• Title/Summary/Keyword: Preclinical research

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Emerging Co-signaling Networks in T Cell Immune Regulation

  • Jung, Keunok;Choi, Inhak
    • IMMUNE NETWORK
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    • v.13 no.5
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    • pp.184-193
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    • 2013
  • Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

Physiological approach of CADASIL animal model and its predictable implication (CADASIL 동물모델의 생리학적 접근 및 연구적 가치의 예측)

  • Jung, Sung-Cherl;Ko, Eun-A
    • Journal of Medicine and Life Science
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    • v.16 no.3
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    • pp.55-59
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    • 2019
  • Cerebral vessels are functionally and structurally specialized to provide adequate blood flow to brain which shows high metabolic rates. Cerebral hemorrhage or ischemic infarction due to cerebrovascular injury or occlusion can cause the immediate brain damage, and if not treated rapidly, can lead to serious or permanent brain damages, and sometimes life-threatening. Unlike these popular cerebrovascular diseases, there are diseases caused by genetic problems. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of them. CADASIL does not show the high incidence, but it is considered to be significantly affected by regional obstructiveness such as islands and therefore, to be an important genetic disease in Jeju. This paper aims to summarize the possibility of animal model research that can provide preclinical data for CADASIL disease research and to evaluate its applicability in future research plans.

The Pharmacological Properties of Silymarin and Its Constituents

  • Antika, Lucia Dwi;Dewi, Rita Marleta
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.68-77
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    • 2021
  • Silymarin is a standardized extract obtained from the seeds and fruits of Silybum marianum L., or commonly called milk thistle, a member of Carduus marianum family that contains mix of flavonolignans. Some epidemiological and preclinical studies revealed that S. marianum L. has been used for herbal remedies for centuries for its pharmacological activity. In this review, pharmacological studies in vitro and in vivo of silymarin are discussed thoroughly stressing on antioxidant, antimicrobial, antiviral, and anti-carcinogenic aspects of silymarin. In addition, the protective influences of silymarin on some organs such as heart, liver, bone, and neuron tissue are reviewed as well. This review would be useful for further study regarding the potential of natural plant, notably silymarin, and its therapeutic potential in the prevention and treatment of diseases.

New in vitro multiple cardiac ion channel screening system for preclinical Torsades de Pointes risk prediction under the Comprehensive in vitro Proarrhythmia Assay concepta

  • Jin Ryeol An;Seo-Yeong Mun;In Kyo Jung;Kwan Soo Kim;Chan Hyeok Kwon;Sun Ok Choi;Won Sun Park
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.267-275
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    • 2023
  • Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of IKr and INa currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of IKr and ICa currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of ICa currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

Genotoxicity and Interference with Cell Cycle Activities by an Ethanolic Extract from Thai Plumbago indica Roots in Human Lymphocytes in vitro

  • Thitiorul, Sumon;Ratanavalachai, Treetip;Tanuchit, Sermkiat;Itharat, Arunporn;Sakpakdeejaroen, Intouch
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2487-2490
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    • 2013
  • In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.

The Effects of Preclinical Objective Structured Clininal Examination(OSCE) on Knowledge, Nursing Students Confidence in Core Fundamental Nursing Skills and Self-Efficacy (임상실습 전 객관화된 구조화 임상수행평가(OSCE)가 간호대학생의 지식, 핵심기본간호술 자신감 및 자기효능감에 미치는 효과)

  • Son, Yu-Lim;Park, Pil-Nam;Ko, Soon-Hee
    • Journal of Korean Clinical Health Science
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    • v.5 no.2
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    • pp.850-863
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    • 2017
  • Purpose. The purpose of this study was to investigate effects of preclinical OSCE(Objective Structured Clinical Evaluation) on knowledge, confidence in their Core fundamental nursing skills and self-efficacy in nursing students. Method. The research design was a one group pretest-posttest design and it was done to assess changes in knowledge, confidence in core fundamental nursing skills and self-efficacy from pre to the post-test which was given after the OSCE. Data were collected from March 5 to April 7, 2016 from 37 nursing students who were taking the 15-hours using OSCE learning module at one Gyeongbuk-do, P-city. This practicum was composed of 4 core fundamental nursing skills and 5 other fundamental nursing skills. The knowledge consisted of a 10-item by researchers and the confidence of core fundamental nursing skills consisted of an 9-item NRS and the self-efficacy consisted of a 17-item 5-point scale and measured in both the pretest and posttest. The collected data were analyzed with SPSS IBM 20.0 program for the frequency, percentage, x2-test, and paired t-test. Rusult. The results showed that although scores of knowledge of OSCE learning module were significanlty increased from 5.22 to 7.03(t=5.30, p<.001). There were significantly increased in scores of confidence in core fundamental nursing skills from 5.13 to 7.27(t=10.01, p<.001), In the sub-scales of each core fundamental nursing skills was scored the highest. otherwise, there was no significant difference in self-efficacy(t=1.42, p=.161). Conclusions. Based on the results, this study suggests that OSCE module development activities for nursing students in nursing education-learning in order to improve nursing skills.

