• Journal of Korean Neurosurgical Society
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• v.57 no.5
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• pp.323-328
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• 2015

Objective : Malignant gliomas are the most common primary tumors of the central nervous system and the prognosis of patients with gliomas is poor. The combination of interferon-bata (IFN-${\beta}$) and temozolomide (TMZ) has shown significant additive antitumor effects in human glioma xenograft models. Considering that the poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor, the tropism of human bone marrow-derived mesenchymal stem cells (MSC) for malignant gliomas can be exploited to therapeutic advantages. We investigated the combination effects of TMZ and MSCs that secrete IFN-${\beta}$ on gliomas. Methods : We engineered human MSCs to secret mouse IFN-${\beta}$ (MSC-IFN-${\beta}$) via adenoviral transduction and confirmed their secretory capacity using enzyme-linked immunosorbent assays. In vitro and in vivo experiments were performed to determine the effects of the combined TMZ and MSC-IFN-${\beta}$ treatment. Results : In vitro, the combination of MSC-IFN-${\beta}$ and TMZ showed significantly enhanced antitumor effects in GL26 mouse glioma cells. In vivo, the combined MSC-IFN-${\beta}$ and TMZ therapy significantly reduced the tumor size and improved the survival rates compared to each treatment alone. Conclusion : These results suggest that MSCs can be used as an effective delivery vehicle so that the combination of MSC-IFN-${\beta}$ and TMZ could be considered as a new option for the treatment of malignant gliomas.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.97-101
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• 2003

The salivary glands produce 1.5L of fluid per day. As in other exocrine organs, the general mechanism in the salivary glands is that water movement occurs secondary to osmotic driving forces created by active salt transport. Therefore, high water permeability in the salivary glands is expected to have a variety of aquaporin (AQP), a water channel. Although some AQPs have been known to be present in the salivary glands, roles of parasympathetic nerve in AQP expression have not yet been examined. This study was designed to examine the changes of AQPs and extracellular signal-regulated kinase (ERK) in the submandibular glands after parasympathetic denervation. Right chorda-lingual nerve was cut, and each right (experiment) and left (control) submandibular gland was excised at 1, 3, 7, 14, 30 days after denervation. The denervated right submandibular glands were resulted in weight loss and morphologic changes, including cell loss and atrophy, as the time elapsed after parasympathetic denervation increased, whereas there were no histologic alteration in control side. AQP5 which is known to reside in apical membrane and secretory caraliculi of the submandibular acini were gradually underexpressed according, as the time after denervation increased. Expression of AQP4 in submandibular ductal epithelium was down-regulated after denervation. Besides, AQP3 and 8, which is known to be present in basolateral membrane of the glandular acini, were gradually underexpressed after denervation, similar to the pattern of other types. Expression of ERK, a mitogen-activated protein kinase, was downregulated after parasympathetic denervation in the submandibular gland. These results suggest that parasympathetic nervous system regulates the expression of AQPs in salivary glands, and is in part mediated by ERK pathway.

• Animal cells and systems
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• v.9 no.2
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• pp.101-105
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• 2005

[ ${\beta}ig-h3$ ] is a secretory protein that is induced by $TGF-{\beta}$ and implicated in various disease conditions including fibrosis. We have previously reported that ${\beta}ig-h3$ expression is implicated in astrocyte response to brain injury. In this study, we further investigated potential roles of ${\beta}ig-h3$ protein in the injured central nervous system (CNS). We specifically assessed whether the treatment of microglial cells with ${\beta}ig-h3$ can regulate microglial activity. Microglial cells are the prime effector cells in CNS immune and inflammatory responses. When activated, they produce a number of inflammatory mediators, which can promote neuronal injury. We prepared conditioned medium from the stable CHO cell line transfected with human ${\beta}ig-h3$ cDNA. We then examined the effects of the conditioned medium on the LPS- or $IFN-{\gamma}-mediated$ induction of proinflammatory molecules in microglial cells. Preincubation with the conditioned medium significantly attenuated LPS-mediated upregulation of $TNF-{\alpha},\;IL-1{\beta}$, iNOS and COX-2 mRNA expression in BV2 murine microglial cells. It also reduced $IFN-{\gamma}-mediated$ upregulation of $TNF-{\alpha}$ and COX-2 mRNA expression but not iNOS mRNA expression. Assays of nitric oxide release correlated with the mRNA data, which showed selective inhibition of LPS-mediated nitric oxide production. Although the regulatory mechanisms need to be further investigated, these results suggest that astrocyte-derived ${\beta}ig-h3$ may contribute to protection of the CNS from immune-mediated damage via controlling microglial inflammatory responses.

