The χ_{b}(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider at sqrt[s]=7  TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4  fb^{-1}, these states are reconstructed through their radiative decays to Υ(1S,2S) with Υ→μ^{+}μ^{-}. In addition to the mass peaks corresponding to the decay modes χ_{b}(1P,2P)→Υ(1S)γ, a new structure centered at a mass of 10.530±0.005(stat)±0.009(syst)  GeV is also observed, in both the Υ(1S)γ and Υ(2S)γ decay modes. This structure is interpreted as the χ_{b}(3P) system.

ObjectiveEosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) can have similar clinical and histological features. Proton pump inhibitors (PPIs) are used to distinguish the disorders, with the assumption that only GORD can respond to PPIs. Oesophageal expression of eotaxin-3 stimulated by Th2 cytokines might contribute to oesophageal eosinophilia in EoE. Th2 cytokine effects on the oesophagus in GORD are not known. The objective of the authors was to explore the molecular mechanisms of Th2 cytokines on eotaxin-3 expression by oesophageal squamous cells from patients with GORD and EoE, and the effects of omeprazole on that eotaxin-3 expression.DesignUsing telomerase-immortalised and primary cultures of oesophageal squamous cells from GORD and EoE patients, the authors measured eotaxin-3 protein secretion stimulated by Th2 cytokines (interleukin (IL)-4 and IL-13). Eotaxin-3 promoter constructs were used to study transcriptional regulation. Cytokine-induced eotaxin-3 mRNA and protein expression were measured in the presence or absence of omeprazole.ResultsThere were no significant differences between EoE and GORD primary cells in cytokine-stimulated eotaxin-3 protein secretion levels. In EoE and GORD cell lines, IL-4 and IL-13 activated the eotaxin-3 promoter, and significantly increased eotaxin-3 mRNA and protein expression. Omeprazole blocked the cytokine-stimulated increase in eotaxin-3 mRNA and protein expression in EoE and GORD cell lines.ConclusionOesophageal squamous cells from GORD and EoE patients express similar levels of eotaxin-3 when stimulated by Th2 cytokines, and omeprazole blocks that eotaxin-3 expression. These findings suggest that PPIs might have eosinophil-reducing effects independent of effects on acid reflux and that response to PPIs might not distinguish EoE from GORD.

ABSTRACT: Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-ODN 1826, in cardiac functional recovery after T-H. Trauma-hemorrhage was induced in a murine model by soft tissue injury and blood withdrawals from the jugular vein to a mean arterial pressure of 35±5 mm Hg. Mice were treated with CpG-ODN 1826 (10 μg/30g body weight) by intra-peritoneal injection one hour prior to T-H (N=5-8/group). Hemodynamic parameters were measured before, during hemorrhage, and at 60 min after T-H. Trauma-hemorrhage significantly decreased the mean arterial pressure and left ventricular pressure compared with sham controls. In contrast, CpG-ODN administration significantly attenuated the decrease in arterial pressure and left ventricular pressure due to T-H. Trauma-hemorrhage markedly decreased myocardial levels of phosphorylated Akt by 57.9%. However, CpG-ODN treatment significantly blunted the decrement in phospho-Akt by activating the PI3K/Akt signaling pathway. The PI3K inhibitor LY294002 partially abolished CpG-induced cardioprotection, indicating that additional signaling pathways are involved in the protective effect of CpG-ODNafter T-H. We observed that CpG-ODN treatment also significantly attenuated the decrease in myocardial phospho-ERK levels after T-H. Inhibition of ERK by U0126 also partially abolished the cardioprotective effect of CpG-ODN after T-H. Our data suggests that CpG-ODN significantly attenuates T-H-induced cardiac dysfunction. The mechanisms involve activation of both PI3K/Akt and ERK signaling pathways. The TLR9 agonist, CpG-ODN 1826, may provide a novel treatment strategy for preventing or managing cardiac dysfunction and enhancing recovery in T-H patients.

Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study - 67.5%(27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0%(20/40) had low estimated glomerular filtration rate (eGFR)(<60 mL/min/1.73m(2)). We compared the efficacy and adverse effects of TAC (0.04-0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m(2) per month)/prednisone for six months followed by azathioprine (Aza)(100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6-8 ng/mL or 4-6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy (P < 0.001), compared with the CYC group (4.9 ± 19.4 g/day), P = 0.001, and 65.0%(13/20) achieved partial remission at one month, compared with the CYC group (0/20), P < 0.001. The incidence of complete remission (CR) was significantly higher in the TAC group than in the CYC group (55.0% vs.15.0% by five months, P = 0.008, and 75.0% vs.40.0% by 12 months, P = 0.025, respectively). The significant improvement in serum anti-dsDNA and systemic lupus erythematosus (SLE) disease activity index (DAI) was in the TAC group relative to the CYC group at 12 months (P = 0.031, P = 0.003, respectively). The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m(2) at baseline to 93.75 ± 28.52 mL/min/1.73m(2) after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.

Atomistic simulation has been performed to systematically investigate the Mn-site doping of h-YMnO(3)(hexagonal yttrium manganese oxide). It is found that tetravalent dopants are the most energetically favorable for incorporation into a crystal lattice. For divalent dopants, hole compensation is the more likely charge compensation mechanism, whereas for dopants with mixed valence, the divalent state is the energetically preferred form. Structural and local polarization changes caused by Mn-site doping are also investigated. The tilting angle of the MnO(5) trigonal bipyramid is suppressed for all of the dopants investigated, with the reduction dependent on the dopant ion radius, while the influence on buckling is closely related to the valence of the dopants. Our results reveal that both electrostatic and size effects play important roles in the ferroelectric polarization of h-YMnO(3).

Increased vascular resistance in the fetoplacental circulation is a characteristic of preeclampsia. However, the potential molecular mechanisms of this condition remain obscure. The current study aimed to determine the direct effect of the peptide antigen corresponding to the second extracellular loop of the angiotensin II type 1 receptor (AT1R-EC(II)) activating autoantibody (AT1-AA), a novel risk factor in preeclamptic patients, on fetoplacental villus stem blood vessels. Immunohistochemistry revealed that AT1 receptors were localized in the veins and arteries of human placental villi. Among 58 serum samples from preeclamptic patients, 28 (48.28%) were proved AT1-AA-positive by enzyme linked immunosorbent assay [P < 0.01 vs. 2/51 (3.92%) in the normal pregnancy group]. Total IgGs purified from AT1-AA-positive patients' sera (AT1-AA-IgGs) were added to isolated normal human placental blood vessels. The IgG significantly constricted both the villus veins and arteries in a dose-dependent manner in vitro, which could be blocked by the peptide corresponding to the human AT1R-EC(II), anti-human IgG or the AT1 receptor antagonist losartan. Additionally, the venous constriction induced by AT1-AA-IgGs remained unchanged even at the end of the experiment (about half an hour), but the vasoconstriction caused by the AT1 receptor agonist angiotensin II underwent desensitization within three minutes. Collectively, our results demonstrated that AT1-AA in preeclamptic sera can directly constrict fetoplacental villus blood vessels without desensitization via the AT1 receptor in vitro, which might contribute to poor fetoplacental perfusion in preeclampsia. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.

We have previously reported that human umbilical cord blood-derived stromal cells (hUCBDSCs) are able to enhance the expansion of CFU-Meg in vitro, particularly promote the megakaryocytic lineage recovery, and effectively protect the survival of irradiated mice. In this study, we demonstrated that hUCBDSCs secreted SDF-1 to stimulate PECAM-1 expression in HEL cells (MK cell line), and consequently promoted the proliferation and migration of HEL cells. On the other hand, SDF-1 knock down in hUCBDSCs or PECAM-1 knock down in HEL cells diminished or abrogated the above effect. In addition, SDF-1/PECAM-1 probably activated PI3K/Akt and MAPK/ERK1/2 pathways. This report for the first time defines a SDF-1/PECAM-1 signaling pathway in the proliferation and migration of MKs, which provides supportive evidence for the clinical applications of hUCBDSCs in the treatment of megakaryocytic injury.

