• Korean Journal of Food Science and Technology
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• v.54 no.2
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• pp.155-162
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• 2022

This study investigated the immunostimulatory effect of enzymatic porcine placental hydrolyzate (EPPH) in cyclophosphamide (Cy)-treated rats. This effect of EPPH prevented Cy-induced decreases in body, spleen, and thymus weights and natural killer (NK) cell activity. The numbers of immune cells, such as white blood cells, granulocytes, and lymphocytes, and mid-range absolute counts were significantly higher compared to the control group. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-2, IL-12, and immunoglobulin G (IgG) were notably reduced by Cy, while EPPH prevented these effects. Histopathological analysis of spleen samples revealed the protective effect of EPPH against Cy-induced immunosuppression. The findings demonstrate that EPPH can alleviate immunosuppression by cell viability, tissue damage, and regulation of the levels of cytokines. EPPH may have value as a component of immunostimulatory agents or an ingredient in functional foods.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.628-635
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• 2022

Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4⁺ T-helper cells, CD19⁺ B-cells, and CD4⁺ and CD25⁺ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.423-432
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• 2022

Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORT^TM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.

• Journal of Life Science
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• v.32 no.3
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• pp.196-201
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• 2022

Insects have been proposed as new protein sources for human nutrition, and protein availability is affected by insect characteristics. Fermentation can be used to obtain a variety of insect-based ingredients and products with unique properties, but its effect on protein availability is unknown. Fermented cricket (Gryllus bimaculatus) powder consists mainly of protein, and its oral administration has been reported to improve hair growth in androgenetic alopecia. The purpose of this study was to evaluate the hair-promoting activity of fermented cricket powder in an animal model using male C57BL/6 mice (25-30 g). The abdominal hair of the mouse (2x2.5 cm) was gently removed, and the groups fed as follows: Intact controls (no cricket powder); cricket powder only; and fermented cricket powder only. Food was applied daily for 11 weeks. Observational and physical examinations were performed and the results of the different groups compared. The application of fermented cricket powder significantly (p<0.01) promoted hair growth compared to the intact controls. The C57BL/6 results confirmed increased growth after seven weeks when the proportion of anagen follicles had increased by about 125% and 120% in the control and cricket powder groups, respectively. In conclusion, fermented cricket powder can be seen as a promising alternative alopecia treatment because it promotes hair growth, and, given the powder's composition, trace elements such as amino acids may have contributed to these effects.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• Journal of Periodontal and Implant Science
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• v.54 no.2
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• pp.96-107
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• 2024

Purpose: Deproteinized bovine bone or synthetic hydroxyapatite are 2 prevalent bone grafting materials used in the clinical treatment of peri-implant bone defects. However, the differences in bone formation among these materials remain unclear. This study evaluated osteogenesis kinetics in peri-implant defects using 2 types of deproteinized bovine bone (Bio-Oss^® and Bio-Oss/Collagen^®) and 2 types of synthetic hydroxyapatite (Apaceram-AX^® and Refit^®). We considered factors including newly generated bone volume; bone, osteoid, and material occupancy; and bone-to-implant contact. Methods: A beagle model with a mandibular defect was created by extracting the bilateral mandibular third and fourth premolars. Simultaneously, an implant was inserted into the defect, and the space between the implant and the surrounding bone walls was filled with Bio-Oss, Bio-Oss/Collagen, Apaceram-AX, Refit, or autologous bone. Micro-computed tomography and histological analyses were conducted at 3 and 6 months postoperatively (Refit and autologous bone were not included at the 6-month time point due to their rapid absorption). Results: All materials demonstrated excellent biocompatibility and osteoconductivity. At 3 months, Bio-Oss and Apaceram-AX exhibited significantly greater volumes of formation than the other materials, with Bio-Oss having a marginally higher amount. However, this outcome was reversed at 6 months, with no significant difference between the 2 materials at either time point. Apaceram-AX displayed notably slower bioresorption and the largest quantity of residual material at both time points. In contrast, Refit had significantly greater bioresorption, with complete resorption and rapid maturation involving cortical bone formation at the crest at 3 months, Refit demonstrated the highest mineralized tissue and osteoid occupancy after 3 months, albeit without statistical significance. Conclusions: Overall, the materials demonstrated varying post-implantation behaviors in vivo. Thus, in a clinical setting, both the properties of these materials and the specific conditions of the defects needing reinforcement should be considered to identify the most suitable material.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.2
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• pp.119-129
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• 2024

The cutaneous lymphatic system in humans plays a crucial role in draining interstitial fluid and activating the immune system. Environmental factors, such as ultraviolet light and natural aging, often affect structural changes of such lymphatic vessels, causing skin dysfunction. However, some limitations still exist because of no alternatives to animal testing. To better understand the skin lymphatic system, a biomimetic microfluidic platform, skin-lymph-on-a-chip, was fabricated to develop a novel in vitro skin lymphatic model of humans and to investigate the molecular and physiological changes involved in lymphangiogenesis, the formation of lymphatic vessels. Briefly, the platform involved co-culturing differentiated primary normal human epidermal keratinocytes (NHEKs) and dermal lymphatic endothelial cells (HDLECs) in vitro. Based on our system, Lymphanax^TM, which is a condensed Panax ginseng root extract obtained through thermal conversion for 21 days, was applied to evaluate the lymphangiogenic effect, and the changes in molecular factors were analyzed using a deep-learning-based algorithm. Lymphanax^TM promoted healthy lymphangiogenesis in skin-lymphon-a-chip and indirectly affected HDELCs as its components rarely penetrated differentiated NHEKs in the chip. Overall, this study provides a new perspective on Lymphanax^TM and its effects using an innovative in vitro system.

• Journal of the Korea Society of Computer and Information
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• v.29 no.7
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• pp.33-40
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• 2024

The live weight of livestock is important information for managing their health and housing conditions, and it can be used to determine the optimal amount of feed and the timing of shipment. In general, it takes a lot of human resources and time to weigh livestock using a scale, and it is not easy to measure each stage of growth, which prevents effective breeding methods such as feeding amount control from being applied. In this paper, we aims to improve the accuracy of weight measurement of piglets, weaned pigs, nursery pigs, and fattening pigs by collecting, analyzing, learning, and predicting video and image data in animal husbandry and pig farming. For this purpose, we trained using Pytorch, YOLO(you only look once) 5 model, and Scikit Learn library and found that the actual and prediction graphs showed a similar flow with a of RMSE(root mean square error) 0.4%. and MAPE(mean absolute percentage error) 0.2%. It can be utilized in the mammalian pig, weaning pig, nursery pig, and fattening pig sections. The accuracy is expected to be continuously improved based on variously trained image and video data and actual measured weight data. It is expected that efficient breeding management will be possible by predicting the production of pigs by part through video reading in the future.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.66-77
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• 2023

Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10⁶ cells), renal artery moderate dose (RA-MD) (1.0×10⁶ cells), renal artery high dose (RA-HD) (2.0×10⁶ cells), tail vein low dose (TV-LD) (0.5×10⁶ cells), tail vein moderate dose (TV-MD) (1.0×10⁶ cells), and tail vein high dose (TV-HD) (2.0×10⁶ cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions: Our findings confirm the efficacy and safety of high dose (2×10⁶ cells) injection of hBMSC via the tail vein.