bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Abdominal Aortic Aneurysm Formation Is Mediated by IL-17 and Attenuated by Mesenchymal Stem Cell Treatment
Authors: Sharma Ashish K. , Lu Guanyi , Jester Andrea , Johnston William F. , Zhao Yunge , Hajzus Vanessa A. , Saadatzadeh M. Reza , Su Gang , Bhamidipati Castigliano M. , Mehta Gaurav S. , Kron Irving L. , Laubach Victor E. , Murphy Michael P. , Ailawadi Gorav , Upchurch Gilbert R.
Published: September 2012

Background—

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T-cell–produced IL-17 modulates inflammation and smooth muscle cell activation, leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation.

Methods and Results—

Human aortic tissue demonstrated a significant increase in IL-17 and IL-23 expression in AAA patients compared with control subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild-type; WT), IL-23
−/−
or IL-17
−/−
mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7, and 14 after perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts, and IL-17–producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α, and IFN-γ) was significantly attenuated in elastase-perfused IL-17
−/−
and IL-23
−/−
mice compared with WT mice on day 14. Cellular infiltration (especially IL-17–producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17
−/−
mice compared with WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice.

Conclusions—

These results demonstrate that CD4+ T-cell–produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.
Effect of Complete Revascularization on 10-Year Survival of Patients With Stable Multivessel Coronary Artery Disease
Authors: Vieira Ricardo D'Oliveira , Hueb Whady , Gersh Bernard J. , Lima Eduardo Gomes , Pereira Alexandre Costa , Rezende Paulo Cury , Garzillo Cibele Larrosa , Hueb Alexandre Ciappina , Favarato Desiderio , Soares Paulo Rogério , Ramires José Antonio Franchini , Filho Roberto Kalil
Published: September 2012

Background—

The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).

Methods and Results—

This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (
P
=0.001). The IR group had more prior myocardial infarction than the CR group (56.2%×39.2%,
P
=0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%;
P
=0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (
P
=0.05).

Conclusions—

Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI.

Clinical Trial Registration Information—

URL:
http://www.controlled-trials.com
. Registration number: ISRCTN66068876.
Clampless Off-Pump Versus Conventional Coronary Artery Revascularization
Authors: Börgermann Jochen , Hakim Kavous , Renner André , Parsa Amin , Aboud Anas , Becker Tobias , Masshoff Marc , Zittermann Armin , Gummert Jan Fritz , Kuss Oliver
Published: September 2012

Background—

This study aimed to assess if clampless off-pump coronary artery bypass grafting (CABG) decreases risk-adjusted mortality, stroke rate, and morbidity in unselected patients in comparison to conventional CABG.

Methods and Results—

Between July 2009 and November 2010, data of 1282 consecutive patients undergoing isolated CABG were prospectively recorded. In 30.8% (n=395), clampless off-pump revascularization was used, either with the PAS-Port automated central venous anastomosis system (n=310) or as total arterial revascularization without central anastomoses (n=85). Propensity score (PS) matching was performed based on 15 preoperative risk variables to correct for selection bias. In-hospital mortality and stroke rate as primary end point, as well as major complications and follow-up outcome of clampless off-pump (lessOPCAB) and conventional CABG (cCABG) were compared in 394 matched patient pairs (total: 788 patients). The clampless off-pump technique decreased the in-hospital rate of death (odds ratio, 0.25; 95% confidence interval, 0.05–1.18,
P
=0.080) and stroke (odds ratio, 0.36; 95% confidence interval, 0.13–0.99,
P
=0.048) significantly. Complications such as low cardiac output syndrome, prolonged ventilation and rethoracotomy were also reduced by lessOPCAB. Over a 2-year follow-up period overall survival, cerebrovascular and major adverse event rate were significantly lower in the lessOPCAB group, while the repeat revascularization rate was comparable.

Conclusions—

In a retrospective PS-matched analysis, clampless off-pump CABG lowers mortality, stroke rate and other morbidity in an unselected group of patients with coronary artery disease.
Cost-Effectiveness Analysis for Surgical, Angioplasty, or Medical Therapeutics for Coronary Artery Disease
Authors: Vieira Ricardo D'Oliveira , Hueb Whady , Hlatky Mark , Favarato Desiderio , Rezende Paulo Cury , Garzillo Cibele Larrosa , Lima Eduardo Gomes , Soares Paulo Rogério , Hueb Alexandre Ciappina , Pereira Alexandre Costa , Ramires José Antonio Franchini , Filho Roberto Kalil
Published: September 2012

Background—

The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n=203), percutaneous coronary intervention (PCI, n=205), or medical treatment alone (MT, n=203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies.

