• Journal of Environmental Health Sciences
• /
• v.24 no.2
• /
• pp.126-133
• /
• 1998

Effects of B(a)P on preimplantation mouse embryos in vitro were studied. Preimplantation mouse embryos were exposed to a concentration of 0.3, 1, 3 and 10 $\mu$M B(a)P for 72 hrs. The toxicological effects of B(a)P were evaluated by morphological observation of embryos up to the blastocyst stage, and by measuring DNA, RNA and protein synthesis by radioactive precursor incorporation. At 1 $\mu$M B(a)P did not affect preimplantation development but interfered with hatching and ICM formation. Suppressing effect of ICM formation was dose dependent. At the eight cell stage, the developmental rate was decreased at above 3 $\mu$M of B(a)P. At the blastocyst stage, attachment and trophoblast outgrowth were diminished at the 10 $\mu$M of B(a)P and ICM formation was decreased at 1 $\mu$M of B(a)P. Inner cell number of blastocyst was decreased dose dependently. So, number of ICM was one of the most sensitive and toxicological end point. The RNA incorporation rate of 0.1 $\mu ^3$H-uridine was dosedependent and the protein incroporation of 0.5 $\mu Ci ^{35}$S-methionine showed a significant decrease after 48 hrs. But the DNA incorporation rate of methyl-$^3$H thymidine was not affected. Our results suggested that B(a)P did not affect the DNA replication but transcription was inhibited by dose dependent manner. There delay of development during the blastocyst stage was mainly due to the inhibition of RNA synthesis followed by protein synthesis.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.2
• /
• pp.414-424
• /
• 2007

Adenophorae Radix (AR), Liriopis Tuber (LT), Dendrobii Monile (DM), Polygonati Officinalis (PO), Polygonati Rhizoma (PR) have been used to treated a variety condition/diseases in traditional oriental medicine. The present study was conducted to investigate the immunmodulatory effects of the water-extracted AR, LT, DH, PO and PR. In spleen cell proliferation assay, DH was significantly enhanced mitogenic activity compared with control group. In RT-PCR, DH ad PO induced IL-2 and IFNr cytokine gene expression in mouse spleen cells. Methotrexate(MTX), immune supression agent, was significantly inhibited mouse spleen cell proliferation(1600 mg/ml). In spite of MTX treatement, DH and PO sustained the spleen cell proliferation, In the flow cytometry analysis, DH stimulated mouse spleen cells showed an increase in B-cell phenotype (CD45R/B220). The water-extracted DH and PO inhibited NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cell. DH induced IL-2 and IFNg gene expression in human peripheral mononuclear cells. The GC-MS analysis show that the main component of water-extracted DH was b-Nitroethyl alcohol. The main components of water-extracted PO were Dipirartril-tropico, Methyl sulfoxide and Demsodrox. These data suggest that among these extracts, DH has a protective effcet of immune suppression caused by MTX. DH may be enhance cellular and humoral immune response by the regulation of cytokine gene expression, NO production and B cell production.

• YAKHAK HOEJI
• /
• v.43 no.4
• /
• pp.494-501
• /
• 1999

The skin whitening effects of pine needle extract, hop extract and chestnut inner shell extract were evaluated both in vitro and in B 16 mouse melanoma cell lines. Each extracts significantly inhibited tyrosinase activity, dopa auto-oxidation and melanin biosynthesis in vitro and in B 16 cell lines. In vitro, hop extract inhibited melanin biosynthesis 15 times stronger than kojic acid at $10{\;}\mu\textrm{g}/ml$ concentration. Each extracts were stronger inhibitors of melanin biosynthesis than kojic acid in B 16 mouse melanoma cell at less than $4{\;}\mu\textrm{g}/ml$ concentration. These results show that extracts fo pine needle, hop and chestnut inner shell could be developed as skin whitening component of cosmetics.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.318.2-318.2
• /
• 2002

The effects of oxidative stress on the alterations of different antioxidant enzyme activity on mouse melanoma cells(B16F10) was investigated. Oxidative stress was induced by the exposeure to hydrogen peroxide(H2O2). B 16F 10 cells were exposed Phellinus linteus Ex. in combination with H2O2 and measured the time course of changes in cell viability and antioxidant enzyme activity. CAT activity peaked at 12 hr. On the contrary, SOD and GPX activity was maximum at 6 hr. The cell viability of Pheltinus linteus extracts in combination with hydrogen peroxide was higher than hydrogen peroxide alone.

