bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of propolis on CCL5 and IFN-γ expression by peripheral blood mononuclear cells from leishmaniasis patients
Authors: Amarante Marla Karine , Watanabe Maria Angélica Ehara , Conchon-Costa Ivete , Fiori Leandra Lopes , Oda Julie Massayo Maeda , Búfalo Michelle Cristiane , Sforcin José Maurício 
Published: November 2011

Abstract

Objectives
Mucocutaneous leishmaniasis is associated with a strong Th1 immune response to Leishmania, which modulates chemokines and their receptors expression, affecting their migratory capacity. There are no antileishmanial vaccines available and chemotherapy still relies on the potentially toxic pentavalent antimonials. Propolis is a bee product with immunomodulatory and antiparasite activities, and researchers have been attracted to its potential for the development of new drugs. This work investigated the effects of propolis on CCL5 and IFN-γ expression by peripheral blood mononuclear cells (PBMC) in order to evaluate a possible immunomodulatory action of propolis in patients with leishmaniasis compared to healthy control subjects.

Methods
PBMC were incubated in the absence or presence of propolis and the evaluation of a possible cytotoxicity of propolis was carried out using MTT assay. The expression level of CCL5 and IFN-γ was determined by real-time PCR.

Key findings
Our data indicated that propolis modulates the immune response of leishmaniasis patients in vitro, affecting CCL5 and IFN-γ expression by PBMC.

Conclusions
Data suggested that propolis drives an anti-inflammatory response depending on concentration. Although propolis is a potential source of new and selective drugs for the treatment of leishmaniasis, its usefulness in the therapeutics should be further investigated.
Susceptibility of glucocorticoids to colonic metabolism and pharmacologic intervention in the metabolism: implication for therapeutic activity of colon-specific glucocorticoid 21-sulfate sodium at the target site
Authors: Kong Hyesik , Lee Yonghyun , Kim Hyunjeong , Hong Sungchae , Kim Dae-Duk , Yoon Jeong-Hyun , Jung Yunjin , Kim Young Mi 
Published: November 2011

Abstract

Objectives
The systemic side effects of glucocorticoids have prevented their long-term use for treatment of inflammatory bowel disease. Colon-specific delivery of glucocorticoids has been adopted as a strategy to circumvent the toxicological trouble. Glucocorticoids delivered to the large intestine might undergo metabolisms by colonic microflora, which should affect therapeutic availability at the target site. It was investigated whether the susceptibility of glucocorticoids to the colonic metabolisms and pharmacologic intervention in the metabolism could modulate the therapeutic availability of colon-targeted glucocorticoids.

Methods
Various glucocorticoids and their derivatives, glucocorticoid 21-sulfate sodium compounds, were incubated in the cecal contents in the presence or absence of reduction inhibitors and the change in the levels of the drugs was monitored.

Key findings
The accumulation profiles of the corresponding glucocorticoids liberated from glucocorticoid 21-sulfate sodium compounds vary, depending on the metabolic susceptibility of glucocorticoids. Reduction inhibitors prevented the cecal metabolisms of glucocorticoids, which was most prominent for prednisolone (PD) and methylprednisolone (MP). Moreover, reduction inhibitors increased the accumulated amount of MP and PD released from PD- and MP-21-sulfate sodium in the cecal contents.

Conclusions
Our data provide information useful for selection of a glucocorticoid and a pharmacologic strategy for the design of an efficient colon-specific glucocorticoid prodrug.
Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration
Authors: Carosio Roberta , Pistoia Vito , Orienti Isabella , Formelli Franca , Cavadini Elena , Mangraviti Salvatore , Montaldo Paolo G , Ognio Emanuela , Emionite Laura , Zuccari Guendalina 
Published: November 2011

Abstract

Objectives
The major limitation to successful chemotherapy of neuroblastoma (NB) is the toxicity and the poor bioavailability of traditional drugs.