Methods and Results—

We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19 967.00 for PCI; and $18 263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (
P
<0.01) and versus CABG (
P
<0.01) and CABG versus PCI (
P
=0.01). The event-free plus angina-free costs were $16 553.00, $25 831.00, and $24 614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (
P
=0.04), and versus CABG (
P
<0.001); there was no difference between CABG and PCI (
P
>0.05).

Conclusions—

In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI.

Clinical Trial Registration Information—

www.controlled-trials.com
. Registration number: ISRCTN66068876.
Three-Dimensional Echocardiographic Analysis of Mitral Annular Dynamics
Authors: Levack Melissa M. , Jassar Arminder S. , Shang Eric K. , Vergnat Mathieu , Woo Y. Joseph , Acker Michael A. , Jackson Benjamin M. , Gorman Joseph H. , Gorman Robert C.
Published: September 2012

Background—

Proponents of flexible annuloplasty rings have hypothesized that such devices maintain annular dynamics. This hypothesis is based on the supposition that annular motion is relatively normal in patients undergoing mitral valve repair. We hypothesized that mitral annular dynamics are impaired in ischemic mitral regurgitation and myxomatous mitral regurgitation.

Methods and Results—

A Philips iE33 echocardiographic module and X7–2t probe were used to acquire full-volume real-time 3-dimensional transesophageal echocardiography loops in 11 normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients with myxomatous mitral regurgitation. Image analysis was performed using Tomtec Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was selected for the initiation of annular tracking using the semiautomated program. Continuous parameters were normalized in time to provide for uniform systolic and diastolic periods. Both ischemic mitral regurgitation (9.98±155 cm
2
) and myxomatous mitral regurgitation annuli (13.29±3.05 cm
2
) were larger in area than normal annuli (7.95±1.40 cm
2
) at midsystole. In general, ischemic mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral regurgitation, annular dynamics were also markedly abnormal with the mitral annulus dilating rapidly in early systole in response to rising ventricular pressure.

Conclusions—

In both ischemic mitral regurgitation and myxomatous mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible annuloplasty devices used in mitral valve repair are, therefore, unlikely to result in either normal annular dynamics or normal anatomy.
Changes in Microvascular Reactivity After Cardiopulmonary Bypass in Patients With Poorly Controlled Versus Controlled Diabetes
Authors: Feng Jun , Liu Yuhong , Chu Louis M. , Singh Arun K. , Dobrilovic Nikola , Fingleton James G. , Clements Richard T. , Bianchi Cesario , Sellke Frank W.
Published: September 2012

Background—

We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients undergoing coronary artery bypass grafting (CABG).

Methods and Results—

Skeletal muscle arterioles were harvested before and after CPB from the UDM patients (hemoglobin A1c [HbA1c]=9.0±0.3), the CDM patients (HbA1c=6.3±0.15), and the ND patients (HbA1c=5.2±0.1) undergoing CABG surgery (n=10/group). In vitro relaxation responses of precontracted arterioles to endothelium-dependent vasodilators adenosine 5′-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P, and SNP of arterioles from the UDM patients were decreased as compared with microvessels from the ND or CDM patients (
P
<0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all 3 groups compared with pre-CPB responses (
P
<0.05). However, these decreases were more pronounced in the UDM group (
P
<0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other 2 groups compared with pre-CPB. The expression of protein kinase C (PKC)-α, PKC-β, protein oxidation, and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (
P
<0.05).

Conclusions—

Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-β and enhanced oxidative and nitrosative stress.
Cerebral Microembolization After Bioprosthetic Aortic Valve Replacement
Authors: Al-Atassi Talal , Lam Khanh , Forgie Melissa , Boodhwani Munir , Rubens Fraser , Hendry Paul , Masters Roy , Goldstein William , Bedard Pierre , Mesana Thierry , Ruel Marc
Published: September 2012

Background—

No human physiological data exists on whether aspirin only is as effective as warfarin plus aspirin in preventing cerebral microembolization in the early postoperative period after bioprosthetic aortic valve replacement (bAVR).

