• Title/Summary/Keyword: First-in-human dose

검색결과 161건 처리시간 0.032초

Etiological and pathophysiological enigmas of severe coronavirus disease 2019, multisystem inflammatory syndrome in children, and Kawasaki disease

  • Rhim, Jung-Woo;Kang, Jin-Han;Lee, Kyung-Yil
    • Clinical and Experimental Pediatrics
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    • 제65권4호
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    • pp.153-166
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    • 2022
  • During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host's immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study's findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.

Millettia erythrocalyx 에탄올 추출물의 항산화 활성 및 항암 활성에 관한 연구 (Antioxidative and Anticancer Activities of Ethanol Extract of Millettia erythrocalyx)

  • 진수정;오유나;손유리;최선미;권현주;김병우
    • 생명과학회지
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    • 제28권1호
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    • pp.50-57
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    • 2018
  • Millettia erythrocalyx는 콩과(Fabaceae)에 속하는 식물로 중국, 태국, 인도 등 열대 아열대 지역에 분포하며, 항바이러스 활성을 보유하고 있다는 보고가 있으나 항산화능과 항암활성 등에 관한 연구는 보고된 바가 없다. 따라서 본 연구에서는 M. erythrocalyx의 에탄올 추출물(EEME)을 사용하여 항산화능을 측정하고, 인체간암세포주인 HepG2에 대한 항암활성과 그 분자적 기전에 관하여 분석하였다. 먼저 DPPH radical scavenging activity를 통해 분석한 결과, EEME의 $IC_{50}$$2.74{\mu}g/ml$로 뛰어난 항산화능을 보유하였음을 확인하였다. 또한 EEME 농도 의존적으로 HepG2 세포의 성장을 억제하였다. EEME의 HepG2 세포 사멸 효과의 기전을 분석하기 위하여 세포주기를 분석한 결과, EEME 농도의존적으로 SubG1 세포가 증가하였으며, Annexin V 염색과 DAPI 염색을 통해 apoptotic 세포 및 apoptotic body가 증가됨을 확인하였다. 또한 apoptosis 관련 단백질들의 발현변화를 분석한 결과, EEME 처리에 의해 사멸수용체인 Fas와 pro-apoptotic 단백질인 Bax의 발현이 증가되었으며, caspase-3, -8, -9가 활성화되고 최종적으로 PARP가 분해되어 apoptosis가 유도되었음을 확인하였다. 이러한 결과들로부터 EEME는 내인성 및 외인성 경로를 통한 apoptosis 유도에 의하여 HepG2 세포의 증식을 억제하는 항암활성을 보유하였음을 확인하였다.

TET2MCNP: A Conversion Program to Implement Tetrahedral-mesh Models in MCNP

  • Han, Min Cheol;Yeom, Yeon Soo;Nguyen, Thang Tat;Choi, Chansoo;Lee, Hyun Su;Kim, Chan Hyeong
    • Journal of Radiation Protection and Research
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    • 제41권4호
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    • pp.389-394
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    • 2016
  • Background: Tetrahedral-mesh geometries can be used in the MCNP code, but the MCNP code accepts only the geometry in the Abaqus input file format; hence, the existing tetrahedral-mesh models first need to be converted to the Abacus input file format to be used in the MCNP code. In the present study, we developed a simple but useful computer program, TET2MCNP, for converting TetGen-generated tetrahedral-mesh models to the Abacus input file format. Materials and Methods: TET2MCNP is written in C++ and contains two components: one for converting a TetGen output file to the Abacus input file and the other for the reverse conversion process. The TET2MCP program also produces an MCNP input file. Further, the program provides some MCNP-specific functions: the maximum number of elements (i.e., tetrahedrons) per part can be limited, and the material density of each element can be transferred to the MCNP input file. Results and Discussion: To test the developed program, two tetrahedral-mesh models were generated using TetGen and converted to the Abaqus input file format using TET2MCNP. Subsequently, the converted files were used in the MCNP code to calculate the object- and organ-averaged absorbed dose in the sphere and phantom, respectively. The results show that the converted models provide, within statistical uncertainties, identical dose values to those obtained using the PHITS code, which uses the original tetrahedral-mesh models produced by the TetGen program. The results show that the developed program can successfully convert TetGen tetrahedral-mesh models to Abacus input files. Conclusion: In the present study, we have developed a computer program, TET2MCNP, which can be used to convert TetGen-generated tetrahedral-mesh models to the Abaqus input file format for use in the MCNP code. We believe this program will be used by many MCNP users for implementing complex tetrahedral-mesh models, including computational human phantoms, in the MCNP code.

