Biphasic Nature Research Articles

The neurovascular unit and systemic biology in stroke - implications for translation and treatment.

Ischaemic stroke is a leading cause of disability and death for which no acute treatments exist beyond recanalization. The development of novel therapies has been repeatedly hindered by translational failures that have changed the way we think about tissue damage after stroke. What was initially a neuron-centric view has been replaced with the concept of the neurovascular unit (NVU), which encompasses neuronal, glial and vascular compartments, and the biphasic nature of neural-glial-vascular signalling. However, it is now clear that the brain is not the private niche it was traditionally thought to be and that the NVU interacts bidirectionally with systemic biology, such as systemic metabolism, the peripheral immune system and the gut microbiota. Furthermore, these interactions are profoundly modified by internal and external factors, such as ageing, temperature and day-night cycles. In this Review, we propose an extension of the concept of the NVU to include its dynamic interactions with systemic biology. We anticipate that this integrated view will lead to the identification of novel mechanisms of stroke pathophysiology, potentially explain previous translational failures, and improve stroke care by identifying new biomarkers of and treatment targets in stroke.

The effect of mono‐diglycerides on the mechanical properties, microstructure, and physical stability of an edible rice bran wax–gelatin biphasic gel system

AbstractBigels are prepared by homogenization of an organogel and hydrogel. Bigels can offer improved properties such as enhanced physical stability and the ability to interact with both hydrophilic and lipophilic moieties and substances when compared to other gelled systems due to its semi‐solid internal phase, biphasic nature, and supramolecular interactions between components. The objective of this study was to determine the effect of mono‐diglycerides (MDG) on the supramolecular structure and interactions, physical stability, and mechanical properties of a rice bran wax–gelatin bigels. The organogel‐to‐hydrogel (OG:HG) ratios tested were 60:40, 70:30, and 80:20 with MDG incorporated at four concentrations (0.5%, 1%, 2%, 3% [w/w]). Bigels were analyzed using nuclear magnetic resonance spectroscopy, confocal scanning laser microscopy (CSLM), Fourier transform infrared spectroscopy (FTIR), texture analysis, and liquid binding capacity studies. The results showed that MDG have a dual effect on the structural organization and stability of the systems; they act as emulsifiers and/or crystallization modifiers. CSLM and FTIR showed that the addition of MDG had the greatest effect on the microstructure of the 60:40 OG:HG ratio, where MDG concentrations 0.5% and 1% (w/w) exhibited a reduction in the size of the oleogel regions while concentrations 2% and 3% (w/w) showed a phase inversion. MDG addition resulted in a gradual decrease in bigel hardness, but an enhancement of physical stability.

Flexion of Nrf2 by tea phytochemicals: A review on the chemopreventive and chemotherapeutic implications

Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2), the redox-sensitive transcription factor, plays a key role in stress-defense and detoxification. Nrf2 is tightly controlled by its negative regulator cum sensor Kelch-[ECH]-associated protein 1 (Keap1). Nrf2 is well known for its dual nature owing to its cancer preventive and cancer promoting abilities. Modulation of this biphasic nature of Nrf2 signaling by phytochemicals may be a potential cancer preventive and anticancer therapeutic strategy. Phytocompounds may either act as Nrf2-activator or Nrf2-inhibitor depending on their differential concentration and varied cellular environment. Tea is not just the most popular global beverage with innumerable health-benefits but has well-established chemopreventive and chemotherapeutic effects. Various types of tea infusions contain a wide range of bioactive compounds, such as polyphenolic catechins and flavonols, which are endowed with potent antioxidant properties. Despite of their rapid biotransformation and poor bioavailability, regular tea consumption is risk-reductive for several cancer forms. Tea catechins show their dual Nrf2-modulatory effect by directly acting on Nrf2-Keap1 or their upstream regulators and downstream effectors in a highly case-specific manner. In this review, we have tried to present a comprehensive evaluation of the Nrf2-mediated chemopreventive and chemotherapeutic applications of tea in various preclinical cancer models, the Nrf2-modulatory mechanisms, and the limitations which need to be addressed in future research.

Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells

Rat pheochromocytoma (PC12) cells were treated with the proteasome inhibitor MG-132 and morphological changes were recorded. Initially, neuronal differentiation was induced but after 24 h signs of morphological deterioration became apparent. We performed nuclear staining, flow cytometry and WST-1 assay then analyzed signal transduction pathways involving Akt, p38 MAPK (Mitogen-Activated Protein Kinase), JNK (c-Jun N-terminal Kinase), c-Jun and caspase-3. Stress signaling via p38, JNK and c-Jun was active even after 24 h of MG-132 treatment, while the survival-mediating Akt phosphorylation declined and the executor of apoptosis (caspase-3) was activated by that time and apoptosis was also observable. We examined subcellular localization of stress signaling components, applied kinase inhibitors and dominant negative H-Ras mutant-expressing PC12 cells in order to decipher connections of stress-mediating pathways. Our results are suggestive of that treatment with the proteasome inhibitor MG-132 has a biphasic nature in PC12 cells. Initially, it induces neuronal differentiation but prolonged treatments lead to apoptosis.

Tissue-Scale Biomechanical Testing of Brain Tissue for the Calibration of Nonlinear Material Models.

Brain tissue is one of the most complex and softest tissues in the human body. Due to its ultrasoft and biphasic nature, it is difficult to control the deformation state during biomechanical testing and to quantify the highly nonlinear, time-dependent tissue response. In numerous experimental studies that have investigated the mechanical properties of brain tissue over the last decades, stiffness values have varied significantly. One reason for the observed discrepancies is the lack of standardized testing protocols and corresponding data analyses. The tissue properties have been tested on different length and time scales depending on the testing technique, and the corresponding data have been analyzed based on simplifying assumptions. In this review, we highlight the advantage of using nonlinear continuum mechanics based modeling and finite element simulations to carefully design experimental setups and protocols as well as to comprehensively analyze the corresponding experimental data. We review testing techniques and protocols that have been used to calibrate material model parameters and discuss artifacts that might falsify the measured properties. The aim of this work is to provide standardized procedures to reliably quantify the mechanical properties of brain tissue and to more accurately calibrate appropriate constitutive models for computational simulations of brain development, injury and disease. Computational models can not only be used to predictively understand brain tissue behavior, but can also serve as valuable tools to assist diagnosis and treatment of diseases or to plan neurosurgicalprocedures. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Amphiphilic Polymer Co‐Network: A Versatile Matrix for Tailoring the Photonic Energy Transfer in Wearable Energy Harvesting Devices

AbstractIn recent years, Förster resonance energy transfer (FRET) and related topics have received marked attention both as a subject of scientific investigation and due to its many potential applications. However, the state‐of‐the‐art matrix materials for the FRET need to be improved in terms of universal loading for all types of luminescent moieties and the matrix integrability with real‐life devices, but without sacrificing the FRET efficiency, i.e., maintaining the proximity of the embedded donors and acceptors. Amphiphilic polymer co‐networks (APCNs) are investigated as versatile matrix materials for hosting luminescent materials and realizing highly efficient FRET between hydrophobic inorganic donors (CsPbBr3 nanocrystals) and hydrophilic organic acceptors (Rhodamine B). APCNs are advantageous owing to the unique properties of their hydrophilic and hydrophobic biphasic nature and the uniformly distributed nano‐domains. The energy transfer rate can be tailored in a straightforward way by manipulating the nano‐domain sizes and volumetric distribution, so steering donor–acceptor pair loading and distances. Consequently, APCNs are used as luminescent solar concentrators for fiber solar cells, demonstrating the ability to enhance existing solar‐energy harvesting electronics via photonic energy transfer steering. APCN is demonstrated as a powerful matrix for future photonic applications in the field of energy harvesting and energy generation.

