• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.1
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• pp.25-33
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• 1998

Cyclooxygenase (COX) is an enzyme involved in the conversion of arachidonic acid to prostaglandins (PGs), and exists in two forms, COX-1 and COX-2. COX has been reported to be involved in early implantation by secretion of PGs which causes permeability of vessels and reaction of decidual cells around the implantation site. Recently, in mice and sheep studies, COX-1 and COX-2 expression in the endometrium has been reported to be different according to implantation and stages of the estrous cycle, but expression of COX-1 and COX-2 in human endometrium during the menstrual cycle has not yet been established. The purpose of this study was to observe the variances of COX-1 and COX-2 expression by immunohistochemical staining in endometrial samples obtained from human hysterectomy specimens and biopsies of women of reproductive age according to different stages of the menstrual cycle. Also, we attempted to observe COX-1 and COX-2 expression in the epithelial and stromal cells of the endometrium obtained during the mid-secretory phase, which were cultured separately. COX-2 showed a cyclic pattern of expression according to the different stages of the menstrual cycle and was strongly expressed particularly at the mid-secretory phase which corresponds to the time of implantation. However, COX-1 tended to be increased in the early proliferative, and mid- and late secretory phases, but was also expressed in the whole menstrual cycle showing no particular pattern. In the separately cultured cells COX-1 was expressed in epithilial cells and COX-2 in the stromal cells. The above results suggest that since COX-2 is expressed at the same time as implantation and cultured cells display a specific secretory pattern, COX-2 has inductive endocrine enzyme properties and has an important effect on endometrial cells during implantation. Also, COX-2 expression in endometrial cells may be utilized as a useful marker of endometrial maturation.

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.83-86
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• 2014

Poly(A) polymerase (PAP) play an essential role for maturation of mRNA by adding the adenylate residues at the 3' end. PAP functions are regulated through protein-protein interaction at its C-terminal region. In this study, cyclophilin A (CypA), a member of the peptidyl-prolyl cis-trans isomerase family, was identified as a partner protein interacting with the C-terminal region PAP. The interaction between PAP and CypA was inhibited by the immunosuppressive drug cyclosporine A. Deletion analysis revealed that the N-terminal 56 residues of CypA are sufficient for the interaction with PAP. Interestingly, we observed that PAP and CypA colocalize in the nucleus during SDF-1-induced chemotaxis, implying that CypA could be involved in the regulation of polyadenylation by PAP in the chemotactic cells.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.75-79
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• 2013

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.364-367
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• 2011

Background: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin $E_2$ ($PGE_2$) and prostaglandin $I_2$ ($PGI_2$) and that these PGs regulate biological functions of T and B cells. Methods: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to $PGE_2$ and $PGI_2$ production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. Results: Both $PGE_2$ and $PGI_2$ productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). Conclusion: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.1
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• pp.49-60
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• 2008

Objective: This study was carried out to investigate the effects of 3-dimensional co-culture of human endometrial cells decidualized with progesterone and TGF-${\beta}1$ on the development of 2-cell mouse embryos. Methods: Stromal and epithelial cells isolated from human endometrial tissue were immunostained for cytokeratin and vimentin. Expression of TGF-${\beta}1$, its receptor-1, -2, integrin-${\beta}3$ and prolactin in mono or co-culture according to three different hormone conditions was investigated by RT-PCR. Differential staining was used to investigate the number of ICM and trophectoderm of hatched mouse blastocysts in different three conditions. Results: The immunohistochemical study was positive for cytokeratin or vimentin and confirmed that epithelial and stromal cells were isolated from endometrial tissue successfully. In co-culture, TGF-${\beta}1$, its receptor-1, integrin-${\beta}3$ and prolactin except TGF-${\beta}1$-r2 were expressed in progesterone dominant condition. The hatching and attaching rate were higher in the co-culture with decidualized cells (p<0.05). However, we observed that lots of the incomplete hatched blactocysts attached on non-decidualized cells. The ICM number of hatched mouse blastocysts was higher in co-culture with decidualized and non decidualized cells than media only culture (p<0.05). The trophectoderm number of hatched blastocyst was higher in the co-culture with decidualized cells than non-decidualized cells or media only culture (p<0.05). Conclusion: The administration of progesterone, estrogen and TGF-$\beta$ could induce decidualization of stromal and epithelial cells isolated from human endometrial tissue using 3-dimensional co-culture, and the decidualization of human endometrial cells could increase the hatching and attaching rate of 2-cell mouse embryos.

