bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protease-Activated Receptor 2 Deficiency Reduces Cardiac Ischemia/Reperfusion Injury
Authors: Antoniak Silvio , Rojas Mauricio , Spring Denise , Bullard Tara A. , Verrier Edward D. , Blaxall Burns C. , Mackman Nigel , Pawlinski Rafal 
Published: August 2010

Objective—To investigate the effect of protease-activated receptor (PAR) 2 deficiency on ischemia/reperfusion (I/R) injury–induced infarct size, inflammation, heart remodeling, and cardiac function.Methods and Results—PAR-2 signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac I/R injury is unknown. PAR-2−/−mice and wild-type littermates were subjected to 30 minutes of ischemia and up to 4 weeks of reperfusion. Infarct size, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinases, and inflammatory gene expression were assessed 2 hours after reperfusion. Changes in heart size and function were measured by echocardiography up to 4 weeks after reperfusion. Infarct size was significantly reduced in hearts of PAR-2−/−mice compared with wild-type littermates. In addition, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinase, and expression of proinflammatory genes were significantly attenuated in injured hearts of PAR-2−/−mice. Finally, PAR-2−/−mice were protected from postinfarction remodeling and showed less impairment in heart function compared with wild-type littermates up to 4 weeks after I/R injury.Conclusion—PAR-2 deficiency reduces myocardial infarction and heart remodeling after I/R injury.
Upregulation of Nox4 by TGFβ1 Oxidizes SERCA and Inhibits NO in Arterial Smooth Muscle of the Prediabetic Zucker Rat
Authors: Tong XiaoYong , Hou Xiuyun , Jourd'heuil David , Weisbrod Robert M. , Cohen Richard A. 
Published: August 2010

Rationale:Vascular smooth muscle cell (SMC) migration is an important pathological process in several vascular occlusive diseases, including atherosclerosis and restenosis, both of which are accelerated by diabetes mellitus.Objective:To determine the mechanisms of abnormal vascular SMC migration in type 2 diabetes, the obese Zucker rat (ZO), a model of obesity and insulin resistance, was studied.Methods and Results:In culture, ZO aortic SMCs showed a significant increase in Nox4 mRNA and protein levels compared with the control lean Zucker rat (ZL). The sarco-/endoplasmic reticulum Ca2+ATPase (SERCA) nitrotyrosine-294,295 and cysteine-674 (C674)-SO3H were increased in ZO SMCs, indicating oxidant stress. Unlike ZL SMC, nitric oxide (NO) failed to inhibit serum-induced SMC migration in ZO. Transfection of Nox4 small interference RNA or overexpression of SERCA2b wild type, but not C674S mutant SERCA, restored the response to NO. Knockdown of Nox4 also decreased SERCA oxidation in ZO SMCs. In addition, transforming growth factor-β1 via Smad2 was necessary and sufficient to upregulate Nox4, oxidize SERCA, and block the antimigratory action of NO in ZO SMCs. Corresponding to the results in cultured SMCs, immunohistochemistry confirmed that Nox4 and SERCA C674-SO3H were significantly increased in ZO aorta. After common carotid artery injury, knockdown of Nox4 by adenoviral Nox4 short hairpin RNA decreased Nox4 and SERCA C674-SO3H staining and significantly decreased injury-induced neointima.Conclusion:These studies indicate that the upregulation of Nox4 by transforming growth factor-β1 in ZO SMCs is responsible for the impaired response to NO by a mechanism involving the oxidation of SERCA C674. Knockdown of Nox4 inhibits oxidation of SERCA, as well as neointima formation, after ZO common carotid artery injury.
Cartilage Intermediate Layer Protein Gene is Associated with Lumbar Disc Degeneration in Male, but Not Female, Collegiate Athletes
Authors: Min Seok-Ki , Nakazato Koichi , Yamamoto Yosuke , Gushiken Koji , Fujimoto Hideo , Fujishiro Hitone , Kobayakawa Yuri , Hiranuma Kenji 
Published: August 2010

