bluuebunny/crossref_metadata_2025 huggingface dataset:
Teissier's problem on inequalities of nef divisors
Authors: Cutkosky Steven Dale
Published: January 2015

Teissier has proven remarkable inequalities [Formula: see text] for intersection numbers si = (ℒi ⋅ ℳd-i) of a pair of nef line bundles ℒ, ℳ on a d-dimensional complete algebraic variety over a field. He asks if two nef and big line bundles are numerically proportional if the inequalities are all equalities. In this paper, we show that this is true in the most general possible situation, for nef and big line bundles on a proper irreducible scheme over an arbitrary field k. Boucksom, Favre and Jonsson have recently established this result on a complete variety X over an algebraically closed field of characteristic zero. Their proof involves an ingenious extension of the intersection theory on a variety to its Zariski Riemann Manifold. This extension requires the existence of a direct system of nonsingular varieties dominating X. We make use of a simpler intersection theory which does not require resolution of singularities, and extend volume to an arbitrary field and prove its continuous differentiability, extending results of Boucksom, Favre and Jonsson, and of Lazarsfeld and Mustaţă. A goal in this paper is to provide a manuscript which will be accessible to many readers. As such, subtle topological arguments which are required to give a complete proof in [S. Bouksom et al., J. Algebraic Geometry18 (2009) 279–308] have been written out in this manuscript, in the context of our intersection theory, and over arbitrary varieties.
Graphs and complete intersection toric ideals
Authors: Bermejo I. , García-Marco I. , Reyes E.
Published: January 2015

Our purpose is to study the family of simple undirected graphs whose toric ideal is a complete intersection from both an algorithmic and a combinatorial point of view. We obtain a polynomial time algorithm that, given a graph G, checks whether its toric ideal PG is a complete intersection or not. Whenever PG is a complete intersection, the algorithm also returns a minimal set of generators of PG. Moreover, we prove that if G is a connected graph and PG is a complete intersection, then there exist two induced subgraphs R and C of G such that the vertex set V(G) of G is the disjoint union of V(R) and V(C), where R is a bipartite ring graph and C is either the empty graph, an odd primitive cycle, or consists of two odd primitive cycles properly connected. Finally, if R is 2-connected and C is connected, we list the families of graphs whose toric ideals are complete intersection.
Computation of the norm factor group over Henselian fields and tame Brauer group of generalized local fields
Authors: Motiee Mehran
Published: January 2015

Let F be a Henselian field. For a finite extension K of F, the norm factor group [Formula: see text] is computed. As an application, structure of the tame Brauer group of a generalized local field is determined. In particular, we observe that every torsion divisible abelian group is realizable as the tame Brauer group of a generalized local field.
Coquasitriangular structures on Hopf quivers
Authors: Huang Hua-Lin , Tao Wen-Qing
Published: January 2015

The complete list of the coquasitriangular structures of the graded Hopf algebra over a connected Hopf quiver is given.
Non-hyperbolic splitting of quadratic pairs
Authors: Becher Karim Johannes , Dolphin Andrew
Published: January 2015

We show that a non-hyperbolic quadratic pair on a central simple algebra Brauer equivalent to a quaternion algebra stays non-hyperbolic over some splitting field of the quaternion algebra. This extends a result previously only known for fields of characteristic different from two. Our presentation is free from restrictions on the characteristic of the base field.
Cellular covers of ℵ1-free abelian groups
Authors: Rodríguez José L. , Strüngmann Lutz
Published: January 2015

In this paper, we first show that for every natural number n and every countable reduced cotorsion-free group K there is a short exact sequence [Formula: see text] such that the map G → H is a cellular cover over H and the rank of H is exactly n. In particular, the free abelian group of infinite countable rank is the kernel of a cellular exact sequence of co-rank 2 which answers an open problem from Rodríguez–Strüngmann [J. L. Rodríguez and L. Strüngmann, Mediterr. J. Math.6 (2010) 139–150]. Moreover, we give a new method to construct cellular exact sequences with prescribed torsion free kernels and cokernels. In particular we apply this method to the class of ℵ1-free abelian groups in order to complement results from the cited work and Göbel–Rodríguez–Strüngmann [R. Göbel, J. L. Rodríguez and L. Strüngmann, Fund. Math.217 (2012) 211–231].
About Dixmier's conjecture
Authors: Moskowicz Vered
Published: January 2015

The well-known Dixmier conjecture [5] asks if every algebra endomorphism of the first Weyl algebra over a characteristic zero field is an automorphism.

