-
Marshall Griffith opublikował 5 miesięcy, 2 tygodnie temu
high yields, and in vitro evaluation suggested [125I]TZ6544 has high potential to be used for screening new S1PR2 compounds and investigating the pathophysiology of S1PR2 functions. The availability of [125I]TZ6544 may facilitate the development of therapeutics and imaging agents targeting S1PR2. ADVANCES IN KNOWLEDGE [125I]TZ6544 showed increased expression of S1PR2 in diabetic rat kidney and can be used to determine binding potency of S1PR2 compounds.In this work, we describe the synthesis and characterization of the SPIONP-CUR conjugate between curcumin (CUR) and superparamagnetic iron oxide nanoparticles (SPIONPs), in addition to its application in photodynamic therapy (PDT) using a protocol free of organic solvents as a dispersant. The SPIONP-CUR conjugate was characterized by X-ray diffraction, transmission electron microscopy, zeta potential measurements, Fourier transform infrared spectroscopy, thermogravimetry, magnetometry and magnetic hyperthermia assays. The SPIONP-CUR conjugation occurred by bonding between the keto-enol moiety of CUR and the iron atoms present on the surfaces of the SPIONPs. The conjugate showed heating power under an alternating magnetic field (AMF) and photodynamic action when irradiated with blue LED light. In experiments using PDT against Staphylococcus aureus in the planktonic phase, it was demonstrated that with application of blue light at 3.12 J cm-2, the conjugate (dispersed in water) caused a total reduction of the bacterial load. In the absence of light, the reduction was insignificant, even after 24 h of contact with the bacteria.The liposomes are among the most promising types of drug delivery systems but low stability significantly limits their application. Some approaches proposed to overcome this drawback may affect the liposomes toxicity profile. It is assumed that developed by us and presented here stabilization method involving formation of silicone network within the liposomal bilayer will improve elastomechanical properties of vesicles while not deteriorating their biocompatibility. The silicone-stabilized liposomes were prepared by base-catalyzed polycondensation process of the 1,3,5,7-tetramethylcyclotetrasiloxane (D4H) within the liposomal bilayer. The systematic biological in vitro studies of vesicles obtained were carried out. Moreover, the elastomechanical features investigation employing atomic force microscopy (AFM) measurements was performed. These properties of the liposome membrane are of great importance since they define the nanocarriers’ stability as well as play a significant role in their cellular uptake via endocytosis. Applying the Derjaguin-Muller-Toporov (DMT) model, the elastic modulus of the silicone-stabilized liposomes was determined and compared to that characteristic for the pristine liposomes. The in vitro biological evaluation of silicone-stabilized liposomes demonstrated that these vesicles are not toxic for blood cells isolated from healthy donors and they do not induce oxidative stress in HepG2 cells. AFM results confirmed the stabilizing effect of silicone and revealed that the silicone network improves the elastomechanical properties of the resulted liposomes. This is the first report demonstrating that the silicone-stabilized liposomes retain biocompatibility of pristine liposomes’ while acquire significantly better elastomechanical features.
The study aims to evaluate the seasonal variation of out-of hospital cardiac arrest (OHCA) in a tourist-intensive area.
Data of all OHCA treated by the Emergency Medical Service of Lecce (LE-EMS), Italy, between 2013 and 2017, were retrospectively analyzed and complemented with information about tourist flows, in order to determine the influence of the seasonal variation of population on incidence and outcome.
Tourist arrivals were around 1,700,000 per year, mostly in summer, adding up to 803,161 residents. The occurrence of OHCA did not show a monthly variation when referring to the resident population (p=0.90). When taking into account the tourist flows, a difference in occurrence of OHCA across months was found, with the highest rate of arrests in December and the lowest in August (10.3 vs 3.4 per 100,000 persons, p<0.01). No difference was found in terms of EMS arrival time and event survival rate between summer and the rest of the year (13.6 vs 13.8min, p=0.55, and 4.4% vs 4.5%, p=0.86, respectively).
In summer tourism areas, the occurrence of OHCA is unchanged throughout the year, while the actual population presents seasonal increases. Summer enhancement of provincial EMS may contribute to maintain the performance of emergency care.