Background The authors previously identified a significant association between lumbar disc degeneration (LDDG) and cartilage intermediate layer protein (CILP) single nucleotide polymorphism (SNP) in collegiate male judokas. Hypothesis A significant association between LDDG and the CILP SNP is observed in Japanese collegiate athletes. Study Design Cross-sectional study; Level of evidence, 3. Methods The participants were 601 trained collegiate athletes (male, 403; female, 198) from 7 different sports. Lumbar disc degeneration was evaluated using T2-weighted magnetic resonance imaging. Genotyping of the CILP gene (1184T/C) was performed by using DNA sequencing. Results Among the 601 collegiate athletes, the odds ratio (OR) for the occurrence of LDDG with the CILP C allele was 1.4 (95% confidence interval [CI], 1.05-1.86). By using logistic regression analysis concomitant with the interaction term and the Wald test, the authors found that weight (OR, 1.04; 95% CI, 1.02-1.06), CILP genotype (CT: OR, 2.0; 95% CI, 1.24-3.15; CC: OR, 2.9; 95% CI, 1.09-7.74), and gender (OR, 2.1; 95% CI, 1.21-3.67) were significant risk factors for LDDG. These analyses also indicated that there was no effect of the CILP genotype on LDDG in female athletes. Conclusion The CILP SNP 1184T/C is a risk factor for male collegiate athletes. Information regarding the CILP gene polymorphism may be important for preventing and managing lumbar disc diseases, especially in male athletes.
Time to Ditch AD-AS?
Authors: Grieve Roy H. 
Published: August 2010

Complementing previous, often ignored criticism of the AD-AS model - to the effect that this widely-used construction is inherently inconsistent - this note argues that a (rare) defence of the model by Peter Kennedy fails to convince and that the model does indeed, as alleged, give rise to confusing and misleading expositions of the working of the macroeconomy. JEL classification: A22, B22, E10.
Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1α dependent pathway
Authors: Fu Hua , Luo Fengming , Yang Li , Wu Wenchao , Liu Xiaojing 
Published: August 2010

Abstract

Background
Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time.

Results
Expression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs.

Conclusion
Our results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1α activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1α mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation.
Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation
Authors: Bouchard Maxime , de Caprona Dominique , Busslinger Meinrad , Xu Pinxian , Fritzsch Bernd 
Published: August 2010

AbstractBackgroundPax2;5;8transcription factors play diverse roles in vertebrate and invertebrate organogenesis, including the development of the inner ear. Past research has suggested various cochlear defects and some vestibular defects inPax2null mice but the details of the cochlear defects and the interaction with otherPaxfamily members in ear development remain unclear.ResultsWe show thatPax2;8double null mice do not develop an ear past the otocyst stage and show little to no sensory as well as limited and transient neuronal development, thus indicating that these two family members are essential for overall ear morphogenesis and sustained neurosensory development. In support of functional redundancy between Pax proteins,Pax2can be substituted by aPax5minigene, a gene normally not expressed in the embryonic mouse ear. There is no detectable morphological defect inPax8null mice suggesting thatPax2expression can compensate forPax8. Conversely,Pax8cannot compensate forPax2leading to a cochlear phenotype not fully appreciated previously: Cochlear development is delayed until E15.5 when the cochlea extrudes as a large sack into the brain case. Immunocytochemistry and tracing from the brain show that a cochlear spiral ganglia form as a small addition to the inferior vestibular ganglion. However, the empty cochlear sack, devoid of any sensory epithelium development as indicated by the absence of Sox2 or MyoVII expression, nevertheless develop a dense innervation network of small neurons situated in the wall of the cochlear sack.ConclusionsCombined these data suggest thatPax2is needed for organ of Corti formation and is directly or indirectly involved in the coordination of spiral ganglion formation which is partially disrupted in thePax2null ears. All threePaxgenes can signal redundantly in the ear with their function being determined primarily by the spatio-temporal expression driven by the three distinct promoters of these genes.
Characterisation of the Vitis viniferaPR10 multigene family
Authors: Lebel Sylvain , Schellenbaum Paul , Walter Bernard , Maillot Pascale 
Published: August 2010

Abstract

Background
Genes belonging to the pathogenesis related 10 (PR10) group have been studied in several plant species, where they form multigene families. Until now, such an analysis has not been performed in Vitis vinifera, although three different PR10 genes were found to be expressed under pathogen attack or abiotic stress, and during somatic embryogenesis induction. We used the complete genome sequence for characterising the whole V. vinifera PR10 gene family. The expression of candidate genes was studied in various non-treated tissues and following somatic embryogenesis induction by the auxin 2,4-D.

Results
In addition to the three V. vinifera PR10 genes already described, namely VvPR10.1, VvPR10.2 and VvPR10.3, fourteen different PR10 related sequences were identified. Showing high similarity, they form a single cluster on the chromosome 5 comprising three pseudogenes. The expression of nine different genes was detected in various tissues. Although differentially expressed in non-treated plant organs, several genes were up-regulated in tissues treated with 2,4-D, as expected for PR genes.

