Abstract：
:Graft-versus host disease (GVHD) remains the most significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dissociation of graft versus-leukemia (GVL) activity from GVHD has yet to be achieved. In this study, we used γ-secretase inhibitor (GSIs, DAPT) to inhibit Notch signaling in GVHD and GVL murine model. We found that CD11c+CD80+ dendritic cells (DCs) were up-regulated but did not enhance GVHD. Regulatory T cells (Tregs) and central memory T cells that express high levels of CD62L and CD44 had an expansion after Notch inhibition. Reduced Tumor Necrosis Factor-α and increased Interferon-γ production were found, which might be ascribed to the expansion of Tregs and central memory T cells, and result in increased sensitivity of tumor cells to cytotoxic T lymphocyte activity. Fas Receptor-Fas Ligand interaction plays a critical role in GVL instead of aGVHD. Fas Ligand expressions were similar in recipients with or without Notch inhibition, suggesting that GVL activity was maintained. We showed that Notch inhibition could enhances GVL while reducing GVHD via modulating host DCs and donor T cell activity, and the production of inflammatory cytokines.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Luo X,Xu L,Liu L,Li Y,Tan Hdoi
10.1016/j.ejphar.2018.10.004subject
Has Abstractpub_date
2019-01-15 00:00:00pages
226-232eissn
0014-2999issn
1879-0712pii
S0014-2999(18)30581-8journal_volume
843pub_type
杂志文章abstract：:Circadian rhythms in mammals are generated by master pacemaker cells located within the suprachiasmatic nucleus of the hypothalamus. In hamsters, the suprachiasmatic nucleus contains a small collection of cells immunoreactive for substance P, the endogenous ligand of tachykinin neurokinin 1 (NK1) receptors. In additio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.10.012
更新日期：2005-12-19 00:00:00
abstract：:Characteristics of [3H]flunitrazepam ([3H]FLU) binding to cortical and cerebellar membrane receptors were examined following chronic (six days) administration of phenobarbital (PB) to C57B1 mice. Following PB treatment, the number of [3H]FLU binding sites (Bmax) was significantly reduced in both cerebral cortex and in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90497-7
更新日期：1984-08-17 00:00:00
abstract：:Diazepam (10(-5)-3 X 10(-4) M) selectively enhanced the negative inotropic responses of guinea-pig atria and the relaxation of guinea-pig taenia coli caused by adenosine and ATP. In the atria, the effect of 2-chloroadenosine, a stable analog of adenosine, was not affected by diazepam. Segments of guinea-pig atria or t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90346-2
更新日期：1985-07-11 00:00:00
abstract：:The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracellular microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo-oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate (ADP...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00848-6
更新日期：1999-01-08 00:00:00
abstract：:Several reports suggest that enteric cholinergic neurons are subject to a tonic inhibitory modulation, whereas few studies are available concerning the role of facilitatory pathways. Glutamate, the main excitatory neurotransmitter in the central nervous system (CNS), has recently been described as an excitatory neurot...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)02147-2
更新日期：2003-08-22 00:00:00
abstract：:Phasic release of calcium from the sarcoplasmic reticulum occurs in all mammalian cardiac preparations when the intracellular calcium concentration is sufficiently high. The phasic calcium release is often sufficient to trigger electrophysiological responses and aftercontractions. These can be detrimental to normal ca...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90551-7
更新日期：1989-11-07 00:00:00
abstract：:Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basolateral membrane aft...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.03.036
更新日期：2014-06-15 00:00:00
abstract：:In cystic fibrosis respiratory epithelial cells, the absence or dysfunction of the chloride channel CFTR (Cystic Fibrosis Transmembrane conductance Regulator) results in reduced chloride ion transport. In contrast, Ca2+-stimulated Cl- secretion is intact in cystic fibrosis airway epithelia. One possible target for dru...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.06.103
更新日期：2008-09-11 00:00:00
abstract：:Four analogues of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, a mammalian FMRFamide-like peptide with antiopiate properties, were synthesized with N-terminus modifications and were shown to have high affinity for F8Famide binding sites. The degradation rate of these analogues in mouse brain slices was 3 times lower than that...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90463-e
更新日期：1992-11-03 00:00:00
abstract：:To substantiate the notion that cocaine behavioral effects may be influenced by gamma-aminobutyric acid (GABA) neurotransmission male Wistar rats were injected with gabapentin (a cyclic GABA analogue), tiagabine (a GABA reuptake inhibitor), or vigabatrin (a GABA transaminase inhibitor) before acute or repeated treatme...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.05.011
更新日期：2006-07-17 00:00:00
abstract：:We investigated the effect of probucol, a lipid-lowering agent with antioxidant properties, on HCl plus ethanol-induced gastric mucosal injury and on the healing of acetic acid-induced gastric ulcers in rats. When the free radical-scavenging activity of probucol was measured by an electron spin resonance technique, th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00448-8
更新日期：1998-08-07 00:00:00
abstract：:In the mouse tail-flick test, neither the racemate of N-allylnormetazocine (NANM) nor its optical isomers showed antinociceptive activity. However, all three antagonized morphine's tail-flick effects. In the phenylquinone test in mice, the racemate and (-)-isomer of NANM showed agonist activity and antagonized morphin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90476-4
更新日期：1983-07-22 00:00:00
abstract：:The direct effects or right atrial pacing and nitroglycerin on myocardial oxygen balance were studied in isolated canine hearts. Whereas atrial pacing produced an increase in myocardial oxygen consumption (MVO2) and no change in the affinity of hemoglobin for oxygen (P-50), an intracoronary infusion of nitroglycerin d...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90244-7
