• Title/Summary/Keyword: Preclinical research

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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.

Development of Root Perforation Filling Material using Demineralized Dentin Paste (치아들을 탈회동결건조처리하여 제작한 치근천공부 충전재 개발 I: 예비실험연구)

  • Choi, Yong-Hun;Bae, Ji-Hyun;Park, Ji-Hoon;Kim, Young-Kyun;Yun, Pil-Young;Hwang, Ji-Yeon;Um, In-Woong;Lee, Chong-Heon
    • The Journal of the Korean dental association
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    • v.50 no.9
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    • pp.574-585
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    • 2012
  • Purpose : This study was performed to evaluate the healing response around the root perforation restorative material. Materials and Methods : Four beagle dogs were used for experimental study. Endodontic treatment was performed at four maxillary premolars and artificial perforation was formed at furcation area of pulp chamber. Canal was filled with gutta percha cone and the perforation was sealed with MTA at group 1. At group 2, canal was filled and the perforation was sealed with dentin paste. Tooth paste was fabricated using extracted human teeth. Histologic examination of furcation area was performed 2, 4, 8 and 12 weeks after experiment. Results : New trabecular bone formation was observed around the MTA and tooth paste. Lamellar bone was observed as time is over. There were no inflammatory reaction in both groups. Conclusion : There is a possibility which endodontic filling material can be developed using extracted teeth.

The Role of Nuclear Receptor Subfamily 1 Group H Member 4 (NR1H4) in Colon Cancer Cell Survival through the Regulation of c-Myc Stability

  • Lee, Yun Jeong;Lee, Eun-Young;Choi, Bo Hee;Jang, Hyonchol;Myung, Jae-Kyung;You, Hye Jin
    • Molecules and Cells
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    • v.43 no.5
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    • pp.459-468
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    • 2020
  • Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

Endoscopic Fluorescence Angiography with Indocyanine Green : A Preclinical Study in the Swine

  • Cho, Won-Sang;Kim, Jeong Eun;Kim, Sae Hoon;Kim, Hee Chan;Kang, Uk;Lee, Dae-Sic
    • Journal of Korean Neurosurgical Society
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    • v.58 no.6
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    • pp.513-517
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    • 2015
  • Objective : Microscopic indocyanine green (ICG) angiography is useful for identifying the completeness of aneurysm clipping and the preservation of parent arteries and small perforators. Neuroendoscopy is helpful for visualizing structures beyond the straight line of the microscopic view. We evaluated our prototype of endoscopic ICG fluorescence angiography in swine, which we developed in order to combine the merits of microscopic ICG angiography and endoscopy. Methods : Our endoscopic ICG system consists of a camera, a light source, a display and software. This system can simultaneously display real-time visible and near infrared fluorescence imaging on the same monitor. A commercially available endoscope was used, which was 4 mm in diameter and had an angle of $30^{\circ}$. A male crossbred swine was used. Results : Under general anesthesia, a small craniotomy was performed and the brain surface of the swine was exposed. ICG was injected via the ear vein with a bolus dose of 0.3 mg/kg. Visible and ICG fluorescence images of cortical vessels were simultaneously observed on the display monitor at high resolution. The real-time merging of the visible and fluorescent images corresponded well. Conclusion : Simultaneous visible color and ICG fluorescent imaging of the cortical vessels in the swine brain was satisfactory. Technical improvement and clinical implication are expected.

Restoration of Calvarial Defect Using a Variety of Xenogenous Tooth Bone Graft Material: Animal Study (다양한 이종치아 골이식재를 이용한 두개골 결손부 수복: 동물 연구)

  • Kim, Young-Kyun;Kim, Jong-Hwa;Hwang, Ji-Yeon;Um, In-Woong;Jeong, Dongjun;Yun, Pil-Young
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.34 no.5
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    • pp.299-310
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    • 2012
  • Purpose: The purpose of this study was to evaluate the histological healing process of 3 different types of xenogenic tooth bone graft material and xenogenic bone graft material. Methods: Three types of human tooth bone graft material (chips, crowns, and roots) and BioOss (Geistlich Pharma AG, Wolhausen, Switzerland) was filled at the preformed 4 round-shaped calvarial bone defects of beagle dogs. The beagles were sacrificed at 2, 4, 8, and 12 weeks, respectively, for radiological and histological evaluation. Results: Increased strength and radiopacity were detected in all graft material groups in time-dependent manner. New bone was formed and matured surrounding the graft material histologically. Also, a new bone was directly integrated with graft material. Conclusion: It was expected that newly developed tooth bone graft material would show good bone healing capacity if it was used as a graft material for the restoration of bony defect.

