• Journal of Veterinary Clinics
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• v.39 no.5
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• pp.235-239
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• 2022

A 10-year-old neutered male Siberian Husky presented with paraparesis and severe lethargy. On physical examination, the patient was unable to weight-bear and walk and exhibited significant muscle mass loss in both hindlimbs and generalized truncal alopecia with a dull coat of hair. On neurological examination, cranial lumbar vertebral pain, hind limb cross-extensor reflex, delayed hindlimb postural reaction, upper motor neuron bladder dysfunction, and total absence of cutaneous trunci reflex were identified. Computed tomography revealed diffuse idiopathic skeletal hyperostosis and spondylosis deformans of the cervical and thoracolumbar vertebrae. In addition, a generalized decrease in bone mineral density of the vertebrae was identified. Magnetic resonance imaging showed hyperplasia of the epidural fat compressing the spinal cord in the thoracolumbar region and concurrent mild multiple intervertebral disc herniations. No specific findings were observed in cerebrospinal fluid analysis. Blood analysis of thyroid function revealed decreased total T4 and free T4 levels, and increased TSH levels. The patient was tentatively diagnosed with spinal epidural lipomatosis (SEL) secondary to hypothyroidism. The patient was treated with levothyroxine, firocoxib, and gabapentin. Clinical signs gradually improved, and the patient showed normal ambulation 40 days after treatment initiation. SEL is extremely rare in dogs. To the best of our knowledge, this is the first case report of SEL secondary to hypothyroidism that was treated conservatively. Secondary SEL can be sufficiently managed by treating the underlying cause, if possible.

• BMB Reports
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• v.54 no.5
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• pp.278-283
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• 2021

Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4⁺ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.

• BMB Reports
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• v.55 no.5
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• pp.226-231
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• 2022

It is well-known that some species of lizard have an exceptional ability known as caudal autotomy (voluntary self-amputation of the tail) as an anti-predation mechanism. After amputation occurs, they can regenerate their new tails in a few days. The new tail section is generally shorter than the original one and is composed of cartilage rather than vertebrae bone. In addition, the skin of the regenerated tail distinctly differs from its original appearance. We performed a proteomics analysis for extracts derived from regenerating lizard tail tissues after amputation and found that endoplasmin (ENPL) was the main factor among proteins up-regulated in expression during regeneration. Thus, we performed further experiments to determine whether ENPL could induce chondrogenesis of tonsil-derived mesenchymal stem cells (T-MSCs). In this study, we found that chondrogenic differentiation was associated with an increase of ENPL expression by ER stress. We also found that ENPL was involved in chondrogenic differentiation of T-MSCs by suppressing extracellular signal-regulated kinase (ERK) phosphorylation.

• Women's Health Nursing
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• v.28 no.2
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• pp.112-122
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• 2022

Purpose: The prevalence of osteoporosis in postmenopausal women is increasing, and diabetes patients have decreased bone density. Their health-related quality of life (HRQoL) is diminished by the resultant physical dysfunction and depression. The purpose of this study was to identify factors influencing HRQoL in postmenopausal women with diabetes and osteoporosis. Methods: This was a secondary data analysis of the Seventh Korea Health and Nutrition Examination Survey (2016-2018), which utilized a complex, multistage probability sample design. The participants in the study were 237 women with diabetes and osteoporosis. To evaluate the factors that influenced HRQoL, a complex-samples general linear model was constructed, and the Bonferroni correction was performed. Results: In this sample of women aged 45 to 80 years (mean±standard deviation, 71.12±7.21 years), the average HRQoL score was 0.83±0.18 out of 1.0. Factors influencing HRQoL were age (70s: t=-3.74, p<.001; 80s: t=-3.42, p=.001), walking for exercise more than 5 days a week (t=-2.83, p=.005), cerebrovascular disease (t=-8.33, p<.001), osteoarthritis (t=-2.04, p=.014), hypertension (t=2.03, p=.044), higher perceived stress (t=-2.17, p=.032), poor glycemic control (t=3.40, p=.001), waist circumference (t=-2.76, p=.007), sitting time per day (t=-2.10, p=.038), and a longer postmenopausal period (t=3.09, p=.002). Conclusion: In order to improve the HRQoL of postmenopausal women with osteoporosis and diabetes, it is necessary to implement intervention strategies that enable the effective management of chronic diseases, while preventing the complications of diabetes and minimizing stress through physical activity.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.210-217
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• 2023

Background: Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose: To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods: A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results: No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ~60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ~50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion: The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

• Nutrition Research and Practice
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• v.16 no.sup1
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• pp.57-69
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• 2022

BACKGROUND/OBJECTIVES: Vitamin D is produced in the skin during sun exposure and is also ingested from foods. The role of vitamin D needs to be considered in the prevention and management of various diseases. Moreover, since the majority of Koreans spend their days indoors, becoming susceptible to the risk of vitamin D deficiency. The current study aims to prepare a basis for determining dietary reference intake of vitamin D in Korea, by reviewing the evidence against various diseases and risks. MATERIALS/METHODS: Literature published in Korea and other countries between 2014 and 2018 was prioritized based on their study design and other criteria, and evaluated using the RoB 2.0 assessment form and United States Department of Agriculture Nutrition Evidence Library Conclusion Statement Evaluation Criteria. RESULTS: Of the 1,709 studies, 128 studies were included in the final systematic analysis after screening. To set the dietary reference intakes of vitamin D based on the selected articles, blood 25(OH)D levels and indicators of bone health were used collectively. Blood vitamin D levels and ultraviolet (UV) exposure time derived from the Korean National Health and Nutrition Examination Survey were analyzed to establish the dietary reference intakes of vitamin D for each stage of the life cycle. The adequate intake levels of vitamin D, according to age and gender, were determined to be in the range of 5-15 ㎍/day, and the tolerable upper intake level was established at 25-100 ㎍/day. CONCLUSIONS: The most important variable for vitamin D nutrition is lifestyle. A balanced diet comprising foods with high contents of vitamin D is important, as is vitamin D synthesis after UV exposure. The adequate intake level of vitamin D mentioned in the 2015 Dietary Reference Intakes for Korean (KDRI) remained unchanged in the 2020 KDRI for the management of vitamin D nutrition in Koreans.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.69.1-69.11
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• 2023

Background: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. Objectives: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. Methods: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. Results: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca⁺⁺-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca²⁺-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. Conclusions: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

• 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.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.14.1-14.17
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• 2022

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.