CRISPR-dcas9 Optogenetic Nanosystem for the Blue Light-Mediated Treatment of Neovascular Lesions.

Vascular endothelial growth factor (VEGF) is the key regulator in neovascular lesions. The anti-VEGF injection is a major way to relieve retinal neovascularization and treat these diseases. However, current anti-VEGF therapeutics show significant drawbacks. The reason is the inability to effectively control its therapeutic effect. Therefore, how to controllably inhibit the VEGF target is a key point for preventing angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed for the precise regulation of pathologic neovascularization. This system is composed of a light-controlled regulatory component and transcription inhibition component. They work together to controllably and effectively inhibit the target gene's VEGF. The opto-CRISPR nanosystem achieved precise regulation according to individual differences, whereby the expression and interaction of gene was activated by light. The following representative model laser-induced choroid neovascularization and oxygen-induced retinopathy were taken as examples to verify the effect of this nanosystem. The results showed that the opto-CRISPR nanosystem was more efficacious in the light control group (NV area effectively reduced by 41.54%) than in the dark control group without light treatment. This strategy for the CRISPR-optogenetic gene nanosystem led to the development of approaches for treating severe eye diseases. Besides, any target gene of interest can be designed by merely replacing the guide RNA sequences in this system, which provided a method for light-controlled gene transcriptional repression.

A novel Cu-metal-organic framework with two-dimensional layered topology for electrochemical detection using flexible sensors.

We present a novel Cu-metal-organic framework (MOF) with two-dimensional layered topology and techniques to integrate it with flexible sensors for electrochemical detection. The unique Cu-MOF is formed by coordinating Cu2+ ions with carboxylic oxygen groups, resulting in layered structures interlayerly connected by hydrogen bonds. The resulting flexible sensors exhibit capability in detecting ascorbic acid (AA), hydrogen peroxide (H2O2) and L-Histidine (L-His) with detection limits of 2.94, 4.1 and 5.3 µM, respectively. The linear ranges of the sensors compare favorably with other sensors based on rigid platforms that offer similar sensitivity. According to the result of cytotoxicity study, the MOFs-modified flexible sensors exhibit good biocompatibility to cells, suggesting potential use in in vivo chemical detection. The results presented here demonstrate applications of MOFs in facilitating highly stable electrochemical detection in flexible electronics, and provide fundamental knowledge about structure-dependent electrochemical properties of MOFs and changing behaviors of flexible MOFs membranes under external strain. More MOFs-based flexible sensors may be developed to explore different properties of MOFs by varying their compositions and structures for healthcare and clinic applications.

Hyperbaric oxygen may improve vascular endothelial function in patients undergoing coronary stent implantation.

Background: Hyperbaric oxygen (HBO2) therapy improves myocardial function and reduces clinical restenosis in coronary arteries. This study aims to evaluate whether the HBO2 therapy can improve vascular endothelial dysfunction in patients undergoing coronary stent implantation. Methods: The retrospective study included 115 patients undergoing coronary stent implantation. Patients receiving HBO2 therapy were included in the HBO2 group (n=55) and those without HBO2 therapy were included as controls (n=60). The levels of brachial artery endothelial-dependent flow-mediated dilation (FMD), endothelial-independent nitrate-mediated dilatation (NMD), nitric oxide (NO), endothelin-1(ET-1), calcitonin gene-related peptide (CGRP) and high-sensitivity C-reactive protein (hs-CRP) were used to evaluate vascular endothelial function. Results: There were no significant differences with regard to the above parameters at baseline in either group (p⟩0.05). In both the HBO2 and control groups the levels of FMD, NO and CGRP after treatment were significantly higher than those before treatment (p⟨0.05). The levels of hs-CRP and ET-1 after treatment were significantly lower than those before treatment (p⟨0.05). After treatment, the levels of FMD, NO and CGRP in the HBO2 group were significantly higher than those of the control group (p⟨0.05), whereas the hs-CRP and ET-1 levels were significantly lower than those of the control group (p⟨0.05). Conclusion: Using HBO2 therapy as an adjunct treatment in patients undergoing coronary stent implantation may significantly improve vascular endothelial function. HBO2 therapy may have the potential to alter the course of coronary artery disease in the future. Further randomized, multicenter, prospective studies are needed.

