Spatially-aware group interaction design framework for collaborative room-oriented immersive systems.

Room-oriented immersive systems are human-scale built environments that enable collective multi-sensory immersion in virtual space. Although such systems are currently seeing increasing applications in public realms, limited understanding remains regarding how humans interact with the virtual environments displayed within. Synthesizing virtual reality ergonomics and human-building interaction (HBI) knowledge allows us to investigate these systems meaningfully. In this work, we develop a model of content analysis based on hardware components of the Collaborative-Research Augmented Immersive Virtual Environment Laboratory (CRAIVE-Lab) and the Cognitive Immersive Room (CIR) at Rensselaer Polytechnic Institute. Situating ROIS as a joint cognitive system, this model consists of five categories of qualitative factors: 1) general design approach; 2) topological relationships; 3) features of tasks; 4) hardware-specific design modalities; and 5) interactive qualities. We probe the comprehensiveness of this model using existing design scenarios at the CRAIVE-Lab and the CIR featuring both application-based and experience-based designs. Through these case studies, the robustness of this model in its representation of design intention is observed, with limitations on temporal constraints. In creating this model, we establish foundations for more detailed assessments of the interactive qualities of systems alike.

Root Extract of Lindera aggregata (Sims) Kosterm. Modulates the Th17/Treg Balance to Attenuate DSS-Induced Colitis in Mice by IL-6/STAT3 Signaling Pathway.

Ulcerative colitis (UC) is a chronic, idiopathic and relapsing inflammatory disease of the gastrointestinal tract that has a prolonged disease duration. Lindera aggregata (Sims) Kosterm. is a traditional Chinese herb which has been used to treat gastrointestinal diseases for thousand years. However, there are few reports about the application of L. aggregata in the treatment of UC at present. Herein, we investigated the therapeutic effect of the root extract of L. aggregata (LREE) against UC and explored its underlying mechanisms based on IL-6 signaling pathway and the balance of T helper (Th) 17 and regulatory T (Treg) cells. Results showed that LREE could not only decrease the production and secretion of IL-6, but also could inhibit the signal transduction of IL-6/STAT3 signaling pathway. Moreover, LREE could significantly inhibit the differentiation of CD4+ T cells to Th17 cells in vitro and decrease the proportion of Th17 cells in mesenteric lymph nodes (MLNs) of model mice in vivo. Besides, LREE could also alleviate the disease symptoms, reduce intestinal permeability and improve histopathological changes of colitis model mice. Together, LREE can significantly inhibit the production and secretion of IL-6, regulate IL-6/STAT3 signal transduction, and modulate the balance of Th17 and Treg cells and effectively attenuate UC.

[Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport].

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor.

Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.

Application of a DSS colitis model in toxicologically assessing norisoboldine.

In standard nonclinical drug safety evaluation studies, limitations exist in predicting the clinical risk of a drug based only on data from healthy animals. To obtain more comprehensive toxicological information on norisoboldine (NOR), we conducted an exploratory study using C57BL/6 mice in addition to healthy mice as models of dextran sodium sulfate (DSS) colitis to evaluate the safety of NOR. The healthy mice and DSS colitis mice were exposed to 30 or 90 mg NOR/kg body weight or water for 15 days. Compared with the model control group, 90 mg/kg of NOR aggravated the symptoms and colonic lesions of the DSS colitis mice and even caused death in two animals. No significant adverse effects were observed in the healthy mice. These different toxic reactions to NOR in the healthy and DSS colitis mice indicate that NOR toxicity varies by status among animals and suggests that the DSS colitis mouse model may be more susceptible, accurate and comprehensive in evaluating the safety of NOR. In conclusion, 90 mg/kg of NOR may be safe for healthy mice but not for DSS colitis mice. The DSS colitis mouse model, with many features similar to those of human colitis patients, may be a novel choice to counteract the deficiencies of using healthy mice to evaluate the safety of anti-inflammatory bowel disease (IBD) drugs, and further research is required.

Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid.

To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean Cmax of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high Cmax in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, Cmax, csf and AUCcsf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.

