• Molecules and Cells
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• v.44 no.12
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• pp.861-878
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• 2021

The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

• The Korea Journal of Herbology
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• v.32 no.3
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• pp.79-87
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• 2017

Objectives : This study aimed to investigate the protective effects of an herbal mixture of Atractylodes macrocephala and Taraxacum spp. (ATC) on ulcerative colitis. We have previously screened traditional medicinal herbs to discover the effective candidate by the animal model. A. macrocephala and T. spp were identified as one of the effective herbs in the screening process. Methods : Experimental colitis was induced in male Balb/c mice by administering drinking water containing dextran sulfate sodium, which mimics the clinical and histological features of ulcerative colitis in human. ATC at doses of 30, 100 or 300 mg/kg were orally administered to mice twice per day for 10 consecutive days. To evaluate the damage from experimentla ulcerative colitis, body weight, colon length, disease activity index, myeloperoxidase and histological changes were measured and analyzed. Results : The administration of dextran sulfate sodium with drinking water resulted in markedly reduced colon length, severe body weight loss, increased levels of myeloperoxidase activity and histological damages in mice. ATC treatment significantly ameliorated the colon shortening, histological damage, body weight loss and disease activity index score in a dose-dependent manner. ATC also attenuated the colonic myeloperoxidase activity which reflects the severity and extent of inflammatory damage of colon. Conclusions : ATC exerts protective effects against inflammatory colonic structural damage induced by epithelial barrier integrity impairment. ATC also inhibits weight loss and related symptoms of UC which can be considered as the functional recovery of colon.

• Korean Journal of Clinical Pharmacy
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• v.34 no.3
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• pp.141-154
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• 2024

Background: As preexisting comorbidities are risk factors for Coronavirus Disease 19 (COVID-19), improved tools are needed for screening or diagnosing COVID-19 in clinical practice. Difficulties of including vulnerable patient data may create data imbalance and hinder the provision of well-performing prediction tools, such as artificial intelligence (AI) models. Thus, we systematically reviewed studies on AI prognosis prediction in patients infected with COVID-19 and existing comorbidities, including cancer, to investigate model performance and predictors dependent on patient data. PubMed and Cochrane Library databases were searched. This study included research meeting the criteria of using AI to predict outcomes in COVID-19 patients, whether they had cancer or not. Preprints, abstracts, reviews, and animal studies were excluded from the analysis. Majority of non-cancer studies (54.55 percent) showed an area under the curve (AUC) of >0.90 for AI models, whereas 30.77 percent of cancer studies showed the same result. For predicting mortality (3.85 percent), severity (8.33 percent), and hospitalization (14.29 percent), only cancer studies showed AUC values between 0.50 and 0.69. The distribution of comorbidity data varied more in non-cancer studies than in cancer studies but age was indicated as the primary predictor in all studies. Non-cancer studies with more balanced datasets of comorbidities showed higher AUC values than cancer studies. Based on the current findings, dataset balancing is essential for improving AI performance in predicting COVID-19 in patients with comorbidities, especially considering age.

• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.41-47
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• 2009

Background: Discogenic pain can develop into chronic low back pain that is very difficult to treat effectively, because the pathogenesis of the disease still remains controversial. To clarify the pathogenesis, numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The aim of this study was to determine the most efficacious method and dose of complete Freund's adjuvant (CFA) injection into intervertebral disc to develop a discogenic pain in a rat. Methods: CFA was injected into the L5-L6 or L4-L5 disc of male Sprague-Dawley rats in various conditions including a dose of CFA (10, 20, or 50 uL), drilling, injection site sealing using cyanoacrylate, and injection velocity. Sham animals were subjected to the same procedure, except for the CFA injection. Mechanical and heat allodynia were serially measured at both hindpaws until 8 weeks post-operatively. Serial MRI analyses were performed to observe degenerative changes of the discs. In addition, CGRP & Substance P-immunoreactivities (ir) in the superficial dorsal horn were evaluated at 4 weeks using immunohistochemistry. Results: Each condition provoked various problems such as development of hindpaw paralysis, CFA leakage, and no pain development. Mid-sagittal T2 MRI revealed no significant degenerative changes in the CFA injected disc. The CGRP-ir of the bilateral superficial dorsal horns at the level of L5-L6 was significantly increased in the CFA group. Conclusions: A total of 10 uL CFA injection into L5-L6 disc for a period of 10 minutes using a 26-gauge needle without drilling was the most efficacious way to develop discogenic pain animal model.