Methods
We synthesised an amphiphilic dextrin derivative (DX-OL) able to host fenretinide (4-HPR) by complexation. In this study, we have investigated the effects of 4-HPR-loaded amphipilic dextrin (DX-OL/4-HPR) in comparison with 4-HPR alone both in vitro on human NB cells and in vivo in pseudometastatic NB models. The haemolysis assay was used as a measure of the potential damage caused by the pharmaceutical formulation in vivo. Pharmacokinetic experiments were performed to assess drug plasma levels in mice treated with free or complexed 4-HPR.

Key findings
DX-OL/4-HPR exerted a more potent cytotoxic activity on NB cells. Complexed 4-HPR significantly increased the proportion of sub-G1 cells with respect to free 4-HPR. Dextrin derivatives showed no haemolytic activity, indicating their suitability for parenteral administration. DX-OL/4-HPR increased the lifespan and the long-term survival of treated mice over controls. The analysis of drug plasma levels indicates that the complexed drug has a higher AUC due to a reduced clearance from the blood.

Conclusions
Our data suggest that DX-OL/4-HPR is an injectable formulation that is able to improve drug aqueous solubility and bioavailability.
Metabolism of cryptolepine and 2-fluorocryptolepine by aldehyde oxidase
Authors: Stell J Godfrey P , Wheelhouse Richard T , Wright Colin W 
Published: November 2011

Abstract

Objectives
To investigate the metabolism of cryptolepine and some cryptolepine analogues by aldehyde oxidase, and to assess the implications of the results on the potential of cryptolepine analogues as antimalarial agents.

Methods
The products resulting from the oxidation of cryptolepine and 2-fluorocryptolepine by a rabbit liver preparation of aldehyde oxidase were isolated and identified using chromatographic and spectroscopic techniques. The antiplasmodial activity of cryptolepine-11-one was assessed against Plasmodium falciparum using the parasite lactate dehydrogenase assay.

Key findings
Cryptolepine was oxidized by aldehyde oxidase give cryptolepine-11-one. Although 2-fluorocryptolepine was found to have less affinity for the enzyme than cryptolepine, it was a better substrate for aldehyde oxidase than the parent compound. In contrast, quindoline, the 11-chloro- , 2,7-dibromo- and 2-methoxy analogues of cryptolepine were not readily oxidized. Cryptolepine-11-one was found to be inactive against P. falciparum in vitro raising the possibility that the effectiveness of cryptolepine as an antimalarial, may be compromised by metabolism to an inactive metabolite by liver aldehyde oxidase.

Conclusions
Cryptolepine and 2-fluorocryptolepine are substrates for aldehyde oxidase. This may have implications for the design and development of cryptolepine analogues as antimalarial agents.
International disease monitoring, July to September 2011
Authors: Roberts H. , Lopez M. 
Published: November 2011

African swine fever continues to spread in western Russia
Deboned and matured beef imports to the EU from Paraguay suspended due to foot‐and‐mouth disease
Spread of a new clade of highly pathogenic avian influenza in south‐east Asia
Rabies case in France in an illegally imported pet dog
Re‐emergence of West Nile fever in southern Europe
These are among matters discussed in the international disease monitoring report for July to September 2011, prepared by Defra's Animal Health and Veterinary Laboratories Agency
ATM-Mediated DNA Damage Signals Mediate Immune Escape through Integrin-αvβ3–Dependent Mechanisms
Authors: Jinushi Masahisa , Chiba Shigeki , Baghdadi Muhammad , Kinoshita Ichiro , Dosaka-Akita Hirotoshi , Ito Koyu , Yoshiyama Hironori , Yagita Hideo , Uede Toshimitsu , Takaoka Akinori 
Published: November 2011

