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1.
Background
Pathological angiogenesis plays an essential role in tumor aggressiveness and leads to unfavorable prognosis. The aim of this study is to detect the potential role of Retinoblastoma binding protein 2 (RBP2) in the tumor angiogenesis of non-small cell lung cancer (NSCLC).Methods
Immunohistochemical staining was used to detect the expression of RBP2, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34. Two pairs of siRNA sequences and pcDNA3-HA-RBP2 were used to down-regulate and up-regulate RBP2 expression in H1975 and SK-MES-1 cells. An endothelial cell tube formation assay, VEGF enzyme-linked immunosorbent assay, real-time PCR and western blotting were performed to detect the potential mechanisms mediated by RBP2 in tumor angiogenesis.Results
Of the 102 stage I NSCLC specimens analyzed, high RBP2 protein expression is closely associated with tumor size (P = 0.030), high HIF-1α expression (P = 0.028), high VEGF expression (P = 0.048), increased tumor angiogenesis (P = 0.033) and poor prognosis (P = 0.037); high MVD was associated with high HIF-1α expression (P = 0.034), high VEGF expression (P = 0.001) and poor prognosis (P = 0.040). Multivariate analysis indicated that RBP2 had an independent influence on the survival of patients with stage I NSCLC (P = 0.044). By modulating the expression of RBP2, our findings suggested that RBP2 protein depletion decreased HUVECs tube formation by down-regulating VEGF in a conditioned medium. RBP2 stimulated the up-regulation of VEGF, which was dependent on HIF-1α, and activated the HIF-1α via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, VEGF increased the activation of Akt regulated by RBP2.Conclusions
The RBP2 protein may stimulate HIF-1α expression via the activation of the PI3K/Akt signaling pathway under normoxia and then stimulate VEGF expression. These findings indicate that RBP2 may play a critical role in tumor angiogenesis and serve as an attractive therapeutic target against tumor aggressiveness for early-stage NSCLC patients. 相似文献2.
Michaela Loebig Johanna Klement André Schmoller Simone Betz Nicole Heuck Ulrich Schweiger Achim Peters Bernd Schultes Kerstin M. Oltmanns 《PloS one》2010,5(9)
Background
This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI) as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed.Methodology/Principal Findings
Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20–25 kg/m2), 15 low weight (BMI<20 kg/m2), and 15 obese (BMI>30 kg/m2) male subjects aged 18–30 years and the insulin sensitivity index (ISI) was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145), cortisol (P = 0.840), and norepinephrine (P = 0.065) levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008) with higher concentrations in obese subjects as compared to normal weight (P = 0.061) and low weight subjects (P = 0.002). Pearson''s correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010) but no correlation of VEGF with ISI (r = 0.224; P = 0.175).Conclusions/Significance
Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes. 相似文献3.
Giovanni Tarantino Susan Costantini Carmine Finelli Francesca Capone Eliana Guerriero Nicolina La Sala Saverio Gioia Giuseppe Castello 《PloS one》2014,9(9)
Background
Non-Alcoholic Fatty Liver Disease (NAFLD) is a distinct coronary artery disease (CAD) risk factor. The atherosclerotic process predisposing to CAD includes altered lipid profile and inflammatory processes. The available evidence suggests that increased circulating levels of eotaxin, an eosinophil chemoattractant cytokine implicated in allergic responses, are detected in the serum of patients with CAD. Relationships were sought between serum eotaxin on the one hand, and intima-media thickness—an early predictor of the atherosclerotic process, hepatic steatosis, arterial blood pressure values, as well as inflammation/immune markers and angiogenetic factors—on the other.Methods
Eighty obese patients with NAFLD, diagnosed at ultrasonography, without evident cytolysis, formed our study population. Anthropometric measures, metabolic profile, serum concentrations of interleukin-1β, C-reactive protein, interleukin-6, fibrinogen, ferritin, TNF-α, spleen size, vascular endothelial growth factor, platelet-derived growth factor-BB and heat shock protein-70 were evaluated.Results
Serum eotaxin concentrations were distinctly associated with TNF α, IL-6, IL-1β, VEGF and PDGF-BB levels but not with CRP, fibrinogen, heat shock protein-70 or spleen size. Among the metabolic and anthropometric parameters, a significant predictive power emerged when comparing eotaxin to insulin resistance, expressed as HOMA. NAFLD was distinctly associated with HOMA (P = 0.0005). Intima-media thickness was well predicted by both eotaxin levels and severity of NAFLD at ultrasonography, although no relation was detected between these last two variables.Discussion and Conclusion
A role for insulin resistance in mediating the interplay between eotaxin and other inflammation/immune parameters could be evidenced in the induction/maintenance of atherosclerosis of obese patients with NAFLD. 相似文献4.
