• Journal of Veterinary Clinics
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• v.40 no.2
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• pp.113-118
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• 2023

Skin and joint diseases are relatively common in dogs. Nutritional complementation is one of the various management strategies for these disorders. This study evaluated the safety and clinical efficacy of Kyungokgo-gamibang in dogs with skin and joint diseases. Thirty dogs with diseases were included and divided into three groups: control group (n = 15), skin group (n = 10), and joint group (n = 5). The skin and joint groups were fed skin and joint gums composed of Kyungokgo-gamibang extract with standard treatment for four weeks. The control group included dogs with skin diseases who were administered standard skin infection treatment for 4 weeks. The physical and laboratory results showed no remarkable adverse effects of Kyungokgo-gamibang extract after its administration in dogs. Clinical efficacy was evaluated using quality of life scale, and levels of cytokines, including interferon-γ, interleukin (IL)-2, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, and tumor necrosis factor-α, for 4 weeks in all groups. Dermatologic clinical scales were performed for 4 weeks in the control and skin groups. Both the control and skin groups had significantly decreased dermatologic clinical scales, including pruritus and erythema scales (p < 0.05). Among the cytokine levels, only IL-2 concentration was significantly decreased in the skin group after 4 weeks of administration of the Kyungokgo-gamibang extract (p = 0.032). There was no significant difference between the levels of cytokines on days 0 and 28 in the joint group. The quality of life scale was significantly increased after week 4 compared to week 0 in the skin (p = 0.008) and joint groups (p = 0.041). This study suggests that Kyungokgo-gamibang extract can be applied in managing dogs affected by skin and joint diseases without adverse effects.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.3
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• pp.206-212
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• 2023

Objective: The aim of the present study was to evaluate the associations between hematologic parameters related to systemic inflammation and insulin resistance-associated metabolic parameters in women with polycystic ovary syndrome (PCOS). Methods: Eighty-two women between the ages of 18 and 35 years who were diagnosed with PCOS were included in this study. A 2-hour 75-g oral glucose tolerance test (OGTT) was administered to all study participants; fasting and postprandial glucose and insulin levels were measured simultaneously during the 2-hour OGTT. Hematologic parameters were derived from a standard complete blood count and a differential count of fasting-state blood samples. The correlations between hematologic parameters and insulin resistance-associated clinical and metabolic parameters were evaluated using the Spearman rank correlation and partial correlation coefficients. Hematologic parameters related to systemic inflammation were compared between the two groups, categorized by the presence or absence of insulin resistance. Results: Significant differences in the absolute neutrophil count, absolute monocyte count, platelet count, and neutrophil-lymphocyte ratio were found between the insulin-resistant group and insulin-nonresistant group. Correlation analysis found that all hematological parameters, except for the platelet-lymphocyte ratio, were associated with at least one insulin resistance-associated metabolic parameter. However, these significant correlations between hematological and metabolic parameters were attenuated after controlling for the effects of other covariates using partial correlation analysis. Conclusion: The association between hematologic parameters indicative of systemic inflammation and insulin resistance-associated metabolic parameters seems to be strongly influenced by other anthropometric covariates in women with PCOS.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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• pp.33-46
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• 2023

Objectives We investigated anti-obesity effects of Menthae Herba hydrosol in obese mice. Methods Animals were divided into four groups, and treatments were performed for 7 weeks. After the treatment, serum lipid profiles, weight and pathological morphology in liver, kidney, adipose tissue were measured. Also, hepatic protein and gene expression levels of lipid metabolism-related factors were analyzed. Results Body weight was decreased in P3% group. In P1% (group fed high-fat diet and 1% Menthae Herba hydrosol) and P3% (group fed high-fat diet and 3% Menthae Herba hydrosol) group, weight of white adipose tissue, serum levels of triglyceride and blood urea nitrogen were decreased, and weight of muscle was increased. Also, liver, kidney and epididymal adipocyte size were reduced in P1% and P3% group. Adenosine monophosphate-activated protein kinase was increased and sterol regulatory element binding protein-1c (SREBP-1c) was decreased in P3% group. mPeroxisome proliferator-activator receptor-γ, mMonocyte chemotactic protein-1 were decreased in P1% and P3% group. In P3% group, mSREBP-1c was decreased and mCarnitine palmitoyl transferase-1 was increased. And mUncoupling protein 1 in brown adipose tissue was increased. Conclusions These results suggest that Menthae Herba hydrosol has a worthy effect on anti-obesity.