Echinostoma ilocanum Infection in Two Residents of Savannakhet Province, Lao PDR

  • Chai, Jong-Yil;Sohn, Woon-Mok;Cho, Jaeeun;Eom, Keeseon S.;Yong, Tai-Soon;Min, Duk-Young;Hoang, Eui-Hyug;Phommasack, Bounlay;Insisiengmay, Bounnaloth;Rim, Han-Jong
    • Parasites, Hosts and Diseases
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    • 제56권1호
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    • pp.75-79
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    • 2018
  • Adult specimens of Echinostoma ilocanum (Garrison, 1908) Odhner, 1911 (Trematoda: Echinostomatidae) were recovered from 2 riparian people who resided along the Mekong River in Savannakhet Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, they revealed echinostome eggs together with eggs of Opisthorchis viverrini (and minute intestinal fluke eggs) and hookworms. To recover the adult flukes, they were treated with praziquantel 30-40 mg/kg in a single dose and purged with magnesium salts. A total of 658 adult fluke specimens were recovered from the 2 people; 456 from case 1 and 202 from case 2. Specimens from case 1 consisted of 335 echinostomes (301 E. ilocanum and 34 species undetermined), 120 O. viverrini, and 1 Haplorchis taichui, and those from case 2 consisted of 36 E. ilocanum, 134 O. viverrini, and 32 H. taichui. Thus, the number of E. ilocanum specimens was 337 in total (average per person, 168.5). From this study, it is suggested that foodborne intestinal flukes and liver flukes are highly prevalent along the Mekong River in Savannakhet Province. The present report describes for the first time human infections with E. ilocanum in Lao PDR.

Expression and Characterization of Protein Latcripin-3, an Antioxidant and Antitumor Molecule from Lentinula edodes C91-3

  • Ann, Xiao-Hua;Lun, Yong-Zhi;Zhang, Wei;Liu, Ben;Li, Xing-Yun;Zhong, Min-Tao;Wang, Xiao-Li;Cao, Jing;Ning, An-Hong;Huang, Min
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.5055-5061
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    • 2014
  • In this study, an anti-oxidant and anti-tumor protein Latcripin-3 of Lentinula edodes C91-3 was expressed in Escherichia coli. for the first time. According to the cDNA library, the full-length gene of Latcripin-3 was cloned by the methods of 3'-full rapid amplification of cDNA Ends (RACE) and 5'-full RACE. The structural domain gene of Latcripin-3 was inserted into the pET32 a(+). The functional protein of Latcripin-3 was expressed in Rosetta-gami (DE3) E. coli, evaluated by Western blotting and mass spectrometry. DPPH testing showed that the protein Latcripin-3 can scavenge free radicals remarkably well. The activity of functional protein Latcripin-3 on A549 cells was studied with flow cytometry and the MTT method. The MTT assay results showed that there was a decreases in cell viability in a dose-dependent and time-dependent manner in protein Latcripin-3 treated groups. Flow cytometry demonstrated that Latcripin-3 can induce apoptosis and block S phase dramatically in human A549 lung cancer cells as compared to the control group. At the same time, the cell ultrastructure observed by transmission electron microscopy supported the results of flow cytometry. This research offers new insights and advantages for identifying anti-oxidant and anti-tumor proteins.

감송향물추출물의 HO-1 발현 촉진을 통한 세포보호 작용 및 항염작용 (Cytoprotective and Anti-inflammatory Effects of Nardostachys jatamansi Water Extract Via Expression of HO-1)

