共查询到20条相似文献,搜索用时 31 毫秒
1.
Murali Ravoori Aneta J. Czaplinska Charles Sikes Lin Han Evan M. Johnson Wei Qiao Chaan Ng Dianna D. Cody William A. Murphy Jr Kim-Anh Do Nora M. Navone Vikas Kundra 《PloS one》2010,5(3)
Background
To compare nondestructive in vivo and ex vivo micro-computed tomography (μCT) and ex vivo dual-energy-X-ray-absorptiometry (DXA) in characterizing mineralized cortical and trabecular bone response to prostate cancer involving the skeleton in a mouse model.Methodology/Principal Findings
In vivo μCT was performed before and 10 weeks after implantation of human prostate cancer cells (MDA-PCa-2b) or vehicle into SCID mouse femora. After resection, femora were imaged by nondestructive ex vivo specimen μCT at three voxel sizes (31 µ, 16 µ, 8 µ) and DXA, and then sectioned for histomorphometric analysis of mineralized bone. Bone mineral density (BMD), trabecular parameters (number, TbN; separation, TbSp; thickness, TbTh) and mineralized bone volume/total bone volume (BV/TV) were compared and correlated among imaging methods and histomorphometry. Statistical tests were considered significant if P<0.05. Ten weeks post inoculation, diaphyseal BMD increased in the femur with tumor compared to the opposite femur by all modalities (p<0.005, n = 11). Diaphyseal BMD by in vivo μCT correlated with ex vivo 31 and 16 µm μCT and histomorphometry BV/TV (r = 0.91–0.94, P<0.001, n = 11). DXA BMD correlated less with bone histomorphometry (r = 0.73, P<0.001, n = 11) and DXA did not distinguish trabeculae from cortex. By in vivo and ex vivo μCT, trabecular BMD decreased (P<0.05, n = 11) as opposed to the cortex. Unlike BMD, trabecular morphologic parameters were threshold-dependent and when using “fixed-optimal-thresholds,” all except TbTh demonstrated trabecular loss with tumor and correlated with histomorphometry (r = 0.73–0.90, P<0.05, n = 11).Conclusions/Significance
Prostate cancer involving the skeleton can elicit a host bone response that differentially affects the cortex compared to trabeculae and that can be quantified noninvasively in vivo and nondestructively ex vivo. 相似文献2.
Objective
This study was designed to (1) investigate the expression profiles of resistin in db/db mice and its dynamic association with metabolic parameters; and (2) evaluate the effects of Rosiglitazone on production of resistin.Methods
Db/db mice and their lean litter mates were used for this study. Epididymal fat tissue was excised from mice of different age (from 5 to 12 weeks) for ex vivo incubation. Resistin,along with adiponectin,in serum and conditioned culture medium of epididymal fat pads were measured with immunoassays. The gene expression of resistin was determined by real-time PCR. Rosiglitazone or the vehicle (PBS) was administered into db/db mice by daily intra-gastric gavage. Differentiated 3T3-L1 adipocytes were used for in vitro evaluation.Results
The secretion of resistin from the fat pads in db/db mice was significantly lower than that in lean mice (P<0.01). The mRNA expression of the resistin gene in fat tissue of db/db mice at the age of 5 weeks was decreased by 60.5% compared to lean controls (p<0.05). Serum levels of resistin were comparable between the obese and lean groups, perhaps due to the increased total fat mass in db/db mice. Correlation analysis showed that serum resistin levels were positively correlated to resistin secretion from fat pads(r = 0.844,P = 0.000), while negatively associated with the body weight (r = −0.515, P = 0.000) and fasting glucose level (r = −0.357, P = 0.002). Notably, treatment with rosiglitazone increased the serum resistin levels by 66.4%(P<0.05)in db/db mice. In 3T3-L1 adipocytes, Rosiglitazone (10 uM) markedly enhanced the secretion of resistin by 120% (P<0.01) and its gene expression by 78.1% (P<0.05).Conclusion
Both resistin gene expression and its secretion from the epididymal adipose tissue were decreased in db/db obese mice, while the insulin-sensitizing drug rosiglitazone increased resistin production. Our results do not support the role of resistin as an etiological link between obesity and diabetes. 相似文献3.
