Conclusions CD133 may play an important role in chemoresistance a

Conclusions CD133 may play an important role in chemoresistance and recurrence, thus representing a promising predictive marker for the prognosis of gastric cancer. J. Surg. Oncol. 2012; 106: 9991004. (c) 2012 Wiley Periodicals, Inc.”
“Aims: To

compare the existing model estimates of the appropriate rates of PI3K inhibitor radiotherapy for lung, breast and prostate cancers with actual radiotherapy rates in rural, semi-urban and urban areas, and in areas with short and long drive distances to cancer clinics in British Columbia.\n\nMaterials and methods: : All registered cases of lung, breast and prostate cancer diagnosed in British Columbia between 1997 and 2007 were identified. The proportion of cancers treated within 1 (RT(1y)) and 5 years (RT(5y)) of diagnosis were calculated according to rural, semi-urban and urban area, and areas associated with short and long drive distances to cancer clinics in British Columbia.\n\nResults: RT(1y) for lung, breast and prostate in urban https://www.selleckchem.com/products/ag-881.html and rural areas were 47/45%, 57/46% and 31/30%, and for short and long drive times were 47/44%, 56/50% and 31/31% compared with model estimates for initial radiotherapy needs of 41-45%, 57-61% and 32-37%, respectively. RT5y for lung, breast and prostate in urban and rural areas were 52/47%, 59/48% and 42/39%, and for short and long drive times were 51/47%, 57/50% and 42/42% compared with model estimates for overall radiotherapy needs of

66-83%, 57-61% and 60-61%, respectively.\n\nConclusions: Radiotherapy rates vary between and within urban and rural areas in British Columbia. Radiotherapy rates for breast and lung cancer patients are higher, and closer to model estimates BAY 73-4506 inhibitor of need, in urban areas and short drive time areas. Radiotherapy rates do not vary with drive time or rural versus urban classification for patients with prostate cancer. (C) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.”
“Background/Aims: The association between clinical symptoms and sleep disorders in functional dyspepsia (FD)-overlap syndrome has not been studied in detail.\n\nMethods: The subjects were

139 patients with FD, 14 with irritable bowel syndrome (IBS), 12 with nonerosive reflux disease (NERD), and 41 healthy volunteers. Gastric motility was evaluated with the C-13-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and Self-Rating Questionnaire for Depression (SRQ-D) scores to determine depression status. Sleep disorders were evaluated with Pittsburgh Sleep Quality Index (PSQI) scores.\n\nResults: There were no significant differences in age, body-mass index, alcohol intake, and smoking rate between patients with FD alone and those with FD-overlap syndrome. The postprandial abdominal fullness score in patients with FD-NERD-IBS was significantly greater than that in patients with FD-NERD overlap syndrome (p<0.

CONCLUSIONS: Expression of activated LXR alpha blocks proliferati

CONCLUSIONS: Expression of activated LXR alpha blocks proliferation of human colorectal cancer cells and slows the growth of xenograft tumors in mice. It also reduces

intestinal tumor formation after administration of chemical carcinogens, and in Apc(min/+) mice. LXR agonists therefore might be developed as therapeutic treatments for colorectal cancer.”
“Aims Although several factors contribute to wound healing, bacterial infections and the presence of biofilm can significantly affect healing. Despite that this clearly indicates that therapies should address biofilm in wounds, only few wound care products have been evaluated for their antibiofilm effect. For this reason, NU7026 we developed a rapid quantification approach to investigate

the efficacy of wound care products on wounds infected with Staphylococcus spp. Methods and Results An in vitro chronic wound infection model was used in which a fluorescent Staph.aureus strain was used to allow the rapid quantification of the bacterial burden after treatment. A good correlation was observed between the fluorescence signal and the bacterial counts. When evaluated in selleck compound this model, several commonly used wound dressings and wound care products inhibited biofilm formation resulting in a decrease between one and seven log CFU per biofilm compared with biofilm formed in the absence of products. In contrast, most dressings only moderately affected mature biofilms. Conclusion Our model allowed the rapid quantification of the bacterial burden after treatment. However, the efficacy of treatment varied between the different types of

