• IMMUNE NETWORK
• /
• v.16 no.3
• /
• pp.189-194
• /
• 2016

Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes. On the other hand, the chemokine levels of CCL2, CCL7-8, CCL11, CXCL1-3, CXCL6 and CXCL10-11 were dominantly expressed in preadipocytes compared to adipocytes. Interestingly, CXCL14 was the most dominant chemokine expressed in adipocytes compared to preadipocytes. Moreover, there is significantly higher protein level of CXCL14 in conditioned media from adipocytes. In addition, we analyzed the data of the chemokine signatures in adipocytes obtained from healthy lean and obese postmenopausal women based on Gene Expression Omnibus (GEO) dataset. Adipocytes from obese individuals had significantly higher levels in chemokine signature as follows: CCL2, CCL13, CCL18-19, CCL23, CCL26, CXCL1, CXCL3 and CXCL14, as compared to those from lean ones. Also, among the chemokine networks, CXCL14 appeared to be the highest levels in adipocytes from both lean and obese women. Taken together, these results identify CXCL14 as an important chemokine induced during adipogenesis, requiring further research elucidating its potential therapeutic benefits in obesity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.28 no.1
• /
• pp.59-72
• /
• 2024

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

• Parasites, Hosts and Diseases
• /
• v.62 no.1
• /
• pp.98-116
• /
• 2024

Epigenetic writers including DNA and histone lysine methyltransferases (DNMT and HKMT, respectively) play an initiative role in the differentiation and development of eukaryotic organisms through the spatiotemporal regulation of functional gene expressions. However, the epigenetic mechanisms have long been suspected in helminth parasites lacking the major DNA methyltransferases DNMT1 and DNMT3a/3b. Very little information on the evolutionary status of the epigenetic tools and their role in regulating chromosomal genes is currently available in the parasitic trematodes. We previously suggested the probable role of a DNMT2-like protein (CsDNMT2) as a genuine epigenetic writer in a trematode parasite Clonorchis sinensis. Here, we analyzed the phylogeny of HKMT subfamily members in the liver fluke and other platyhelminth species. The platyhelminth genomes examined conserved genes for the most of SET domain-containing HKMT and Disruptor of Telomeric Silencing 1 subfamilies, while some genes were expanded specifically in certain platyhelminth genomes. Related to the high gene dosages for HKMT activities covering differential but somewhat overlapping substrate specificities, variously methylated histones were recognized throughout the tissues/organs of C. sinensis adults. The temporal expressions of genes involved in eggshell formation were gradually decreased to their lowest levels proportionally to aging, whereas those of some epigenetic tool genes were re-boosted in the later adult stages of the parasite. Furthermore, these expression levels were significantly affected by treatment with DNMT and HKMT inhibitors. Our data strongly suggest that methylated histones are potent epigenetic markers that modulate the spatiotemporal expressions of C. sinensis genes, especially those involved in sexual reproduction.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.2
• /
• pp.159-168
• /
• 2004

Background : In recent years, numerous human tumor specific antigens such as melanoma antigen gene(MAGE) that is recognized by autologous cytotoxic T lymphocytes have been identified. MAGE is expressed in many human malignancies in various organs, such as lung, breast, stomach, esophagus and leukemia. Therefore MAGE has been studied widely for tumor diagnosis and immunotherapy. But, so far there were no clinical studies evaluating the role of MAGE in pleural effusion. We investigated the expression of MAGE in the patients with exudative pleural effusion for it's diagnostic utility and the results were compared with those of cytologic examinations. Methods : Diagnostic thoracentesis was performed in 44 consecutive patients with exudative pleural effusion during 6 months. We examined the expression of MAGE and cytology with the obtained pleural effusion. Expression of MAGE was interpreted by means of a commercial kit using RT-PCR method. Enrolled patients were divided into two groups such as malignant and benign and we analyzed its' sensitivity and specificity. Results : There were no significant differences between two groups in age, sex, white blood cell counts in pleural fluid, pleural fluid/serum protein ratio and pleural fluid/serum LDH ratio. The sensitivity and specificity of MAGE were 72.2% and 96.2% respectively and the positive predictive value and negative predictive value of MAGE were also 92.9% and 83.3% respectively. The sensitivity and negative predictive value of cytologic examinations were 66.7% and 81.3% respectively. There were no significant differences between sensitivities of MAGE and cytologic examinations but false positive result of MAGE was found in 1 case of tuberculous pleurisy. Conclusion : MAGE is a sensitive and specific marker for the differential diagnosis between benign and malignant effusion in patients with exudative pleural effusion. And MAGE would provide the equal sensitivity compared with that of cytologic examination in patients with malignant pleural effusion if 5mL of the pleural fluid is examined.

