Effects of Ezetimibe on Endothelial Progenitor Cells and Microparticles in High-Risk Patients

Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34⁺/CD133⁺/KDR⁺), EMP (CD51⁺), and PMP (CD42⁺/CD31⁺) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34⁺/KDR⁺ EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51⁺ EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.     

Is high prevalence of vitamin D deficiency a correlate for attention deficit hyperactivity disorder?

The aim of the study was to determine the association between vitamin D and attention deficit hyperactivity disorder (ADHD), and difference in the level of vitamin D in ADHD children and control. This a case–control study carried out in school health and primary health care clinics. A total of 1,331 children and adolescents who were diagnosed with ADHD based on clinical criteria and standardized questionnaires were enrolled in this study and were matched with 1,331 controls, aged 5–18 years old. Data on body mass index (BMI), clinical biochemistry variables including serum 25-hydroxyvitamin D were collected. The study found significant association between ADHD and vitamin D deficiency after adjusting for BMI and sex (adj. OR 1.54; 95 % CI 1.32–1.81; P < 0.001). Majority of the ADHD children were in the age group 5–10 years (40.7 %), followed by 11–13 years (38.4 %). The proportion of BMI <85th percentile was significantly over represented in ADHD group as compared to healthy control (87.8 vs. 83 %; P < 0.001, respectively), while on the other hand, BMI >95th percentile was over represented in the control than ADHD group (7.6 vs. 4.6 %; P < 0.001, respectively). Mean values of vitamin D (ng/mL) were significantly lower in ADHD children (16.6 ± 7.8) than in healthy children (23.5 ± 9.0) (P < 0.001). There was significant correlation between vitamin D deficiency and age (r = ?0.191, P = 0.001); calcium (r = 0.272, P = 0.001); phosphorous (r = 0.284, P = 0.001); magnesium (r = 0.292, P = 0.001); and BMI (r = 0.498, P = 0.001) in ADHD children. The vitamin D deficiency was higher in ADHD children compared to healthy children.     

Seasonal variations in larval biomass and biochemical composition of brown shrimp, Crangon crangon (Decapoda, Caridea), at hatching

The “brown shrimp”, Crangon crangon (Linnaeus 1758), is a benthic key species in the North Sea ecosystem, supporting an intense commercial fishery. Its reproductive pattern is characterized by a continuous spawning season from mid-winter to early autumn. During this extended period, C. crangon shows significant seasonal variations in egg size and embryonic biomass, which may influence larval quality at hatching. In the present study, we quantified seasonal changes in dry weight (W) and chemical composition (CHN, protein and lipid) of newly hatched larvae of C. crangon. Our data revealed significant variations, with maximum biomass values at the beginning of the hatching season (February–March), a decrease throughout spring (April–May) and a minimum in summer (June–September). While all absolute values of biomass and biochemical constituents per larva showed highly significant differences between months (P < 0.001), CHN, protein and lipid concentrations (expressed as percentage values of dry weight) showed only marginally significant differences (P < 0.05). According to generalized additive models (GAM), key variables of embryonic development exerted significant effects on larval condition at hatching: The larval carbon content (C) was positively correlated with embryonic carbon content shortly after egg-laying (r ² = 0.60; P < 0.001) and negatively with the average incubation temperature during the period of embryonic development (r ² = 0.35; P < 0.001). Additionally, water temperature (r ² = 0.57; P < 0.001) and food availability (phytoplankton C; r ² = 0.39; P < 0.001) at the time of hatching were negatively correlated with larval C content at hatching. In conclusion, “winter larvae” hatching from larger “winter eggs” showed higher initial values of biomass compared to “summer larvae” originating from smaller “summer eggs”. This indicates carry-over effects persisting from the embryonic to the larval phase. Since “winter larvae” are more likely exposed to poor nutritional conditions, intraspecific variability in larval biomass at hatching is interpreted as part of an adaptive reproductive strategy compensating for strong seasonality in plankton production and transitory periods of larval food limitation.     

