• Title/Summary/Keyword: Preclinical

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Network Pharmacological Analysis of Cnidii Fructus Treatment for Gastritis (벌사상자의 위염 치료 적용에 대한 네트워크 약리학적 분석)

  • Young-Sik Kim;Seungho Lee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.38 no.1
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    • pp.22-26
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    • 2024
  • The purpose of this study was to identify the applicability, main compounds, and target genes of Cnidii Fructus (CF) in the treatment of gastritis using network pharmacology. The compounds in CF were searched in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC). The target gene information of the compounds was collected from pubchem and cross-compared with the gastritis-related target gene information collected from Genecard to derive the target genes. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the derived target genes. Afterwards, network analysis between compounds and disease target genes was performed using cytoscape. We identified 121 active compounds and 139 target genes associated with gastritis. Pathways derived from the GO biological process and KEGG pathway DB primarily focus on target genes related to inflammation (IL-6, IL-8, TNF production, NF-κB transcription factor activity, and NF-κB signaling pathway) and cell death (PI3K-Akt, FoxO). Major targets for CF treatment of gastritis include TP53, TNF, BCL2, EGFR, NFKB1, ABCB1, PPARG, PTGS2, IL6, IL1B, and SOD1, along with major compounds such as coumarin, osthol, hexadecanoic acid, oleic acid, linoleic acid, and stigmasterol. This study provided CF's applicability for gastritis, related compounds, and target information. Evaluating CF's effectiveness in a preclinical gastritis model suggests its potential use in clinical practice for digestive system diseases.

Preclinical Study on Biodistribution of Mesenchymal Stem Cells after Local Transplantation into the Brain

  • Narayan Bashyal;Min Gyeong Kim;Jin-Hwa Jung;Rakshya Acharya;Young Jun Lee;Woo Sup Hwang;Jung-Mi Choi;Da-Young Chang;Sung-Soo Kim;Haeyoung Suh-Kim
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.415-424
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    • 2023
  • Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

Nursing Students' Clinical Competence and Decision-Making: Impact of a Multiple-components Practice-based Learning (간호학생의 임상수행능력과 임상의사결정: 다중요소 실습기반교육의 효과)

  • Xianqi Gao;Yoonjeong Lee;Moonkyoung Park
    • Journal of Industrial Convergence
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    • v.22 no.3
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    • pp.79-89
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    • 2024
  • This study is a one-group pre-post experimental design that investigates the effects of a practice-based learning program with multiple components on the clinical competence of nursing students, and clinical decision-making. From May 4 to 29, 2020, a total of 60 third-year nursing students with no clinical practice experience were divided into two teams and participated in multi-component practice-based education for two weeks each, and the data of the final 51 students were included in the analysis. Following the practicum, there was a significant increase in clinical competence (t=-4.74, p<.001) and self-confidence in clinical decision-making (t=-8.41, p<.001), and a decrease in anxiety related to clinical decision-making (t=2.54, p=.014). The findings suggest that a multi-component, practice-based learning approach for nursing students can enhance their clinical competence, reduce preclincal anxiety and increase confidence in clinical decision-making in patient care.

Single Oral Dose Toxicity Test of Jeopgoltang Extracts in Sprague-Dawley Rat (접골탕(接骨湯) 2.0의 Sprague-Dawley 랫드를 이용한 단회경구투여 독성시험)

  • YoungJin Choi;HyoJung Kim;Se-Jin Kim;JunSub Kim;Jiwoon Jeong;HyunHee Leem;BoGyung Jang;YuJin Park;Jungtae Leem;Gi-Sang Bae;Bitna Kweon;Dong-Uk Kim
    • The Korea Journal of Herbology
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    • v.39 no.2
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    • pp.19-25
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    • 2024
  • Objectives : Jeopgoltang (JGT) is a new Korean herbal medicine formulation that is used to treat bone fractures. Although JGT is frequently used in clinical practice, there is a lack of scientific evidence on its safety. This study aimed to evaluate the preclinical toxicity of JGT using a single oral dose toxicity test in Sprague-Dawley (SD) rats. Methods : Five male and female rats per group were orally administered 1,250, 2,500, or 5,000 mg/kg of JGT after fasting for 12 h. Mortality and changes in clinical signs, body weight, and necropsy findings were monitored for 14 days according to the guidelines of the Korean Ministry of Food and Drug Safety and Organisation for Economic Co-operation and Development (OECD). Results : No significant clinical signs or mortality were observed after a single administration of up to 5,000 mg/kg. In addition, no significant necropsy findings related to JGT administration were observed. Conclusions: In conclusion, these results suggest that approximate Lethal Dose (ALD) of JGT on SD rats is over 5,000 mg/kg.