Ethyl acetate extract from Inula helenium L. inhibits the proliferation of pancreatic cancer cells by regulating the STAT3/AKT pathway.

Sesquiterpene lactones are bioactive compounds that have been identified as responsible for the anticancer activity of the medicinal herb, Inula helenium L. (IHL). However, the mechanisms of action involved in the anti­pancreatic cancer activity of IHL have yet to be elucidated. The present study used an optimized extraction strategy to obtain sesquiterpene lactones from IHL (the resulting product termed ethyl acetate extract of IHL; EEIHL), and examined the potential mechanisms involved in the anti­pancreatic cancer activity of EEIHL. Ethanol and ethyl acetate were used to extract sesquiterpene lactones from IHL to give the final product EEIHL. Cell Counting Kit­8, colony formation and Annexin V/propidium iodide assays were used to detect the anti­proliferative activity of EEIHL. Cell migration was determined with a wound healing assay. mRNA and protein expression levels were analyzed by reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. It was identified that low concentrations of EEIHL caused CFPAC­1 cell cycle arrest in the G0/G1 phase, whereas high concentrations of EEIHL induced mitochondria­dependent apoptosis. In addition, EEIHL could inhibit the phosphorylation of the signal transducer and activator of transcription (STAT)3/AKT pathway, potentially resulting in impeded cell mobility. In conclusion, EEIHL could activate mitochondrial­dependent apoptosis and inhibit cell migration through the STAT3/AKT pathway in CFPAC-1 cells.

Protective effect of Lycium barbarum polysaccharides against cadmium-induced testicular toxicity in male mice.

The present study was performed to determine whether Lycium barbarum polysaccharides (LBPs) would protect mice against cadmium (Cd)-induced testicular toxicity. Seventy-two male mice were randomly divided into six groups with twelve mice per group. Four groups were administered orally with cadmium chloride (5.0 mg per kg body weight) for 35 days and treated in combination with LBPs (0, 10.0, 33.3 or 100 mg kg-1) from one week before exposure to Cd until the end of the experiment. The other two groups were administered orally with vehicle or LBP (100 mg kg-1) only. Pretreatment with LBP ameliorated the Cd-induced reduction in the body weights, sperm motility as well as the level of testosterone in serum. Moreover, Cd-induced increase in the abnormal sperms was reduced and effects of Cd on the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were reversed. Histopathological examination further confirmed that the LBPs effectively attenuated Cd-induced degeneration of seminiferous tubules. Thus, LBPs attenuated Cd-induced testicular injury by improving the activity of antioxidant enzymatic activity and lowering the oxidative stress, so it could be a potential auxiliary therapeutic agent for Cd-induced testicular toxicity.

Effects of Linderae radix extracts on a rat model of alcoholic liver injury.

Traditional treatments have a poor effect on alcoholic liver diseases. Linderae radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., has been frequently used in traditional Chinese medicine for treating various diseases, and has been shown to exhibit a protective effect on liver injury. In the present study, LR extracts were made using various solvents, and then administrated to rats to establish a model of ethanol-induced liver injury. The study aimed to investigate the therapeutic effects and potential mechanism of LR extracts on acute alcoholic liver injury. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycercide (TG), cholesterol (TC), methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) were determined using an automatic biochemistry analyzer. In addition, pathological examination was performed by hematoxylin-eosin staining. The levels of MDA and SOD, and the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in liver tissue were investigated immunohistochemically. The expression of cytochrome P450 2E1 (CYP2E1) mRNA was quantified by reverse transcription-quantitative polymerase chain reaction. The results indicated that LR extracts improved the histopathological status and decreased the serum levels of ALT, AST, TG, TC and MDA. Furthermore, the levels of MDA and inflammatory mediators (NF-κB, TNF-α and IL-1ß) were decreased in liver tissues, and the overexpression of CYP2E1 mRNA induced by ethanol treatment. LR extracts exhibited a protective effect on alcoholic liver injury and the mechanism may be associated with the anti-inflammatory and anti-oxidative action.