Abstract
Although the tumor microenvironment plays a critical role in tumor progression and metastasis, the relationship between chemotherapy resistance and modulation of the tumor microenvironment remains unclear. Here, we report a novel mechanism showing how constitutive DNA damage signals in therapy-resistant tumor cells suppress antitumor immunity in an integrin-αvβ3–dependent manner. Integrin-αvβ3 was upregulated on various therapy-resistant tumor cells through chronic activation of ATM/Chk2-and NFκB-mediated pathways. Inhibiting tumor-specific expression of integrin-αvβ3 improved therapeutic responses to anticancer drugs by stimulating endogenous host immune systems. Mechanistic investigations revealed that tumor-specific integrin-αvβ3 expression targeted dendritic cells, facilitating their ability to phagocytose viable therapy-resistant tumor cells and thereby impaired their ability to cross-prime antigen-specific T lymphocytes. Together, our results clarify the detrimental effects of constitutive DNA damage signals to chemosensitivity and antitumor immunity. Furthermore, these findings suggest that integrin-αvβ3 targeting may benefit patients' refractory to current anticancer regimens by defeating DNA damage signaling-induced immune escape. Cancer Res; 72(1); 56–65. ©2011 AACR.
EpCAM/CD3-Bispecific T-cell Engaging Antibody MT110 Eliminates Primary Human Pancreatic Cancer Stem Cells
Authors: Cioffi Michele , Dorado Jorge , Baeuerle Patrick A. , Heeschen Christopher 
Published: November 2011

Abstract
Purpose: Tumor-initiating cells with stem-like properties, also termed cancer stem cells (CSC), have been shown to sustain tumor growth as well as metastasis and are highly resistant to chemotherapy. Because pancreatic CSCs have been isolated on the basis of EpCAM expression, we investigated whether a targeted immunotherapy to EpCAM using the bispecific T-cell–engaging antibody MT110 is capable of eradicating CSCs.
Experimental Design: We studied in vitro and in vivo the effects of MT110 on CSCs using both established cell lines as well as primary cells of human pancreatic cancer.
Results: Although established cell lines were more responsive to MT110-engaged T cells, also primary cells showed a time- and dose-dependent response to treatment with the bispecific antibody. In addition, the population of highly tumorigenic CSCs was efficiently targeted by the EpCAM/CD3-bispecific antibody MT110 in vitro and in vivo using a mouse model of established primary pancreatic cancer. Pancreatic cancer cells derived from metastases were slightly more resistant to MT110 treatment on the basis of in vivo tumorigenicity studies. This appeared to be related to a higher frequency of an EpCAM-negative subpopulation of CSCs.
Conclusions: Cytotoxic T cells can be effectively redirected against primary human pancreatic cancer cells by T-cell–engaging BiTE antibody MT110 including a subpopulation of highly tumorigenic CSCs. Clin Cancer Res; 18(2); 465–74. ©2011 AACR.
Association of Testosterone Levels With Endothelial Function in Men
Authors: Empen Klaus , Lorbeer Roberto , Dörr Marcus , Haring Robin , Nauck Matthias , Gläser Sven , Krebs Alexander , Reffelmann Thorsten , Ewert Ralf , Völzke Henry , Wallaschofski Henri , Felix Stephan B. 
Published: November 2011

Objective—
Because population-based data are lacking, we assessed the cross-sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania.

Methods and Results—

Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04–1.63;
P
=0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06–1.76;
P
=0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD.

Conclusion—
Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men.
Transforming Growth Factor-β–Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21
Authors: Kumarswamy Regalla , Volkmann Ingo , Jazbutyte Virginija , Dangwal Seema , Park Da-Hee , Thum Thomas 
Published: November 2011

Objective—
MicroRNAs are a class of small ribonucleotides regulating gene/protein targets by transcript degradation or translational inhibition. Transforming growth factor-β (TGF-β) is involved in cardiac fibrosis partly by stimulation of endothelial-to-mesenchymal transition (EndMT). Here, we investigated whether microRNA (miR)-21, a microRNA enriched in fibroblasts and involved in general fibrosis, has a role in cardiac EndMT.

