Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood–brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer’s disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson’s disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research

Facile Fabrication of Ultrafine Copper Nanoparticles in Organic Solvent

A facile chemical reduction method has been developed to fabricate ultrafine copper nanoparticles whose sizes can be controlled down to ca. 1 nm by using poly(N-vinylpyrrolidone) (PVP) as the stabilizer and sodium borohyrdride as the reducing agent in an alkaline ethylene glycol (EG) solvent. Transmission electron microscopy (TEM) results and UV–vis absorption spectra demonstrated that the as-prepared particles were well monodispersed, mostly composed of pure metallic Cu nanocrystals and extremely stable over extended period of simply sealed storage

Prehospital critical care for out-of-hospital cardiac arrest: An observational study examining survival and a stakeholder-focused cost analysis

© 2016 The Author(s). Background: Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care. Methods: This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK. Discussion: Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service provision. If no clinical benefit is found, the public and charities providing these services can consider concentrating their efforts on other areas of prehospital care. Trial registration: ISRCTN registry ID ISRCTN18375201

Phonon-driven spin-Floquet magneto-valleytronics in MoS2

Two-dimensional materials equipped with strong spin-orbit coupling can display novel electronic, spintronic, and topological properties originating from the breaking of time or inversion symmetry. A lot of interest has focused on the valley degrees of freedom that can be used to encode binary information. By performing ab initio time-dependent density functional simulation on MoS2, here we show that the spin is not only locked to the valley momenta but strongly coupled to the optical E '' phonon that lifts the lattice mirror symmetry. Once the phonon is pumped so as to break time-reversal symmetry, the resulting Floquet spectra of the phonon-dressed spins carry a net out-of-plane magnetization (approximate to 0.024 mu(B) for single-phonon quantum) even though the original system is non-magnetic. This dichroic magnetic response of the valley states is general for all 2H semiconducting transition-metal dichalcogenides and can be probed and controlled by infrared coherent laser excitation

Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

<p>Abstract</p> <p>Background</p> <p>It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound.</p> <p>Methods</p> <p>5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres.</p> <p>Results</p> <p>5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t_1/2, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (V_D, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05).</p> <p>Conclusion</p> <p>In our model system, 5-FU/PEG-PBLG nanoparticles changed the pharmacokinetic behavior of 5-FU, thus increasing its anticancer activity. 5-Fluorouracil loaded nanoparticles have potential as a novel anticancer drug that may have useful clinical applications.</p

Novel method of real-time PCR-based screening for common fetal trisomies

Background The non-invasive prenatal test (NIPT) is based on next generation sequencing (NGS) and is used for screening for fetal trisomy. However, it is time-consuming and technically difficult. Recently, peptide nucleic acid (PNA) probe-based real-time polymerase chain reaction (RT-PCR) was developed. This study aimed to examine the performance of the RT-PCR-based NIPT for screening of common fetal trisomies Methods From stored maternal plasma, RT-PCR was performed using Patio™ NIPT Detection Kit. In melting curve analysis, the height of melting peaks of target chromosome and reference chromosome was calculated as a peak ratio. The adjusted peak ratio of 8 markers with correction factors in each target chromosome was summated and calculated to z-score. The cut-off value for each target chromosome was established for classification (low risk vs. high risk for trisomy) whose performance was obtained in the validation phase. Results 330 plasma samples from pregnant women with normal fetus and 22 trisomy cell-line samples were used to establish the optimal cut-off values for z-score of each target chromosome. In the validation phase, 1023 samples from pregnant women including 22 cases with fetal trisomy and 1001 cases of normal control were used. The RT-PCR-based NIPT showed 95.45% sensitivity [95% confidence interval (CI) 77.16–99.88%], 98.60% specificity (95% CI 97.66–99.23%), and 98.53% accuracy (95% CI 97.59–99.18%) for the identification of trisomy 21, 18, or 13. Of 1023 samples, fifteen cases were mismatched for classification [one case as a false negative (false negative rate: 4.5%) and 14 cases as false positives (false positive rate: 1.4%)]. Conclusion The RT-PCR-based NIPT showed high sensitivity and specificity for the detection of common fetal trisomies and it could be a feasible alternative to NGS-based NIPT.This study was supported by the Technology Innovation Program (or Industrial Strategic Technology Development Program) (N0002392) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). And this work was funded by grants (HI16C0628) from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Shear Forces during Blast, Not Abrupt Changes in Pressure Alone, Generate Calcium Activity in Human Brain Cells

Blast-Induced Traumatic Brain Injury (bTBI) describes a spectrum of injuries caused by an explosive force that results in changes in brain function. The mechanism responsible for primary bTBI following a blast shockwave remains unknown. We have developed a pneumatic device that delivers shockwaves, similar to those known to induce bTBI, within a chamber optimal for fluorescence microscopy. Abrupt changes in pressure can be created with and without the presence of shear forces at the surface of cells. In primary cultures of human central nervous system cells, the cellular calcium response to shockwaves alone was negligible. Even when the applied pressure reached 15 atm, there was no damage or excitation, unless concomitant shear forces, peaking between 0.3 to 0.7 Pa, were present at the cell surface. The probability of cellular injury in response to a shockwave was low and cell survival was unaffected 20 hours after shockwave exposure