• Title/Summary/Keyword: preclinical study

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Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice

  • Jung Ah Kim;Sung-Hee Kim;Jeong Jin Kim;Hyuna Noh;Su-bin Lee;Haengdueng Jeong;Jiseon Kim;Donghun Jeon;Jung Seon Seo;Dain On;Suhyeon Yoon;Sang Gyu Lee;Youn Woo Lee;Hui Jeong Jang;In Ho Park;Jooyeon Oh;Sang-Hyuk Seok;Yu Jin Lee;Seung-Min Hong;Se-Hee An;Joon-Yong Bae;Jung-ah Choi;Seo Yeon Kim;Young Been Kim;Ji-Yeon Hwang;Hyo-Jung Lee;Hong Bin Kim;Dae Gwin Jeong;Daesub Song;Manki Song;Man-Seong Park;Kang-Seuk Choi;Jun Won Park;Jun-Won Yun;Jeon-Soo Shin;Ho-Young Lee;Ho-Keun Kwon;Jun-Young Seo;Ki Taek Nam;Heon Yung Gee;Je Kyung Seong
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.7.1-7.19
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    • 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.

High Rate of Gangrenous Adnexal Torsion: Dilemma of a Missing Silent Cancer

  • Sukkong, Kanchanok;Sananpanichkul, Panya;Teerakidpisan, Prasong;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.4981-4984
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    • 2016
  • Background: Adnexal torsion results in ischemia of structures distal to twisted pedicle and acute onset of pain is responsible for about 3% of all gynecologic emergencies. Ovarian torsion classically occurs in a pathological enlarged ovary, as with cancer, but diagnosis remains a challenge. Objective: Our purpose was to evaluate clinical risk factors predictive of torsion with gangrenous adnexa. Material and methods: A retrospective descriptive study and chart review of surgically proven ovarian torsion/adnexal torsion cases at the Obstetrics and Gynecology Department of Prapokklao Hospital, Chanthaburi, Thailand between January 2011 and December 2015 was conducted. Result: Seventy-eight cases were identified. Mean age at presentation was 35.5 years. The average maximum diameter of the ovarian tumors was 10.8 cm. The percentage of gangrenous ovarian cysts in this study was 46.2 (36/78). The precision to determine the pathological site by patient, physician and ultrasonography was 8.5, 24.2 and 83.3 percent, respectively with statistically significant variation. Conclusion: Ovarian/adnexal torsion remains a challenge condition especially in young nulliparous women. Sophisticated investigation does not guarantee ovary preservation. Combining clinical acumen, appropriate tests and detailed consideration may be the best practice at the present time.

In Vivo Non Invasive Molecular Imaging for Immune Cell Tracking in Small Animals

  • Youn, Hyewon;Hong, Kee-Jong
    • IMMUNE NETWORK
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    • v.12 no.6
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    • pp.223-229
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    • 2012
  • Clinical and preclinical in vivo immune cell imaging approaches have been used to study immune cell proliferation, apoptosis and interaction at the microscopic (intra-vital imaging) and macroscopic (whole-body imaging) level by use of ex vivo or in vivo labeling method. A series of imaging techniques ranging from non-radiation based techniques such as optical imaging, MRI, and ultrasound to radiation based CT/nuclear imaging can be used for in vivo immune cell tracking. These imaging modalities highlight the intrinsic behavior of different immune cell populations in physiological context. Fluorescent, radioactive or paramagnetic probes can be used in direct labeling protocols to monitor the specific cell population. Reporter genes can also be used for genetic, indirect labeling protocols to track the fate of a given cell subpopulation in vivo. In this review, we summarized several methods dealing with dendritic cell, macrophage, and T lymphocyte specifically labeled for different macroscopic whole-body imaging techniques both for the study of their physiological function and in the context of immunotherapy to exploit imaging-derived information and immune-based treatments.

