bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous endothelial cells as accelerators of hematopoietic reconstitution
Authors: Mizer J Christopher , Ichim Thomas E , Alexandrescu Doru T , Dasanu Constantin A , Ramos Famela , Turner Andrew , Woods Erik J , Bogin Vladimir , Murphy Michael P , Koos David , Patel Amit N 
Published: January 2013

AbstractDespite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a) ability to regulate secretion of cytokines based on biological need; b) long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c) potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC) in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.
Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy
Authors: Castañon Eduardo , Bosch-Barrera Joaquim , López Inés , Collado Víctor , Moreno Marta , López-Picazo José María , Arbea Leire , Lozano María Dolores , Calvo Alfonso , Gil-Bazo Ignacio 
Published: January 2013

Abstract

Background
Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy).

Methods
We have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy.

Results
Id1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R = 0.579, p = 0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p = 0.002). A trend towards significance for a worse progression free survival (30 vs 1 months, p = 0.219) and a lower response rate to the treatment (RR = 50% vs 87.5%, p = 0.07) were also observed.

Conclusions
A correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.
A mathematical model with time-varying delays in the combined treatment of chronic myeloid leukemia
Authors: Berezansky Leonid , Bunimovich-Mendrazitsky Svetlana , Domoshnitsky Alexander 
Published: January 2013

AbstractIn this paper, we propose and analyze a mathematical model for the treatment of chronic myelogenous (myeloid) leukemia (CML), a cancer of the blood. Our main focus is on the combined treatment of CML based on imatinib therapy and immunotherapy. Treatment with imatinib is a molecular targeted therapy that inhibits the cells involved in the chronic CML pathogenesis. Immunotherapy based on interferon alfa-2a (IFN-α) increases cancer cell mortality and leads to improvement of outcomes of the combined therapy. Interaction between CML cancer cells and effector cells of the immune system is modeled by a system of non-linear differential equations, where we introduced biologically motivated time-varying delays in the treatment terms. The analysis of the described system shows the existence of a unique global positive solution and a unique non-trivial equilibrium. We also derive explicit local and global stability conditions for the non-trivial equilibrium.
Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways
Authors: Lei Qi , Pan Xiao-Qing , Villamor Antonio N , Asfaw Tirsit S , Chang Shaohua , Zderic Steven A , Malykhina Anna P 
Published: January 2013

Abstract

Background
Bladder pain of unknown etiology has been associated with co-morbid conditions and functional abnormalities in neighboring pelvic organs. Mechanisms underlying pain co-morbidities include cross-sensitization, which occurs predominantly via convergent neural pathways connecting distinct pelvic organs. Our previous results showed that colonic inflammation caused detrusor instability via activation of transient receptor potential vanilloid 1 (TRPV1) signaling pathways, therefore, we aimed to determine whether neurogenic bladder dysfunction can develop in the absence of TRPV1 receptors.

Methods
Adult male C57BL/6 wild-type (WT) and TRPV1−/− (knockout) mice were used in this study. Colonic inflammation was induced by intracolonic trinitrobenzene sulfonic acid (TNBS). The effects of transient colitis on abdominal sensitivity and function of the urinary bladder were evaluated by cystometry, contractility and relaxation of detrusor smooth muscle (DSM) in vitro to various stimuli, gene and protein expression of voltage-gated sodium channels in bladder sensory neurons, and pelvic responses to mechanical stimulation.

Results
Knockout of TRPV1 gene did not eliminate the development of cross-sensitization between the colon and urinary bladder. However, TRPV1−/− mice had prolonged intermicturition interval and increased number of non-voiding contractions at baseline followed by reduced urodynamic responses during active colitis. Contractility of DSM was up-regulated in response to KCl in TRPV1−/− mice with inflamed colon. Application of Rho-kinase inhibitor caused relaxation of DSM in WT but not in TRPV1−/− mice during colonic inflammation. TRPV1−/− mice demonstrated blunted effects of TNBS-induced colitis on expression and function of voltage-gated sodium channels in bladder sensory neurons, and delayed development of abdominal hypersensitivity upon colon-bladder cross-talk in genetically modified animals.