Near-infrared light remotely up-regulate autophagy with spatiotemporal precision via upconversion optogenetic nanosystem.

In vivo noninvasively manipulating biological functions by the mediation of biosafe near infrared (NIR) light is becoming increasingly popular. For these applications, upconversion rare-earth nanomaterial holds great promise as a novel photonic element, and has been widely adopted in optogenetics. In this article, an upconversion optogenetic nanosystem that was promised to achieve autophagy up-regulation with spatiotemporal precision was designed. The implantable, wireless, recyclable, less-invasive and biocompatible system worked via two separated parts: blue light-receptor optogenetics-autophagy upregulation plasmids, for protein import; upconversion rods-encapsulated flexible capsule (UCRs-capsule), for converting tissue-penetrative NIR light into local visible blue light. Results validated that this system could achieve up-regulation of autophagy in vitro (in both HeLa and 293T cell lines) and remotely penetrate tissue (∼3.5 mm) in vivo. Since autophagy serves at a central position in intracellular signalling pathways, which is correlative with diverse pathologies, we expect that this method could establish an upconversion material-based autophagy up-regulation strategy for fundamental and clinical applications.

Evaluation of hyperbaric oxygen effects on slow coronary flow patients using gated myocardial perfusion imaging tomography.

Hyperbaric oxygen (HBO2) is widely used in clinical settings for many disease treatments. To investigate the potential effects of hyperbaric oxygen on patients with slow coronary flow (SCF) we retrospectively analyzed 98 patients who were diagnosed with SCF by coronary artery angiography. Of these, 50 patients received conventional treatment only (control group; the other 48 patients received hyperbaric oxygen treatment for four weeks in addition to the routine therapy (HBO2 group). By using gated myocardial perfusion tomography examination before and after treatment, we observed that 71 out of 148 (47.9%) subsegments of injured myocardium improved in the control group, while 108 out of 151 (71.5%) subsegments of injured myocardium improved in the HBO2 group (P ⟨ 0.05). Furthermore, the peak filling rate (PFR), time of peak filling rate (TPFR) and mean filling rate during the first one-third of the filling time (MFR/3) were all significantly improved in HBO2-treated patients compared to those who received conventional treatment only. However, we did not detect any significant effects of only treatment on left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), nor on left ventricular ejection fraction (LVEF). Our results indicate that hyperbaric oxygen therapy can be a beneficial and effective medication to improve myocardial perfusion and left ventricular diastolic function in SCF patients.

The Effect of Hyperbaric Oxygen Therapy on Myocardial Perfusion after the Implantation of Drug-Eluting Stents.

AIM: The study is to investigate hyperbaric oxygen therapy (HBOT) on myocardial perfusion of patients after the implantation of drug-eluting stents (DES) METHODS: From December 2013 to December 2015, a total of 115 patients with CAD who received DES implantation were included in this retrospective study. They were divided into HBOT group (n=55) and control group (n=60) according to different treatments retrospectively. Gated myocardial perfusion single photon emission computed tomography (SPECT) was conducted in all the patients. Endothelin-1 (ET-1), high sensitivity C reactive protein (hs-CRP) and nitric oxide (NO) were detected by the corresponding assay kits. RESULTS: After HBOT treatment in HBOT group, SPECT results showed that the improvement rate of impaired sub-segments in patients of HBOT was significantly higher than that in control group (P<0.05), and the parameters of PFR, TPFR, MFR/3 were displayed with marked differences between the two groups (P<0.05). The laboratory results demonstrated a statistically increased level of NO and decreased levels of ET-1 and hs-CRP between the two groups (P<0.05). CONCLUSIONS: HBO may improve myocardial blood perfusion, reduce inflammation and vascular endothelial dysfunction, and further improve myocardial microcirculation in patients after the implantation of drug-eluting stents.