Fluoranthene enhances p53 expression and decreases mutagenesis induced by benzo[a]pyrene.

Fluoranthene (Fla) is the most abundant polycyclic aromatic hydrocarbon (PAH) in diesel particulate extracts. Benzo[a]pyrene (BaP) is genotoxic and is a prototype of PAH carcinogens. Fla's toxicity and mutagenicity are minor relative to BaP's. Our data showed that Fla enhanced BaP-induced p53 expression and promoted BaP-induced cell death. In contrast, Fla decreased BaP-induced mutagenesis. Fla had almost no influence on the cell cycle. However, the effect of cotreatment with BaP (1µM) and Fla (10µM) in regulating the cell cycle was greater than that of BaP (2µM) alone. It is known that BaP activates the aryl hydrocarbon receptor (AhR), and, in turn, the AhR induces cytochrome P450 (Cyp)1a1 expression. The expression of Cyp1a1 corresponds well with the induction of apoptosis and mutagenesis by BaP. Fla did not activate the AhR or antagonize BaP's induction of AhR activity and Cyp1a1 expression. Therefore, the actions of Fla on BaP's toxicity were independent of the AhR signal and Cyp1a1. In summary, results indicated that Fla directs BaP-treated cells into death rather than mutagenesis, consequently preventing cells from being transformed. The novel cooperation between Fla and BaP provides valuable information for how to increase expression of the p53 tumor suppressor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin's suppression of 1-nitropyrene-induced p53 expression is mediated by cytochrome P450 1A1.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 1-nitropyrene (1-NP), and benzo[a]pyrene (BaP) are toxic environmental pollutants. TCDD was shown to suppress p53 expression in response to genotoxic stress and hypoxic conditions. However, the mechanism of TCDD's actions is not clearly understood. Our data showed that pretreatment with TCDD abolished 1-NP- but not BaP-induced p53 and mouse double minute 2 (MDM2; HDM2 in humans) expressions. TCDD suppressed 1-NP- but not BaP-induced p53 activity, and in contrast, pifithrin-alpha (PFT-α), a p53 inhibitor, suppressed both 1-NP- and BaP-induced p53 activity. In the presence of nutlin-3, an HDM2 inhibitor, TCDD was still able to suppress 1-NP-induced p53 expression. However, TCDD-activated HDM2 did not distinctly cause the degradation of BaP- or nutlin-3-induced p53 expression. Accordingly, TCDD's suppression of 1-NP-induced p53 expression was compound-specific, and the contribution of HDM2 to the abolition of 1-NP-induced p53 was limited. ß-Naphthoflavon (ß-NF), an aryl hydrocarbon receptor (AHR) agonist, mimicked TCDD's action and abolished 1-NP-induced p53 expression. In the presence of CH-223191, an AHR antagonist, TCDD was unable to abolish 1-NP-induced p53 expression. Results indicate that activation of the AHR is required for TCDD's suppression of 1-NP's induction of p53. Cytochrome P450 (CYP) 1A1 is an AHR-targeting gene and a xenobiotic-metabolizing enzyme. TCDD was unable to abolish 1-NP's induction of p53 in CYP1A1-deficient cells, the CYP1A1 transcript of which was degraded by small hairpin RNA-CYP1A1. Both TCDD and PFT-α are potent CYP1A1 inducers and decreased 1-NP-induced cell death and mutagenesis. In summary, TCDD induced detoxification of 1-NP's toxicity, which was mediated by the CYP1A1 enzyme.

[Effects of three traditional Chinese medicine with pungent-flavor, warm-nature and meridian tropism in lung on lung-yang deficiency rats induced by compound factors].

