• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.170-176
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• 2021

Anthocyanins are considered as one of the major functional components including cyanidin-3-glucoside and peonidin-3-glucoside anthocyanins of black rice (Oryza sativa L., BR) aleurone layer (OAL) extract. The immunomodulatory biological effects of OAL has rarely been evaluated. This study has extensively studied the immunomodulatory effects of BR in immunosuppressed mice by CPA. The immunostimulatory effects of BR extract in in vivo at 150 (OAL-1) and 300 mg/kg body weight (OAL-2) for OAL groups were measured and compared to the normal group (CON) ingested with distilled water only or other groups. After the 14 days of oral administration, immune related organ weights, serum immunoglobulin (Ig) A and IgG, and cytokines (IL-12, TNF-α) levels, splenocytes proliferation rate, and NK cell activity were evaluated as immune related biomarkers. The serum IgA and IgG values in the OAL-treated groups increased to the level of the CON. OAL significantly and effectively controlled the IL-12 and TNF-α levels and NK activity compared to the negative control (NC) group. The results suggest that BR aleurone layer with immunomodulatory activities has a great potential as a functional food by itself or as a supplement.

• BMB Reports
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• v.53 no.12
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1155-1164
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• 2019

Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 log-fold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-$HDMS^E$) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, $HIF-1{\alpha}$, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including $HIF-1{\alpha}$ signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.

• Journal of Medicine and Life Science
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• v.17 no.3
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• pp.65-73
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• 2020

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease of the cerebral small blood vessels caused by mutations in the NOTCH3 gene on chromosome 19. Although CADASIL was known as a rare disease, recent research has suggested that the NOTCH variants could be found frequently even in the general population. The main clinical features included recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive decline. On brain magnetic resonance imaging, patients with CADASIL showed multifocal white matter hyperintensity lesions, lacunar infarcts, microbleeds, and brain atrophy. Among them, lacunar infarcts and brain atrophy are important in predicting the clinical outcomes of patients with CADASIL. In the Jeju National University Hospital, we have diagnosed 213 CADASIL patients from 2004 to 2020. Most NOTCH3 mutations were located in exon 11 (94.4%), and p.Arg544Cys was the most common mutation. The mean age at diagnosis was 61.0±12.8 years. The most common presenting symptoms were ischemic stroke (24.4%), followed by cognitive impairment(15.0%), headache (8.9%), and dizziness(8.0%). Although the exact prevalence of CADASIL in Jeju is still unknown, the disease prevalence could be as high as 1% of the population considering the prevalence reported in Taiwan. Therefore, it is necessary to discover efficient biomarkers and genetic tests that can accurately screen and diagnose patients suspected of having CADASIL in this region. Ultimately, it is urgent to explore the exact pathogenesis of the disease to identify leading substances of treatment potential, and for this, multi-disciplinary research through active support from the Jeju provincial government as well as the national government is essential.

• The Korea Journal of Herbology
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• v.36 no.2
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• pp.31-42
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• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• Journal of Radiation Protection and Research
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• v.45 no.4
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• pp.163-170
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• 2020

Background: Gut microflora contributes to the nutritional metabolism of the host and to strengthen its immune system. However, if the intestinal barrier function of the living body is destroyed by radiation exposure, the intestinal bacteria harm the health of the host and cause sepsis. Therefore, this study aims to trace short-term radiation-induced changes in the mouse gut microflora-dominant bacterial genus, and analyze the degree of intestinal epithelial damage. Materials and Methods: Mice were irradiated with 0, 2, 4, 8 Gy X-rays, and the gut microflora and intestinal epithelial changes were analyzed 72 hours later. Five representative genera of Actinobacteria, Firmicutes, and Bacteroidetes were analyzed in fecal samples, and the intestine was pathologically analyzed by Hematoxylin-Eosin and Alcian blue staining. In addition, DNA fragmentation was evaluated by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results and Discussion: The small intestine showed shortened villi and reduced number of goblet cells upon 8 Gy irradiation. The large intestine epithelium showed no significant morphological changes, but the number of goblet cells were reduced in a radiation dose-dependent manner. Moreover, the small intestinal epithelium of 8 Gy-irradiated mice showed significant DNA damaged, whereas the large intestine epithelium was damaged in a dose-dependent manner. Overall, the large intestine epithelium showed less recovery potential upon radiation exposure than the small intestinal epithelium. Analysis of the intestinal flora revealed fluctuations in lactic acid bacteria excretion after irradiation regardless of the morphological changes of intestinal epithelium. Altogether, it became clear that radiation exposure could cause an immediate change of their excretion. Conclusion: This study revealed changes in the intestinal epithelium and intestinal microbiota that may pave the way for the identification of novel biomarkers of radiation-induced gastrointestinal disorders and develop new therapeutic strategies to treat patients with acute radiation syndrome.

