• Journal of Periodontal and Implant Science
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• v.52 no.2
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• pp.170-180
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• 2022

Purpose: This study was conducted to assess the effect of hard and/or soft tissue grafting on immediate implants in a preclinical model. Methods: In 5 mongrel dogs, the distal roots of P2 and P3 were extracted from the maxilla (4 sites in each animal), and immediate implant placement was performed. Each site was randomly assigned to 1 of the following 4 groups: i) gap filling with guided bone regeneration (the GBR group), ii) subepithelial connective tissue grafting (the SCTG group), iii) GBR and SCTG (the GBR/SCTG group), and iv) no further treatment (control). Non-submerged healing was provided for 4 months. Histological and histomorphometric analyses were performed. Results: Peri-implant tissue height and thickness favored the SCTG group (height of periimplant mucosa: 1.14 mm; tissue thickness at the implant shoulder and ±1 mm from the shoulder: 1.14 mm, 0.78 mm, and 1.57 mm, respectively; median value) over the other groups. Bone grafting was not effective at the level of the implant shoulder and on the coronal level of the shoulder. In addition, simultaneous soft and hard tissue augmentation (the GBR/SCTG group) led to a less favorable tissue contour compared to GBR or SCTG alone (height of periimplant mucosa: 3.06 mm; thickness of peri-implant mucosa at the implant shoulder and ±1 mm from the shoulder: 0.72 mm, 0.3 mm, and 1.09 mm, respectively). Conclusion: SCTG tended to have positive effects on the thickness and height of the periimplant mucosa in immediate implant placement. However, simultaneous soft and hard tissue augmentation might not allow a satisfactory tissue contour in cases where the relationship between implant position and neighboring bone housing is unfavorable.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.19-25
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• 2017

Objective : The Sinseon-yukza-hwan (SSY), a Korean medicinal formula which includes Radix Rehmanniae Preparata and other medicinal herbs, has long been used for treatment of alopecia and gray hair through oral administration. This study is designed to enhance the utilization of natural materials in hair and scalp-related cosmetics. Possibility of SSY as an antioxidant was examined from its 50% ethanol extract. Methods : The antioxidative capacities were evaluated by determining total phenolic and flavonoid contents, 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), reducing power and hydroxyl radical scavenging activity. Results : Total polyphenol and flavonoid contents of SSY were 25.53 mg TE, tannic acid equivalent/g and 18.90 mg RE, rutin equivalent/g, respectively, which correlated strongly its antioxidative activity. The DPPH and ABTS free radical scavenging activities of SSY at $0.1mg/m{\ell}{\sim}5mg/ml$ were ranged from 20% to 85% and 10% to 58%, respectively. Also the hydroxyl radical scavenger activity and reducing power increased in SSY-treated group, which were significantly lower in SSY-compared to BHA-treated group. But the highest reducing power was shown as 79% from SSY-treated group, which was higher value than 65% from BHA-treatment. These results showed that SSY extract effectively inhibited the generation of free radicals in the all assay system with dose-dependent manners. Conclusions : Thus, the present study provide preclinical data to support the expanded application of SSY, which could be potential candidates for natural antioxidants.

• Archives of Plastic Surgery
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• v.48 no.6
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• pp.703-713
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• 2021

The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen-mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.7-13
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• 2022

Purpose: Preimplantation genetic testing for monogenic disorders (PGT-M) has been successfully used to prevent couples with monogenic disorders from passing them on to their child. Charcot-Marie-Tooth Disease (CMT) is a genetic disorder characterized by progressive extremity muscle degeneration and loss of sensory function. For the first time in Korea, we report our experience of applying single nucleotide polymorphism genotyping and karyomapping for PGT-M of CMT disease. Materials and Methods: Prior to clinical PGT-M, preclinical tests were performed using genotypes of affected families to identify informative single-nucleotide polymorphisms associated with mutant alleles. We performed five cycles of in vitro fertilization PGT-M in four couples with CMT1A, CMT2A, and CMT2S in CHA Fertility Center, Seoul Station. Results: From July 2020 through August 2021, five cycles of PGT-M with karyomapping in four cases with CMT1 and CMT2 were analyzed retrospectively. A total of 17 blastocysts were biopsied and 15 embryos were successfully diagnosed (88.2%). Ten out of 15 embryos were diagnosed as unaffected (66.7%). Five cycles of PGT-M resulted in four transfer cycles, in which four embryos were transferred. Three clinical pregnancies were achieved (75%) and the prenatal diagnosis by amniocentesis for all three women confirmed PGT-M of karyomapping. One woman delivered a healthy baby uneventfully and two pregnancies are currently ongoing. Conclusion: This is the first report in Korea on the application of karyomapping in PGT-M for CMT patients. This study shows that karyomapping is an efficient, reliable and accurate diagnostic method for PGT-M in various types of CMT diseases.

• 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.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.319-329
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• 2023

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

• BMB Reports
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• v.56 no.3
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• Journal of Medicine and Life Science
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• v.18 no.3
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• pp.41-48
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• 2021

The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopamine-related developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.

• Herbal Formula Science
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• v.31 no.3
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• pp.171-182
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• 2023

Objectives : Saposhnikoviae Radix (SR) and Glehniae Radix (GR) have been frequently used in traditional medicine to treat diseases related to 'wind' syndrome, but there have been cases where it has been mixed in a state where the plant of origin is not clear. In this study, to select materials for conducting preclinical cerebral infarction research, the network pharmacology analysis method was used to select suitable medicinal materials for the study. Methods : In this study, a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) based network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3 were applied, then networks of bioactive compounds, target proteins, and target diseases was constructed. STRING database was used to construct a protein-protein interaction network. Results : It was confirmed that SR rather than GR has various target proteins and target diseases based on network pharmacological analysis using TCMSP database. And it was analyzed that the bioactive compounds only in SR act more on neurovascular diseases, and both drugs are expected to be effectively used for cardiovascular diseases. Conclusions : In our future study, SR will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• 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.