Background
Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213.Methods
A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain reaction (PCR) and direct sequencing.Results
The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06–1.76). Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17–2.03) and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16–2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia.Conclusions
Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women. 相似文献5.
Purpose
This study investigates the differential aqueous concentrations of interleukin 6, 8, 1β (IL-6, IL-8, IL-1β, respectively), serum amyloid A (SAA), transforming growth factor (TGF)-β, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in eyes with macular edema as a result of a branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).Principal Findings
Significantly higher concentrations of IL-6, IL-8, IL-1β, TGF-β, bFGF, SAA, and VEGF were found in the aqueous humor of CRVO and BRVO patients than in the aqueous humor of control patients. A significant correlation was observed between the concentration of bFGF and the inner central macular thickness (CMT) of BRVO patients (r = 0.688; P = 0.02). A significant correlation was observed between the concentration of SAA and both the full and outer CMT of the ischemic group (r = 0.545 and 0.683, respectively; P = 0.04 and 0.01, respectively). In the non-ischemic group, the level of IL-6 was significantly associated with inner CMT (r = 0.560; P = 0.03). The full and outer CMT was significantly reduced in CRVO patients when compared with BRVO patients (P = 0.02 and 0.02, respectively) after injection of intravitreal bevacizumab (IVB) at 4 weeks.Significance
Serum amyloid A as a major protein involved in the acute and chronic stages of inflammation, and IL-6 and bFGF were significantly associated with the extent of macular edema in patients with RVO. Besides VEGF, other inflammatory cytokines and angiogenesic factors may be associated with RVO. This finding may have implications for the medical treatment of RVO. 相似文献6.
Halvor Rollag Thor Ueland Anders ?sberg Anders Hartmann Alan G. Jardine Atul Humar Mark D. Pescovitz Angelo A. Bignamini P?l Aukrust 《PloS one》2013,8(4)
Background
While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.Patients and Methods
Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.Results
The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.Conclusion
Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease. 相似文献7.
Marte Eilertsen Sigve Andersen Samer Al-Saad Yury Kiselev Tom Donnem Helge Stenvold Ingvild Pettersen Khalid Al-Shibli Elin Richardsen Lill-Tove Busund Roy M. Bremnes 《PloS one》2014,9(9)
Introduction
Monocarboxylate transporters (MCTs) 1–4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.Methods
Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I–IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.Results
In univariate analyses; ↓MCT1 (P = 0.021) and ↑MCT4 (P = 0.027) expression in cancer cells, and ↑MCT1 (P = 0.003), ↓MCT2 (P = 0.006), ↓MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3–2.8, P = 0.001), ↓MCT2 (HR: 2.4, CI 95%: 1.5–3.9, P<0.001), ↓MCT3 (HR: 1.9, CI 95%: 1.1–3.5, P = 0.031) and ↑MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1–2.7, P = 0.016) were significant independent poor prognostic markers for DSS.Conclusions
We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments. 相似文献8.