We bring a hopefully easier to solve conjecture, called the γ, δ conjecture, and show that it is equivalent to the Dixmier conjecture.

In the group generated by automorphisms and anti-automorphisms of A1, all the involutions belong to one conjugacy class, hence:

• Every involutive endomorphism from (A1, γ) to (A1, δ) is an automorphism (γ and δ are two involutions on A1).

• Given an endomorphism f of A1 (not necessarily an involutive endomorphism), if one of f(X), f(Y) is symmetric or skew-symmetric (with respect to any involution on A1), then f is an automorphism.
Some characterizations of pseudo Cohen–Macaulay modules
Authors: Nhan Le Thanh , Chinh Nong Quoc
Published: January 2015

Let (R, 𝔪) be a Noetherian local ring and M a finitely generated R-module with dim M = d. Following Cuong and the first author [N. T. Cuong and L. T. Nhan, J. Algebra267 (2003) 156–177], M is called pseudo Cohen–Macaulay if [Formula: see text] for a system of parameters [Formula: see text] of M, where [Formula: see text]. In this paper, first we improve some known results on pseudo Cohen–Macaulay modules. Then we study the localizations of pseudo Cohen–Macaulay modules in order to introduce the pseudo Cohen–Macaulayness for the non-local case. Finally, we give characterizations for the formal power series ring and the polynomial ring being pseudo Cohen–Macaulay.
Gate-modulated electronic transport through a graphene nanoribbon composed of nanoribbons of different widths
Authors: Liu Wen , Cheng Jie , Zhao Jian-Hua , Xia Cai-Juan , Liu De-Sheng
Published: January 2015

Based on the non-equilibrium Green's function (NEGF) method combined with the density functional theory (DFT), we have studied the gate-modulated electronic properties of a graphene nanoribbon (GNR) which is composed of two GNRs of different widths. The results show that the charge transport is greatly modulated by the applied gate. Negative differential resistance (NDR) behaviors is found in such a system. With the increase in the gate, the NDR behaviors will disappear and reappear. Furthermore, under certain gate voltages multiple NDR behavior is found, the origin of which is attributed to the change of the number of effective transport channels and the variation of delocalization degree of the orbitals within the bias window. Interestingly, low bias NDR behavior is obtained which is desirable for integrated circuits from the point view of power consumption.
Zariski Topologies for Coprime and Second Submodules
Authors: Abuhlail Jawad
Published: January 2015

Let M be a non-zero module over an associative (not necessarily commutative) ring. In this paper, we investigate the so-called second and coprime submodules of M. Moreover, we topologize the spectrum Spec s (M) of second submodules of M and the spectrum Spec c (M) of coprime submodules of M, study several properties of these spaces and investigate their interplay with the algebraic properties of M.
Zero Product Determined Jordan Algebras, II
Authors: Grašič Mateja
Published: January 2015

The Albert algebra and the Jordan algebra of a nondegenerate symmetric bilinear form are shown to be zero product determined.
PUBLIC DELIBERATION ABOUT SALMON RESTORATION IMPACTS: DIFFERENCES IN THE INPUT OF CITIZENS IN DIFFERENT COMMUNITY ROLES
Authors: HARRIS CHARLES C. , BECKER DENNIS R. , NIELSEN ERIK A. , MCLAUGHLIN WILLIAM J.
Published: January 2015

We conducted a deliberative participatory process for social impact assessment (SIA), where interactive, community-based forums (ICFs) gathered public input about community impacts of alternatives for salmon recovery in the Inland Northwest of the United States. After residents were provided information about alternatives and engaged in facilitated discussions, we elicited their understandings of community conditions and judgments of socio-economic impacts.

