PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-17 (17)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
Document Types
author:("Li, yanji")
1.  Blunted Nocturnal Cortisol Rise is Associated With Higher Carotid Artery Intima-Media Thickness (CIMT) in Overweight African American and Latino Youth 
Psychoneuroendocrinology  2013;38(9):1658-1667.
Background
Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical atherosclerosis in youth has yet to be investigated. The objectives of this study were to: 1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; 2) assess ethnic differences in these relationships and 3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).
Methods
One hundred and fifty-six overweight and obese African-American and Latino children (ages 8–17, 86M/70F, 55 African-American /101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR=salivary cortisol rise from 2200hrs to awakening at 0530hrs), cortisol awakening response (CAR=salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol.
Results
Using linear regression, salivary cortisol0530hrs and NCR were negatively associated with CIMT (βstandardized = −0.215 and −0.220, p<0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol2200hrs, morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR <0.44µg/dL, n=52) had significantly greater CIMT than those with HIGH NCR (NCR ≥0.91 µg/dL, n=52; 0.632±0.008 vs. 0.603±0.008mm p=0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (−0.028±0.009, p=0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all pinteraction=0.28–0.97). CRP, IL-6 and TNF-α were not associated with CIMT (p>0.05). IL-6 was inversely related to NCR (r=−0.186, p=0.03), but it did not explain the relationship between NCR and CIMT.
Conclusions
Salivary cortisol0530hrs and NCR, but not CAR, nocturnal salivary cortisol 2200hrs, morning serum cortisol or overnight urinary free cortisol, were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.
doi:10.1016/j.psyneuen.2013.01.011
PMCID: PMC3722251  PMID: 23433749
Obesity; cardiovascular risk; carotid artery; intima media thickness; cortisol
2.  Decrease of Pirimiphos-Methyl and Deltamethrin Residues in Stored Rice with Post-Harvest Treatment 
A modified quick, easy, cheap, effective, rugged (QuEChERS) method with multi-walled carbon nanotubes (MWCNTs) as reversed-dispersive solid phase extraction (r-DSPE) material was applied to the analysis of pirimiphos-methyl and deltamethrin residues in stored rice. Two dustable powder (DP) formulations (2% pirimiphos-methyl and deltamethrin DP; 5% pirimiphos-methyl DP) were applied in simulated storehouse trials in the lab. The residues and dissipation of the two pesticides in stored rice were investigated. Slow dissipation of both pesticides was observed in stored rice. The half-lives of pirimiphos-methyl were 23.9–28.9 days, and those of deltamethrin were 23.9–24.8 days. Residues of pirimiphos-methyl from application rates of 4.5–6.75 a.i. mg/kg (active ingredient milligram per kilogram) and 10–15 a.i. mg/kg were 1.6–3.8 mg/kg and 3.0–4.5 mg/kg at 60 days Pre-harvest Interval (PHI). Residues of deltamethrin from an application rate of 0.5–0.75 a.i. mg/kg were 0.13–0.14 mg/kg at 60 days PHI. Both pesticides residues were below the Maximum Residue Limits (MRLs) established by the Codex Alimentarius Commission (CAC). Therefore, at the recommended dosages they are safe for use on stored rice.
doi:10.3390/ijerph110505372
PMCID: PMC4053915  PMID: 24840352
pirimiphos-methyl; deltamethrin; rice; post-harvest treatment; residue; dissipation
3.  Indo-Pacific Warm Pool Area Expansion, Modoki Activity, and Tropical Cold-Point Tropopause Temperature Variations 
Scientific Reports  2014;4:4552.
The tropical cold-point tropopause temperature (CPTT), a potentially important indicator of global climate change, is of particular importance for understanding changes in stratospheric water vapor levels. Since the 1980s, the tropical CPTT has shown not only interannual variations, but also a decreasing trend. However, the factors controlling the variations in the tropical CPTT since the 1980s remain elusive. The present study reveals that the continuous expansion of the area of the Indo-Pacific warm pool (IPWP) since the 1980s represents an increase in the total heat energy of the IPWP available to heat the tropospheric air, which is likely to expand as a result. This process lifts the tropical cold-point tropopause height (CPTH) and leads to the observed long-term cooling trend of the tropical CPTT. In addition, our analysis shows that Modoki activity is an important factor in modulating the interannual variations of the tropical CPTT through significant effects on overshooting convection.