• Journal of Life Science
• /
• v.17 no.4 s.84
• /
• pp.482-492
• /
• 2007

Infection with Shiga-like toxin (SLT)-producing Escherichia coli causes a spectrum of illnesses with high morbidity and mortality. Host mediators play an important role in the pathogenesis of SLT-I toxicity. We here investigated the effect of SLT-I on tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ production, effect of $TNF-{\alpha}$ on glycolipid globotriaosyleramide (Gb3) expression, and relationship between Gb3 level and differential susceptibility of cells to SLT-I. In this study, we observed that detectable levels of $TNF-{\alpha}$ are produced 6 hrs after induction and continued to increase during 48 hrs by SLT-I. It was also found that Vero cells and dendritic cells expressed high levels of Gb3, 83% and 68%, respectively, and that macrophages had a low level of Gb3 (29%) and showed refractory to cytotoxicity against SLT-I. Vero cells and dendritic cells expressing high levels of Gb3 were highly susceptible to SLT-I. furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. These results suggest that the expression of Gb3 is necessary, but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its receptor, Gb3, in the pathogenesis of E. coli O157 infection.

• Journal of Acupuncture Research
• /
• v.22 no.3
• /
• pp.215-225
• /
• 2005

Objective : It has long been known about the osteogenic effect of CTF-HAS on bone tissues. However, it has not been determined the effect of CTF-HAS on cancer cells. The purpose of this study is to screen the CTF-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cells lines. Oligonucleotide microarray approach were employed to screen the differential expression genes. Methods : CTF-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of CTF-HAS(0.1, 0.5, 1.5, 10, $20mg/m{\ell}$) for 24 h. Cytotoxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with $1.5mg/m{\ell}$ of CTF-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide genechip (Human genome U133 Plus 2.0., Affimatrix Co.). ResuIts : It has no cytotoxic effects on HepG2 cells in all concentrations (0.1, 0.5, 1.5, 10, $20mg/m{\ell}$). More than twofold up-regulated genes were 19 genes. The number of more than twofold down-regulated genes was 13. Discussion : This study showed the screening of CTF-HAS mediated differentially regulated genes using combined approaches of oligonucleotide microarray. The screened genes will be used for the better understanding in therapeutic effect of CTF-HAS on cancer field.

• The korean journal of orthodontics
• /
• v.23 no.2 s.41
• /
• pp.229-248
• /
• 1993

[ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.

• Journal of Life Science
• /
• v.15 no.2 s.69
• /
• pp.253-260
• /
• 2005

Mitotic centromere-associated kinesin (MCAK), which is a member of the Kin I (internal motor domain) subfamily of kinesin-related proteins, is known to play a role in mitotic segregation of chromosome during M phase of the cell cycle. In the present study, we have produced a rat polyclonal antibody using human MCAK (HsMCAK) expressed in E. coli as the antigen. The antibody specifically recognized the HsMCAK protein (81 kDa), and could detect its nuclear localization in human Jurkat T cells and 293T cells by Western blot analysis. The specific stage of the cell cycle was obtained through blocking by either hydroxyl urea or nocodazole and subsequent releasing from each blocking for 2, 4, and 7 h. While the protein level of HsMCAK reached a maximum level in the S phase with slight decline in the $G_{2}-M$ phase, the electrophoretic mobility shift from $p81^{MCAK}\;to\;p84^{MCAK}$ began to be induced in the late S phase and reached a maximum level in the $G_{2}/M $ phase, and then it disappeared as the cells enter into the $G_{1}$ phase. Immunocytochemical analysis revealed that HsMCAK protein localized to centrosome and nucleus at the interphase, whereas it appeared to localize to the spindle pole, centromere of the condensed mitotic DNA, spindle fiber, or midbody, depending on the specific stage of the M phase. These results demonstrate that a rat polyclonal antibody raised against recombinant HsMCAK expressed in E. coli specifically detects human MCAK, and indicate that the electrophoretic mobility shift from $p81^{MCAK}\;to\;p84^{MCAK}$, which may be associated with its differential intracellular localization during the cell cycle, fluctuates with a maximum level of the shift at the $G_{2}-M$ phase.