OBJECTIVE: To observe the effects of three traditional Chinese medicine (TCM) such as Amomi Fructus Rotundus, Perillae Folium and Angelicae Dahuricae Radix on lung-yang deficiency rats induced by compound factors. METHOD: Lung-yang deficiency rats were established with three-factor combination, such as smoking (exogenous evil effect on lung), swimming in common and ice water (cold body and exhaustoin) and drinking ice water (inhale cold). Meanwhile, rats were given water extracts of the three TCM by intragastric administration for 24 days everyday. Indexes such as general behavior, weight, rectal temperature, back temperature and grip strength were observed. Blood was collected to determine NO, IgG in blood serum. Lung and heart were dissected to measure organs index. RESULT: The water extracts of Amomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix could markedly heighten weight, back temperature, grip strength, content of IgG in blood serum, reduce content of NO in blood serum, lung index and heart index. The water extracts of Amomi Fructrs Rotundus and Perillae Folium could heighten rectal temperature. CONCLUSION: Amomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix were TCM with pungent-flavor, warm-nature and meridian tropism in lung, which could improve the symptoms of physique emaciation, aversion to cold of the back, weary and acratia and so on. It provides an important reference for the regularity of the properties theories about pungent-flavor, warm-nature and meridian tropism in lung.

1,10-phenanthroline stabilizes mRNA of the carcinogen-metabolizing enzyme, cytochrome P450 1a1.

1,10-phenanthroline (phen), flufenamic acid, and indomethacin are inhibitors of aldo-keto reductases 1C1 (AKR1C1), but only phen decreased the benzo[a]pyrene (BaP)-induced cytochrome P450 1a1 (Cyp1a1) protein level. Therefore the decrease in the BaP-induced Cyp1a1 protein level was not due to inhibition of Akr1c1, but to phen itself. Phen decreased the BaP-induced Cyp1a1 promoter activity and protein expression, and in contrast, it increased Cyp1a1 mRNA, resulting from an increase in mRNA stability. Phen is also known as a transition metal ion-chelator. Along with the phen study, we also found that Zn(2+), Fe(2+) and Cu(2+) increased Cyp1a1 mRNA and protein stability. Our results show that phen stabilized the mRNA of Cyp1a1, although it decreased cell viability. In addition, Zn(2+) and Fe(2+) highly neutralized phen's suppression of Cyp1a1 protein expression, but they only slightly neutralized phen's promotion of mRNA stability and suppression of cell viability, and had no effect on phen's suppression of promoter activity. Phen's effect on Cyp1a1 expression was reversible, which indicates that phen is non-covalently linked to its target. This report elucidates a new role for phen of stabilizing Cyp1a1 mRNA, and provides information for further studies on mRNA stabilization.

1-Nitropyrene stabilizes the mRNA of cytochrome P450 1a1, a carcinogen-metabolizing enzyme, via the Akt pathway.

Cytochrome P450 1a1 (Cyp1a1) is a phase I xenobiotic-metabolizing enzyme, the expression of which is mainly driven by the aryl hydrocarbon receptor (AhR). Cyp1a1 messenger (m)RNA is labile. Our study indicates that 1-nitropyrene (1-NP) highly induced Cyp1a1 protein expression, although its induction of AhR transactivation activity was negligible. The fact that the nuclear receptors, CAR, FXR LXR, or PXR, did not induce Cyp1a1 expression indicates that they do not mediate 1-NP's action. When the AhR transcript was degraded by small hairpin (sh)RNA-AhR, 1-NP-induced Cyp1a1 expression largely decreased. In addition, 1-NP did not induce Cyp1a1 in AhR pathway-deficient mutant cells, which indicates that the AhR is essential for 1-NP's action. When Cyp1a1's turnover was examined, 1-NP was able to stabilize the 1-NP- and benzo[a]pyrene (BaP)-induced Cyp1a1 mRNA, but not protein. 1-NP-induced Cyp1a1 mRNA stabilization was mediated by Akt, but not by p38 MAPK, MEK1/2, or JNK. Among aryl hydrocarbons with four annealed phenyl rings, including pyrene, 1-NP, fluoranthene, 3-nitrofluoranthene, chrysene, and 6-nitrochrysene, only 1-NP was able to stabilize Cyp1a1 mRNA. 1-NP's action was gene specific. In conclusion, stabilizing Cyp1a1 mRNA greatly contributed to 1-NP-induced Cyp1a1 expression, which provides new insight into gene regulation by the AhR ligand and mRNA stabilization.

