Background: The transplantation of organs between phylogenetically disparate or harmonious species has invariably failed due to the occurrence of hyperacute rejection or accerelated acute rejection. But, concordant cardiac xenograft offer us an opportunity to study xenotransplantation in the absence of hyperacute rejection. Current therapeutics for the prolongation of survival of rodent concordant xenotransplantation are not ideal with many regimens having a high mortality rate. Cyclosporine A & Mycophenolate Mofetil are new immunosuppresive agent which has been shown to be effective at prolonging survival of allograft, as purine synthesis inhibitor. Material and Method: We used white mongrel rats as recipient and mice as donor, divided 4 groups(n=6), control group(Group 1) has no medication or pretreatment, Group 2 has splenectomy as pretreatment 7∼10 days before transplantation, Group 3 has Cyclosporine A treatment group, Group 4 has combined treatment of Cyclosporine A & Mycophenolate Mofetil(RS 61443). We compared survival time. Reuslt: We can't find significant difference of survival time between each groups. Conclusion: We concluded that rejection of cardiac xenograft was different from rejection of allograft, and new immunossuppresive Agent(Mycophenolate Mofetil, Cyclosporine A) was not effective for prolongation of survival time after cardiac xenograft.
The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.
The free radical theory of aging was introduced in 1956 by Denham Harman. This aging theory proposed that normal aging results from random deleterious damage to tissues by free radical and supplying antioxidant lead to decrease oxidative damage, inhibit aging process. In this study, we investigated antioxidantive effects of four Korean constitutional prescriptions for 'Soum' constitution - Palmulgunjatang(Y1), Sipyimiguanjungtang(Y2), Osuyubujayijungtang(Y3) and Seungyangyikkibujatang(Y4). Antioxidative activity of this prescriptions was examined by 1,1-diphenyl-2-picrylhyrdazyl radicals, superoxide anion radicals, peroxyl radical, hydroxyl radical scavenging effects and erythrocyte hemolysis inhibitory effects. Y2 and Y3 were shown to have relatively high antioxidative activity on this methods. In additions, result of the cytoprotective effects of Korean constitutional prescriptions agianst 2,2'-azobis(amidinopropane) dihydrochloride (AAPH), a free radical initiator, induced cytotoxcity in human hepatoblastoma cell line was similarly obtained. On the basis of this result, we assayed the antioxidative effects of Y2 and Y3 on experimental oxidative damage, induced in mouse by 100mg/kg AAPH. Male ICR mouse were given oral administration of 500mg/kg Y2 and Y3 for 4 weeks. Thiobarbuturic acid reactive substance (TBARS) and protein degradation level in liver, plasma and brain as index of oxidative damage were decreased and thiol compound, total antioxidant status in plasma were increased by Y2 administration. But, Y3 injected group was decreased only protein degradation level in brain. Also, glutathione, a potent water-soluble endogenous antioxidant, concentration was increased by Y2 and Y3 administration in liver and brain. However, superoxide dismutase and catalase activity as a major antioxidative enzyme in vivo were not shown change by Y2 and Y3 administration. On the basis of these result, Y2 have an antioxidative effects on both water-soluble fraction and lipid-solube fraction in cell and tissues. But, Y3 has a lower antioxidative effects on lipid-soluble fraction than Y2 in cell and tissues. These results suggest that Y2 has a antioxidative effects by protect the tissue against oxygen free radical mediated oxidative damage and Y3 has a limited antioxidaitve effects on water-soluble fraction in vivo. Therefore, we make report that Y2 is more effective prescriptions for anti-aging or therapeutics of diseases.
Atopic dermatitis (AD) is a common chronic inflammatory disease associated with a cutaneous hypersensitivity reaction to an allergen. Although the incidence of AD is increasing these days, therapeutics has yet to be developed for its treatment. The aim of this study was conducted in order to compare and investigate the characteristic between the Castanea crenata inner shell extract (CS) and the Castanea crenata inner shell extract fermented by Lactobacillus bifermentans (FCS) for an anti-atopic medication. The total polyphenol and flavonoid contents were similar to CS and FCS. In the DPPH and superoxide anion radical scavenging, the CS and FCS had the potential for antioxidant activities. Both of them did not exhibit cytotoxicity to HS68 cells. The evaluation of the anti-inflammatory activity in Raw264.7 cells demonstrated that the FCS has inhibited the LPS-induced production of nitric oxide as compared to the CS. The anti-atopic dermatitis test was done through the induction of DNCB in AD hairless mice. The FCS has inhibited the development of the atopic dermatitis-like skin lesion by transdermal water loss, melanin and erythema of the skin as compared to the CS. Moreover, the pro-inflammatory cytokine IL-$1{\beta}$ and TNF-${\alpha}$ production in hairless mice were inhibited by the FCS treatment. It indicates that the fermentation of the Castanea crenata inner shell has the potential for the treatment of atopic dermatitis.