A detailed investigation to study the pattern of the interplay of Cyclic AMP Receptor Protein (CRP) of E. coli with its different classes of promoters

The activity of most of the promoters in Escherichia coli, involved in the metabolism of sugars other than glucose, is controlled by a CRP (cAMP receptor protein) or CAP (catabolite activator protein). CRP-dependent promoters are differentiated into various classes (Class I, Class II, and Class III) based on its cognate binding site’s position on DNA. The promoters regulated by CAP are differentially regulated by this transcriptional factor and it is also imperative to mention that these promoters vary greatly in respect to the binding site of CAP to its cognate binding site, it has also been reported that either it overlaps with the binding site of RNA polymerase or it present upstream to it. In Class I CAP-dependent promoters, a particular CAP molecule makes protein-protein interaction for the start of transcription. In Class II CAP-dependent promoters, a particular CAP molecule makes multiple interactions for the start of transcription. At last, in Class III-CAP dependent promoters, more than one CAP molecule is involved and activation of transcription is done synergistically. It has also been documented that CAP shows a kind of biphasic behavior in some promoters. So, the main focus of this work is to find out whether this biphasic behavior is true for other E. coli promoters as well. Experiments have been performed to know more about this biphasic nature and the various patterns of interactions of catabolite activator protein (CAP) of E. coli with its different classes of promoters.

Stød Timing and Domain in Danish

This study investigates the timing of stød, a type of phonological nonmodal phonation related to creaky voice in Danish, relative to the syllable. Stød-bearing syllables are characterized by high fundamental frequency (F0) and modal phonation at the beginning of the syllable followed by nonmodal, often creaky phonation and low F0 towards the end of the syllable (the stød phase proper). However, the timing of these two phases relative to the syllable and to each other has been debated. To investigate this, F0 throughout the word and the timing of the stød phase proper relative to the syllable were analyzed in five types of monosyllabic words. The results show that across word types the first stød phase (high F0) coordinates with the syllable rhyme onset, whilst the second phase is timed to the center of the sonorant rhyme, in contrast to previous hypotheses of stød timing. This relationship is formalized using the framework of Articulatory Phonology. In doing so, two additions to the theory are proposed to account for the biphasic nature of stød and the timing of the stød phase proper relative to the syllable.

Molecular mechanism and regulation of neurovascular coupling in the human brain: The influence of thermoheliox

An experimental study of the dynamics of the BOLD (blood oxygen level dependent) signal by functional magnetic resonance imaging was carried out. It was found that the dynamic responses of the BOLD-signal, have a biphasic character. Through kinetic modeling methods, it was shown that the biphasic nature of the hemodynamic response is based on negative feedback, with Ca2+ pulse inhibited by vasodilation products (NO and prostaglandins). The effect of thermoheliox (inhalation of a mixture of helium and oxygen at 70 °C) on functional hemodynamics was studied. It was shown that preliminary inhalation of thermoheliox stimulates and prolongs hemodynamic impulses.

Dynamic alteration of poroelastic attributes as determinant membrane nanorheology for endocytosis of organ specific targeted gold nanoparticles