Methods and Results—

We prospectively enrolled 56 patients who had no other indication for oral anticoagulation, who underwent bAVR and received, in an open-label fashion, either daily warfarin (for INR 2.0–3.0) plus 81 mg of aspirin (n=28) or 325 mg of aspirin only (n=28). Cerebral microembolization was quantified at 4 hours (baseline) and at 1 month postoperatively, by recording 1-hour bilateral middle cerebral artery (MCA) microembolic signals (MES). Platelet-function analysis (PFA) of closure times (CT) on collagen was also used as a marker of platelet-dependent activation. Follow-up to 1 year was complete. Preoperative demographics and baseline platelet function were equivalent in both groups. There was no mortality, stroke, or transient ischemic attack at 1 year in either group. No significant differences were found in the proportion of patients with MES among those receiving warfarin plus aspirin versus aspirin only, at baseline (68% versus 82%, respectively;
P
=0.4) and at 1 month (46% versus 43%;
P
=1.0) after bAVR. The total MES and PFA were also equivalent between groups, at baseline and follow-up.

Conclusions—

Early after bAVR, the effects of these 2 antithrombotic regimens on cerebral microembolization and platelet function are equivalent. These data bring new mechanistic support to the premise that aspirin only may safely be used early after bAVR in patients who have no other indication for oral anticoagulation.
Administration of Cardiac Stem Cells in Patients With Ischemic Cardiomyopathy: The SCIPIO Trial
Authors: Chugh Atul R. , Beache Garth M. , Loughran John H. , Mewton Nathan , Elmore Julius B. , Kajstura Jan , Pappas Patroklos , Tatooles Antone , Stoddard Marcus F. , Lima Joao A.C. , Slaughter Mark S. , Anversa Piero , Bolli Roberto
Published: September 2012

Background—

SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit
+
cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

Methods and Results—

A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5±1.6% to 35.1±2.4% [
P
=0.004, n=8] and 41.2±4.5% [
P
=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: −6.9±1.5 g [−22.7%] at 4 months [
P
=0.002, n=9] and −9.8±3.5 g [−30.2%] at 12 months [
P
=0.039, n=6]). LV nonviable mass decreased even more (−11.9±2.5 g [−49.7%] at 4 months [
P
=0.001] and −14.7±3.9 g [−58.6%] at 12 months [
P
=0.013]), whereas LV viable mass increased (+11.6±5.1 g at 4 months after CSC infusion [
P
=0.055] and +31.5±11.0 g at 12 months [
P
=0.035]).

Conclusions—

Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration.

Clinical Trial Registration—

This study is registered with clinicaltrials.gov, trial number NCT00474461.
African American, Black Caribbean, and Non-Hispanic White Feelings of Closeness Toward Other Racial and Ethnic Groups
Authors: Thornton Michael C. , Taylor Robert Joseph , Chatters Linda M.
Published: September 2012

This study examines African Americans’, Black Caribbeans’, and non-Hispanic Whites’ perceptions of closeness to other racial and ethnic groups. The study uses data from a national probability sample, the National Survey of American Life ( N = 6,082), and provides the first investigation of this topic among Black Caribbeans. Study findings reveal both similarities and significant differences between African Americans and Black Caribbeans in their levels of closeness to other groups. African Americans and Black Caribbeans were similar in their levels of closeness to Whites, American Indians, and Asian Americans. African Americans felt significantly closer to Black people in the United States than did Black Caribbeans. Conversely, Black Caribbeans felt significantly closer than African Americans to Black people from the Caribbean, Spanish-speaking people, and Black people in Africa. Non-Hispanic Whites felt significantly closer to Asian Americans than did either African Americans or Black Caribbeans. These and other findings are discussed in detail and reaffirm the continued importance of race in American life and intergroup relations.
Ethanol extract of paeonia suffruticosa Andrews (PSE) induced AGS human gastric cancer cell apoptosis via fas-dependent apoptosis and MDM2-p53 pathways
Authors: Choi Hyeong Sim , Seo Hye-Sook , Kim Ji Hye , Um Jae-Young , Shin Yong Cheol , Ko Seong-Gyu
Published: September 2012

Background

The root bark of Paeonia suffruticosa Andrews (PSE), also known as Moutan Cortex, has been widely used in Asia to treat various diseases. The molecular mechanisms by which PSE exerts its anti-oxidant and anti-inflammatory activities are well known, but its anti-cancer activity is not yet well understood. Here, we present evidence demonstrating that PSE can be used as a potent anti-cancer agent to treat gastric cancer.