In summer tourism areas, the occurrence of OHCA is unchanged throughout the year, while the actual population presents seasonal increases. Summer enhancement of provincial EMS may contribute to maintain the performance of emergency care.One of the significant challenges to treat tuberculosis is the phenotypic resistance adapted by the latent or dormant Mycobacterium tuberculosis (M. tuberculosis) cells against most of the available drugs. Different in-vitro assay such as oxygen depletion model and nutrient starvation models have contributed to unravelling the pathogen phenotypic resistance but are too cumbersome for application to high-throughput screening (HTS) assays. In this context, non-replicating streptomycin-starved 18b (SS18b) mutant strain of M. tuberculosis provided a simple and reproducible model. This model mimics latent tuberculosis and is best suited for screening medicinally appropriate libraries. Using SS18b strain in a resazurin reduction microplate assay (REMA), high-throughput screening of ChemDiv library constituting of 30,000 compounds resulted in the identification of 470 active compounds. Clustering and scaffolding based medicinal chemistry analysis characterized these hits into 15 scaffolds. Seven most potent compounds exhibiting an MIC ≤ 1 μg/ml against SS18b were non-toxic in HepG2 cell line (selective Index ≥ 160). Our screening revealed seven novel compounds exhibiting activity against the non-replicating form of M tuberculosis. 8002-7516 was the most promising compound showing intracellular killing and could be optimized to develop a lead drug candidate.Identification of skeletal relics is crucial for medicolegal purposes. Sex estimation is one of the critical parts providing the identification of skeletal relics. In forensic practice, sex estimation requires multidisciplinary studies of such as forensic medicine, anatomy, dentistry and radiology. Recently, radiological studies on this subject have been increasing with the developing technology. The objective of this study is to examine the usage of radiological dimensions of foramen magnum for sex estimation in human skulls by developing discriminant functions in Turkish population. We analyzed 600 (300 males and 300 females) Computerized Tomography (CT) images of Turkish individuals aged between 21 and 50. Four measurements were obtained from CT images. All measurements in males were significantly greater than in females, and they provided the higher sex classification accuracy. The area of the foramen magnum calculated by Radinsky’s formula was the best measurement for sex estimation with a 75% accuracy rate. In conclusion, the CT images of foramen magnum show sexual dimorphism in our population. To use population specific data would be the most appropriate approach for sex estimation.G-quadruplex is a non-canonical nucleic acid structure formed by the folding of guanine rich DNA or RNA. The conformation and function of G-quadruplex are determined by a number of factors, including the number and polarity of nucleotide strands, the type of cations and the binding targets. Recent studies led to the discovery of additional advantageous attributes of G-quadruplex with the potential to be used in novel biosensors, such as improved ligand binding and unique folding properties. G-quadruplex based biosensor can detect various substances, such as metal ions, organic macromolecules, proteins and nucleic acids with improved affinity and specificity compared to standard biosensors. The recently developed G-quadruplex based biosensors include electrochemical and optical biosensors. A novel G-quadruplex based biosensors also show better performance and broader applications in the detection of a wide spectrum of pathogens, including SARS-CoV-2, the causative agent of COVID-19 disease. This review highlights the latest developments in the field of G-quadruplex based biosensors, with particular focus on the G-quadruplex sequences and recent applications and the potential of G-quadruplex based biosensors in SARS-CoV-2 detection.Conducting studies on sharp particulate matter (PM) gradients in Asian residential communities is difficult due to their complex building arrangements and various emission sources, particularly road traffic. In this study, a synthetic methodology, combining numerical simulations and minor field observations, was set up to investigate the dispersion of traffic-related PM in a typical Asian residential community and its contribution to PM exposure. A Lagrangian particle model (GRAL) was applied to estimate the spatiotemporal variation of the traffic-related PM increments within the community. A detailed topography dataset with 5 m horizontal resolution was used to simulate a micro-scale flow field. The model performance was comprehensively validated using both in-situ and mobile observations. The coefficient of determination (R2) of the simulated vs. observed PM2.5 reached 0.81 by an artery road, and 0.85 in alleys without significant road traffic. The maximum increments of kerbside PM exposure concentration contributed by road traffic during rush hour were found to be 38% (PM10) and 40% (PM2.5). This synthetic method was used to assess the impact of synoptic wind and canyon orientation on residents’ PM2.5 exposure related to traffic exhaust. Perfect exponential decay curves of traffic-related PM2.5 were found within canyons. The decrease of road-traffic PM2.5 on five different floor levels, compared with that on kerbside levels, ranged between 42% and 100%. The results demonstrated that in complex Asian communities, Lagrangian particle models such as GRAL can simulate the spatial distribution of PM10 and PM2.5 and assess the residents’ outdoor exposure.Dissolved organic matter (DOM) is an essential factor in natural waters to affect the bioavailability of hydrophobic organic compounds (HOCs). Climate warming may influence the partition of HOCs between DOM and water as well as the physiology of organisms. Thus, we hypothesized that elevated temperature might affect the bioavailability of HOCs in the presence of DOM. To test this hypothesis, the effect of temperature on the bioavailability of pyrene to Daphnia magna (D. magna) in water-DOM (fulvic acid) system was investigated. The results showed that, although the concentration of freely dissolved pyrene increased slightly with temperature in the presence of DOM when the level of total dissolved pyrene was kept constant, D. magna immobilization (increased by 50.0-167%) and internal body burden of pyrene (increased by 18.4-41.5%) increased significantly with every 4 °C increase in temperature (16, 20, 24 °C). The main reasonable explanation for this result is that elevated temperature promoted pyrene uptake by D.