Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.
Sex steroids are known to be involved in skeletal muscle development (anabolic effect) and are frequently used in medicines. It has been known that pork contains a variety of steroids that are mainly synthesized in the gonads (testis and ovary). Thus, the present study was conducted to evaluate the effects of anabolic steroids of pork on the proliferation and differentiation of myogenic satellite cells (MSC). Three different methods (M1, M2, and M3) were developed for the isolation and purification of steroids from porcine tissues. Among three extraction methods that we developed, M3 was the best method with respect to the quantities of steroids and the induction of MSC proliferation. Hormonal analysis showed that the steroid hormone levels were the highest in muscle and fat of intact male than those of castrated males and females. In addition, the highest serum levels of nandrolone and testosterone were detected in intact males, whereas estrone and $17{\beta}$-estradiol levels were similar in the entire experimental serum samples. Expression of androgen receptor (AR), myoD, desmin, and myogenin in bovine muscle cells were significantly up-regulated by the treatment of steroid extracts. The highest increas of myogenin and AR mRNA abundance were observed in the MSCs treated with M3 extract (p<0.001). Altogether, the present research showed the positive effect of steroids on MSC proliferation and differentiation in vitro. These results would certainly imply a beneficial effect of pork consumption on human muscle development.
Journal of the Korean Society of Food Science and Nutrition
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v.45
no.6
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pp.789-796
/
2016
The anti-lipogenic effect of cereal samples on high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) in mice was studied. We divided C57BL/6 mice into various groups based on 8 weeks of treatment with three types of cereal samples (HSD+WR, HSD diet containing 40% white rice; HSD+MCG, HSD diet containing 40% mixed cereal grain; HSD+AO-MCG, HSD diet containing 40% mixed antiobesity-cereal grain). After the experimental period, body weight changes, liver weights, serum lipid profiles, and hepatic fatty acid metabolism-related gene expression levels were determined. We found that HSD+WR, HSD+MCG, and HSD+AO-MCG treatments reduced body weight and liver weight, especially HSD+MCG and HSD+AO-MCG effectively reduced levels of serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol. However, high density lipoprotein cholesterol levels increased compared to the control group. Furthermore, expression of hepatic lipogenic genes such as sterol regulatory element-binding protein-1c, acetyl-coenzyme A carboxylase, fatty acid synthase, stearoyl-coenzyme A desaturase-1, cluster of differentiation, and $PPAR-{\gamma}$ (peroxisome proliferator activated receptor ${\gamma}$) decreased, whereas expression of ${\beta}-oxidation$ genes such as $PPAR-{\alpha}$ and carnitine palmitoyl transferase-1 increased following HSD+MCG and HSD+AO-MCG treatment compared with levels in HSD+WR and control groups. These results suggest that the functional cereal samples, especially HSD+AO-MCG treatment, improved hepatic steatosis triggered by an HSD-induced imbalance in hepatic lipid metabolism.
Platycodin D, a major component of Platycodi radix, is known to have various activities including anti-inflammatory, anti-hyperlipidemic, anti-tumor activities and others. Recently, it was reported that platycodin D inhibits fat accumulation and adipogenesis. The aim of this study was to investigate whether various adipogenic regulators are modulated by platycodin D treatment during the adipogenesis of 3T3-L1 cells. mRNA levels of terminal markers of adipogenesis such as ADIPOQ (adiponectin) and GLUT (glucose transporter) 4, which were quantified by real time PCR, were decreased by platycodin D treatment. mRNA expression of PPAR (peroxisome proliferator-activated receptor) $\gamma$ and C/EBP (CCAAT/enhaner binding protein) $\alpha$, which are central transcription factors of adipogenesis, were also decreased by platycodin D treatment. To elucidate the detailed molecular mechanism of platycodin D-induced inhibition of adipogenesis, we analyzed mRNA expression of upstream regulators of PPAR$\gamma$ and C/EPB$\alpha$. mRNA levels of the pro-adipogenic regulators, KROX20 and KLF (Kruppel-like factor) 15 were markedly down-regulated by platycodin D treatment. On the other hand, mRNA expression of CHOP (C/EBP homologous protein), an anti-adipogenic regulator, was significantly up-regulated by platycodin D treatment. mRNA levels of other pro-adipogenic regulators, C/EBP$\beta$ and C/EPB$\delta$, were not affected by platycodin D treatment, and another anti-adipogenic regulator, C/EBP$\gamma$ was also not affected by platycodin D treatment. Taken together, these results suggest that platycodin D-induced inhibition of adipogenesis is mediated by gene interactions including the down-regulation of pro-adipogenic regulators, KROX20 and KLF15, and the up-regulation of an anti-adipogenic regulator, CHOP.
Park, Jung Ae;Jin, Kyong-Suk;Oh, You Na;Hyun, Sook Kyung;Choi, Yung Hyun;Kwon, Hyun Ju;Kim, Byung Woo
Journal of Life Science
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v.23
no.1
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pp.69-78
/
2013
Vitis amurensis Rupreche, a sort of grape, grows naturally in Asian countries. It is known for important biological effects such as antioxidation, anti-inflammation, neuroprotection, and angiogenesis inhibition. Although its root is used as a traditional folk medicine in Korea, the root's biological activities are poorly studied. In the present study, the effects of V. amurensis root methanol extract (VARM) and its solvent fractions on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. The VARM significantly suppressed adipocyte differentiation, lipid accumulation, and the triglyceride (TG) content of 3T3-L1 preadipocytes in a dose-dependent manner, without cytotoxicity. To identify active molecules, the VARM was fractionated with a series of organic solvents including dichloromethane ($CH_2Cl_2$), ethyl acetate (EtOAc), and n-butanol (n-BuOH). All the fractions also showed inhibition of lipid accumulation in the 3T3-L1 preadipocytes. The $CH_2Cl_2$ fraction showed the most powerful anti-obesity effect through the modulation of cytidine-cytidine-adenosine-adenosinethymidine (CCAAT)/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) gene and protein expression. Oleanolic acid was one of the main active compounds involved in the anti-obesity activity of the V. amurensis root. These results provide important new insight into the potential potent anti-adipogenic effect of the V. amurensis root and illustrate that one of the main compounds involved in this effect is oleanolic acid.
