• Herbal Formula Science
• /
• 제31권3호
• /
• pp.145-156
• /
• 2023

Objectives : This study aimed to select candidate herbal medicines to be used in preclinical studies of cerebral infarction using the network pharmacology research method. Methods : Oral bioavailability (OB), drug likeness (DL), Caco-2, and blood-brain barrier (BBB) permeability were employed in this study's network pharmacology analysis method to choose compounds with potential efficacy. The following formulas were utilized for the values of each variable used in this study: OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3. The relationships between target proteins and diseases that are assumed to be involved in the chosen bioavailable chemicals were built in a network manner using the aforementioned factors, and proteins thought to play a significant role were identified. Results : Sudan III was obtained as a result of selecting compounds related to ischemic stroke in consideration of pharmacokinetic characteristics such as digestion and absorption and practicality using the TCMSP database. Medicinal herbs Gardeniae Fructus (GF) contains sudan III, and it was confirmed that compounds in GF were highly related to brain diseases, and the mechanism involved through the KEGG pathway was confirmed. GF, which has sudan III related to ischemic stroke and is also involved in other neurological diseases, is expected to be used for ischemic stroke treatment. Conclusions : GF has been predicted to have potential for ischemic stroke treatment, and can be used for future preclinical studies.

• Clinical and Experimental Reproductive Medicine
• /
• 제27권1호
• /
• pp.47-57
• /
• 2000

Objective: The effects of cryopreservation with or without coculture on the in vitro development of blastomere-biopsied 8-cell mouse embryos were investigated. This experimental study was originally designed for the setup of a preclinical mouse model for the preimplantation genetic diagnosis (PGD) in human. Methods: Eight-cell embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BL(표현불가)/CBA(표현불가)). Using micromanipulation, one to four blastomeres were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acid Tyrode's solution (ATS). A slow-freezing and rapid-thawing protocol with 1.5M dimethyl sulfoxide (DMSO) and 0.1M sucrose as cryoprotectant was used for the cryopreservation of blastomere- biopsied 8-cell mouse embryos. After thawing, embryos were cultured for 110 hours in Ham's F-10 supplemented with 0.4% bovine serum albumin (BSA). In the coculture group, embryos were cultured for 110 hours on the monolayer of Vero cells in the same medium. The blastocyst formation was recorded, and the embryos developed beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. Results: The survival rate of embryos after cryopreservation was significantly lower in the blastomere-biopsied (7/8, 6/8, 5/8, and 4/8 embryos) groups than in the non-biopsied, zona intact (ZI) group. Without the coculture, the blastocyst formation rate of embryos after cryopreservation was not significantly different among ZI, the zona drilling only (ZD), and the balstomere-biopsied groups, but it was significantly lower than in the non-cryopreserved control group. The mean number of cells in embryos beyond blastocyst stage was significantly higher in the control group ($50.2{\pm}14.0$) than in 6/8 ($26.5{\pm}6.2$), 5/8 ($25.0{\pm}5.5$), and 4/8 ($17.8{\pm}7.8$) groups. With the coculture using Vero cells, the blastocyst formation rate of embryos after cryopreservation was significantly lower in 5/8 and 4/8 groups, compared with the control, 7/8, and 6/8 groups. The mean number of cells in embryos beyond blastocyst stage was also significantly lower in 4/8 group ($25.9{\pm}10.2$), compared with the control ($50.2{\pm}14.0$), 7/8 ($56.0{\pm}22.2$), and 6/8 ($55.3{\pm}25.5$) groups. Conclusion: After cryopreservation, blastomere-biopsied mouse embryos have a significantly impaired developmental competence in vitro, but this detrimental effect might be prevented by the coculture with Vero cells in 8-cell mouse embryos biopsied one or two blastomeres. Biopsy of mouse embryos after ZD with ATS is a safe and highly efficient preclinical model for PGD of human embryos.

• Toxicological Research
• /
• 제22권2호
• /
• pp.153-156
• /
• 2006

The acute toxicity of STB-HO-BM was evaluated in Sprague Dawley (SS) rats and beagle dogs. STB-HO-BM was administered orally to rats at dose levels of 0 and 2,000mg/kg/day and to dogs at dose levels of 0, 500, 1,000 and 2,000 mg/kg/day. In these experiments, there were no death and clinical changes which were related to STB-HO-BM administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of STB-HO-BM 2,000 mg/kg in SD rats and up to 2,000mg/kg in beagle dogs was proved to be safe, and it is thought that STB-HO-BM may not show any toxicity in its clinical use.

• Toxicological Research
• /
• 제22권2호
• /
• pp.135-144
• /
• 2006

This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.