Alterations in serum selenium levels and their relation to troponin I in acute myocardial infarction

Selenium (Se) is an essential trace element with antioxidant function. The aim of the present study was to estimate the alterations of Se serum level during the acute phase of myocardial infarction and its relation to biomarkers of myocardial necrosis. Serum Se levels were measured at admission and after 24 h in 60 consecutive patients with acute coronary syndrome (both with and without ST elevation). Troponin I (TnI) was assessed at admission and then twice daily for 3 days; patients with normal levels were excluded. Fifty-five patients with acute MI (positive TnI) were included into the analysis. During the first day of hospitalization, patients received standard therapy, including acetylsalicylic acid, clopidogrel, and heparin or enoxaparin; all underwent urgent coronary angiography and percutaneous intervention, when appropriate. Mean Se levels at baseline and 24 h later were comparable (67.1 ± 2.1 vs. 67.2 ± 1.8 μg/L, ns). Linear regression has shown significant correlation between baseline Se levels and peak TnI (y = 3.4x ? 116, r ² = 0.13, P = 0.008). Positive correlation was found also between the peak TnI and the difference from baseline to 24 h (y = 2.2x + 115, r ² = 0.08, P = 0.04). Moreover, close negative correlation was observed between baseline Se levels and the difference from baseline to 24 h (y = ?0.9x + 62.7, r ² = 0.55, P<0.001). Our results have shown marked individual changes in Se levels during the acute phase of MI as well as correlation between Se levels and peak TnI. These results suggest that alterations in serum Se may be related to the extent of myocardial infarction.     

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin–angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin–angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = ?0.28, P < 0.01), urinary sodium (r = ?0.22, P < 0.05) and serum AGT (r = ?0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.     

Genetic polymorphims of estrogen receptor alpha −397 PvuII (T>C) and −351 XbaI (A>G) in a portuguese population: prevalence and relation with breast cancer susceptibility

Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between ?397 PvuII (T>C) and ?351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case–control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR–RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95 % CI 0.070–0.456; P < 0.001) or heterozigozity (OR 0.223; 95 % CI 0.089–0.561; P = 0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95 % CI 0.049–1.035; P = 0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95 % CI 0.194–0.843; P = 0.014), compared with PX (PPXX + PPXx + PpXX + PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D = 0.044, r² = 0.049, X² = 5.216, P = 0.022) and controls (D = 0.090, r² = 0.139, X² = 16.819, P < 0.001), but not in the entire sample population analyzed as a whole (D = 0.087, r² = 0.0076, X² = 1.733, P = 0.188). In conclusion, in this case–control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.     

Aortic Pulse Wave Velocity is Associated with Measures of Subclinical Target Organ Damage in Patients with Mild Hypertension

We evaluated the temporal association between aortic arterial stiffness and subclinical target organ damage, including renal function decline, left ventricular geometric remodeling, and left ventricular diastolic dysfunction in patients with mild hypertension. Automatic pulse wave velocity (PWV) measuring system was applied to examine carotid-femoral PWV (CFPWV) reflecting aortic arterial stiffness in 644 essential hypertensive patients. Clinical data were collected, and cardiac structure and function were assessed by echocardiography. CFPWV was significantly and positively associated with left ventricular mass index (r = 0.153, P = 0.018), relative wall thickness (r = 0.235, P < 0.001), and left atrial diameter (r = 0.192, P = 0.003), and negatively with E/A ratio (r = ?0.361, P < 0.001) and creatinine clearance (r = ?0.248, P < 0.001). Logistic regression analysis demonstrated that CFPWV remained significantly correlated with renal function decline (P = 0.011), left ventricular diastolic dysfunction (P = 0.009) and left ventricular geometric remodeling (P = 0.020). Higher CFPWV was independently associated with greater burden of subclinical disease in renal impairment, left ventricular geometric remodeling and diastolic dysfunction.     

Two novel SNPs in the coding region of the bovine PRDM16 gene and its associations with growth traits

As a zinc-finger protein, PR domain containing 16 (PRDM16) controls brown fat determination by stimulating brown fat-selective genes expression while suppressing the expression of genes selective for white fat cells, whose mutations were associated with myelodysplastic syndrome (MDS) and leukemogenesis in human and murine model of leukemia. To date, no polymorphisms of PRDM16 gene in bovine had been reported. Herein, PCR-SSCP and DNA sequencing methods were employed to screen the genetic variation within PRDM16 gene in 1031 Chinese indigenous bovine. The results revealed two novel silent mutations: XM_001788152: m.1641T>C (547aa), 1881G>A (627aa). Hence, we described the PvuII and HaeIII forced PCR–RFLP methods for detecting these mutations, respectively. In the forced PCR–RFLP analysis with PvuII, the frequencies of bovine PRDM16-C allele varied from 0.044 to 0.506 in four Chinese native breeds. In the forced PCR–RFLP analysis with HaeIII, the frequencies of bovine PRDM16-G allele were 0.474, 0.494, 0.576 and 0.906 for Jiaxian (JX), Nanyang (NY), Qinchuan (QC) and Chinese Holstein (CH) population. Significant statistical differences between genotypic frequencies implied that both of the polymorphic loci were significantly associated with cattle breeds by the chi square test (χ² = 190.058, P < 0.001 and χ² = 118.239, P < 0.001 for PvuII; χ² = 209.842, P < 0.001 and χ² = 108.711, P < 0.001 for HaeIII). The associations of the PvuII and HaeIII forced PCR–RFLPs of bovine PRDM16 loci with growth traits were analyzed in Nanyang breed. The two SNPs were associated with body weight and average daily gain in Nanyang aged 12 months, individuals with genotype TT and AA showed significantly better body weight (P < 0.05) and average daily gain (P < 0.01) at 12 months, respectively.     