dressings and/or wound care products. Significance and Impact of the Study Our model can be used to compare the efficacy of wound care products to inhibit biofilm formation and/or eradicate mature biofilms. In addition, the results indicate that treatment of infected wounds should be started as soon as possible and that novel products with more potent antibiofilm activity are needed.”
“Duez H, Staels B. Rev-erb-alpha: an integrator of circadian rhythms and metabolism. J Appl Physiol 107: 1972-1980, 2009. First published August 20, 2009; doi:10.1152/japplphysiol.00570.2009.-The endogenous circadian clock ensures daily selleck kinase inhibitor rhythms in diverse behavioral and physiological processes, including locomotor activity and sleep/wake cycles, but also food intake patterns. Circadian rhythms are generated by an internal clock system, which synchronizes these daily variations to the day/night alternance. In addition, circadian oscillations may be reset by the time of food availability in peripheral metabolic organs. Circadian rhythms are seen in many metabolic pathways (glucose and lipid metabolism, etc.) and endocrine secretions (insulin, etc.). As a consequence, misalignment of the internal timing system vs.

Our a-priori hypothesis was that

Our a-priori hypothesis was that SB273005 schizophrenia patients would show an increased prevalence of the nontaster phenotype compared with controls. The genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38 were assayed for 176 schizophrenia patients and 229 healthy control individuals, and the two-allele haplotypes were estimated. There was an over-representation of the major PTC nontaster haplotype among patients of European descent, relative to control individuals of similar ancestry.

Patients and controls of African ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may be used to identify subsets of schizophrenia patients who potentially harbor vulnerability genes in this region of chromosome 7q. Psychiatr Genet 22:286-289 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Chagas disease is a major endemic disease caused by the protozoan parasite Trypanosoma cruzi. This parasitic disease is widely distributed throughout Latin America, affecting 10 million people. There are also reports of canine infection in the southern part of the United States. Dogs are considered the predominant domestic reservoir for 7: cruzi in many

areas of endemicity. In Mexico, selleck kinase inhibitor dog infection by this parasite has been poorly studied. In this work 209 dogs from six villages in Jalisco, Mexico, were assessed to detect anti-T cruzi antibodies by ELISA and Western blot. Seventeen (17) seropositive dogs (8.1 %) were detected by both tests, representing a seropositive value similar to that found in some southern states of Mexico where the infection is present. No statistical differences were observed concerning the age and sex of infected and non-infected dogs. The major antigens recognized by positive sera were 26, 32, 66 and 80 kDa. These proteins are candidates to develop a specific diagnostic method for canine Chagas.

No antibodies against HSP16 protein were found in 7: cruzi seropositive sera. This is the first report of canine serology of Chagas disease in this central part of Mexico. This report will contribute to the knowledge of the infection status of domestic reservoirs in Citarinostat inhibitor the state of Jalisco, Mexico. (C) 2014 Asociacion Argentina de Microbiologia. Published by Elsevier Espana, S.L. All rights reserved.”
“Background: Slug, a regulator of epithelial mesenchymal transition, was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. This study aimed to determine the clinical significance of Slug overexpression in ESCC and determine its correlation with clinicopathological parameters and disease prognosis for ESCC patients.


“Numerical methods based on the Reynolds Averaged Navier-S


“Numerical methods based on the Reynolds Averaged Navier-Stokes (RANS) and Large Eddy Simulation (LES) equations are applied to the thermal selleck prediction of flows representative of those found in and around electronics systems and components. Low Reynolds number flows through a heated ribbed channel, around a heated cube and within a complex electronics system case are investigated using linear

and nonlinear LES models, hybrid RANS-LES and RANS-Numerical-LES (RANS-NLES) methods. Flow and heat transfer predictions using these techniques are in good agreement with each other and experimental data for a range of grid resolutions. Using second order central differences, the RANS-NLES method performs well for all simulations. (C) 2011 Elsevier Inc. All rights reserved.”
“In GDC-0994 in vitro current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells

are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicide gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic Staurosporine cell line efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in

the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter is activated by E2F only in cancer cells and therefore may be more cancer cell-specific than E2F1 promoter to drive gene expression. We show here that the ARF promoter has lower activity in normal growing fibroblasts and shows higher cancer cell-specificity compared to the E2F1 promoter.

