bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: a one-year follow-up study
Authors: An Xuanqi , Yu Dong , Zhang Ruiyan , Zhu Jinzhou , Du Run , Shi Yuhang , Xiong Xiaowei 
Published: June 2012

Abstract

Background
The aim of our study was to explore and evaluate the relationship between insulin resistance and progression of coronary atherosclerotic plaques. With the great burden coronary heart disease is imposing on individuals, healthcare professionals have already embarked on determining its potential modifiable risk factors in the light of preventive medicine. Insulin resistance has been generally recognized as a novel risk factor based on epidemiological studies; however, few researches have focused on its effect on coronary atherosclerotic plaque progression.

Methods
From June 7, 2007 to December 30, 2011, 366 patients received their index coronary angiogram and were subsequently found to have coronary atherosclerotic plaques or normal angiograms were consecutively enrolled in the study by the department of cardiology at the Ruijin Hospital, which is affiliated to the Shanghai Jiaotong University School of Medicine. All patients had follow-up angiograms after the 1-year period for evaluating the progression of the coronary lesions. The modified Gensini score was adopted for assessing coronary lesions while the HOMA-IR method was utilized for determining the state of their insulin resistance. Baseline characteristics and laboratory test results were described and the binomial regression analysis was conducted to investigate the relationship between insulin resistance and coronary atherosclerotic plaque progression.

Results
Index and follow-up Gensini scores were similar between the higher insulin lower insulin resistant groups (9.09 ± 14.33 vs 9.44 ± 12.88, p = 0.813 and 17.21 ± 18.46 vs 14.09 ± 14.18, p =0.358). However the Gensini score assessing coronary lesion progression between both visits was significantly elevated in the higher insulin resistant group (8.13 ± 11.83 versus 4.65 ± 7.58, p = 0.019). Multivariate logistic binomial regression analysis revealed that insulin resistance (HOMA-IR > 3.4583) was an independent predictor for coronary arterial plaque progression (OR = 4.969, p = 0.011). We also divided all the participants into a diabetic (n = 136) and a non-diabetic group (n = 230), and HOMA-IR remained an independent predictor for atherosclerosis plaque progression.

Conclusions
Insulin resistance is an independent predictor of atherosclerosis plaque progression in patients with coronary heart disease in both the diabetic and non-diabetic population.
Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells
Authors: Aragonès Gemma , Saavedra Paula , Heras Mercedes , Cabré Anna , Girona Josefa , Masana Lluís 
Published: June 2012

Abstract

Background
Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro.

Methods
In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt).

Results
We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production.

Conclusion
These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
Engineering of daidzein 3’-hydroxylase P450 enzyme into catalytically self-sufficient cytochrome P450
Authors: Choi Kwon-Young , Jung EunOk , Jung Da-Hye , An Byeo-Ri , Pandey Bishnu Prasad , Yun Hyungdon , Sung Changmin , Park Hyung-Yeon , Kim Byung-Gee 
Published: June 2012

AbstractA cytochrome P450 (CYP) enzyme, 3’-daidzein hydroxylase, CYP105D7 (3’-DH), responsible for daidzein hydroxylation at the 3’-position, was recently reported. CYP105D7 (3’-DH) is a class I type of CYP that requires electrons provided through electron transfer proteins such as ferredoxin and ferredoxin reductase. Presently, we constructed an artificial CYP in order to develop a reaction host for the production of a hydroxylated product. Fusion-mediated construction with the reductase domain from self-sufficient CYP102D1 was done to increase electron transfer efficiency and coupling with the oxidative process. An artificial self-sufficient daidzein hydroxylase (3’-ASDH) displayed distinct spectral properties of both flavoprotein and CYP. The fusion enzyme catalyzed hydroxylation of daidzein more efficiently, with akcat/Kmvalue of 16.8 μM-1 min-1, which was about 24-fold higher than that of the 3’-DH-camA/B reconstituted enzyme. Finally, a recombinantStreptomyces avermitilishost for the expression of 3’-ASDH and production of the hydroxylated product was developed. The conversion that was attained (34.6%) was 5.2-fold higher than that of the wild-type.
Expression of osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor-related apoptosis-inducing ligand, stromal cell-derived factor-1 and their receptors in epithelial metastatic breast cancer cell lines
Authors: Labovsky Vivian , Vallone Valeria B Fernández , Martinez Leandro M , Otaegui Julian , Chasseing Norma A 
Published: June 2012

