• Preventive Nutrition and Food Science
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• v.2 no.2
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• pp.96-100
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• 1997

Carcinogenicity of di(2-ethylhexyl)phthalate(DEHP) to the mose forestomach and its inhibitor activity for the initiation of Benzo[a]pyrene(BP)-induced mouse forestomach neoplasia were studied on the mouse forestomach carcinogenesis regimen. One hundred female ICR mice(6~7 weeks of age) were hosed in a poly-carbonate cage (4 mice/cage) in a humidity- and temperature-controlled room subjected to a semipurified diet for a week. Mice were divided into 4 treatment groups (25 mice/treatment): Basal diet, DEHP, BP, and BP+DEHP. On Monday and wednesday, 0.1ML DEHP mixed with 0.1ml olive oil (for DEHP and DEHP+BP treatment groups) or 0.1ml saline+0.1ml olive oil (for basal diet group) was intubated, p.o., and on Friday, 2mg BP dissolved in 0.2ml olive oil (for BP and BP+DEHP treatment groups) was intubated, p.o. This cycle was repeated for 4 weeks. Beginning with the first intubation of BP an continuing thereafter, body weight and food intake were recorded once and twice weekly, respectively. All surviving mice were sacrificed 22 weeks after the first dose of BP intubation and countered forestomach tumor. No tumor was formed by DEHP treatment. 5.75 tumors per mouse was formed by BP treatment, whereas its number was reduced to 4.53 by BP+DEHP treatment. Similar results were seen in the tumor incidence. Body weight gain was not affected by DEHP treatment, when compared to that b basal diet treatment. The body weight was significantly reduced by BP treatment, but its reduction was recovered to the level of the basal diet group by BP+DEHP treatment. No significant difference was seen in food intake among all treatment groups. These results indicate that DEHP lacks carcinogenic activity to the mose forestomach and rather inhibits the initiation of BP-induced mose forestomach neoplasia.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.16.1-16.20
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• 2022

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103⁺CD11b^- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103⁺CD11b^- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103⁺CD11b^- DCs in mice infected with LM might affect to increase of Foxp3⁺ regulatory T cells. Changes of major subset of DCs from CD103⁺ to CD103^- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.4
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• pp.237-243
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• 2002

Objective : The aim of this study was to evaluate the influence of different media on blastulation, mean cell number, percentage of inner cell mass (ICM) of total cells and ICM : trophectoderm (TE) ratio in mice. Materials and methods: A total 552 two cell embryos were retrieved from ICR female mice (4 weeks old) at 48 hr after hCG injection (mated just after hCG injection) and cultured in MEM (n=276) or TCM (n=276) supplemented with 20% hFF. The grading of blastocysts from zona-intact (ZiB) to -escape (hatching and hatched, ZeB) was performed at 72 hours after culture. Total, TE and ICM cell numbers were analyzed by differential staining of blastocyst. Statistical analysis was performed using t-test with SigmaPlot-2001. P-values < 0.05 were accepted as statistically significant. Results: The blastulation rate in MEM ($64.9{\pm}4.95%$) was significantly higher (p=0.0031) than that in TCM ($57.2{\pm}5.22%$). No differences were found in the number of ZiB and ZeB between MEM ($31.9{\pm}2.62$, $33.0{\pm}4.58%$), and TCM ($27.2{\pm}4.28$, $30.1{\pm}4.58%$). A total 314 blastocysts (MEM=166; TCM=148) were stained differentially. Mean cell number of blastocysts was significantly higher (p=0.0002) in TCM ($73.1{\pm}3.3$) than in MEM ($61.7{\pm}2.5$). Differential staining was successfully performed in 155 blastocysts (MEM=77; TCM=78). The percentage of ICM was significantly higher in MEM than in TCM ($20.9{\pm}1.3$ vs. $17.1{\pm}1.2%$, p=0.0281). The ICM : TE ratio was higher in TCM than in MEM (1 : $4.85{\pm}0.68$ vs. 1 : $3.78{\pm}0.78$, NS). Conclusion: These results show that MEM increase the blastocyst formation and percentage of ICM of total cells comparing with TCM in mice.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4609-4615
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• 2014

Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.

