The present study examines the long-term neuropeptidergic and neuroplastic adaptations associated with the expression

of locomotor sensitization to a low dose nicotine challenge and social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Our data show that the expression of behavioral sensitization to nicotine and abstinence-related anxiety are detected in nicotine pre-exposed HRs even across a long (3 wks) abstinence. Moreover, these behavioral effects of nicotine are accompanied by a persistent imbalance between neuropeptide Y and corticotrophin releasing factor systems, and a persistent increase in brain-derived neurotrophic factor (BDNF) and spinophilin EPZ-6438 datasheet mRNA levels in the amygdala. Furthermore, treatment with the cannabinoid receptor 1 antagonist, AM251 (5 mg/kg) during a short (1 wk) abstinence is ineffective in reversing nicotine-induced anxiety, fluctuations in BDNF and spinophilin mRNAs, and the neuropeptidergic dysregulations in the amygdala; although this treatment is effective

in reversing the expression of locomotor sensitization to challenge nicotine even after a long abstinence. Interestingly, the identical AM251 treatment administered during the late phase of a long abstinence further augments anxiety and associated changes in BDNF and spinophilin AMN-107 manufacturer mRNA in the basolateral nucleus of the amygdala in nicotine pre-exposed HRs. These findings implicate long-lasting neuropeptidergic and neuroplastic changes in the amygdala in vulnerability to the behavioral effects of nicotine in the novelty-seeking phenotype. Published by Elsevier Ltd.”
“Evolutionary psychologists GDC-0449 mouse explore the adaptive function of traits and behaviors that characterize modern Homo sapiens. However, evolutionary psychologists have yet to incorporate the phylogenetic relationship between modern Homo sapiens and humans’ hominid and pongid relatives (both living and extinct) into their theorizing. By considering the specific

timing of evolutionary events and the role of evolutionary constraint, researchers using the phylogenetic approach can generate new predictions regarding mating phenomena and derive new explanations for existing evolutionary psychological findings. Especially useful is the concept of the adaptive workaround-an adaptation that manages the maladaptive elements of a pre-existing evolutionary constraint. The current review organizes 7 features of human mating into their phylogenetic context and presents evidence that 2 adaptive workarounds played a critical role as Homo sapiens’s mating psychology evolved. These adaptive workarounds function in part to mute or refocus the effects of older, previously evolved adaptations and highlight the layered nature of humans’ mating psychology.

Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.

Methods: Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance

use disorder Selleckchem WH-4-023 (cannabis>alcohol>cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On

baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n = 24) was 466.6 mg +/- 227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison https://www.selleckchem.com/products/lonafarnib-sch66336.html purposes.

Results: On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, https://www.selleck.cn/products/ldk378.html compared

to controls. Plasma sIL-2R further increased after quetiapine treatment (p = 0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p<0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r = -0.524; p = 0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.

Conclusion: These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related. (C) 2011 Elsevier Inc. All rights reserved.”
“We investigated whether a young human leukocyte antigen (HLA)-matched unrelated donor (MUD) should be preferred as donor to an HLA-identical sibling (MRD) for older patients with myelodysplastic syndrome (MDS) (>= 50 years) who underwent allogeneic stem cell transplantation (AHSCT).

Pravastatin at a dose of 10 mg/kg/day was administrated directly into the duodenum via cannula from 2 days after induction of PDH. Progression of pancreatic fibrosis and expression levels of transforming growth factor-beta 1 and tumor necrosis factor-alpha mRNA were markedly attenuated after commencement CB-5083 of pravastatin compared with untreated group with PDH. In addition, pravastatin treatment markedly improved pancreatic exocrine function and significantly elevated expression level of interleukin (IL)-10 and superoxide dismutase activity in the pancreas compared with the untreated group with PDH. These results revealed that pravastatin substantially attenuates the progression of pancreatic inflammation,

fibrosis and exocrine dysfunction probably by its anti-oxidative property and overproduction of IL-10 in animal model of chronic pancreatitis. These results provide an experimental evidence that pravastatin exerts beneficial effect for progression of chronic pancreatitis. Laboratory Investigation (2011) 91, 872-884; doi:10.1038/labinvest.2011.41; published online 7 March 2011″
“Whole-body imaging with fluorescent proteins is a powerful technology with many applications in small animals. Brighter, red-shifted proteins can make whole-body imaging more sensitive owing to reduced absorption by tissues and less scatter. A new protein called Katushka has been isolated.