Kim, Chung-Sook;Ha, Hye-Kyung;Kim, Hye-Jin;Lee, Je-Hyun;Song, Kye-Yong
Korean Journal of Food Science and Technology
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v.34
no.4
/
pp.710-718
/
2002
It is reported that Pueraria Radix contains phtoestrogens whereas flower, and bud of Pueraria lobata Ohwi were not known. In the present study, we determined the amount of phytoestrogen in each portion of P. lobata Ohwi and carried out therapeutic effects of osteoporosis. The amounts of genistein, daidzein, and formononetin in Pueraria Radix (PR), Pueraria Flos (PF), and young Pueratia Folium (PL) were quantitated using a HPLC system. Proliferation of osteoblast and growth inhibitory effect on osteoclast were measured in order to screen their effects on osteoporosis. Proliferation of osteoblast-like cells (Saos-2) was analyzed by both MTT methods and alkaline phosphatase (ALP) assays. Growth inhibitory effect on osteoclast was also detected as Tartrate resistant acid phosphatase (TRAP) assay. Ovariectomized rat as an in vivo animal model was selected and administrations of PR were 1 g/kg/day (PR-1) and 5 g/kg/day (PR-5) for 9 weeks, respectively. Trabecular bone areas (TBAs) of tibia and lumbar were analyzed usibg histomorphological methods. Results show that PR contains the highest level of daidzein ($10435{\pm}2143\;mg/kg$ of dried herb) and stimulated ALP activity, approximately 160% of the control. Growth inhibitory effect on osteoclast by both PR and daidzein were almost identical with control although $IC_{50}$ of genistein was $5.81{\times}10^{-7}$ M. Increases in body weight of OVX rats were suppressed by administration of PR but wet weights of uterus in PR-5 group were increased (p<0.05). Plasma ALP and HDL-cholesterol levels were decreased following ages (p<0.01), and LDL-cholesterol level was also decreased in PR-5 group at 20 week of age (p<0.01). TBAs of tibia and lumbar in PR-1 and PR-5 groups were higher than those of the control although the values were less than those of the sham group (each p<0.01) In conclusion, administrations of PR prevented loss of TBAs of tibia and lumber in OVX rats, while PL and PF did not (p<0.01).
Objectives Lumbar herniated intervertebral disc (L-HIVD) is common disease in which Western-Korean collaborative treatment is performed in Korea. This study aimed to analyze Western-Korean collaborative treatment utilization of Korean patients with L-HIVD using Health Insurance Review & Assessment Service's Patients Sample Data. Methods This study used the Health Insurance Review & Assessment Service-National Patient Sample (HIRA-NPS) in 2018. Claim data of L-HIVD patients were extracted. The claim data were rebuilt with the operational concept of 'episode of care' and divided into Korean medicine episode group (KM), Western medicine episode group (WM) and collaborative treatment episode group (CT). General characteristics, medical expenses and healthcare utilization were analyzed. In addition, the difference of average visit day and average medical expenses between non-collaborative group (KM plus WM) and CT were analyzed by the propensity score matching method. Results A Total of 64,333 patients and 365,745 claims were extracted. The number of episodes of WM, KM and CT was 69,383 (92.97%), 3,903 (5.23%), and 1,341 (1.80%) respectively. The frequency of collaborative treatment episode was higher in women and the age of 50s. The most frequently described treatment in CT was acupuncture therapy. As a result of the propensity score matching, the number of visit days and medical expenses in the collaborative treatment group was higher than in the non-collaborative group. Conclusions The analysis of healthcare utilization of Korean-Western collaborative treatment may be used as basic data for establishing medical policies and systematic collaborative treatment model in the future.