更新日期：1975-11-01 00:00:00
abstract：:The coronavirus disease-19 (COVID-19) outbreak that is caused by a highly contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a zoonotic pandemic, with approximately 24.5 million positive cases and 8.3 lakhs deaths globally. The lack of effective drugs or vaccine provoked the research fo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173688
更新日期：2021-01-05 00:00:00
abstract：:The interaction of 5 alpha-pregnane-3 alpha-ol-20-one (5 alpha 3 alpha P), a progesterone metabolite, with the GABAA receptor chloride channel complex was investigated at the pituitary level. In nanomolar concentrations this steroid potentiated the inhibitory effect of muscimol (a GABAA agonist) on prolactin release f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90627-4
更新日期：1989-09-01 00:00:00
abstract：:Cyclosporin A is shown to attenuate antinociceptive effects of morphine, development and expression of morphine-induced tolerance and dependency via nitric oxide (NO) pathway. In the present study, the effect of systemic cyclosporin A on morphine-induced conditioned place preference (CPP) and the probable involvement ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.11.025
更新日期：2005-01-10 00:00:00
abstract：:Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaes...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00670-2
更新日期：1996-01-18 00:00:00
abstract：:The effect of nimodipine was studied on EEG power density spectra as well as on 31P-NMR spectra of the brain before, during and after four-vessel occlusion (FVO) in the restrained conscious rat. EEG-spectral analysis: eight rats were submitted to 5 min FVO and four of them received nimodipine (1 mg/kg orally) 75 min b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90799-5
更新日期：1986-06-24 00:00:00
abstract：:3H-angiotensin binding sites have been studied in a particulate fraction prepared from rat adrenal glands. This binding is rapid and reversible, of high affinity (KD29 degrees C = 3-5 X 10(-9) M) and with demonstrable specificity for the angiotensin II octapeptide. The number of binding sites varies with endogenous an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90042-5
更新日期：1977-06-15 00:00:00
abstract：:The prefrontal cortex and the mediodorsal thalamic nucleus are reciprocally connected through excitatory amino acid pathways. Cortical excitatory responses resulting from activation of either the mediodorsal thalamic nucleus-prefrontal cortex pathway (short latency) or the recurrent collaterals of prefrontal cortex-me...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00377-w
更新日期：1995-10-04 00:00:00
abstract：:In this study we demonstrate allograft survival in a rat model of renal transplantation using the delta1-opioid receptor antagonist, 7-(benzospiroindanyl)naltrexone [corrected]. Treatment with 7-(benzospiroindanyl)naltrexone [corrected] caused 50% of the rats to survive longer than 100 days (untreated, 11 +/- 3 days)....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00477-4
更新日期：1998-07-31 00:00:00
abstract：:Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01467-4
更新日期：2001-11-23 00:00:00
abstract：:Tamsulosin (10(-10)-10(-9) M) or prazosin (10(-9)-10(-8) M) concentration dependently blocked the tension responses to electrical field stimulation (0.3 ms duration, 80 V and 20 Hz) in human hyperplastic prostate with lC50 values of (1.93 +/- 0.26) x 10(-10) M and (2.11 +/- 0.21) x 10(-9) M, respectively. The relative...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00197-5
更新日期：1996-06-03 00:00:00
abstract：:The intrathecal injection of a variety of selective kappa-opioid receptor ligands did not result in significant inhibition of thermal nociceptive tail flick responses in rats. In contrast, these compounds dose dependently inhibited pressure nociceptive responses. Cross-tolerance studies revealed that the kappa-opioid ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90223-8
更新日期：1987-06-04 00:00:00
abstract：:Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with additional antioxidant properties. Doxorubicin (DOX) is an anticancer drug that exerts oxidation-mediated adverse cardiovascular effects. This study examined the effects of nicorandil on DOX-induced cytotoxicity in human umbilical vein end...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172542
更新日期：2019-09-15 00:00:00
abstract：:Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)00627-j
更新日期：1995-01-05 00:00:00
abstract：:The spontaneous firing rate of the noradrenergic neurons of the locus coeruleus and of the serotonergic neurons of the dorsal raphe was recorded with extracellular microelectrodes in chloral hydrate-anesthetized rats. A quantitative comparison of the effect of five tricyclic antidepressants, of tranylcypromine and of ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90368-6
更新日期：1979-08-01 00:00:00
abstract：:The concentration dependences of the Ca(2+)-sensitizing and the phosphodiesterase-inhibitory effects of levosimendan (the (-) enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile) and its active metabolite, OR-1896 (the (-) enantiomer of N-[4-(1,4,5,6-tetrahydro-4-methyl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.12.005
更新日期：2004-02-13 00:00:00
abstract：:The breakdown of the relaxation-inducing second messengers cAMP and cGMP is mediated by phosphodiesterases. Inhibitors of functionally present phosphodiesterases can be expected to induce relaxation by increasing the basic amount of cAMP and/or cGMP. In the cat gastric fundus, vinpocetine, which has some selectivity f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00009-a
更新日期：1995-03-24 00:00:00
abstract：:Preclinical data, performed in a limited number of pain models, suggest that functional blockade of metabotropic glutamate (mGlu) receptors may be beneficial for pain management. In the present study, effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective mGlu5 receptor antagonist, were examined in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.11.005
更新日期：2004-12-15 00:00:00