Immunosignature: Serum Antibody Profiling for Cancer Diagnostics

  • Chapoval, Andrei I;Legutki, J Bart;Stafford, Philip;Trebukhov, Andrey V;Johnston, Stephen A;Shoikhet, Yakov N;Lazarev, Alexander F
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4833-4837
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    • 2015
  • Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

Model Systems in Radiation Biology: Implication for Preclinical Study of Radiotherapy (방사선 생물학을 위한 모델 시스템: 방사선치료의 전임상 연구)

  • Kim, Wanyeon;Seong, Ki Moon;Yang, Hee Jung;Youn, HyeSook;Youn, BuHyun
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1558-1570
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    • 2012
  • In radiation biology, analysis of various mechanisms in response to radiation has been accomplished with the use of model organisms. These model organisms are powerful tools for providing a biologically intact in vivo environment to assess physiological and pathophysiological processes affected by radiation. Accumulated data using these models have been applied to human clinical studies (including the evaluation of radiotherapeutic efficacy) and discovery of radiotherapy reagents. However, there are few studies to provide overall integrated information about these useful model organisms. Thus, this review summarizes the results of radiation biology studies using four well-known model organisms: yeast, Caenorhabditis elegans, Drosophila melanogaster, and mice.

Evaluation and Genome Mining of Bacillus stercoris Isolate B.PNR1 as Potential Agent for Fusarium Wilt Control and Growth Promotion of Tomato

  • Rattana Pengproh;Thanwanit Thanyasiriwat;Kusavadee Sangdee;Juthaporn Saengprajak;Praphat Kawicha;Aphidech Sangdee
    • The Plant Pathology Journal
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    • v.39 no.5
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    • pp.430-448
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    • 2023
  • Recently, strategies for controlling Fusarium oxysporum f. sp. lycopersici (Fol), the causal agent of Fusarium wilt of tomato, focus on using effective biocontrol agents. In this study, an analysis of the biocontrol and plant growth promoting (PGP) attributes of 11 isolates of loamy soil Bacillus spp. has been conducted. Among them, the isolates B.PNR1 and B.PNR2 inhibited the mycelial growth of Fol by inducing abnormal fungal cell wall structures and cell wall collapse. Moreover, broad-spectrum activity against four other plant pathogenic fungi, F. oxysporum f. sp. cubense race 1 (Foc), Sclerotium rolfsii, Colletotrichum musae, and C. gloeosporioides were noted for these isolates. These two Bacillus isolates produced indole acetic acid, phosphate solubilization enzymes, and amylolytic and cellulolytic enzymes. In the pot experiment, the culture filtrate from B.PNR1 showed greater inhibition of the fungal pathogens and significantly promoted the growth of tomato plants more than those of the other treatments. Isolate B.PNR1, the best biocontrol and PGP, was identified as Bacillus stercoris by its 16S rRNA gene sequence and whole genome sequencing analysis (WGS). The WGS, through genome mining, confirmed that the B.PNR1 genome contained genes/gene cluster of a nonribosomal peptide synthetase/polyketide synthase, such as fengycin, surfactin, bacillaene, subtilosin A, bacilysin, and bacillibactin, which are involved in antagonistic and PGP activities. Therefore, our finding demonstrates the effectiveness of B. stercoris strain B.PNR1 as an antagonist and for plant growth promotion, highlighting the use of this microorganism as a biocontrol agent against the Fusarium wilt pathogen and PGP abilities in tomatoes.

Clinical Review of the Current Status and Utility of Targeted Alpha Therapy (표적 알파 치료의 현황 및 유용성에 대한 임상적 고찰)

  • Sang-Gyu Choi
    • Journal of radiological science and technology
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    • v.46 no.5
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    • pp.379-394
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    • 2023
  • Targeted Alpha Therapy (TAT) is a new method of cancer treatment that protects normal tissues while selectively killing tumor cells using high cytotoxicity and short range of alpha particles, and target alpha therapy is a highly specific and effective cancer treatment strategy, and its potential has been proven through many clinical and experimental studies. This treatment method accurately delivers alpha particles by selecting specific molecules present in cancer tissue, which has an effective destruction and tumor suppression effect on cancer cells, and one of the main advantages of target alpha treatment is the physical properties of alpha particles. Alpha particles have a very high energy and short effective distance, interacting with target molecules in cancer tissues and having a fatal effect on cancer cells, which is known to cause DNA damage and cell death in cancer cells. TAT has shown positive results in preclinical and clinical studies for various types of cancers, especially those that resist or are unresponsive to existing treatments, but there are several challenges and limitations to overcome for successful clinical transition and application. These include the provision and production of suitable alpha radioisotopes, optimization of target vectors and delivery formulations, understanding and regulation of radiological effects, accurate dosage calculation and toxicity assessment. Future research should focus on developing new or improved isotopes, target vectors, transfer formulations, radiobiological models, combination strategies, imaging techniques, etc. for TAT. In addition, TAT has the potential to improve the quality of life and survival of cancer patients due to the possibility of a new treatment for overcoming cancer, and to this end, prospective research on more carcinomas and more diverse patient groups is needed.

Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice

  • Jun-Man Hong;Jin-Hee Kim;Gwang-Hoon Kim;Hyun-Mu Shin;Young-il Hwang
    • International Journal of Stem Cells
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    • v.15 no.3
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    • pp.291-300
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    • 2022
  • Background and Objectives: Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail. Methods and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton's jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG1 and IgG2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220+ GL7+) and memory T cells (CD62L+ CD44+) both in CD4+ and CD8+ subsets. Similar results were obtained for C57BL/6 mice. Conclusions: hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.