bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-κB
Authors: Bolati Dilinaer , Shimizu Hidehisa , Yisireyili Maimaiti , Nishijima Fuyuhiko , Niwa Toshimitsu 
Published: March 2013

Abstract

Background
Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients, accelerating the progression of CKD. In CKD rat kidney, the expressions of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its related genes are downregulated. AST-120, an oral sorbent, reduces serum indoxyl sulfate and slows the progression of CKD. The present study aimed to determine whether indoxyl sulfate downregulates Nrf2 expression in human proximal tubular cells and rat kidneys and whether AST-120 upregulates Nrf2 expression in CKD rat kidneys.

Methods
Effects of indoxyl sulfate on expression of Nrf2 were determined using HK-2 cells as human proximal tubular cells and the following animals: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH+IS). Further, AST-120 was administered to subtotally nephrectomized CKD rats to determine its effect on the expression of Nrf2.

Results
Indoxyl sulfate downregulated Nrf2 expression in HK-2 cells. The indoxyl sulfate-induced downregulation of Nrf2 expression was alleviated by an inhibitor of nuclear factor-κB (NF-κB) (pyrrolidine dithiocarbamate) and small interfering RNA specific to NF-κB p65. DN+IS, DH, and DH+IS rats showed decreased renal expression of Nrf2 and its downstream target genes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), and increased renal expression of 8-hydroxydeoxyguanosine (8-OHdG), a marker of reactive oxygen species (ROS), compared with DN. Thus, indoxyl sulfate, as well as hypertension, downregulated renal expression of Nrf2 in rats. AST-120 upregulated renal expression of Nrf2, HO-1 and NQO1 and suppressed renal expression of 8-OHdG compared with control CKD rats.

Conclusions
Indoxyl sulfate downregulates renal expression of Nrf2 through activation of NF-κB, followed by downregulation of HO-1 and NQO1 and increased production of ROS. Further, AST-120 upregulates renal expression of Nrf2 in CKD rats by removing serum indoxyl sulfate, followed by upregulation of HO-1 and NQO1 and decreased production of ROS.
The effect of sunlight exposure on interleukin-6 levels in depressive and non-depressive subjects
Authors: Levandovski Rosa , Pfaffenseller Bianca , Carissimi Alicia , Gama Clarissa S , Hidalgo Maria Paz Loayza 
Published: March 2013

AbstractBackgroundThe objective of this epidemiological study was to evaluate the effect of length of sunlight exposure on interleukin 6 (IL-6) levels in depressive and non-depressive subjects.MethodsThis was a cross-sectional study with 154 subjects (54 males, mean age: 43.5 ± 12.8 years) who were living in a rural area in south Brazil. Chronobiological and light parameters were assessed using the Munich Chronotype Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Depressive symptoms were assessed with the Beck Depression Inventory. Plasma levels of inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon) were collected during the daytime and measured.ResultsIL-6 levels showed a positive correlation with light exposure (r = 0.257; p < 0.001) and a negative correlation with the mid-sleep phase on work-free days (r = -0.177; p = 0.028). Multiple linear regression analysis showed that only the length of light exposure was an independent factor for predicting IL-6 levels (ß = 0.26; p = 0.002). In non-depressed subjects, exposure to a different intensity of light did not affect IL-6 levels (t = -1.6; p = 0.1). However, when the two depressive groups with low and high light exposure were compared, the low light exposure group had lower levels of IL-6 compared with the high light exposure group (t = -2.19 and p = 0.0037).ConclusionsThe amount of time that participants are exposed to sunlight is directly related to their IL-6 levels. Additionally, depressed subjects differ in their IL-6 levels if they are exposed to light for differing amounts of time.
Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2
Authors: Wagner Anika E , Boesch-Saadatmandi Christine , Breckwoldt Dorothea , Schrader Charlotte , Schmelzer Constance , Döring Frank , Hashida Koji , Hori Osamu , Matsugo Seiichi , Rimbach Gerald 
Published: March 2013

Abstract

Background
Both resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid.

Methods
The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays.

Results
Here, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid.

Conclusions
Unlike heme oxygenase-1 (which is highly regulated by Nrf2) paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter) induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.
Differential impact of metabolic syndrome on subclinical atherosclerosis according to the presence of diabetes
Authors: Won Ki-Bum , Chang Hyuk-Jae , Kim Hyeon-Chang , Jeon Kyewon , Lee Hancheol , Shin Sanghoon , Cho In-Jeong , Park Sung-Ha , Lee Sang-Hak , Jang Yangsoo 
Published: March 2013