doi:10.1038/srep04552
PMCID: PMC3971398  PMID: 24686481
4.  Nonrigid Registration of Lung CT Images Based on Tissue Features 
Nonrigid image registration is a prerequisite for various medical image process and analysis applications. Much effort has been devoted to thoracic image registration due to breathing motion. Recently, scale-invariant feature transform (SIFT) has been used in medical image registration and obtained promising results. However, SIFT is apt to detect blob features. Blobs key points are generally detected in smooth areas which may contain few diagnostic points. In general, diagnostic points used in medical image are often vessel crossing points, vascular endpoints, and tissue boundary points, which provide abundant information about vessels and can reflect the motion of lungs accurately. These points generally have high gradients as opposed to blob key points and can be detected by Harris. In this work, we proposed a hybrid feature detection method which can detect tissue features of lungs effectively based on Harris and SIFT. In addition, a novel method which can remove mismatched landmarks is also proposed. A series of thoracic CT images are tested by using the proposed algorithm, and the quantitative and qualitative evaluations show that our method is statistically significantly better than conventional SIFT method especially in the case of large deformation of lungs during respiration.
doi:10.1155/2013/834192
PMCID: PMC3845410  PMID: 24324526
5.  p23 co-chaperone protects the aryl hydrocarbon receptor from degradation in mouse and human cell lines 
Biochemical pharmacology  2012;84(6):838-850.
The aryl hydrocarbon receptor (AhR) is a ligand-sensitive transcription factor which is responsible for most 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicities. Without ligand, the AhR complex is cytoplasmic and contains p23. Our objective was to investigate whether the wild type p23 levels are important for the AhR function. We generated eight p23-specific knockdown stable cell lines via either electroporation or lentiviral infection. Five of these stable cell lines were generated from a mouse hepatoma cell line (Hepa1c1c7) and three were from human hepatoma and cervical cell lines (Hep3B and HeLa). All of them expressed lower AhR protein levels, leading to reduced ligand-induced, DRE-driven downstream activity. The AhR protein levels in p23-specific knockdown stable cells were reversed back to wild type levels after exogenous p23 was introduced. Reduction of the AhR protein levels in these stable cells was caused by a decrease in the AhR message levels and an increase of the AhR protein degradation in the absence of ligand. This ligand-independent degradation of AhR was insensitive to MG132, suggesting that the 26S proteasome was not responsible for the degradation. In addition, MG132 could not protect AhR from the ligand-induced degradation in both mouse and human p23-knockdown stable cells.
doi:10.1016/j.bcp.2012.06.018
PMCID: PMC3418383  PMID: 22759865
p23 co-chaperone; aryl hydrocarbon receptor; AhR; protein degradation; dioxin
6.  Persistence of the metabolic syndrome and its influence on carotid artery intima media thickness in overweight Latino children 
Atherosclerosis  2009;206(2):594-598.
Objective
The objective of this study was to examine the influence of persistence of the MetS (MetS) and its individual components over a 3-year period on carotid intima media thickness (CIMT) in overweight Latino children.
Methods
Ninety-seven healthy male and female overweight Latino children (mean age at baseline: 11.0±1.8 yrs) were assessed for MetS on four annual evaluations and classified according to the persistence of MetS: NEVER (0 annual visits with the MetS, n=53), INTERMITTENT (1 or 2 visits with the MetS, n=28), and PERSISTENT (3 or 4 visits with the MetS, n=16). CIMT was measured with high-resolution B-mode ultrasound (7.9±0.7 months after the most recent MetS assessment; mean age: 14.6±1.8 yr).
Results
PERSISTENT MetS was associated with significantly higher CIMT (0.647mm±0.018 compared to (0.600mm±0.007 in those who NEVER had MetS, p<0.01). This difference remained significant after controlling for gender, baseline age, total fat mass, total lean tissue mass and insulin sensitivity. PERSISTENT high waist circumference and PERSISTENT high blood pressure were also significantly associated with higher mean CIMT, but these differences were no longer significant after controlling for total fat and lean tissue mass. Baseline systolic blood pressure and 2-hour glucose were significantly related to CIMT independent of all other MetS components (p<0.05).
