• Journal of Acupuncture Research
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• v.37 no.2
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• pp.128-135
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• 2020

Background: Classical acupuncture is being used in the treatment of rheumatoid arthritis (RA). To explore the biological response to acupuncture, a network-based analysis was performed on gene expression data collected from an animal model of RA treated with acupuncture. Methods: Gene expression data were obtained from published microarray studies on blood samples from rats with collagen induced arthritis (CIA) and non-CIA rats, both treated with manual acupuncture. The weighted gene co-expression network analysis was performed to identify gene clusters expressed in association with acupuncture treatment time and RA status. Gene ontology and pathway analyses were applied for functional annotation and network visualization. Results: A cluster of 347 genes were identified that differentially downregulated expression in association with acupuncture treatment over time; specifically in rats with CIA with module-RA correlation at 1 hour after acupuncture (-0.27; p < 0.001) and at 34 days after acupuncture (-0.33; p < 0.001). Functional annotation showed highly significant enrichment of porphyrin-containing compound biosynthetic processes (p < 0.001). The network-based analysis also identified a module of 140 genes differentially expressed between CIA and non-CIA in rats (p < 0.001). This cluster of genes was enriched for antigen processing and presentation of exogenous peptide antigen (p < 0.001). Other functional gene clusters previously reported in earlier studies were also observed. Conclusion: The identified gene expression networks and their hub-genes could help with the understanding of mechanisms involved in the pathogenesis of RA, as well understanding the effects of acupuncture treatment of RA.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.54 no.3
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• pp.299-306
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• 2009

In nitrogen-limited conditions, rhizobia lead to formation of nitrogen-fixing nodules on the roots of leguminous plants. The process of nodulation is autoregulated by pre-existing nodules in the same root system. The altered profile of sap proteins by inoculation with B. japonicum may indicate presence of a signal responsible for autoregulation transferred through stem. The 20 kDa protein enhanced by innoculation significantly decreased in intensity from 2.5 to 7 days after inoculation (DAI). However 6 kDa protein did increase during such a transition period. Western blot analysis showed that both 20 kDa and 6 kDa were cross-reacted with the SKTI antiserum. This suggests that SKTI may be involved in soybean nodulation by specific induction and degradation in stem sap during early stage of nodulation. RNAi technique and Agrobacterium rhizogenes-mediated transformation were applied to investigate the function of SKTI in nodulation. We have found that the number of rhizobium-induced nodule was much less in SKTIi-silenced hairy roots than the non-silenced. Indeed the quantitative RT-PCR showed that the expression level of SKTI gene was reduced over 40% in the transgenic hairy roots compared to the non-transgenic. It appears that the observed early induction of SKTI and degradation into small peptide in a specific time manner may be involved in autoregulation of nodulation in soybean and the specific mechanism of such regulation remains to be investigated.

• Korean Journal of Community Nutrition
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• v.3 no.4
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• pp.574-582
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• 1998

This study was carried out to discover the effects of eating habits and health-related life style on blood pressure, $\gamma$-Glutamic acid Peptide Transferase($\gamma$-GPT), blood glucose and High Density Lipoprotein-Cholesterol(HDL-C). 185 subjects(85 male, 100 female) were selected, who were living in the Cheonju area aged 40#s to 60#s. The mean systollic blood pressure(SBP), diastollic blood pressure (DBP), $\gamma$-GPT, fasting blood sugar(FBS) and HDL-C for all the subjects were 118mmHg, 77mmHg, 281U/l, 90mg/dl and 45mg/dl, respectively. The SBP and DBP for subuects over 60 years old were 126mmHg and 81mmHg and were significantly higher than subjects in their 40#s and 50#s(p<0.001, p<0.005). The HDL-C of the group that rarely ate breakfast was 57mg/dl and that was significantly higher than the 44mg/dl scored by those who ate breakfast everyday(p<0.05). The SBP for subjects having a snack 2-3 times/week was 125mmHg and that was significantly higher than the 114mmHg of those having a snack everyday(p<0.05). The $\gamma$-GPT for subjects consuming alcohol everyday was 44IU/L and that was significantly higher than 18IU/I of the non-drinking group(p<0.001). The $\gamma$-GPT of light smokers was 53IU/I and that was significantly higher than the 22IU/I for non-smoking participants(p<0.001). The DBP, SBP, $\gamma$-GPT, FBS and HDL-C related to exercise not significantly different. The SBP(p<0.001) and DBP(p-0.01) between age group was positively correlated. The $\gamma$-GPT between drinking frequency(p<0.001), drinking quantity(p<0.05), and smoking(p<0.05) was also positively correlated. The FBS between exercises had a negative correlation(p<0.05), and the HDL-C between breakfast had a negative correlation(p<0.05). These results indicate that decreasing drinking and smoking, when combined with appropriate exercise, will decrease the $\gamma$-GPT and fasting blood sugar level, and help preventing adult diseases.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.494-504
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• 2024