• The Korea Journal of Herbology
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• v.22 no.4
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• pp.145-153
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• 2007

Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Toosendan fructus(TOF) has been traditionally used in treatment of abdominal pain and parasite. In this study, we investigated the therapeutic effects and action mechanism of Toosendan fructus (TOF) in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Method : Eight-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histophatological profiles. Toosendan fructus(TOF) and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopahological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. Also, the prostates were observed by hematological alterations of WBC, RBC, hemoglobin, hematocrit and platelet. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Toosendan fructus(TOF) showed a diminished range of the tissue damage. Epithelial score was improved in Toosendan fructus(TOF) than that of the control. The epithelio-stromal ratio was lower in Toosendan fructus(TOF) when compared to that of the control. Also, the examination of bloods were not observed hematological change. Conclusions : These findings suggest that Toosendan fructus(TOF) may protect the glandular epithelial cells and may take hematological safety. We concluded that Toosendan fructus(TOF) may could be a useful remedy agents for treating the chronic non-bacterial prostatitis.

• Korean Journal of Veterinary Research
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• v.48 no.1
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• pp.111-117
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• 2008

Gastrointestinal stromal tumor (GIST) is one of the mesenchymal tumors originated from gastrointestinal submucosa. A 10 year-old, male, mixed breed dog with persistent diarrhea, anorexia and lethargy was referred to Haemaru Animal Referral Hospital. Large mass originated from the transverse colon was observed and large amount of ascites and free gas were found on abdominal radiography and ultrasonography. The ascites was septic exudate mixed with bacteria that consisted with intestinal perforation. There was no metastatic lesion. This mass was tentatively diagnosed as adenocarcinoma, leiomyosarcoma (LMS) and lymphosarcoma and surgical resection and histilogical examination were planned. However, according to owner's request, the patient was euthanized and then the necropsy was performed. About 10 cm sized mass originated from the cecum, ascending colon and transverse colon was adhered to surrounding mesentery and the perforation and large amount of ascites were observed. GIST was suspected on histopathologic examination and confirmed according to CD 117 expression in immunohistochemistry. GIST, derived from interstitial cells of Cajal, can be distinguished from LMS and leiomyoma (LM) on the basis of expression of CD117 (KIT) immunohistochemically. GIST has a different biological behavior and clinical course compared with LMS and LM, therefore definite diagnosis for GIST using immunohistochemistry is clinically important to predict the precise prognosis of the patient.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.284-287
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• 2010

We report the case of a 68-year-old man with a stromal tumor of uncertain malignant potential (STUMP), which had metastasized to the lung. The patient complained of an enlarged mass in the anterior chest. Chest computed tomography (CT) showed a sternal abscess with multiple nodules in both lungs. A thoracoscopic lung biopsy of the nodules and incision/drainage of the sternal mass were performed simultaneously. CT of the pelvis revealed an enlarged prostate with irregular cystic lesions in the pelvis. Prostate biopsy was done and demonstrated hypercellular stroma with minimal cytological atypia, a distinct pattern of STUMP. The sternal abscess proved to be tuberculosis and the lung lesion was consistent with STUMP, which had spread from the prostate. However, to our knowledge, the tuberculous abscess might not be assoicated with STUMP in the lung. The patient refused surgical prostatectomy and was discharged with anti-tuberculosis medication. On one-year follow up, the patient had no evidence of disease progression.

• The Journal of Internal Korean Medicine
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• v.28 no.4
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• pp.779-790
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• 2007

Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. GLS (Gleditsiae Spina) has traditionally been used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of GLS in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Method : We observed four experimental objects of normal group, control group, testosterone group, and GLS group. Rats were treated with 17$\beta$-estradiol after castration for induction of experimental non-bacteral prostatitis, which is similar to human chronic prostatitis in histophatological profiles. GLS and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopahological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. Also, the prostates were observed by hematological alterations of WBC, RBC, hemoglobin, hematocrit and platelet. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with GLS showed a diminished range of tissue damage. Epithelial score was improved in GLS over that of the control. The epithelial-stromal ratio was lower in GLS when compared to that of the control. Conclusion : These findings suggest that GLS may protect the glandular epithelial cells. We concluded that GLS could be a useful remedy agent for treating chronic non-bacterial prostatitis.