Methods and Results—
TGF-β treatment of endothelial cells significantly increased miR-21 expression and induced EndMT characterized by suppression of endothelial and increase of fibroblast markers. Overexpression of miR-21 alone also stimulated EndMT. Importantly, miR-21 blockade by transfection of specific microRNA inhibitors partly prevented TGF-β-induced EndMT. Mechanistically, miR-21 silenced phosphatase and tensin homolog in endothelial cells, resulting in activation of the Akt-pathway. Akt inhibition partly restored TGF-β-mediated loss of endothelial markers during EndMT. In vivo, pressure overload of the left ventricle led to increased expression of miR-21 in sorted cardiac endothelial cells, which displayed molecular and phenotypic signs of EndMT. This was attenuated by treatment of mice subjected to left ventricular pressure overload with an antagomir against miR-21.

Conclusion—
TGF-β-mediated EndMT is regulated at least in part by miR-21 via the phosphatase and tensin homolog/Akt pathway. In vivo, antifibrotic effects of miR-21 antagonism are partly mediated by blocking EndMT under stress conditions.
Inhibition of MicroRNA-29 Enhances Elastin Levels in Cells Haploinsufficient for Elastin and in Bioengineered Vessels—Brief Report
Authors: Zhang Pei , Huang Angela , Ferruzzi Jacopo , Mecham Robert P. , Starcher Barry C. , Tellides George , Humphrey Jay D. , Giordano Frank J. , Niklason Laura E. , Sessa William C. 
Published: November 2011

Objective—
The goal of this study was to determine whether antagonizing microRNA (miR)-29 enhances elastin (ELN) levels in cells and tissues lacking ELN.

Methods and Results—
miR-29 mimics reduced ELN levels in fibroblasts and smooth muscle cells, whereas miR-29 inhibition increased ELN levels. Antagonism of miR-29 also increased ELN levels in cells from patients haploinsufficient for ELN and in bioengineered human vessels.

Conclusion—
miR-29 antagonism may promote increased ELN levels during conditions of ELN deficiencies.
NADPH Oxidase 4 Mediates Monocyte Priming and Accelerated Chemotaxis Induced by Metabolic Stress
Authors: Ullevig Sarah , Zhao Qingwei , Lee Chi Fung , Seok Kim Hong , Zamora Debora , Asmis Reto 
Published: November 2011

Objective—
Metabolic disorders increase monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis in mice. The goal of this study was to determine the molecular mechanisms responsible for the enhanced responsiveness of monocytes to chemoattractants induced by metabolic stress.

Methods and Results—

Chronic exposure of monocytes to diabetic conditions induced by human LDL plus high D-glucose concentrations (LDL+HG) promoted NADPH Oxidase 4 (Nox4) expression, increased intracellular H
2
O
2
formation, stimulated protein
S
-glutathionylation, and increased chemotaxis in response to MCP-1, platelet-derived growth factor B, and RANTES. Both H
2
O
2
added exogenously and overexpression of Nox4 mimicked LDL+HG-induced monocyte priming, whereas Nox4 knockdown protected monocytes against metabolic stress-induced priming and accelerated chemotaxis. Exposure of monocytes to LDL+HG promoted the
S
-glutathionylation of actin, decreased the F-actin/G-actin ratio, and increased actin remodeling in response to MCP-1. Preventing LDL+HG-induced protein
S
-glutathionylation by overexpressing glutaredoxin 1 prevented monocyte priming and normalized monocyte chemotaxis in response to MCP-1. Induction of hypercholesterolemia and hyperglycemia in C57BL/6 mice promoted Nox4 expression and protein
S
-glutathionylation in macrophages, and increased macrophage recruitment into MCP-1–loaded Matrigel plugs implanted subcutaneous in these mice.

Conclusion—

By increasing actin-
S
-glutathionylation and remodeling, metabolic stress primes monocytes for chemoattractant-induced transmigration and recruitment to sites of vascular injury. This Nox4-dependent process provides a novel mechanism through which metabolic disorders promote atherogenesis.
Calpains Contribute to Vascular Repair in Rapidly Progressive Form of Glomerulonephritis: Potential Role of Their Externalization
Authors: Letavernier Béatrice , Zafrani Lara , Nassar Dany , Perez Joëlle , Levi Charlène , Bellocq Agnès , Mesnard Laurent , Sachon Emmanuelle , Haymann Jean-Philippe , Aractingi Selim , Faussat Anne-Marie , Baud Laurent , Letavernier Emmanuel 
Published: November 2011

Objective—
Calpains, calcium-activated proteases, mediate the angiogenic signals of vascular endothelial growth factor. However, their involvement in vascular repair has not been investigated and the underlying mechanisms remain to be fully elucidated.

