• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• Journal of Life Science
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• v.29 no.4
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• pp.402-409
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• 2019

Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.45 no.1
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• pp.37-47
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• 2019

Recently, due to the increase in skin diseases caused by particulate matter, endocrine disruptor and environmental changes, the trend of development of cosmetic materials has been shifting to the more safe and effective ingredients based on natural materials rather than existing synthetic compounds like steroids and antihistamines. This study aimed to develop a new natural cosmetic materials using oriental herbs such as Eucommiae cortex, Alpinia oxyphylla Miquel and Bombyx batryticatus. First, DPPH assay was performed to examine the antioxidative activity of the herbal extract (Mix) and 98.8% DPPH radical scavenging activity was confirmed at $400{\mu}g/mL$ concentration of it. In order to confirm the whitening efficacy of oriental herbal extracts(mix), the amount of melanin synthesized after stimulation of ${\alpha}-MSH$ with B16F10 cells was measured. Results showed that it was decreased to 27.1% comparing with the only ${\alpha}-MSH$ treated group, which confirmed the whitening efficacy. Also, both nitric oxide(NO) production and iNOS and COX-2 expression were significantly reduced in RAW264.7 macrophages activated by LPS in the presence of the extracts(Mix). The mRNA expression of the inflammatory cytokines such as $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ was also analyzed to confirm the inhibition effect of the extracts on inflammation. Finally, to confirm the enhancement of skin barrier function, the expression of claudin 1 gene, a tight junction protein, was observed using human keratinocyte HaCaT cells and increased as concentration dependent manner. From these results, it is concluded that the oriental herbal extracts(Mix) containing Eucommiae cortex, Alpinia oxyphylla Miquel and Bombyx batryticatus is effective for antioxidant, anti-inflammation, skin whitening, and skin barrier and thus could be applied as a new natural cosmetic material.

• Journal of Food Hygiene and Safety
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• v.36 no.6
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• pp.528-536
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• 2021

The purpose of the study was to investigate the content of sinigrin, an index component, in Brassica juncea extract and to evaluate the differentiation of lipocytes, inhibition of production of reactive oxygen species (ROS) and reduction of protein production by lipogenic factors (PPARγ, C/EBPα, aP2) in the processing of Brassica juncea extract and sinigrin in 3T3-L1 preadipocytes which induces Bisphenol A (BPA), an endocrine disrupting environmental hormone. From the investigation, the content of sinigrin in Brassica juncea extract, measured by HPLC, is found to be 21.27±0.2 mg/g. The XTT assay result on BPA-derived 3T3-L1 adipocytes shows there is no cytotoxicity found from 180 µM of sinigrin and 300 ㎍/mL of Brassica juncea extract. Moreover, both intracellular lipid accumulation and ROS production during differentiation of lipocyte are significantly reduced in cells processed with Brassica juncea extract and sinigrin. Lastly, it was also found that the production of transcription factors of lipocyte differentiation, PPARγ, C/EBPα and aP2, were found to be suppressed by the application of Brassica juncea extract and sinigrin. Such results reveals that Brassica juncea is effective in not only suppressing lipid accumulation in the environmental hormone bisphenol A-derived lipocyte, but also in reducing the ROS. The sinigrin-containing Brassica juncea is highly expected to be used in natural functional supplements that prevents the lipid metabolism disorders caused by BPA. There are necessities for additional clinical research and follow-up studies on the in vivo model to verify the relevant mechanisms.

• Development and Reproduction
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• v.15 no.4
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• pp.373-383
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• 2011

Tributyltin (TBT) is one of endocrine disrupters which are known as having similar function to sex steroid hormone inducing apoptosis in various tissues of rodents. Recently, it has been reported that TBT induces apoptosis in thymus causing the decreased thymic function, but little is known about the mechanism. To elucidate the mechanism, three-week-old SD female rats were orally administrated with TBT 1, 10, and 25 mg per body weight (kg) and sesame oil as a control for 7 days. On day 8, the thymi were obtained and weighed, and then the number of thymocytes was counted. We also performed H&E staining, TUNEL assay, and Annexin V flow cytometric analysis to examine the apoptosis rates and the structure in the thymus. Next, we investigated the adipogenesis and apoptosis-related mRNA expression levels in the thymi by real-time PCR. The thymic weight and the number of thymocytes were decreased by TBT in a dose-dependent manner. As a result of the H&E staining, the boundary between cortical and medullary area was blurred in the thymi of TBT treated rats compared to those of controls. In the results of TUNEL assay and Annexin V flow cytometric analysis, apoptosis rates in the thymus were increased after TBT treatment. The expression levels of thymic epithelial cell marker genes such as EVA, KGF, AIRE, and IL-7 were significantly decreased in the thymi of TBT treated rats, but $PPAR{\gamma}$, aP2, PEPCK, and CD36 were significantly increased. The expression of $TNF{\alpha}$ and TNFR1 as apoptosis-related genes also was significantly increased after TBT treatment. The present study demonstrates that TBT can increase the expression of adipogenesis and apoptosis-related genes leading to apoptosis in the thymus. These results suggest that the increased adipogenesis of thymus by TBT exposure might induce apoptosis in the thymus resulting in a loss in thymic immune function.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.654-658
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• 2002

Purpose : Endocrine and immune systems are connected and interdependent. Adrenal glands play an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. These steroids have an antagonistic effect on the T cell progression into Th1 and Th2 cells and on the induction of correlated interleukins. Therefore we evaluated the role of adrenal androgen and cortisol as immune modulators in Kawasaki disease( KD) with changes of T cell immunity. Methods : From April to August in 2001, we examined serum DHEAS and 24 hour urine free cortisol(F) before administration of immunoglobulin and steroids by radioimmunoassay in 14 KD patients. It's clinical severity was determined by Harada score and coronary lesion. Results : The age of the patient group ranged from 4 months to 4 years; its average age was 2.3 years. Three patients(21.4%) were below 1 year, 2(14.3%) between 1 and 2 years, 5(35.7%) between 2 and 3 years, 4(28.6%) between 3 and 4 years of age. Male to female ratio was 1:1.3. DHEAS was significantly decreased in patients($11.1{\pm}6.0{\mu}g/dL$) more than controls($81.6{\pm}13.3{\mu}g/dL$)(P<0.05). Twenty-four hour urine free cortisol was significantly increased in patients($36.9{\pm}21.9{\mu}g/dL$) more than controls($13.6{\pm}5.5{\mu}g/dL$)(P<0.05). Ratio of DHEAS/F was decreased remarkably in patients($0.33{\pm}0.20$) more than controls($6.65{\pm}2.56$)(P=0.016). There was no difference between ratio of DHEAS/F and Harada score, but its ratio was very low in patients with coronary aneurysm. Conclusion : These data demonstrate that there are changes of DHEAS and cortisol in acute stage of KD and the dis-equilibrium between two steroids may be relevant in the T cell immune response induction of Kawasaki disease. These changes support the use of DHEAS/F ratio as one of the predictive factors of coronary arteries complication.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.