bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute treatment with polyphenol quercetin improves postischemic recovery of isolated perfused rat hearts after global ischemia
Authors: Barteková Monika , Čarnická Slávka , Pancza Dezider , Ondrejčáková Mária , Breier Albert , Ravingerová Táňa 
Published: May 2010

Quercetin is a plant-derived bioflavonoid with potentially beneficial effects on the cardiovascular system. Studies focused on the efficiency of flavonoids against ischemia–reperfusion (I/R) injury have demonstrated that quercetin exerts robust protective effects in renal, cerebral, and hepatic I/R models. However, there is only limited evidence about the effect of quercetin on myocardial I/R injury. Therefore, the aim of the current study was to examine the effect of quercetin on isolated rat heart during ischemia and reperfusion. Rat hearts perfused according to Langendorff at 37 °C were examined during 25 min global ischemia followed by 120 min reperfusion. Quercetin (15 µmol/L) was administered either 15 min before ischemia (group Q1), or during the entire reperfusion period (group Q2). Changes in functional parameters of the hearts were measured during the initial 40 min of reperfusion. At the end of the experiment, the hearts were stained with tetrazolium to estimate the size of infarction (IS). Our study showed that quercetin improved postischemic recovery of functional parameters of isolated hearts in both treated groups. This improvement was manifested by significantly higher values of left ventricular developed pressure (LVDP) and the maximal rates of pressure development and fall (+(dP/dt)maxand –(dP/dt)max) and by significantly lower increase of end-diastolic pressure. Coronary flow was not significantly changed during reperfusion in the group treated before ischemia, but was significantly increased in the group treated during reperfusion. Quercetin also significantly reduced IS in both groups, more markedly in postischemically treated group. We conclude that acute quercetin treatment exerts significant positive effects on isolated hearts during I/R injury. These results are consistent with the beneficial effects of quercetin and other flavonoids on the cardiovascular system.
AN INTEGRATED MODEL FOR PROCESS SELECTION AND QUALITY IMPROVEMENT IN MULTI-STAGE PROCESSES
Authors: MUSTAJIB M. IMRON , IRIANTO DRADJAD 
Published: May 2010

All production processes produce variance around the desired target value of quality characteristic. This variance affects the product quality level. Accordingly variance reduction needs to be done as the main goal of quality improvement programs. However effort to improve quality of each product unit must take into account to improvement costs. This paper proposes an optimization model for quality improvement in multi-stage processes using a non linear programming model by selecting alternatives process and determining unit of production of each stage to maximize profit as the difference between total income and total relevant cost. Total cost includes manufacturing cost, quality loss cost, rework and scrap cost, and quality improvement implementation cost. This optimization model is implemented in make-to-order manufacturer that produces crimper (a parts of joining plastic packages in packaging machine) which consist of five main stage manufacturing processes. Sensitivity analysis shows that the optimal solution is not sensitive if little changes occur in the constraints scenario. Thus, adding the value constraint on the quality specification, stage capacity, and quality improvement budget will not improve the objective function.
CADASIL and migraine: A narrative review
Authors: Liem Michael K , Oberstein Saskia AJ Lesnik , van der Grond Jeroen , Ferrari Michel D , Haan Joost 
Published: May 2010

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown. Possible mechanisms of the excess of migraine with aura are an increased susceptibility to cortical spreading depression (CSD) or a different expression of CSD. It is also possible that the brainstem migraine area is involved in CADASIL. Last, it is possible that the NOTCH3 mutation acts as a migraine aura susceptibility gene by itself. In this narrative review we summarize the literature about migraine in CADASIL, with a special focus on what CADASIL might teach us about the pathophysiology of migraine.
Interictal pain in cluster headache
Authors: Marmura Michael J , Pello Scott J , Young William B 
Published: May 2010

Introduction: Cluster headache is characterized by severe attacks of unilateral pain, but many patients experience symptoms more commonly associated with migraine such as persistent pain. Patients and methods: We evaluated cluster headache patients using a questionnaire and chart review to determine clinical characteristics. Results: Twenty-four of 50 subjects reported interictal pain outside of their acute attacks. Sixteen reported persistent pain more than half the time while in cycle. Unlike acute attacks, this pain was generally mild. Conclusions: Subjects with persistent interictal pain were more likely to have chronic cluster, allodynia, and suboptimal response to sumatriptan, suggesting that interictal pain in cluster headache may predict a more severe disease process.
The leader intron of AtMHX can elicit, in the absence of splicing, low-level intron-mediated enhancement that depends on the internal intron sequence
Authors: Akua Tsofit , Berezin Irina , Shaul Orit 
Published: May 2010

Abstract

Background
Introns stimulate gene expression in a wide range of organisms by increasing the levels of mature mRNA, without affecting mRNA stability. Although introns sometimes function as transcriptional enhancers, they usually stimulate expression by a process termed intron-mediated enhancement (IME). The mechanism of IME is largely unknown. While splicing per se is not sufficient for IME, as evident from the fact that not all introns increase expression, it is not clear yet whether splicing of the enhancing introns is essential for enhancement. The leader intron (LI) of the Arabidopsis AtMHX gene was previously shown to substantially increase the expression of the AtMHX promoter. Here we investigated whether this LI acts as a transcriptional enhancer and whether its splicing is essential for IME.