Conclusions

PR10 genes form a multigene family in V. vinifera, as found in birch, apple or peach. Seventeen closely related PR10 sequences are arranged in a tandem array on the chromosome 5, probably reflecting small-scale duplications during evolution. Various expression patterns were found for nine studied genes, highlighting functional diversification. A phylogenetic comparison of deduced proteins with PR10 proteins of other plants showed a characteristic low intraspecific variability. Particularly, a group of seven close tandem duplicates including VvPR10.1, VvPR10.2 and VvPR10.3 showed a very high similarity, suggesting concerted evolution or/and recent duplications.
The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats
Authors: Chang Ting-Kuo , Huang Chang-Hung , Huang Chun-Hsiung , Chen Hsuan-Chiang , Cheng Cheng-Kung 
Published: August 2010

Abstract

Background
Loss of bone quality and deterioration of articular cartilage are commonly seen after menopause. While exercise may protect against tissue degeneration, a clear link has yet to be established. The aim of the present study is to investigate the influence of long-term treadmill exercise on changes in bone mass and articular cartilage in ovariectomized rats.

Methods
Sixty female Sprague-Dawley rats were randomly assigned to 4 groups: ovariectomized (OVX), ovariectomized plus treadmill exercise (OVX-RUN), treadmill exercise alone (RUN), and control (CON) groups. After 36 weeks, the following variables were compared among the 4 groups. Bone mass was evaluated by trabecular bone volume and bone mineral density (BMD). Articular cartilage in the knee joints was evaluated by histology analysis and a modified Mankin score.

Results
Rats in the ovariectomized groups (OVX and OVX-RUN) had significantly lower BMD and bone mass than the non-ovariectomized rats (CON and RUN), indicating that exercise did little to preserve bone mass. However, the sedentary OVX group had a significantly worse modified Mankin score (7.7 ± 1.4) than the OVX-RUN group (4.8 ± 1.0), whose scores did not differ significantly from the other 2 non-operated groups. The articular cartilage in the sedentary OVX rats was relatively thinner, hypocellular, and had more clefts than in the other 3 groups.

Conclusion
This study suggests that long-term exercise protects articular cartilage in OVX rats but does not retard the loss of bone mass seen in after menopause.
Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment
Authors: Huas Dominique , Debiais Françoise , Blotman Francis , Cortet Bernard , Mercier Florence , Rousseaux Chantal , Berger Véronique , Gaudin Anne-Françoise , Cotté François-Emery 
Published: August 2010

Abstract

Background
Adherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance.

Methods
This was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis.

Results
785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life.

Conclusion
Compliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.
Factors affecting costs and utilization of type 2 diabetes healthcare: a cross-sectional survey among 15 hospitals in urban China
Authors: Wang Weibing , Fu Chaowei , Zhuo Haijing , Luo Jianfeng , Xu Biao 
Published: August 2010

Abstract

Background
Type 2 Diabetes mellitus (T2DM) affects persons of all ages, while also placing heavy economic burdens on national economies and healthcare systems. The study aims to investigate the determinants of direct medical cost (DMC), out-of-pocket (OOP) proportion of the cost, and healthcare utilization associated with T2DM.

Methods
This cross-sectional study was conducted in four major cities in China. Eligible subjects were adult outpatients who received treatment at one of 15 sampled secondary or tertiary hospitals and consecutively enrolled between March 2007 and May 2007. Generalized estimating equations were used to determine impact factors associated with DMC and healthcare utilization.

Results
Insurance schemes and receiving insulin therapy were significantly associated with a higher annual DMC of T2DM. For each increase in number of complications, there was about 33% increase in annual DMC. Insurance schemes were significantly associated with the proportions of DMC from pocket. A 7% significantly lower proportion of DMC was paid and 23% more clinic visits (AOR = 1.232, P < 0.001) were made by patients admitted at secondary hospitals than tertiary hospitals. The group with higher income (> 2000 CNY/month) paid 23% less from their pocket, compared with the lower income group. The number of complications also significantly increased the outpatient visits (AOR = 1.064, P < 0.001).

Conclusions
It implies that preventing complications through the use of more effective treatment regimens is important in order to control the healthcare expenditures of the diseases. Healthcare reform needs to be focused on the medical insurance system and redistribution of patients in hospitals of different levels.
Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent
Authors: Puliyappadamba Vineshkumar T , Cheriyan Vino T , Thulasidasan Arun Kumar T , Bava Smitha V , Vinod Balachandran S , Prabhu Priya R , Varghese Ranji , Bevin Arathy , Venugopal Shalini , Anto Ruby John 
Published: August 2010

Abstract

Background
Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell proliferation and angiogenesis. We observed that the proliferative index of nicotine is different in the lung cancer cell lines H1299 (p53-/-) and A549 (p53+/+) which indicates that the mode of up-regulation of survival signals by nicotine might be different in cells with and without p53.