• Toxicological Research
• /
• 제17권
• /
• pp.193-196
• /
• 2001

Issuance of certification and licensing for toxicologists authorized by the Japanese Society of Thxicology (JST) became effective on July 24, 1997. The certification system consists of examination, eligibility requirements for the applicants, authorization/license by the board of trustees of JST, and the re-certification of previously authorized qualification. In the last 2-3 years, about 30-40% of candidates for the examination have succeeded. The Committee has estimated that the level of the examination would be sufficient to determine qualified toxicologists. This updated status and a detailed explanation are to be presented at the workshop. In global terms, the JST special committee agrees that "harmonization of certification/registration procedure for qualified toxicologists means to ensure/set the minimum requirement for the global authorization of qualified toxicologists". The following items in global authorization are ad-dressed for further discussion: (1) What's the benefit\ulcorner (2) Toxicological safety assessment standards, and (3) the JST position for authorization.orization.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
• /
• 한국식품영양과학회 2003년도 정기총회 및 54차 학술발표회:건강기능식품의 유효성평가
• /
• pp.74-77
• /
• 2003

A new health paradigm may be evolving that would place emphasis on the positive aspects of diet, identifying components that are physiologically active and that contribute to the prevention of disease onset. It has been increasingly difficult to evaluate the impact of new bioactive materials and food products on the well being of society. Thus, testing systems for both health function and toxicity have become very elaborate, complex, and interrelated, making their interpretation difficult and open to controversy. To select the proper starting materials, to screen the appropriate health functionality and to determine the efficacy of product, a reliable, reproducible, sensitive and predictive assay is required. Particularly, in uitro assay is the first stage in preclinical test on physiologically active materials and have many advantages in terms of time, cost and convenience. However, several factors as well as some limitations should be considered in this assay system. This presentation, therefore, will address the use of in uitro assays for evaluating physiological functionality of foods coupled with general consideration.

• Journal of Animal Reproduction and Biotechnology
• /
• 제36권4호
• /
• pp.175-182
• /
• 2021

Pluripotent stem cells could self-renew and differentiate into various cells. In particular, porcine pluripotent stem cells are useful for preclinical therapy, transgenic animals, and agricultural usage. These stem cells have naïve and primed pluripotent states. Naïve pluripotent stem cells represented by mouse embryonic stem cells form chimeras after blastocyst injection. Primed pluripotent stem cells represented by mouse epiblast stem cells and human embryonic stem cells. They could not produce chimeras after blastocyst injection. Populations of embryonic stem cells are not homogenous; therefore, reporter systems are used to clarify the status of stem cells and to isolate the cells. For this reason, studies of the OCT4 reporter system have been conducted for decades. This review will discuss the naïve and primed pluripotent states and recent progress in the development of porcine OCT4 reporter systems.

• Molecules and Cells
• /
• 제45권12호
• /
• pp.896-910
• /
• 2022

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.

• IMMUNE NETWORK
• /
• 제24권2호
• /
• pp.7.1-7.19
• /
• 2024

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10⁵ plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10² PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10² PFU-virus-infected lungs from 2 dpi, but not in 1×10⁵ PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10⁵ PFU; however, 1×1² PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

• Journal of Periodontal and Implant Science
• /
• 제52권4호
• /
• pp.338-350
• /
• 2022

Purpose: Various studies have investigated 3-dimensional (3D)-printed implants using Ti6Al-4V powder; however, multi-root 3D-printed implants have not been fully investigated. The purpose of this study was to explore the stability of multirooted 3D-printed implants with lattice and solid structures. The secondary outcomes were comparisons between the 2 types of 3D-printed implants in micro-computed tomographic and histological analyses. Methods: Lattice- and solid-type 3D-printed implants for the left and right mandibular third premolars in beagle dogs were fabricated. Four implants in each group were placed immediately following tooth extraction. Implant stability measurement and periapical X-rays were performed every 2 weeks for 12 weeks. Peri-implant bone volume/tissue volume (BV/TV) and bone mineral density (BMD) were measured by micro-computed tomography. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were measured in histomorphometric analyses. Results: All 4 lattice-type 3D-printed implants survived. Three solid-type 3D-printed implants were removed before the planned sacrifice date due to implant mobility. A slight, gradual increase in implant stability values from implant surgery to 4 weeks after surgery was observed in the lattice-type 3D-printed implants. The marginal bone change of the surviving solid-type 3D-printed implant was approximately 5 mm, whereas the value was approximately 2 mm in the lattice-type 3D-printed implants. BV/TV and BMD in the lattice type 3D-printed implants were similar to those in the surviving solid-type implant. However, BIC and BAFO were lower in the surviving solid-type 3D-printed implant than in the lattice-type 3D-printed implants. Conclusions: Within the limits of this preclinical study, 3D-printed implants of double-rooted teeth showed high primary stability. However, 3D-printed implants with interlocking structures such as lattices might provide high secondary stability and successful osseointegration.