• Journal of Embryo Transfer
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• v.28 no.3
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• pp.257-263
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• 2013

The endometrium undergoes a cyclic growth and tissue remodeling as changes of epithelial cells, and plasminogen activators (PAs) are related to endometrium tissue remodeling. This study was to evulate expression of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) in porcine uterine epithelial cells. In results, the uPA and tPA were expressed in uterine tissue, epithelium and secretory glands in porcine endometrial cell. In addition, the uPA and tPA were expressed in cultured epithelial cells, and it were mainly expressed in cytoplasm. In porcine uterine tissue and epithelial cells, uPA activity was higher than activity in tPA. In PAs mRNA expression levels, uPA mRNA level was significantly higher than tPA mRNA level (P<0.05). The fluorescence intensity of uPA protein was also higher than fluorescence intensity of tPA protein, and uPA protein expression was significantly higher than in tPA protein expression (P<0.05). Therefore, we suggest that a physiological function in porcine uterine epithelial cells should be more influenced by uPA than in tPA during pre-ovulatory phase.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2031-2033
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• 2016

Background: Symptomatic multiple myeloma (MM) is an acquired B-cell malignant proliferation of antibody secreting plasma cells, characterized by end organ damage due to monoclonal immunoglobulin secretion. The aim of this study wa to determine the stage stratification according to an international scoring system in adult Pakistani MM patients at presentation. Materials and Methods: This single centre retrospective study extendedfrom January 2012 to December 2015. Data were retrieved from the departmental maintained records. Results: A total of 39 patients were diagnosed at our center with MM during the period of the study, 25 males and 14 females. Age ranged between 36 and 81 with a mean of $54.5{\pm}14.8$ and a median of 57 years. Common presenting complaints included fatigue (80.9%), backache (79.3%) and bone pain (66.2%). Overall, 9 patients were in ISS stage I (23%), 12 were in stage II (30.7%) and 18 were in stage III (46.1%). Out of the total, 29 (74.3%) had kappa immunoglobulin andthe remaining 10 (25.6%) had lambda type myelomas. IgG myeloma was commonest, seen in 26 (66.6%) followed by IgA in 11 (28.2%) with non secretory myeloma in one (2.5%) and light chain disease also in one patient (2.5%). Conclusions: MM in Pakistani patients is seen in a relatively young population with male predominance. Primarily patients are symptomatic and risk stratification revealed a predominance of advanced stage III disease in our setting.

• Progress in Medical Physics
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• v.12 no.1
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• pp.59-70
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• 2001

Adrenal chromaffin cells secrete catecholamine in response to acetylcholine. The secretory response has absolute requirement for extracellular calcium, indicating that $Ca^{2+}$ influx through voltage operated $Ca^{2+}$ channels is the primary trigger of the secretion cascade. Although the existence of various types of $Ca^{2+}$ channels has been explored using patch clamp technique in adrenal chromaffin cells, there is still disagreement with the types of $Ca^{2+}$ channels existed in different species. Therefore, we have tried to identify several distinct types of $Ca^{2+}$ channels in rat chromaffin cells. By using nicardipine(L type channel blocker), $\omega$-CgTx GVIA(N type channel blocker), and $\omega$-AgaTx VIA(P type channel blocker), it was identified that L, N, and P type $Ca^{2+}$ channel exist in rat adrenal chromaffin cells and the order of contribution of each channel type to whole cell $Ca^{2+}$ current was L type> N type> P type. type> P type.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.6
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• pp.783-788
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• 2002