Conclusions
Persistence of the MetS over a 3-year period was uniquely associated with increased CIMT during childhood. Children with hypertension, persistent abdominal adiposity and impaired glucose tolerance may also be at higher risk for elevated CIMT.
doi:10.1016/j.atherosclerosis.2009.03.013
PMCID: PMC3767145  PMID: 19446812
CIMT; obesity; children; MetS
7.  Subclinical atherosclerosis in Latino youth: Progression of carotid intima media thickness (CIMT) and its relationship to cardiometabolic risk factors 
The Journal of pediatrics  2011;158(6):935-940.
Objective
To assess carotid artery intima media thickness (CIMT) change over two years in overweight Latino adolescents and examine its relationship to cardiometabolic risk.
Study design
72 healthy overweight male and female Latino adolescents (mean age: 14.5±1.7 yrs; mean BMI: 31.5±6.9 kg/m2) were evaluated at baseline and 2 years later for: CIMT by high resolution B-mode ultrasound, the metabolic syndrome and its features, body composition by DEXA and MRI, and glucose/insulin measures by fasting blood, and oral and intravenous glucose tolerance tests.
Results
Baseline CIMT did not differ from 2-year follow-up; however 38 participants increased CIMT (0.017±0.003mm; +2.8%) and 34 decreased (-0.019±0.002mm; −3.1%). ANCOVA analyses showed that participants with CIMT progression had higher baseline LDL-cholesterol and total cholesterol (91.3±3.4 and 150.3±3.9mg/dL) compared with those with CIMT regression (78.1±3.6 and 135.6±4.2mg/dL, p<0.05), independent of sex, baseline CIMT, age, and height. In multivariate regression, LDL-cholesterol was the sole predictor of CIMT progression, but the effect was small (odds of CIMT progression increased by 3% for each 1 mg/dL higher baseline LDL-cholesterol [95% CI: 1.004-1.006, p=0.03].
Conclusions
These results indicate a high variability in the magnitude of CIMT change in growing overweight Latino youth and support the use of LDL-cholesterol to assess sub-clinical atherosclerosis risk in this population.
doi:10.1016/j.jpeds.2010.12.008
PMCID: PMC3767153  PMID: 21238987
Obesity; Cardiovascular disease risk; Ultrasound imaging
8.  Cinnamoyl-based Nrf2-Activators Targeting Human Skin Cell Photo-oxidative Stress 
Free radical biology & medicine  2008;45(4):385-395.
Strong experimental evidence suggests the involvement of photo-oxidative stress mediated by reactive oxygen species as a crucial mechanism of solar damage relevant to human skin photoaging and photocarcinogenesis. Based on the established role of antioxidant response element (ARE)-mediated gene expression in cancer chemoprevention, we tested the hypothesis that small molecule Nrf2-activators may serve a photo-chemopreventive role by targeting skin cell photo-oxidative stress. A luciferase-based reporter gene assay was used as a primary screen for the identification of novel agents that modulate the Nrf2-Keap1 signaling pathway. A series of cinnamoyl-based electrophilic Michael acceptors including cinnamic aldehyde and methyl-1-cinnamoyl-5-oxo-2-pyrrolidine-carboxylate was identified as potent Nrf2-activators. Hit confirmation was performed in a secondary screen, based on immunodetection of Nrf2 protein upregulation in human Hs27 skin fibroblasts, HaCaT keratinocytes, and primary skin keratinocytes. Bioefficacy profiling of positive test compounds in skin cells demonstrated compound-induced upregulation of hemeoxygenase I and NAD(P)H-quinone oxidoreductase, two Nrf2 target genes involved in the cellular antioxidant response. Pretreatment with cinnamoyl-based Nrf2-activators suppressed intracellular oxidative stress and protected against photo-oxidative induction of apoptosis in skin cells exposed to high doses of singlet oxygen. Our pilot studies suggest feasibility of developing cinnamoyl-based Nrf2-activators as novel photo-chemopreventive agents targeting skin cell photo-oxidative stress.
doi:10.1016/j.freeradbiomed.2008.04.023
PMCID: PMC3710742  PMID: 18482591
Nrf2; skin cancer; photo-oxidative stress; photo-chemoprevention; Michael acceptor; cinnamic aldehyde; singlet oxygen
9.  Suppression of the hypoxia inducible factor-1 function by redistributing the aryl hydrocarbon receptor nuclear translocator from nucleus to cytoplasm 
Cancer Letters  2012;320(1):111-121.