Conclusions
The lack of TRPV1 receptors does not eliminate the development of cross-sensitization in the pelvis. However, the function of the urinary bladder significantly differs between WT and TRPV−/− mice especially upon development of colon-bladder cross-sensitization induced by transient colitis. Our results suggest that TRPV1 pathways may participate in the development of chronic pelvic pain co-morbidities in humans.
Molecular cloning and expression analysis of peptidase genes in the fish-pathogenic scuticociliate Miamiensis avidus
Authors: Seo Jung Soo , Jeon Eun Ji , Jung Sung Hee , Park Myoung Ae , Kim Jin Woo , Kim Ki Hong , Woo Sung Ho , Lee Eun Hye 
Published: January 2013

Abstract

Background
Parasite peptidases have been actively studied as vaccine candidates or drug targets for prevention or treatment of parasitic diseases because of their important roles for survival and/or invasion in the host. Like other parasites, the facultative histophagous ciliate Miamiensis avidus would possess peptidases that are closely associated with the invasion into the host tissue and survival in the host.

Results
The 17 genes encoding peptidases, including seven cathepsin-like cysteine peptidases, four serine carboxypeptidases, a eukaryotic aspartyl protease family protein, an ATP-dependent metalloprotease FtsH family protein, three leishmanolysin family proteins and a peptidase family M49 protein were identified from a Miamiensis avidus cDNA library by BLAST X search. Expression of genes encoding two cysteine peptidases, three leishmanolysin-like peptidases and a peptidase family M49 protein was up-regulated in the cell-fed ciliates compared to the starved ciliates. Especially, one cysteine peptidase (MaPro 4) and one leishmanolysin-like peptidase (MaPro 14) were transcribed more than 100-folds in the cell-fed ciliates.

Conclusions
The genetic information and transcriptional characteristics of the peptidases in the present results would be helpful to elucidate the role of peptidases in the invasion of scuticociliates into their hosts.
Effect of engineered TiO2and ZnO nanoparticles on erythrocytes, platelet-rich plasma and giant unilamelar phospholipid vesicles
Authors: Šimundić Metka , Drašler Barbara , Šuštar Vid , Zupanc Jernej , Štukelj Roman , Makovec Darko , Erdogmus Deniz , Hägerstrand Henry , Drobne Damjana , Kralj-Iglič Veronika 
Published: January 2013

Abstract

Background
Massive industrial production of engineered nanoparticles poses questions about health risks to living beings. In order to understand the underlying mechanisms, we studied the effects of TiO2 and ZnO agglomerated engineered nanoparticles (EPs) on erythrocytes, platelet-rich plasma and on suspensions of giant unilamelar phospholipid vesicles.

Results
Washed erythrocytes, platelet-rich plasma and suspensions of giant unilamelar phospholipid vesicles were incubated with samples of EPs. These samples were observed by different microscopic techniques. We found that TiO2 and ZnO EPs adhered to the membrane of washed human and canine erythrocytes. TiO2 and ZnO EPs induced coalescence of human erythrocytes. Addition of TiO2 and ZnO EPs to platelet-rich plasma caused activation of human platelets after 24 hours and 3 hours, respectively, while in canine erythrocytes, activation of platelets due to ZnO EPs occurred already after 1 hour. To assess the effect of EPs on a representative sample of giant unilamelar phospholipid vesicles, analysis of the recorded populations was improved by applying the principles of statistical physics. TiO2 EPs did not induce any notable effect on giant unilamelar phospholipid vesicles within 50 minutes of incubation, while ZnO EPs induced a decrease in the number of giant unilamelar phospholipid vesicles that was statistically significant (p < 0,001) already after 20 minutes of incubation.

Conclusions
These results indicate that TiO2 and ZnO EPs cause erythrocyte aggregation and could be potentially prothrombogenic, while ZnO could also cause membrane rupture.
MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma
Authors: Sarver Aaron L , Thayanithy Venugopal , Scott Milcah C , Cleton-Jansen Anne-Marie , Hogendoorn Pancras CW , Modiano Jaime F , Subramanian Subbaya 
Published: January 2013

Abstract

Background
Deregulation of microRNA (miRNA) transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma.

Methods
Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance.

Results
Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death) and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs) in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544.

Conclusions
We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.
Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy
Authors: Lin Tsung-Li , Wang Shyu-Jye , Fong Yi-Chin , Hsu Chin-Jung , Hsu Horng-Chaung , Tsai Chun-Hao 
Published: January 2013

Abstract

Background
Long-term alendronate therapy may lead to atypical femoral fractures in a very few patients. However, the management protocol to optimize fracture healing remains undetermined. The purpose of this study was to describe the time to union of atypical femoral fractures after surgical nailing in patients on long-term alendronate therapy, with continuation of alendronate or discontinuation of alendronate, and administration of bone-forming agents.