Methods and Results—
A rapidly progressive form of glomerulonephritis in wild type and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor, was studied. Calpastatin transgene expression prevented the repair of peritubular capillaries and the recovery of renal function, limiting mouse survival. In vitro analysis detected a significant reduction of both intracellular and extracellular calpain activities in transgene expressing cells, whereas Western blotting revealed that proangiogenic factors vascular endothelial growth factor and norepinephrine increased calpain exteriorization. In vitro, extracellular calpains increased endothelial cell proliferation, migration and capillary tube formation. In vivo, delivery of nonpermeable extracellular calpastatin was sufficient to blunt angiogenesis and vascular repair. Endothelial cell response to extracellular calpains was associated with fibronectin cleavage, generating fibronectin fragments with proangiogenic capacity. In vivo, fibronectin cleavage was limited in the kidney of calpastatin transgenic mice with nephritis.

Conclusion—
This study demonstrates that externalized calpains participate in angiogenesis and vascular repair, partly by promoting fibronectin cleavage and thereby amplifying vascular endothelial growth factor efficiency. Thus, manipulation of calpain externalization may have therapeutic implications to control angiogenesis.
The Cox-Maze Procedure for Lone Atrial Fibrillation
Authors: Weimar Timo , Schena Stefano , Bailey Marci S. , Maniar Hersh S. , Schuessler Richard B. , Cox James L. , Damiano Ralph J. 
Published: November 2011

Background—
The Cox-Maze procedure (CMP) has achieved high success rates in the therapy of atrial fibrillation (AF) while becoming progressively less invasive. This report evaluates our experience with the CMP in the treatment of lone AF over 2 decades and compares the original cut-and-sew CMP-III to the ablation-assisted CMP-IV, which uses bipolar radiofrequency and cryoenergy to create the original lesion pattern.

Methods and Results—

Data were collected prospectively on 212 consecutive patients (mean age, 53.5±10.4 years; 78% male) who underwent a stand-alone CMP from 1992 through 2010. The median duration of preoperative AF was 6 (interquartile range, 2.9–11.5) years, with 48% paroxysmal and 52% persistent or long-standing persistent AF. Univariate analysis with preoperative and perioperative variables used as covariates for the CMP-III (n=112) and the CMP-IV (n=100) was performed. Overall, 30-day mortality was 1.4%, with no intraoperative deaths. Freedom from AF was 93%, and freedom from AF off antiarrhythmics was 82%, at a mean follow-up time of 3.6±3.1 years. Freedom from symptomatic AF at 10 years was 85%. Only 1 late stroke occurred, with 80% of patients not receiving anticoagulation therapy. The less invasive CMP-IV had significantly shorter cross-clamp times (41±13 versus 92±26 minutes;
P
<0.001) while achieving high success rates, with 90% freedom from AF and 84% freedom from AF off antiarrhythmics at 2 years.

Conclusions—
The CMP, although simplified and shortened by alternative energy sources, has excellent results, even with improved follow-up and stricter definition of failure.
Atrophy of Spared Gray Matter Tissue Predicts Poorer Motor Recovery and Rehabilitation Response in Chronic Stroke
Authors: Gauthier Lynne V. , Taub Edward , Mark Victor W. , Barghi Ameen , Uswatte Gitendra 
Published: November 2011

Background and Purpose—
Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage.

Methods—
Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery.

Results—
Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy.

Conclusions—
Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.
Explaining How Brain Stimulation Can Evoke Memories
Authors: Jacobs Joshua , Lega Bradley , Anderson Christopher 
Published: November 2011

Abstract
An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the “high school-ness” of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.