• Journal of Veterinary Science
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• v.21 no.2
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• pp.26.1-26.14
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• 2020

Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selected Kras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) and Streptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

• Biomaterials and Biomechanics in Bioengineering
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• v.3 no.3
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• pp.141-155
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• 2016

Two-dimensional (2D) cell culture and in vivo cancer model systems have been used to understand cancer biology and develop drug delivery systems for cancer therapy. Although cell culture and in vivo model studies have provided critical contribution about disease mechanism, these models present important problems. 2D tissue culture models lack of three dimensional (3D) structure, while animal models are expensive, time consuming, and inadequate to reflect human tumor biology. Up to the present, scaffolds and 3D matrices have been used for many different clinical applications in regenerative medicine such as heart valves, corneal implants and artificial cartilage. While tissue engineering has focused on clinical applications in regenerative medicine, scaffolds can be used in in vitro tumor models to better understand tumor relapse and metastasis. Because 3D in vitro models can partially mimic the tumor microenvironment as follows. This review focuses on different scaffold production techniques and polymer types for tumor model applications in cancer tissue engineering and reports recent studies about in vitro 3D polymeric tumor models including breast, ewing sarcoma, pancreas, oral, prostate and brain cancers.

• Journal of The Korean Society of Agricultural Engineers
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• v.54 no.2
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• pp.55-65
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• 2012

In the winter season, when the ventilation system is operating, the fresh cold air from the slot-type openings of broiler house which directly reached the animal zone can cause various problems such as thermal stress, decreasing of feed and water consumption, occurrence of respiratory disease, and etc. Therefore it is very important to control the trajectory of aero-flow from the slot openings to induce an efficient thermal heat change. Jet-drop distance model was proposed to predict and control the jet-trajectory. However their study was restricted due to the small scaled model and difficulties of measuring the Jet-drop distance. In this study, CFD was applied to analyze qualitatively and quantitatively the jet-drop distance in a real broiler house. The various variables were considered such as installed slot-angle, designed ventilation rate, and the outdoor ambient temperature. From the present study, two linear-regression models using the Jet-drop factor and corrected Archimedes number, and their R-squared values 0.744 and 0.736, respectively, were used. From this study, the applicability of CFD on the analysis of Jet-drop distance model was confirmed.

• Journal of Convergence Korean Medicine
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• v.2 no.1
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• pp.13-22
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• 2021

Objectives: Atopic dermatitis (AD) is an easily recurrent inflammatory skin disease. Since AD has complex pathology, people have been investigating it on different aspects with various experimental models. One of them is in vivo model which has spontaneously developed AD-like skin lesions by various inducers. Methods: In this study, two kinds of mouse species were applied in the experiment; BALB/c and C57BL/6 mice. We compared features among the animal species making AD mouse model with protein allergen, ovalbumin. AD-like skin lesions were induced by ovalbumin on two kinds of scheme and were evaluated with the histological results and size of spleen which is a critical immunological organ. Also, we measured the level of immunoglobulin E in serum. In addition, we investigated the results of ovalbumin induced-AD-like skin lesions along with obesity. Results and Conclusion: We evaluated weight of organs and thickness of epidermis. These results suggest the possibility of the appropriate in vivo experimental model for AD or the comorbidity with obesity.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.