AbstractBackgroundWhile breast cancer (BC) is the major cause of death among women worldwide, there is no guarantee of better patient survival because many of these patients develop primarily metastases, despite efforts to detect it in its early stages. Bone metastasis is a common complication that occurs in 65-80 % of patients with disseminated disease, but the molecular basis underlyingdormancy,dissemination and establishment of metastasis is not understood. Our objective has been to evaluate simultaneously osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), stromal cell-derived factor-1 (SDF-1), and their receptors (R) in 2 human BC cell lines, MDA-MB-231 and MCF-7.MethodsOPG, RANKL, TRAIL and SDF-1 expression and release, in addition to the expression of their receptors has been investigated using immunofluorescence, immunocytochemistry and ELISA analyses.ResultsMCF-7 cells released higher levels of OPG in conditioned media (CM) than MDA-MB-231 cells; 100 % of both types of cell expressed OPG, RANKL, TRAIL and SDF-1. Moreover, 100 % in both lines expressed membrane RANKL and RANK, whereas only 50 % expressed CXCR4. Furthermore, 100 % expressed TRAIL-R1 and R4, 30-50 % TRAIL-R2, and 40-55 % TRAIL-R3.ConclusionsMCF-7 and MDA-MB-231 cells not only released OPG, but expressed RANKL, TRAIL and SDF-1. The majority of the cells also expressed RANK, CXCR4 and TRAIL-R. Since these ligands and their receptors are implicated in the regulation of proliferation, survival, migration and future bone metastasis during breast tumor progression, assessment of these molecules in tumor biopsies of BC patients could be useful in identifying patients with more aggressive tumors that are also at risk of bone metastasis, which may thus improve the available options for therapeutic intervention.
Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
Authors: Stanislaus Anthony , Bakhtiar Athirah , Salleh Diyana , Tiash Snigdha , Fatemian Tahereh , Hossain Sharif , Akaike Toshihiro , Chowdhury Ezharul Hoque 
Published: June 2012

Abstract

Background
RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression.

Results
Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs.

Conclusion
Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.
Gene expression changes as markers of early lapatinib response in a panel of breast cancer cell lines
Authors: O’Neill Fiona , Madden Stephen F , Aherne Sinead T , Clynes Martin , Crown John , Doolan Padraig , O’Connor Robert 
Published: June 2012

Abstract

Background
Lapatinib, a tyrosine kinase inhibitor of HER2 and EGFR and is approved, in combination with capecitabine, for the treatment of trastuzumab-refractory metastatic breast cancer. In order to establish a possible gene expression response to lapatinib, a panel of breast cancer cell lines with varying sensitivity to lapatinib were analysed using a combination of microarray and qPCR profiling.

Methods
Co-inertia analysis (CIA), a data integration technique, was used to identify transcription factors associated with the lapatinib response on a previously published dataset of 96 microarrays. RNA was extracted from BT474, SKBR3, EFM192A, HCC1954, MDAMB453 and MDAMB231 breast cancer cell lines displaying a range of lapatinib sensitivities and HER2 expression treated with 1 μM of lapatinib for 12 hours and quantified using Taqman RT-PCR. A fold change ≥ ± 2 was considered significant.

Results
A list of 421 differentially-expressed genes and 8 transcription factors (TFs) whose potential regulatory impact was inferred in silico, were identified as associated with lapatinib response. From this group, a panel of 27 genes (including the 8 TFs) were selected for qPCR validation. 5 genes were determined to be significantly differentially expressed following the 12 hr treatment of 1 μM lapatinib across all six cell lines. Furthermore, the expression of 4 of these genes (RB1CC1, FOXO3A, NR3C1 and ERBB3) was directly correlated with the degree of sensitivity of the cell line to lapatinib and their expression was observed to “switch” from up-regulated to down-regulated when the cell lines were arranged in a lapatinib-sensitive to insensitive order. These included the novel lapatinib response-associated genes RB1CC1 and NR3C1. Additionally, Cyclin D1 (CCND1), a common regulator of the other four proteins, was also demonstrated to observe a proportional response to lapatinib exposure.

Conclusions
A panel of 5 genes were determined to be differentially expressed in response to lapatinib at the 12 hour time point examined. The expression of these 5 genes correlated directly with lapatinib sensitivity. We propose that the gene expression profile may represent both an early measure of the likelihood of sensitivity and the level of response to lapatinib and may therefore have application in early response detection.
Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach
Authors: Perluigi Marzia , Di Domenico Fabio , Blarzino Carla , Foppoli Cesira , Cini Chiara , Giorgi Alessandra , Grillo Caterina , De Marco Federico , Butterfield David A , Schininà Maria E , Coccia Raffaella 
Published: June 2012

