Search

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.

MicroRNA (miRNA) dysfunction has been confirmed as a key event of ischemic stroke appearance. This study is aimed at revealing the role of miR-429 in the angiogenesis of HBMECs. The HBMECs were treated with oxygen and glucose deprivation (OGD) to establish the ischemic cell model. The qRT-PCR was used to measure the expression levels of the miR-429 in the serums of the patients or cells, and CCK-8, wound healing assay, and tube formation assay were used to observe the effects of miR-429 on the phenotype of HBMECs. Moreover, the Targetscan, dual-luciferase reporter assay, and Western blot were used to reveal the downstream target and regulation mechanism of miR-429 in OGD-induced HBMECs. The results showed that miR-429 was significantly upregulated in the serums of the patients, and overexpressed miR-429 could extremely inhibit the viability, migration, and tube formation of OGD-induced HBMECs. Furthermore, it was found that SNAI2 was a downstream factor of miR-429, and SNAI2 could rescue the effects of miR-429 on OGD-induced HBMECs. Besides, the Western blot showed that miR-429 could affect the activity of GSK-3β/β-catenin pathway via inhibiting the expression of SNAI2. In conclusion, this study suggests that miR-429 inhibits the angiogenesis of HBMECs through SNAI2-mediated GSK-3β/β-catenin pathway.

ObjectivesPredicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture.Materials and MethodsThis was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those ResultsA total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation.ConclusionsThe ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.

BACKGROUND The aim of this study was to retrospectively analyze the incidence of complications of intracranial complex aneurysms embolization by stent-assisted coils, and to investigate the causes of complications and corresponding treatment methods. MATERIAL AND METHODS A total of 71 patients with subarachnoid hemorrhage (SAH) underwent stent-assisted coil embolization from 2015 to 2018 were enrolled in this study. Among them, 59 cases were single aneurysm, 12 cases were multiple aneurysms (11 cases with 2 aneurysms and 1 case with 3 aneurysms), for a total of 84 aneurysms. All enrolled patients received stent angioplasty except for 1 case. RESULTS There were 62 aneurysms (73.81%) treated with complete tamponade, 21 aneurysms (25.00%) treated with near-total tamponade and 1 aneurysm (1.19%) treated with partial tamponade. All aneurysms were evaluated based on GOS (Glascow outcome scale): 55 cases had GOS of 5 scores, 12 cases had GOS of 4 scores, 3 cases had GOS of 3 scores, and 1 case had GOS of 1 score. There were 67 SAH patients with good prognosis (GOS of 4-5 scores). In our study, the incidence of complications was 12.7%. Three cases experienced acute thrombosis, 2 cases experienced aneurysm rupture during embolization, and 1 case experienced postoperative focal ischemic changes with mild neurological deficits. CONCLUSIONS Stent-assisted coil embolization is safe, effective, and feasible for the treatment of intracranial ruptured aneurysms. Patients had a favorable outcome of as high as 94.4%. However, clinical skills should be improved to reduce the occurrence of complications. Prompt and timely treatment for complications of intracranial ruptured aneurysm is also of great significance.

Ischemic stroke is the leading cause of disabilities worldwide. MicroRNA-377 (miR-377) plays important roles in ischemic injury. The present study focused on the mechanisms of miR-377 in protecting ischemic brain injury in rats. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Primary rat microglial cells and brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD). The concentrations of cytokines (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, MMP2, COX2, and iNOS) in the culture medium were measured by specific ELISA. Tube formation assay was for the in vitro study of angiogenesis. Luciferase reporter assay was performed to confirm whether VEGF and EGR2 were direct targets of miR-377. The MCAO rats were intracerebroventricular (ICV) injection of miR-377 inhibitor to assess its protective effects in vivo. MiR-377 levels were decreased in the rat brain tissues at 1, 3, and 7 d after MCAO. Both microglia cells and BMECs under OGD showed markedly lower expression levels of miR-377 while higher expression levels of EGR2 and VEGF compared to those under normoxia conditions. Knockdown of miR-377 inhibited microglial activation and the release of pro-inflammatory cytokines after OGD. Suppression of miR-377 promoted the capillary-like tube formation and cell proliferation and migration of BMECs. The anti-inflammation effect of EGR2 and the angiogenesis effect of VEGF were regulated by miR-377 after OGD. Inhibition of miR-377 decreased cerebral infarct volume and suppressed cerebral inflammation but promoted angiogenesis in MCAO rats. Knockdown of miR-377 lessened the ischemic brain injury through promoting angiogenesis and suppressing cerebral inflammation. J. Cell. Biochem. 119: 327-337, 2018. © 2017 Wiley Periodicals, Inc.