Methods

The effects of the ethanol extract of PSE on cell proliferation were determined using an MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) assay. Cell cytotoxicity induced by the PSE extact is measured using an LDH leakage assay. Flow cytometry was used to analyze the cell cycle and to measure the subG0/G1 apoptotic cell fraction. Apoptosis induced by the PSE extact is also examined using a DNA fragmentation assay. Western blot analysis is used to measure the levels of apoptotic proteins such as Fas receptor, caspase-8, caspase-3, PARP, Bax, Bcl-2, MDM2, and p53.

Results

This study demonstrated that treating AGS cells with the PSE extact significantly inhibited cell proliferation and induced cytotoxicity in a dose- and time-dependent manner. The PSE extract also induced apoptosis in AGS cells, as measured by flow cytometry and a DNA fragmentation assay. We found that the PSE extract induced apoptosis via the extrinsic Fas-mediated apoptosis pathway, which was concurrent with the activation of caspases, including caspase-8 and caspase-3, and cleavage of PARP. The MDM2-p53 pathway also played a role in the apoptosis of AGS cells that was induced by the PSE extract.

Conclusions

These results clearly demonstrate that the PSE extact displays growth-suppressive activity and induces apoptosis in AGS cells. Our data suggest that the PSE extact might be a potential anti-cancer agent for gastric cancer.
Widespread and persistent invasions of terrestrial habitats coincident with larval feeding behavior transitions during snail-killing fly evolution (Diptera: Sciomyzidae)
Authors: Chapman Eric G , Przhiboro Andrey A , Harwood James D , Foote Benjamin A , Hoeh Walter R
Published: September 2012

Background

Transitions in habitats and feeding behaviors were fundamental to the diversification of life on Earth. There is ongoing debate regarding the typical directionality of transitions between aquatic and terrestrial habitats and the mechanisms responsible for the preponderance of terrestrial to aquatic transitions. Snail-killing flies (Diptera: Sciomyzidae) represent an excellent model system to study such transitions because their larvae display a range of feeding behaviors, being predators, parasitoids or saprophages of a variety of mollusks in freshwater, shoreline and dry terrestrial habitats. The remarkable genusTetanocera(Tetanocerini) occupies five larval feeding groups and all of the habitat types mentioned above. This study has four principal objectives: (i) construct a robust estimate of phylogeny forTetanoceraand Tetanocerini, (ii) estimate the evolutionary transitions in larval feeding behaviors and habitats, (iii) test the monophyly of feeding groups and (iv) identify mechanisms underlying sciomyzid habitat and feeding behavior evolution.

Results

Bayesian inference and maximum likelihood analyses of molecular data provided strong support that the Sciomyzini, Tetanocerini andTetanoceraare monophyletic. However, the monophyly of many behavioral groupings was rejected via phylogenetic constraint analyses. We determined that (i) the ancestral sciomyzid lineage was terrestrial, (ii) there was a single terrestrial to aquatic habitat transition early in the evolution of the Tetanocerini and (iii) there were at least 10 independent aquatic to terrestrial habitat transitions and at least 15 feeding behavior transitions during tetanocerine phylogenesis. The ancestor ofTetanocerawas aquatic with five lineages making independent transitions to terrestrial habitats and seven making independent transitions in feeding behaviors.

Conclusions

The preponderance of aquatic to terrestrial transitions in sciomyzids goes against the trend generally observed across eukaryotes. Damp shoreline habitats are likely transitional where larvae can change habitat but still have similar prey available. Transitioning from aquatic to terrestrial habitats is likely easier than the reverse for sciomyzids because morphological characters associated with air-breathing while under the water's surface are lost rather than gained, and sciomyzids originated and diversified during a general drying period in Earth's history. Our results imply that any animal lineage having aquatic and terrestrial members, respiring the same way in both habitats and having the same type of food available in both habitats could show a similar pattern of multiple independent habitat transitions coincident with changes in behavioral and morphological traits.
Metagenomic analysis reveals a functional signature for biomass degradation by cecal microbiota in the leaf-eating flying squirrel (Petaurista alborufus lena)
Authors: Lu Hsiao-Pei , Wang Yu-bin , Huang Shiao-Wei , Lin Chung-Yen , Wu Martin , Hsieh Chih-hao , Yu Hon-Tsen
Published: September 2012

Background

Animals co-evolve with their gut microbiota; the latter can perform complex metabolic reactions that cannot be done independently by the host. Although the importance of gut microbiota has been well demonstrated, there is a paucity of research regarding its role in foliage-foraging mammals with a specialized digestive system.