Sali A Guerron AD Gordish-Dressman H Spurney CF Iantorno M Hoffman EP Nagaraju K 《PloS one》2012,7(4):e34204
Background
Dmdmdx (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations.Methods and Findings
We performed nine pre-clinical efficacy trials (treated N = 129, untreated N = 106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of GCs on dystrophin-deficient skeletal and cardiac muscles of mdx mice. Our results indicate that continuous GC treatment results in early (e.g., at 50 days) improvements in normalized parameters such as grip strength, motor coordination and maximal in vitro force contractions on isolated EDL muscle, but these initial benefits are followed by a progressive loss of muscle strength after 100 days. We also found a significant increase in heart fibrosis that is reflected in a significant deterioration in cardiac systolic function after 100 days of treatment.Conclusion
Continuous administration of prednisone to mdx mice initially improves skeletal muscle strength, but further therapy result in deterioration of muscle strength and cardiac function associated with enhanced cardiac fibrosis. These results suggest that GCs may not serve as an appropriate positive control for long-term mdx mouse preclinical trials. 相似文献4.
Billy Sperlich Dennis-Peter Born Kimmo Kaskinoro Kari K. Kalliokoski Marko S. Laaksonen 《PloS one》2013,8(4)
The purpose of this experiment was to investigate skeletal muscle blood flow and glucose uptake in m. biceps (BF) and m. quadriceps femoris (QF) 1) during recovery from high intensity cycle exercise, and 2) while wearing a compression short applying ∼37 mmHg to the thigh muscles. Blood flow and glucose uptake were measured in the compressed and non-compressed leg of 6 healthy men by using positron emission tomography. At baseline blood flow in QF (P = 0.79) and BF (P = 0.90) did not differ between the compressed and the non-compressed leg. During recovery muscle blood flow was higher compared to baseline in both compressed (P<0.01) and non-compressed QF (P<0.001) but not in compressed (P = 0.41) and non-compressed BF (P = 0.05; effect size = 2.74). During recovery blood flow was lower in compressed QF (P<0.01) but not in BF (P = 0.26) compared to the non-compressed muscles. During baseline and recovery no differences in blood flow were detected between the superficial and deep parts of QF in both, compressed (baseline P = 0.79; recovery P = 0.68) and non-compressed leg (baseline P = 0.64; recovery P = 0.06). During recovery glucose uptake was higher in QF compared to BF in both conditions (P<0.01) with no difference between the compressed and non-compressed thigh. Glucose uptake was higher in the deep compared to the superficial parts of QF (compression leg P = 0.02). These results demonstrate that wearing compression shorts with ∼37 mmHg of external pressure reduces blood flow both in the deep and superficial regions of muscle tissue during recovery from high intensity exercise but does not affect glucose uptake in BF and QF. 相似文献
5.
Riccardo Di Giminiani Leila Fabiani Giuliano Baldini Giovanni Cardelli Aldo Giovannelli Jozsef Tihanyi 《PloS one》2014,9(11)
Objective
To investigate the acute residual hormonal and neuromuscular responses exhibited following a single session of mechanical vibration applied to the upper extremities among different acceleration loads.Methods
Thirty male students were randomly assigned to a high vibration group (HVG), a low vibration group (LVG), or a control group (CG). A randomized double-blind, controlled-parallel study design was employed. The measurements and interventions were performed at the Laboratory of Biomechanics of the University of L''Aquila. The HVG and LVG participants were exposed to a series of 20 trials ×10 s of synchronous whole-body vibration (WBV) with a 10-s pause between each trial and a 4-min pause after the first 10 trials. The CG participants assumed an isometric push-up position without WBV. The outcome measures were growth hormone (GH), testosterone, maximal voluntary isometric contraction during bench-press, maximal voluntary isometric contraction during handgrip, and electromyography root-mean-square (EMGrms) muscle activity (pectoralis major [PM], triceps brachii [TB], anterior deltoid [DE], and flexor carpi radialis [FCR]).Results
The GH increased significantly over time only in the HVG (P = 0.003). Additionally, the testosterone levels changed significantly over time in the LVG (P = 0.011) and the HVG (P = 0.001). MVC during bench press decreased significantly in the LVG (P = 0.001) and the HVG (P = 0.002). In the HVG, the EMGrms decreased significantly in the TB (P = 0.006) muscle. In the LVG, the EMGrms decreased significantly in the DE (P = 0.009) and FCR (P = 0.006) muscles.Conclusion
Synchronous WBV acutely increased GH and testosterone serum concentrations and decreased the MVC and their respective maximal EMGrms activities, which indicated a possible central fatigue effect. Interestingly, only the GH response was dependent on the acceleration with respect to the subjects'' responsiveness. 相似文献6.