• The Journal of Korean Medicine
• /
• v.17 no.1 s.31
• /
• pp.374-406
• /
• 1996

This study has been carried out to investigate the types of differential diagnosis of amnesia. The results are as follows; 1. Amnesia has various types of differential diagnosis(辨證分型) ; deficiency of both the heart and spleen(心脾兩虛型), deficiency of the heart(心虛型), deficiency of the kidney(腎虛型), breakdown of the coordination between the heart and the kidney(心腎不交型), mental confusion due to phlegm(痰迷心竅型), accumulation of stagnant blood(蓄血型), internal injury by seven emotion (七情所傷型). 2. The type of deficiency of both the heart and spleen(心脾兩虛型) occurs when the heart and spleen is injured by overthinking(思慮過度), The symptoms are heart palpitation(心悸), continuous palpitation(??), insomnia(少寐), hypochondric discomfort(心煩), dream disturbed sleep(多夢), being easy to be scared(易驚), dizziness(眩暈), these are caused by blood deficiency of the heart(心血不足), poor appetite(飮食不振), loss of appetite(納?), short breath(氣短), sense of turgid abdormen(腹部膨滿感), loose stool(泥狀便), these are caused by deficiency of the spleen(脾虛), lassitude and weakness (身倦乏力), lassitude of the extremities (四肢無力), dim complexion (面色少華), pale lips(舌質淡), thready and feeble(脈細弱無力), these are caused by deficiency of both qi and the blood(氣血虛損). The remedy is nourishing the heart-blood(養心血) and regulating the spleen(理脾土). I can prescribe the recipes such as Guibitang(歸脾湯), Gagambosimtang(加減補心湯), Seongbitang(醒脾湯), Insin-guisadan(引神歸舍丹), Insamyangyoungtang(人蔘養榮湯), Sojungjihwan(小定志丸), Yungjigo(寧志膏), Palmijungjihwan(八味定志丸), etc., 3. The type of deficiency of the heart(心虛型) occurs when the heart-blood is injured by the mental tiredness(神勞) and so blood cannot nourish the heart. The symptoms are amnesia(健忘), short breath(氣短), heart palpitation(心悸), perspire spontaneously(自汗), facial pallidness(顔面蒼白), pale lips (舌質淡白), feeble pulse and lassitude(脈虛無力), intermittent pulse(結代脈). The remedy is nourishing the hart and blood and allaying restlessness(補心益血安神). I can prescribe the recipes such as Chenwangbosimdan(天王補心丹), Jeongji-hwan(定志丸), Gaesimhwan(開心丸), Youngjigo(寧志膏), Chilseonghwan(七聖丸), Baegseogyoungtang(白石英湯), Oseohwan(烏犀丸), Yangsinhwan(養神丸), Guisindan(歸神丹), Bogsinsan(茯神散), Jinsamyohyangsan(辰砂妙香散), Cheongeumboksinsan(千金茯神散), Samjotang(蔘棗湯), jangwonhwan(壯元丸), Sa gunjatang(四君子湯) minus rhizoma atractylodis macrocephalae(白朮) plus rhizoma acori graminei(石菖蒲), radix polygalae(遠志), cinnabaris(朱砂), etc. 4. The type of deficiency of the kidney(腎虛型) occurs when the kidney-qi and kidney-essence is deficient(腎氣腎精不足) and so it cannot nourish the brain. The symptoms arc amnesia(健忘), ache at the waist and lassitude in the lower extremities(腰산腿軟), dizziness and tinnitus(頭暈耳嗚), emmission and premature ejaculation(遺精早泄), burning sensation of the five centres(五心煩熱), flushed tongue(舌紅), rapid and small palse(脈細數). The remedy is nourishing the kidney and strengthen the essence(補腎益精). I can prescribe the recipes such as Gagamgobonhwan(加減固本丸), Jeongjihwan(定志丸), Gongseongchlmjungdan(孔聖枕中丹), Yugmigihwanghwan(六味地黃丸) plus ra-dix polygalae(遠志), fructus schizandrae(五味子), Yugmigihwanghwan(六味地黃丸) plus radix polygalae(遠志), fructus schizandrae(五味子), rhizoma acori graminei(石菖蒲), semen zizyphi spinosae(酸棗仁), Palmihwan(八味丸) plus fructus schizandrae(五味子), semen zizyphi spinosae(酸棗仁). etc., 5. The type of breakdown of the coordination between the heart and the kidney (心腎不交型) occurs when the heart-fire(心火) and kidney-fluid(腎水) are imbalanced. The symptoms are amnesia(健忘), hypochondric discomfort(心煩), insomnia(失眠), dizziness and tinnitus(頭最耳嗚), feverish sensation m the palms and soles(手足心熱), emmision(遺精), ache at the waist and lassitude in the lower extremities(腰?