Results

In this study, a 16S rRNA gene survey and metagenomic sequencing were used to characterize genetic diversity and functional capability of cecal microbiota of the folivorous flying squirrel (Petaurista alborufus lena). Phylogenetic compositions of the cecal microbiota derived from 3 flying squirrels were dominated by Firmicutes. Based on end-sequences of fosmid clones from 1 flying squirrel, we inferred that microbial metabolism greatly contributed to intestinal functions, including degradation of carbohydrates, metabolism of proteins, and synthesis of vitamins. Moreover, 33 polysaccharide-degrading enzymes and 2 large genomic fragments containing a series of carbohydrate-associated genes were identified.

Conclusions

Cecal microbiota of the leaf-eating flying squirrel have great metabolic potential for converting diverse plant materials into absorbable nutrients. The present study should serve as the basis for future investigations, using metagenomic approaches to elucidate the intricate mechanisms and interactions between host and gut microbiota of the flying squirrel digestive system, as well as other mammals with similar adaptations.
Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum
Authors: Heider Sabine A E , Peters-Wendisch Petra , Wendisch Volker F
Published: September 2012

Background

Corynebacterium glutamicum contains the glycosylated C50 carotenoid decaprenoxanthin as yellow pigment. Starting from isopentenyl pyrophosphate, which is generated in the non-mevalonate pathway, decaprenoxanthin is synthesized via the intermediates farnesyl pyrophosphate, geranylgeranyl pyrophosphate, lycopene and flavuxanthin.

Results

Here, we showed that the genes of the carotenoid gene cluster crtE-cg0722-crtBIY

e

Y

f

Eb are co-transcribed and characterized defined gene deletion mutants. Gene deletion analysis revealed that crtI, crtEb, and crtY

e

Y

f
, respectively, code for the only phytoene desaturase, lycopene elongase, and carotenoid C45/C50 ɛ-cyclase, respectively. However, the genome of C. glutamicum also encodes a second carotenoid gene cluster comprising crtB2I2-1/2 shown to be co-transcribed, as well. Ectopic expression of crtB2 could compensate for the lack of phytoene synthase CrtB in C. glutamicum ΔcrtB, thus, C. glutamicum possesses two functional phytoene synthases, namely CrtB and CrtB2. Genetic evidence for a crtI2-1/2 encoded phytoene desaturase could not be obtained since plasmid-borne expression of crtI2-1/2 did not compensate for the lack of phytoene desaturase CrtI in C. glutamicum ΔcrtI. The potential of C. glutamicum to overproduce carotenoids was estimated with lycopene as example. Deletion of the gene crtEb prevented conversion of lycopene to decaprenoxanthin and entailed accumulation of lycopene to 0.03 ± 0.01 mg/g cell dry weight (CDW). When the genes crtE, crtB and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were overexpressed in C. glutamicum ΔcrtEb intensely red-pigmented cells and an 80 fold increased lycopene content of 2.4 ± 0.3 mg/g CDW were obtained.

Conclusion

C. glutamicum possesses a certain degree of redundancy in the biosynthesis of the C50 carotenoid decaprenoxanthin as it possesses two functional phytoene synthase genes. Already metabolic engineering of only the terminal reactions leading to lycopene resulted in considerable lycopene production indicating that C. glutamicum may serve as a potential host for carotenoid production.
Transcriptome analysis of rice root responses to potassium deficiency
Authors: Ma Tian-Li , Wu Wei-Hua , Wang Yi
Published: September 2012

Background

Potassium (K+) is an important nutrient ion in plant cells and plays crucial roles in many plant physiological and developmental processes. In the natural environment, K+ deficiency is a common abiotic stress that inhibits plant growth and reduces crop productivity. Several microarray studies have been conducted on genome-wide gene expression profiles of rice during its responses to various stresses. However, little is known about the transcriptional changes in rice genes under low-K+ conditions.

Results

We analyzed the transcriptomic profiles of rice roots in response to low-K+ stress. The roots of rice seedlings with or without low-K+ treatment were harvested after 6 h, and 3 and 5 d, and used for microarray analysis. The microarray data showed that many genes (2,896) were up-regulated or down-regulated more than 1.2-fold during low-K+ treatment. GO analysis indicated that the genes showing transcriptional changes were mainly in the following categories: metabolic process, membrane, cation binding, kinase activity, transport, and so on. We conducted a comparative analysis of transcriptomic changes between Arabidopsis and rice under low-K+ stress. Generally, the genes showing changes in transcription in rice and Arabidopsis in response to low-K+ stress displayed similar GO distribution patterns. However, there were more genes related to stress responses and development in Arabidopsis than in rice. Many auxin-related genes responded to K+ deficiency in rice, whereas jasmonic acid-related enzymes may play more important roles in K+ nutrient signaling in Arabidopsis.