LC-MS/MS Assay Validation for a New Immune Modulator, JHL45, and its Major Metabolite in Plasma: Application to Pharmacokinetic Studies in Rats

  • Baek, In-Hwan;Chae, Jung-Woo;Song, Gyu-Yong;Kwon, Kwang-Il
    • Bulletin of the Korean Chemical Society
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    • v.30 no.11
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    • pp.2631-2636
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    • 2009
  • JHL45, a novel immune modulator for anti-atopic dermatitis and allergic airway disease, was synthesized from decursin isolated from Angelica gigas. In order to conduct a pharmacokinetic study of JHL45, an analytical method, ideally one that uses a minimal amount of biological sample must first be validated. In this study, a HPLC-MS/MS method was developed and validated for the quantification of JHL45 and its major metabolite, (+)-decursinol, from 10 ${\mu}L$ of rat plasma. JHL45 was stable under the analysis conditions, and intra- and inter-day accuracies exceeded 90.06%, with a precision variability ${\leq}$ 13.16% for each analyte. The mean values for Cmax, AUC8h, half-life of JHL45 in rats after intravenous administration of 5 mg/kg JHL45 were 24.59 μg/mL, 10.02 ${\mu}g{\cdot}h/mL$, and 1.88 h, respectively. The validated method herein will be useful for further pharmacokinetic studies of JHL45, as well as in preclinical and clinical phases.

Teratogenicity Study of SKI 2053R, a New Platinum Anticancer Agent, in Rabbits (새로운 백금착물 항암제 SKI 2053R의 토끼 최기형성시험)

  • 김종춘;김갑호;박종일;김형진;정문구
    • Biomolecules & Therapeutics
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    • v.7 no.3
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    • pp.292-299
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    • 1999
  • SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.

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Real-time monitoring of ultra-high dose rate electron beams using bremsstrahlung photons

  • Hyun Kim;Dong Hyeok Jeong;Sang Koo Kang;Manwoo Lee;Heuijin Lim;Sang Jin Lee;Kyoung Won Jang
    • Nuclear Engineering and Technology
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    • v.55 no.9
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    • pp.3417-3422
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    • 2023
  • Recently, as the clinically positive biological effects of ultra-high dose rate (UHDR) radiation beams have been revealed, interest in flash radiation therapy has increased. Generally, FLASH preclinical experiments are performed using UHDR electron beams generated by linear accelerators. Real-time monitoring of UHDR beams is required to deliver the correct dose to a sample. However, it is difficult to use typical transmission-type ionization chambers for primary beam monitoring because there is no suitable electrometer capable of reading high pulsed currents, and collection efficiency is drastically reduced in pulsed radiation beams with ultra-high doses. In this study, a monitoring method using bremsstrahlung photons generated by irradiation devices and a water phantom was proposed. Charges collected in an ionization chamber located at the back of a water phantom were analyzed using the bremsstrahlung tail on electron depth dose curves obtained using radiochromic films. The dose conversion factor for converting a monitored charge into a delivered dose was determined analytically for the Advanced Markus® chamber and compared with experimentally determined values. It is anticipated that the method proposed in this study can be useful for monitoring sample doses in UHDR electron beam irradiation.

The biomechanical and biological effect of supercooling on cortical bone allograft

  • MuYoung Kim ;Hun-Young Yoon
    • Journal of Veterinary Science
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    • v.24 no.6
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    • pp.79.1-79.16
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    • 2023
  • Background: The need for a storage method capable of preserving the intrinsic properties of bones without using toxic substances has always been raised. Supercooling is a relatively recently introduced preservation method that meets this need. Supercooling refers to the phenomenon of liquid in which the temperature drops below its freezing point without solidifying or crystallizing. Objectives: The purpose of this study was to identify the preservation efficiency and applicability of the supercooling technique as a cortical bone allograft storage modality. Methods: The biomechanical effects of various storage methods, including deep freezing, cryopreservation, lyophilization, glycerol preservation, and supercooling, were evaluated with the three-point banding test, axial compression test, and electron microscopy. Additionally, cortical bone allografts were applied to the radial bone defect in New Zealand White rabbits to determine the biological effects. The degree of bone union was assessed with postoperative clinical signs, radiography, micro-computed tomography, and biomechanical analysis. Results: The biomechanical properties of cortical bone grafts preserved using glycerol and supercooling method were found to be comparable to those of normal bone while also significantly stronger than deep-frozen, cryopreserved, and lyophilized bone grafts. Preclinical research performed in rabbit radial defect models revealed that supercooled and glycerol-preserved bone allografts exhibited significantly better bone union than other groups. Conclusions: Considering the biomechanical and biological superiority, the supercooling technique could be one of the optimal preservation methods for cortical bone allografts. This study will form the basis for a novel application of supercooling as a bone material preservation technique.