The present analysis focuses on the proposition that citizens engaged in the ICF process who represented diverse roles, based on community domains such as business, health-care, and education, would significantly differ in their judgments about those socio-economic impacts. We collected data on 705 community residents in forums conducted in 27 communities across the Inland Northwest. Results affirm that differences in roles and associated lifestyles, ideologies, and political viewpoints were related to differences in judgments of community conditions and contentiousness of planning alternatives. Implications for the ICF process and its effectiveness for SIA, as well as for other kinds of participatory processes, are discussed.
A Rapid, Green and Controllable Strategy to Fabricate Electrodeposition of Reduced Graphene Oxide Film as Sensing Materials for Determination of Taxifolin
Authors: Wu Yanju , Lv Mingxiu , Li Bei , Ge Junda , Gao Lin
Published: January 2015

The electrodeposition of a film of reduced graphene oxide (ERGO) with well-dispersed on a glassy carbon electrode (GCE) was achieved using cyclic voltammetry (CV) in a graphene oxide (GO) colloidal solution. Using square wave adsorptive stripping voltammetry (SWASV), the ERGO film was applied for the first time, in developing a high-sensitive electrochemical sensor for detection of taxifolin. Compared with bare GCE, the resulting electrodes (ERGO/GCE) exhibited excellent response toward the oxidation of taxifolin by significantly enhancing the oxidation peak currents and the decreased peak-to-peak separation. Under selected conditions, the reduction peak currents had linear relationship with taxifolin concentration in the range of 5.0 × 10-8 – 1.5 × 10-6 mol L-1, with detection limit of 4.0 × 10-9 mol L-1. Besides, the method was successfully applied to the quantitative determination of taxifolin in the Prince's-feather fruit with satisfactory results.
Advantages of Hydrothermal Synthesis to Produce Tunable TiO2 Nanomicro Sized Photocatalysts and Their Effect in Lignin Degradation
Authors: Rangel R. , Cortés J. A. , Lara J. , Quintana P. , Alvarado-Gil J. J. , Contreras O.
Published: January 2015

Studies on photocatalytic degradation of lignin are scarce, even though it is an effective method for treatment of industrial effluents. In the present work, an advanced oxidation process (AOPs), leading to the photodegradation of lignin aqueous solutions, is proposed by using microstructured (T-MT) and nanostructured (T-NT) titanium dioxide compounds. Hydrothermal synthesis, in accordance with an experimental factorial design considering time of synthesis, NaOH concentration and synthesis temperature, was used to produce tunable TiO 2 photocatalysts for further study of its effects on the degradation of lignin. Photocatalytic reactions were conducted in a micro reactor batch system under UV irradiation. The catalysts were analyzed by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), surface area and porosity analyzer (BET), energy-dispersive X-ray spectroscopy (EDS) and UV-Vis diffuse reflectance spectroscopy. In order to optimize the yield reaction, an experimental factorial design was performed. According to our results, nanostructured TiO 2 consisting in different structural features and light absorption properties were produced using this method. It is shown that T-MT and T-NT compounds exhibit a wide range of values, for the kinetic parameters, in photoinduced degradation of methylene blue (MB) and lignin.
A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence
Authors: Zamunér Fernando Tadeu , Karia Bruno Takao Real , de Oliveira Cleyton Zanardo , Santos Carlos Roberto dos , Carvalho André Lopes , Vettore André Luiz
Published: January 2015

Despite significant advances in the treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate has not changed in the last decades. Therefore, the development of novel therapeutic strategies is pursued. Cancer–testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted expression pattern, and are considered ideal targets for tumor-specific immunotherapeutic approaches. In this study, using an in silico approach, we selected, among 139 previously described CTA, candidates to be evaluated in 89 HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1 (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations with recognized clinical features for poor outcome. Furthermore, MAGEA3/6 positivity was associated with significantly better disease-free survival (DFS, P = 0.014), and the expression of this antigen was shown to be an independent prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/6 is shown to be an independent marker for DFS. Mol Cancer Ther; 14(3); 828–34. ©2015 AACR.
Clinical Relevance of Studies on the Accuracy of Visual Inspection for Detecting Caries Lesions: A Systematic Review
Authors: Gimenez Thais , Piovesan Chaiana , Braga Mariana M. , Raggio Daniela P. , Deery Chris , Ricketts David N. , Ekstrand Kim R. , Mendes Fausto Medeiros
Published: January 2015

