• Journal of Veterinary Science
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• v.24 no.6
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• pp.79.1-79.16
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• 2023

Background: The need for a storage method capable of preserving the intrinsic properties of bones without using toxic substances has always been raised. Supercooling is a relatively recently introduced preservation method that meets this need. Supercooling refers to the phenomenon of liquid in which the temperature drops below its freezing point without solidifying or crystallizing. Objectives: The purpose of this study was to identify the preservation efficiency and applicability of the supercooling technique as a cortical bone allograft storage modality. Methods: The biomechanical effects of various storage methods, including deep freezing, cryopreservation, lyophilization, glycerol preservation, and supercooling, were evaluated with the three-point banding test, axial compression test, and electron microscopy. Additionally, cortical bone allografts were applied to the radial bone defect in New Zealand White rabbits to determine the biological effects. The degree of bone union was assessed with postoperative clinical signs, radiography, micro-computed tomography, and biomechanical analysis. Results: The biomechanical properties of cortical bone grafts preserved using glycerol and supercooling method were found to be comparable to those of normal bone while also significantly stronger than deep-frozen, cryopreserved, and lyophilized bone grafts. Preclinical research performed in rabbit radial defect models revealed that supercooled and glycerol-preserved bone allografts exhibited significantly better bone union than other groups. Conclusions: Considering the biomechanical and biological superiority, the supercooling technique could be one of the optimal preservation methods for cortical bone allografts. This study will form the basis for a novel application of supercooling as a bone material preservation technique.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.2.1-2.22
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• 2022

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.207-243
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• 2016

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.179-187
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• 2011

Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• Journal of Gastric Cancer
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• v.19 no.4
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

• Journal of Periodontal and Implant Science
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• v.52 no.5
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• pp.370-382
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• 2022

Purpose: The aim of this study was to evaluate the preclinical results of 2 types of commercially available deproteinized bovine bone mineral (DBBM) when applied to alveolar bone defects in dogs. Methods: This study was conducted using 6 beagles. Alveolar defects in the mandible were formed and filled with 2 DBBMs produced by a similar procedure. Defects were randomly assigned to be filled using DBBM 1 or 2. All defects were covered with a collagen membrane and had a healing period of 12 weeks. After the dogs were sacrificed, histological, histomorphometric, and linear/volumetric analyses were performed. Results: Both DBBM groups showed similar histological findings, demonstrating that bone remodeling had occurred and new bone had formed. The residual bone particles were surrounded by newly formed vital bone. In the histomorphometric analysis, the ratio of the area of vital bone and residual bone substitute in DBBM 2 (38.18% and 3.47%, respectively) was higher than that of DBBM 1 (33.74% and 3.41%, respectively), although the difference was not statistically significant. There were also no statistically significant differences between both groups in linear and volumetric analyses using micro-computed tomography scans and digitized images of dental casts. Conclusions: In the present study, DBBM 1and 2, which were produced by similar processes, showed similar results in histological, histomorphometric, and volumetric analyses. Further studies are needed to identify more specific differences between the 2 DBBMs.

• Journal of Periodontal and Implant Science
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• v.52 no.4
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• pp.325-337
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• 2022

Purpose: The aim of this study was to investigate the effect of (1) the size of the bony access window and (2) collagen membrane coverage over the window in sinus floor elevation in a rabbit sinus model. Methods: Small bony access windows (SW; ø 2.8 mm) were made in 6 rabbits and large windows (LW; ø 6 mm) in 6 other rabbits. Both sinuses in each rabbit were allocated to groups with or without coverage of a collagen membrane (CM) on the window, resulting in 4 groups: SW, LW, SW+CM, and LW+CM. After 4 weeks of healing, micro-computed tomographic, histologic, and histomorphometric analyses were performed. Results: Bony healing in the window area was incomplete in all groups, but most bone graft particles were well confined in the augmented cavity. Histologically, the pattern of new bone formation was similar in all groups. Histomorphometrically, the percentage of newly formed bone was greater in the groups with CM than in the groups without CM, and in the groups with SW than in the groups with LW (12.92%±6.40% in the SW+CM group, 4.21%±7.73% in the SW group, 10.45%±4.81% in the LW+CM group, 11.77%±3.83% in the LW group). The above differences were not statistically significant (P>0.05). Conclusions: The combination of a small bony access window and the use of a collagen membrane over the window favored new bone formation compared to other groups, but this result should be further investigated due to the limitations of the present animal model.

• 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.