Murali Ravoori Jyoti Duggal Mihai Gagea Lin Han Sheela Singh Ping Liu Wei Wei Dustin K. Ragan James A. Bankson Jingfei Ma Vikas Kundra 《PloS one》2013,8(3)
Purpose
Prostate imaging requires optimization in young and old mouse models. We tested which MR sequences and field strengths best depict the prostate gland in young and old mice; and, whether prostate MR signal, size, and architecture change with age.Technique
Magnetic resonance imaging (MRI) of the prostate of young (2 months) and old (18 months) male nude mice (n = 6) was performed at 4.7 and 7 T and SCID mice (n = 6) at 7 T field strengths, using T1, fat suppressed T1, DWI, T2, fat suppressed T2, as well as T2-based- and proton density-based Dixon “water only” sequences. Images were ranked for best overall sequence for prostate visualization, prostate delineation, and quality of fat suppression. Prostate volume and signal characteristics were compared and histology was performed.Results
T2-based-Dixon “water only” images ranked best overall for prostate visualization and delineation as well as fat suppression (n = 6, P<0.001) at both 4.7 T and 7 T in nude and 7T in SCID mice. Evaluated in nude mice, T2-based Dixon “water only” had greater prostate CNR and lower fat SNR at 7 T than 4.7 T (P<0.001). Prostate volume was less in older than younger mice (n = 6, P<0.02 nude mice; n = 6, P<0.002 SCID mice). Prostate T2 FSE as well as proton density-based and T2-based-Dixon “water only” signal intensity was higher in younger than older mice (P<0.001 nude mice; P<0.01 SCID mice) both at 4.7 and 7 T. This corresponded to an increase in glandular hyperplasia in older mice by histology (P<0.01, n = 6).Conclusion
T2-based Dixon “water only” images best depict the mouse prostate in young and old nude mice at 4.7 and 7 T. The mouse prostate decreases in size with age. The decrease in T2 and T2-based Dixon “water only” signal with age corresponds with glandular hyperplasia. Findings suggest age should be an important determinant when choosing models of prostate biology and disease. 相似文献7.
Bish LT Yarchoan M Sleeper MM Gazzara JA Morine KJ Acosta P Barton ER Sweeney HL 《PloS one》2011,6(6):e20856
Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6–9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease. 相似文献
8.
Alanna C. Morrison Joshua C. Bis Shih-Jen Hwang Georg B. Ehret Thomas Lumley Kenneth Rice Donna Muzny Richard A. Gibbs Eric Boerwinkle Bruce M. Psaty Aravinda Chakravarti Daniel Levy 《PloS one》2014,9(10)
Background
Genome-wide association studies (GWAS) identified multiple loci for blood pressure (BP) and hypertension. Six genes – ATP2B1, CACNB2, CYP17A1, JAG1, PLEKHA7, and SH2B3 – were evaluated for sequence variation with large effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP).Methods and Results
Targeted genomic sequence was determined in 4,178 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Common variants (≥50 minor allele copies) were evaluated individually and rare variants (minor allele frequency, MAF≤1%) were aggregated by locus. 464 common variants were identified across the 6 genes. An upstream CYP17A1 variant, rs11191416 (MAF = 0.09), was the most significant association for SBP (P = 0.0005); however the association was attenuated (P = 0.0469) after conditioning on the GWAS index single nucleotide polymorphism (SNP). A PLEKHA7 intronic variant was the strongest DBP association (rs12806040, MAF = 0.007, P = 0.0006) and was not in LD (r2 = 0.01) with the GWAS SNP. A CACNB2 intronic SNP, rs1571787, was the most significant association with PP (MAF = 0.27, P = 0.0003), but was not independent from the GWAS SNP (r2 = 0.34). Three variants (rs6163 and rs743572 in the CYP17A1 region and rs112467382 in PLEKHA7) were associated with BP traits (P<0.001). Rare variation, aggregately assessed in the 6 regions, was not significantly associated with BP measures.Conclusion
Six targeted gene regions, previously identified by GWAS, did not harbor novel variation with large effects on BP in this sample. 相似文献9.
Christopher F. Spurney Hee-Jae Cha Arpana Sali Gouri S. Pandey Emidio Pistilli Alfredo D. Guerron Heather Gordish-Dressman Eric P. Hoffman Kanneboyina Nagaraju 《PloS one》2010,5(1)
Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tβ4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8–10 weeks old, were treated with 150 µg of Tβ4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tβ4 and amount of fibrosis were quantified using immunohistochemistry and Gomori''s tri-chrome staining, respectively. Mdx mice treated with Tβ4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tβ4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tβ4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy. 相似文献
10.
