Selective, Sensitive and Label-Free Detection of Fe3+ Ion in Tap Water Using Highly Fluorescent Graphene Quantum Dots.

Graphene quantum dots (GQDs) as a new type of fluorescent carbon nanomaterials, showing excellent photoluminescence properties, biocompatibility, photoelectric properties, have become the current research focus. Iron element as an essential element in the human body and an important part of hemoglobin, is very important for human health, so the detection of ferric ions has great significance. In this paper, GQDs with strong blue light emission were prepared through pyrolysis treatment using citric acid as a carbon source. Through characterization by transmission electron microscopy (TEM) and fluorescence spectrometer, it was observed that the GQDs have a uniform particle size distribution and highly fluorescent intensity with a quantum yield of 27.4%. Due to the strong quenching effect of Fe3+ on GQDs fluorescence, GQDs was used as a green and facile fluorescence sensor to detect Fe3+ selectively and sensitively. The GQDs fluorescence sensor shows a sensitive response to Fe3+ in a wide linear range (3.5 × 10-6-6.7 × 10-4 M), a low detection limit of 1.6 µM (S/N = 3) and good selectivity. Importantly, the new sensor realizes the detection of Fe3+ ions in tap water because of its low detection limit, wide linear range, and high sensitivity.

Inhibition of the superantigenic activities of Staphylococcal enterotoxin A by an aptamer antagonist.

Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy for the treatment of SEA-induced diseases. Through a systematic evolution of ligands by exponential enrichment process, we obtained an aptamer (S3) that could bind SEA with both high affinity and specificity, with a Kd value 36.93 ± 7.29 nM (n = 3). This aptamer antagonist effectively inhibited SEA-mediated human peripheral blood mononuclear cells proliferation and inflammatory cytokines (IFN-γ, TNF-α, IL-2 and IL-6) secretion. Moreover, PEGylated S3 significantly reduced mortality in murine lethal toxic shock models established by lipopolysaccharide-potentiated SEA. Therefore, this novel aptamer antagonist has the potential to become a new strategy for treating S. aureus infections and SEA-induced diseases.

Neutralization of staphylococcal enterotoxin B by an aptamer antagonist.

Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd = 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a "double-hit" mouse model of SEB-induced TSS, established via sensitization with d-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS.

A label-free aptasensor for highly sensitive detection of ATP and thrombin based on metal-enhanced PicoGreen fluorescence.

A label-free fluorescence aptasensor for highly selective and sensitive detection of ATP and thrombin was developed by using PicoGreen (PG) as signal molecule and surface-bound metal-enhanced fluorescence (MEF) substrates (silver island films, SIFs) as signal enhancers. On binding with ATP or thrombin, aptamers undergo structure switching, leading to a reduction of fluorescence intensity of PG. Chang of fluorescence intensity can be magnified by SIFs. The limit of detection for ATP and thrombin is 1.3 nM and 0.073 nM, respectively. The fluorescence quenching efficiency is linear in the logarithmic scale with ATP concentration range from 10 nM to 100 µM (R(2)=0.995) and thrombin concentration range from 0.1 nM to 100 nM (R(2)=0.997). The coefficients of variation of the intra-assay reproducibility and inter-assay reproducibility for ATP (10 µM) assay are 3.8% and 5.2%, respectively. In addition, the aptasensor is stable and can be reliably used for ATP measurement in biological samples. Overall, the aptasensor can be a useful and cost effective tool for the specific detection of ATP, thrombin and potentially other biomolecules in biological samples.

Development of aptamer oligonucleotides as anticoagulants and antithrombotics for cardiovascular diseases: current status.

Aptamers are short DNA/RNA oligonucleotides selected by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) based on affinity for target molecules. Since aptamers have several advantages over monoclonal antibodies, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, they are promising novel diagnostic and therapeutic agents. In this review, we will describe the development of aptamers against thrombin, von Willebrand factor (vWF), factor IX, and factor XII as potential anticoagulants or antithrombotics for cardiovascular diseases, especially those that have entered clinical trials.

H19 inhibits RNA polymerase II-mediated transcription by disrupting the hnRNP U-actin complex.

BACKGROUND: H19 was one of the earliest identified, and is the most studied, long noncoding RNAs. It is presumed that H19 is essential for regulating development and disease conditions, and it is associated with carcinogenesis for many types. However the biological function and regulatory mechanism of this conserved RNA, particularly with respect to its effect on transcription, remain largely unknown. METHODS: We performed RNA pulldown, RNA immunoprecipitation and deletion mapping to identify the proteins that are associated with H19. In addition, we employed EU (5-ethynyl uridine) incorporation, immunoprecipitation and Western blotting to investigate the functional aspects of H19. RESULTS: Our research further verifies that H19 is bound to hnRNP U, and this interaction is located within the 5' 882 nt region of H19. Moreover, H19 disrupts the interaction between hnRNP U and actin, which inhibits phosphorylation at Ser5 of the RNA polymerase II (Pol II) C-terminal domain (CTD), consequently preventing RNA Pol II-mediated transcription. We also showed that hnRNP U is essential for H19-mediated transcription repression. CONCLUSIONS: In this study, we demonstrate that H19 inhibits RNA Pol II-mediated transcription by disrupting the hnRNP U-actin complex. GENERAL SIGNIFICANCE: These data suggest that H19 regulates general transcription and exerts wide-ranging effects in organisms.