Genetic association of lipid metabolism related SNPs with myocardial infarction in the Pakistani population

Myocardial infarction (MI) is the major cardiovascular disease. This can be caused by mutual interaction of environmental and genetic factors. The current study was designed to investigate the role of lipid metabolism related genetic polymorphisms with the onset of MI in Punjabi population of Pakistan. A total of 384 subjects was studied from April 2011 to July 2012. To determine the genetic associations with MI, the single nucleotide polymorphisms (SNPs) were genotyped by sequencing, as well as one label extension method. Out of eight SNPs in four candidate genes, seven genetic variants were significantly (P < 0.05) associated with elevated risk of MI. In current study two SNPs rs662799 risk allele G (P = 0.03) and rs3135506 risk allele C (P = 0.05) of APOA5 were found to be associated with significant higher risk of triglyceride levels, irrespective of age, sex, obesity, diabetes, hypertension and smoking. Gene variants (rs1558861, rs662799 and rs10750097) in APOA5 showed almost complete linkage disequilibrium and their minor allele frequencies (0.34, 0.28, and 0.41 respectively) were more prevalent (P < 0.05) in cases than controls. We further revealed risk haplotypes (C-T-G-A, G-C-A-G; P = 0.001) and protective haplotypes (G-T-A-G, C-C-G-A; P = 0.005) between these four SNPs for the progression of MI. Current study confirms the correlation between lipid metabolism related SNPs with MI and supports the role of APOA5 in raising plasma triglyceride levels in Pakistanis. However further studies are needed for delineating the role of these SNPs.     

Antiangiogenic Effect of Methotrexate and PUVA on Psoriasis

Vascular endothelial growth factor (VEGF) is important factor for angiogenesis in psoriasis. Methotrexate and psoralen and ultraviolet light A (PUVA) mainly target the T cell-mediated immunopathology of psoriasis. Our work aimed at estimating VEGF mRNA in psoriatic patients and investigating whether the standard therapeutic modalities (methotrexate and PUVA) exert their antiangiogenic activity through altering VEGF levels. Twenty-four chronic plaque psoriasis patients were enrolled. Patients were divided into two groups (12 patients each); group A received intramuscular methotrexate and group B was treated by PUVA three times/week in a PUVA 1000 cabin for 10 weeks each. Twelve healthy volunteers served as controls. A skin biopsy was taken from lesional skin before and after treatment for RT-PCR detection of VEGF mRNA. Capillary perfusion scanning using LASER Doppler perfusion imaging was performed on the same psoriatic plaque before and after treatment and was also done for the controls. Following both methotrexate and PUVA, a significant reduction in the amount of VEGF mRNA (P < 0.001 and P = 0.002, respectively) and capillary perfusion (P = 0.002) occurred. These reductions were significantly higher in the methotrexate group (P < 0.001 and  P = 0.001, respectively) than in the PUVA group. The percentage of clinical improvement in the examined psoriatic plaque was significantly positively correlated with the percentage of reduction in the amount of VEGF mRNA (r = 0.850, P < 0.001) and the percentage of reduction in the capillary perfusion (r = 0.684, P < 0.001). Both modalities may exert an antiangiogenic effect. Methotrexate appears to have possibly a more potent antiangiogenic effect than PUVA.     

Morphology, sociality, and ecology: can morphology predict pairing behavior in coral reef fishes?