AbstractBackgroundThe UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.ResultsThe expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.ConclusionsDespite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.
Physicians’ attitudes towards office-based delivery of methadone maintenance therapy: results from a cross-sectional survey of Nova Scotia primary-care physicians
Authors: Dooley Jessica , Asbridge Mark , Fraser John , Kirkland Susan 
Published: June 2012

Abstract

Background
Approximately 90,000 Canadians use opioids each year, many of whom experience health and social problems that affect the individual user, families, communities and the health care system. For those who wish to reduce or stop their opioid use, methadone maintenance therapy (MMT) is effective and supporting evidence is well-documented. However, access and availability to MMT is often inconsistent, with greater inequity outside of urban settings. Involving community based primary-care physicians in the delivery of MMT could serve to expand capacity and accessibility of MMT programs. Little is known, however, about the extent to which MMT, particularly office-based delivery, is acceptable to physicians. The aim of this study is to survey physicians about their attitudes towards MMT, particularly office-based delivery, and the perceived barriers and facilitators to MMT delivery.

Methods
In May 2008, facilitated by the College of Physicians and Surgeons of Nova Scotia, a cross-sectional, e-mail survey of 950 primary-care physicians practicing in Nova Scotia, Canada was administered via the OPINIO on-line survey software, to assess the acceptability of office-based MMT. Logistic regressions, adjusted for physician sociodemographic characteristics, were used to examine the association between physicians’ willingness to participate in office-based MMT, and a series of measures capturing physician attitudes and knowledge about treatment approaches, opioid use, and methadone, as well as perceived barriers to MMT.

Results
Overall, 19.8% of primary-care physicians responded to the survey, with 56% who indicated that they would be willing to be involved in MMT under current or similar circumstances; however, willingness was associated with numerous attitudinal and systemic factors. The barriers to involvement in MMT that were frequently cited included a lack of training or experience in MMT, lack of support services, and potential challenges of working with an MMT patient population.

Conclusions
Study findings provide valuable information to help facilitate greater involvement of primary-care physicians in MMT, while highlighting concerns around administration, support, and training. Even limited uptake by primary-care physicians would greatly enhance MMT access in Nova Scotia, particularly for methadone clients located in rural communities. These findings are applicable broadly, to any jurisdictions where office-based MMT is not currently available.
An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery
Authors: Lee Ni-Chung , Falk Darin J , Byrne Barry J , Conlon Thomas J , Clement Nathalie , Porvasnik Stacy , Jorgensen Marda L , Potter Mark , Erger Kirsten E , Watson Rachael , Ghivizzani Steven C , Chiu Hung-Chuan , Chien Yin-Hsiu , Hwu Wuh-Liang 
Published: June 2012

Abstract

Background
The appropriate tropism of adeno-associated virus (AAV) vectors that are systemically injected is crucial for successful gene therapy when local injection is not practical. Acidic oligopeptides have been shown to enhance drug delivery to bones.

Methods
In this study six-L aspartic acids (D6) were inserted into the AAV2 capsid protein sequence between amino acid residues 587 and 588. 129SVE mice were injected with double-stranded wild-type- (WT-) or D6-AAV2 mCherry expression vectors (3.24 x 1010 vg per animal) via the superficial temporal vein within 24 hours of birth.

Results
Fluorescence microscopy and quantitative polymerase chain reaction confirmed higher levels of mCherry expression in the paraspinal and gluteus muscles in the D6-AAV2 injected mice. The results revealed that although D6-AAV2 was less efficient in the transduction of immortalized cells stronger mCherry signals were detected over the spine and pelvis by live imaging in the D6-AAV2-injected mice than were detected in the WT-AAV2-injected mice. In addition, D6-AAV2 lost the liver tropism observed for WT-AAV2.

Conclusions
An acidic oligopeptide displayed on AAV2 improves axial muscle tropism and decreases liver tropism after systemic delivery. This modification should be useful in creating AAV vectors that are suitable for gene therapy for diseases involving the proximal muscles.
Genomic characterization of explant tumorgraft models derived from fresh patient tumor tissue
Authors: Monsma David J , Monks Noel R , Cherba David M , Dylewski Dawna , Eugster Emily , Jahn Hailey , Srikanth Sujata , Scott Stephanie B , Richardson Patrick J , Everts Robin E , Ishkin Aleksandr , Nikolsky Yuri , Resau James H , Sigler Robert , Nickoloff Brian J , Webb Craig P 
Published: June 2012

