• Title/Summary/Keyword: Preclinical research

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Discovery of New Proteinase Inhibitor for the Treatment of Osteoporosis

  • 손문호
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.04a
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    • pp.89-99
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    • 2001
  • ■ Cathepsin K is a attractive target for selectively and efficiently modulating the osteoclastic bone resorption. ■ OST-1857 is a lead compound which is specifically targeted to cathepsin K and showed efficacy in TPTX rats. ■ OST-compounds are in process of the preclinical study, joined by Yuhan research center.

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The G115 standardized ginseng extract: an example for safety, efficacy, and quality of an herbal medicine

  • Bilia, Anna R.;Bergonzi, Maria C.
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.179-193
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    • 2020
  • Ginseng products on the market show high variability in their composition and overall quality. This becomes a challenge for both consumers and health-care professionals who are in search of high-quality, reliable ginseng products that have a proven safety and efficacy profile. The botanical extract standardization is of crucial importance in this context as it determines the reproducibility of the quality of the product that is essential for the evaluation of effectiveness and safety. This review focuses on the well-characterized and standardized ginseng extract, G115, which represents an excellent example of an herbal drug preparation with constant safety and efficacy within the herbal medicinal products. Over the many decades, extensive preclinical and clinical research has been conducted to evaluate the efficacy and safety of G115. In vitro and in vivo studies of G115 have shown pharmacological effects on physical performance, cognitive function, metabolism, and the immune system. Furthermore, a significant number of G115 clinical studies, most of them double-blind placebo-controlled, have reinforced the findings of preclinical evidence and proved the efficacy of this extract on blood glucose and lipid regulation, chronic obstructive pulmonary disease, energy, physical performance, and immune and cognitive functions. Clinical trials and 50 years of presence on the market are proof of a good safety profile of G115.

Establishment of a [18F]-FDG-PET/MRI Imaging Protocol for Gastric Cancer PDX as a Preclinical Research Tool

  • Bae, Seong-Woo;Berlth, Felix;Jeong, Kyoung-Yun;Suh, Yun-Suhk;Kong, Seong-Ho;Lee, Hyuk-Joon;Kim, Woo Ho;Chung, June-Key;Yang, Han-Kwang
    • Journal of Gastric Cancer
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    • v.20 no.1
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    • pp.60-71
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    • 2020
  • Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([18F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [18F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [18F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [18F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

Generation of Neural Progenitor Cells from Pig Embryonic Germ Cells

  • Choi, Kwang-Hwan;Lee, Dong-Kyung;Oh, Jong-Nam;Kim, Seung-Hun;Lee, Mingyun;Jeong, Jinsol;Choe, Gyung Cheol;Lee, Chang-Kyu
    • Journal of Animal Reproduction and Biotechnology
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    • v.35 no.1
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    • pp.42-49
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    • 2020
  • As a preclinical study, many researchers have been attempted to convert the porcine PSCs into several differentiated cells with transplantation of the differentiated cells into the pigs. Here, we attempted to derive neuronal progenitor cells from pig embryonic germ cells (EGCs). As a result, neuronal progenitor cells could be derived directly from pig embryonic germ cells through the serum-free floating culture of EB-like aggregates (SFEB) method. Treating retinoic acid was more efficient for inducing neuronal lineages from EGCs rather than inhibiting SMAD signaling. The differentiated cells expressed neuronal markers such as PAX6, NESTIN, and SOX1 as determined by qRT-PCR and immunostaining. These data indicated that pig EGCs could provide valid models for human therapy. Finally, it is suggested that developing transgenic pig for disease models as well as differentiation methods will provide basic preclinical data for human regenerative medicine and lead to the success of stem cell therapy.

A study on a present condition of research on the experimental model in oriental medicine (실험동물의 병증(病證) 모형에 대한 연구현황 소고 - 중의(中醫) 자료를 중심으로 -)

  • Choi, Sun-Mi
    • Korean Journal of Oriental Medicine
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    • v.1 no.1
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    • pp.69-99
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    • 1995
  • In order to develop experimental research in oriental medicine, it is necessary to make experimental model of diagnostic pattern(證), On model of the condition of a disease maked in china, there are cold-pattern(寒證), heat-pattern(熱證), deficiency of vital energy-pattern(氣虛證), blood-deficiency-pattern(血虛證), yin-deficiency-pattern(陰虛證), yang-deficiency-pattern(陽虛證), deficiency of both yin and yang-pattern(陰陽俱虛證), yang-exhaustion-pattern(亡陽證), blood stasis-pattern(血瘀證), pattern of defferential diagnosis according to states of viscera(臟腑辨證).