Finally, selleck

Finally, IWR-1-endo ic95 the Multithreaded Application Real-Time executor (MARTe) framework is used for building applications particularly optimised for exploring multi-core architectures. In the past year, four new systems based on this philosophy have been installed and are now part of JET’s routine operation. The focus of the present work is on the configuration aspects that enable these new systems’ real-time capability. Details are given about the common real-time configuration of these systems, followed by a brief description of each system together with results regarding their real-time performance. A cycle time jitter analysis of a user-space MARTe based application

synchronizing over a network is also presented. The goal is to compare its deterministic performance while running on a vanilla and on a Messaging Real time Grid (MRG) Linux kernel.”
“Background: this website Allergic disorders, such as seasonal rhinitis and asthma, are increasing causes of morbidity worldwide and often result from exposure to airborne pollen. Pollen allergy has a remarkable clinical impact all over Europe. In fact, epidemiological longitudinal studies confirm that pollen species usually considered with low allergenic potential became more recently responsible for intense allergic reactions. In this study, we aimed to characterize major pollen proteolytic activity and evaluate

its contribution to the immunologic and inflammatory response to airborne allergens.\n\nMethods: Proteolytic activity in four pollen diffusates with distinct allergenicity, Olea europaea,

Dactylis glomerata, Cupressus sempervirens and Pinus sylvestris, was evaluated through several enzymatic assays. The action of pollen proteases on the paracellular integrity of Calu-3, grown at the air-liquid interphase, was evaluated through a transepithelial permeability assay. Immunoblot and immunofluorescence experiments were performed to analyse the disruption of intercellular complexes. Degradation of bioactive peptides by pollen crude extracts JIB 04 was assessed by mass spectrometry.\n\nResults: All pollen diffusates were shown to have high molecular weight proteases with serine and/or aminopeptidase activity. These proteases increased Calu-3 transepithelial permeability through disruption of transmembrane adhesion proteins: occludin, claudin-1 and E-cadherin. Moreover, they were able to degrade airway bioactive peptides and were not blocked by endogenous protease inhibitors.\n\nConclusion: Pollen grains with distinct allergenic abilities release proteases that might be involved in the sensitization to a range of airborne allergens by facilitating allergen delivery across the epithelium and also contribute directly to the inflammation characteristic of allergic diseases.

RESULTS: No differences in patient characteristics or endoscopic

RESULTS: No differences in patient characteristics or endoscopic procedures were observed between the two groups. The incidence of PEP was 4.2% (1/24) and 29.0% (9/31) in the Stent and no-stent groups, respectively, with the no-stent group having a significantly higher incidence (P = 0.031). The PEP severity was mild for all the patients in the stent group. In contrast, 8 had mild PEP and 1 had moderate PEP in the no-stent

group. The mean serum amylase levels (means +/- SD) 3 h after ERCP (183.1 +/- 136.7 vs 463.6 +/- 510.4 IU/L, P = 0.006) and on the day after selleck screening library ERCP (209.5 +/- 208.7 vs 684.4 +/- 759.3 IU/L, P = 0.002) were significantly higher in the no-stent group. A multivariate analysis identified the absence of pancreatic stenting (P = 0.045; odds ratio, 9.7; 95%CI: 1.1-90) as a significant risk factor for PEP. CONCLUSION: In patients with difficult cannulation in whom the bile duct is cannulated using P-GW, a pancreatic stent should be placed even if EST has been performed. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.”
“Sarcoidosis is

a multisystem granulomatous disorder characterized by marked T-cell Bafilomycin A1 expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naive sarcoidosis patients (n

= 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer selleck chemicals T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes.”
“In this report, we elaborate on a letter that Spallanzani wrote to Bonnet reporting his findings on regeneration in worms, snails, tadpoles, and salamanders. The letter (original in French and translated in English; see Supplementary Material, which is available online) was written to discuss whether or not regeneration in these animals supports Bonnet’s theory on germs.

1%) CONCLUSION: Cervical length and the estriol to estradiol

1%).\n\nCONCLUSION: Cervical length and the estriol to estradiol ratio represent good predictive indicators of the response to the induction of labor in postterm pregnancies.”
“Limbs ischaemia represents a rare event during the neonatal period. The present paper reports an unusual case of precocious arm ischemia that occurred immediately after birth and successfully treated with a peripheral nerve blockade.\n\nPeripheral nerve blockade resulted in an effective and safe therapeutic approach able to allow the salvaging of the limbs.”
“Background: Controversy continues about screening mammography, in part