AbstractBackgroundThere is resurgence within drug and biomarker development communities for the use of primary tumorgraft models as improved predictors of patient tumor response to novel therapeutic strategies. Despite perceived advantages over cell line derived xenograft models, there is limited data comparing the genotype and phenotype of tumorgrafts to the donor patient tumor, limiting the determination of molecular relevance of the tumorgraft model. This report directly compares the genomic characteristics of patient tumors and the derived tumorgraft models, including gene expression, and oncogenic mutation status.MethodsFresh tumor tissues from 182 cancer patients were implanted subcutaneously into immune-compromised mice for the development of primary patient tumorgraft models. Histological assessment was performed on both patient tumors and the resulting tumorgraft models. Somatic mutations in key oncogenes and gene expression levels of resulting tumorgrafts were compared to the matched patient tumors using the OncoCarta (Sequenom, San Diego, CA) and human gene microarray (Affymetrix, Santa Clara, CA) platforms respectively. The genomic stability of the established tumorgrafts was assessed across serialin vivogenerations in a representative subset of models. The genomes of patient tumors that formed tumorgrafts were compared to those that did not to identify the possible molecular basis to successful engraftment or rejection.ResultsFresh tumor tissues from 182 cancer patients were implanted into immune-compromised mice with forty-nine tumorgraft models that have been successfully established, exhibiting strong histological and genomic fidelity to the originating patient tumors. Comparison of the transcriptomes and oncogenic mutations between the tumorgrafts and the matched patient tumors were found to be stable across four tumorgraft generations. Not only did the various tumors retain the differentiation pattern, but supporting stromal elements were preserved. Those genes down-regulated specifically in tumorgrafts were enriched in biological pathways involved in host immune response, consistent with the immune deficiency status of the host. Patient tumors that successfully formed tumorgrafts were enriched for cell signaling, cell cycle, and cytoskeleton pathways and exhibited evidence of reduced immunogenicity.ConclusionsThe preservation of the patient’s tumor genomic profile and tumor microenvironment supports the view that primary patient tumorgrafts provide a relevant model to support the translation of new therapeutic strategies and personalized medicine approaches in oncology.
Overexpression of ribosome binding protein 1 (RRBP1) in breast cancer
Authors: Telikicherla Deepthi , Marimuthu Arivusudar , Kashyap Manoj Kumar , Ramachandra Y L , Mohan Sujatha , Roa Juan Carlos , Maharudraiah Jagadeesha , Pandey Akhilesh 
Published: June 2012

Abstract
The molecular events that lead to malignant transformation and subsequent metastasis of breast carcinoma include alterations in the cells at genome, transcriptome and proteome levels. In this study, we used publicly available gene expression databases to identify those candidate genes which are upregulated at the mRNA level in breast cancers but have not been systematically validated at the protein level. Based on an extensive literature search, we identified ribosome binding protein 1 (RRBP1) as a candidate that is upregulated at the mRNA level in five different studies but its protein expression had not been investigated. Immunohistochemical labeling of breast cancer tissue microarrays was carried out to determine the expression of RRBP1 in a large panel of breast cancers. We found that RRBP1 was overexpressed in 84% (177/219) of breast carcinoma cases tested. The subcellular localization of RRBP1 was mainly observed to be in the cytoplasm with intense staining in the perinuclear region. Our findings suggest that RRBP1 is an interesting molecule that can be further studied for its potential to serve as a breast cancer biomarker. This study also demonstrates how the integration of biological data from available resources in conjunction with systematic evaluation approaches can be successfully applied to clinical proteomics.
Stability and superstability of generalized quadratic ternary derivations on non-Archimedean ternary Banach algebras: a fixed point approach
Authors: Park Choonkil , Gordji Madjid Eshaghi , Cho Yeol Je 
Published: June 2012

Abstract
Using fixed point method, we prove the Hyers-Ulam stability and the superstability of generalized quadratic ternary derivations on non-Archimedean ternary Banach algebras. Indeed, we investigate the Hyers-Ulam stability and the superstability of the system of functional equations

f

(

[

a
b
c

]

)

=

f

(

a

)

b

2

c

2

+

a

2

f

(

b

)

c

2

+

a

2

b

2

f

(

c

)

;

g

(

[

a
b
c

]

)

=

g

(

a

)

b

2

c

2

+

[

a

2

f

(

b

)

c

2

]

+

[

a

2

b

2

f

(

c

)

]

;

g

(

u
x
+
v
y

)

+
g

(

u
x
-
v
y

)

=
2

u

2

g

(

x

)

+
2

v

2

g

(

y

)

;

f

(

u
x
+
v
y

)

+
f

(

u
x
-
v
y

)

=
2

u

2

f

(

x

)

+
2

v

2

f

(

y

)

in non-Archimedean ternary Banach algebras.

Mathematics Subject Classification 2010: Primary 39B52; 47H10; 39B72; 46L57; 17B40; 13N15; 17A40; 20N10.