A case of limb shaking transient ischaemic attack due to internal carotid artery dissection: an unusual presentation of fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) has a high prevalence of associated nontraumatic carotid artery dissection, which could further result in transient ischaemic attack (TIA) or stroke. Limb shaking TIA is an unusual form of TIA that is commonly discribed in elderly patients with atherosclerotic backgrounds, while there are limited data about it in patients with FMD. Furthermore, discussions of limb shaking TIA in nonelderly patients are scarce. CASE PRESENTATION: An Asian 47-year-old female presented with intermittent involuntary movement of the left upper limb accompanied by neck torsion. The episode stopped soon after changing to the supine position. On native source images of time-of-flight magnetic resonance angiography (TOF-MRA), the right internal carotid artery showed a "dual lumen sign" with an intimal flap. On contrast-enhanced magnetic resonance angiography and sagittal black-blood T1WI, an intravascular haematoma with irregular lumen stenosis was observed, which overall indicated right internal carotid artery dissection. Digital subtraction angiography showed the characteristic "string-of-beads" appearance in the left internal carotid artery, and the presence of this sign pointed to the diagnosis of FMD. The patient was finally diagnosed with limb shaking TIA due to internal carotid dissection with fibromuscular dysplasia. The patient was prescribed dual anti-platelet therapy. The limb shaking vanished soon after admission with no reoccurrence in the three-month follow-up. CONCLUSIONS: This case demonstrates that limb shaking TIA can present in patients with FMD. Limb shaking TIA in nonelderly patients can be caused by multiple diseases, and more detailed patient guidance is required in clinical practice.

MiR-421 Aggravates Neurotoxicity and Promotes Cell Death in Parkinson's Disease Models by Directly Targeting MEF2D.

Parkinson's disease (PD) is a severe neurodegenerative disease characterized by selective loss of dopaminergic neurons, which reduces quality of life of patients and poses a heavy burden to the society. The pathological mechanism of PD remains unclear, and increasing efforts are aimed to solve this problem. MiRNAs are a kind of small noncoding RNA regulating target gene expression. Previous studies have shown that dysregulation of miRNAs is involved in the development of PD. In the present study, we determined that miR-421 and MEF2D are increased and decreased, respectively, in a cellular model of PD. The data on the mechanism of action indicate that miR-421 directly binds to MEF2D mRNA and negatively regulates MEF2D expression. An increase in miR-421 disrupted the Bcl2/Bax system. Functional assays indicated that enhanced miR-421 promotes cell death by negative modulation of MEF2D expression. Inhibition of miR-421 or restoration of MEF2D protected neurons from neurotoxicity in cellular and animal models of PD. Our study is the first to demonstrate that miR-421 is decreased in PD models and to determine a novel putative mechanism of PD pathogenesis.

A Cellular Compatible Chitosan Nanoparticle Surface for Isolation and In Situ Culture of Rare Number CTCs.

Circulating tumor cell (CTC) isolation has attracted a great deal of research interest in recent years. However, there are still some challenges, including purity as well as viability of the captured CTCs, resulting from nanoscale structures and inorganic nanomaterials. Here, a chitosan nanoparticle surface is first fabricated by electrospray to provide a cellular compatible interface. The "soft" substrate, further modified by polyethylene glycol (PEG) as an antifouling molecule and DNA aptamer as a specific capture molecule, has a hydrophilic nature and is capable of specific capture of viable rare CTCs from artificial white blood cell (WBC) samples. Furthermore, a subsequent in situ culture strategy based on the developed cellular compatible soft interface is introduced for further purification and proliferation of the captured rare number target cells. The WBCs are weeded out after 2 d, and after a 7 d proliferation nearly 200 MCF-7 cells are obtained from 7 target cells with more than 90% purity. This work provides a promising strategy for viable isolation and purification of rare CTCs and it has great potential for achieving clinical validity.

The role of miR-145 in microvasculature.

Increasing evidence suggests that microRNAs(miRs) play a crucial role in the cardiovascular system, and recent studies have revealed a significant role of miRs in vascular biology and disease, miR-145 is one of the most-studied miRs, and especially in the vascular smooth muscle cell (VSMCs) proliferation, differentiation, and phenotypic switching. In cardiovascular system, miR-145 is not only important for heart and vascular development but also plays an essential role in cardiac pathological factors, such as hypertrophy, and ischemia. However, its potential role in microvasculature has not been systematically evaluated yet. We are just beginning to understand the regulation of miR in vascular biology. In particular, the miR biogenesis and regulatory pathways in the vascular system have not yet been well characterized, This review focuses on the basic biology and mechanism of action of miR-145 specifically pertaining to microvascular development, pericyte and disease, In addition it addresses the potential for miR-145 to be used therapeutically in the treatment of microvascular disease.

miR­497/MIR497HG inhibits glioma cell proliferation by targeting CCNE1 and the miR­588/TUSC1 axis.

Emerging evidence has shown that microRNA (miR)­497 serves pivotal roles in tumorigenesis, cancer progression, metastasis and chemotherapy resistance in several types of cancer. In the present study, the expression and biological functions of miR­497 host gene (MIR497HG) were investigated in glioma tissue. The expression levels of miR­497 and MIR497HG were measured in glioma, adjacent non­cancerous and normal brain tissue and their association with the prognosis of patients with glioma were analyzed. The biological roles of miR­497 and MIR497HG were investigated in glioma cell lines. In addition, bioinformatics analysis, luciferase reporter assay and functional experiments were performed to identify and validate the downstream targets of miR­497 or MIR497HG. The expression levels of miR­497 and MIR497HG were downregulated in glioma tissue and cell lines compared with those in adjacent non­cancerous and normal brain tissue and normal human cortical neuron cell line. Patients with low miR­497 or MIR497HG expression levels exhibited a poor prognostic outcome. In addition, forced overexpression of miR­497 or MIR497HG significantly inhibited the proliferation and cell cycle progression of glioma cell lines. Furthermore, the results indicated that miR­497 and MIR497HG exerted their biological functions by direct targeting of cyclin E1 and miR­588/tumor suppressor candidate 1. In summary, the data indicated that miR­497 and MIR497HG served as tumor suppressors and may be used as potential therapeutic targets and prognostic biomarkers in glioma.