BackgroundEfficacy of targeted drug delivery using nanoparticles relies on several factors including the uptake mechanisms such as phagocytosis, macropinocytosis, micropinocytosis and receptor mediated endocytosis. These mechanisms have been studied with respect to the alteration in signaling mechanisms, cellular morphology, and linear nanomechanical properties (NMPs). Commonly employed classical contact mechanics models to address cellular NMPs fail to address mesh like structure consisting of bilayer lipids and proteins of cell membrane. To overcome this technical challenge, we employed poroelastic model which accounts for the biphasic nature of cells including their porous behavior exhibiting both solid like (fluid storage) and liquid like (fluid dissipate) behavior.ResultsIn this study, we employed atomic force microscopy to monitor the influence of surface engineering of gold nanoparticles (GNPs) to the alteration of nonlinear NMPs such as drained Poisson’s ratio, effective shear stress, diffusion constant and pore dimensions of cell membranes during their uptake. Herein, we used pancreatic cancer (PDAC) cell lines including Panc1, AsPC-1 and endothelial cell (HUVECs) to understand the receptor-dependent and -independent endocytosis of two different GNPs derived using plectin-1 targeting peptide (PTP-GNP) and corresponding scrambled peptide (sPEP-GNP). Compared to untreated cells, in case of receptor dependent endocytosis of PTP-GNPs diffusion coefficient altered ~ 1264-fold and ~ 1530-fold and pore size altered ~ 320-fold and ~ 260-fold in Panc1 and AsPC-1 cells, respectively. Whereas for receptor independent mechanisms, we observed modest alteration in diffusion coefficient and pore size, in these cells compared to untreated cells. Effective shear stress corresponding to 7.38 ± 0.15 kPa and 20.49 ± 0.39 kPa in PTP-GNP treatment in Panc1 and AsPC-1, respectively was significantly more than that for sPEP-GNP. These results demonstrate that with temporal recruitment of plectin-1 during receptor mediated endocytosis affects the poroelastic attributes of the membrane.ConclusionThis study confirms that nonlinear NMPs of cell membrane are directly associated with the uptake mechanism of nanoparticles and can provide promising insights of the nature of endocytosis mechanism involved for organ specific drug delivery using nanoparticles. Hence, nanomechanical analysis of cell membrane using this noninvasive, label-free and live-cell analytical tool can therefore be instrumental to evaluate therapeutic benefit of nanoformulations.Graphical

Modelling physiological costs to assess impacts of climate change on amphibians in Yellowstone National Park, U.S.A

Amphibians are vital elements of ecosystems, serving as predator and prey. Their biphasic nature makes them dependent on aquatic and terrestrial habitats; as wet-skinned ectotherms, they are vulnerable to a range of environmental threats, including climate change. Yellowstone National Park (YNP) is becoming warmer and drier, and some wetlands important to amphibians have diminished. Continued climate change is predicted to reduce snowpack, soil moisture, and forest cover. We used data from models of future climate and vegetation cover to mechanistically model how climate change might affect the movements of Western Toads (Anaxyrus boreas) across the landscape of three test areas in YNP for the years 2050 and 2090, compared to 2000 as a baseline. Least-cost path analysis produced mixed results: for 2050 and 2090, physiological costs of movement increased in one test area and decreased in another; they were mixed in the third. These changes generally reflect the preference by toads for more open forests. Estimating costs for other species of YNP amphibians produced more negative results. For Columbia Spotted Frogs (Rana luteiventris) and Boreal Chorus Frogs (Pseudacris maculata) (both more aquatic and less adapted to terrestrial habitats), movement costs increased by about 2–15X. Reduced frequency or duration of rain events might limit the nocturnal movements of Western Tiger Salamanders (Ambystoma mavortium). Climate change may not have negative impacts on all amphibians throughout YNP, but increased movement costs for terrestrial habitats will accentuate effects of drying wetlands in at least parts of YNP. Land management actions that preserve habitat structure of both forest and low shrub cover may help mitigate continued drying conditions of climate change.

ANALYSIS OF THE INFLUENCE OF PROLONGED IRRADIATION ON HEMATOPOIETIC PROGENITOR CELLS IN GEL DIFFUSION CHAMBERS USING MATHEMATICAL MODELLING.