Effect of polydeoxyribonucleotide with xenogeneic collagen matrix on gingival phenotype modification: a pilot preclinical study

  • Hyun-Chang Lim;Chang-Hoon Kim;Han-Kyu Lee;Gyewon Jeon;Yeek Herr;Jong-Hyuk Chung
    • Journal of Periodontal and Implant Science
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    • v.53 no.6
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    • pp.417-428
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    • 2023
  • Purpose: To investigate the effect of xenogeneic collagen matrix (XCM) with polydeoxyribonucleotide (PDRN) for gingival phenotype modification compared to autogenous connective tissue graft. Methods: Five mongrel dogs were used in this study. Box-type gingival defects were surgically created bilaterally on the maxillary canines 8 weeks before gingival augmentation. A coronally positioned flap was performed with either a subepithelial connective tissue graft (SCTG) or XCM with PDRN (2.0 mg/mL). The animals were sacrificed after 12 weeks. Intraoral scanning was performed for soft tissue analysis, and histologic and histomorphometric analyses were performed. Results: One animal exhibited wound dehiscence, leaving 4 for analysis. Superimposition of STL files revealed no significant difference in the amount of gingival thickness increase (ranging from 0.69±0.25 mm to 0.80±0.31 mm in group SCTG and from 0.48±0.25 mm to 0.85±0.44 mm in group PDRN; P>0.05). Histomorphometric analysis showed no significant differences between the groups in supracrestal gingival tissue height, keratinized tissue height, tissue thickness, and rete peg density (P>0.05). Conclusions: XCM soaked with PDRN yielded comparable gingival augmentation to SCTG.

Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

Acute Kidney Injury Models: Focus on the Therapeutic Effects of Stem Cell in Preclinical Approach (줄기세포 연구를 위한 급성신장손상 모델)

  • Nam, Hyun-Suk;Woo, Jae-Seok;Woo, Heung-Myong
    • Journal of Veterinary Clinics
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    • v.27 no.5
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    • pp.533-539
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    • 2010
  • Stem cell-based therapy is under intensive investigation to treat acute renal failure (ARF). The purpose of this study was to evaluate available ARF models, and suggest a model appropriate to therapeutic evaluation of the stem cells in preclinical approach by determining the optimum concentration of nephrotoxic agents and duration of ischemia induction. Three different types of available acute kidney injury (AKI) animal models were analyzed using rats: Cisplatin (saline, 5 and 7.5 mg/kg, IP) or glycerol (saline, 8 and 10 ml/kg, IM)-induced nephrotoxicity as toxic models and ischemia-induced (sham, 35 and 45 minutes) nephropathy as an ischemic model. The relevance and applicability to investigate especially the regenerative ability of stem cells were evaluated regarding morphology, renal function and survival at this time point. In the point of renal function, 10 ml glycerol/kg and 7.5 mg cisplatin/kg model in toxic models and 45 min model in ischemia models showed significant decrease for the longer observation time compared to 8 ml glycerol/kg, 5 mg cisplatin/kg and the 35 min ischemia models, respectively. All groups were observed no mortality except 45 min-ischemia model with 50% survival. Histological significant alterations including cast formation in the tubular lumen, tubular necrosis and apoptosis were revealed on the second day in either ischemiaor glycerol-induced models, and on day 5 in cisplatin-induced models. The results indicate that ischemia 35 min-, cisplatin 7.5 mg/kg- and glycerol 10 ml/kg-induced AKI would be ideal animal models to monitor a outcome parameter related to the therapeutic effects on renal function with noninvasive techniques in the same animal at multiple time points. Our findings also suggest that the best time points for the functional or histological interpretation of renal will be on day 2 in both glycerol- and ischemia-induced AKI models and on day 5 in cisplatin-induced AKI.