Morphology can contain valuable information about the ecological performance of reef fishes, but it has rarely been used in combination with social traits. Social behavior is known to influence the ecological role of fishes; however, the ecological basis for pairing in reef fishes is not well understood. Field observations of 2,753 individuals, in 47 species in six families of biting reef fishes (Acanthuridae, Chaetodontidae, Kyphosidae, Labridae, Pomacanthidae, Siganidae), were used in combination with six morphological measurements, to examine the morphology of fishes in different social systems. A principal components analysis of morphological traits segregated species with high proportions of pairing individuals from non-pairing species along principal component 1, explaining 40.8 % of the variation. Pairing species were characterized by large eyes, concave foreheads, pointed snouts, deep bodies, and small maximum sizes. There was a significant positive relationship between these morphological traits (i.e., scores on PC1) and the prevalence of pairing within the Chaetodontidae (r ² = 0.59; P = 0.026), Siganidae (r ² = 0.72; P = 0.004), and Acanthuridae (r ² = 0.82; P < 0.001). This was consistent when traits were corrected for phylogenetic effects. No pattern was evident in the scarine Labridae (r ² = 0.15; P = 0.17). The morphological characteristics found among pairing species suggest that pairing species share common ecological traits, including foraging for small prey items in micro-topographically complex environments such as reef crevices. These ecological traits may have played a role in the evolution of pairing behavior and subsequently led to the development of reproductive patterns based on monogamy.     

Local effects of forest fragmentation on diversity of aquatic insects in tropical forest streams: implications for biological conservation

The influence of forest fragmentation (habitat isolation) on biological and ecological diversity of aquatic insects was investigated in streams of fragmented forests in Hulu Gombak (6 streams) and Gunung Angsi (5 streams) and un-fragmented forest of Berembun (6 streams) in peninsular Malaysia. Several environmental parameters including canopy cover, DO, temperature and pH differed significantly among the three catchments (P < 0.05). We found that taxonomic richness in Berembun forest was significantly different from Gunung Angsi (P < 0.05), but not with Hulu Gombak forests (P > 0.05). Nestedness pattern that measures the effect of habitat isolation on taxonomic assemblages showed that aquatic insect’s community in un-fragmented forest (Berembun) was less nested (T = 54.4), indicating high diversity compared to highly nested (less diverse) in the two fragmented forests (Hulu Gombak, T = 30.45 and Gunung Angsi, T = 35.45). Taxa similarity in Berembun streams was negatively correlated with the geographical distance among streams (Mantel test, r = ? 0.462, P < 0.05). Such correlation was absent in both Gunung Angsi and Hulu Gombak streams. Forest fragmentation in Hulu Gombak and Gunung Angsi measured as the distance of the forests from the nearest forested area had negative effect on aquatic insects diversity (r ² = ? 0.149, P < 0.05), but not on their abundances (r ² = 0.003, P > 0.05). We concluded that local habitat conditions were the most important in shaping the aquatic insects community among streams of both unfragmented and fragmented forests.     

Size at maturity of Mediterranean marine fishes

In this review we collected data on the length at maturity (L_m) and maximum reported total length (L_max) of 565 Mediterranean marine fish stocks, representing 150 species, 68 families, 24 orders and 3 classes. Overall, L_m ranged from 2 cm, for the males of the toothcarp Aphanius fasciatus, to 350 cm, for the females of the bluntnose sixgill shark Hexanchus griseus. L_m was positively linearly related with L_max for Actinopterygii (logL_m = ?0.123 + 0.92 × logL_max; r ² = 0.87, n = 471, P < 0.001) and Elasmobranchii (logL_m = ?0.008 + 0.922 × logL_max; r ² = 0.90, n = 92, P < 0.001) with the two slopes being significantly different (ANCOVA: F = 2,904, P < 0.001). The reproductive load (L_m/L_max) ranged between 0.23 (sand steenbras Lithognathus mormyrus) and 0.94 (angular roughshark Oxynotus centrina and thornback ray Raja clavata). The mean L_m/L_max was significantly (ANOVA, F = 34.14, P < 0.001) lower for Actinopterygii (mean = 0.59, SD = 0.122, n = 471) compared to Elasmobranchii (mean = 0.70, SD = 0.132, n = 92) and Holocephali (mean = 0.77, SD = 0.077, n = 2). The L_m/L_max was significantly (ANOVA, F = 43.80, P < 0.001) higher for species providing some form of parental care, i.e. guarders, bearers, nesters (mean L_m/L_max ± SD = 0.68 ± 0.141, n = 111) compared to non-guarders (mean L_m/L_max ± SD = 0.59 ± 0.123, n = 454). The mean L_m/L_max displayed a remarkable constancy with longitude (northern and southern Mediterranean coastline: ANOVA, F = 0.01, P = 0.93), latitude (western, central and eastern regions: ANOVA, F = 1.25, P = 0.29) and habitat (ANOVA, F = 0.85, P = 0.51).     

Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes

Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day^?1 doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = ?0.50, p < 0.03) and heart (r = ?0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.     

Association between cytokines and methylation of SOCS-1 in serum of patients with ankylosing spondylitis

In this study, we aim to determine the relationship between methylation level of an inflammatory-related gene, SOCS-1 in serum samples of patients with ankylosing spondylitis (AS) and their degree of inflammation as well as serum cytokine level. Quantitative real time methylation specific PCR was performed to examine the promoter methylation of SOCS-1 in serum samples of 43 HLA-B27+ AS patients and 6 B27+ healthy controls. Degree of inflammation was accessed by spondylopathy, sacroiliitis as well as acute phase reactant, erythrocyte sedimentation rate and C-reactive protein (CRP). Serum IL-6 and TNF-α level was determined by ELISA assay. SOCS-1 methylation can only be found in serums samples from patients but not normal control. Methylation of SOCS-1 significantly associated with severity of patient’s spondylopathy (P < 0.005), sacroiliitis (P < 0.005) and acute phase reactant CRP (P = 0.0278). AS patients also exhibited higher serum IL-6 (P < 0.001) and TNF-α level (P < 0.001). Importantly, patients with high serum IL-6 or TNF-α level demonstrated a significantly higher SOCS-1 methylation (P < 0.001). In conclusion, this proof-of-principle study suggested that methylation of SOCS-1 can be detected in serum of HLA-B27+ AS patients but not in B27+ controls. The pathogenic potential of SOCS-1 methylation in AS deserves further investigation.     

Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma

The long intergenic non-coding RNA LINC00312, also called NAG7, was first cloned by our group. Our previous studies have found that LINC00312 could inhibit proliferation and induce apoptosis in nasopharyngeal carcinoma (NPC) cells but also stimulate NPC cell invasion. However, the relevance of LINC00312 in NPC progression or in patient outcomes has not been reported. This study aims to assess the possible correlations of LINC00312 expression with NPC progression and its potential prognostic predictive ability in NPC outcomes. A NPC tissue microarray, which included 561 normal and NPC tissue cores, was used to detect LINC00312 expression, and we found that LINC00312 was significantly down-regulated in NPC tissues compared with non-cancerous nasopharyngeal epithelium tissues. Positive expression of LINC00312 was negatively correlated with tumor size (P < 0.001) but positively correlated with lymph node metastasis (P = 0.002). A receiver operating characteristic (ROC) analysis revealed that LINC00312 expression could distinguish non-cancerous patients from NPC patients (P < 0.001, sensitivity: 72.1 %, specificity: 87.7 %). We also found that LINC00312 was strongly negatively correlated with EBER-1, a non-coding RNA transcribed by Epstein-Barr Virus, in NPC (r = ?0.384, P < 0.001). In the final logistic regression analysis model, the abnormal expression of LINC00312 and EBER-1 were found to be independent contributors to nasopharyngeal carcinogenesis (P < 0.001, P < 0.001, respectively). A survival analysis revealed that LINC00312 could predict a good prognosis of no lymph node metastasis (Disease Free Survival (DFS): P = 0.005, Overall Survival (OS): P = 0.001) and a poor prognosis of lymph node metastasis (DFS: P = 0.011, OS: P = 0.001) in NPC patients. Low expression of LINC00312 was an independent risk factor for OS in multivariate analyses (P = 0.017). These observations indicated that LINC00312 could represent a potential biomarker for metastasis, progression and prognosis in NPC.     

Oxidized Low Density Lipoprotein and Inflammation in Gout Patients

To analyze the levels of oxidized low density lipoprotein (ox-LDL) and inflammatory cytokines in the plasma of gout patients. The levels of ox-LDL, hypersensitive C-reactive protein (hs-CRP), interleukin-1β, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in the plasma of 41 gout patients [28 in acute phase episode, 13 in intermittent phase (IP)], and in 40 healthy controls. The relationship between ox-LDL and inflammation was also explored by measuring the levels of several pro-inflammatory cytokines in the plasma. The plasma levels of ox-LDL, hs-CRP, IL-6 and TNF-α were significantly increased in patients with gout in the acute phase compared to those in the IP group and healthy controls (P < 0.05), but the levels of TGF-β were significantly lower in the acute phase group than in the IP group and healthy controls (P < 0.01). The levels of ox-LDL in the gout patients in the IP were significantly higher than those in healthy controls (P < 0.05). Correlation analysis indicated that the levels of ox-LDL were positively correlated with hs-CRP, IL-6 and TNF-α (r = 0.343, r = 0.386, r = 0.659, P < 0.01, respectively), but negatively correlated with TGF-β levels in patients in the acute phase (r = ?0.240, P < 0.05). The levels of ox-LDL in gout patients were significantly higher than those in healthy controls. The changes in ox-LDL levels may be associated with enhanced inflammation in gout patients.     