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.346.1-346.11
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• 2018

Background: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) ($2.6{\leq}DAS28$ < 3.2). Results: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (-0.38 vs. -0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

• The Korean Journal of Nuclear Medicine Technology
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• v.17 no.1
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• pp.76-79
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• 2013

Purpose: It is very important to establish the appropriate reference range in the laboratory for preventing mistakes like false positive or false negative. Because the reference range in the laboratory is standard of patient test results interpretation. Proinsulin is precursor hormone of insulin, and the importance is increasing for diagnosing diabetes or insulinoma. Proinsulin reagent used in our laboratory is produced in the USA, and the reference range provided by manufacturer was adapted to our reference range after the validation test. But, it is generally recommend for the every laboratory to establish the their own reference range. So, we decided to re-evaluate the reference range with our patients' test results. Materials and Methods: Among 737 patients who had been to health promotion center in our hospital between Dec. $8^{th}$ 2011 and Dec. $21^{st}$ 2011, 563 patients are chosen with exception of diabetics patients and patients showing abnormal test results in Fasting Glucose, HbA1c, Insulin, and C-peptide. The 563 test results (275 males and 288 females) were classified with three groups(entire, male, female), and analysis of normal distribution was performed with aid of SPSS(version 19.0). Because Each group didn't show normal distribution, the reference range was set from the lowest limit of 2.5% to the highest limit of 97.5% with Percentile method used in non-normal distribution. Results: When evaluation values are sorted in ascending order, the entire range is 4.5~52.0 pM and 5.3~51.9 pM for male and 4.5~52.0 pM for female. The calculated reference range with percentile method shows 6.7~26.5 pM for entire group, 6.8~26.5 pM for male and 6.7~26.5 pM for female, respectively. Conclusion: The reference range provided by reagent manufacturer is 6.4~9.4 pM and the one established in this study is 6.7~26.5 pM. This difference might be caused by racial characteristics between Western people and Koreans. So an ideal reference range can be gotten with normal population visiting to every hospital. Our hospital has been using the newly re-establishing reference range under consultation with the department of endocrinology since Aug. $1^{st}$ 2012.

• Journal of Chest Surgery
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• v.40 no.6 s.275
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• pp.407-413
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• 2007

Background: The brain natriuretic peptide (BNP) level has been reported in some studies to be associated with the occurrence of atrial fbrillation (AF). The aim of this study is to evaluate the potential usefulness of the BNP level as a predictor of the occurrence of postoperative (postop) AF and to assess the relationship of the BNP level with the onset of AF and the restoration of sinus rhythm. Material and Method: From January 1, 2005 to February 28, 2006, 82 patients without a history of atrial arrhythmia that had undergone cardiac surgery were enrolled in the study. Blood samples for plasma BNP were drawn daily for all these patients from the preoperative (preop) day to the 7th postop day. The patient records were reviewed and postop EKGs were checked daily for AF until the time of discharge. Result: Patients were divided into two groups based on development of postop AF. Postoperative AF developed in 26 patients (31.7%). There was no significant statistical difference in age, sex distribution, preop left ventricle ejection fraction, hypertension, left ventricular hypertrophy, or the use of beta blockers between the non-postop AF and postop AF group. More patients in the AF group had undergone valve surgery (39.3% versus 76.9%, p=0.002). The preop left atrium size was significantly larger in the AF patients ($43.8{\pm}10.3 mm$ versus $49.8{\pm}11.5 mm$, p=0.029). The preop plasma BNP levels were higher in the postop AF patients ($144.1{\pm}20.8 pg/mL$ versus $267.5{\pm}68 pg/mL$, p=0.034). In the postop AF group, the plasma BNP level was the highest on the 3rd postop day. Postop AF developed in most patients by the 3rd postop day; restored sinus rhythm developed by the 7th postop day. Conclusion: Elevated plasma BNP levels may lead to the occurrence of postop AF in patients undergoing cardiac surgery. Patients who have a high risk of postop AF should be considered for aggressive prophylactic antiarrhythmic therapy.

• Journal of Periodontal and Implant Science
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• v.47 no.5
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.22-29
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• 2015

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.