because of the risk of false-negative and false-positive mammograms. Pre-test breast cancer risk factors may improve the positive and negative predictive value of screening.\n\nPurpose: To create a model that estimates the potential impact Quisinostat inhibitor of pre-test risk prediction using clinical and genomic information on the reclassification of women with abnormal mammograms (BI-RADS3 and BI-RADS4 [Breast Imaging-Reporting and Data System]) above and below the threshold for breast biopsy.\n\nMethods: The current study modeled 1-year breast cancer risk in women with abnormal screening mammograms using existing data on breast cancer risk factors, 12 validated breast cancer single-nucleotide

polymorphisms (SNPs), and probability of cancer given the BI-RADS category. Examination was made AG-881 of reclassification of women above and below biopsy thresholds of 1%, 2%, and 3% risk. The Breast Cancer Surveillance Consortium data were collected from 1996 to 2002. Data analysis

was conducted in 2010 and 2011.\n\nResults: Using a biopsy risk threshold of 2% and the standard risk factor model, selleckchem 5% of women with a BI-RADS3 mammogram had a risk above the threshold, and 3% of women with BI-RADS4A mammograms had a risk below the threshold. The addition of 12 SNPs in the model resulted in 8% of women with a BI-RADS3 mammogram above the threshold for biopsy and 7% of women with BI-RADS4A mammograms below the threshold.\n\nConclusions: The incorporation of pre-test breast cancer risk factors could change biopsy decisions for a small proportion of women with abnormal mammograms. The greatest impact comes from standard breast cancer risk factors. (Am J Prev Med 2013;44(1):15-22) (C) 2013 American Journal of Preventive Medicine”
“Introduction: The inability to experience pleasure, anhedonia, is recognized as al hallmark symptom of depression. A 14-item, self-report scale developed for the assessment of hedonic capacity: the Snaith-Hamilton Pleasure Scale (SHAPS) has proved to be a reliable and valid psychometric instrument.\n\nObjective: Because there are no versions of the scale in other languages, our objective in this study was to translate the instrument into spanish and to determine if the new version maintained the validity and reliability of its original english version.

Conclusion: Ce6-PDT induced ROS production to activate p38MAPK pr

Conclusion: Ce6-PDT induced ROS production to activate p38MAPK probably to prevent SW620 cells from photodamage. Inhibition of p38MAPK activation accelerated cell apoptosis, meanwhile enhanced autophagy Nepicastat manufacturer may act as a cytoprotective process in SW620 cells. (C) 2014 Elsevier B.V. All rights reserved.”
“Nanosized bicalutamide particles have been obtained by anti-solvent precipitation after screened DMSO and EtOH as co-solvents. The produced nanoparticles have been characterized by scanning electron microscopy (SEM), Fourier transform

infrared spectrophotometry (FTIR), X-ray diffraction (XRD) and a dissolution test. The mean particle size of bicalutamide is about 450 nm with a narrow distribution. The results of the dissolution test show that dissolution rate of the produced nanoparticles are higher than that of the raw material. Besides, DFT calculations of the bicalutamide conformers have firstly been presented. It is found that the calculated geometry structure of lower-energy conformer is very similar to the experimental structure existing within the crystal lattice. The solvent effects have been taken into account based on the polarizable continuum model (PCM). The computed results appear that the introduction

of dielectric medium has obvious effect on the molecular geometry of bicalutamide. (C) 2008 Elsevier B.V. All rights reserved.”
“6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[ 1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine

derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). SNS-032 in vitro Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function selleck chemicals llc through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02-10 mu M) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPK alpha expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G(0)/G(1) phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation.

Continuous SiC reinforced aluminum composites (3D-SiC/Al) have hi

Continuous SiC reinforced aluminum composites (3D-SiC/Al) have higher thermal conductivities and lower coefficients of thermal expansion (CETs) www.selleckchem.com/products/lcl161.html than those of particulate SiC reinforced aluminum composites (SiCp /Al) with the same SiC volume fraction. The co-continuous structures of both the SiC reinforcement and the Al matrix in 3D-SiC/Al can be the reason behind

this phenomena. As a result, when SiC volume fraction values were the same, 3D-SiC/Al composites will be more suitable for electronic packaging applications comparing with SiCp/Al composite. (c) 2013 Elsevier Ltd. and Techna Group S.r.l. All rights reserved.”
“Background: Uncorrected refractive errors are the main cause of vision impairment in school-aged children. The current study focuses on the effectiveness of school eye screening in correcting