determining of the functional activity of mice bone marrow hematopoietic progenitor cells, cultivated in gel diffusion chambers, on the stages of hematopoiesis recovery after their prolonged irradiation in the lethal dose in a comparative aspect with the method of colony forming in spleen using mathematical model. The method of cell cultivation in gel diffusion chambers, cytological methods, mathematical modeling, and statistical methods of research were used. Bone marrow samples extracted from the femur of mice irradiated with a total dose of 8 Gy with a power 0.0028 Gy/min were cultivated in diffusion chambers with semi solid agar in the abdominal cavity of CBA recipient mice. Comparative analysis of the colonyforming efficiency of progenitor cells (CFU) was carried out during cultivation in gel diffusion chambers in the process of hematopoiesis recovery for 30 days, as well as in the spleen of lethally irradiated animals, in accordance with the mathematical model. Analysis of colony forming kinetics in gel diffusion chambers after prolonged exposure to ionizing radiation indicated the biphasic nature of hematopoiesis recovery. Thus, in the first few days after the irradiation a drop in the number of CFU is observed compared to the control, which continues until the 9th day. Subsequently there is a sharp increase in the number of CFU in cell culture, which continues until the complete recovery of hematopoiesis. The obtained data, recalculated per mouse femur, correspond to the results of colony forming in the spleen of irradiated animals, described by K. S. Chertkov and taken as a basis while developing our mathematical model, as well as to its parameters, which describe the process of hematopoiesis recovery. Conformity of the indices obtained during the cultivation using the method of gel diffusion chambers of mice bone marrow prolongedly irradiated at a total dose of 8 Gy with a power 0.0028 Gy/min, to the results of colony forming in spleen of lethally irradiated mice, which were the basis for mathematical model development, is the evidence of the feasibility of using a mathematical model to assess the process of hematopoiesis recovery by progenitor cells of different maturation levels, and the experimental approach of CFU growing in gel diffusion chambers can be considered as an additional method of researching the hematopoiesis recovery along with the spleen colony method.

Pharmacokinetics of adrenaline autoinjectors.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first-line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10min to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.

Predictors of severe leptospirosis: a multicentre observational study from Central Malaysia

BackgroundLeptospirosis is a re-emerging disease with vast clinical presentations, that ranges from subclinical or mild to severe and fatal outcomes. Leptospirosis can be managed well if diagnosed earlier, however, similar clinical presentations by several other febrile illnesses or co-infections, and laboratory diagnostic challenges due to the biphasic nature of the illness, often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study.MethodsA prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity.ResultsAmong the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet < 150 × 109/L as factors associated with severe illness. Acute kidney injury, alanine aminotransferase > 50 IU and platelet < 150 × 109/L were defined as the independent factors for severity.ConclusionsLungs, liver and kidney involvement and septic shock were found as the prognostic factors for severe leptospirosis. Acute kidney injury, high level of alanine aminotransferase and low level of platelets were found to be independent predictors of severity.

Solid State Chemical Interaction Between Ti and Al-Si Alloys

Diffusion couples of Ti and biphasic alloy Al-7wt%Si were produced and heat-treated at 535 °C for between 1 and 200 hours. The nature and thickness of the phases present in the reaction layer sequence were characterized using conventional techniques such as microprobe analysis and transmission electron microscopy. For short interaction times the interfacial reaction layer consists mainly of silicides, whereas aluminides are formed after times longer than 40h. This variation in the spatial reaction layer sequence over time is explained by the biphasic nature of one of the diffusion couple end-members, with high activity for both elements, and by the huge difference between the composition of the first phase formed at the initial interface and the average composition of the biphasic end-member. This situation, which can be observed in other systems, illustrates the difficulty of confirming that a true diffusion path has been attained in a diffusion couple. Most of the criteria that were first proposed by Kirkaldy and Brown, can apparently be fulfilled, but the system could continue shifting over time towards a more stable configuration. In some systems, as in the case of Al-Si-Ti, the slow kinetics can be problematic, making it impossible to predict a radical change in material properties.

High-affinity P2Y2 and low-affinity P2X7 receptor interaction modulates ATP-mediated calcium signaling in murine osteoblasts.