It is the brightest known protein learn more with emission at wavelengths longer than 620 nm. This new protein offers the potential for non-invasive whole-body imaging of numerous cellular and molecular processes VX-770 in live animals.”
“The current study investigated the effects of paradoxical sleep deprivation and intermittent hypoxia by examining whether a combination of the two would induce anxiety-like alterations in behavior. The neurochemical effects of these manipulations were investigated by measuring cortical, striatal and hippocampal monoamine concentrations. Wistar Hannover rats were submitted to subchronic (3 days) intermittent hypoxia exposure (alternating cycles of 2 min room air-2

min 10% O(2) from 0700-1900 h) and paradoxical sleep deprivation using the single platform method. Rats were randomly assigned to four different protocols: 1) control, 2) intermittent hypoxia during the light period (12 h/day), 3) paradoxical sleep deprivation (24 h/day), and 4) intermittent hypoxia combined with paradoxical sleep deprivation. Rats subjected to intermittent hypoxia showed no modification in the behavioral or neurochemical parameters assessed. Although paradoxical sleep deprivation did not produce alterations in anxiety-like behavior, the rats did increase exploratory activity in the elevated plus-maze. Moreover, a significant increase in striatal epinephrine and hippocampal homovanilic acid (HVA) concentrations was found in the paradoxical sleep deprivation groups, but not in the intermittent hypoxia/paradoxical sleep deprivation group.

No overt judgments were made by participants. In control children the N400 amplitude to both semantically and phonologically incongruent words was enlarged relative to congruent words. Dyslexic children exhibited a dissociation of priming effects depending on whether semantic or phonological primes were used. Semantic

priming elicited an N400 effect comparable to controls, though delayed. In phonological priming, the dyslexics differed from controls in both the phonologically incongruent and congruent conditions showing reduced N400 amplitude in the former and enhanced N400 in the latter. This pattern suggests that when faced with phonological priming, dyslexics show abnormal neural responses related to both integration of similarities between the consecutive stimuli and the ability to detect incongruent stimuli. Semantic priming seems relatively intact in dyslexics, MK-1775 concentration however neural responses to contextual incongruency are delayed. (C) 2010 Elsevier Ltd. All rights reserved.”
“Glioblastoma is the most frequent and malignant brain tumour. For many years, the conventional treatment has been maximal surgical resection followed by radiotherapy

(RT), with a median survival time of less than 10 months. Previously, the use of adjuvant chemotherapy (given after RT) has failed to demonstrate a statistically significant survival advantage. Recently, a randomized phase III trial has confirmed the benefit of temozolomide (TMZ) and has defined a new standard of care for the treatment of patients with high-grade brain tumours. The results showed click here an increase of 2.5 months in median survival, and 16.1% in 2 year survival, for patients receiving RT with TMZ compared with RT alone. It is not clear whether the major benefit of TMZ comes from either concomitant administration of TMZ with RT, or from six cycles of adjuvant TMZ, or both.

The objectives were to develop our original model, which addressed survival after RT, to construct SPTLC1 a new module to assess the potential

role of TMZ from clinical data, and to explore its synergistic contribution in addition to radiation. The model has been extended to include radiobiological parameters. The addition of the linear quadratic equation to describe cellular response to treatment has enabled us to quantify the effects of radiation and TMZ in radiobiological terms.

The results indicate that the model achieves an excellent fit to the clinical data, with the assumption that TMZ given concomitantly with RT synergistically increases radiosensitivity. The alternative, that the effect of TMZ is due only to direct cell killing, does not fit the clinical data so well. The addition of concomitant TMZ appears to change the radiobiological parameters. This aspect of our results suggests possible treatment developments.

Our observations need further evaluations in real clinical trials, may suggest treatment strategies for new trials, and inform their design. (C) 2009 Elsevier Ltd. All rights reserved.

Using a primary neuronal cell culture system, HCF-1 was localized to the Golgi apparatus in unstimulated neurons, a unique location for a transcriptional coactivator. Upon disruption of the Golgi body, HCF-1 was rapidly relocalized to the nucleus in contrast to other Golgi apparatus-associated proteins. The location of HCF-1 is distinct from that of CREB3, an endoplasmic reticulum-resident HCF-1 interaction partner that has been proposed to sequester HCF-1. The results support the model

that HCF-1 is an important component of the viral latency-reactivation cycle and that it is regulated by association with a component that is distinct from the identified LY2109761 clinical trial HCF-1 interaction factors.”
“Emerging studies suggest an important role for the innate immune response in replication-defective adenovirus (Ad)-mediated acute liver toxicity. Specifically, classical innate immune cells (including NK cells, neutrophils, and Kupffer cells) have all been implicated in the GSK1904529A supplier development of Ad-mediated acute liver toxicity. The nonclassical innate immune T cell, the gamma delta T cell, has been implicated in the pathophysiology of several viral infections that predominantly affect the mucosa and brain, but the specific role in the pathology of AdLacZ-mediated

acute liver inflammation and injury as well as accompanying vector clearance is largely unknown. In the present study, we demonstrated that a CXCL9-CXCR3-dependent mechanism governed the accumulation of gamma delta T cells in the livers of mice infected with Ad expressing the Escherichia coli LacZ gene (AdLacZ). We also showed a critical role for gamma delta T cells in initiating acute liver toxicity after AdLacZ administration, driven in part by the ability of gamma delta T cells to promote the recruitment MAPK inhibitor of the conventional