The aryl hydrocarbon receptor nuclear translocator (ARNT) heterodimerizes with hypoxia inducible factor-1α (HIF-1α), followed by upregulation of genes that are essential for carcinogenesis. We utilized a novel peptide (Ainp1) to address whether the HIF-1α signaling could be suppressed by an ARNT-mediated mechanism. Ainp1 suppresses the HIF-1α-dependent luciferase expression in Hep3B cells and this suppression can be reversed by ARNT. Ainp1 reduces the interaction between ARNT and HIF-1α, suppresses the formation of the HIF-1 gel shift complex, and suppresses the ARNT recruitment to the vegf promoter. These effects are partly mediated by redistribution of the nuclear ARNT contents to the cytoplasm.
doi:10.1016/j.canlet.2012.01.037
PMCID: PMC3319868  PMID: 22306343
ARNT-interacting peptide; HIF-1α; ARNT; AhR; anticancer; Hep3B
10.  E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks 
Cell Cycle  2011;10(8):1287-1294.
The E2F1 transcription factor is post-translationally modified and stabilized in response to various forms of DNA damage to regulate the expression of cell cycle and pro-apoptotic genes. E2F1 also forms foci at DNA double-strand breaks (DSBs) but the function of E2F1 at sites of damage is unknown. Here we demonstrate that the absence of E2F1 leads to spontaneous DNA breaks and impaired recovery following exposure to ionizing radiation. E2F1 deficiency results in defective NBS1 phosphorylation and foci formation in response to DSBs but does not affect NBS1 expression levels. Moreover, an increased association between NBS1 and E2F1 is observed in response to DNA damage, suggesting that E2F1 may promote NBS1 foci formation through a direct or indirect interaction at sites of DNA breaks. E2F1 deficiency also impairs RPA and Rad51 foci formation indicating that E2F1 is important for DNA end resection and the formation of single-stranded DNA at DSBs. These findings establish new roles for E2F1 in the DNA damage response, which may directly contribute to DNA repair and genome maintenance.
doi:10.4161/cc.10.8.15341
PMCID: PMC3117137  PMID: 21512314
E2F; NBS1; RPA; RAD51; DNA damage response
11.  ZmbZIP60 mRNA is spliced in maize in response to ER stress 
BMC Research Notes  2012;5:144.
Background
Adverse environmental conditions produce ER stress and elicit the unfolded protein response (UPR) in plants. Plants are reported to have two "arms" of the ER stress signaling pathway-one arm involving membrane-bound transcription factors and the other involving a membrane-associated RNA splicing factor, IRE1. IRE1 in yeast to mammals recognizes a conserved twin loop structure in the target RNA.
Results
A segment of the mRNA encoding ZmbZIP60 in maize can be folded into a twin loop structure, and in response to ER stress this mRNA is spliced, excising a 20b intron. Splicing converts the predicted protein from a membrane-associated transcription factor to one that is targeted to the nucleus. Splicing of ZmbZIP60 can be elicited in maize seedlings by ER stress agents such as dithiothreitol (DTT) or tunicamycin (TM) or by heat treatment. Younger, rather than older seedlings display a more robust splicing response as do younger parts of leaf, along a developmental gradient in a leaf. The molecular signature of an ER stress response in plants includes the upregulation of Binding Protein (BIP) genes. Maize has numerous BIP-like genes, and ER stress was found to upregulate one of these, ZmBIPb.