The P2 purinergic receptor family implicated in many physiological processes, including neurotransmission, mechanical adaptation and inflammation, consists of ATP-gated non-specific cation channels P2XRs and G-protein coupled receptors P2YRs. Different cells, including bone forming osteoblasts, express multiple P2 receptors; however, how P2X and P2Y receptors interact in generating cellular responses to various doses of [ATP] remains poorly understood. Using primary bone marrow and compact bone derived osteoblasts and BMP2-expressing C2C12 osteoblastic cells, we demonstrated conserved features in the P2-mediated Ca2+ responses to ATP, including a transition of Ca2+ response signatures from transient at low [ATP] to oscillatory at moderate [ATP], and back to transient at high [ATP], and a non-monotonic changes in the response magnitudes which exhibited two troughs at 10−4 and 10−2 M [ATP]. We identified P2Y2 and P2X7 receptors as predominantly contributing to these responses and constructed a mathematical model of P2Y2R-induced inositol trisphosphate (IP3) mediated Ca2+ release coupled to a Markov model of P2X7R dynamics to study this system. Model predictions were validated using parental and CRISPR/Cas9-generated P2Y2 and P2Y7 knockouts in osteoblastic C2C12-BMP cells. Activation of P2Y2 by progressively increasing [ATP] induced a transition from transient to oscillatory to transient Ca2+ responses due to the biphasic nature of IP3Rs and the interaction of SERCA pumps with IP3Rs. At high [ATP], activation of P2X7R modulated the response magnitudes through an interplay between the biphasic nature of IP3Rs and the desensitization kinetics of P2X7Rs. Moreover, we found that P2Y2 activity may alter the kinetics of P2X7 towards favouring naïve state activation. Finally, we demonstrated the functional consequences of lacking P2Y2 or P2X7 in osteoblast mechanotransduction. This study thus provides important insights into the biophysical mechanisms underlying ATP-dependent Ca2+ response signatures, which are important in mediating bone mechanoadaptation.

Can Cannabidiol Affect the Efficacy of Chemotherapy and Epigenetic Treatments in Cancer?

The success of cannabinoids with chronic neuropathic pain and anxiety has been demonstrated in a multitude of studies. With the high availability of a non-intoxicating compound, cannabidiol (CBD), an over-the-counter medication, has generated heightened interest in its use in the field of oncology. This review focuses on the widespread therapeutic potential of CBD with regard to enhanced wound healing, lowered toxicity profiles of chemotherapeutics, and augmented antitumorigenic effects. The current literature is sparse with regard to determining the clinically relevant concentrations of CBD given the biphasic nature of the compound’s response. Therefore, there is an imminent need for further dose-finding studies in order to determine the optimal dose of CBD for both intermittent and regular users. We address the potential influence of regular or occasional CBD usage on therapeutic outcomes in ovarian cancer patients. Additionally, as the development of chemoresistance in ovarian cancer results in treatment failure, the potential for CBD to augment the efficacy of conventional chemotherapeutic and epigenetic drugs is a topic of significant importance. Our review is focused on the widespread therapeutic potential of CBD and whether or not a synergistic role exists in combination with epigenetic and classic chemotherapy medications.

First report on establishment and characterization of a carcinosarcoma tumour cell line model of the bladder

Carcinosarcoma of the urinary bladder is a very rare and aggressive subtype of bladder cancer with poor prognosis. Characteristically carcinosarcomas exhibit biphasic nature with both epithelial and mesenchymal differentiation. Limited information is available regarding its clinical features and appropriate treatments due to its rarity. Development of tumour models can further our understanding of bladder carcinosarcoma. We report establishment and characterization of the first-ever bladder carcinosarcoma cell line MaS-3. It is established by the outgrow method from 86 year-old caucasian male who underwent a radical pelvic resection after neoadjuvant radiotherapy. MaS-3 showed carcinosarcoma profile with high conformity with to the original tumour in terms of immunocytochemistry. Proteome analysis also aligned the MaS-3 cell line with the carcinosarcoma specimen rather than corresponding non-malignant tissue. Chemotherapy sensitivity testing revealed a great sensitivity of MaS-3 growth to 5-Fluorouracil, Gemcitabine and Cisplatin, with almost no impact of Irinotecan. Additionally, the suitability of MaS-3 for 3D in vitro experiments was also demonstrated. The newly established cell line MaS-3 shows typical characteristics of the tumour and may thus be a useful in vitro model system for studying the tumour biology and developing future of treatments of this rare but very aggressive entity.