T cell, the CD8(+) T cell, into the liver. Furthermore, reduced hepatic injury in AdLacZ-infected gamma delta T-cell-deficient mice was associated with lower hepatic levels of gamma interferon (IFN-gamma) and CXCL9, an IFN-gamma-inducible chemokine. Finally, our study highlighted a key role for IFN-gamma and CXCL9 cross talk acting in a feedback loop to drive the proinflammatory effects of gamma delta T cells during AdLacZ-mediated acute liver toxicity. Specifically, intracellular IFN-gamma produced by activated hepatic gamma delta T cells interacts with hepatocytes to mediate hepatic CXCL9 production, with the consequent accumulation of CXCR3-bearing gamma delta T cells in the liver to cause acute liver damage without vector clearance.”
“The RNA-dependent RNA polymerase (RdRp) is a central piece in the replication machinery of RNA viruses. In picornaviruses this essential RdRp activity also uridylates the VPg peptide, which then serves as a primer for RNA synthesis.

0001). At up to 7.7 years of followup 1.1% of 35,737 vs 2.5% of 3,268 men with impregnated vs nonimpregnated implants underwent initial revision due to infection.

Conclusions:

To our knowledge this long-term outcome analysis provides the first substantial URMC-099 mouse clinical evidence of a decrease in costly infection related revision using an antibiotic impregnated inflatable penile prosthesis.”
“Purpose: Co-administration of the 5 alpha-reductase inhibitor dutasteride increases the oral testosterone bioavailability in men with experimentally induced hypogonadism. We examined oral testosterone with and without dutasteride administration in hypogonadal men for 28 days.

Materials and Methods: We randomly assigned 43 hypogonadal men to twice daily oral doses of 150, 250 or 400 mg testosterone with 0.25 mg dutasteride, 400 mg testosterone alone or 0.25 mg dutasteride alone for 28 days in a multicenter study. Subjects underwent pharmacokinetic profiling of serum hormones on days 1 and 28. A total of 32 men completed all study procedures.

Results: Serum testosterone increased in all groups on testosterone compared with that in the dutasteride only group. At the 400 mg dose the combination of

selleckchem testosterone and dutasteride resulted in average testosterone concentrations that were 2.7 and 4.6 times higher than in the testosterone only group on days 1 and 28, respectively (p < 0.01). On day 28 average testosterone was 20% to 30% lower in all groups on testosterone and dutasteride, and 50% lower in the testosterone only group compared with day 1. Serum dihydrotestosterone was suppressed in all groups on dutasteride and increased in the testosterone only group.

Conclusions: Oral testosterone administration resulted in a therapeutic serum testosterone concentration in hypogonadal men. Dutasteride improved the oral bioavailability of testosterone while suppressing dihydrotestosterone. Compared with day 1, testosterone was decreased after 28 days of administration. Additional study is warranted of oral testosterone with dutasteride

for testosterone deficiency.”
“Reactive oxygen species (ROS) are potent regulators of transmitter release in chemical synapses, but the mechanism of this action remains almost unknown. Presynaptic modulation can change either the release probability Selleckchem VX770 or the time course of quantal release, which was recently recognized as an efficient mechanism determining synaptic efficiency. The nonuniform structure and a big size of the frog neuromuscular junction make it a useful model to study the action of ROS in compartments different in release probability and in time course of transmitter release. The time course (or kinetics) of quantal release could be estimated by measuring the dispersion of the synaptic delays for evoked uniquantal endplate currents (EPCs) under low release probability.

92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85.

Interpretation The body of evidence, although PRT062607 purchase limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies.”
“During liver regeneration in vivo carbon monoxide (CO) and nitric oxide (NO) are supposed to play a significant role. We raise the question whether CO

and NO are involved in the growth process of cultured hepatocytes. Rat hepatocytes were stimulated into proliferation, growth being estimated by DNA content, mRNA by quantitative RT-PCR, and inducible NO synthase (iNOS) LY294002 nmr activity by GC-MS. Dexamethasone proved obligatory for fast proliferation. It suppressed the spontaneous rise of iNOS-mRNA in cultures devoid of glucocorticoids, but did not counteract the rise in mRNA in actively dividing cultures. Expression of iNOS-mRNA and cell growth were further enhanced by LiCl (10 mM). NOS activity was completely suppressed by the iNOS-specific inhibitors N-(3-(aminomethyl)benzyl) acetamidine (1400 W,100 mu M) and L-N(6)-(1-iminoethyl)lysine (L-NIL,