Conclusions
The splicing of ZmbZIP60 mRNA is an indicator of ER stress in maize seedlings resulting from adverse environmental conditions such as heat stress. ZmbZIP60 mRNA splicing in maize leads predictively to the formation of active bZIP transcription factor targeted to the nucleus to upregulate stress response genes. Among the genes upregulated by ER stress in maize is one of 22 BIP-like genes, ZmBIPb.
doi:10.1186/1756-0500-5-144
PMCID: PMC3369818  PMID: 22417282
IRE1; bZIP transcription factor; mRNA splicing; Unfolded protein response; Binding protein; Chaperone; Heat stress; Corn
12.  The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism 
We explored whether modulation of the estrogen receptor (ER) signaling is possible through an aryl hydrocarbon receptor nuclear translocator (Arnt)-dependent mechanism. We utilized the Arnt-interacting protein 2 (Ainp2) to examine whether the presence of Ainp2 in MCF-7 cells would interfere with the Arnt-mediated ER signaling. We found that Arnt increased the 17 beta-estradiol (E2)-dependent luciferase activity and Ainp2 significantly suppressed this Arnt-mediated luciferase activity. Ainp2 significantly suppressed 25% of the E2- and Arnt-dependent upregulation of the GREB1 message. No suppression of the ER target gene expression by Ainp2 was detected in Arnt-knockdown MCF-7 cells and in Arnt-independent ER signaling. Although Ainp2 did not interact with ER alpha and ER beta, it suppressed the ER alpha::Arnt interaction and reduced the E2-driven recruitment of Arnt to the GREB1 promoter. We concluded that Ainp2 suppresses the ER signaling by not allowing Arnt to participate in the ER-dependent, Arnt-mediated activation of gene transcription.
doi:10.1016/j.abb.2010.07.022
PMCID: PMC2936660  PMID: 20674540
estrogen receptor; Arnt; Ainp2; Arnt-interacting protein
13.  Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus 
European Heart Journal  2009;30(24):3064-3073.
Aims
To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU).
Methods and results
In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima–media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P ≤ 0.036 and r = 0.46, P ≤ 0.055) and with an improvement in endothelium-related ΔMBF to CPT and to adenosine (r = 0.46, P ≤ 0.038 and r = 0.36, P ≤ 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in ΔMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P ≤ 0.001 by one-way analysis of variance).
Conclusion
In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.
doi:10.1093/eurheartj/ehp482
PMCID: PMC2792718  PMID: 19914919
Cardiovascular disease prevention; Carotid IMT; Coronary artery calcification; Coronary circulation; Endothelium; Diabetes mellitus; Positron emission tomography
14.  A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling 
FEBS letters  2009;583(18):3039-3044.
We used a xenograft model to investigate whether the aryl hydrocarbon receptor deletion construct CΔ553 suppresses tumor growth. HeLa cells that were infected with CΔ553 expressing adenovirus (Ad553) formed very small tumors whereas the control adenovirus-infected cells formed large tumors at day 15. CΔ553 inhibited the formation of the HIF-1 DNA complex and suppressed the induction of the HIF-1α target proteins CAIX and GLUT1. The Ad553 tumors had less HIF-1 function since they showed reduced microvessel formation and lesser amounts of HIF-1α, Arnt, phospho-Akt, CAIX, and GLUT1. Proteasome-mediated Arnt degradation was enhanced in Ad553-infected HeLa cells and tumors.
doi:10.1016/j.febslet.2009.08.013
PMCID: PMC2747505  PMID: 19695250
15.  Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction 
Toxicology and applied pharmacology  2008;230(3):383-389.
Drinking water contaminated with arsenic, a human carcinogen, is a worldwide health issue. An understanding of cellular signaling events in response to arsenic exposure and rational designing of strategies to reduce arsenic damages by modulating signaling events are important to fight against arsenic-induced diseases. Previously, we reported that activation of the Nrf2-mediated cellular defense pathway confers protection against toxic effects induced by sodium arsenite [As(III)] or monomethylarsonous acid [MMA(III)]. Paradoxically, arsenic has been reported to induce the Nrf2-dependent signaling pathway. Here, we report the unique mechanism of Nrf2 induction by arsenic. Similar to tert-butylhydroquinone (tBHQ) or sulforaphane (SF), arsenic induced the Nrf2-dependent response through enhancing Nrf2 protein levels by inhibiting Nrf2 ubiquitination and degradation. However, the detailed action of arsenic in Nrf2 induction is different from that of tBHQ or SF. Arsenic markedly enhanced the interaction between Keap1 and Cul3, subunits of the E3 ubiquitin ligase for Nrf2, which led to impaired dynamic assembly/disassembly of the E3 ubiquitin ligase and thus decreased its ligase activity. Furthermore, induction of Nrf2 by arsenic is independent of the previously identified C151 residue in Keap1 that is required for Nrf2 activation by tBHQ or SF. Distinct mechanisms of Nrf2 activation by seemingly harmful and beneficial reagents provide a molecular basis to design Nrf2-activating agents for therapeutic intervention.
doi:10.1016/j.taap.2008.03.003
PMCID: PMC2610481  PMID: 18417180
16.  Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2 
Carcinogenesis  2008;29(6):1235-1243.