Although visual inspection is the most commonly used method for caries detection, and consequently the most investigated, studies have not been concerned about the clinical relevance of this procedure. Therefore, we conducted a systematic review in order to perform a critical evaluation considering the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature. The eligible studies were those which (1) assessed the accuracy of the visual method for detecting caries lesions on occlusal, approximal or smooth surfaces, in primary or permanent teeth, (2) used a reference standard, and (3) reported data about sample size and accuracy of the methods. Aspects related to clinical relevance and the methodological quality of the studies were evaluated. 96 of the 5,578 articles initially identified met the inclusion criteria. In general, most studies failed in considering some clinically relevant aspects: only 1 included study validated activity status of lesions, no study considered its prognosis, 79 studies did not consider a clinically relevant outcome, and only 1 evaluated a patient-centred outcome. Concerning methodological quality, the majority of the studies presented a high risk of bias in sample selection. In conclusion, studies on the accuracy of the visual method for caries detection should consider clinically relevant outcomes besides accuracy; moreover, they should be conducted with higher methodological quality, mainly regarding sample selection.
Clinical Features, Surgical Treatment, and Long-Term Outcome in Pediatric Patients with Moyamoya Disease in China
Authors: Bao Xiang-Yang , Duan Lian , Yang Wei-Zhong , Li De-Sheng , Sun Wei-Jian , Zhang Zheng-Shan , Zong Rui , Han Cong
Published: January 2015

Background: There was few detailed demographic and clinical data about Chinese patients with moyamoya disease. Here we describe the clinical features, surgical treatment, and long-term outcome of pediatric patients with moyamoya disease at a single institution in China. Methods: Our cohort included 288 pediatric patients with moyamoya disease. The demographic and clinical characteristics were obtained by retrospective chart review and long-term outcome was evaluated using the stroke status. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. The risk of subsequent stroke was determined using the Kaplan-Meier method. Results: The median age for the onset of symptoms was 8.0 years. The ratio of female to male patients was 1:1. Familial occurrence of moyamoya disease was 9.4%. The incidence of postoperative complications was 4.2%. Postoperative ischemic events were identified as predictors of unfavorable clinical outcome, while older age of symptom onset was associated with a favorable clinical outcome. The Kaplan-Meier estimate stroke risk was 5% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 9% after surgery for all patients treated with surgical revascularization. Overall, 86% of patients had an independent life with no significant disability. Conclusion: This long-term survey demonstrated that most surgically treated pediatric patients with MMD maintain good outcomes. Our results indicate that an early diagnosis and active intervention before the establishment of irreversible hemodynamic change are essential to achieve a favorable clinical outcome.
Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway
Authors: Liu Li , You Qi , Tu Yingfeng , Li Quanyi , Zheng Lihong , Li Xuan , Gu Jing , Wang Guonian
Published: January 2015

Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay. Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ. Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.
Increased Levels of Type 1 Interferon in a Type 1 Diabetic Mouse Model Induce the Elimination of B Cells from the Periphery by Apoptosis and Increase their Retention in the Spleen
Authors: Badr Badr Mohamed , Moustafa Nadia Ahmed , Eldien Heba M. Saad , Mohamed Amany O. , Ibrahim Hany M. , El-Elaimy Ibrahim A. , Mahmoud Mohamed H. , Badr Gamal
Published: January 2015

Background: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. Aims: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. Methods: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. Results: We observed that induction of T1D was accompanied by a marked destruction of β cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. Conclusion: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.
Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway
Authors: Dong Jangchuan , Lin Jing , Wang Boyuan , He Shaolin , Wu Chun , Kushwaha Kishan Kumar , Mohabeer Nilesh , Su Yousu , Fang Hongcheng , Huang Kai , Li Dazhu
Published: January 2015

Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway. Methods and Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl3. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. Conclusion: This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases.
AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway
Authors: Luo Xia , Deng Lingyan , Lamsal Laxmi Pangeni , Xu Wenjuan , Xiang Cheng , Cheng Liming
Published: January 2015

Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK) has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f). Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1) whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1). In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.
Des-Gamma-Carboxy Prothrombin (DCP) Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells
Authors: Zhang Yu-Sheng , Chu Jia-Hui , Song Zhi-Yu , Cui Shu-Xiang , Qu Xian-Jun
Published: January 2015

