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Immunomodulatory Activity of Water Extract of Ulmus macrocarpa in Macrophages (유근피 추출물이 대식세포 면역조절에 미치는 영향)

  • Kwon, Da Hye;Kang, Hye-Joo;Choi, Yung Hyun;Chung, Kyung Tae;Lee, Jong Hwan;Kang, Kyung Hwa;Hyun, Sook Kyung;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.26 no.1
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    • pp.50-58
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    • 2016
  • The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

The Effects of Temperature on Maintaining the Stability of Water Quality in Biofloc-based Zero-water Exchange Culture Tanks (Biofloc을 기반으로 한 무 환수 사육 시스템의 수질 안정 유지에 미치는 수온의 영향)

  • Cho, Seo-Hyun;Jeong, Jong-Heon;Kim, Myung-Hee;Lee, Kyu-Tae;Kim, Dae-Jung;Kim, Kwang-Hyun;Oh, Sang-Pil;Han, Chang-Hee
    • Journal of Life Science
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    • v.25 no.5
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    • pp.496-506
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    • 2015
  • This study explored adequate water temperature ranges for maintaining stable water quality in a biofloc- based zero-water exchange culture system. Five experimental tanks with the following temperatures were set up: 10℃, 15℃, 20℃, 25℃, and 30℃. First, a biofloc-based culture system was developed in the experimental tanks; then, the tanks were stocked with goldfish and went without a water exchange for 60 days. Conditions for developing a biofloc-based culture system and stable water quality in low concentrations of inorganic nitrogen compounds at 10℃, 15℃, 20℃, 25℃, and 30℃ were maintained after 17, 26, 43, 68, and 78 days, respectively. Beginning from when the goldfish were stocked in the biofloc-based culture tanks, concentrations of $NH_4{^+}-N$ remained constant and at low levels at 10℃ and 15℃, but they showed a gradual increase at 20℃, 25℃, and 30℃. Concentrations of $NO_2{^-}-N$ and $NO_3{^-}-N$ at 10℃ and 15℃ did not remain at low levels and immediately increased. While $NO_2{^-}-N$ concentrations at above 20℃ remained constant and stable at relatively low levels, $NO_3{^-}-N$ concentrations showed a gradual increase. Conditions of 15℃ and below could not maintain low and stable concentrations of $NO_2{^-}-N$. In the pH range of 4.0 to 6.0, $NH_4{^+}-N$ concentration decreased as the pH rose. However, there was no correlation between pH and $NH_4{^+}-N$ concentration in the pH range of 6.0 to 8.0. These results indicate that pH levels should be kept at pH 6.0 and above to maintain a low and stable concentration of $NH_4{^+}-N$ at above 20℃.

Ethanol Extracts of Mori Folium Inhibit Adipogenesis Through Activation of AMPK Signaling Pathway in 3T3-L1 Preadipocytes (3T3-L1 세포에서 상엽이 유발하는 AMPK signaling pathway를 통한 adipogenesis 억제에 관한 연구)

  • Ji, Seon Young;Jeon, Keong Yoon;Jeong, Jin Woo;Hong, Su Hyun;Huh, Man Kyu;Choi, Yung Hyun;Park, Cheol
    • Journal of Life Science
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    • v.27 no.2
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    • pp.155-163
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    • 2017
  • Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

Inhibitory Effects of Schisandrae Fructus Ethanol Extract on the Production of Matrix Metalloproteinases in in vitro and in vivo Osteoarthritis Models (In vitro 및 in vivo 퇴행성관절염 모델에서 오미자 에탄올 추출물에 의한 matrix metalloproteinases의 생성 억제)