AbstractBackgroundMetabolic syndrome (MS) is associated with increased risks of diabetes and atherosclerotic cardiovascular disease. However, data on the impact of MS and its individual components on subclinical atherosclerosis (SCA) according to diabetes status are scarce.MethodsSurrogate markers of SCA, brachial–ankle pulse wave velocity (baPWV), and carotid intima–medial thickness (IMT) and plaque were assessed in 2,560 subjects (60 ± 8 years, 33% men) who participated in baseline health examinations for a community-based cohort study.ResultsThe participants included 2,149 non-diabetics (84%) and 411 diabetics (16%); 667 non-diabetics (31%) and 285 diabetics (69%) had MS, respectively. Diabetics had significantly higher baPWV and carotid IMT, and more plaques than non-diabetics (p < 0.001, respectively). Individuals with MS had significantly higher baPWV and carotid IMT than those without MS only among non-diabetics (p < 0.001, respectively). Among MS components, increased blood pressure was significantly associated with the exacerbation of all SCA markers in non-diabetics. The number of MS components was significantly correlated with both baPWV and carotid IMT in non-diabetics (baPWV: r = 0.302, p < 0.001; carotid IMT: r = 0.217, p < 0.001). Multiple regression showed both MS and diabetes were significantly associated with baPWV (p < 0.001, respectively), carotid IMT (MS: p < 0.001; diabetes: p = 0.005), and the presence of plaque (MS: p = 0.041; diabetes: p = 0.002).ConclusionsMS has an incremental impact on SCA in conditions without diabetes. The identification of MS and its individual components is more important for the risk stratification of CVD in non-diabetic individuals.
Environmental determinant of malaria cases among travellers
Authors: Texier Gaëtan , Machault Vanessa , Barragti Meili , Boutin Jean-Paul , Rogier Christophe 
Published: March 2013

Abstract

Background
Approximately 125 million travellers visit malaria-endemic countries annually and about 10,000 cases of malaria are reported after returning home. Due to the fact that malaria is insect vector transmitted, the environment is a key determinant of the spread of infection. Geo-climatic factors (such as temperature, moisture, water quality) determine the presence of Anopheles breeding sites, vector densities, adult mosquito survival rate, longevity and vector capacity. Several studies have shown the association between environmental factors and malaria incidence in autochthonous population. The association between the incidence of clinical malaria cases among non-immune travellers and environmental factors is yet to be evaluated. The objective of the present study was to identify, at a country scale (Ivory Coast), the environmental factors that are associated with clinical malaria among non-immune travellers, opening the way for a remote sensing-based counselling for malaria risk prevention among travellers.

Methods
The study sample consisted in 87 cohorts, including 4,531 French soldiers who travelled to Ivory Coast, during approximately four months, between September 2002 and December 2006. Their daily locations were recorded during the entire trip. The association between the incidence of clinical malaria and other factors (including individual, collective and environmental factors evaluated by remote sensing methods) was analysed in a random effect mixed Poisson regression model to take into account the sampling design.

Results
One hundred and forty clinical malaria cases were recorded during 572,363 person-days of survey, corresponding to an incidence density of 7.4 clinical malaria episodes per 1,000 person-months under survey. The risk of clinical malaria was significantly associated with the cumulative time spent in areas with NDVI > 0.35 (RR = 2,42), a mean temperature higher than 27°C (RR = 2,4), a longer period of dryness during the preceding month (RR = 0,275) and the cumulative time spent in urban areas (RR = 0,52).

Conclusions
The present results suggest that remotely-sensed environmental data could be used as good predictors of the risk of clinical malaria among vulnerable individuals travelling through African endemic areas.
RETRACTED ARTICLE: Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells
Authors: Panka David J , Liu Qingjun , Geissler Andrew K , Mier James W 
Published: March 2013

Abstract
Background
The studies reported herein were undertaken to determine if the angiostatic function of p53 could be exploited as an adjunct to VEGF-targeted therapy in the treatment of renal cell carcinoma (RCC).

Methods
Nude/beige mice bearing human RCC xenografts were treated with various combinations of sunitinib and the HDM2 antagonist MI-319. Tumors were excised at various time points before and during treatment and analyzed by western blot and IHC for evidence of p53 activation and function.

Results
Sunitinib treatment increased p53 levels in RCC xenografts and transiently induced the expression of p21waf1, Noxa, and HDM2, the levels of which subsequently declined to baseline (or undetectable) with the emergence of sunitinib resistance. The development of resistance and the suppression of p53-dependent gene expression temporally correlated with the induction of the p53 antagonist HDMX. The concurrent administration of MI-319 markedly increased the antitumor and anti-angiogenic activities of sunitinib and led to sustained p53-dependent gene expression. It also suppressed the expression of the chemokine SDF-1 (CXCL12) and the influx of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) otherwise induced by sunitinib. Although p53 knockdown markedly reduced the production of the angiostatic peptide endostatin, the production of endostatin was not augmented by MI-319 treatment.

Conclusions
The evasion of p53 function (possibly through the expression of HDMX) is an essential element in the development of resistance to VEGF-targeted therapy in RCC. The maintenance of p53 function through the concurrent administration of an HDM2 antagonist is an effective means of delaying or preventing the development of resistance.
Dysfunctional HDL and progression of atherosclerosis in HIV-1-infected and -uninfected adults
Authors: Kelesidis Theodoros , Yang Otto O , Kendall Michelle A , Hodis Howard N , Currier Judith S 
Published: March 2013

Abstract

Background
HDL function rather than absolute level may be a more accurate indicator for risk of developing atherosclerosis. Dysfunctional HDL has increased redox activity and reduced antioxidant properties, but it is unknown whether abnormal HDL function is associated with progression of atherosclerosis in HIV-1-infected subjects.