• Journal of Digital Convergence
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• v.20 no.2
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• pp.311-316
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• 2022

Tertomotide is a peptide fragment of hTert and developed as a vaccine targeting cancer. It has been reportedly known to ameliorate inflammatory symptoms in clinical tests and in animal studies. However, the therapeutic potential of tertomotide is not supposed to be comparable to conventional anti-inflammatory agents due to low druglikeness In order to treat inflammations present in varous lesion, the structure of tertomotide is required to be modified. In this context, 12 octapeptides were designed based on tertomotide and screened for the anti-inflammatory activity in activated monocyte by measuring TNF-α secretion. As a result, some octapeptides has been exerted anti-inflammatory activity, comparable to or better than tertomotide and estradiol, known anti-inflammatory agents. This result is supposed to be helpful for developing therapeutic purpose exploiting other tertomotide-derived peptides and would be an example for designing novel drug based on active biomolecules with undesirable structure by convergence study of biology and computer-aided medicinal chemistry.

• 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.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.917-933
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• 2023

BACKGROUND/OBJECTIVES: As peanuts germinate, the content of the components beneficial to health, such as resveratrol, increases within the peanut sprout. This study examined whether the ethanol extract of peanut sprout tea (PSTE) inhibits breast cancer growth and metastasis. MATERIALS/METHODS: After orthotopically injecting 4T1 cells into BALB/c mice to induce breast cancer, 0, 30, or 60 mg/kg body weight/day of PSTE was administered orally. Angiogenesis-related protein expression in the tumors and the degree of metastasis were analyzed. 4T1 and RAW 264.7 cells were co-cultured, and reverse transcription polymerase chain reaction was performed to measure the crosstalk between breast cancer cells and macrophages. RESULTS: PSTE reduced tumor growth and lung metastasis. In particular, PSTE decreased matrix metalloproteinase-9, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor-A, F4/80, CD11c, macrophage mannose receptor, macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 expression in the tumors. Moreover, PSTE prevented 4T1 cell migration, invasion, and macrophage activity in RAW 264.7 cells. PSTE inhibited the crosstalk between 4T1 cells and RAW 264.7 cells and promoted the macrophage M1 subtype while inhibiting the M2 subtype. CONCLUSIONS: These results suggest that PSTE blocks breast cancer growth and metastasis to the lungs. This may be because the PSTE treatment inhibits the crosstalk between mammary cancer cells and macrophages and inhibits the differentiation of macrophages into the M2 subtype.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.328-336
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• 2023

Purpose: Human peripheral blood mononuclear cell (PBMC)-based in vitro systems can be of great value in the development and assessment of vaccines but require the right medium for optimal performance of the different cell types present. Here, we compare three commonly used media for their capacity to support innate and adaptive immune responses evoked in PBMCs by Toll-like receptor (TLR) ligands and whole inactivated virus (WIV) influenza vaccine. Materials and Methods: Human PBMCs were cultured for different periods of time in Roswell Park Memorial Institute (RPMI), Dulbecco's minimal essential medium (DMEM), or Iscove's modified DMEM (IMDM) supplemented with 10% fetal calf serum. The viability of the cells was monitored and their responses to TLR ligands and WIV were assessed. Results: With increasing days of incubation, the viability of PBMCs cultured in RPMI or IMDM was slightly higher than that of cells cultured in DMEM. Upon exposure of the PBMCs to TLR ligands and WIV, RPMI was superior to the other two media in terms of supporting the expression of genes related to innate immunity, such as the TLR adaptor protein gene MyD88 (myeloid differentiation factor 88), the interferon (IFN)-stimulated genes MxA (myxovirus resistance protein 1) and ISG56 (interferon-stimulated gene 56), and the leukocyte recruitment chemokine gene MCP1 (monocyte chemoattractant protein-1). RPMI also performed best with regard to the activation of antigen-presenting cells. As for adaptive immunity, when stimulated with WIV, PBMCs cultured in RPMI or IMDM contained higher numbers of IFNγ-producing T cells and secreted more immunoglobulin G than PBMCs cultured in DMEM. Conclusion: Taken together, among the different media assessed, RPMI was identified as the optimal medium for a human PBMC-based in vitro vaccine evaluation system.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.31.1-31.16
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• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.303-312
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• 2024

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone-treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.