腿軟), flushed tongue(舌紅), rapid pulse(脈數). The remedy is coordinating each other(交通心腎). I can prescribe the recipes such as Gangsimdan(降心丹), Jujaghwan(朱雀丸), Singyotang(神交湯), Simsinyang- gyotang(心腎兩交湯), Yugmihwan(六味丸) plus fructus schizandrae(五味子), radix polygalae(遠志), Yugmihwan(六味丸) plus fructus schizandrae(五味子), radix polygalae(遠志), rhizoma acari graminei(石菖蒲), semen zizyphi spinosae(酸棗仁), etc., 6. The type of mental confusion due to phlegm(痰迷心竅型) occurs when the depressed vital energy(氣鬱) create phlegm retention(痰飮) and phlegm stagnancy(痰濁) put the heart and sprit(心神) out of order. The symptoms arc amnesia(健忘), dizziness(頭暈), chest distress(胸悶), nausea(惡心), dull(神思欠敏), dull and slow facial expression(表情遲鈍), tongue with yellow and greasy fur(舌苔黃?), sliperry pulse(脈滑). The remedy is removing heat from the heart to restore consciousness and dispersing phlegm(淸心化痰開竅) I can prescribe the recipes such as Gamibogryeongtang(加味茯?湯), Goa-rujisiltang(瓜蔞枳實湯), Jusaansinhwan(朱砂安神丸), Dodamtang(導痰湯) plus radix saussurea(木香), Yijintang(二陳湯) plus succus phyllostachyos(竹瀝), rhizoma zingiberis(生薑) Ondamtang(溫膽湯) plus rhizoma acori graminei(石菖蒲), rhizoma curcumae aromaticae(鬱金), etc., 7. The type of accumulation of stagnant blood(蓄血型) occurs when the blood is accumulated in the lower part of body. The symptoms are amnesia(健忘), chest distress(胸悶), icteric skin(身黃), rinsing the mouth but don't wanting eat(漱水不欲燕), madness(發狂), black stool(屎黑), pain in the lower abdomen(小腹硬痛). The remedy is dispersing phlegm and absorb clots (化痰化瘀), I can prescribe the recipes such as Jeodangtang(抵當湯), Daejeodanghwan(代抵當丸), Hyeolbuchugeotang (血府逐瘀湯) plus rhizoma acori graminei (石菖蒲), rhizoma curcumae aromaticae(鬱金), Jusaansinhwan(朱砂安神丸) plus rhizoma curcumae aromaticae(鬱金), radix polygalae(遠志), semen persicae(桃仁), cortex moutan radicis(收丹皮), etc., 8. The type of internal injury by seven emotion(七情所傷型) occurs when the anger injures the will stored in the kidney(腎志). The symptoms are amnesia(健忘), heart palpitation(心悸). hot temper(易怒), being easy to be scared(善驚), panic(易恐). The remedy is relieving the depressed liver and regulating the circulation of qi(疏肝解鬱). I can prescribe the recipes such as Tongultang(通鬱湯), Sihosogantang(柴胡疏肝湯) plus rhizoma acari graminei(石菖蒲), rhizoma curcumae aromaticae(鬱金), etc.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.4
• /
• pp.290-298
• /
• 2007

Background: The currently available diagnostic markers for pleural effusion have a limited role. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role in the myeloid cell mediated inflammatory response, and is up regulated in the body fluid by bacterial or fungal products. This study examined the expression of sTREM-1 in pleural effusion. Methods: Between April 2004 and December 2005, 48 patients with pleural effusions were enrolled in this study. The pleural fluids were taken and analyzed for the total protein, glucose, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and sTREM-1. Bacterial cultures and cytology tests were also performed. Results: The clinical diagnoses were 17 parapneumonic, 14 tuberculous, and 13 malignant effusions. Four patients presented with transudates. The mean ages of the parapneumonic, tuberculous and malignant effusion groups were $57.1{\pm}19.7$, $49.5{\pm}18.6$, $66.9{\pm}15.5$, and $76.0{\pm}18.1$. respectively. The level of sTREM-1 expression was significantly higher in the parapneumonic effusions ($344.0{\pm}488.7$) than in the tuberculous effusions ($81.7{\pm}56.6$) and malignant effusions ($39.3{\pm}19.6$). With a cut-off value of 55.4pg/ml, the sensitivity and specificity for a parapneumonic effusion was 70.6% and 74.1%. Conclusion: sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.