• Journal of Periodontal and Implant Science
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• v.51 no.5
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• pp.329-341
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• 2021

Purpose: Periodontal treatment aims at complete regeneration of the periodontium, and developing strategies for periodontal regeneration requires a deep understanding of the tissues composing the periodontium. In the present study, the stemness characteristics and gene expression profiles of cementum-derived cells (CDCs) were investigated and compared with previously established human stem cells. Candidate marker proteins for CDCs were also explored. Methods: Periodontal ligament stem cells (PDLSCs), pulp stem cells (PULPSCs), and CDCs were isolated and cultured from extracted human mandibular third molars. Human bone marrow stem cells (BMSCs) were used as a positive control. To identify the stemness of CDCs, cell differentiation (osteogenic, adipogenic, and chondrogenic) and surface antigens were evaluated through flow cytometry. The expression of cementum protein 1 (CEMP1) and cementum attachment protein (CAP) was investigated to explore marker proteins for CDCs through reverse-transcription polymerase chain reaction. To compare the gene expression profiles of the 4 cell types, mRNA and miRNA microarray analysis of 10 samples of BMSCs (n=1), PDLSCs (n=3), PULPSCs (n=3), and CDCs (n=3) were performed. Results: The expression of mesenchymal stem cell markers with a concomitant absence of hematopoietic markers was observed in PDLSCs, PULPSCs, CDCs and BMSCs. All 4 cell populations also showed differentiation into osteogenic, adipogenic, and chondrogenic lineages. CEMP1 was strongly expressed in CDCs, while it was weakly detected in the other 3 cell populations. Meanwhile, CAP was not found in any of the 4 cell populations. The mRNA and miRNA microarray analysis showed that 14 mRNA genes and 4 miRNA genes were differentially expressed in CDCs vs. PDLSCs and PULPSCs. Conclusions: Within the limitations of the study, CDCs seem to have stemness and preferentially express CEMP1. Moreover, there were several up- or down-regulated genes in CDCs vs. PDLSCs, PULPSCs, and BMSCs and these genes could be candidate marker proteins of CDCs.

• Nutrition Research and Practice
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• v.13 no.6
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• pp.543-554
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• 2019

BACKGROUND/OBJECTIVES: The elderly are reported to have a high prevalence of nutritional anemia when they have lower intakes of nutrients or chronic diseases. This study was conducted to compare nutritional status according to nutritional anemia and to determine associations between nutritional anemia and chronic diseases in Korean elderly. SUBJECTS/METHODS: This study utilized data on 3,258 elderly aged ${\geq}65$ years gathered during the $6^{th}$ Korea National Health and Nutrition Examination Survey 2013-2015. Subjects were divided into nutritional anemia (NA) group (n = 415) and non-NA group (n = 2,843) by hemoglobin concentration. Nutrient intakes were assessed using dietary intake data obtained using the 24-hour recall method. The odds ratios (ORs) for nutritional anemia by chronic diseases were determined. Statistical analysis was performed using SPSS Ver. 23.0. RESULTS: Of 3,258 subjects, 12.7% had nutritional anemia. Intakes of potatoes, pulses, and mushrooms by males and potatoes, fruits, meats, eggs, and seafood by females were significantly lower in NA group than in non-NA group. The proportion of the subjects whose intakes of protein, vitamin A, vitamin $B_1$, vitamin $B_2$, niacin, and iron less than estimated average requirement (EAR) were significantly higher in NA group compared to non-NA group. After adjusting for age, the number of family members, energy intake, and alcohol drinking, ORs for nutritional anemia in the subjects with diabetes and myocardial infarction or angina pectoris were significantly higher by 1.74 times and 1.59 times as compared to the subjects without those diseases, respectively. However, ORs for nutritional anemia in the subjects with obesity, abdominal obesity, and hypertriglyceridemia were significantly lower by 0.64 times, 0.60 times, and 0.59 times as compared to the subjects without those diseases, respectively. CONCLUSIONS: The results of this study suggested that nutritional management should be done to enable the Korean elderly to consume foods with high hematopoietic nutrients density to prevent nutritional anemia. Korean elderly need to make regular efforts to check for nutritional anemia.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.73-82
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• 2021