Purpose
Obstructive sleep apnea (OSA) is a common disorder affecting 15–24% of the adults and is associated with increased risk of hypertension and atherosclerosis. The exact mechanisms underlying hypertension in OSA are not entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and a number of other diseases. We sought to determine the role of YKL-40 in endothelial dysfunction and hypertension in OSA.Methods
We studies 23 normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40, vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1or sFlt-1 were measured in plasma using ELISA methodology.Results
N-OSA subjects aged 49.1±2.3 years and H-OSA aged 51.3±1.9 years with BMI 36.1±1.6 and 37.6±1.9 kg/m2, respectively. The apnea-hypopnea index (AHI) was 41±5 events/hr in N-OSA and 46±6 in H-OSA with comparable degree of oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3%±0.8) compared to N-OSA (13.2%±0.6, P<0.0001). Plasma YKL-40 was significantly elevated in H-OSA (55.2±7.9 ng/ml vs. 35.6±4.2 ng/ml in N-OSA, P = 0.02) and had an inverse relationship with FMD (r = −0.52, P = 0.013). There was a significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF availability, and YKL-40 (r = 0.42, P = 0.04).Conclusion
The levels of plasma YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial-dependent vasodilatory capacity whereas there was a positive correlation between sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in part, due to perturbation of VEGF signaling, and may contribute to endothelial dysfunction and hypertension in OSA. 相似文献9.
Salvatore Sotgia Angelo Zinellu Arduino A. Mangoni Gianfranco Pintus John Attia Ciriaco Carru Mark McEvoy 《PloS one》2014,9(1)
Background
Despite the increasing interest towards the biological role of L-ergothioneine, little is known about the serum concentrations of this unusual aminothiol in older adults. We addressed this issue in a representative sample of community-dwelling middle-aged and older adults.Methods
Body mass index, estimated glomerular filtration rate, serum concentrations of L-ergothioneine, taurine, homocysteine, cysteine, glutathione, cysteinylglycine, and glutamylcysteine were evaluated in 439 subjects (age 55–85 years) randomly selected from the Hunter Community Study.Results
Median L-ergothioneine concentration in the entire cohort was 1.01 IQR 0.78–1.33 µmol/L. Concentrations were not affected by gender (P = 0.41) or by presence of chronic medical conditions (P = 0.15). By considering only healthy subjects, we defined a reference interval for L-ergothioneine serum concentrations from 0.36 (90% CI 0.31–0.44) to 3.08 (90% CI 2.45–3.76) µmol/L. Using stepwise multiple linear regression analysis L-ergothioneine was negatively correlated with age (rpartial = −0.15; P = 0.0018) and with glutamylcysteine concentrations (rpartial = −0.13; P = 0.0063).Conclusions
A thorough analysis of serum L-ergothioneine concentrations was performed in a large group of community-dwelling middle-aged and older adults. Reference intervals were established. Age and glutamylcysteine were independently negatively associated with L-ergothioneine serum concentration. 相似文献10.
Paul T. Williams Xue-Qiao Zhao Santica M. Marcovina B. Greg Brown Ronald M. Krauss 《PloS one》2013,8(2)
Objective
Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses.Methods
Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments.Results
The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2–24.6 nm) and LDL-IVa (23.3–24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values.Conclusions
Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol.Trial Registration
ClinicalTrials.gov NCT00000553 相似文献11.
Satu Piril? Mervi Taskinen Maila Turanlahti Merja Kajosaari Outi M?kitie Ulla M. Saarinen-Pihkala Heli Viljakainen 《PloS one》2014,9(10)
Objective
Both osteoporosis and cardiovascular disease (CVD) are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low phy-sical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD) and turnover markers (BTMs) in apparently healthy cohort.Design
A cross-sectional assessment of 155 healthy 32-year-old adults (74 males) was performed for skeletal status, CVD risk factors and lifestyle factors.Methods
We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP), collagen I carboxy-terminal telopeptide (ICTP) and urine collagen I aminoterminal telopeptide (U-NTX), as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were asses-sed using DXA scanning. Associations were tested with partial correlations in crude and adjusted mo-dels. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria) with multivariate analysis.Results
Osteocalcin and P1NP correlated inversely with insulin (R = −0.243, P = 0.003 and R = −0.187, P = 0.021) and glucose (R = −0.213, P = 0.009 and R = −0.190, P = 0.019), but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = −0.162, P = 0.053 and R = −0.093, P = 0.266) and with glucose (R = −0.099, P = 0.240 and R = −0.133, P = 0.110), respectively. Whole body BMD associated in-versely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model.Conclusions
In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass, no association continued to be present. In addition to fat mass, lifestyle factors, especially physical activity, modified the associations between CVD and bone charac-teristics. Prospective studies are needed to specify the role of mediators and lifestyle factors in the prevention of CVD and osteoporosis. 相似文献12.