Results
Expression in transformed Arabidopsis plants of an AtMHX::GUS construct from which the LI was eliminated was similar to a construct that included only the minimal promoter fused to GUS. Yet, almost no expression was seen in constructs that included the LI in addition to the minimal promoter or the LI inserted in various locations in the promoter. While the LI enhanced 272-fold the expression of the weak AtMHX promoter, only a 3-fold enhancement was observed for the strong CaMV 35S promoter. In the context of the AtMHX promoter, an unspliceable version of the LI that had mutated 5' and 3' splice sites mediated a low-level (5-fold) enhancement. Eliminating the internal 320 nt of the 416 nt unspliceable intron resulted in loss of ability to mediate low-level enhancement.

Conclusions
Although AtMHX promoter shows almost no expression in the absence of its LI, this intron does not act as a transcriptional enhancer and is unable to support expression in the absence of the enhancer elements of the promoter. It is also shown that the same intron can have very different contributions to expression of different promoters. Our results also demonstrate that while splicing is essential for substantial IME, in the absence of splicing low-level enhancement can be obtained. Notably, it is shown that the internal intron sequence plays a significant role in mediating the low-level enhancement of unspliced introns.
Nutrigenomics Therapy of Hepatisis C Virus Induced-hepatosteatosis
Authors: Liu Qing , Bengmark Stig , Qu Shen 
Published: May 2010

Abstract
Nutrigenomics is a relatively new branch of nutrition science, which aim is to study the impact of the foods we eat on the function of our genes. Hepatosteatosis is strongly associated with hepatitis C virus infection, which is known to increase the risk of the disease progression and reduce the likelihood of responding to anti- virus treatment. It is well documented that hepatitis C virus can directly alter host cell lipid metabolism through nuclear transcription factors. To date, only a limited number of studies have been on the effect of human foods on the nuclear transcription factors of hepatitis C virus -induced hepatosteatosis.
Three nutrients, selected among 46 different nutrients: β-carotene, vitamin D2, and linoleic acid were found in a cell culture system to inhibit hepatitis C virus RNA replication. In addition, polyunsaturated fatty acids (PUFAs) especially arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) have been demonstrated to inhibit hepatitis C virus RNA replication. These PUFAs, in particular the highly unsaturated n-3 fatty acids change the gene expression of PPARa and SREBP, suppress the expression of mRNAs encoding key metabolic enzymes and hereby suppress hepatic lipogenesis and triglyceride synthesis, as well as secretion and accumulation in tissues. A recent prospective clinical trial of 1,084 chronic hepatitis C patients compared to 2,326 healthy subjects suggests that chronic hepatitis C patients may benefit from strict dietary instructions.
Increasing evidence suggest that some crucial nuclear transcription factors related to hepatitis C virus -associated hepatosteatosis and hepatitis C virus RNA itself can be controlled by specific anti- hepatitis C virus nutrition. It seems important that these findings are taken into account and specific nutritional supplements developed to be used in combination with interferon as adjunctive therapy with the aim to improve both the early as well as the sustained virological response.
The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer
Authors: Dai Fuqiang , Liu Lunxu , Che Guowei , Yu Nanbin , Pu Qiang , Zhang Shangfu , Ma Junliang , Ma Lin , You Zongbing 
Published: May 2010

Abstract

Background
Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time.

Methods
Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).

Results
The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time.

Conclusions
The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.
Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence
Authors: Bravo-Cuellar Alejandro , Ortiz-Lazareno Pablo C , Lerma-Diaz Jose M , Dominguez-Rodriguez Jorge R , Jave-Suarez Luis F , Aguilar-Lemarroy Adriana , del Toro-Arreola Susana , de Celis-Carrillo Ruth , Sahagun-Flores Jose E , de Alba-Garcia Javier E Garcia , Hernandez-Flores Georgina 
Published: May 2010

Abstract

Background
Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells.

Methods
HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IκBα and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot.

Results
PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IκBα levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR.

Conclusion
PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.
The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein
Authors: Kim Jihoon , Harada Ryuichi , Kobayashi Masaki , Kobayashi Natsuki , Sode Koji 
Published: May 2010

Abstract

Background
Parkinson's disease (PD) involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha-synuclein. Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. However, no inhibitor for truncated alpha-synuclein has been reported yet.

Results
In this study, we first characterized the aggregation and cytotoxicity of C-truncated alpha-synuclein119 and alpha-synuclein133 which have been found in both the normal and the pathogenic brain. Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. We showed that PQQ dramatically inhibits the fibril formation of C-terminal truncated alpha-synuclein110119, and 133 as well as the mixtures of full-length alpha-synuclein with these truncated variants. Moreover, PQQ decreases the cytotoxicity of truncated alpha-synuclein.