Hsp90 is often overexpressed with activated form in cancer cells, and many key cellular proteins are dependent upon the Hsp90 machinery (these proteins are called "client protein"). Nowadays, more client proteins and more inhibitors of Hsp90 are being discovered. Chaetocin has been identified as an inhibitor of histone methyl transferase SUV39H1. Herein, we find that Chaetocin is an inhibitor of Hsp90 which binds to the C-terminal of Hsp90α. Chaetocin inhibited a variety of Hsp90 client proteins including AMl1-ETO and BCL-ABL, the mutant fusion-protein in the K562 and HL-60 cells. SUV39H1 mediates epigenetic events in the pathophysiology of hematopoietic disorders. We found that inhibition of Hsp90 by Chaetocin and 17-AAG had ability to induce degradation of SUV39H1 through proteasome pathway. In addition, SUV39H1 interacted with Hsp90 through co-chaperone HOP. These results suggest that SUV39H1 belongs to a client protein of Hsp90. Moreover, Chaetocin was able to induce cell differentiation in the two cells in the concentration range of Hsp90 inhibition. Altogether, our results demonstrate that SUV39H1 is a new client protein of Hsp90 degradated by Chaetocin as a novel C-terminal inhibitor of Hsp90. The study establishes a new relationship of Chaetocin and SUV39H1, and paves an avenue for exploring a new strategy to target SUV39H1 by inhibition of Hsp90 in leukemia.

• Journal of Yeungnam Medical Science
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• v.39 no.4
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• pp.300-308
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• 2022

Background: This study investigated the prognostic impact of spine magnetic resonance imaging (MRI) in patients newly diagnosed with multiple myeloma (MM). Methods: We retrospectively evaluated 214 patients who were newly diagnosed with MM between March 2015 and December 2019. The patients were classified into five different infiltration patterns based on spine MRI as follows: (1) normal appearance, (2) focal, (3) diffuse, (4) combined focal and diffuse infiltration, and (5) "salt-and-pepper." Results: Forty patients (18.7%) showed a normal appearance, whereas focal, diffuse, combined focal and diffuse infiltration, and "salt-and-pepper" patterns were identified in 68 (31.8%), 40 (18.7%), 52 (24.3%), and 14 patients (6.5%), respectively. The patients with normal and "salt-and-pepper" patterns were younger than patients with other patterns (median age, 61.6 vs. 66.8 years; p=0.001). Moreover, 63% and 59.3% of patients with normal and "salt-and-pepper" patterns were scored International Staging System (ISS) stage I and revised ISS (R-ISS) stage I, respectively, whereas only 12.5% of patients with other patterns were scored ISS stage I and R-ISS stage I. Patients with normal and "salt-and-pepper" patterns had a better prognosis than those with other patterns, whereas relapse and death rates were significantly higher in patients with focal, diffuse, and combined MRI patterns. Conclusion: Characteristic MRI findings have a significant prognostic value for long-term survival in patients newly diagnosed with MM. In particular, focal, diffuse, and combined focal and diffuse infiltration patterns are unfavorable prognostic factors.

• Natural Product Sciences
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• v.29 no.1
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• pp.42-49
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• 2023

This study investigated the effect of ethanol extracts of horsetail, alfalfa, ortie, chêne and aleppo oak on blood coagulation in vitro. Extraction was performed by the maceration method. Extracts were mixed with platelet and plasma, then prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet aggregation tests were conducted. Alfalfa extract had a dose-dependent effect on the PT. Ortie, and horsetail, reduced the PT significantly compared to control group. Alfalfa, horsetail, and ortie reduced the APTT, but their effect was insignificant compared to the control group. The pooled extract showed the highest effect compared to the single extracts in a dose-dependent manner. Horsetail and alfalfa induced platelet aggregation in response to arachidonic acid but not in response to collagen. In the case of ortie, no aggregation occurred regarding the arachidonic acid, and incomplete was observed in response to collagen. Interestingly, blood clotting occurred immediately after adding the chêne, aleppo oak and the pooled extract, and therefore platelet poor plasma (PPP) and platelet rich plasma (PRP) became jelly. Generally, chêne and aleppo oak, as well as pooled extract, were more effective in inducing both primary and secondary coagulation pathways via shortening the PT and APTT, and induction of platelet aggregation.