Development of a multi-modal imaging system for single-gamma and fluorescence fusion images

  • Young Been Han;Seong Jong Hong;Ho-Young Lee;Seong Hyun Song
    • Nuclear Engineering and Technology
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    • v.55 no.10
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    • pp.3844-3853
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    • 2023
  • Although radiation and chemotherapy methods for cancer therapy have advanced significantly, surgical resection is still recommended for most cancers. Therefore, intraoperative imaging studies have emerged as a surgical tool for identifying tumor margins. Intraoperative imaging has been examined using conventional imaging devices, such as optical near-infrared probes, gamma probes, and ultrasound devices. However, each modality has its limitations, such as depth penetration and spatial resolution. To overcome these limitations, hybrid imaging modalities and tracer studies are being developed. In a previous study, a multi-modal laparoscope with silicon photo-multiplier (SiPM)-based gamma detection acquired a 1 s interval gamma image. However, improvements in the near-infrared fluorophore (NIRF) signal intensity and gamma image central defects are needed to further evaluate the usefulness of multi-modal systems. In this study, an attempt was made to change the NIRF image acquisition method and the SiPM-based gamma detector to improve the source detection ability and reduce the image acquisition time. The performance of the multi-modal system using a complementary metal oxide semiconductor and modified SiPM gamma detector was evaluated in a phantom test. In future studies, a multi-modal system will be further optimized for pilot preclinical studies.

Effect of Acupuncture on Sciatica in Rat Models: Systematic Review and Meta-analysis (좌골신경통 백서모델에서 침치료의 효과: 체계적 문헌고찰 및 메타분석)

  • Yoon, Ye-Ji;Kim, Soojeon;Cho, Jae-Heung;Kim, Koh-Woon;Song, Mi-Yeon
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.1
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    • pp.79-93
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    • 2020
  • Objectives While sciatic neuropathy is one of the common symptoms which have the lifetime incidence of 13~40%, still there is no consensus about the standardized and the most effective conservative treatment. In addition, the importance of systematic review and meta-analysis of preclinical are growing as they could suggest possible effective treatment strategy for future studies. Therefore, we conducted systematic review and meta-analysis to estimate analgesic effect of acupuncture on sciatica in rat models. Methods Systematic search was conducted for all controlled comparative preclinical trials which assessed analgesic effect of acupuncture in sciatica rat models. Database of PubMed, EMBASE, Web of Science, CNKI and 6 Korean databases were used. The primary outcome was pain, which is evaluated by stimulus behavior tests in rat models. We assessed the methodological quality with Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool. RevMan 5.3 was used for meta-analysis and subgroup analysis was conducted according to treatment site, acupuncture point, treatment period and frequency used in electroacupuncture. Results 14 studies were finally included following our inclusion criteria. The data from meta-analysis indicated that the acupuncture significantly improved the result values of behavior tests for pain evaluation, compared to no-treatment control group in animal models (standardized mean difference=4.43, 95% confidence interval 3.16 to 5.69, Z=6.84, p<0.00001; χ2=68.02, p<0.00001; I2=82%). The results of subgroup analysis indicate that acupuncture treatment of unilateral site, distal acupoints, longer treatment period and applying 2/100 Hz frequency in electroacupuncture could be more effective. Conclusions Systematic review and meta-analysis of animal studies are getting important for the future clinical studies and the improvement of heatlh care. Therefore the results of the study would provide evidence and better design for the forthcoming studies.

A Study on Development of Wrinkle Evaluation Software and Verification of Skin Wrinkle Improvement of Cog Suture (주름 평가 소프트웨어 개발과 Cog형 봉합사의 피부 주름 개선 검증에 관한 연구)

  • Jeong, Jin-Hyoung;Lee, Sang-Sik
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.12 no.4
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    • pp.336-342
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    • 2019
  • With the entry of an aging society, the average life span of accreditation has been extended. Therefore, interest in the appearance of men and women in modern society has increased. It is the wrinkles of the face that can judge the most outwardly. People tend to have various kinds of treatments to have a clean, wrinkle-free and resilient healthy skin regardless of sex. There is a lot of practice of lifting procedures in one of the procedures. A suture using a melting thread is a method of lifting by squeezing it into the skin as a non-incision type centering on a region where the thread can be fixed in the skin by injecting it into the subcutaneous fat layer. To evaluate the lifting efficacy of Cog - type suture for the improvement of skin wrinkles, preclinical experiments were conducted. We developed a wrinkle evaluation program using Labview. Data from preclinical experiments were used at 8 weeks after suturing. The average wrinkle depth was 415.6 mm in the control group. At 8 weeks, the depth of wrinkles was deepened to 888.3mm due to the aging process of the control group. On the other hand, the depth of the wrinkles before surgery was 640.3 mm in the suture group. It was confirmed that the depth of wrinkles decreased to 566.5mm at 8th week after the suture operation.