Background/Aims: Des-gamma-carboxy prothrombin (DCP), an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells, is known as a marker for HCC. Recent studies indicated that high levels of DCP are associated with the malignant potential of HCC. In this study, we aimed to investigate the association of DCP with gefitinib treatment failure in HCC and whether DCP counteracts gefitinib-induced growth inhibition and apoptosis of HCC. Methods: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western blotting was performed to analyze the expressions of molecules related to the apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR) pathway. Results: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of proliferation and stimulation of apoptosis. DCP prevented the activation of the apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic effects of DCP also arose from its ability to up-regulate EGFR, c-Met and hepatocyte growth factor (HGF) in HCC cells. Conclusion: DCP antagonized gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP might thus lead to low response rates or possibly no response to gefitinib in patients with HCC.
Pamidronate Attenuates Diastolic Dysfunction Induced by Myocardial Infarction Associated with Changes in Geometric Patterning
Authors: Gonçalves Andréa F. , Congio Luiz Henrique , dos Santos Priscila P. , Rafacho Bruna P. M. , Pereira Bruna L. B. , Claro Renan F. T. , Costa Nara A. , Chiuso-Minicucci Fernanda , Azevedo Paula S. , Polegato Bertha F. , Okoshi Katashi , Pereira Elenize J. , Okoshi Marina P. , Paiva Sergio A. R. , Zornoff Leonardo A. M. , Minicucci Marcos F.
Published: January 2015

Background/Aims: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. Methods: Male Wistar rats were assigned to four groups: a sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. Results: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. Conclusion: Pamidronate attenuates diastolic dysfunction following MI.
Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome
Authors: Wang Yan-ge , Xiong Xin , Chen Zhu-yue , Liu Kan-ling , Yang Jin-hua , Wen Qiang , Wu Fang-qin , Hu Xiao-fan , Peng Yu-dong , Wu Jing-jing , Lian Yi-tian , Zhang Wen-cai , Cheng Long-xian
Published: January 2015

Aim: The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS). Methods: The frequency of MDSCs in peripheral blood was determined by flow cytometry, and mRNA expression in purified MDSCs was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The suppressive function of MDSCs isolated from different groups was also determined. The plasma levels of certain cytokines were determined using Bio-Plex Pro™ Human Cytokine Assays. Results: The frequency of circulating CD14+HLA-DR-/low MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-33 were markedly increased in ACS patients compared to stable angina (SA) or control patients. Furthermore, MDSCs from ACS patients were more potent suppressors of T-cell proliferation and IFN-γ production than those from the SA or control groups at ratios of 1:4 and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF-α. Conclusions: We observed an increased frequency and suppressive function of MDSCs in ACS patients, a result that may provide insights into the mechanisms involved in ACS.
Ketamine Interferes with the Proliferation and Differentiation of Neural Stem Cells in the Subventricular Zone of Neonatal Rats
Authors: Huang He , Liu Lu , Li Bing , Zhao Pan-Pan , Xu Chun-Mei , Zhu Yang-Zi , Zhou Cheng-Hua , Wu Yu-Qing
Published: January 2015

Background: Previous studies have shown ketamine can alter the proliferation and differentiation of neural stem cells (NSCs) in vitro. However, these effects have not been entirely clarified in vivo in the subventricular zone (SVZ) of neonatal rats. The present study was designed to investigate the effects of ketamine on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in vivo. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were administered four injections of 40 mg/kg ketamine at 1-h intervals, and then 5-bromodeoxyuridine (BrdU) was injected intraperitoneally at PND-7, 9 and 13. NSC proliferation was assessed with Nestin/BrdU double-labeling immunostaining. Neuronal and astrocytic differentiation was evaluated with β-tubulin III/BrdU and GFAP/BrdU double-labeling immunostaining, respectively. The expressions of nestin, β-tubulin III and GFAP were measured using Western blot analysis. The apoptosis of NSCs and astrocytes in the SVZ of neonatal rats was evaluated using nestin/caspase-3 and GFAP/caspase-3 double-labeling immunostaining. Results: Neonatal ketamine exposure significantly reduced the number of nestin/BrdU and GFAP/BrdU double-positive cells in the SVZ. Meanwhile, the expressions of nestin and GFAP in the SVZ from the ketamine group were significantly decreased compared those in the control group. Still, no double-positive cells for nestin/caspase-3 and GFAP/caspase-3 were found after ketamine exposure. In addition, the neuronal differentiation of NSCs in the SVZ was markedly promoted by ketamine with an increased number of β-tubulin III/BrdU double-positive cells and enhanced expression of β-tubulin III. These effects of ketamine on the NSCs in the SVZ often lasted at least 1 week after ketamine anesthesia. Conclusion: In the present study, it was demonstrated that ketamine could alter neurogenesis by inhibiting the proliferation of NSCs, suppressing their differentiation into astrocytes and promoting the neuronal differentiation of the NSCs in the SVZ of neonatal rats during a critical period of their neurodevelopment.
Knockdown of Polycomb-Group RING Finger 6 Modulates Mouse Male Germ Cell Differentiation in Vitro
Authors: Sun Jin , Wang Jian , He Lin , Lin Yi , Wu Ji
Published: January 2015