Materials and Techniques for Implantable Nutrient Sensing Using Flexible Sensors Integrated with Metal-Organic Frameworks.

The combination of novel materials with flexible electronic technology may yield new concepts of flexible electronic devices that effectively detect various biological chemicals to facilitate understanding of biological processes and conduct health monitoring. This paper demonstrates single- or multichannel implantable flexible sensors that are surface modified with conductive metal-organic frameworks (MOFs) such as copper-MOF and cobalt-MOF with large surface area, high porosity, and tunable catalysis capability. The sensors can monitor important nutriments such as ascorbicacid, glycine, l-tryptophan (l-Trp), and glucose with detection resolutions of 14.97, 0.71, 4.14, and 54.60 × 10-6 m, respectively. In addition, they offer sensing capability even under extreme deformation and complex surrounding environment with continuous monitoring capability for 20 d due to minimized use of biological active chemicals. Experiments using live cells and animals indicate that the MOF-modified sensors are biologically safe to cells, and can detect l-Trp in blood and interstitial fluid. This work represents the first effort in integrating MOFs with flexible sensors to achieve highly specific and sensitive implantable electrochemical detection and may inspire appearance of more flexible electronic devices with enhanced capability in sensing, energy storage, and catalysis using various properties of MOFs.

[Efficacy of ACEI in the treatment of hypertension and the effect of secondary prevention in patients complicated with coronary heart disease and stroke].

OBJECTIVE: To investigate the efficacy of ACEI drugs in the treatment of hypertension patients and the effect of two levels of prevention of hypertension complicated with coronary heart disease and stroke. METHDOS: 210 cases of hypertension patients in our hospital from January 2012 to December 2015 were randomly divided into experimental group and control group, 105 cases in each group. According to the conventional symptomatic treatment, the experimental group was given lisinopril treatment, while control group was given the captopril treatment. Changes of blood pressure parameters and the level of baPWV in two groups were observed before and after treatment coronary heart disease and stroke, recurrence rate and death rate were compared in these two groups. RESULTS: No significant difference of SBP, DBP, PP and baPWV between two groups before treatment (P>0.05). The indexes of the two groups were significantly decreased after 1 months and 3 months, and the level of patients in the experimental group was lower than that of the control group (P<0.05). The recurrence rate in the experimental group was lower than those in the control group (P<0.05). CONCLUSIONS: ACEI drugs in the treatment of hypertension can effectively reduce the level of blood pressure, improve arterial elasticity function, reduce the recurrence rate and mortality rate of coronary heart disease and stroke. The effect of antihypertensive and two levels of prevention of hypertension complicated with coronary heart disease and stroke of lisinopril is positive.

The personal genome browser: visualizing functions of genetic variants.

Advances in high-throughput sequencing technologies have brought us into the individual genome era. Projects such as the 1000 Genomes Project have led the individual genome sequencing to become more and more popular. How to visualize, analyse and annotate individual genomes with knowledge bases to support genome studies and personalized healthcare is still a big challenge. The Personal Genome Browser (PGB) is developed to provide comprehensive functional annotation and visualization for individual genomes based on the genetic-molecular-phenotypic model. Investigators can easily view individual genetic variants, such as single nucleotide variants (SNVs), INDELs and structural variations (SVs), as well as genomic features and phenotypes associated to the individual genetic variants. The PGB especially highlights potential functional variants using the PGB built-in method or SIFT/PolyPhen2 scores. Moreover, the functional risks of genes could be evaluated by scanning individual genetic variants on the whole genome, a chromosome, or a cytoband based on functional implications of the variants. Investigators can then navigate to high risk genes on the scanned individual genome. The PGB accepts Variant Call Format (VCF) and Genetic Variation Format (GVF) files as the input. The functional annotation of input individual genome variants can be visualized in real time by well-defined symbols and shapes. The PGB is available at http://www.pgbrowser.org/.