Conclusions

According to the microarray data, fewer rice genes showed transcriptional changes in response to K+ deficiency than to phosphorus (P) or nitrogen (N) deficiency. Thus, transcriptional regulation is probably more important in responses to low-P and -N stress than to low-K+ stress. However, many genes in some categories (protein kinase and ion transporter families) were markedly up-regulated, suggesting that they play important roles during K+ deficiency. Comparative analysis of transcriptomic changes between Arabidopsis and rice showed that monocots and dicots share many similar mechanisms in response to K+ deficiency, despite some differences. Further research is required to clarify the differences in transcriptional regulation between monocots and dicots.
Kalanchoe tubiflora extract inhibits cell proliferation by affecting the mitotic apparatus
Authors: Hsieh Yi-Jen , Yang Ming-Yeh , Leu Yann-Lii , Chen Chinpiao , Wan Chin-Fung , Chang Meng-Ya , Chang Chih-Jui
Published: September 2012

Background

Kalanchoe tubiflora (KT) is a succulent plant native to Madagascar, and is commonly used as a medicinal agent in Southern Brazil. The underlying mechanisms of tumor suppression are largely unexplored.

Methods

Cell viability and wound-healing were analyzed by MTT assay and scratch assay respectively. Cell cycle profiles were analyzed by FACS. Mitotic defects were analyzed by indirect immunofluoresence images.

Results

An n-Butanol-soluble fraction of KT (KT-NB) was able to inhibit cell proliferation. After a 48 h treatment with 6.75 μg/ml of KT, the cell viability was less than 50% of controls, and was further reduced to less than 10% at higher concentrations. KT-NB also induced an accumulation of cells in the G2/M phase of the cell cycle as well as an increased level of cells in the subG1 phase. Instead of disrupting the microtubule network of interphase cells, KT-NB reduced cell viability by inducing multipolar spindles and defects in chromosome alignment. KT-NB inhibits cell proliferation and reduces cell viability by two mechanisms that are exclusively involved with cell division: first by inducing multipolarity; second by disrupting chromosome alignment during metaphase.

Conclusion

KT-NB reduced cell viability by exclusively affecting formation of the proper structure of the mitotic apparatus. This is the main idea of the new generation of anti-mitotic agents. All together, KT-NB has sufficient potential to warrant further investigation as a potential new anticancer agent candidate.
Development and feasibility of a set of quality indicators relative to the timeliness and organisation of care for new breast cancer patients undergoing surgery
Authors: Ferrua Marie , Couralet Mélanie , Nitenberg Gérard , Morin Sandrine , Serin Daniel , Minvielle Etienne
Published: September 2012

Background

Because breast cancer is a major public health issue, it is particularly important to measure the quality of the care provided to patients. Survival rates are affected by the timeliness of care, and waiting times constitute key quality criteria. The aim of this study was to develop and validate a set of quality indicators (QIs) relative to the timeliness and organisation of care in new patients with infiltrating, non-inflammatory and metastasis-free breast cancer undergoing surgery. The ultimate aim was to use these QIs to compare hospitals.

Methods

The method of QI construction and testing was developed by COMPAQ-HPST. We first derived a set of 8 QIs from consensus guidelines with the aid of experts and professional associations and then tested their metrological properties in a panel of 60 volunteer hospitals. We assessed feasibility using a grid exploring 5 dimensions, discriminatory power using the Gini coefficient as a measure of dispersion, and inter-observer reliability using the Kappa coefficient.

Results

Overall, 3728 records were included in the analyses. All 8 QIs showed acceptable feasibility (but one QI was subject to misinterpretation), fairly strong agreement between observers (Kappa = 0.66), and wide variations in implementation among hospitals (Gini coefficient < 0.45 except for QI 6 (patient information)). They are thus suitable for use to compare hospitals and measure quality improvement.