Ray-Hwang Yuan Ko-Tung Chang Yu-Ling Chen Hey-Chi Hsu Po-Huang Lee Po-Lin Lai Yung-Ming Jeng 《PloS one》2013,8(6)
The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry. The S100P protein was expressed in 173 of the 305 (56.7%) HCC tumors. The expression of S100P correlated with female sex (P = 0.0162), high serum α-fetoprotein level (P = 0.0001), high tumor grade (P = 0.0029), high tumor stage (P = 0.0319), the presence of the p53 mutation (P = 0.0032), and the absence of the β-catenin mutation (P = 0.0489). Patients with HCC tumors that expressed S100P were more likely to have early tumor recurrence (ETR) (P = 0.0189) and lower 5-year survival (P = 0.0023). The multivariate analysis confirmed that S100P expression was an independent prognostic factor in HCC. The combinatorial analysis showed an additive unfavorable prognostic interaction between S100P expression and the p53 mutation. In contrast, the β-catenin mutation was associated with better prognosis in both S100P-positive and -negative HCCs. Furthermore, S100P expression was a predictor of survival in HCC patients with high tumor stage or ETR (P = 0.0026 and P = 0.0002, respectively). Our study indicates the expression of the S100P protein is a novel independent predictor for poor prognosis in HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage or ETR. 相似文献
11.
Koramannil Radha Saradalekshmi Nanoth Vellichiramal Neetha Sanish Sathyan Indu V. Nair Chandrasekharan M. Nair Moinak Banerjee 《PloS one》2014,9(5)
DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient''s gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022) were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023) and allele (P = 0.0063) increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia. 相似文献
12.
Thomas Reinert Michael Borre Anders Christiansen Gregers G. Hermann Torben F. ?rntoft Lars Dyrskj?t 《PloS one》2012,7(10)
Background
Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation markers that showed significant diagnostic value. We evaluated the significance of the biomarkers for early detection of tumor recurrence in urine.Methodology/Principal Findings
The methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens were measured by real-time PCR (MethyLight). We analyzed 390 urine sediments from 184 patients diagnosed with NMIBC. Urine from 35 age-matched control individuals was used to determine the methylation baseline levels. Recurrence was diagnosed by cystoscopy and verified by histology. Initially, we compared urine from bladder cancer patients and healthy individuals and detected significant hypermethylation of all six markers (P<0.0001) achieving sensitivity in the range 82%–89% and specificity in the range 94%–100%. Following, we validated the urinary hypermethylation for use in recurrence surveillance and found sensitivities of 88–94% and specificities of 43–67%. EOMES, POU4F2, VIM and ZNF154 were more frequently methylated in urine from patients with higher grade tumors (P≤0.08). Univariate Cox regression analysis showed that five markers were significantly associated with disease recurrence; HOXA9 (HR = 7.8, P = 0.006), POU4F2 (HR = 8.5, P = 0.001), TWIST1 (HR = 12.0, P = 0.015), VIM (HR = 8.0, P = 0.001), and ZNF154 (HR = 13.9, P<0.001). Interestingly, for one group of patients (n = 15) we found that hypermethylation was consistently present in the urine samples despite the lack of tumor recurrences, indicating the presence of a field defect.Conclusion/Significance
Methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens are promising diagnostic biomarkers for bladder cancer recurrence surveillance. 相似文献13.