Background
Intravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations.Methods
The distribution of serum lactic dehydrogenase (LDH) values was used as a surrogate measure of intravascular hemolysis in a contemporaneous patient group and an historical adult population from the Cooperative Study of Sickle Cell Disease (CSSCD), all with sickle cell anemia. Chronic hyper-hemolysis was defined by the top LDH quartile and was compared to the lowest LDH quartile.Results
Hyper-hemolysis subjects had higher systolic blood pressure, higher prevalence of leg ulcers (OR 3.27, 95% CI 1.92-5.53, P<0.0001), priapism (OR 2.62, 95% CI 1.13-6.90, P = 0.03) and pulmonary hypertension (OR 4.32, 95% CI 2.12-8.60, P<0.0001), while osteonecrosis (OR 0.32, 95% CI 0.19-0.54, P<0.0001) and pain (OR 0.23, 95% CI 0.09-0.55, P = 0.0004) were less prevalent. Hyper-hemolysis was influenced by fetal hemoglobin and α thalassemia, and was a risk factor for early death in the CSSCD population (Hazard Ratio = 1.97, P = 0.02).Conclusions
Steady state LDH measurements can identify a chronic hyper-hemolysis phenotype which includes less frequent vasooclusive pain and earlier mortality. Clinicians should consider sickle cell specific therapies for these patients, as is done for those with more frequent acute pain. The findings also suggest that an important class of disease modifiers in sickle cell anemia affect the rate of hemolysis. 相似文献13.
Purpose
To characterize the early ocular-surface changes or tear inflammatory-mediators levels following small-incision lenticule extraction (ReLEx smile) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK).Methods
Forty-seven myopic subjects were recruited for this prospective study. Fifteen underwent ReLEx smile and thirty-two underwent FS-LASIK. Corneal fluorescein (FL) staining, tear break-up time (TBUT), Schirmer I test (SIT), ocular surface disease index (OSDI) and central corneal sensitivity were evaluated in all participants. Tears were collected and analyzed for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF) and intercellular adhesion molecule-1 (ICAM-1) levels using multiplex magnetic beads. All measurements were preformed preoperatively and 1 day, 1 week, 1 month and 3 months postoperatively.Results
FL scores in ReLEx smile group were lower than those of FS-LASIK group 1 week postoperatively (P = 0.010). Compared to the FS-LASIK group, longer TBUT were observed in ReLEx smile group 1 month (P = 0.029) and 3 months (P = 0.045) postoperatively. No significant differences were found in tear secretion for the two groups (P>0.05). OSDI scores were higher in FS-LASIK group 1 month after surgery (P = 0.020). Higher central corneal sensitivity was observed in ReLEx smile group 1 week, 1 month and 3 months (P<0.05) postoperatively. Compared to FS-LASIK group, lower and faster recovery of IL-6 and NGF levels in tears was observed in ReLEx smile group postoperatively (P<0.05). Tears TNF-α and ICAM-1 concentrations were not significantly different between the two groups at any follow-up time (P>0.05). Moreover, IL-6 and NGF levels correlated with ocular surface changes after ReLEx smile or FS-LASIK.Conclusions
In the early postoperative period, ReLEx smile results in milder ocular surface changes than FS-LASIK. Furthermore, the tear inflammatory mediators IL-6 and NGF may play a crucial role in the ocular surface healing process following ReLEx smile and FS-LASIK. 相似文献14.
Khalid M. Alkharfy Nasser M. Al-Daghri Paul M. Vanhoutte Soundararajan Krishnaswamy Aimin Xu 《PloS one》2012,7(10)
Background
Elevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related co-morbidities including insulin resistance, dyslipidemia and hypertension.Objectives
The present study examined the relationship between serum level of RBP4 and various risk factors related to cardiovascular disease (CVD) in men and women.Methods
284 subjects (139 males, 145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44), were assessed for anthropometric and biochemical parameters related to obesity, diabetes and CVD. In addition, serum levels of several adipokines, including fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were measured using specific immunoassays.Results
Serum RBP4 level correlated significantly with principal component derived from known risk factors of CVD (β = 0.20±0.06, P = 0.002). Significance of this correlation was limited to women (β = 0.20±0.06, P = 0.002) and it persisted even after adjusting for BMI (β = 0.19±0.06, P = 0.002). Overall (n = 284) serum RBP4 values significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of CVD subjects was significantly higher than healthy control (P = 0.001) and non-obese diabetes (P = 0.04) groups, but this difference was attributable to differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P = 0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between CVD and other groups.Conclusions
Results of this study indicate a significant correlation between serum RBP4 and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women. 相似文献15.