Conclusions

Of the 8 QIs, 3 are ready for nationwide implementation (time to surgery, time to postoperative multidisciplinary team meeting (MDTM), conformity of MDTM). Four are suitable for use only in hospitals offering surgery with on-site postoperative treatment (waiting time to first appointment after surgery, patient information, time to first postoperative treatment, and traceability of information relating to prognosis). Currently, in the French healthcare system, a patient receives cancer care from different institutions whose databases cannot as yet be easily merged. Nationwide implementation of QIs covering the entire care pathway will thus be a challenge.
Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study
Authors: Nematy Mohsen , Alinezhad-Namaghi Maryam , Rashed Masoud Mahdavi , Mozhdehifard Mostafa , Sajjadi Seyedeh Sania , Akhlaghi Saeed , Sabery Maryam , Mohajeri Seyed Amir R , Shalaey Neda , Moohebati Mohsen , Norouzy Abdolreza
Published: September 2012

Background

Previous research has shown that Ramadan fasting has beneficial effects on cardiovascular risk factors, however there are controversies. In the present study, the effect of Ramadan fasting on cardiovascular risk factors has been investigated.

Method

This is a prospective observational study that was carried out in a group of patients with at least one cardiovascular risk factor (including history of documented previous history of either coronary artery disease (CAD), metabolic syndrome or cerebro-vascular disease in past 10 y). Eighty two volunteers including 38 male and 44 female, aged 29–70 y, mean 54.0 ± 10 y, with a previous history of either coronary artery disease, metabolic syndrome or cerebro-vascular disease were recruited. Subjects attended the metabolic unit after at least 10 h fasting, before and after Ramadan who were been fasting for at least 10 days. A fasting blood sample was obtained, blood pressure was measured and body mass index (BMI) was calculated. Lipids profile, fasting blood sugar (FBS) and insulin, homocysteine (hcy), high-sensitivity C-reactive protein (hs-CRP) and complete blood count (CBC) were analyzed on all blood samples.

Results

A significant improvement in 10 years coronary heart disease risk (based on Framingham risk score) was found (13.0 ± 8 before Ramadan and 10.8 ±7 after Ramadan, P <0.001, t test).There was a significant higher HDL-c, WBC, RBC and platelet count (PLT), and lower plasma cholesterol, triglycerides, LDL-c, VLDL-c, systolic blood pressure, body mass index and waist circumference after Ramadan (P <0.05, t test). The changes in FBS, insulin,Homeostasis Model Assessment Insulin Resistance (HOMA-IR), hcy, hs-CRP and diastolic blood pressure before and after Ramadan were not significant (P >0.05, t test).

Conclusions

This study shows a significant improvement in 10 years coronary heart disease risk score and other cardiovascular risk factors such as lipids profile, systolic blood pressure, weight, BMI and waist circumference in subjects with a previous history of cardiovascular disease.
Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A
y
mice
Authors: Beppu Fumiaki , Hosokawa Masashi , Niwano Yoshimi , Miyashita Kazuo
Published: September 2012

Background

Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin.

Methods

Diabetic/obese KK-A

y
mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively.

Results

Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes.

Conclusions

Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-A

y
mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.
Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands
Authors: Verduyn S Cora , Biesma Bonne , Schramel Franz MNH , van der Scheer Feike W , Langenfeld Merel K , de Peuter Maria A , Dingemans Anne-Marie C
Published: September 2012

Background

Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+). From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis); paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis.

Methods

Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals.

Results

The Quality Adjusted progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5) for Pac/Carb and 8.3 (7.0; 9.9) for gefitinib.

Conclusions

In the Dutch health care setting, the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to standard doublet chemotherapy is further supported by the Quality Adjusted PFS, which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy.
Percutaneous microwave coagulation for eradication of VX2 tumors subcutaneously in rabbits
Authors: Zhou Wenbin , Ding Qiang , Liu Xiaoan , Jiang Yanni , Chen Ling , Zhang Yifen , Xia Tiansong , Wang Shui
Published: September 2012

Background

Percutaneous microwave coagulation (PMC) has been accepted as a promising modality in the treatment of tumors in well-vascularized tissues such as liver tumors and hysteromyoma. However, PMC for treatment of tumors in low blood-flow tissues has been seldom reported. The aim of this study was to determine the feasibility and safety of PMC for the treatment of tumors in low blood-flow tissues in a rabbit model.

Methods

Fifteen rabbits with VX2 tumors implanted subcutaneously underneath the right second nipple were divided into a PMC group (n = 9) and a control group (n = 6). PMC was performed with output power of 40 W for one to two minutes. The therapeutic efficacy was evaluated by magnetic resonance imaging (MRI), physical examinations, survival rate, and histology. The cosmetic outcome after PMC was also assessed.