500 mu M), however, without a decrease in hepatocyte growth. Proliferation was attenuated only by very high concentrations this website (>0.5 mM) of N-nitro-L-arginine methyl ester NAME) and asymmetric dimethylarginine (ADMA). Various NO donors (at 100 mu M) did not stimulate cell growth. The furoxan CAS 1609 stimulated growth, decreased iNOS-mRNA expression and transiently increased haem oxygenase-1 (HO-1)-mRNA without releasing considerable amounts of NO. 1H-[1,2,4]Oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) attenuated the action

of CAS 1609. Proliferation was stimulated by Co-protoporphyrin and tricarbonyldichlororuthenium(II) dimer (CORM-2). We conclude that CAS 1609 triggers hepatocyte mitosis most likely via direct, NO-independent induction of HO-1 expression, pointing to CO as a growth-promoting signal in the proliferation cascade in cultured hepatocytes. (C) 2010 Elsevier Inc. All rights reserved.”
“Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder.

Peripheral blood mononuclear cells were isolated and antigen specific interferon-gamma secretion of isolated

T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase.

Results: In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared Epacadostat clinical trial with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase.

Conclusions: Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses selleck against prostate specific antigens strongly increased

after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells.”
“Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy (H-1 MRS), we aimed to determine if

abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART.

Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent H-1 MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed.

Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per Alpelisib microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014).

In telomerase-immortalized human umbilical vein endothelial cells, LANA-1 was demonstrated to repress interleukin-8 expression, which was involved in neutrophil recruitment to the inflammatory site. Through an in vitro transmigration assay, we determined a suppressive

effect of LANA-1 on neutrophil chemotaxis. Our work suggests that KSHV LANA-1 is a negative modulator of acute inflammation and sheds light on a new mechanism by which KSHV during the latent life cycle evades the host innate immune response.”
“Rationale Hippocampal interneurons release gamma-aminobutyric acid (GABA) Epigenetics inhibitor and produce fast GABA(A)- and slow GABA(B)-inhibitory postsynaptic potentials (IPSPs). The regulation of GABA(B) eIPSPs or the interneurons that produce them are not well understood.

In addition, while both mu-opioid receptors (mu ORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.

Objectives This study tests the TGF-beta inhibitor hypotheses that: (1) all interneurons can initiate both GABA(A) and GABA(B) inhibitory postsynaptic potentials; (2) GABA(B) responses are insensitive to mGluR-triggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABA(B) responses are produced by interneurons that express mu OR; and (4) CB1R-dependent and mu OR-dependent response interact.

Materials and methods Pharmacological and electrophysiological approaches were used in acute

rat hippocampal slices. High resistance microelectrode recordings were made from pyramidal cells, while interneurons were stimulated extracellularly.

Results GABA(B) responses were found to be produced by interneurons that release GABA via either presynaptic N-type or P/Q-type calcium channels but that they AMN-107 supplier are insensitive to suppression by eCBs or eCB-mediated iLTD. GABA(B) IPSPs were sensitive to suppression by a mu OR agonist, suggesting a major source of GABA(B) responses is the mu OR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a mu OR agonist in 6/13 slices.

Conclusions GABA(B) responses cannot be produced by all interneurons. CB1R or mu OR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R- and mu OR-mediated responses can interact.”
“According to a common conception in behavioral decision research, two cognitive processes-overestimation and overweighting-operate to increase the impact of rare events on people’s choices. Supportive findings stem primarily from investigations in which people learn about options via descriptions thereof. Recently, a number of researchers have begun to investigate risky choice in settings in which people learn about options by experiential sampling over time.

We review recent evidence from lesion, pharmacological

and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited Selleck ARS-1620 by the movement of salient locations between events. (C) 2012 Elsevier Ltd. All rights reserved.”
“Disulfides are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active Cys Pairs by scanning

the Protein Data Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational Quisinostat manufacturer differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association DNA ligase with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity.”
“Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear

factor-kappa B activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated pathway, in part, by decreasing levels of the antiapoptotic proteins XIAP and Mcl-1. MRx102 is a triptolide derivative, currently in preclinical development. Here we show that MRx102 potently promoted apoptosis in AML cell lines, with EC50 values of 14.5+/-0.6 nM and 37.0+/-0.9 nM at 48 h for OCI-AML3 and MV4-11 cells, respectively. MRx102, at low nanomolar concentrations, also induced apoptosis in bulk, CD34(+) progenitor, and more importantly, CD34(+)CD38(-) stem/progenitor cells from AML patients, even when they were protected by coculture with bone marrow derived mesenchymal stromal cells. MRx102 decreased XIAP and Mcl-1 protein levels and inhibited RNA synthesis in OCI-AML3 cells.