Paul T. Williams 《PloS one》2013,8(11)
Purpose
To assess the dose-response relationships between cause-specific mortality and exercise energy expenditure in a prospective epidemiological cohort of walkers.Methods
The sample consisted of the 8,436 male and 33,586 female participants of the National Walkers'' Health Study. Walking energy expenditure was calculated in metabolic equivalents (METs, 1 MET = 3.5 ml O2/kg/min), which were used to divide the cohort into four exercise categories: category 1 (≤1.07 MET-hours/d), category 2 (1.07 to 1.8 MET-hours/d), category 3 (1.8 to 3.6 MET-hours/d), and category 4 (≥3.6 MET-hours/d). Competing risk regression analyses were use to calculate the risk of mortality for categories 2, 3 and 4 relative to category 1.Results
22.9% of the subjects were in category 1, 16.1% in category 2, 33.3% in category 3, and 27.7% in category 4. There were 2,448 deaths during the 9.6 average years of follow-up. Total mortality was 11.2% lower in category 2 (P = 0.04), 32.4% lower in category 3 (P<10−12) and 32.9% lower in category 4 (P = 10−11) than in category 1. For underlying causes of death, the respective risk reductions for categories 2, 3 and 4 were 23.6% (P = 0.008), 35.2% (P<10−5), and 34.9% (P = 0.0001) for cardiovascular disease mortality; 27.8% (P = 0.18), 20.6% (P = 0.07), and 31.4% (P = 0.009) for ischemic heart disease mortality; and 39.4% (P = 0.18), 63.8% (P = 0.005), and 90.6% (P = 0.002) for diabetes mortality when compared to category 1. For all related mortality (i.e., underlying and contributing causes of death combined), the respective risk reductions for categories 2, 3 and 4 were 18.7% (P = 0.22), 42.5% (P = 0.001), and 57.5% (P = 0.0001) for heart failure; 9.4% (P = 0.56), 44.3% (P = 0.0004), and 33.5% (P = 0.02) for hypertensive diseases; 11.5% (P = 0.38), 41.0% (P<10−4), and 35.5% (P = 0.001) for dysrhythmias: and 23.2% (P = 0.13), 45.8% (P = 0.0002), and 41.1% (P = 0.005) for cerebrovascular diseases when compared to category 1.Conclusions
There are substantial health benefits to exceeding the current exercise guidelines. 相似文献14.
Danjie Jiang Dawei Zheng Lingyan Wang Yi Huang Haibo Liu Leiting Xu Qi Liao Panpan Liu Xinbao Shi Zhaoyang Wang Lebo Sun Qingyun Zhou Ni Li Limin Xu Yanping Le Meng Ye Guofeng Shao Shiwei Duan 《PloS one》2013,8(3)
PLA2G7 gene product is a secreted enzyme whose activity is associated with coronary heart disease (CHD). The goal of our study is to investigate the contribution of PLA2G7 promoter DNA methylation to the risk of CHD. Using the bisulphite pyrosequencing technology, PLA2G7 methylation was measured among 36 CHD cases and 36 well-matched controls. Our results indicated that there was a significant association between PLA2G7 methylation and CHD (adjusted P = 0.025). Significant gender-specific correlation was observed between age and PLA2G7 methylation (males: adjusted r = −0.365, adjusted P = 0.037; females: adjusted r = 0.373, adjusted P = 0.035). A breakdown analysis by gender showed that PLA2G7 methylation was significantly associated with CHD in females (adjusted P = 0.003) but not in males. A further two-way ANOVA analysis showed there was a significant interaction between gender and status of CHD for PLA2G7 methylation (gender*CHD: P = 6.04E−7). Moreover, PLA2G7 methylation is associated with the levels of total cholesterols (TC, r = 0.462, P = 0.009), triglyceride (TG, r = 0.414, P = 0.02) and Apolipoprotein B (ApoB, r = 0.396, P = 0.028) in females but not in males (adjusted P>0.4). Receiver operating characteristic (ROC) curves showed that PLA2G7 methylation could predict the risk of CHD in females (area under curve (AUC) = 0.912, P = 2.40E−5). Our results suggest that PLA2G7 methylation changes with aging in a gender-specific pattern. The correlation between PLA2G7 methylation and CHD risk in females is independent of other parameters including age, smoking, diabetes and hypertension. PLA2G7 methylation might exert its effects on the risk of CHD by regulating the levels of TC, TG, and ApoB in females. The gender disparities in the PLA2G7 methylation may play a role in the molecular mechanisms underlying the pathophysiology of CHD. 相似文献
15.
《PLoS genetics》2009,5(12)
The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P≤5×10−8). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P≤0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2×10−19 for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9×10−8, n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5×10−6, n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2×10−3, n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk. 相似文献
16.
Jing Li Rou Jiang Wen-Sheng Liu Qing Liu Miao Xu Qi-Sheng Feng Li-Zhen Chen Jin-Xin Bei Ming-Yuan Chen Yi-Xin Zeng 《PloS one》2013,8(12)
Background
Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.Methods
A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.Results
Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×109/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×109/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417–0.748; P<0.001), DFS (HR = 0.669, 95% CI = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).Conclusions
The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients. 相似文献17.