Results

In the PMC group, tumor eradication was achieved in six rabbits (66.7%) without any evidence of tumor recurrence and metastasis as proven by MRI and histological examinations. The mean greatest and shortest tumor diameters of these six rabbits were 1.83 and 1.33 cm, respectively. Slight epidermal burns, which proved reversible, were found in seven rabbits (77.8%). The PMC group had a significantly longer survival than those in the control group (P = 0.0097). The four rabbits with coagulated tumors survived more than three months with their tumors becoming nonpalpable and undetectable by MRI and histological examinations.

Conclusions

PMC is feasible and safe in the treatment of tumors in low blood-flow tissues in a rabbit model. Attention should be paid to avoid skin burns with PMC.
Real-time assessment of cigarette smoke particle deposition in vitro
Authors: Adamson Jason , Hughes Sophie , Azzopardi David , McAughey John , Gaça Marianna D
Published: September 2012

Background

Recently there has been a rapid increase in approaches to assess the effects of cigarette smoke in vitro. Despite a range of gravimetric and chemical methods, there is a requirement to identify simpler and more reliable methods to quantify in vitro whole smoke dose, to support extrapolation and comparisons to human/in vivo dose. We have previously characterised an in vitro exposure system using a Borgwaldt RM20S smoking machine and a chamber exposing cellular cultures to whole smoke at the air-liquid interface. In this study we demonstrate the utility of a quartz crystal microbalance (QCM), using this exposure system, to assess real-time cigarette smoke particulate deposition during a 30 minute smoke exposure. Smoke was generated at various dilutions (1:5–1:400, smoke:air) using two cigarette products, 3R4F Kentucky reference and 1 mg commercially available cigarettes. The QCM, integrated into the chamber, assessed particulate deposition and data generated were compared to traditional chemical spectrofluorometric analysis.

Results

The QCM chamber was able to detect mass differences between the different products within the nanogram range. 3R4F reference cigarette smoke deposition ranged from 25.75 ±2.30 μg/cm2 (1:5) to 0.22 ±0.03 μg/cm2 (1:400). 1 mg cigarette smoke deposition was less and ranged from 1.42 ±0.26 μg/cm2 (1:5), to 0.13 ±0.02 μg/cm2 (1:100). Spectrofluorometric analysis demonstrated statistically significant correlation of particulate deposition with the QCM (p < 0.05), and regression R2 value were 97.4 %. The fitted equation for the linear model which describes the relationship is: QCM = −0.6796 + 0.9744 chemical spectrofluorescence.

Conclusions

We suggest the QCM is a reliable, effective and simple tool that can be used to quantify smoke particulate deposition in real-time, in vitro and can be used to quantify other aerosols delivered to our chamber for assessment.
Efficacy of ‘Itrifal Saghir’, a combination of three medicinal plants in the treatment of obesity; A randomized controlled trial
Authors: Kamali Seyed Hamid , Khalaj Ali Reza , Hasani-Ranjbar Shirin , Esfehani Mohammad Mehdi , Kamalinejad Mohammad , Soheil Omidmalayeri , Kamali Seyed Ali
Published: September 2012

Background

Herbal combination of Itrifal Saghir (triphala) has been widely used in traditional medicine. And brings health benefits such as antioxidant effect and scavenger of hydroxyl radicals and nitric oxide radicals activity and substantiated in traditional medicine a anti-obesity.

Material and method

In this study we aimed to assess the efficacy of this herbal medicinal on reduction of weight and body mass index (BMI) of simple obese subjects in comparison with placebo. Obese subjects aged between 16 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial using a parallel design. Subjects were randomly assigned to take 5 grams of either the Itrifal Saghir (n = 31) or placebo (n = 31), 2 times daily for 12 weeks. Measures of body weight, BMI, waist circumference (WC), hip circumference (HC), were assessed at baseline and once every four weeks during the 12 week treatment period. The safety was evaluated by means of measuring the liver and kidney function. Homeostasis model of insulin resistance (HOMA-IR) was calculated as [fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5].

Results

Compared to placebo group, in treatment group the mean difference of effective weight loss was 4.82Kg (CI95% 3.52 - 6.11, ρ < 0.001), the mean of decrease in waist circumference was 4.01 cm (CI 95% 2.13 - 5.90, ρ < 0.001), and the mean decrease in hip circumference was 3. 21 cm (CI 95% 1.96 - 4.45, ρ < 0.001) in treated subjects. No adverse effects or significant changes in liver and kidney function tests were observed in both placebo and treated groups.

Conclusions

Itrifal Saghir appears to produce a positive effect on weight loss in obese subjects.