Findings
From January 2004 to December 2011, the records of patients at our institution on long-term alendronate therapy for more than 36 months and sustaining atypical femoral fractures that had undergone surgical nailing, with continuation of alendronate or discontinuation of alendronate and administration of bone-forming agents were reviewed.
During the 8-year study period, we treated 10 atypical femoral fractures with surgical nailing in 7 consecutive osteopenic or osteoporotic patients on long-term alendronate therapy for more than 36 months. There were no post-operative complications or needs for revision surgery. All fractures achieved union during follow-up. Mean union time was 23.5 months (range, 18–31 months) for 6 fractures with continuation of alendronate after surgery, and 4.5 months (range, 4–5 months) for 4 fractures with discontinuation of alendronate and administration of bone-forming agents after surgery.

Conclusions
Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy.
Statin use and ocular inflammatory disease risk
Authors: Yunker Jacob J , McGwin Gerald , Read Russell W 
Published: January 2013

Abstract

Background
This study aims to evaluate the effect of oral statin medication use on the subsequent development of ocular inflammatory disease (OID). A retrospective nested case–control study was carried out on patient records from the Birmingham Veterans Affairs Medical Center. All male patients with a new diagnosis of OID over a 5-year period were included. Ten control subjects (without OID) were age-matched to each OID case. Prescription files of all subjects were queried for statin use. Information on selected comorbid medical conditions was also obtained. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of OID development in the context of statin use, controlling for comorbid conditions.

Results
Ninety-two incident cases of OID were identified. A trend toward a reduction in the risk of new OID development was found in patients that used statins compared to those that did not (OR 0.50, 95% CI 0.20 to 1.23, p = 0.13). The longer the duration of statin use, the greater is the effect.

Conclusions
Use of oral statins may be associated with a reduced risk for the development of OID. This reduced risk increases with increasing duration of use. Larger clinical studies would be required to definitively establish the effectiveness of statins in lowering the incidence of OID.
PDLIM2 restricts Th1 and Th17 differentiation and prevents autoimmune disease
Authors: Qu Zhaoxia , Fu Jing , Ma Huihui , Zhou Jingjiao , Jin Meihua , Mapara Markus Y , Grusby Michael J , Xiao Gutian 
Published: January 2013

Abstract

Background
PDLIM2 is essential for the termination of the inflammatory transcription factors NF-κB and STAT but is dispensable for the development of immune cells and immune tissues/organs. Currently, it remains unknown whether and how PDLIM2 is involved in physiologic and pathogenic processes.

Results
Here we report that naive PDLIM2 deficient CD4+ T cells were prone to differentiate into Th1 and Th17 cells. PDLIM2 deficiency, however, had no obvious effect on lineage commitment towards Th2 or Treg cells. Notably, PDLIM2 deficient mice exhibited increased susceptibility to experimental autoimmune encephalitis (EAE), a Th1 and/or Th17 cell-mediated inflammatory disease model of multiple sclerosis (MS). Mechanistic studies further indicate that PDLIM2 was required for restricting expression of Th1 and Th17 cytokines, which was in accordance with the role of PDLIM2 in the termination of NF-κB and STAT activation.

Conclusion
These findings suggest that PDLIM2 is a key modulator of T-cell-mediated immune responses that may be targeted for the therapy of human autoimmune diseases.
Glibenclamide inhibits cell growth by inducing G0/G1 arrest in the human breast cancer cell line MDA-MB-231
Authors: Núñez Mariel , Medina Vanina , Cricco Graciela , Croci Máximo , Cocca Claudia , Rivera Elena , Bergoc Rosa , Martín Gabriela 
Published: January 2013

Abstract

Background
Glibenclamide (Gli) binds to the sulphonylurea receptor (SUR) that is a regulatory subunit of ATP-sensitive potassium channels (KATP channels). Binding of Gli to SUR produces the closure of KATP channels and the inhibition of their activity. This drug is widely used for treatment of type 2-diabetes and it has been signaled as antiproliferative in several tumor cell lines. In previous experiments we demonstrated the antitumoral effect of Gli in mammary tumors induced in rats. The aim of the present work was to investigate the effect of Gli on MDA-MB-231 breast cancer cell proliferation and to examine the possible pathways involved in this action.

Results
The mRNA expression of the different subunits that compose the KATP channels was evaluated in MDA-MB-231 cells by reverse transcriptase-polymerase chain reaction. Results showed the expression of mRNA for both pore-forming isoforms Kir6.1 and Kir6.2 and for the regulatory isoform SUR2B in this cell line. Gli inhibited cell proliferation assessed by a clonogenic method in a dose dependent manner, with an increment in the population doubling time. The KATP channel opener minoxidil increased clonogenic proliferation, effect that was counteracted by Gli. When cell cycle analysis was performed by flow cytometry, Gli induced a significant cell-cycle arrest in G0/G1 phase, together with an up-regulation of p27 levels and a diminution in cyclin E expression, both evaluated by immunoblot. However, neither differentiation evaluated by neutral lipid accumulation nor apoptosis assessed by different methodologies were detected. The cytostatic, non toxic effect on cell proliferation was confirmed by removal of the drug.
Combination treatment of Gli with tamoxifen or doxorubicin showed an increment in the antiproliferative effect only for doxorubicin.