Crosstalk between activated forms of the aryl hydrocarbon receptor and glucocorticoid receptor.

Pyrene, benzo[a]pyrene (BaP), and indeno[1,2,3-cd]pyrene (IND) are poly cyclic aromatic hydrocarbons (PAHs) with four to six annealed phenyl rings. Dexamethasone (Dex) is a synthetic agonist of glucocorticoids. The aryl hydrocarbon receptor (AhR) ligands, BaP and IND, did not directly activate the glucocorticoid receptor (GR), and Dex did not activate the AhR either. Whenever BaP and IND were added to Dex-treated cultures, they were present with Dex for longer periods, and higher enhancement of Dex-induced transactivation of the GR was found, which indicates that the freshly activated AhR is essential for synergistic interactions with the activated GR. The degree of enhancement of Dex-induced transactivation of the GR by PAHs, BaP approximately IND>pyrene, paralleled the potency of PAHs in activating the AhR. This synergistic interaction was more distinct in ovarian granulosa cells (HO23) than in HepG2, 293T, or HeLa cells. In contrast, Dex suppressed AhR-mediated expressions, including AhR and cytochrome P450 (CYP) 1 A1 expressions. Dex also counteracted the BaP-induced decrease in cell viability. Crosstalk between the AhR and GR was independent of their expression levels. We concluded that the AhR functionally cross-reacts with the GR, through which transactivation activity of the GR is further enhanced, and in contrast, transactivation activity of the AhR is inhibited. This report shows the significance of in vitro endocrine-related results, which provide a clue for molecular studies of an interactive mechanism between the AhR and GR, and should be confirmed by future in vivo studies.

Aldo-keto reductase 1C2 is essential for 1-nitropyrene's but not for benzo[a]pyrene's induction of p53 phosphorylation and apoptosis.

It is reported that diesel exhaust particles contain more 1-nitropyrene (1-NP) than benzo[a]pyrene (B[a]P), both of which are potent carcinogenic compounds. In this study, we show that 1-NP is more potent in reducing cell viability than B[a]P, pyrene, nitrobenzene, and nitromethane. Aldo-keto reductases (AKRs) are enzymes which metabolize polycyclic aromatic hydrocarbons into active metabolites that form PAH-DNA-adducts causing mutagenesis of DNA. We found that the AKR1C2 inhibitor, ursodeoxycholic acid (UA), inhibited 1-NP-induced, but not B[a]P-induced, phosphorylation of p53 and cleavage of poly (ADP-ribose) polymerase (PARP). 1-NP-induced apoptosis was also suppressed by UA, as detected by Hoechst 33342 staining, flow cytometric analysis of subG0/G1 phase and annexin V binding to phosphatidylserine. The AKR1C1 and 1C4 inhibitor, 1,10-phenanthroline (Phen), inhibited the toxic effects of both 1-NP and B[a]P. In contrast, the AKR7A1 and 7A5 inhibitors, succinate and citrate, did not influence the toxic effects of 1-NP or B[a]P. In addition, several metabolic and signaling pathways were analyzed, these were used to compare the results of the toxic effect of AKRs on 1-NP and B[a]P. Through the application of kinase inhibitors, results indicated that p38-MAPK, but not ERK1/2 or JNK, was essential for mediating both 1-NP's and B[a]P's induction of the phosphorylation of p53 and cleavage of PARP. Neither ellipticine, a CYP1A1 inhibitor, nor 2,6-diisopropylphenol, a CYP1A2 and 2B1 inhibitor, blocked the toxic effects of 1-NP and B[a]P, which indicates that neither CYP1A1, 1A2, nor 2B1 is essential for the transformation of 1-NP and B[a], into toxic metabolites. AKR1C2 was constitutively expressed in HepG2 cells and was not regulated by 1-NP or B[a]P. In conclusion, this is the first report on AKRs' actions toward nitro-PAH in cells. The metabolic and signaling pathways for the toxic effects of both 1-NP and B[a]P are similar except that AKR1C2 plays differential role between them. The results provide valuable information for further investigations on AKRs.