Drug resistance during chemotherapy is the major obstacle to the successful treatment of many cancers. Here, we report that inhibition of NF-E2-related factor 2 (Nrf2) may be a promising strategy to combat chemoresistance. Nrf2 is a critical transcription factor regulating a cellular protective response that defends cells against toxic insults from a broad spectrum of chemicals. Under normal conditions, the low constitutive amount of Nrf2 protein is maintained by the Kelch-like ECH-associated protein1 (Keap1)-mediated ubiquitination and proteasomal degradation system. Upon activation, this Keap1-dependent Nrf2 degradation mechanism is quickly inactivated, resulting in accumulation and activation of the antioxidant response element (ARE)-dependent cytoprotective genes. Since its discovery, Nrf2 has been viewed as a ‘good’ transcription factor that protects us from many diseases. In this study, we demonstrate the dark side of Nrf2: stable overexpression of Nrf2 resulted in enhanced resistance of cancer cells to chemotherapeutic agents including cisplatin, doxorubicin and etoposide. Inversely, downregulation of the Nrf2-dependent response by overexpression of Keap1 or transient transfection of Nrf2–small interfering RNA (siRNA) rendered cancer cells more susceptible to these drugs. Upregulation of Nrf2 by the small chemical tert-butylhydroquinone (tBHQ) also enhanced the resistance of cancer cells, indicating the feasibility of using small chemical inhibitors of Nrf2 as adjuvants to chemotherapy to increase the efficacy of chemotherapeutic agents. Furthermore, we provide evidence that the strategy of using Nrf2 inhibitors to increase efficacy of chemotherapeutic agents is not limited to certain cancer types or anticancer drugs and thus can be applied during the course of chemotherapy to treat many cancer types.
doi:10.1093/carcin/bgn095
PMCID: PMC3312612  PMID: 18413364
17.  Carotid artery intima–media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure 
AIDS (London, England)  2005;19(9):927-933.
Context
The impact of HIV infection and exposure to antiretroviral therapy on the development of subclinical atherosclerosis is incompletely understood.
Objective
To compare intima–media thickness (IMT) of the carotid artery between HIV-infected subjects receiving protease inhibitor-containing regimens and subjects not receiving these regimens and to compare differences in the IMT of the carotid artery between HIV-infected subjects and HIV-uninfected subjects.
Methods
A prospective matched cohort study in university-based outpatient clinics. Groups of three individuals (triads) matched on the following characteristics were enrolled: age, sex, race/ethnicity, smoking status, blood pressure and menopausal status. Group 1, HIV-infected subjects with continuous use of protease inhibitor (PI) therapy for ≥ 2 years; group 2, HIV-infected subjects without prior PI use; and group 3: HIV-uninfected. Ultrasonographers at six sites sent standardized ultrasound images to a central reading site for carotid IMT measurements. Carotid IMT was compared within the HIV-infected groups (1 and 2) and between the HIV-infected and uninfected groups in a matched analysis.
Results
One hundred and thirty-four individuals were enrolled in 45 triads. The median IMT in groups 1, 2 and 3 was 0.690, 0.712 and 0.698 mm, respectively. There were no statistically significant differences in IMT between groups 1 and 2, or in the combined HIV groups compared with the HIV uninfected group. Significant predictors of carotid IMT in a multivariate model included high-density lipoprotein (HDL) cholesterol, the interaction of HDL cholesterol and triglycerides, age and body mass index.
Conclusions
We found no association between PI inhibitor exposure or HIV infection and carotid IMT.
PMCID: PMC1373680  PMID: 15905673
atherosclerosis; HIV infection; carotid intima; media thickness; protease inhibitors

Results 1-17 (17)