Park, Hyoung-Jin;Lee, Yun-Lyul;Kwon, Hyeok-Yil;Shin, Won-Im
The Korean Journal of Physiology
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v.20
no.1
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pp.1-7
/
1986
It has been well documented that the peripheral autonomic nervous system plays an important role in exocrine pancreatic secretion. However, the role of the central nervous system in pancreatic function is still obscure even though the central nervous system has been known to control gastrointestinal functions through the autonomic nervous system. Since the reticular formation in the mesencephalone seems to integrate the autonomic function, the present study was undertaken to investigate a possible influence of the reticular formation upon the exocrine pancreatic secretion. Twenty·two albino rats fasted for 24 hours were anesthetized by intraperitoneal injection of urethane in a dose of 1 g/kg, The pancreatic duct was cannulated to collect pancreatic juice and bile juice was diverted to the jejunum. The gastroduodenal junction was ligated to Prevent passage of gastic juice into the duodenum. A pair of electrodes were bilaterally inserted in the reticualr formation of the mesencephalone with aid of a stereotaxic apparatus. When the volume of pancreatic juice secreted for 10 min became constant, the reticular formation was electrically stimulated for 10 min. Parameters of the electical stimulation was 1.3V, 40 Hz and 2 msec. When the pancreatic secretion returned to the level before the electrical stimulation, cervical vagotomy (11 rats) or administration of propranolol (11 rats) in a dose of 0.1 mg/kg through the jugular vein was carried out. Ten minutes after the treatment, the electrical stimulation of the reticular formation was repeated. The brain was fixed by perfusion of 10% formaline solution through the heart, and then placement of the electrode tip was examined histologically. Protein concentration and amylase activity in samples of Pancreatic secretion were measured. The electrical stimulation of the reticular formation significantly increased in volume $({\mu}l/10\;min)$, Protein output $({\mu}g/10\;min)$ and amylase output (U/10 min) in the pancreatic secretion. The stimulatroy effects were not affected by the cervical vagotomy but completely abolished by propranolol. Meantime, it was also observed that both vagotomy and propranolol significantly reduced the pancreatic secretory function. These results indicate that the reticular formation in the mesencephalone may exert a stimulatory effect upon the Pancreatic secretory function not through the vagus nerve but through the sympathetic pathway in anesthetized rats.
Park, In-Jae;Park, Sung-Hwan;Yun, Ji-Hyun;Choi, Goo-Hee;Kim, Hyun-Jung;Seo, Yun-Hee;Cho, Ju-Hyun
Journal of Food Hygiene and Safety
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v.32
no.6
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pp.536-541
/
2017
The object of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis of an stress-induced SD rat model. Rats were randomly divided into six groups: Normal (normal group), Control (stress-induced gastritis), Ranitidine (stress-induced gastritis and ranitidine 50 mg/kg), LJF-HE-L (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 30 mg/kg), LJF-HE-M (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 60 mg/kg), LJF-HE-H (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 120 mg/kg). In groups treated with LJF-HE, gastric mucosal damage and pepsin activity were reduced. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r) in the gastric lesions. The plasma levels of IL-$1{\beta}$ slightly but significantly decreased in LJF-HE treated groups compared to control. The plasma level of PGE2 was also significantly increased in LJF-HE treated groups. These results suggest that LJF-HE has the ability to reduce of the severity stress-induced gastritis.
Kim, Sung-Kon;Kim, Nam-Kuk;Yoon, Du-Hak;Kim, Tae-Hun;Yang, Boo-Keun;Lee, Hyun-Jeong
Journal of Animal Science and Technology
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v.52
no.4
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pp.265-270
/
2010
Adipogenesis has been one of the most intensely studied models of cellular differentiation. During adipogenesis, differential expression of many adipogenesis related genes lead to profound changes in cellular, morphological, and physiological characteristics of the differentiating cells. The aim of the present study was to examine the expression levels of adipogenic candidate genes, cAMP early repressor (ICER), nephroblastoma over-expressed protein (NOV), heat shock protein beta 1 (HSPB1) and succinate dehydrogenase (SDH), during adipogenesis of bovine mesenchymal stem cells (BMSC). The BMSC were cultured in DMEM / low glucose medium with adipogenic inducers for 6 days and the expression of various candidate genes which seemed related to adipogenesis were measured by real-time PCR. This study showed that the expression of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) and fatty acid binding protein 4 (FABP4) genes as adipogenic indicators were increased to 3.11 and 3.11 folds on day 6 than on day 0, respectively (p<0.05). To determine whether candidate genes were related to adipogenesis, the expression levels of ICER, NOV, HSPB1, and SDH genes were measured during adipogenesis in BMSC. Our results showed that the expression level of ICER gene was significantly increased to 4.12 folds (0.01729 vs. 0.07138; p<0.05), whereas NOV, HSPB1, and SDH genes were decreased to 2.89, 3.18 and 2.36 folds, respectively, on day 6 when compared to day 0. These results suggest that these candidate genes have stimulatory or inhibitory effects on adipogenesis in BMSC, indicating that these genes may be directly or indirectly related to the adipogenic event of adipose precursor cells.
In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.
The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.
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