Paul T. Williams 《PloS one》2013,8(12)
Purpose
Identify predictors of breast cancer mortality in women who exercised below (<7.5 metabolic equivalent hours/week, MET-hours/wk), at (7.5 to 12.5 MET-hours/wk), or above (≥12.5 MET-hours/wk) recommended levels.Methods
Cox proportional hazard analyses of baseline pre-diagnosis MET-hours/wk vs. breast cancer mortality adjusted for follow-up age, race, baseline menopause, and estrogen and oral contraceptive use in 79,124 women (32,872 walkers, 46,252 runners) from the National Walkers'' and Runners'' Health Studies.Results
One-hundred eleven women (57 walkers, 54 runners) died from breast cancer during the 11-year follow-up. The decline in mortality in women who exercised ≥7.5 MET-hours/wk was not different for walking and running (P = 0.34), so running and walking energy expenditures were combined. The risk for breast cancer mortality was 41.5% lower for ≥7.5 vs. <7.5 MET-hours/wk (HR: 0.585, 95%CI: 0.382 to 0.924, P = 0.02), which persisted when adjusted for BMI (HR: 0.584, 95%CI: 0.368 to 0.956, P = 0.03). Other than age and menopause, baseline bra cup size was the strongest predictor of breast cancer mortality, i.e., 57.9% risk increase per cup size when adjusted for MET-hours/wk and the other covariates (HR: 1.579, 95%CI: 1.268 to 1.966, P<0.0001), and 70.4% greater when further adjusted for BMI (HR: 1.704, 95%CI: 1.344 to 2.156, P = 10−5). Breast cancer mortality was 4.0-fold greater (HR: 3.980, 95%CI: 1.894 to 9.412, P = 0.0001) for C-cup, and 4.7-fold greater (HR: 4.668, 95%CI: 1.963 to 11.980, P = 0.0004) for ≥D-cup vs. A-cup when adjusted for BMI and other covariates. Adjustment for cup size and BMI did not eliminate the association between breast cancer mortality and ≥7.5 MET-hour/wk walked or run (HR: 0.615, 95%CI: 0.389 to 1.004, P = 0.05).Conclusion
Breast cancer mortality decreased in association with both meeting the exercise recommendations and smaller breast volume. 相似文献18.
Jui-Ting Hsu Ying-Ju Chen Jung-Ting Ho Heng-Li Huang Shun-Ping Wang Fu-Chou Cheng Jay Wu Ming-Tzu Tsai 《PloS one》2014,9(9)
Objective
The objective of this study was to evaluate the relationship between the trabecular bone microarchitecture and cortical bone morphology by using micro-computed tomography (micro-CT) and dental cone-beam computed tomography (dental CT).Materials and Methods
Sixteen femurs and eight fifth lumbar vertebrae were collected from eight male Sprague Dawley rats. Four trabecular bone microarchitecture parameters related to the fifth lumbar vertebral body (percent bone volume [BV/TV], trabecular thickness [TbTh], trabecular separation [TbSp], and trabecular number [TbN]) were calculated using micro-CT. In addition, the volumetric cancellous bone grayscale value (vCanGrayscale) of the fifth lumbar vertebral body was measured using dental CT. Furthermore, four cortical bone morphology parameters of the femoral diaphysis (total cross-sectional area [TtAr], cortical area [CtAr], cortical bone area fraction [CtAr/TtAr], and cortical thickness [CtTh]) were calculated using both micro-CT and dental CT. Pearson analysis was conducted to calculate the correlation coefficients (r) of the micro-CT and dental CT measurements. Paired-sample t tests were used to compare the differences between the measurements of the four cortical bone morphology parameters obtained using micro-CT and dental CT.Results
High correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV [r = 0.84] and TbTh [r = 0.84]) measured using micro-CT were observed. The absolute value of the four cortical bone morphology parameters may be different between the dental CT and micro-CT approaches. However, high correlations (r ranged from 0.71 to 0.90) among these four cortical bone morphology parameters measured using the two approaches were obtained.Conclusion
We observed high correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV and TbTh) measured using micro-CT, in addition to high correlations between the cortical bone morphology measured using micro-CT and dental CT. Further experiments are necessary to validate the use of dental CT on human bone. 相似文献19.
20.
Tao Yang Yu Liang Yan Zhang Qing Gu Guo Chen Xin-Hai Ni Xiu-Zhang Lv Zhi-Hong Liu Chang-Ming Xiong Jian-Guo He 《PloS one》2013,8(8)