Vascular protection by ethanol extract of Morus alba root bark: Endothelium-dependent relaxation of rat aorta and decrease of smooth muscle cell migration and proliferation

Copyright © 2018 Nisha Panth et al. This is an open access article distributed under the Creative Commons Attribution License Morus alba (white mulberry) is native to the northern part of Korea and popularly used as a traditional medicine due to its numerous health benefits against human's disease. However, the possibility that M. alba may also affect the cardiovascular system remains unexplored. This study sought to investigate the vascular protective effects of the root bark extract of M. alba (MAE). Vascular reactivity was performed in organ baths using isolated rat thoracic aorta, while platelet derived growth factor (PDGF) induced proliferation and migration of vascular smooth muscle cells (VSMCs) were studied by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and wound healing assay, respectively. MAE evoked a concentration dependent vasorelaxation following endothelium-dependent pathway. However, vessel relaxations in response to MAE were markedly reduced after endothelium removal; treatment of endothelial nitric oxide synthase inhibitor, guanylyl cyclase inhibitor, and nonspecific potassium channel inhibitor, however, was not altered by cyclooxygenase inhibitor. Furthermore, MAE also significantly blunted contractile response to vasoconstrictor agent, phenylephrine. Taken together, the current evidence revealed that MAE is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, nitric oxide cyclic-guanosine monophosphate (NO-cGMP) pathway in combination with potassium (K + ) channel activation. Moreover, MAE inhibited proliferation and migration of VSMCs induced by PDGF. Therefore, MAE could be a promising candidate of natural medicine for preventing and controlling cardiovascular diseases linked with endothelial dysfunction

The QGP phase in relativistic heavy-ion collisions

The dynamics of partons, hadrons and strings in relativistic nucleus-nucleus collisions is analyzed within the novel Parton-Hadron-String Dynamics (PHSD) transport approach, which is based on a dynamical quasiparticle model for partons (DQPM) matched to reproduce recent lattice-QCD results - including the partonic equation of state - in thermodynamic equilibrium. The transition from partonic to hadronic degrees of freedom is described by covariant transition rates for the fusion of quark-antiquark pairs or three quarks (antiquarks), respectively, obeying flavor current-conservation, color neutrality as well as energy-momentum conservation. The PHSD approach is applied to nucleus-nucleus collisions from low SIS to RHIC energies. The traces of partonic interactions are found in particular in the elliptic flow of hadrons as well as in their transverse mass spectra.Comment: To be published by Springer in Proceedings of the International Symposium on `Exciting Physics', Makutsi-Range, South Africa, 13-20 November, 201

BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer.

BRCA1 mutation or depletion correlates with basal-like phenotype and poor prognosis in breast cancer but the underlying reason remains elusive. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with downregulation of the expression of the pleiotropic tumour suppressor FOXO3. Knockdown of BRCA1 by small interfering RNA (siRNA) resulted in downregulation of FOXO3 expression in the BRCA1-competent MCF-7, whereas expression of BRCA1 restored FOXO3 expression in BRCA1-defective HCC70 and MDA-MB-468 cells, suggesting a role of BRCA1 in the control of FOXO3 expression. Treatment of HCC70 and MDA-MB-468 cells with either the DNA methylation inhibitor 5-aza-2'-deoxycitydine, the N-methyltransferase enhancer of zeste homologue 2 (EZH2) inhibitor GSK126 or EZH2 siRNA induced FOXO3 mRNA and protein expression, but had no effect on the BRCA1-competent MCF-7 cells. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNMT1/3a/b and histone H3 lysine 27 trimethylation (H3K27me3) are recruited to the endogenous FOXO3 promoter, further advocating that these proteins interact to modulate FOXO3 methylation and expression. In addition, ChIP results also revealed that BRCA1 depletion promoted the recruitment of the DNA methyltransferases DNMT1/3a/3b and the enrichment of the EZH2-mediated transcriptional repressive epigenetic marks H3K27me3 on the FOXO3 promoter. Methylated DNA immunoprecipitation assays also confirmed increased CpG methylation of the FOXO3 gene on BRCA1 depletion. Analysis of the global gene methylation profiles of a cohort of 33 familial breast tumours revealed that FOXO3 promoter methylation is significantly associated with BRCA1 mutation. Furthermore, immunohistochemistry further suggested that FOXO3 expression was significantly associated with BRCA1 status in EZH2-positive breast cancer. Consistently, high FOXO3 and EZH2 mRNA levels were significantly associated with good and poor prognosis in breast cancer, respectively. Together, these data suggest that BRCA1 can prevent and reverse FOXO3 suppression via inhibiting EZH2 and, consequently, its ability to recruit the transcriptional repressive H3K27me3 histone marks and the DNA methylases DNMT1/3a/3b, to induce DNA methylation and gene silencing on the FOXO3 promoter

Applications of Nature-Inspired Algorithms for Dimension Reduction: Enabling Efficient Data Analytics

In [1], we have explored the theoretical aspects of feature selection and evolutionary algorithms. In this chapter, we focus on optimization algorithms for enhancing data analytic process, i.e., we propose to explore applications of nature-inspired algorithms in data science. Feature selection optimization is a hybrid approach leveraging feature selection techniques and evolutionary algorithms process to optimize the selected features. Prior works solve this problem iteratively to converge to an optimal feature subset. Feature selection optimization is a non-specific domain approach. Data scientists mainly attempt to find an advanced way to analyze data n with high computational efficiency and low time complexity, leading to efficient data analytics. Thus, by increasing generated/measured/sensed data from various sources, analysis, manipulation and illustration of data grow exponentially. Due to the large scale data sets, Curse of dimensionality (CoD) is one of the NP-hard problems in data science. Hence, several efforts have been focused on leveraging evolutionary algorithms (EAs) to address the complex issues in large scale data analytics problems. Dimension reduction, together with EAs, lends itself to solve CoD and solve complex problems, in terms of time complexity, efficiently. In this chapter, we first provide a brief overview of previous studies that focused on solving CoD using feature extraction optimization process. We then discuss practical examples of research studies are successfully tackled some application domains, such as image processing, sentiment analysis, network traffics / anomalies analysis, credit score analysis and other benchmark functions/data sets analysis

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al

Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

Development of FRET Assay into Quantitative and High-throughput Screening Technology Platforms for Protein–Protein Interactions

Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research and is a very powerful tool in elucidating protein interactions in many cellular processes. Ubiquitination and SUMOylation are multi-step cascade reactions, involving multiple enzymes and protein–protein interactions. Here we report the development of dissociation constant (Kd) determination for protein–protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology. These developments are based on steady state and high efficiency of fluorescent energy transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The developments in theoretical and experimental procedures for protein interaction Kd determination and cell-based HTS provide novel tools in affinity measurement and protein interaction inhibitor screening. The Kd determined by FRET between SUMO1 and Ubc9 is compatible with those determined with other traditional approaches, such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both Kd determination and cell-based HTS, carried out in 384-well plate format, provide powerful tools for large-scale and high-throughput applications