• The Korean Journal of Physiology and Pharmacology
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• 제18권4호
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• pp.313-320
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• 2014

The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia + vitamin E (250 mg/kg $BW^*d$) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p<0.001), interferon-gamma ($IFN-{\gamma}$) (p<0.01) and malondialdehyde (MDA) (p<0.001), and decreased the serum erythropoietin (EPO) activity (p<0.05). Administration of vitamin E significantly increased the S-IgA (p<0.001) in ileum and significantly improved the expression levels of occludin and $I{\kappa}B{\alpha}$, and decreased the expression levels of hypoxia-inducible factor 1 alpha and 2 alpha ($HIF-1{\alpha}$ and $HIF-2{\alpha}$), Toll-like receptors (TLR4), P-$I{\kappa}B{\alpha}$ and nuclear factor-${\kappa}B$ p65(NF-${\kappa}B$ P65) in ileum compared to the HH group. This study suggested that vitamin E protectis from intestinal injury caused by high altitude hypoxia environment. These effects may be related to the HIF and TLR4/NF-${\kappa}B$ signaling pathway.

• Parasites, Hosts and Diseases
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• 제51권1호
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• 대한한의학회지
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• 제33권4호
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• pp.26-36
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• 2012

Objectives: To establish scientific and objective evidence for the use of a Korean medicine, articles regarding Hwangryeonhaedok-tang (HRHDT), a herbal medicine frequently used in Korean medical clinics and hospitals, were gathered and analyzed. Methods: The articles were classified as being from domestic or international journals, and by their year of publication. The mechanisms of the anti-inflammatory and antipyretic effects of HRHDT were investigated. Results: Of the 25 articles analyzed, 7 were published from Korea, 7 were from China, and 11 were from Japan. HRHDT showed anti-inflammatory and antipyretic effects through the regulation of the expression of Th1 cytokines including interleukin-2 (IL-2), IL-8, interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$); and Th2 cytokines including IL-4, IL-6, and IL-12, which inhibit leukotriene B4 (LTB4), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inflammatory cells. It also lowered preprodynorphin (PPD), and corticotropin-releasing factor (CRF) in the peripheral nerve system and hypothalamus. Conclusions: We speculate that the anti-inflammatory and antipyretic effects could be related to the therapeutic efficacy of HRHDT in removing pathogenic fire and heat.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.279-282
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• 2003

To investigate the effect of fluoxetine, one of selective serotonin reuptake inhibitors (SSRIs), on the immune system, human peripheral blood mononuclear cells (PBMC) were treated with fluoxetine $(10^{-7}\;M)$ for 24 h, and immune-related genes were analyzed by cDNA microarray. Expression of the immunerelated genes such as CD107b (LAMP-2), CD47 receptor (thrombospondin receptor), CD5 antigen-like (scavenger receptor cysteine rich family), copine III (CPNE3), interleukin (IL)-18 (interferon-gammainducing factor), integrin alpha 4 (CD49d), integrin alpha L subunit (CD11a), IL-3 receptor alpha subunit, L apoferritin, and small inducible cytokine subfamily A (Cys-Cys) member 13 (SCYA13) was induced by fluoxetine. This result suggests that fluoxetine may affect the immune system, and provides fundamental data for the involvement of SSRIs on immunoregulation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.245-251
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• 2015

Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-${\alpha}$) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-${\alpha}$ (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP), and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE-IFN-${\alpha}$ group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-${\alpha}$ group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-${\alpha}$ combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. Conclusions: The use of the TACE and IFN-${\alpha}$ combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

• 동의생리병리학회지
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• 제28권6호
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• pp.593-600
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• 2014