Conclusions
Our results demonstrate that PQQ inhibits the amyloid fibril formation and cytotoxicity of the C-truncated alpha-synuclein variants. We believe that PQQ is a strong candidate for a reagent compound in the treatment of PD.
Expression of migration-related genes is progressively upregulated in murine Lineage-Sca-1+c-Kit+ population from the fetal to adult stages of development
Authors: Ciriza Jesús , García-Ojeda Marcos E 
Published: May 2010

Abstract
Introduction
Hematopoietic stem cells (HSCs) follow a genetically programmed pattern of migration during development. Extracellular matrix and adhesion molecules, as well as chemokines and their receptors, are important in adult HSC migration. However, little is known about the role these molecules play at earlier developmental stages.

Methods
We have analyzed by quantitative polymerase chain reaction (qPCR) array the expression pattern of extracellular matrix and adhesion molecules as well as chemokines and chemokine receptors in Lineage-Sca-1+c-Kit+ (LSK) cells at different stages of development, in order to characterize the role played by these molecules in LSK. Data were represented by volcano plots to show the differences in expression pattern at the time points studied.

Results
Our results show marked changes in the expression pattern of extracellular matrix, adhesion molecules, chemokines and their receptors with developmental age, particularly in later stages of development. Ten molecules were significantly increased among the LSK populations studied. Our screen identified the upregulation of Col4a1, as well as molecules involved in its degradation (Mmp2, Timp2), with development. Other genes identified were Sell, Tgfbi, and Entpd1. Furthermore, we show that the expression of the chemokines Ccl4, Ccl9, Il18 and the chemokine receptor Cxcr4 increases in LSK cells during development.

Conclusions
Several genes are upregulated in the LSK population in their transition to the bone marrow microenvironment, increasing at later stages of development. This gene pattern should be emulated by embryonic stem cell-derived hematopoietic progenitors in order to improve their properties for clinical applications such as engraftment.
Lipoatrophy Induced by Subcutaneous Insulin Infusion: Ultrastructural Analysis and Gene Expression Profiling
Authors: Milan G. , Murano I. , Costa S. , Pianta A. , Tiengo C. , Zulato E. , Centobene C. , Bruttomesso D. , Cinti S. , Vettor R. 
Published: May 2010

Context and Objective: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions.Setting and Patients: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes.Results: SAT was present in LA lesions characterized by: 1) smaller, unilocular perilipin-positive adipocytes, with lipofuscin granules; 2) some “slimmed cells” losing lipid droplets as those we observed during starvation; and 3) numerous perivascular preadipocytes. We did not identify inflammatory cells. SAT in LA areas displayed a strong leptin down-regulation and an increase of AEBP1, a preadipocyte marker.Conclusions: Our results clearly indicate that the remarkable reduction in fat cell lipid droplets and adipocyte size justifies the decrease of SAT without a reduction in adipocyte number because of necrosis or apoptosis. Thus, immune cells and any other toxic damaging fat cells were not involved in the generation of LA. We speculate that adipocytes chronically exposed to high local insulin concentrations could become severely insulin resistant, dramatically increasing lipolysis and giving rise to “slimmed cells.” Clinical LA regression could be explained by the active recruitment of preadipocytes, even if they were unable to differentiate and regenerate adipose tissue unless the insulin injection was removed.
An Acetylation Switch Modulates the Transcriptional Activity of Estrogen-Related Receptor α
Authors: Wilson Brian J. , Tremblay Annie M. , Deblois Geneviève , Sylvain-Drolet Guillaume , Giguère Vincent 
Published: May 2010

AbstractPosttranslational modifications are instrumental to achieve gene- and tissue-specific regulatory outcomes by transcription factors. Nuclear receptors are dynamically modulated by several types of posttranslational modifications including phosphorylation, methylation, acetylation, ubiquitination, and sumoylation. The estrogen-related receptor α (ERRα, NR3B1) is phosphorylated on multiple sites, and sumoylated in the amino-terminal region in a phosphorylation-dependent manner. Here we demonstrate that ERRα interacts with and is acetylated by p300 coactivator associated factor (PCAF) in vitro and in mouse liver. Purified PCAF acetylated the DNA-binding domain of ERRα on four highly-conserved lysines. In addition, coexpression of PCAF reduced the transcriptional activity of ERRα and, reciprocally, a deacetylase screen identified histone deacetylase 8 (HDAC8) and sirtuin 1 homolog (Sirt1) as independent enhancers of ERRα transcriptional function. HDAC8 and Sirt1 were also demonstrated to interact directly with ERRα in vivo and to deacetylate and increase the DNA binding affinity of ERRα in vitro. The removal of PCAF increases the DNA binding of ERRα in vivo, whereas the removal of Sirt1 and HDAC8 decreases it as assessed by chromatin immunoprecipitation assay. Altogether, our results show that ERRα is an acetylated protein and imply the existence of a dynamic acetylation/deacetylation switch involved in the control of ERRα transcriptional activity.