• 동의생리병리학회지
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• 제21권3호
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• pp.709-713
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• 2007

Basement membranes (BMs) are extracellular matrices associated with epithelia, endothelia, muscle, fat and peripheral nerve. They are involved in cell survival, migration, differentiation. BMs functions also include tissue formation and provide mechanical stability as a selective barriers. Laminins are heterotrimeric glycoproteins found in BMs and have a crucial role in cell adhesion and signalling. Madin-Darby canine kidney (MDCK) cells are the best established mammalian model for studying epithelial cell biology The cells form an epithelial monolayer, with tight junctions separating an apical surface from a basolateral membrane facing the filter support and neighboring cells. In this study, using MDCK cells, the synthesis of the BM protein such as laminin with or without methanol extract of Chrysanthemum morifolium (CM) stimulation was analyzed by immunoblotting and CM showed significant increased cell density and enhanced synthesis of laminin.

• Journal of Ginseng Research
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• 제46권1호
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• pp.115-125
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• 2022

Background: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. Methods: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Results: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. Conclusion: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

• Journal of Audiology & Otology
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• 제23권2호
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• pp.69-75
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• 2019

Background and Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. Materials and Methods: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. Results: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. Conclusions: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.

• 한국자원식물학회지
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• 제36권3호
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• pp.207-218
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• 2023

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

• 대한청각학회지
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• 제23권2호
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• pp.69-75
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• 2019

Background and Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. Materials and Methods: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. Results: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. Conclusions: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.

• BMB Reports
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• 제39권4호
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• pp.339-345
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• 2006

The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood-retinal barrier (BRB), is an endothelial barrier constructed by an extensive network of endothelial cells, astrocytes and neurons to form functional 'neurovascular units', which has an important role in maintaining a precisely regulated microenvironment for reliable neuronal activity. Although failure of the BNB may be a precipitating event or a consequence, the breakdown of BNB is closely related with the development and progression of CNS diseases. Therefore, BNB is most essential in the regulation of microenvironment of the CNS. The BNB is a selective diffusion barrier characterized by tight junctions between endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB have been shown to be astrocyte dependent, for it is formed by the CNS capillary endothelial cells, surrounded by astrocytic end-foot processes. Given the anatomical associations with endothelial cells, it could be supposed that astrocytes play a role in the development, maintenance, and breakdown of the BNB. Therefore, astrocytes-endothelial cells interaction influences the BNB in both physiological and pathological conditions. If we better understand mutual interactions between astrocytes and endothelial cells, in the near future, we could provide a critical solution to the BNB problems and create new opportunities for future success of treating CNS diseases. Here, we focused astrocyte-endothelial cell interaction in the formation and function of the BNB.

• 대한수의학회지
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• 제30권4호
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• pp.361-371
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• 1990

The present observations were focussed mainly on the morphological findings of the utero-vaginal(U-V) glands in normal laying domestic hens and the storage of cock spermatozoa in the U-V glands at various times after artificial insemination(AI). These domestic hens were assigned to three group of PMS-treated, GnRH-treated before last AI, and control group. The hens were sacrified at intervals of 1,3,7,12 and 19 days after AI. Histological sections of U-V junctions were prepared and the morphological structures of the U-V glands were observed and then were scored about the spermatozoa presence in the U-V gland. 1. The U-V glandular tubules were mostly unbranched with single columnar epithelium. Also these tubules were occassionally observed as one circular-rotated tubules or 2 to 3 branched convoluted tubules in special shapes. The numbers of the convoluted curves per tubule were $4.3{\pm}3.3$ and the ranges of convoluted curve number were straight to 16 curves. 2. The inside and outside diameters of the glandular tubules were $6.5{\pm}3.5{\mu}m$, and $35.2{\pm}4.7{\mu}m$, respectively, and the tubular lengths of the U-V glands were $219.3{\pm}115.7{\mu}m$. 3. Storaged spermatozoa in the U-V glands of all three group hens were intensively stained by hematoxylin, and packed in tight, longitudinally parallel bundles within the tubules. In addition, numbers of completely spermatozoa-filled glands were tend to increase or decrease in proportion to the numbers of partially spermatozoa-filled glands. Also U-V glands containing spermatozoa tend to be present collectively in the any zone of U-V junction. 4. In the control group, the numbers of glands containing spermatozoa in the hens at 1,3,7,12, and 19 days after AI were found to be 22.9, 33.3, 35.8, 8.6, and 0% respectively. 5. In the PMS-treated group, the numbers of glands containing spermatozoa in the hens at 1,3,7,12, and 19 days after AI were found to be 33.6, 29.7, 26.8, 8.2 and 0% respectively. 6. In the GnRH-treated group, the numbers of glands containing spermatozoa in the hens at 1,3,7,12, and 19 days after AI were found to be 19.7, 40.8, 20.4, and 0% respectively.

• 대한본초학회지
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• 제35권4호
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• pp.17-23
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• 2020

Objectives : In this study, we investigated the protective effects of Charybdis japonica (C. japonica) water extract on the acute reflux esophagitis in rat models. Methods : Twenty rats were divided into four groups for examination: normal control group (n=6), the reflux esophagitis group (n=6), reflux esophagitis treated with positive control group (ranitidine 40 mg/kg, n=6), reflux esophagitis treated with C. japonica group (100 mg/kg, n=6). All rats fasted for 18 hr and then were induced with reflux esophagitis by a pylorus and forestomach ligation operation. After 4 hr, the rats were sacrificed. The proinflammatory cytokine and proteins expression measured by western bolt assay, and the histopathological analysis of the esophageal mucosa measured by hematoxylin and eosin staining. Results : C. japonica administration significantly was protecting esophageal mucosal damage upon histological analysis of reflux esophagitis in rats. The C. japonica treatment confirmed the protection of the reduction of claudin-5, an evaluation index of the damage of tight junctions in the reflux esophagitis. C. japonica was also found to inhibit the expression of proteins such as COX-2 and TNF-α in the rat esophagus. C. japonica markedly attenuated the activation of NF-κB and phosphorylation of IκBα at the same time. Conclusion : These results indicated that C. japonica suppressed the development of esophagitis through the modulation of inflammation by regulating NF-κB activation. Based on these findings, we concluded that C. japonica can prevent reflux esophagitis.

• IMMUNE NETWORK
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• 제21권4호
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• pp.26.1-26.28
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• 2021

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4⁺ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.