Application of Optimized Gompertz Algorithm for Estimation of Controlled Drug Release (Gompertz modeling을 이용한 약물유출 예측시스템의 최적화)

  • Choe, Se-Woon;Woo, Young Woon
    • Journal of the Korea Society of Computer and Information
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    • v.19 no.12
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    • pp.219-225
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    • 2014
  • A Gompertz modeling, sigmoid in shape, is a widely used application for social science, natural science, engineering, and medical research to allow confident approximation and accurate analysis and has been applied to estimate an elderly population on aging of population. Due to the high toxicity of currently available drug delivery vehicles, various efforts have been made to reduce side-effects in clinical fields, but its application to preclinical and clinical studies is limited and there are some difficulties to optimize the parameters of Gompertz modeling applicable to preclinical studies. Therefore, in this study, we demonstrated the ability of sickle red blood cells loaded by hypotonic dialysis then photosensitized and light-activated ex vivo for controlled release and simultaneously optimized Gompertz function to evaluate controlled drug release properties of photosensitized sickle red blood cells to reduce pain-related treatments in cancer patients.

A Study on the attitudes toward Research and Development of herbal products (제약업계의 한약제제 연구개발 현황 및 허가에 대한 인식도 조사 연구)

  • Shin, Hyeun-Kyoo;Kim, Yun-Kyung;Kang, Chang-Hee;Choi, Sun-Mi
    • Korean Journal of Oriental Medicine
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    • v.7 no.1
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    • pp.77-84
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    • 2001
  • A survey was conducted to investigate the attitudes of pharmaceutical companies toward the status and permission of R & D of herbal products. The survey's results showed that some of them(42.9%) was conducting the R&D, and others(57.1%) were not conducting. As the results of analysis on the reason of R&D conducting, some of them(42.3%) answered that R&D of herbal products is more effective and powerful than these of synthetic products. And 23.1% answered that the cost of R&D is low and the time required is short. And another 23.1% answered that it has marketability and competitive power. As the results of analysis on the marketability of herbal products in Pharmaceutical Market, most of them(78.6%) answered that it seems enough. As the result of the comparison of synthetic drug and herbal products, the proportion of R&D investment on herbal products was lower than synthetic products in the preclinical study, the first clinical study and the second clinical study, and higher than in the third clinical study and the NDA. And the periods of R&D was long in most procedure except synthesis of new materials. As the results of analysis on the recognition of related regulation, most of them(73%) was yes. And 35.2% of the subjects thinks it enough.

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Suggestions for Potentially Useful Herbal Medicines for Treating Insomnia in COVID-19 Era: A Mini-Review

  • Suh, Hyo-Weon;Kwon, Chan-Young;Kim, Jong Woo
    • Journal of Oriental Neuropsychiatry
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    • v.32 no.2
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    • pp.95-109
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    • 2021
  • Objectives: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Mental sequelae occurring in patients with COVID-19 and the general population are important concerns. In Korea, herbal medicine is used nationwide to respond to this pandemic. It can be prescribed by COVID-19 telemedicine center of Korean medicine (KM). Among some herbal medicines, Gamiguibi-tang is the only herbal medicine prescribed for individuals with mental health, especially for those with insomnia. In this mini-review, the objective of this study was to summarize the evidence of some promising herbal medicines available for treating primary insomnia based on existing clinical and preclinical studies. Methods: A research team was formed for KM clinical practice guidelines for insomnia (version 1.0). Team members were provided with a list of references of relevant herbal medicines for insomnia. To gather evidence from clinical studies with appropriate sample sizes, among the list of references, randomized controlled trials for primary insomnia that included 50 subjects or more per arm and used herbal medicine were included in the final analysis. Moreover, pre-clinical studies examining the mechanism of action of each herbal medicine and studies on herb-drug interactions, were searched and summarized. Results: Four herbal medicines (Ondam-tang, Sanjoin-tang, Guibi-tang, and Hyeolbuchugeo-tang) were reviewed based on existing clinical and preclinical studies. Based on findings of existing studies, some suggestions of herbal medicines for insomnia in the COVID-19 era in Korea were suggested. Conclusions: Data of this study could be used to prepare a future revision of the manual of COVID-19 telemedicine center of KM.

Therapeutic Potential of Active Components from Acorus gramineus and Acorus tatarinowii in Neurological Disorders and Their Application in Korean Medicine

  • Cheol Ju Kim;Tae Young Kwak;Min Hyeok Bae;Hwa Kyoung Shin;Byung Tae Choi
    • Journal of Pharmacopuncture
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    • v.25 no.4
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    • pp.326-343
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    • 2022
  • Neurological disorders represent a substantial healthcare burden worldwide due to population aging. Acorus gramineus Solander (AG) and Acorus tatarinowii Schott (AT), whose major component is asarone, have been shown to be effective in neurological disorders. This review summarized current information from preclinical and clinical studies regarding the effects of extracts and active components of AG and AT (e.g., α-asarone and β-asarone) on neurological disorders and biomedical targets, as well as the mechanisms involved. Databases, including PubMed, Embase, and RISS, were searched using the following keywords: asarone, AG, AT, and neurological disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety, epilepsy, and stroke. Meta-analyses and reviews were excluded. A total of 873 studies were collected. A total of 89 studies were selected after eliminating studies that did not meet the inclusion criteria. Research on neurological disorders widely reported that extracts or active components of AG and AT showed therapeutic efficacy in treating neurological disorders. These components also possessed a wide array of neuroprotective effects, including reduction of pathogenic protein aggregates, antiapoptotic activity, modulation of autophagy, anti-inflammatory and antioxidant activities, regulation of neurotransmitters, activation of neurogenesis, and stimulation of neurotrophic factors. Most of the included studies were preclinical studies that used in vitro and in vivo models, and only a few clinical studies have been performed. Therefore, this review summarizes the current knowledge on AG and AT therapeutic effects as a basis for further clinical studies, and clinical trials are required before these findings can be applied to human neurological disorders.