The multiple roles for Sox2 in stem cell maintenance and tumorigenesis.

The Sry-containing protein Sox2 initially was known to regulate the self-renewal of the mouse and human embryonic stem cells (ESCs). It is also important for the maintenance of stem cells in multiple adult tissues including the brain and trachea, and it is one of the key transcription factors for establishing induced pluripotent stem cells. Recently, overexpression and gene amplification of Sox2 have been associated with the development of squamous cell carcinoma in multiple tissues such as the lung and esophagus. These different roles for Sox2 involve a complicated regulatory networks consisting of microRNAs, kinases and signaling molecules. While the levels of Sox2 are modulated transcriptionally and translationally, post-translational modification is also important for the various functions of Sox2. In clinics, high levels of Sox2 are correlated with poor prognosis and increased proliferation of cancer stem cells. Therefore targeting Sox2 can be potentially explored for a new therapeutic avenue to treat cancers. This review will focus on the different roles for Sox2 in stem cell maintenance and its oncogenic roles in the context of signal transcription and microRNA regulation. We will also review the main upstream and downstream targets of Sox2, which can be potentially used as therapeutic measures to treat cancer with abnormal levels of Sox2.

The impact of acute atrial fibrillation on the prothrombotic state in patients with essential hypertension.

OBJECTIVES: To investigate whether acute atrial fibrillation (AF) creates a prothrombotic state in hypertensive patients, and to assess the evolution in research indices after cardioversion. DESIGN AND METHODS: Plasma levels of von Willebrand factor (vWf), soluble P-selectin and fibrin D-dimers were measured in hypertensive patients with acute AF pre-cardioversion and at 1, 7, 14, and 30days post-cardioversion. The results were compared with hypertensive controls and healthy controls. RESULTS: Pre-cardioversion plasma vWf levels in acute AF patients were similar to those of controls; however, post-cardioversion, the vWf levels increased significantly and only returned to baseline levels 14days later. Compared with controls, acute AF patients had higher levels of fibrin D-dimers, which lasted at least 14days after cardioversion. CONCLUSIONS: This study demonstrated that hypertensive patients with acute AF have an abnormal prothrombotic state, which persists for up to 14days after cardioversion.

MMP-2 and TIMP-2 gene polymorphisms and susceptibility to atrial fibrillation in Chinese Han patients with hypertensive heart disease.

BACKGROUND: MMP-2 and TIMP-2 play important roles in the pathogenesis of arrhythmogenic atrial remodeling, and may contribute to the development and persistence of atrial fibrillation (AF). Functional polymorphisms in the promoter of MMP-2 and TIMP-2 gene may modulate an individual's susceptibility to AF. METHODS: A total of 881 hypertensive heart disease patients from Chinese Han population (128 with and 753 without AF) were recruited in this study. The genotypes of the MMP2-1306C>T and -735C>T polymorphisms and TIMP-2 -418G>C polymorphisms were determined using PCR based method. The plasma concentration of TIMP-2 was measured by enzyme-linked immunosorbent assay in a subgroup with 81 patients. RESULTS: Both genotype distribution and allele frequency of the TIMP-2 -418G>C polymorphism were significantly different between the AF and control group (P=0.005 and P=0.001, respectively). The C allele carriers (GC+CC) had a significantly increased risk of AF compared with the GG homozygotes (odds ratio,1.77, 95% CI 1.21-2.92, P=0.009) in a logistic regression model after adjustment for age, left atrial dimension, left ventricular mass index, and antihypertensive drugs. The C allele carriers also had reduced levels of plasma TIMP-2 levels compared with GG homozygotes in both AF patients and control subjects. No relationship was found in this cohort between the presence of the MMP-2 -1306C>T and -735C>T polymorphism and AF. CONCLUSIONS: The TIMP-2 -418G>C polymorphism is significantly associated with an increased susceptibility to AF in Chinese Han patients with hypertensive heart disease. The -418C allele, which is associated with a decreased expression of TIMP-2, might be a genetic risk for the development of AF in this cohort.

Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in patients with hypertensive heart disease.

BACKGROUND: The activated renin-angiotensin-aldosterone system has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that functional genetic variations of angiotensin-converting enzyme (ACE) and CYP11B2 genes may influence the susceptibility to AF in patients with hypertensive heart disease. METHODS: The I/D polymorphism of ACE was detected by polymerase chain reaction (PCR), and the -344C/T polymorphism of the CYP11B2 gene was detected using PCR and subsequent cleavage by HaeIII restriction endonuclease. RESULTS: The overall distribution of ACE I/D genotypes in patients with and without AF was significantly different (p=0.001). The frequency of the DD genotype was significantly higher in patients with AF than in patients without AF (20.6% vs. 8.1%, OR 2.94, 95% CI 1.64-5.26, p<0.001). The frequency of the D allele was significantly higher in the AF group than in the non-AF group (p=0.001). After adjustment for age and left atrial dimension, multivariable analysis showed that the DD genotype of the ACE gene was an independent risk factor for AF in patients with hypertensive heart disease. No relationship between -344 C/T CYP11B2 polymorphism and AF was found in this cohort. CONCLUSIONS: Our study suggests that ACE I/D polymorphism is associated with AF and the DD genotype may be an independent predictive factor for AF in patients with hypertensive heart disease.