  • Jeong, Jin-Woo;Lee, Hye Hyeon;Kim, Hong Jae;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Hong, Su-Hyun;Kim, Bum Hoi;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1207-1214
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    • 2017
  • Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. SF extracts have been recently reported to attenuate the inflammatory responses in SW1353 human chondrocyte cells in in vitro and monosodium iodoacetate (MIA)-induced cartilage degradation in in vivo osteoarthritis (OA) models. However, their protective and therapeutic potentials against OA in primary culture chondrocytes and animal models remain unclear. Therefore, we investigated the effects of the ethanol extract of SF on the activity of matrix metalloproteinases (MMPs), biomarkers for diagnosis of OA, on interleukin $(IL)-1{\beta}-induced$ primary cultured rat cartilage chondrocytes and MIA-induced osteoarthritis in a rat model. Our data indicated that SF treatment significantly reduced the mRNA expression and enzyme activity of MMP-1, -3 and -13 in $IL-1{\beta}-induced$ primary cultured rat cartilage chondrocytes. The chondro-protective effects of SF were then analyzed in a rat OA model using a single intra-articular injection of MIA in the right knee joint. According to our results, the elevated levels of MMP-1 and -3 were markedly ameliorated by SF administration. Collectively, these findings indicate that SF could be a candidate for the treatment of OA.

Fragipan Formation within Closed Depressions in Southern Wisconsin, United States (미국 위스콘신 남부지방의 소규모 저습지에 나타나는 이쇄반층(Fragipan)의 형성과정에 관한 연구)

  • Park S.J.;Almond P.;McSweeney K.;Lowery B.
    • Journal of the Korean Geographical Society
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    • v.41 no.2 s.113
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    • pp.150-167
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    • 2006
  • This study was conducted to determine the pedogenesis of dense subsurface horizons (denoted either Bx or Bd) observed within closed depressions and in toeslope positions at loess-covered glacial tillplains in southern Wisconsin. Some of these dense subsurface horizons, especially those occurring within depressions, show a close morphological resemblance to fragipans elsewhere, even though the existence of fragipans has not been previously reported in southern Wisconsin. The spatial occurrence of fragipans was first examined over the landscape to characterize general soil-landscape relationships. Detailed physico-chemical and micromorphological analyses were followed to investigate the development of fragipans within a closed depression along a catenary sequence. The formation of fragipans at the study site is a result of sequential processes of physical ripening and accumulation of colloidal materials. A very coarse prismatic structure with a closely packed soil matrix was formed via physical ripening processes of loess deposited in small glacial lakes and floodplains that existed soon after the retreat of the last glacier. The physically formed dense horizons became hardened by the accumulation of colloidal materials, notably amorphous Si. The accumulation intensity of amorphous Si varies with mass balance relationships, which are governed by topography and local drainage conditions. Well-developed Bx horizons evolve at closed depressions where net accumulation of amorphous Si occurs, but the collapsed layers remain as Bd horizons at other locations where soluble Si has continuously been removed downslope or downvalley. Hydromorphic processes caused by the presence of fragipans are degrading upper parts of the prisms, resulting in the formation of an eluvial fragic horizon (Ex).

THE INDUCTION OF BONE REGENERATION AT FURCATION LESIONS WITH PULPECTOMY AND FURCATION CURETTAGE IN PRIMARY MOLARS (유구치 치근분지부 병소의 치수절제술과 소파술에 의한 골재생)

  • Lee, Seung-Hyun;Woo, Youn-Sun;Kim, Jae-Moon;Jeong, Tae-Sung;Kim, Shin
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.4
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    • pp.628-633
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    • 2005
  • Deep caries in primary molars without early intervention frequently induce a pulpal disease and consequent furcation lesion with fistulous openings Up to now, majority of the textbooks on pediatric dentistry and literatures have described that extraction of the inflicted teeth is indicated for these cases and in reality these teeth have usually been extracted in the dental clinics. However when we recognize the excellent capacity of bone regeneration in children and the presence of numerous accessory canals at furcation areas, the removal of infection source in pulp by pulpectomy and inflammatory granulation tissues at furcation areas by furcal curettage might open the possibility of rapid healing at the furcation regions. In this report, 10 cases of primary molars in 3 to 6-year-old children with fistulous openings and furcation lesions in moderate size of 2 to 4mm in depth radiolucency at furcation lesion have been chosen. After pulpectomy and furcal curettage, evident bone regeneration was detected radiographically in all cases. Through the cases, we came to realize that all the cases previously described are not the indications of extraction and this approach could make many cases with pulp and furca combined lesions survive and remain healthy in the children's dental arches. However, in order for this approach to acquire objective appropriateness, it is thought that more scrupulous evaluation is desirable on the various factors regarding the indication such as the extent of furcation lesions, absorption status of teeth, amount of covering bone on succeeding teeth and so on.