This study is aimed to investigate the anti-inflammatory effect of Euphorbiae kansui radix methanol extract (ERE) in lipopolysaccharide(LPS)-stimulated mouse peritoneal macrophages. Peritoneal macrophages were obtained from thioglycollate-injected Balb/c mice. Cells were stimulated with LPS or LPS plus interferon-gamma (IFN-${\gamma}$) in the presence of ERE and various inflammatory markers were assayed. Finally, LPS-induced signaling molecules were measured. ERE up to $400{\mu}g/m{\ell}$, was not cytotoxic to ERE inhibited LPS/IFN-${\gamma}$-induced nitric oxide (NO), inducible NO synthase. ERE also reduced the levels of cyclooxygenase-2 and the proinflammatory cytokines such as tumor necrosis factor-${\alpha}$, interleukin(IL)-6 and IL-12. The inhibitory effect of ERE on LPS-induced $I{\kappa}B{\alpha}$ degradation was weak but phosphorylation of JNK, p38 and ERK1/2 was strongly suppressed. Our data indicated that the anti-inflammatory effect of ERE in LPS-stimulated macrophages was partly mediated by its inhibition of JNK, p38 and ERK1/2.

• 동의생리병리학회지
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• 제22권2호
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• pp.422-426
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• 2008

In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced ${\beta}-cell$ death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of ${\beta}-cell$ destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with $interleukin-1{\beta}$ ($IL-1{\beta}$) and $interferon-{\gamma}$ ($IFN-{\gamma}$) resulted in a reduction of cell viability. RTE protected $IL-1{\beta}$ and $IFN-{\gamma}$-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of $IL-1{\beta}$ and $IFN-{\gamma}$-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of $NF{-\kappa}B$ activation. The $IL-1{\beta}$ and $IFN-{\gamma}$-stimulated RIN cells showed increases in $NF{-\kappa}B$ binding activityand $I{\kappa}B{\alpha}$ degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced $I{\kappa}B{\alpha}$ degradation and $NF{-\kappa}B$ activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in $IL-1{\beta}$ and $IFN-{\gamma}$-treated islets.

• International Journal of Industrial Entomology and Biomaterials
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• 제7권2호
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• pp.139-144
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• 2003

Over 350 million people worldwide are chronic carriers of hepatitis B virus (HBV). Chronic viral infections of the liver can progress to cirrhosis, which may ultimately lead to hepatic failure or the development of hepatocellular carcinoma. There are two antiviral drugs on the market approved for clinical management of chronic HBV infections; interferon-alpha and the nucleoside analog lamivudine. However, they showed adverse side-effects. In the rational drug design for such therapies we would like to utilize antiviral drugs that inhibit the HBV replication in the liver. Investigation of natural extracts of silkworm exhibiting antiviral potential was held in the functional HBV polymerase activity and the release of virion particle in the HepG2.2.15 cell lines. HBV-producing transgenic mouse fed with silkworm DNJ molecule was shown as an inhibitor of serum HBV particles. We could represent this DNJ molecule as an antiviral potential complementing conventional therapies after preclinical tests against WHBV-infected animal model, woodchuck.

• IMMUNE NETWORK
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• 제5권1호
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1316-1321
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• 2009

Multiple beneficial properties of Opuntia ficus indica (OPF) are well established. In the present study, we have investigated the immunological role of OPF extract (OPFE) on murine splenocytes. OPFE dose- and time-dependently enhanced the proliferation of splenocytes without cytotoxicity. Our results also showed that the number of $CD4^+$ helper T cells and CD45R/$B220^+$ pan B cells increased markedly, but not $CD8^+$ cytotoxic T cells or $CD11b^+$ granulocytes/macrophages. In addition, OPFE significantly decreased the production levels of T helper (Th) 1 type cytokines, interferon (IFN)-$\gamma$, and tumor necrosis factor (TNF)-$\alpha$, although had no significantly differences in those of interleukin (IL)-4, a Th2 type cytokine in concanavalin A (Con A)-stimulated blastogenic cells. Furthermore, OPFE alone strongly increased IL-4 production and decreased TNF-$\alpha$ production even in the absence of Con A. On the basis of these results, this study suggests that OPFE enhances immunity by regulating the pro- and anti-inflammatory response, indicating that this extract exerts a marked immunomodulatory effect, confirming its usefulness as therapy for immune-related diseases.