Background: Polycomb-group RING finger 6 (PCGF6), one of six PCGF homologs, is the core component of the PRC1 complex that plays critical roles in epigenetic transcriptional silencing in higher eukaryotes. However, the biological functions of PCGF6 are unknown. Method: qRT-PCR and Western blot were used to detect the expression profile of PCGF6 in testes. Fluorescent immunohistochemistry was used to examine the cellular localization of PCGF6 protein in testes. Cell proliferation was tested by performing CCK-8 and EdU incorporation assay. Cell cycle and haploid cell population analysis was determined by flow cytometry using propidium iodide DNA staining. Co-immunoprecipitation experiment was conducted using PCGF6 antibody to obtain interacting protein of PCGF6. Luciferase reporter assays were performed to examine the promoter activity of PCGF6 in cells overexpressing OVOL1 and PLZF. Results: PCGF6 was expressed predominantly in meiotic and post-meiotic male germ cells, could negatively regulate the proliferation of GC-2 spd cells, an immortalized mouse spermatogenic cell line, and could modulate the differentiation of GC-2 spd cells in vitro. PCGF6 could indirectly interact with HSPA2, a key factor that is essential for male meiosis, and OVOL1 and PLZF, two key transcription factors that are involved in spermatogenesis, could positively and negatively modulate Pcgf6 promoter activity, respectively. PCGF1, BMI1, and PCGF5 are also highly expressed in mouse testes like PCGF6. Conclusion: PCGF6 may play important roles in male germ cell development.
Hyperketonemia (Acetoacetate) Upregulates NADPH Oxidase 4 and Elevates Oxidative Stress, ICAM-1, and Monocyte Adhesivity in Endothelial Cells
Authors: Kanikarla-Marie Preeti , Jain Sushil K.
Published: January 2015

Background/Aims: The incidence of developing microvascular dysfunction is significantly higher in type 1 diabetic (T1D) patients. Hyperketonemia (acetoacetate, β-hydroxybutyrate) is frequently found along with hyperglycemia in T1D. Whether hyperketonemia per se contributes to the excess oxidative stress and cellular injury observed in T1D is not known. Methods: HUVEC were treated with ketones in the presence or absence of high glucose for 24 h. NOX4 siRNA was used to specifically knockdown NOX4 expression in HUVEC. Results: Ketones alone or in combination with high glucose treatment cause a significant increase in oxidative stress, ICAM-1, and monocyte adhesivity to HUVEC. Using an antisense approach, we show that ketone induced increases in ROS, ICAM-1 expression, and monocyte adhesion in endothelial cells were prevented in NOX4 knockdown cells. Conclusion: This study reports that elevated levels of ketones upregulate NOX, contributing to increased oxidative stress, ICAM-1 levels, and cellular dysfunction. This provides a novel biochemical mechanism that elucidates the role of hyperketonemia in the excess cellular injury in T1D. New drugs targeting inhibition of NOX seems promising in preventing higher risk of complications associated with T1D.
Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2
Authors: Luo Tao , Zou Qian-xing , He Yuan-qiao , Wang Hua-feng , Li Na , Zeng Xu-hui
Published: January 2015