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Review of the Radiation Risk and Clinical Efficacy Associated with Computed Tomography Cancer Screening (암의 조기발견을 위한 CT촬영에서의 임상적 효능과 방사선위해에 대한 고찰)

  • Kim, Hyun Ja
    • Journal of Radiation Protection and Research
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    • v.38 no.4
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    • pp.214-227
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    • 2013
  • Computed tomographic scan as a screening procedures in asymptomatic individuals has seen a steady increase with the introduction of multiple-raw detector CT scanners. This report provides a brief review of the current controversy surrounding CT cancer screening, with a focus on the radiation induced cancer risks and clinical efficacy. 1. A large study of patients at high risk of lung cancer(the National Lung Screening Trial[NLST]) showed that CT screening reduced cancer deaths by 20%(1.33% in those screened compared with 1.67% in those not screened). The rate of positive screening tests was 24.2% and 96.4% of the positive screening results in the low-dose CT group were false-positive. Radiation induced lung cancer risk was estimated the most important in screening population because ERR of radiation induced lung cancer does not show the decrease with increasing age and synergistic connection between smoking and radiation risk. Therefore, the radiation risk may be on the same order of magnitude as the benefit observed in the NLST. Optimal screening strategy remain uncertain, CT lung cancer screening is not yet ready for implementation. 2. Computed tomographic colonography is as good as colonoscopy for detecting colon cancer and is almost as good as colonoscopy for detecting advanced adenomas, but significantly less sensitive and specific for smaller lesions and disadvantageous for subsequent therapeutic optical colonoscopy if polyps are detected. The average effective dose from CT colonography was estimated 8-10 $mS{\nu}$, which could be a significant dose if administered routinely within the population over many years. CT colonography should a) achieve at least 90% sensitivity and specificity in the size category from 6 and 10 mm, b) offer non-cathartic bowl preparation and c) be optimized and standardized CT parameters if it is to be used for mass screening. 3. There is little evidence that demonstrates, for whole-body scanning, the benefit outweighs the detriment. This test found large portion of patient(86~90.8%) had at least one abnormal finding, whereas only 2% were estimated to have clinically significant disease. Annual scans from ages 45 to 75 years would accrue an estimated lifetime cancer mortality risk of 1.9%. There is no group within the medical community that recommends whole-body CT. No good studies indicate the accuracy of screening CT, at this time. The benefit/risk balance for any of the commonly suggested CT screening techniques has yet to be established. These areas need further research. Therefore wild screening should be avoided.

Clinical Investigation of Women with Asthma Worsened During Pregnancy (임신 중 천식의 악화로 내원한 환자의 임상적 고찰)