Modeling left ventricular dynamics using a switched system approach based on a modified atrioventricular piston unit.

The contribution of the longitudinal atrioventricular plane displacement to ventricular pumping has drawn more and more attentions. In this paper, differential equations of the left ventricle (LV) are derived via the atrioventricular piston concept. The contribution of left ventricular radial function to blood flow was converted to an equivalent coefficient. A systemic circulatory model incorporating the modified atrioventricular piston unit was developed on a switched system form by adding some state-dependent switching planes. Simulation results prove that the end-systolic pressure volume relationship of the model with a changing systemic arterial resistance is approximately linear and insensitive to perturbations in afterload. Then the LV model was validated using a data fitting method. A pressure-volume loop from a patient undergoing routine diagnostic cardiac catheterization with LV angiography was used as measurements. Model parameters and the trapezoidal profile of contraction forces were adjusted by a trial method. The root mean squared error between the measured and estimated LV pressure is 2.99 mmHg. The LV compliance is 0.34 ml/mmHg. The ratio between left ventricular and left atrial cross-section is 1.8. Therefore, parameter values used in the modified LV model match physiological data. The model can reproduce the realistic pressure-flow relationship in the LV chamber.

Irregular surface of carotid atherosclerotic plaque is associated with ischemic stroke: a magnetic resonance imaging study.

OBJECTIVE: To determine the association between the irregularity of carotid plaque surface using multidimensional magnetic resonance imaging (MRI) of ipsilateral acute cerebral infarction (ACI) cases. METHODS: Patients with recent cerebrovascular symptoms (stroke or transient ischemic attack < 2 weeks) and atherosclerotic plaque in at least one carotid artery were diagnosed by B-mode ultrasound imaging (intima-media thickness ≥ 1.5 mm) and recruited for the present study. Irregular surface was defined when plaque surface was uneven with high and low fluctuation or plaque with surface ulceration. The irregularity of carotid plaque surface was determined on axial or oblique images alone (single-dimension) and on both axial images and oblique images (multidimensions), separately. Univariate and multivariate logistic regression analyses were performed to calculate the odds ratio (OR) and the corresponding 95% CI of the irregular plaque surface in discriminating the presence of ipsilateral ACI. RESULTS: A total of 217 included subjects (mean age: 60.7 ± 10.2 years, 149 men) were recruited and 89 (41.0%), 88 (40.6%) and 118 (54.4%) of them exhibited irregular plaque surface on axial, oblique and multidimensional MR images, respectively. The OR of irregularity of the plaque surface was determined by multidimensional MRI to be 5.88 (95% CI: 3.16-10.96, P < 0.001) in discriminating the presence of ipsilateral ACI. Following adjustment for clinical confounding factors, this association remained statistically significant (OR = 5.65, 95% CI: 2.53-12.60, P < 0.001). The analysis included further adjustment for the presence of lipid-rich necrotic core, intraplaque hemorrhage and stenosis and the results included that this association also remained statistically significant (OR = 6.08, 95% CI: 2.52-14.68, P < 0.001). CONCLUSIONS: The irregular plaque surface was determined by multidimensional MRI as an independent indicator for ipsilateral acute cerebral infarction.

miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1ß.

Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1ß as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1ß-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

Berberine as a novel light-up i-motif fluorescence ligand and its application in designing molecular logic systems.

Berberine, a new light-up fluorescence ligand, for i-motif structures has been reported. This interaction enabled the development of label-free DNA-based logic gates in response to input signals.

Effects of the short-term application of pantoprazole combined with aspirin and clopidogrel in the treatment of acute STEMI.

The aim of the present study was to determine the effects of the short-term application of pantoprazole on the co-treatment of acute ST-segment elevation myocardial infarction (STEMI) with aspirin and clopidogrel. A total of 207 acute patients showing primary symptoms of STEMI, who received successful emergent percutaneous coronary intervention treatment during hospitalization were randomly divided into two groups. In the test group proton pump inhibitors (PPIs), the patients were treated with a combination of aspirin and clopidogrel and pantoprazole, while those in the control group were treated only with aspirin and clopidogrel. Gastrointestinal bleeding events and major adverse cardiac events (MACEs) were observed in the two groups. Gastrointestinal bleeding events of the two groups mostly occurred within the first week of hospitalization, although the incidence in the PPIs group was significantly higher than that in the control group (p<0.05). However, no significant difference was observed for the incidence of MACEs between the two groups (p>0.05). In conclusion, the results of the present study have shown that the short-term application of pantoprazole combined with aspirin and clopidogrel does not increase the incidence of MACEs in patients with acute STEMI, reduces the risk of gastrointestinal bleeding, and is thus worth promoting clinically, particularly for high-risk groups.

Visual detection of Ca(2+) based on aggregation-induced emission of Au(I)-Cys complexes with superb selectivity.

A label-free optical probe was developed for Ca(2+) detection based on the aggregation-induced emission property of Au(i)-thiolate complexes. Upon incubation with Ca(2+), the Au(I)-cysteine complexes rapidly aggregated through Cys-Ca(2+) interaction, resulting in a luminescent emission of the complexes. The label-free probe was low cost, simple in design and fast in response.