Linda E. Kelemen James D. Brenton Christine Parkinson Hayley C. Whitaker Anna M. Piskorz Ilona Csizmadi Paula J. Robson 《PloS one》2014,9(5)
Background
Serum concentrations of the tumor-associated folate receptor 1 (FOLR1) protein may be a marker for early cancer detection, yet concentrations have also been detected in cancer-free women. We investigated the conditions associated with circulating FOLR1 protein in healthy individuals and sought to clarify the range of normal serum values.Methods
Sera of cancer-free men and women (N = 60) enrolled in a population-based cohort study in Alberta, Canada were analyzed for FOLR1 protein using an electrochemical luminescence immunoassay. Dietary, lifestyle, medical and reproductive history information was collected by questionnaires. Differences in serum FOLR1 concentrations between groups were assessed by non-parametric tests, and predictors of serum FOLR1 concentrations were estimated using multivariable linear regression.Results
Median serum FOLR1 concentration was higher in women (491 pg/ml, range = 327–693 pg/ml) than in men (404 pg/ml, range = 340–682 pg/ml), P = 0.001. FOLR1 concentration was also positively associated with vitamin A intake (P = 0.02), and showed positive trends with age and with oral contraceptive hormone use among women and an inverse trend with body mass index. All variables examined explained almost half of the variation in serum FOLR1 (model R2 = 0.44, P = 0.04); however, the retention of gender (P = 0.003) and vitamin A intake (P = 0.03) together explained 20% (P = 0.001) of serum FOLR1 variation. No other predictor was significant at P<0.05.Conclusions
The positive association between serum FOLR1 concentration and female gender independent of an age effect suggests caution against statements to exploit serum FOLR1 for early cancer detection without further understanding the biological underpinnings of these observations. Serum FOLR1 concentrations may be influenced by the steroid retinoic acid (vitamin A) but do not appear to be associated with folate nutritional status. These findings require confirmation in larger independent studies. 相似文献16.
Background
Several prospective observational studies suggest that gamma-glutamyltransferase(GGT) level is positively associated with risk of hypertension. However, these studies draw inconsistent conclusions. Therefore, we conducted a systematic review and meta-analysis to evaluate the exact association between GGT level and subsequent development of hypertension.Methods
We searched Pubmed, Embase, and Science Citation Index (ISI Web of Science) for prospective cohort studies examining the association between GGT level and hypertension. Then, pooled effect estimates (RRs) for the association between GGT level and hypertension were calculated.Results
A total of 13 prospective cohort studies including 43314 participants and 5280 cases of hypertension were included. The pooled RR of hypertension was 1.94(95%CI: 1.55–2.43; P<0.001) when comparing the risk of hypertension between the highest versus lowest category of GGT levels. Moreover, the risk of hypertension increased by 23% (summary RR: 1.23; 95%CI: 1.13–1.32; P<0.001) per 1 SD logGGT increment. Subgroup analyses showed significant positive associations in each subgroup except in ≧160/95 subgroup (RR: 2.56, 95%CI: 0.87–7.54; P = 0.088) and nondrinkers subgroup (RR: 1.76, 95%CI: 0.88–3.53; P = 0.113). Sensitivity analyses showed no single study significantly affects the pooled RRs. No publication bias was found in our meta-analysis.Conclusions
GGT level is positively associated with the development of hypertension. Further studies are needed to confirm our findings and elucidate the exact mechanisms between GGT level and the incidence of hypertension. 相似文献17.