  • Kwon, Young-Hwan;Kim, Kyung-Kyu;Jung, Hye-Cheol;Lee, Sung-Yong;Kim, Je-Hyeong;Lee, So-Ra;Lee, Sang-Yeub;Lee, Sin-Hyeong;Cho, Jae-Yun;Shim, Jae-Jeong;Kang, Kyung-Ho;Yoo, Se-Hwa;In, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.4
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    • pp.548-554
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    • 1999
  • Background : Asthma is the most common respiratory crisis encountered in clinical practice, occurring in up to 4% of all pregnancies. Pregnancy often appears to alter the course of asthma. But the mechanisms responsible for variable changes in the asthma course during pregnancy remain unknown. Poor control and exacerbations of asthma during pregnancy may result in serious maternal and fetal complications. To investigate the course of asthma during pregnancy in korean women, we did a retrograde study of 27 pregnant women who had been admitted to Korea University Hospital for asthma worsened. Method: Twenty seven pregnant women who had been visited to Korea University Hospital for asthma worsened were enrolled in our retrospective study. We reviewed medical recordings and interviewed patients with asthma. Results: Twenty seven pregnant women with asthma were evaluated, and 25 patients were enrolled to our study. Two patients experienced abortions at 6 weeks and 25 weeks gestation, respectively. The period of asthma worsened was commonly during weeks 20 to 28 of gestation. And all patients wosened were improved during the last 4 weeks of pregnancy. Twenty(80%) of 25 women whose asthma worsened during pregnancy reverted toward their prepregnancy status after delivery(p<0.002). The causes of asthma worsened during pregnancy are reduction or even complete cessaton of medication due to fears about its safety(40%), worsening after upper respiratory infection (28%), and unknown(32%). There were no adverse perinatal outcomes in 25 pregnant asthma subjects. Conclusions: A major problem of therapy for asthma during pregnancy is reduction or even complete cessation of medication due to fears of fetal effects. Therefore, maternal education and optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications.

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A comparative study of three therapeutic modalities in loculated tuberculous pleural effusions (소방이 형성된 결핵성 흉막 질환에서 배액 방법에 따른 치료효과)

  • Lee, Sang Hwa;Lee, So Ra;Lee, Sang Youb;Park, Sang Muyn;Suh, Jung Kyung;Cho, Jae Youn;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.683-692
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    • 1996
  • Background: Although most of the patients with tuberculous pleural effusions completely reabsorbed their effusions and became asymptomatic within 2 to 4 months, later surgical procedures such as decortication is needed in some patients because of dyspnea caused by pleural loculations and thickening despite anti-tuberculous chemotherapy. It is obligatory to secure adequate drainage to prevent the development of complications. But, the best methods for treating loculated tuberculous pleural effusions remain debatable. Recent several reports revealed that intrapleural instillation of fibrinolytic agents is an effective adjunct in the management of complicated empyema and may reduce the need of surgery. Purpose : The effects of catheterization with intrapleural urokinase instillation were prospectively evaluated in the patients with septated tuberculous pleural effusion, and compared with other therapeutic effects of different modalities of therapy such as repeated thoracentesis and small-bored catheterization. Methods : Forty-eight patients diagnosed with tuberculous pleurisy were randomly separated into three groups; control group(n=13), catheter group(n=12), urokinase group(n=22). In urokinase group, dose of 100.000U urokinase was instilled into the pleural cavity via a percutaneous drainage catheter for complete drainage or total dose of 700,000U of urokinase. After two hours clamping, the catheter was opened and intermittently irrigated. The early and late effectiveness of therapies was assessed by radiographically and by measuring the volume of fluid drained from the catheter. Results : There was statistically significantly better result in the urokinase group in respect of frequency of catheterization, frequency of catheter obstruction and the duration of catheterization in early effectiveness(p < 0.05). There were no difference in radiologic improvement of follow-up in later phase chest X-ray between urokinase group and catheter group in later phase(p > 0.05). But there were more failure rates in control group especially honeycomb septa in pleural effusion sonographically than former two groups. And there were no complications of urokinase such as fever or hemorrhage. Conclusion : In the treatment of septated tuberculous pleurisy, there were better results in urokinase than those of catheterization alone in early effectiveness. And there was no difference in radiographic improvement between urokinase group and catheter group. Intrapleural instillation of urokinase is an effective and safe mode of treatment for septated tuberculous pleural effusions and alleviates the need for thoracotomy.

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Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics

  • Xu Chang Jiang;Li Christina YongTao;Kong AhNg Tony
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.249-268
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    • 2005
  • Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.