Findings
We retrospectively measured serum HDL function in 91 subjects from a prospective 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1-uninfected (n=36) or HIV-1+ with (n=29) or without (n=26) protease inhibitor (PI)-based therapy for ≥ 2 years. HDL function was assessed using a biochemical assay that measures the oxidation of dihydrorhodamine 123 (DHR oxidation rate, DOR), in which higher DOR readout corresponds to dysfunctional HDL phenotype.
There were no significant associations between DOR and HIV-1 infection. In univariate analysis of 55 HIV-1-infected subjects, greater waist circumference and lower serum HDL were significantly associated with higher baseline levels of DOR (p=0.01). These subjects had significant increases in levels of DOR over time (3 years) that were associated with white race (p=0.03), higher nadir CD4 count (p<0.001), and lower baseline CIMT (p<0.001). Lower baseline HDL levels, but not function of HDL (p>0.1) (DOR), were significantly associated (p=0.02) with progression of CIMT.

Conclusion
In a small matched cohort study of HIV-1-infected subjects who had a low cardiovascular risk profile, HDL function changed over time and was independently associated with anthropometric parameters of obesity but not with progression of CIMT.
Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study
Authors: Gipson Debbie S , Selewski David T , Massengill Susan F , Wickman Larysa , Messer Kassandra L , Herreshoff Emily , Bowers Corinna , Ferris Maria E , Mahan John D , Greenbaum Larry A , MacHardy Jackie , Kapur Gaurav , Chand Deepa H , Goebel Jens , Barletta Gina Marie , Geary Denis , Kershaw David B , Pan Cynthia G , Gbadegesin Rasheed , Hidalgo Guillermo , Lane Jerome C , Leiser Jeffrey D , Plattner Brett W , Song Peter X , Thissen David , Liu Yang , Gross Heather E , DeWalt Darren A 
Published: March 2013

AbstractBackground and objectivesNephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents.DesignThis cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, social-peer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema.ResultsAll 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics.ConclusionsChildren and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS.
Hashimoto’s Thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer
Authors: Ye Zhi-qiang , Gu Dian-na , Hu Hong-ye , Zhou Yi-li , Hu Xiao-qu , Zhang Xiao-hua 
Published: March 2013

Abstract

Background
To confirm whether clinical and biochemical parameters or Hashimoto’s thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC).

Methods
A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented.

Results
Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97–4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201–3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563–5.435), and microcalcification (OR = 14.486, 95% CI = 11.374–18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634).

Conclusions
The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.
Expression of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine pituitary during the oestrous cycle
Authors: Kiezun Marta , Maleszka Anna , Smolinska Nina , Nitkiewicz Anna , Kaminski Tadeusz 
Published: March 2013

AbstractBackgroundAdiponectin, protein secreted mainly by white adipose tissue, is an important factor linking the regulation of metabolic homeostasis and reproductive processes. The biological activity of the hormone is mediatedviatwo distinct receptors, termed adiponectin receptor 1(AdipoR1) and adiponectin receptor 2 (AdipoR2). The present study analyzed mRNA and protein expression of AdipoR1 and AdipoR2 in the anterior (AP) and posterior (NP) pituitary of cyclic pigs.MethodsThe total of 20 animals was assigned to one of four experimental groups (n = 5 per group) as follows: days 2–3 (early-luteal phase), 10–12 (mid-luteal phase), 14–16 (late-luteal phase), 17–19 (follicular phase) of the oestrous cycle. mRNA and protein expression were analyzed using real-time PCR and Western Blot methods, respectively.ResultsThe lowest AdipoR1 gene expression was detected in AP on days 10–12 relative to days 2–3 and 14–16 (p < 0.05). In NP, AdipoR1 mRNA levels were elevated on days 10–12 and 14–16 (p < 0.05). AdipoR2 gene expression in AP was the lowest on days 10–12, and an expression peak occurred on days 2–3 (p < 0.05). In NP, the lowest (p < 0.05) expression of AdipoR2 mRNA was noted on days 17–19. The AdipoR1 protein content in AP was the lowest on days 17–19 (p < 0.05), while in NP the variations in protein expression levels during the oestrous cycle were negligible. AdipoR2 protein in AP was most abundant on days 10–12, and it reached the lowest level on days 2–3 and 17–19 of the cycle (p < 0.05). The presence of AdipoR2 protein in NP was more pronounced on days 10–12 (p < 0.05).ConclusionsOur study was the first experiment to demonstrate that AdipoR1 and AdipoR2 mRNAs and proteins are present in the porcine pituitary and that adiponectin receptors expression is dependent on endocrine status of the animals.
A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells
Authors: Luo Daya , Wilson James M , Harvel Nikki , Liu Jimei , Pei Lirong , Huang Shuang , Hawthorn LesleyAnn , Shi Huidong 
Published: March 2013

AbstractIn this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition ofin vitrocell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, includingCFL2,LAMC1,TIMP2,ZEB1,CDH11,PRKCA,PTPRJ,PTPRM,LDHB, andSEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c,CFL2, and demonstrated thatCFL2is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.