Conclusions
Our data clearly demonstrated a cytostatic effect of Gli in MDA-MB-231 cells that may be mediated through KATP channels, associated to the inhibition of the G1-S phase progression. In addition, an interesting observation about the effect of the combination of Gli with doxorubicin leads to future research for a potential novel role for Gli as an adjuvant in breast cancer treatment
Mitigation of salt stress in wheat seedlings by halotolerant bacteria isolated from saline habitats
Authors: Ramadoss Dhanushkodi , Lakkineni Vithal K , Bose Pranita , Ali Sajad , Annapurna Kannepalli 
Published: January 2013

Abstract
Eighty four halotolerant bacterial strains were isolated from the saline habitats and screened for growth at different NaCl concentrations. All grew well at 5% NaCl, but only 25% isolates showed growth at 20% NaCl concentration. Five strains SL3, SL32, SL35, J8W and PU62 growing well in 20% NaCl concentrations were further characterized for multiple plant growth promoting traits such as indole −3- acetic acid (IAA) production, HCN and siderophore production, ACC deaminase activity and P-solubilization. None were positive for HCN production and PCR amplification of acd S, the structural gene for ACC deaminase enzyme was found negative. 16S rRNA gene sequencing analysis of the five strains showed them to belong to two genera Bacillus and Hallobacillus. In vitro experiments showed that salt concentrations had significant inhibitory effects on development of seedlings but not on the growth of the bacterial strains. Inoculation of the 5 halotolerant bacterial strains to ameliorate salt stress (80 mM, 160 mM and 320 mM) in wheat seedlings produced an increase in root length of 71.7% in comparison with uninoculated positive controls. In particular, Hallobacillus sp. SL3 and Bacillus halodenitrificans PU62 showed more than 90% increase in root elongation and 17.4% increase in dry weight when compared to uninoculated wheat seedlings at 320 mM NaCl stress indicating a significant reduction of the deleterious effects of NaCl. These results indicate that halotolerant bacteria isolated from saline environments have potential to enhance plant growth under saline stress through direct or indirect mechanisms and would be most appropriate as bioinoculants under such conditions.
Identification and bioactive potential of endophytic fungi isolated from selected plants of the Western Himalayas
Authors: Qadri Masroor , Johri Sarojini , Shah Bhahwal A , Khajuria Anamika , Sidiq Tabasum , Lattoo Surrinder K , Abdin Malik Z , Riyaz-Ul-Hassan Syed 
Published: January 2013

Abstract
This study was conducted to characterize and explore the endophytic fungi of selected plants from the Western Himalayas for their bioactive potential. A total of 72 strains of endophytic fungi were isolated and characterized morphologically as well as on the basis of ITS1-5.8S-ITS2 ribosomal gene sequence acquisition and analyses. The fungi represented 27 genera of which two belonged to Basidiomycota, each representing a single isolate, while the rest of the isolates comprised of Ascomycetous fungi. Among the isolated strains, ten isolates could not be assigned to a genus as they displayed a maximum sequence similarity of 95% or less with taxonomically characterized organisms. Among the host plants, the conifers, Cedrus deodara, Pinus roxburgii and Abies pindrow harbored the most diverse fungi, belonging to 13 different genera, which represented almost half of the total genera isolated. Several extracts prepared from the fermented broth of these fungi demonstrated strong bioactivity against E. coli and S. aureus with the lowest IC50 of 18 μg/ml obtained with the extract of Trichophaea abundans inhabiting Pinus sp. In comparison, extracts from only three endophytes were significantly inhibitory to Candida albicans, an important fungal pathogen. Further, 24 endophytes inhibited three or more phytopathogens by at least 50% in co-culture, among a panel of seven test organisms. Extracts from 17 fungi possessed immuno-modulatory activities with five of them showing significant immune suppression as demonstrated by the in vitro lymphocyte proliferation assay. This study is an important step towards tapping the endophytic fungal diversity from the Western Himalayas and assessing their bioactive potential. Further studies on the selected endophytes may lead to the isolation of novel natural products for use in medicine, industry and agriculture.