  • 박철;정민;서은아;권강범;유도곤
    • 동의생리병리학회지
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    • 제24권4호
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    • pp.624-629
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    • 2010
  • Nardostachys jatamansi water extract (NJ) has long been used for the treatment of inflammation-and immune-mediated disorders in the oriental countries. However, its site of action and pharmacological mechanism are not fully investigated. In this study, the authors tried to explore the cytoprotective and anti-inflammatory actions of NJ. First of all, NJ has no harmful effects on viability of neuronal cell line HT22 cells in the dose range of 300 mg/ml. On the contrary, it shows cytoprotective effects on the cells treated with reactive oxygen species H2O2. Probably the cytoprotective effects of NJ might be caused by its ability to induce well known cytoprotective gene hem oxygenase-1 (HO-1). Furthermore, NJ shows inhibitory effects on the expression of inducible nitric oxide synthase (iNOS) and NO production which are known to destroy the integrity of both cells and tissues. It also inhibits potent proinflammatory cytokine tumor necrosis factor-alpha (TNF-a) production. The blocking effects of NJ on cytopathic and proinflammatory actions of LPS might be caused by the induction of cytoprotective and anti-inflammatory genes HO-1 in macrophages cell line RAW 264.7 cells. The results in this study suggest NJ could be used for the amelioration of inflammation which is underlying mechanism responsible for most chronic diseases.

감초추출물(Glycyrrhiza glabra Extract)의 피부에서의 DNA 손상 방지효과 (Protective Effect of Glycyrrhiza glabra Extract on UV-induced Skin DNA Damage)

  • 신재영;강내규
    • 대한화장품학회지
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    • 제48권1호
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    • pp.33-38
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    • 2022
  • 자외선인 ultraviolet B (UVB)는 피부각질세포의 DNA 잔기에 손상을 준다. 특히, DNA의 pyrimidine 잔기 손상인 cyclobutane pyrimidine dimers (CPD)의 형성은 피부 광노화의 대표적인 지표로 여겨진다. 본 연구에서는 피부 각질세포에서 UVB에 의한 DNA 손상을 완화 시키는 소재로 감초추출물(Glycyrrhiza glabra extract, G. glabra extract)의 효능을 확인하였다. 먼저 피부각질세포에서 UVB 의존적으로 CPD형성이 증가하는 것을 확인하였다. 이후 감초추출물에 의해 UVB 유발 CPD 형성이 유의하게 줄어드는 것을 확인할 수 있었다. 추가로 DNA 손상회복 인자의 mRNA 발현이 감초추출물에 의해 증가하는 것도 확인하였다. 결론적으로 본 연구를 통해 감초추출물의 피부각질세포에서의 DNA 보호 효과를 확인할 수 있었다.

PMSG와 hCG 병용투여에 의해 인공발정 유기된 진도개에서 질상피세포 변화상 (Changes of Vaginal Epithelial Cells in Korea Jin-do Bitches after Induction of Estrus with PMSG and hOG)

  • 이주환;김나리;박인철;오기석;김세라;박상국;문진산;배춘식;김성호
    • 한국임상수의학회지
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    • 제19권4호
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    • pp.418-425
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    • 2002
  • Estrus was induced in 13 anestrus Korea Jin-do bitches by intramuscular injection of pregnant mare serum gonadotropin (PMSG) in a dose of 500 lU once daily for ten consecutive days, followed by an additional single intraveneous injection of 1,000 lU of human chorionic gonadotropin (hCG) on the tenth day. Day-changes of vaginal epithelial cells during the hormone treatment were investigated in each experimental bitches and compared with the those of spontaneous estrus bitches. The first days of vulval bleeding and male acceptance after PMSG treatment were on Day 6.0$\pm$ 1.5 (mean$\pm$ SD) and Day 9.0$\pm$ 1.9, respectively. And in all of 13 bitches, vulval swelling and perineal reflex were shown. The mean durations of proestrus and estrus were 2.9$\pm$ 1.4 (mean$\pm$ SD, range ; 1-6) and 11.5: 1.7 (range ; 8-14) days, respectively, that is, duration of proestrus was significantly shorter than that of the spontneous estrous bitches but duration of estrus was longer than that of the spontaneous estrous bitches. Characteristic features of vaginal cytology during the estrous cycle were the high proportions of large intermediate cell, superficial cell, anuclear cell and erythrocyte in proestrus, superficial cell and anuclear cell in estrus and parabasal cell, small intermediate, large intermediate cell, and leukocyte in diestrus, respectively. The comification index (Cl) was significantly high proportion in proestrus and estrus, when Day 0 was timed from the first day of male acceptance, the Cl was first increased above 80% on Day 0 and maintained above 80% until Day 0 to Day 5 during 6 days and showed a peak on Day 2. Also it was maintained above 90% until Day 2 to Day 3 during 2 days. These results indicated that all 13 ekperimental bitches showed positive estrus detection by the estrus behavior and vaginal smear test after treated with PMSG and hCC. It suggested that vaginal cytology was used to estimate the optimal mating and ovulation time, in consideration of the day when the Cl was maintained above 80% in estrus-induced Korea Jin-do bitches.