Protective Effect of Saengshik Supplementation on Lead Induced Toxicity in Rats (생식의 섭취가 납중독 흰쥐의 피해 경감에 미치는 영향에 관한 연구)

  • Oh, Young-Joo;Kim, Jae-Min;Song, Si-Wan;Ha, Hyo-Cheol;Kim, Hyun-Su
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.7
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    • pp.959-967
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    • 2005
  • Lead is a ubiquitous environmental and industrial pollutant that causes a major health concerns. It is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory and humans, including hematopoietic system, kidneys, liver, and reproductive system. This study was conducted to investigate the effect of Saengshik supplementation on the lead-induced toxicity in rats. Five week old male Sprague­Dawley rats were randomly assigned to five groups for six weeks as followings: control group (CT), lead acetate treated group (PT), and lead acetate groups administered with three different dosages of Saengshik $(SI2.5-12.5\%,\;S25-25\%,\;and\;S50-50\%).$ Lead acetate (12 mg/rat) was intragastrically administered daily for 6 weeks. The results were summarized as follows; Weight gain and food efficiency ratio were significantly lower (p<0.05) in lead administered group compared with those of the control group. Also, significant lead-induced alteration in blood hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and reticulocyte distribution width (RDW) were observed. In the liver of lead-exposed animals, there was an increase in the lipid peroxidation (MDA) and the level of glutathione (GSH), but superoxiede dismutase (SOD) activity did not change. Lead-exposed animals with $25\%\;and\;50\%$ Saengshik supplementation showed marked improvements in the values of MCH, MCV, and RDW. Also, the level of HCT was significantly increased by $50\%$ Saengshik supplementation. The levels of liver MDA in $12.5\%\;and\;50\%$ Saengshik administered groups and GSH level in $50\%$ Saengshik administered group were significantly decreased compared to the lead administered group. Also, hepatic SOD activity tended to increase in the presence of Saengshik supplementation. Furthermore, the accumulation of lead in liver and kidney was reduced by presence of Saneghshik supplementation. Liver lead concentration was significantly reduced by both $25\%\;and\;50\%$ Saengshik supplementations and kidney lead concentration was significantly reduced by the $25\%$ Saengshik supplementation. These results show that Saengshik may have a protective effect against lead intoxication but the mechanism of their effects remains unclear.

Small Animal PET Imaging Study of 68Ga-BAPEN (68Ga-BAPEN 소동물 PET영상 연구)

  • Kim, Ji-Who;Lee, Jae-Sung;Yang, Bo-Yeun;Kim, Su-Jin;Kim, Joong-Hyun;Jeong, Jae-Min;Lee, Dong-Soo
    • Progress in Medical Physics
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    • v.22 no.4
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    • pp.172-177
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    • 2011
  • The purpose of this study was to analyze $^{68}Ga$-BAPEN dynamic PET image in rat myocardium to evaluate potential of this radiotracer as a perfusion imaging agent. Animal PET/CT scan was done in 9 rats during 120 minutes. Especially we synthesized $^{68}Ga$-BAPEN with kit which is simple and low cost method. PET images showed the in vivo dynamic distribution of $^{68}Ga$-BAPEN in the chest region of rats. Initially $^{68}Ga$-BAPEN PET images showed aorta and liver activities and a few minutes later, $^{68}Ga$-BAPEN moved to myocardium. Regions of interest were drawn on myocardium, liver, lung and blood pool. Time-activity curves showed significant uptake of $^{68}Ga$-BAPEN in myocardium. The contrast ratios of myocardial to blood pool, lung and liver at 60 minutes after injection were 1.66, 2.82 and 0.60. To estimate accurate kinetic parameters, 60 minutes after injection was required to PET scan as myocardium image contrast ratios reached to constant values. As a result, $^{68}Ga$-BAPEN would be suitable radiotracer for PET which can applied to diagnosis of myocardial perfusion diseases after further preclinical and clinical investigations.

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials

  • Kwak, Jin Sook;Kim, Ji Yeon;Paek, Ju Eun;Lee, You Jin;Kim, Haeng-Ran;Park, Dong-Sik;Kwon, Oran
    • Nutrition Research and Practice
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    • v.8 no.6
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    • pp.644-654
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    • 2014
  • BACKGROUND/OBJECTIVES: Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. MATERIALS/METHODS: We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). RESULTS: The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. CONCLUSIONS: This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.