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2-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats (1,4-Dichlorobutane의 랫드 2주 반복경구투여독성시험)

  • Kim, Jong-Kyu;Lee, In-Chul;Kim, Sung-Hwan;Baek, Hyung-Seon;Bae, Jin-Sook;Song, Si-Whan;Kim, Jong-Choon;Chung, Yong-Hyun
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.23 no.1
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    • pp.1-10
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    • 2013
  • Objectives: The present study investigated the potential subacute toxicity of 1,4-dichlorobutane (1,4-DCB) by a 2-week repeated oral dose in male Sprague-Dawley rats. Materials and Methods: The test chemical was administered once daily by gavage to male rats at dose levels of 0, 74, 222, 667, and 2000 mg/kg/day for 2 weeks. All rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food and water consumption, urinalysis, hematology, serum biochemistry, gross findings, and organ weights were examined. Results: At 2000 mg/kg/day, treatment-related clinical signs, as evidenced by hypothermia, decreased locomotor activity, piloerection, lying on side, and prone position were observed. All the rats were found dead on test day 2. At 667 mg/kg/day, polyuria, suppressed body weight gain, food consumption, and spleen and thymus weights, and increased adrenal gland and liver weights were observed.Hematological and serum biochemical investigations revealed increases in the alanine aminotransferase, alkaline phosphataseand total bilirubinand decreases in the serum $Na^+$ level, white blood cell count and lymphocyte ratio. There were no treatment-related adverse effects in the 74 and 222 mg/kg/day groups. Conclusions: In the present experimental conditions, target organs were determined to be spleen, thymus,and liver. The no-observed-adverse-effect level was considered to be 222 mg/kg/day in male rats.

Muscimol as a treatment for nerve injury-related neuropathic pain: a systematic review and meta-analysis of preclinical studies

  • Hamzah Adel Ramawad;Parsa Paridari;Sajjad Jabermoradi;Pantea Gharin;Amirmohammad Toloui;Saeed Safari;Mahmoud Yousefifard
    • The Korean Journal of Pain
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    • v.36 no.4
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    • pp.425-440
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    • 2023
  • Background: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain. Methods: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, 2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source. Results: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; P < 0.0001; I2 = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; P < 0.0001; I2 = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; P < 0.0001; I2 = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia (P < 0 .0001). Conclusions: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.

Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

  • Husain, Aliabbas A.;Daginawala, Hatim F.;Warke, Shubangi R.;Kalorey, Devanand R.;Kurkure, Nitin V.;Purohit, Hemant J.;Taori, Girdhar M.;Kashyap, Rajpal S.
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.83-90
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    • 2015
  • Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study

  • Sadighi, Sanambar;Amanpour, Saeid;Behrouzi, Bita;Khorgami, Zhinoos;Muhammadnejad, Samad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2287-2290
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    • 2014
  • Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

Validity and Reliability of a Clinical Performance Examination using Standardized Patients (호흡기계 표준화 환자를 이용한 간호대 학생의 임상수행능력평가 타당도와 신뢰도 검증)

  • Choi, Ja-Yun;Jang, Keum-Seong;Choi, Soon-Hee;Hong, Mi-Soon
    • Journal of Korean Academy of Nursing
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    • v.38 no.1
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    • pp.83-91
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    • 2008
  • Purpose: The purpose of this study was to test the validity of a modified clinical performance examination (CPX) for preclinical students in nursing. Method: 70 nursing students in their second semester of the junior year at C University participated in CPX. Scenarios and checklists were developed by our research team from September to October 2005. Six stations were organized. Evaluation included physical examination of a patient with lung cancer, education on usage of a metered dosage inhaler, and lobectomy postoperative care. Students were randomly assigned to a station. Result: There was a difference in the CPX scores according to stations. The agreement of scoring between trained faculty members and SPs was more than moderate (r=.647). The correlation between the CPX score and the average grade in the previous semester and between the CPX score and the average grade of a paper and pen test of the pulmonary system of adults was low (r=.276; r=.048). Conclusion: Traditional CPX is generally recommended, however, modified CPX is appropriate for preclinical students in the current Korean Nursing school setting if there are additional scoring systems to balance the testing level at each station.