Aesculetin의 항산화 활성과 MMP-9 활성 억제를 통한 암세포 침윤 억제 (Aesculetin Inhibits Cell Invasion through Inhibition of MMP-9 Activity and Antioxidant Activity)

  • 홍수경;김문무
    • 생명과학회지
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    • 제26권6호
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    • pp.673-679
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    • 2016
  • 최근에 종양을 예방하거나 치료하기 위하여 안전하고 효과적인 항암화합물의 개발이 절실하게 요구되고 있다. 그 중에서 전통약재로부터 유래된 천연화합물은 항암후보소재로 관심의 대상이 되어왔다. 본 연구에서 사용된 aesculetin은 약용식물로 널리 알려진 산초나무의 주요 성분이다. Aesculetin은 항염증 및 항균과 같은 다양한 생물학적 효과를 가진다고 보고되었다. 그러나 세포침윤과 관련된 효과는 아직 발견되지 않았다. 그러므로 본 연구에서는 사람섬유아육종세포(HT1080)에서 항산화와 기질금속단백질분해효소(MMPs)에 대한 aesculetin의 효과를 조사하였다. 항산화 효과에 대한 연구에서 aesculetin은 DPPH radical에 대한 소거능뿐 만 아니라 환원력이 우수한 것으로 나타났다. 우선, MTT 실험을 이용하여 HT1080세포에서 aesculetin의 2 μM 이하의 농도에서 독성이 없는 것으로 나타났다. MMP-2와 MMP-9의 활성과 단백질 발현 수준에 대한 aesculetin의 억제효과는 gelatin zymography와 western blot을 이용하여 조사되었다. Aesculetin은 세포침윤과 관련된 MMP-9의 활성의 억제효과가 있는 것으로 나타났다. 더욱이, aesculetin은 TIMP-1의 단백질 발현 수준을 증가시켰으나, PMA로 자극된 MMP-9의 단백질 발현 수준을 감소시켰다. 더불어 aesculetin은 농도의존적으로 암전이와 관련된 세포침윤을 현저하게 억제하였다. 위의 결과들을 바탕으로, aesculetin은 세포침윤과 관련된 MMP의 활성과 발현의 억제를 통해 세포침윤을 예방할 수 있는 소재로서 기대된다.

Improved choleretic effect of Benachio-F®-based formula enriched with fennel extracts

  • Cho, Hye Jin;Im, Jun Su;Kwon, Yong Sam;Kang, Kyung Soo;Kim, Tae Min
    • 한국동물생명공학회지
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    • 제37권1호
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    • pp.27-33
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    • 2022
  • Functional dyspepsia (FD) is a gastrointestinal disorder with diverse symptoms but no structural or organic manifestations. Benachio-F® (herein named 'BF-1') is an over-the-counter liquid digestive formulated with multiple herbal extracts, which has been reported to improve symptoms of FD. A total two experiments were conducted. First, we examined whether BF-1 can modulate the progression of FD through two experimental rat models. A total of three doses (0.3x, 1x, 3x of the human equivalent dose) were used. In the gastric emptying model, both 1x (standard) or 3x (3-fold-concentrated) BF-1 enhanced gastric emptying was compared with that of vehicle-treated animals. In a feeding inhibition model induced by acute restraint stress, treatment with 1x or 3x BF-1 led to a similar degree of restoration in food intake that was comparable to that of acotiamide-treated animals. Among the constituents of BF, fennel is known for its choleretic effect. Thus, we next investigated whether a novel BF-based formula (named 'BF-2') that contains an increased amount of fennel extract (3.5-fold over BF-1), has greater potency in increasing bile flow. BF-2 showed a superior choleretic effect compared to BF-1. Furthermore, the postprandial concentration of serum secretin was higher in animals pretreated with BF-2 than in those pretreated with BF-1, suggesting that the increased choleretic effect of BF-2 is related to secretin production. Our results demonstrate that BF-1 can modulate the pathophysiological mechanisms of FD by exerting prokinetic and stress-relieving effects, and that BF-2 has a better choleretic effect than BF-1.