OBJECTIVE: To investigate the function and mechanism of CYR61 on the migration and invasion of the trophoblast cell line, HTR-8/SVneo cells. STUDY DESIGN: The mRNA and protein levels of NUR77 in the placentas of normal and preeclampsia (PE) women were evaluated using real-time PCR and Western blot, respectively. Paraffin-embedded tissues were processed for localization of NUR77 protein in placental villus by immunohistochemistry. HTR-8/SVneo cells were cultured in the presence of CYR61, Ad-NUR77 or a small interfering RNA for NUR77 (Ad-sinur77). The expression of NUR77 in the HTR-8/SVneo cells was detected and the effects of CYR61 on the migration and invasion of HTR-8/SVneo cells were assessed in wound-healing and transwell experiments, respectively. Gelatin zymography was used to measure the MMP2 release in HTR-8/SVneo cells. RESULTS: NUR77 is significantly decreased in the placenta of women with PE compared with the levels during a normal pregnancy. CYR61 can significantly increase the expression of NUR77 in HTR-8/SVneo cells. CYR61, as well as NUR77, can promote HTR-8/SVneo cells migration and invasion, which can be blocked by Ad-sinur77. Both CYR61 and Ad-nur77 reduced the mRNA expression of TIMP2 in HTR-8/SVneo cells. CONCLUSIONS: CYR61 may promote HTR-8/SVneo cells migration and invasion through the upregulation of NUR77, leading to the increase of MMP2 release and the downregulation of TIMP2 expression.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) of the α/β type is a rare subtype of non-Hodgkin's lymphoma of the skin. Although these tumors usually run an indolent course, disease-related morbidity is often severe. Clinical findings include subcutaneous tumors located on the extremities or trunk, often accompanied by systemic symptoms like fever or fatigue. Due to the low incidence of SPTL, no standardized therapy has been defined so far and there is currently no curative therapy available for this type of non-Hodgkin's lymphoma. By sharing our experience with bexarotene therapy, we present a safe and potentially improved treatment for patients with SPTL. In the case presented, bexarotene was able to induce remission even after recurrence of disease.

Alteration of human leukocyte antigen (HLA) expression, such as decreased HLA I (HLA-A,-B,-C) antigens and elevated non-classical HLA I antigens (HLA-E,-F,-G), was reported to have an unfavorable prognosis in various cancers. In this study, HLA-F expression in 105 primary esophageal squamous cell carcinoma (ESCC) lesions and 62 case-matched adjacent normal tissues, and HLA I antigens among 68 cases were analyzed by immunohistochemistry. Data revealed that HLA-F expression was observed in 58.1%(61/105) of the ESCC lesions and in 54.8%(34/62) of the normal esophageal tissues. Among the 62 case-matched samples, HLA-F expression (lesion vs normal tissue) was up-regulated, unchanged and down-regulated in 13 (21.0%), 6 (9.6%) and 43 (69.4%) cases, respectively. Patients with HLA-F positive had a worse survival than those with HLA-F negative (p=0.040). Patients with up-regulated HLA-F expression (lesion vs normal tissue) had significantly worse survival than those with HLA-F unchanged and down-regulated (p=0.010). Furthermore, decreased HLA I expression was observed in 41.2%(28/68) patients, and was with worse prognosis in comparison to those with preserved HLA I expression (p=0.001). Multivariate analysis using Cox's proportional hazards model revealed that up-regulated HLA-F expression (p=0.026) and down-regulated HLA I expression (p=0.013) could be an independent unfavorable prognostic factor. In conclusion, this study provided the evidence that alteration of HLA I and HLA-F antigen expression was associated with survival in patients with ESCC. © 2012 Wiley-Liss, Inc.