Background: Matrine is a bioactive alkaloid that has a variety of pharmacological effects and is widely used in Chinese medicine. However, its effects on male reproduction are not well known. In this study, we aimed to investigate the in vitro toxicity of matrine on mature mouse sperm. Methods: Mouse cauda epididymal sperm were exposed to matrine (10-200 µM) in vitro. The viability, motility, capacitation, acrosome reaction and fertilization ability of the mouse sperm were examined. Furthermore, the intracellular calcium concentration ([Ca2+]i), calcium (Catsper) and potassium (Ksper) currents, and phosphorylation of extracellular signal regulated kinases 1/2 (p-ERK1/2) of the sperm were analyzed. Results: After exposure to 100 µM or more of matrine, mouse cauda epididymal sperm exhibited a significant reduction in total motility, progressive motility, linear velocity and acrosome reaction rate induced by Ca2+ ionophore A23187. As a result, the fertilization ability of mouse sperm was remarkably decreased by matrine. Our data further demonstrated that matrine significantly reduced sperm [Ca2+]i and [Ca2+]i-related p-ERK1/2; however, both the CatSper and KSper currents, which are thought to interactively regulate Ca2+ influx in sperm, were not affected by matrine. Conclusion: Our findings indicate that matrine inhibits mouse sperm function by reducing sperm [Ca2+]i and suppressing the phosphorylation of ERK1/2.
AMP-Activated Protein Kinase α1 Regulates Cardiac Gap Junction Protein Connexin 43 and Electrical Remodeling Following Pressure Overload
Authors: Alesutan Ioana , Voelkl Jakob , Stöckigt Florian , Mia Sobuj , Feger Martina , Primessnig Uwe , Sopjani Mentor , Munoz Carlos , Borst Oliver , Gawaz Meinrad , Pieske Burkert , Metzler Bernhard , Heinzel Frank , Schrickel Jan Wilko , Lang Florian
Published: January 2015

Background/Aims: Adenosine 5'-monophosphate (AMP)-activated protein kinase (Ampk) modulates a wide array of cellular functions and regulates various ion channels and transporters. In failing human hearts an increased Ampkα1 activity was observed. The present study aimed to uncover the impact of Ampkα1 on cardiac electrical remodeling. Methods: Gene-targeted mice lacking functional Ampkα1 (Ampkα1-/-) and corresponding wild-type mice were exposed to pressure overload by “transverse aortic constriction” (TAC). In vivo electrophysiology was performed with a single catheter technique, myocardial conduction velocities and conduction characteristics investigated in isolated hearts, transcript levels quantified by RT-PCR and protein abundance determined by Western blotting. Moreover, connexin 43 (Cx43) was expressed in Xenopus oocytes with or without coexpression of wild-type or mutant AMPK and Cx43 protein abundance quantified utilizing confocal microscopy. Results: TAC treatment increased Ampkα1 protein expression in cardiac tissue from wild-type mice. TAC further increased left ventricular conduction inhomogeneity and triggered conduction blocks, effects blunted in the Ampkα1-/- mice. TAC treatment decreased Cx43 protein abundance in cardiac tissue, an effect significantly blunted in the Ampkα1-/- mice. TAC treatment did not modify Cx43 mRNA levels but increased ubiquitination of Cx43 protein, an effect mitigated by Ampkα1 deficiency. As shown in Xenopus oocytes, Cx43 cell membrane protein abundance was significantly downregulated by wild-type AMPKWT and constitutively active AMPKγR70Q, but not by catalytically inactive AMPKαK45R. Conclusion: Ampkα1 stimulates ubiquitination of the gap junction protein Cx43, thereby contributing to gap junction remodeling following pressure overload.
Anti-Mycobacterial Peptides: From Human to Phage
Authors: Teng Tieshan , Liu Jiafa , Wei Hongping
Published: January 2015

Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the growing problem of M. tuberculosis resistant to conventional antibiotics, especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial peptides have a few advantages, such as low immunogenicity, selective affinity to prokaryotic negatively charged cell envelopes, and diverse modes of action. In this review, we summarize the recent progress in the anti-mycobacterial peptides, highlighting the sources, effectiveness and bactericidal mechanisms of these antimicrobial peptides. Most of the current anti-mycobacterial peptides are derived either from host immune cells, bacterial extraction, or mycobacteriophages. Besides trans-membrane pore formation, which is considered to be the common bactericidal mechanism, many of the anti-mycobacterial peptides have the second non-membrane targets within mycobacteria. Additionally, some antimicrobial peptides play critical roles in innate immunity. However, a few obstacles, such as short half-life in vivo and resistance to antimicrobial peptides, need overcoming before clinical applications. Nevertheless, the multiple functions of anti-mycobacterial peptides, especially direct killing of pathogens and immune-modulators in infectious and inflammatory conditions, indicate that they are promising candidates for future drug development.
Stimulation of Suicidal Erythrocyte Death by PRIMA-1
Authors: Faggio Caterina , Alzoubi Kousi , Calabrò Salvatrice , Lang Florian
Published: January 2015