Bovine yolk sac at day 24 of pregnancy, and placental membranes (chorion and allantois) from days 70 and 100 of pregnancy were isolated and cultured in a modified minimum essential medium in the presence of $[^{35}S]$methionine. Proteins synthesized and secreted by isolated bovine yolk sac, chorion and allantois were analyzed by fluorography of two-dimensional polyacrylamide gel electrophoresis. Serum-like proteins,transferrin, ${\alpha}$-fetoprotein, ${\alpha}$1-antitrypsin and ${\alpha}$1-acid glycoprotein,were the major protein products of yolk sac. A 21 kDa protein produced by yolk sac was identified immunochemically as retinol-binding protein (RBP). Chorion and allantios from days 70 and 100 of pregnancy were active in protein synthesis and secretion. Both chorion and allantois did not secret serum-like proteins but secreted a number of neutral-to-acidic proteins including RBP. Secretory proteins produced by the yolk sac, chorion and allantois may play important roles in the embryonic development and the successful outcome of pregnancy. Antiserum against bovine placental RBP was employed to the immunocytochemistry by immunoperoxidase method. Immunoreactive RBP was localized in epithelial cells and island-like cell clones of yolk sac. Immunostaining for RBP was detected in simple columnar epithelium of chorion and in simple squamous epithelium of allantois. In the present study, proteins synthesized and secreted by yolk sac at day 24 of pregnancy, chorion and allantois from days 70 and 100 of pregnancy were characterized In addition, RBP was localized in yolk sac, chorion and allantois by immunoperoxidase method. The immunoperoxidase method has been proven to be a very effective technique to identify the cellular source of protein synthesis in extraembryonic membranes.

• Journal of Life Science
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• v.21 no.4
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• pp.613-615
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• 2011

ERp29 is a endoplasmic reticulum (ER) lumenal resident protein that shows sequence similarity to the protein disulfide isomerase family. Its biological function is thought to play a role in the processing of secretory proteins within the ER, possibly by participating in the folding of proteins in the ER. Although some data on ERp29 have been reported, its normal functions are still unclear. To gain insights into the function of ERp29, we identified ARF5 protein as a protein that interacts with ERp29 using yeast two-hybrid screening and GST pull-down assay. Interaction between ERp29 and ARF5 was detected under normal cell conditions but not under ER stress conditions. This result may provide a clue for understanding ERp29 biological functions.

• Korean Journal of Microbiology
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• v.39 no.3
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• pp.135-140
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• 2003

Bacillus sp. secretes high levels of extracellular enzymes into the culture medium. The signal recognition particle (SRP) and the SRP receptor play a central role in targeting pre secretory proteins to the translocase. By the analysis of the DNA microarray of B. lentimorbus WJ5, it was detected that WJ5m12, antifungal activity deficient mutant induced by gamma radiation, had a down-regulated expression of the SRP receptor gene (B. subtitis srb homologue, srbL). To determine the relationship of SRP receptor to antifungal activity, srbL of B. lentimorbus WJ5 was amplified by PCR and ligated into pQE30 vector, and then transferred into WJ5m12. The transformant, WJ5m12::srbL, recovered the antifungal activity. From the 2-DE analysis, the several presecretory proteins accumulated in the mutant cell and decreased to a level of the wild type in WJ5m12::srbL. It seems that the srbL could play an important role in the secretion of the antifungal activity related proteins of B. lentimorbus WJ5.

• The Journal of Korean Medicine
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• v.36 no.1
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• pp.75-85
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• 2015

Objectives: Type 2 diabetes mellitus is a metabolic disease characterized by insulin resistance and high blood glucose level from progressive insulin secretory defect. The rhizome of Atractylodes japonica Koidz. (AJ) has been used for treatment of retention of water in oriental medicine. The aim of this study is to examine the effects of AJ on type 2 diabetes rats. Methods: Type 2 diabetes was induced by 60% high fat diet and low dose streptozotocin. Rats were divided into 4 groups (n = 6); Nor (normal control group), Con (diabetic group treated with vehicle), Met (diabetic group treated with 200 mg/kg metformin) and AJ (diabetic group treated with 100 mg/kg AJ). The body weights and food intakes were measured during the treatment period. After 4 weeks treatment, blood glucose level, HOMA-IR, and protein expressions of IRS-1, p-IRS-1, PPAR-${\gamma}$, and GLUT4 were measured, and histopathological examination of beta cell was performed. Results: Compared with the control group, blood glucose level and HOMA-IR were reduced in rats treated with AJ. Impaired beta cells in pancreas of rats were recovered and phosphorylation of IRS-1 was increased in rats treated with AJ. And also, protein expressions of PPAR-${\gamma}$ and GLUT4 were increased by treatment of AJ. Conclusions: The results suggest that Atractylodes japonica Koidz. may have anti-diabetic effect on type 2 diabetic rats through regulation of blood glucose level and insulin resistance. Therefore Atractylodes japonica Koidz. may have positive effects on patients with type 2 diabetes.