• Fisheries and Aquatic Sciences
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• v.26 no.2
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• pp.97-104
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• 2023

CD96 is a membrane-bound receptor discovered in humans in 1992 that is mainly present in natural killer cells and T cells derived from haematopoietic cells and performs immune functions. Based on the sequence of CD96 obtained from red seabream (Pagrus major), phylogenetic analysis with other species, infections of normal fish, Streptococcus iniae and red sea bream iridovirus (RSIV), and expression analysis was conducted using real-time polymerase chain reaction. Phylogenetic analysis showed the highest homology with Sparus aurata, and multiple sequence analysis confirmed the conservation of major domains between different fish species. Normal fish high expression results were confirmed in the head kidney, and spleen, which are the haematopoietic organs of the fish. High expression levels were confirmed in the gills, liver, spleen, and kidney on day three after RSIV infection. After S. iniae infection, high expression was confirmed in the gills and liver on day one, and high expression was confirmed in the spleen from 12 hours. These results show that PmCD96 functions as an immune gene in P. major and is considered a basic research case for CD96 in fish's hematopoietic organ immune system.

• Molecules and Cells
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• v.46 no.10
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Journal of Genetic Medicine
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• v.20 no.2
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• pp.60-69
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• 2023

Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients-four with MPS I and five with MPS II-underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from -4.09±0.83 to -3.68±0.43 after 1 year of hGH treatment, and to -3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion: This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.

• Journal of Veterinary Clinics
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• v.41 no.3
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• pp.195-199
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• 2024

A free-range wild raccoon dog (Nyctereutes procyonoides) was rescued with cachexia. Physical examination revealed generalized hyperkeratosis and alopecia typical of scabies as well as hypothermia (35.6℃). The patient was obtunded and severely dehydrated (10%). Hematological parameters included a low packed cell volume (PCV; 15%) and hemoglobin concentration, leukocytosis, and hypoglycemia. A blood smear revealed different subtypes of hypochromic leptocytes, indicating a regenerative response against severe anemia. This case was initially tentatively diagnosed as a severe anemia due to chronic external bleeding presumed to be caused by scabies-induced skin injuries. Darbepoetin alpha (DPO), iron dextran, and fluralaner were administered at the initial presentation, and supportive care including oxygen supplementation, warming, and nutritional support was provided. However, on day 5, the PCV dropped to 5.9% presumably caused by rapid rehydration due to drinking water ad libitum. DPO was boosted on days 5 and 6 along with daily iron dextran. On day 21, the PCV had recovered to 19.8%, and a blood smear evaluation showed a strong regenerative response. This case shows that even if severe anemia occurs in a raccoon dog, it can be managed with an appropriate response. In particular, since the rehydration rate due to food intake is faster than the hematopoietic response rate of raccoon dogs, the PCV may decrease rapidly in the early stage of treatment; therefore, diagnostic examination and additional medical management for hematopoiesis are necessary.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.47-52
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• 2003

Background: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin- 3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. Methods: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. Results: The number of CD41a+ cells were $0.54{\pm}0.05{\times}10^4$ (rhIL-11 100 ng/ml), $5.32{\pm}0.23{\times}10^4$ (rhIL-3 100 ng/ml), and $8.76{\pm}0.15{\times}10^4$ (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to $7.47{\pm}0.69{\times}10^4$ (rhIL-3+ rhIL-11), $11.92{\pm}0.19{\times}10^4$ (rhTPO+rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid mediaincluding various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. Conclusion: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically.