• The Journal of Korean Medicine
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• v.44 no.3
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• pp.189-200
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• 2023

Objectives: The purpose of this study is to analyze the current state of quantitative literature evidence for the prescription of 56 herbal medicines covered by health insurance that have been studied in Korea for the past 30 years, to evaluate the reliability of the evidence, and to find out the research direction of herbal medicine prescription in the future. Methods: 56 kinds of herbal medicine prescriptions were searched in domestic literature search databases OASIS, DBpia, and overseas PubMed, classified into chemistry, toxicity, cells, animals, clinical cases, and clinical trial studies, and built into an EBM pyramid structure. Results: When classified according to research contents, there were 61 cases (7.5%) of physicochemical analysis to identify constituent substances, 80 cases (9.8%) of toxicity evaluation, and 672 cases (82.7%) of efficacy evaluation. The efficacy evidence was classified according to the evidence-based medical pyramid structure: 196 cell trials (29.1%), 372 animal trials (55.4%), 89 case and case reporting series (13.3%), 7 comparative case studies (1.1%), and 8 randomized control clinical trials (1.2%). In the pyramid composition, the basis for the validity of 56 kinds of herbal medicines prescribed was 568 cases (84.5%) in cell and animal units, which could not be said to be highly reliable. There was no relationship between the ranking of quantitative literature evidence for herbal medicine prescriptions and the ranking of salary administration. Conclusions: In an era that continues to require scientific evidence for herbal medicine, traditional herbal medicine should secure the basis for safety validity even for the 10th most frequent prescription among 56 herbal medicine prescriptions for consumers. In particular, traditional herbal medicine should increase the quantitative and qualitative level of case reports on related herbal medicine prescriptions, focusing on each clinical society, and move toward comparative case studies and randomized clinical trial so that traditional herbal medicine is positioned as Evidence-based medicine.

• 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.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.165-175
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• 2016

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

• Herbal Formula Science
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• v.31 no.4
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• pp.373-388
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• 2023

Objectives : This study aimed to provide basic data for research by investigating non-clinical experimental studies on herbal medicines and its compounds for precocious puberty. Methods : A search was conducted for all literature until October 2023 using combinations of keywords such as precocious puberty, puberty, and chinese medicine in three databases (Pubmed, OASIS, and ScienceON). Results : 1. In animal experiments, studies were mainly conducted using a model that induced precocious puberty by subcutaneously administering danazol to SD rats on the 5th day after birth, and in cell experiments, precocious puberty was induced by treating GT1-7 cells with kisspeptin 10 or estradiol. 2. Anemarrhenae Rhizoma, Phellodendri Cortex, and Prunellae Spica were mainly used as herbal medicine to evaluate their efficacy on precocious puberty in non-clinical experiments. 3. Macroscopic observation, hematological analysis, histological analysis, and genetic analysis were performed as methods to analyze the experimental results. Conclusions : In this study, the effects of herbal medicine on precocious puberty and non-clinical research methods were confirmed. Based on the results of this study, it is expected that non-clinical effectiveness and mechanism research on materials that are clinically effective in Traditional Korean Medicine will be revitalized.

• International Journal of Molecular Medicine
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• v.44 no.6
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• pp.2171-2180
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• 2019

Pistacia weinmannifolia (Anacardiaceae) has been used in herbal medicine for the treatment of influenza, dysentery and enteritis in China. It was recently observed that P. weinmannifolia root extract (PWRE) exerts anti-inflammatory effects both in in vitro and in vivo models. Based on the results from previous studies, the present study investigated the protective effect of PWRE on airway inflammation and mucus hypersecretion. Treatment with PWRE significantly decreased the number of eosinophils and the levels of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, in the bronchialveolar lavage fluid (BALF) of OVA-exposed mice. PWRE decreased the high serum levels of total and OVA-specific immunoglobulin E. PWRE also effectively inhibited the influx of inflammatory cells into the lung, as well as airway mucus hypersecretion. In addition, the increased level of monocyte chemoattractant protein-1 was significantly decreased with the PWRE treatment in the BALF of OVA-exposed mice and in lipopolysaccharide-stimulated RAW264.7 macrophages. These protective effects of PWRE on OVA-induced pulmonary inflammation were accompanied by the downregulation of mitogen associated protein kinases and nuclear factor-κB activation. Thus, the results from the present study indicate that PWRE could be valuable adjuvant for the treatment of asthma.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.1-6
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• 1991

The effect of 2-deoxy-d-glucose (2-DDG) on $C_3H$ mouse fibrosarcoma(FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo $^{31}P$-MRS, proliferative capacity was observed on flow cytometry(FC) and growth rate was measured after transplantation of $10^6$ viable tumor cells in the dorsum of foot of $C_3Hf/Sed$ mice. One gram of 2-DDG Per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantion was $250mm^3$. Growth rate of Fsall tumor was measured by tumor doubling time and slope on semilog plot. After 2-DDG injection, growth rate slowed down. Tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo $^{31}P$-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and $G_2+M$ phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect of 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.425-433
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• 2004

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.44-52
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• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Food Science of Animal Resources
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• v.29 no.4
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• pp.445-456
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• 2009

Colostrum samples were collected from 36 dairy farms in Gyeonggi-do and one dairy farm in the National Institute of Animal Science (NIAS) for testing. Colostrum samples were analyzed for phisycochemicals (specific gravity, pH, titratable acidity), general components (fat, protein, lactose, total solid, solid non-fat (SNF)), fatty acids, amino acids, minerals, microflora, somatic cells, and Ig (Immunoglobulin). The first colostrum revealed the following data: fat contents were $6.16{\pm}2.39%$, proteins were $14.78{\pm}4.30%$, lactose $2.57{\pm}0.77%$, total solid $24.28{\pm}4.36%$, and SNF $18.12{\pm}4.08%$, whereas the 2nd (or $12^{th}$) colostrum revealed $5.56{\pm}1.76%$ fat, $3.46{\pm}0.41%$ proteins, $4.19{\pm}0.43%$ lactose, $13.90{\pm}1.76%$ total solid, and $8.34{\pm}0.81%$ SNF. Also, the first colostrum revealed the contents of major amino acids as 0.89% aspartic acid, 0.71% threonine, 0.86% serine, 1.75% glutamic acid, 0.64% valine, 0.95% leucine, 0.83% lysine, and 0.95% proline, and those in the 10th colostrum were 0.25% aspartic acid, 0.15% threonine, 0.19% serine, 0.59% glutamic acid, 0.19% valine, 0.35% leucine, 0.31% lysine, and 0.34% proine. Major amino acid contents rapidly decreased as milking times increased. In the first colostrum, the following mineral contents were observed: there were 2,168 ppm in Ca, 1,959 ppm in P, 914 ppm in K, 761 ppm in Na, 287 ppm in Mg, 1.7 ppm in Fe, 14.3 ppm in Zn, and 1.0 ppm in Cu; while in the 10th colostrum, the following ppm contents were 1,389 in Ca, 1,323 in P, 838 in K, 427 in Na, 131 in Mg, 1.0 in Fe, 4.7 in Zn, and 1.3 in Cu. The mineral contents in a colostrum rapidly decreased as milking times increased.

• Journal of Gastric Cancer
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• v.10 no.1
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• pp.5-12
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• 2010

Purpose: The aim of this study was to evaluate the preoperative and postoperative nutritional statuses of patients with gastric cancer and to investigate the nutritional factors that are correlated with perioperative complications. Materials and Methods: From January 2008 to Jun 2008, 669 patients who underwent curative gastrectomy were enrolled in a retrospective study. To evaluate the changes of their nutritional status preoperatively and postoperatively, we measured the total lymphocyte count, the serum albumin, the body weight change and the BMI. The nutritional factors correlated with short-term postoperative complications were analyzed. Results: The total lymphocyte count and serum albumin decreased from the first preoperative day to the $5^{th}$ day after operation, but they tended to increase and approach the normal range 6 months after operation. The only factor correlated with the short-term postoperative complications (defined as the ones that occurred for 30 days) was the serum albumin checked on the $5^{th}$ day after operation. Conclusion: Low serum albumin on the $5^{th}$ day after operation was correlated with postoperative short-term complications. Serum albumin can be the preoperative statistical parameter that can predict the occurrence of postoperative complications.