Induced pluripotent stem cells (iPS) can differentiate into cardiomyocytes (CM) and represent a promising form of cellular therapy for heart regeneration. However, residual undifferentiated iPS derivates (iPSD), which are not fully eliminated by cell differentiation or purification protocols, may form tumors after transplantation, thus compromising therapeutic application. Inhibition of stearoyl-coA desaturase (SCD) has recently been reported to eliminate undifferentiated human embryonic stem cells, which share many features with iPSD. Here, we tested the effects of PluriSin#1, a small-molecule inhibitor of SCD, on iPS-derived CM. We found that plurisin#1 treatment significantly decreased the mRNA and protein level of Nanog, a marker for both cell pluripotency and tumor progression; importantly, we provide evidence that PluriSin#1 treatment at 20 µM for 1 day significantly induces the apoptosis of Nanog-positive iPSD. In addition, PluriSin#1 treatment at 20 µM for 4 days diminished Nanog-positive stem cells in cultured iPSD while not increasing apoptosis of iPS-derived CM. To investigate whether PluriSin#1 treatment prevents tumorigenicity of iPSD after cell transplantation, we intramyocardially injected PluriSin#1- or DMSO-treated iPSD in a mouse model of myocardial infarction (MI). DMSO-treated iPSD readily formed Nanog-expressing tumors 2 weeks after injection, which was prevented by treatment with PluriSin#1. Moreover, treatment with PluriSin#1 did not change the expression of cTnI, α-MHC, or MLC-2v, markers of cardiac differentiation (P0.05, n = 4). Importantly, pluriSin#1-treated iPS-derived CM exhibited the ability to engraft and survive in the infarcted myocardium. We conclude that inhibition of SCD holds the potential to enhance the safety of therapeutic application of iPS cells for heart regeneration.

Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle formore » cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.« less

This paper presents a dual-mode multiband transceiver with DigRF interface implemented in a 0.13-μm CMOS technology. Based on direct conversion architecture, blocks in the transceiver can be configured to simultaneously support wavelength code-division multiple access (WCDMA) band I and four Global System for Mobile Communications (GSM) bands (PCS/DCS/GSM900/GSM850). In the receiver path, the narrowband radio-frequency front-end is comprised of multiple-gated low-noise amplifiers with capacitive desensitization and current-mode passive mixers with the proposed second-order input intercept point (IIP2) calibration to comply for surface-acoustic-wave-less application. In the transmitter path, a high-linearity mixer and parallel Class-AB PA driver are adopted. Low-noise wideband frequency synthesizers with adaptive frequency calibration are proposed to cover all modes and bands. This reconfigurable transceiver achieves -5.6/-2/-6 dBm in-band third-order intercept point for WCDMA/GSM HB/GSM LB respectively, and >;65 dBm IIP2. At the maximum output power, the transmitter achieves 2.3% rms error vector magnitude for WCDMA I and 1.67° phase error for a GSM system.

Traumatic injuries to the brain and spinal cord affect a large percentage of the world’s population. However, there are currently no effective treatments for these central nervous system (CNS) injuries. In our study, we evaluated the neuroprotective role of functionalized multi-walled carbon nanotubes (MWCNTs) carrying brain derived neurotrophic factor (BNDF), nogo-66 receptor (NgR) and Ras homolog gene family member A (RhoA) in spinal cord injury (SCI). Our results showed that transfection into rat cortical neurons with BDNF-DNA significantly elevated the expression of BDNF both in vitro and in vivo. Meanwhile, transfection with NgR-siRNA and RhoA-siRNA resulted in an obvious down-regulation of NgR and RhoA in neuron cells and in injured spinal cords. In addition, the functionalized MWCNTs carrying BDNF-DNA, NgR-siRNA and RhoA-siRNA exhibited remarkable therapeutic effects on injured spinal cord. Taken together, our study demonstrates that functionalized MWCNTs have a potential therapeutic application on repair and regeneration of the CNS.

Cardiac progenitor cells (CPC) are a unique pool of progenitor cells residing in the heart that play an important role in cardiac homeostasis and physiological cardiovascular cell turnover during acute myocardial infarction (MI). Transplanting CPC into the heart has shown promise in two recent clinical trials of cardiac repair (SCIPIO & CADUCEUS). CSCs were originally isolated directly from enzymatically digested hearts followed by cell sorting using stem cell markers. However, long exposure to enzymatic digestion can affect the integrity of stem cell markers on the cell surface and also compromise stem cell function. Here, we describe a two-step procedure in which a large number of intact cardiac progenitor cells can be purified from small amount of heart tissue.

The ability to identify the donor stem cells following transplantation into injured hearts is critical. This is particularly important in evaluating stem cell survival and lineage differentiation into mature cardiovascular cells. Several approaches have been employed for tracking the donor stem cells, including fluorescent dyes and fluorescent protein gene transfer. Here, we will induce a protocol using lentivirus-mediated green fluorescent protein (GFP) to monitor the fate of donor stem cells following transplantation.

The Notch signal pathway directly controls stem cell survival, proliferation, and differentiation. Noncoding RNAs, including small microRNAs (miRNAs) and long noncoding RNAs (LncRNAs), are responsible for fine regulation of gene expression. It is also becoming increasingly evident that miRNAs have a profound impact on the Notch signaling pathway; conversely, Notch signaling can regulate a handful of miRNAs that are involved in the stem cell function. In this chapter, we summarize our current knowledge of Notch-mediated stem cell differentiation and the cross talk between miRNAs and the Notch signal pathway on determining the fate of stem cells.

Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied to deliver small-molecule drugs to the central nervous system (CNS). However, it is unclear whether PBCA nanoparticles can be used as the delivery system for large molecules to potentially treat traumatic brain injury (TBI). In this study, we tested the capacity of PBCA nanoparticles in passing through the blood?brain barrier (BBB) and transporting large molecules into normal and injured brains in the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and then loaded the particles with either horseradish peroxidase (HRP, 44?kDa) or enhanced green fluorescent protein (EGFP, 29?kDa), which were further coated with polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA nanoparticles were intravenously injected into the normal and brain-injured rats. We found that, at 45?min after injection, PBCA nanoparticle-delivered HRP or EGFP was hardly detected in the normal brains of the rats, but a small amount of EGFP carried by PBCA nanoparticles was noted in the normal brains 48?h after administration, which was further confirmed by immunolocalization with anti-EGFP antibodies. In contrast, at 4?h after TBI with a circulation time of 45?min, although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA nanoparticle-delivered HRP or EGFP was widely distributed near injured sites. Together, our findings provide histological evidence that PBCA nanoparticles can be used as an efficient delivery system for large molecules to overcome the barrier in the brain with TBI.

The Notch signal pathway directly controls stem cell survival, proliferation, and differentiation. Noncoding RNAs, including small microRNAs (miRNAs) and long noncoding RNAs (LncRNAs), are responsible for fine regulation of gene expression. It is also becoming increasingly evident that miRNAs have a profound impact on the Notch signaling pathway; conversely, Notch signaling can regulate a handful of miRNAs that are involved in the stem cell function. In this chapter, we summarize our current knowledge of Notch-mediated stem cell differentiation and the cross talk between miRNAs and the Notch signal pathway on determining the fate of stem cells.

A low-phase-noise Σ-Δ fractional-N frequency synthesizer for GSM/PCS/DCS/WCDMA transceivers is presented. The voltage controlled oscillator (VCO) is designed with modified digital controlled capacitor array (DCCA) to extend tuning range and minimize phase noise. A high-resolution adaptive frequency calibration (AFC) technique is proposed to choose frequency bands automatically in short time and increase phase noise immunity. A prototype is implemented in 0.13 μm CMOS technology. Experimental results show that the designed 1.2V wideband frequency synthesizer is locked from 3.05GHz to 5.17GHz within 30μs (20ppm), including 8μs AFC time. The measured in-band phase noise is −95.5 and −101dBc/Hz for 1.955GHz and 948MHz carriers, respectively, and accordingly the out-of-band phase noise is −123, −132dBc/Hz at 1MHz offset, and the reference spur is less than −69dBc.

A 6-GHz low-phase-noise voltage-controlled oscillator (VCO) is proposed. A varactor based coarse tuning method which differs from the traditional switch-capacitor based architecture is adopted. The source feedback resistors and a modified filtering technique are used to suppress low and high frequency noises of current source, respectively. To verify the concept, a prototype VCO is fabricated in 0.13µm CMOS technology. The measurement results show that the VCO has a phase noise of −119dBc/Hz at 1MHz offset and a tuning range of 6.1GHz to 6.7GHz. The VCO core draws only 4.7mA current from 1.2V supply voltage.

We reported 25 cases of cerebellopontine angle (CPA) tumor operation with Ho:YAG laser assistance during the operative procedure. We analysed the surgical effects of Ho:YAG lase r, compare it with CO 2 A Nd:YAG A argon laser, and illustrated its features and parameters. We think that Ho:YAG laser can be used to ablate and vaporize the tumor efficiently in the operation of the CPA tumo rs whose vascular supply is abundant and the texture is very tough. It can be used to reduce the bleeding and cooperate to incise tumor in the operation and improve the curable effect of the surgery. Keywords: Ho: YAG laser cerebellopontine angle tumor 1. INTRODUCTION The operation of CPA tumor is always a challenge to the neurosurgeon not for the total resection of the tumor, but the reservation of the nerve. In recent year, successful application of laser in neurosurgery has been reported. We also report our experience in a series of 25 patients that applied Ho:YAG laser cooperated the operation of CPA tumor from April 1994 through December 2002.

A novel and fast procedure for determining by electron spin resonance the affinity of proteins for nucleic acids is described. The assay makes use of nitroxide radicals which are covalently bound to various polynuleotides to the extent of one probe per 75 to 100 nucleotides. As a test example gene 32 protein was used, a protein known to interact with single stranded nucleic acids. Competition experiments with unlabeled nucleic acids made it feasible to directly monitor the gene 32 protein affinity for different nucleic acids. It was observed that DNA single strands are not necessarily favored by this protein for preferential binding. The experimental data also suggest that the difference in the binding constants for most of the complexes is remarkably large; for instance, (dT)n binds at least 3 to 4 orders of magnitude better to gene 32 protein than (dA)n.