refractive errors. Objectives: 1. To study the magnitude of visual impairment among school children. 2. To assess the compliance of students for refraction testing, procurement and use of spectacles. Materials and Methods: An intervention study was conducted in schools of the north-west district of Delhi, in the rural field practice area of a medical college. Students studying in five government schools in the field practice area were chosen as the study subjects. Results: Out of 1123 students enrolled, 1075 (95.7%) students were screened for refractive errors. Low vision (visual acuity <20/60) in MG-132 solubility dmso the better eye was observed in 31 (2.9%) children INCB28060 inhibitor and blindness (visual acuity <20/200) in 10 (0.9%) children. Compliance with referral for refraction was very low as only 51 (41.5%) out of 123 students could be tested for refraction. Out of 48 students, 34 (70.8%) procured spectacles from family resources but its regular

use was found among only 10 (29.4%) students. The poor compliance among students stems out of various myths and perceptions regarding use of spectacles prevalent in the community. Conclusion: Refractive error is an important cause of avoidable blindness among rural school children. Behavior change communication among rural masses by spreading awareness about eye health and conducting operational research at school and community level to involve parent’s teachers associations and senior students to motivate students for use of spectacles may improve utilization of existing eye health services in rural areas.”
“Previously, we found a significant association between photosystem II efficiency (I broken vertical bar PSII) and photochemical reflectance index (PRI) measured at predawn among different species at different elevations and throughout several seasons. However, this relationship has not been evaluated under varied levels of illumination. Here, we used the Taiwan species Pinus taiwanensis (a conifer distributed at 750-3,000 m a.s.l.), Stranvaesia niitakayamensis (an evergreen tree, 1,700-3,100 m) and two Miscanthus spp.


“Hess BJ Three-dimensional visuo-motor

control of


“Hess BJ. Three-dimensional visuo-motor

control of saccades. J Neurophysiol 109: 183-192, 2013. First published October 10, 2012; doi:10.1152/jn.00513.2012.-Although the motion of the line of sight is a straightforward consequence of a particular rotation of the eye, it is much trickier to predict the rotation underlying a particular motion of the line of sight in accordance with Listing’s law. Helmholtz’s notion of the direction-circle together with the notion of primary and secondary DMH1 solubility dmso reference directions in visual space provide an elegant solution to this reverse engineering problem, which the brain is faced with whenever generating a saccade. To test whether these notions indeed apply for saccades, we analyzed three-dimensional eye movements recorded in four rhesus monkeys. We found that on average saccade trajectories closely matched with the associated direction-circles. Torsional, vertical, and horizontal eye position of saccades scattered around the position predicted by the associated direction-circles 3 Methyladenine with standard deviations of 0.5 degrees, 0.3 degrees,

and 0.4 degrees, respectively. Comparison of saccade trajectories with the likewise predicted fixed-axis rotations yielded mean coefficients of determinations (+/- SD) of 0.72 (+/- 0.26) for torsion, 0.97 (+/- 0.10) for vertical, and 0.96 (+/- 0.11) for horizontal eye position. Reverse engineering of three-dimensional saccadic rotations based on visual information suggests that motor control of saccades,

compatible with Listing’s law, not only uses information on the fixation directions at saccade onset and offset but also relies on the Momelotinib solubility dmso computation of secondary reference positions that vary from saccade to saccade.”
“Non-alcoholic fatty liver disease (NAFLD) is frequently associated with insulin resistance, suggesting its crucial role in the development and progression of NAFLD. We used a mouse model of high-fat, high-fructose (HFHFr) diet-induced NAFLD to examine the effects of retinoids on insulin resistance. Dietary administration of all-trans-retinoic acid (ATRA) significantly improved insulin sensitivity in C57BL/6J mice fed the HFHFr diet, and in KK-A(y) mice but not in the leptin-deficient ob/ob mice. ATRA treatment significantly upregulated hepatic leptin receptor (LEPR) expression. In agreement with these observations, in vitro experiments showed ATRA directly induced LEPR gene expression through RAR alpha. In the livers of C57BL/6J mice administered ATRA, insulin receptor substrate-1 (IRS1) was activated concomitantly with the phosphorylation of Janus kinase-2 and signal transducer and activator of transcription-3 (STAT3). STAT3 phosphorylation was also observed in KK-A(y) but not in ob/ob mice. In in vitro experiments, ATRA significantly enhanced insulin-induced IRS1 tyrosine phosphorylation solely in the presence of leptin.