• Journal of IKEEE
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• v.26 no.3
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• pp.494-499
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• 2022

It is reported that genome-wide RNA-seq profiles has potential as biomarkers of aging. A number of researches achieved promising prediction performance based on gene expression profiles. We develop an age prediction method based on the transcriptome of human dermal fibroblasts by selecting a proper age interval. The proposed method executes multiple rules in a sequential manner and a rule utilizes a classifier and a regression model to determine whether a given test sample belongs to the target age interval of the rule. If a given test sample satisfies the selection condition of a rule, age is predicted from the associated target age interval. Our method predicts age to a mean absolute error of 5.7 years. Our method outperforms prior best performance of mean absolute error of 7.7 years achieved by an ensemble based prediction method. We observe that it is possible to predict age based on genome-wide RNA-seq profiles but prediction performance is not stable but varying with age.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.744-753
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• 2021

Background: Gintonin-enriched fraction (GEF) is a new non-saponin component glycolipoprotein isolated from ginseng root. This study examined the effect of GEF on age-related sarcopenia in old C57BL/6J mice. Methods: Young (3-6 months) and old (20-24 months) C57BL/6J mice received oral GEF (50 mg/kg/day or 150 mg/kg/day) daily for 5 weeks. During the oral administration period, body weight and grip strength were measured weekly. After sacrifice, muscles from the hindlimb were excised and used for hematoxylin and eosin staining and western blotting to determine the effects of GEF on sarcopenia. The thymus was photographed to compare size, and flow cytometry was performed to examine the effect of GEF on immune homeostasis in the thymus and spleen. Blood samples were collected, and the concentrations of pro-inflammatory cytokines and IGF-1 were measured. Results: GEF caused a significant increase in muscle strength, mass, and fiber size in old mice. GEF restored age-related disruption of immune homeostasis by maintaining T cell compartments and regulating inflammatory biomarkers. Thus, GEF reduced common low-grade chronic inflammatory parameters, which are the main cause of muscle loss. Conclusion: GEF maintained immune homeostasis and inhibited markers of chronic inflammation, resulting in anti-sarcopenia effects in aged C57BL/6J mice. Thus, GEF is a potential therapeutic agent that slows sarcopenia in the elderly.

• Genomics & Informatics
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• v.20 no.3
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• pp.27.1-27.13
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• 2022

Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.

• Animal Bioscience
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• v.36 no.1
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• pp.53-62
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• 2023

Objective: In this study, metabolites that changed in the rumen fluid, urine and feces of dairy cows fed different feed ratios were investigated. Methods: Eight Holstein cows were used in this study. Rumen fluid, urine, and feces were collected from the normal concentrate diet (NCD) (Italian ryegrass 80%: concentrate 20% in the total feed) and high concentrate diet (HCD) groups (20%: 80%) of dairy cows. Metabolite analysis was performed using proton nuclear magnetic resonance (NMR) identification, and statistical analysis was performed using Chenomx NMR software 8.4 and Metaboanalyst 4.0. Results: The two groups of rumen fluid and urine samples were separated, and samples from the same group were aggregated together. On the other hand, the feces samples were not separated and showed similar tendencies between the two groups. In total, 160, 177, and 188 metabolites were identified in the rumen fluid, urine, and feces, respectively. The differential metabolites with low and high concentrations were 15 and 49, 14 and 16, and 2 and 2 in the rumen fluid, urine, and feces samples, in the NCD group. Conclusion: As HCD is related to rumen microbial changes, research on different metabolites such as glucuronate, acetylsalicylate, histidine, and O-Acetylcarnitine, which are related to bacterial degradation and metabolism, will need to be carried out in future studies along with microbial analysis. In urine, the identified metabolites, such as gallate, syringate, and vanillate can provide insight into microbial, metabolic, and feed parameters that cause changes depending on the feed rate. Additionally, it is thought that they can be used as potential biomarkers for further research on subacute ruminal acidosis.