Anila Basit Nafees Ahmad Amer Hayat Khan Arshad Javaid Syed Azhar Syed Sulaiman Afsar Khan Afridi Azreen Syazril Adnan Israr ul Haq Syed Saleem Shah Ahmed Ahadi Izaz Ahmad 《PloS one》2014,9(4)
Background
Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).Objectives
The present study was conducted with the aim to evaluate the rate and predictors of culture conversion at two months in MDR-TB patients.Methods
All confirmed pulmonary MDR-TB patients enrolled for treatment at Lady Reading Hospital Peshawar, Pakistan from 1 January to 31 December 2012 and met the inclusion criteria were reviewed retrospectively. Rate and predictors of culture conversion at two months were evaluated.Results
Eighty seven (53.4%) out of 163 patients achieved culture conversion at two months. In a multivariate analysis lung cavitation at baseline chest X-ray (P = 0.006, OR = 0.349), resistance to ofloxacin (P = 0.041, OR = 0.193) and streptomycin (P = 0.017, OR = 0.295) had statistically significant (P<0.05) negative association with culture conversion at two months.Conclusion
A reasonable proportion of patients achieved culture conversion at two months. Factors negatively associated with culture conversion at two months can be easily identified either before diagnosis or early in the course of MDR-TB treatment. This may help in better care of individual patients by identifying them early and treating them vigorously. 相似文献18.
Mathijs A. J. van de Put Lisette Hoeksema Wouter Wanders Ilja M. Nolte Johanna M. M. Hooymans Leonoor I. Los 《PloS one》2014,9(12)
Objective
To determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision.Methods
In a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out.Results
Operated and fellow control eyes differed significantly in mean LogMAR BCVA (P<0.0001), median Log contrast acuity (P<0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P<0.0001), contrast acuity (R = 0.472, P<0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044).Conclusions
A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances. 相似文献19.
Gelin Xu Zhizhong Zhang Qiushi Lv Yun Li Ruidong Ye Yunyun Xiong Yongjun Jiang Xinfeng Liu 《PloS one》2014,9(11)
Background
Allocation of health research funds among diseases has never been evaluated in China. This study aimed to examine the relationship between disease-specific funding levels of National Nature Science Foundation of China (NSFC), the main governmental resource for health research in China, and burden of disease.Methods
Funding magnitudes for 53 diseases or conditions were obtained from the website of NSFC. Measures of disease burden, mortality, years of life lost (YLLs) and disability-adjusted life years (DALYs), were derived from the Global Burden of Disease Study 2010. The relationship between NSFC funding and disease burden was analyzed with univariate linear regression. For each measure associated with funding, regression-derived estimates were used to calculate the expected funds for each disease. The actual and expected funds were then compared. We also evaluated the impacts of changes of disease burden metrics since 1990, and differences from the world averages on NSFC funding.Results
NSFC health research funding was associated with disease burden measured in mortality (R = 0.33, P = 0.02), YLLs (R = 0.39, P = 0.004), and DALYs (R = 0.40, P = 0.003). But none of the changes of mortality (R = 0.22, P = 0.12), YLLs (R = −0.04, P = 0.79) and DALYs (R = −0.003, P = 0.98) since 1990 was associated with the funding magnitudes. None of the differences of mortality (R = −0.11, P = 0.45), YLLs (R = −0.11, P = 0.43) and DALYs (R = −0.12, P = 0.38) from that of the concurrent world averages were associated with the funding magnitudes. Measured by DALY, stroke and COPD received the least funding compared to expected; while leukemia and diabetes received the most funding compared to expected.Conclusion
Although NSFC funding were roughly associated with disease burden as measured in mortality, YLLs and DALYs. Some major diseases such as stroke were underfunded; while others such as leukaemia were overfunded. Change of disease burden during the last 20 years and country-specialized disease burden were not reflected in current allocation of NSFC funds. 相似文献20.
Chi-Sheng Hung Jen-Kuang Lee Chung-Yi Yang Hung-Ren Hsieh Wen-Ya Ma Mao-Shin Lin Pi-Hua Liu Shyang-Rong Shih Jyh-Ming Liou Lee-Ming Chuang Ming-Fong Chen Jou-Wei Lin Jung-Nan Wei Hung-Yuan Li 《PloS one》2014,9(11)