• Herbal Formula Science
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• v.22 no.1
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• pp.93-104
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• 2014

Objectives : Samhwangsasim-tang (SHSST) is a traditional Korean medication, which has been used in Korea for treatment of hypertension and chest pain. Hyperlipidemia and inflammation could influence hypertension and chest pain. This study investigated whether and how SHSST reduces the hyperlipidemia and inflammation related to high-cholesterol diet-induced obesity in rats. Methods : Mice were divided randomly into four groups: the normal diet group, high-cholesterol diet group, low dose treatment group supplemented with 30% ethanol extract of SHSST (L) and high dose treatment group supplemented with 80% ethanol extract of SHSST (H). L and H groups were orally administered with SHSST at the dose of 50mg/kg a day respectively and others were administered with the same volume of physiological saline. Results : Administration of SHSST resulted in a decrease in serum levels of total cholesterol and low-density lipoprotein. Expression of hepatic genes(SREBP2, LXR, LDLR, and HMG-CoA) related with cholesterol metabolism was also suppressed. In addition, SHSST decreased the expression of inflammation-related gene (TNF-${\alpha}$, IL-6, ICAM-1, VCAM-1, TGF-${\beta}1$ and fibronectin). Histological examinations also showed that the size of the adipocytes was smaller in the SHSST treated group than in the high-colesterol diet group. In an in vitro study, SHSST inhibited the production of nitric oxide in a concentration-dependent manner. Conclusions : This study indicates that SHSST has anti-hyperlipidemia and anti-inflammatory effects. It may also suggest that SHSST may be alternative therapy for treatment of hyperlipidemia and its complications.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6393-6398
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• 2013

In this research, we used $GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% $GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The $GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

• Journal of Environmental Health Sciences
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• v.49 no.1
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• pp.22-29
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• 2023

Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for T_H1 cytokines namely, TNF-α and IFN-𝛾 and T_H2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased T_H1 response with elevated TNF-α and IFN-𝛾 levels and downregulated T_H2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to T_H1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant T_H2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of T_H1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to T_H1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

• Journal of Ginseng Research
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• v.13 no.1
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• pp.42-48
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• 1989

The binding of bay region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs) to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of polyacetylenes such as panaxynol and panaxydol on the formation of benzo(a)pyreno (BP)-metabolite-DNA adduct in the liver of ICR mice. Treatment of mice by i.p. administration of polyacetylenes produced a marked reduction in BP metabolite binding to DNA in vitro. Following i.v. administration of (3H)BP(300, ${\mu}$Ci/21 nmoles/0.1 nt DMSO) to mice, radioactivity was detected in the DNA of the liver in vivo. The result of tentative identification of the 4 peaks between the two standard markers for high pressure liquid chromatography showed that the peaks. I, II, III, and IV were BP-phenol oxide-DNA adduct (or BP-diol-epoxide-dCyt. adduct), (-) BP$.$diolepoxide I:dGuO adduct, (+) BP-diol-epoxide I: dGuo adduct, and BP-diol-epoxide II:dGuO adduct, respectively. The minor adduct, (-) BP-diol epoxide I: dGuo was reduced to 6971 of the amount of the control, while the major adduct, (+) BP-diolepoxide I: dGuO(peak II) which was produced from (-) BP-7, 8-diol was reduced to 78% of that of the control. The amount of the minor adduct, BP-diol-epoxide II:dGuo adduct(peak IV) which formed from (+) BP-7, 8-diol was 58% of the control. These results show that the panaxydol is more related to inhibition of the formation of the minor ad- ducts than of the major adducts, which were generally produced from ($\pm$) BP-7, 8-dihydro-dials.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.438-444
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• 2014

Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-${\alpha}$ and IFN-${\gamma}$. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, $500{\mu}g/mL$ of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-${\alpha}$/IFN-${\gamma}$ by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.