Using EEG Alpha States to Understand Learning During Alpha Neurofeedback Training for Chronic Pain.

ObjectiveAlpha-neurofeedback (α-NFB) is a novel therapy which trains individuals to volitionally increase their alpha power to improve pain. Learning during NFB is commonly measured using static parameters such as mean alpha power. Considering the biphasic nature of alpha rhythm (high and low alpha), dynamic parameters describing the time spent by individuals in high alpha state and the pattern of transitioning between states might be more useful. Here, we quantify the changes during α-NFB for chronic pain in terms of dynamic changes in alpha states.MethodsFour chronic pain and four healthy participants received five NFB sessions designed to increase frontal alpha power. Changes in pain resilience were measured using visual analogue scale (VAS) during repeated cold-pressor tests (CPT). Changes in alpha state static and dynamic parameters such as fractional occupancy (time in high alpha state), dwell time (length of high alpha state) and transition probability (probability of moving from low to high alpha state) were analyzed using Friedman’s Test and correlated with changes in pain scores using Pearson’s correlation.ResultsThere was no significant change in mean frontal alpha power during NFB. There was a trend of an increase in fractional occupancy, mean dwell duration and transition probability of high alpha state over the five sessions in chronic pain patients only. Significant correlations were observed between change in pain scores and fractional occupancy (r = −0.45, p = 0.03), mean dwell time (r = -0.48, p = 0.04) and transition probability from a low to high state (r = -0.47, p = 0.03) in chronic pain patients but not in healthy participants.ConclusionThere is a differential effect between patients and healthy participants in terms of correlation between change in pain scores and alpha state parameters. Parameters providing a more precise description of the alpha power dynamics than the mean may help understand the therapeutic effect of neurofeedback on chronic pain.

Synthesis and characterization of palladium nanoparticles by chemical and green methods: A comparative study on hepatic toxicity using zebrafish as an animal model

Nanoparticles synthesized by chemical methods are of a matter of concern, whereas, the green methods are said to be eco-friendly and environmentally safe. In this study, the toxicity of palladium nanoparticles (Pd NPs) synthesized through chemical co-precipitation and green route method using Annona squamosa seed kernels (As-Pd NPs) were evaluated using zebrafish as an animal model. The synthesized nanoparticles (NPs) were characterized using UV‐Visible spectroscopy, Field Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive X-ray (EDX), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS) and Zeta potential. Zebrafish (Danio rerio) were exposed to 0.4 ng/L of Pd NPs and As-Pd NPs for 96-h, further oxidative stress parameters and histological changes were evaluated. The superoxide dismutase (SOD), catalase (CAT) activity and the lipid peroxidation (LPO) levels were elevated in the Pd NPs groups. But in the As-Pd NPs group, the SOD activity showed a biphasic nature while the CAT activity gradually declined till the 96-h compared to the control and Pd NPs groups. The LPO levels in the As-Pd NPs groups showed a measurable increase till 72-h and sudden decline at the end of 96-h. Anomalies in the histological changes such as ruptured hepatocytes, sinusoidal congestion, vacuolation and accumulation of erythrocytes were observed in both the NPs treated groups but As-Pd NPs exhibited lesser lesions than the control and Pd NPs groups. However, our present study reveals the possible reliability of the nanoparticles and the mechanism of scavenging activity suggesting that the As-Pd NPs synthesized by green route are less toxic comparing to the chemically synthesized Pd NPs.