Byeol-Eun, Jeon;Chan-Seong, Kwon;Ji-Eun, Lee;Ye-Lin, Woo;Sang-Woo, Kim
Journal of Life Science
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v.32
no.11
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pp.833-840
/
2022
Chronic inflammation has been shown to be closely associated with tumor development and progression. Nuclear factor kappa B (NF-κB) is composed of a family of five transcription factors. NF-κB signaling plays a crucial role in the inflammatory response and is often found to be dysregulated in various types of cancer, making it an attractive target in cancer therapeutics. In this study, CDC-like kinase 3 (CLK3) was identified as a novel kinase that regulates the NF-κB signaling pathway. Our data demonstrate that CLK3 inhibits the canonical and non-canonical NF-κB pathways. Luciferase assays following the transient or stable expression of CLK3 indicated that this kinase inhibited NF-κB activation mediated by Tumor necrosis factor-alpha (TNFα) and Phorbol 12-myristate 13-acetate (PMA), which are known to activate NF-κB signaling via the canonical pathway. Consistent with data on the ectopic expression of CLK3, CLK3 knockdown using shRNA constructs increased NF-κB activity 1.5-fold upon stimulation with TNFα in HEK293 cells compared with the control cells. Additionally, overexpression of CLK3 suppressed the activation of this signaling pathway induced by NF-κB-inducing kinase (NIK) or CD40, which are well-established activators of the non-canonical pathway. To further examine the negative impact of CLK3 on NF-κB signaling, we performed Western blotting following the TNFα treatment to directly identify the molecular components of the NF-κB pathway that are affected by this kinase. Our results revealed that CLK3 mitigated the phosphorylation/activation of transforming growth factor-α-activated kinase 1 (TAK1), inhibitor of NF-κB kinase alpha/beta (IKKα/α), NF-κB p65 (RelA), NF-κB inhibitor alpha (IκBα), and Extracellular signal-regulated kinase 1/2-Mitogen-activated protein kinase (ERK1/2-MAPK), suggesting that CLK3 inhibits both the NF-κB and MAPK signaling activated by TNFα exposure. Further studies are required to elucidate the mechanism by which CLK3 inhibits the canonical and non-canonical NF-κB pathways. Collectively, these findings reveal CLK3 as a novel negative regulator of NF-κB signaling.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.
Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.
Asia-Pacific Journal of Business Venturing and Entrepreneurship
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v.18
no.2
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pp.35-52
/
2023
Recently, as the non-face-to-face environment has developed due to COVID-19 and environmental pollution, the importance of online digital healthcare is increasing, and venture start-ups and activities such as health care, telemedicine, and digital treatments are also actively underway. This study conducted the impact on the acceptability of digital healthcare smartwatches with an integrated approach of the expanded integrated technology acceptance model (UTAUT2) and the behavioral inference model (BRT). The most advanced integrated technology acceptance model for innovative technology acceptance research was used to identify major factors such as utility expectations, social effects, convenience, price barriers, lack of alternatives, and behavioral intentions. For the study, about 410 responses from ordinary people in their teens to 60s across the country were collected, and based on this, the hypothesis was verified using structural equations after testing reliability and validity of the data. SPSS 23 and AMOS 23 were used for research analysis. Studies have shown that personal innovation has a significant impact on the reasons for acceptance (use value, social impact, convenience of use), attitude, and non-use (price barriers, lack of alternatives, and barriers to use). These results are the same as the results of previous studies that confirmed the influence of the main value of innovative ICT on user acceptance intention. In addition, the reason for acceptance had a significant effect on attitude, but the effect of the reason for non-acceptance was not significant. It can be analyzed that consumers are interested in new ICT products and new services, but purchase them more carefully and selectively. This study has evolved from the acceptance analysis of general-purpose consumer innovation technology to the acceptance analysis of consumer value in smartwatch digital healthcare, which is a new and important area in the future. Industrially, it can contribute to the product's purchase and marketing. It is hoped that this study will contribute to increasing research in the digital healthcare sector, which will play an important role in our lives in the future, and that it will develop into in-depth factors that are more suitable for consumer value through integrated approach models and integrated analysis of consumer acceptance and non-acceptance.
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