The influence of goethite and gibbsite on soluble nutrient dynamics and microbial community composition

Iron and aluminum (oxyhydr)oxides are ubiquitous in the soil environment and have the potential to strongly affect the properties of dissolved organic matter. We examined the effect of oxide surfaces on soluble nutrient dynamics and microbial community composition using an incubation of forest floor material in the presence of (1) goethite and quartz, (2) gibbsite and quartz, and (3) quartz surfaces. Forest floor material was incubated over a period of 154 days. Aqueous extracts of the incubations were harvested on days 5, 10, 20, 30, 60, 90, and 154, and concentrations of P, N, PO₄ ^3?, NO₂ ^?, NO₃ ^?, and organic C were measured in the solutions. Microbial community composition was examined through pyrosequencing of bacterial and fungal small subunit ribosomal RNA genes on selected dates throughout the incubation. Results indicated that oxide surfaces exerted strong control on soluble nutrient dynamics and on the composition of the decomposer microbial community, while possibly having a small impact on system-level respiration. Goethite and gibbsite surfaces showed preferential adsorption of P-containing and high molar mass organic solutes, but not of N-containing compounds. On average, organic C concentrations were significantly lower in water extractable organic matter (WEOM) solutions from oxide treatments than from the control treatment (P = 0.0037). Microbial community composition varied both among treatments and with increasing time of incubation. Variation in bacterial and fungal community composition exhibited strong-to-moderate correlation with length of incubation, and several WEOM physiochemical characteristics including apparent (weight averaged) molar mass, pH and electrical conductivity. Additionally, variation in bacterial community composition among treatments was correlated with total P (r = 0.60, P < 0.0001), PO₄ ^3? (r = 0.79, P < 0.0001), and organic C (r = 0.36, P = 0.015) concentrations; while variation in fungal communities was correlated with organic C concentrations (r = ?0.48, P = 0.0008) but not with phosphorus concentrations. The relatively small impact of oxide surfaces on system-level microbial respiration of organic matter despite their significant effects on microbial community composition and WEOM dynamics lends additional support to the theory of microbial functional redundancy.     

The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study

Introduction

Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.

Results

Patients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).

Conclusions

Plasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.     

Association of Genetic Variants of MTHFR,ENPP1, and ADIPOQ with Myocardial Infarction in Egyptian Patients

The study aimed to investigate the association between MTHFR C677T, ENPP1 K121Q, and ADIPOQ 45 T/G gene polymorphisms and incidence of myocardial infarction (MI) in Egyptian patients. The study included 60 unrelated patients suffering from their first MI and 60 unrelated controls. Patients were recruited from Kasr-El Eini hospital, Cairo University. The previously mentioned polymorphisms were determined in all participants by PCR–RFLP. There was no significant difference in the distribution of genotypes and alleles of MTHFR C677T between groups. In contrast, significant difference was found in the distributions of genotypes and alleles of ENPP1 K121Q and ADIPOQ 45 T/G between MI patients and controls (P = 0.01, P = 0.004, P = 0.009, P = 0.001, respectively). Univariate analysis revealed that 121Q ENPP1 and 45 G ADIPOQ alleles were associated with the increased risk of MI (OR = 3; 95 % CI = 1.45–6.2; P = 0.004 and OR = 5.8; 95 % CI = 1.92–17.54; P = 0.001, respectively). The mutant homozygous genotypes of MTHFR, ENPP1, and ADIPOQ were more prevalent in diabetic hypertensive MI patients than it was among non-diabetic normotensive MI patients. Regarding the coagulation profile, INR (P = 0.009) and PC % (P = 0.022) were significantly different among the three genotypes of MTHFR C677T. The 677 T, 121 Q, and 45G variants were associated with MI in Egyptian patients; however, more studies are needed to determine the possible protective effect for these polymorphisms in our population.