Results
While low concentrations of nicotine induced activation of NF-κB, Akt, Bcl2, MAPKs, AP1 and IAPs in H1299, it failed to induce NF-κB in A549, and compared to H1299, almost 100 times higher concentration of nicotine was required to induce all other survival signals in A549. Transfection of WT-p53 and DN-p53 in H1299 and A549 respectively, reversed the mode of activation of survival signals. Curcumin down-regulated all the survival signals induced by nicotine in both the cells, irrespective of their p53 status. The hypothesis was confirmed when lower concentrations of nicotine induced NF-κB in two more lung cancer cells, Hop-92 and NCI-H522 with mutant p53 status. Silencing of p53 in A549 using siRNA made the cells susceptible to nicotine-induced NF-κB nuclear translocation as in A549 DN-p53 cells.

Conclusions
The present study reveals a detrimental role of nicotine especially in lung cancer patients with impaired p53 status and identifies curcumin as a potential chemopreventive.
Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke
Authors: Sun Chongran , Zhang Han , Li Jin , Huang Hua , Cheng Hongbin , Wang Yajie , Li Ping , An Yihua 
Published: August 2010

Abstract

Background
The relationship between functional improvements in ischemic rats given a neural stem cell (NSC) transplant and the modulation of the class I major histocompatibility complex (MHC) mediated by NSC-derived neurotrophins was investigated.

Methods
The levels of gene expression of nerve growth factor (NGF), brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) were assayed from cultures of cortical NSC from Sprague-Dawley rat E16 embryos. The levels of translated NGF in spent culture media from NSC cultures and the cerebral spinal fluid (CSF) of rats with and without NGF injection or NSC transplant were also measured.

Results
We found a significant increase of NGF, BDNF and NT-3 transcripts and NGF proteins in both the NSC cultures and the CSF of the rats. The immunochemical staining for MHC in brain sections and the enzyme-linked immunosorbent assay of CSF were carried out in sham-operated rats and rats with surgically induced focal cerebral ischemia. These groups were further divided into animals that did and did not receive NGF administration or NSC transplant into the cisterna magna. Our results show an up-regulation of class I MHC in the ischemic rats with NGF and NSC administration. The extent of caspase-III immunoreactivity was comparable among three arms in the ischemic rats.

Conclusion
Readouts of somatosensory evoked potential and the trap channel test illustrated improvements in the neurological function of ischemic rats treated with NGF administration and NSC transplant.
A 176 amino acid polypeptide derived from the mumps virus HN ectodomain shows immunological and biological properties similar to the HN protein
Authors: Herrera Emma , Barcenas Patricia , Hernández Rubicela , Méndez Alfonso , Pérez-Ishiwara Guillermo , Barrón Blanca 
Published: August 2010

Abstract

Background
The hemagglutinin-neuraminidase (HN) protein is the major antigenic determinant of the Mumps virus (MuV) and plays an important role in the viral infectious cycle through its hemagglutination/hemadsorption (HA/HD) and neuraminidase (NA) activities. Objective: analyze the biological and immunological properties of a polypeptide derived from a highly conserved region of the HN ectodomain. Methods: a highly conserved region of the HN gene among several MuV genotypes was chosen to be cloned in a eukaryotic expression vector. The pcDNAHN176-construct was transfected into Vero cells and RNA expression was detected by RT-PCR, while the corresponding polypeptide was detected by immunofluorescence and immunochemistry techniques. The HD and NA activities were also measured. The immunogenic properties of the construct were evaluated using two systems: rabbit immunization to obtain sera for detection of the HN protein and neutralization of MuV infection, and hamster immunization to evaluate protection against MuV infection.

Results
A 567 nucleotide region from the HN gene was amplified and cloned into the plasmid pcDNA3.1. Vero cells transfected with the construct expressed a polypeptide that was recognized by a MuV-hyperimmune serum. The construct-transfected cells showed HD and NA activities. Sera from immunized rabbits in vitro neutralized two different MuV genotypes and also detected both the HN protein and the HN176 polypeptide by western blot. Hamsters immunized with the pcDNAHN176-construct and challenged with MuV showed a mild viral infection in comparison to non-immunized animals, and Th1 and Th2 cytokines were detected in them.

Conclusions
The pcDNAHN176-construct was capable of expressing a polypeptide in Vero cells that was identified by a hyperimmune serum anti Mumps virus, and these cells showed the HD and NA activities of the complete MuV HN protein. The construct also elicited a specific immune response against MuV infection in hamsters.