offline Review (ARIA 10, Varian, USA). Results : Significant differences were found between the FB and DIBH plans for mean heart dose (6.82 vs. 1.91 Gy), heart $V_{30}$ (68.57 vs. $8.26cm^3$), $V_{20}$ (76.43 vs. $11.34cm^3$). The standard deviation of DIBH signal of each patient was ${\pm}0.07cm$, ${\pm}0.04cm$, ${\pm}0.13cm$, respectively. The Maximum and Minimum heart distance on EPID images were measured as 0.32 cm and 0.00 cm. Conclusion : Consequently, using the DIBH technique with radiation therapy for left breast cancer patients is very useful to establish the treatment plan and to reduce the heart dose. In addition, it is beneficial to using the Cine acquisition mode of EPID for the reproducibility evaluation of DIBH.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.254-261
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• 2000

The present study has attempted to look into the mechanism of ras-induced carcinogenesis in a human epithelial cell system. Human epithelial cells immortalized with Ad12-SV40 hybrid virus were used to assess carcinogenic potential of the ras-oncogene. Cells transfected with pSV2-ras showed characteristics of cellular transformation. The transformation parameters such as cell density, soft-agar colony formation, and cell aggregation were significantly increased in the cells expressing ras oncoprotein. In addition, the duration required for the appearance of foci was shortened in the ras-transfected cells. Consistent with other reports, our results demonstrated an evidence that the ras-oncogene induced the cellular transformation of human epithelial cell system. When a high concentration of glucocorticoid was added into the media, transformation process was accelerated. It is speculated that glucocorticoid may provide an advantageous environment for the proliferation of the transformed cells. The induction of the intracellular free calcium concentrations following agonist treatment was significantly lower in the transformed cells than in the control cells. These effects were more manifested in the presence of extracellular cacium, indicating that the transformation process may alter the influx pathway of extracellular calcium. The induction of $IP_3$ following agonist treatment was also lower in the transformed cells than in the control cells. Thus, it is suggested that phospholipase C-coupled pathway was down-regulated in the process of the ras-induced transformation. While the levels of $TGF-{\beta}_1$ and PAI-2 mRNAs were decreased, the level of fibronectin mRNA was increased. The results indicate that mechanism of the ras-induced transformation may be associated with the altered expressions of growth regulatory factors. The present study demonstrates an evidence that the ras-induced cellular transformation may be associated with alteration of signal transduction and growth regulatory factors. The study will contribute to improve the understanding of molecular mechanism of epithelium-derived cancers including oral cancer.