• Herbal Formula Science
• /
• v.5 no.1
• /
• pp.169-178
• /
• 1997

To investigate effect of water extract of Asparagi Tuber(天門冬) on human cancer cell-lines and immunocytes, this research estimated proliferation of A431 cell line, KHOS-NP cell line, mouse thymocytes and mouse splenocytes, Nitric Oxide(NO) from macrophage, apoptosis and subpopulation of the mouse thymocytes. The result were obtained as follows ; 1. Asparagi Tuber inhibited the proliferation of A431 cell line. 2. Asparagi Tuber inhibited the proliferation of KHOS-NP cell line. 3. Asparagi Tuber accelerated the proliferation of mouse thymocytes. 4. Asparagi Tuber inhibited the proliferation of mouse splenocytes. 5. Asparagi Tuber $100{\mu}g/m{\ell}$ inhibited the production of NO from macrophages in vitro, being compared NPS+IFN treated group. 6. Asparagi Tuber inhibited the production of NO from macrophages in vivo, being compared LPS+IFN treated group. 7. Asparagi Tuber accelerated the induction of apoptosis of the mouse thymocytes. 8. In subpopulation Asparagi Tuber increased $T_H$ of the mouse thymocytes, but decreased $T_C/T_S$ of the mouse thymocytes.

• International Journal of Stem Cells
• /
• v.17 no.3
• /
• pp.298-308
• /
• 2024

Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that SIX1 was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples. The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that Six1 expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells. Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.

• BMB Reports
• /
• v.54 no.5
• /
• pp.266-271
• /
• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.3
• /
• pp.211-218
• /
• 2015

The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-${\kappa}B$), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-${\kappa}B$ inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-${\kappa}B$ activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-${\kappa}B$ in mediating inflammatory responses in macrophages.

• Korean Journal of Acupuncture
• /
• v.23 no.2
• /
• pp.137-154
• /
• 2006

Results: 1. In the AlPR-HA group, the incidence of arthritis and arthritis index were significantly decreased. 2. In the AlPR-HA group, the levels of $IL-6,\;IFN-{\gamma},\;TNF-{\alpha},\;IL-1{\beta},\;IgG,\;IgM,\;Anti-collagen\;II$ in serum of the CIA mouse were significantly decreased. 3. In the AlPR-HA group, the levels of $IFN-{\gamma:,\;IFN-{\gamma}\;/IL-4$ in spleen cell culture of the CIA mouse were significantly decreased. 4. In the Hematoxylin and eosin stain, the cartilage destruction and synovial cell proliferation were decreased in the AIPR-HA group. 5. In the Masson's trichrome stain, the collagen fiber expressions were similar with that of the Normal group. 6. In the AlPR-HA group, the expression ratio of $CD3e^+$ to $CD19^+$ cell and $CD4^+$ to $CD8^+$ cell were similarly maintained as Normal group in the CIA mouse lymph nodes. 7. In the AlPR-HA group, $CD3e^+/CD69^+$ cells in the CIA mouse joint and $CD11a^+/CD19^+$ cells and $CD11b^+/Gr-1^+$ cells in the CIA mouse lymph nodes were significantly decreased. 8. In the AIPR-HA group, $CD4^+/CD25^+$ cells were significantly decreased in the CIA mouse spleen cell and were similarly maintained as Normal group in the CIA mouse lymph nodes. Conclusions: These results suggest that AlPR-HA at 51'36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

• IMMUNE NETWORK
• /
• v.11 no.4
• /
• pp.196-202
• /
• 2011

Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.