Background: The anticarcinogenic drug PRIMA-1 (p53 reactivation and induction of massive apoptosis 1) induces suicidal death of tumor cells, an effect in large part attributed to the up-regulation of the proapoptotic transcription factor p53. Erythrocytes are lacking gene transcription but are nevertheless able to enter eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study tested whether PRIMA-1 stimulates eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance from binding of specific antibodies, and ROS formation from DCFDA fluorescence. Results: A 48 h exposure of human erythrocytes to PRIMA-1 (25 µM) significantly increased the percentage of annexin-V-binding cells without significantly influencing [Ca2+]i or forward scatter. PRIMA-1 (100 µM) induced annexin-V-binding was not significantly blunted by removal of extracellular Ca2+ or by the caspase-3 inhibitor zVAD. PRIMA-1 (100 µM) further increased the ceramide abundance at the cell surface and ROS formation. Conclusions: PRIMA-1 stimulates phosphatidylserine translocation at the erythrocyte cell membrane, an effect at least partially due to up-regulation of ceramide abundance and ROS formation.
Do Not Resuscitate Orders for Patients with Intracerebral Hemorrhage: Experience from a Chinese Tertiary Care Center
Authors: Yang Tie-Cheng , Li Jian-Guo , Guo Wei
Published: January 2015

Aim: This study aimed to determine the frequency and determinant factors of do not resuscitate (DNR) orders in patients with intracerebral hemorrhage (ICH) at a university hospital in China. Methods: Data collected from June 2010 to December 2012 for patients with ICH were retrospectively reviewed. The characteristics and care of patients with and without DNR orders and those with early (≤24 h) and late (>24 h) DNR establishment were compared. Results: Formal DNR orders were filed during hospitalization for 64/759 (8.4%) patients with complete medical records enrolled in this study. Patients with DNR orders were older on average (73.1 ± 10.1 vs. 56.0 ± 13.2 years; p < 0.001) and a larger proportion had pre-ICH comorbidity impacting dependency (87.5 vs. 17.0%; p < 0.001) than did those with no DNR order. Patients with DNR orders were in worse clinical condition on arrival than those without a DNR order, as judged by Glasgow Coma Scale scores, and more frequently had large hematoma volumes (78.1 vs. 39.7%; p < 0.001). Conclusions: DNR orders were not used commonly for patients with ICH in this Chinese sample. No relationship between ICH severity and DNR decision making was observed.
VEGF-A Inhibition Ameliorates Podocyte Apoptosis via Repression of Activating Protein 1 in Diabetes
Authors: Bai Xiaoyan , Geng Jian , Li Xiao , Yang Fang , Tian Jianwei
Published: January 2015

Background/Aims: Vascular endothelial growth factor-A (VEGF-A) upregulation and podocyte apoptosis have been documented in diabetes. This study was designed to investigate whether inhibiting VEGF-A could ameliorate podocyte apoptosis in diabetes and the underlying mechanisms. Methods: In vitro, small interfering RNAs (siRNAs) of VEGF-A and activator protein 1 (AP-1, c-fos and c-jun), bevacizumab (VEGF-A inhibitor) and SP600125 (AP-1 inhibitor) were added to high glucose (30 mM) induced podocytes. Luciferase reporter assay was used to investigate whether AP-1 was a direct target of VEGF-A. In vivo, bevacizumab and SP600125 were administered to 12-week-old streptozotocin-induced male Sprague Dawley rats. The level of VEGF-A, c-fos, c-jun and bcl-2 were examined using immunostaining and Western blot analysis. Podocyte apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay, electron microscopy and flow cytometry. Results: Silencing VEGF-A or AP-1 upregulated bcl-2 and ameliorated podocyte apoptosis. Silencing VEGF-A decreased the level of c-fos and c-jun and bevacizumab and SP600125 treatment attenuated podocyte apoptosis. Luciferase reporter activity of VEGF-A-3′-UTR constructs was significantly provoked when stimulated with TGF-β1. In diabetic rat kidneys, VEGF-A co-localized with bcl-2 in podocytes. With bevacizumab and SP600125 treatment, the level of VEGF-A and AP-1 decreased while bcl-2 increased. Podocyte apoptotic rate was reduced with condensed podocyte nuclei less frequently observed. The urine albumin excretion rate (UAER) and albumin/creatinine were improved. Conclusion: This study demonstrates VEGF-A inhibition ameliorates podocyte apoptosis by regulating AP-1 and bcl-2 signaling. AP-1 is a direct target of VEGF-A and a novel player in podocyte apoptosis.