Comparison of PPAR Ligands as Modulators of Resolution of Inflammation,via Their Influence on Cytokines and Oxylipins Release in Astrocytes

Neuroinflammation is a key process of many neurodegenerative diseases and other brain disturbances, and astrocytes play an essential role in neuroinflammation. Therefore, the regulation of astrocyte responses for inflammatory stimuli, using small molecules, is a potential therapeutic strategy. We investigated the potency of peroxisome proliferator-activated receptor (PPAR) ligands to modulate the stimulating effect of lipopolysaccharide (LPS) in the primary rat astrocytes on (1) polyunsaturated fatty acid (PUFAs) derivative (oxylipins) synthesis; (2) cytokines TNFα and interleukin-10 (IL-10) release; (3) p38, JNK, ERK mitogen-activated protein kinase (MAPKs) phosphorylation. Astrocytes were exposed to LPS alone or in combination with the PPAR ligands: PPARα (fenofibrate, GW6471); PPARβ ({"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516, GSK0660); PPARγ (rosiglitazone, GW9662). We detected 28 oxylipins with mass spectrometry (UPLC-MS/MS), classified according to their metabolic pathways: cyclooxygenase (COX), cytochrome P450 monooxygenases (CYP), lipoxygenase (LOX) and PUFAs: arachidonic (AA), docosahexaenoic (DHA), eicosapentaenoic (EPA). All tested PPAR ligands decrease COX-derived oxylipins; both PPARβ ligands possessed the strongest effect. The PPARβ agonist, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 is a strong inducer of pro-resolution substances, derivatives of DHA: 4-HDoHE, 11-HDoHE, 17-HDoHE. All tested PPAR ligands decreased the release of the proinflammatory cytokine, TNFα. The PPARβ agonist {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 and the PPARγ agonist, rosiglitazone induced the IL-10 release of the anti-inflammatory cytokine, IL-10; the cytokine index, (IL-10/TNFα) was more for {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516. The PPARβ ligands, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 and GSK0660, are also the strongest inhibitors of LPS-induced phosphorylation of p38, JNK, ERK MAPKs. Overall, our data revealed that the PPARβ ligands are a potential pro-resolution and anti-inflammatory drug for targeting glia-mediated neuroinflammation.     

Morphological changes induced in erythrocyte membrane by the antiepileptic treatment: An atomic force microscopy study

Atomic force microscopy (AFM), a powerful characterization tool widely applied in problems in a large range of disciplines of the natural sciences, including cellular biology, was used to obtain information about the morphological changes induced in the erythrocyte membrane at the patients with epilepsy that undergo a long time treatment that operates upon one or several neuronal ionic channels, comparative with a healthy donor. This technique allowed non‐invasive imaging of erythrocyte membrane, revealing details and specific characteristics down to the nanometer level with characterization of surface texture parameters, such as average height, average roughness and coefficient of kurtosis at micrometer/nanometer resolution. For the healthy donor the AFM morphology appears to have all the characteristics of a normal red blood cell membrane. Instead, the closer examination of the erythrocytes membrane surface morphology for the samples collected from the patients diagnosed with epilepsy and treated with specific drugs did not reveal similar structures with those obtained for the healthy donor. The nanostructure of the membrane was drastically damaged, depending on the administrated treatment, and probably in time will affect their functionality. Therefore, the anticomital drugs have influence not only at the neuronal level, but also at the red blood cell level.     

Improved Management of the Existing Stock - The Case of Poland

This paper traces the changes which have occurred in housing provision and management in Poland during the period of transition to the market system. It suggests that the changes that have occurred have been greatly influenced by the environment within which the reforms have taken place. It claims that changes in housing management are restricted by historic attitudes yet have proceeded due to financial constraints imposed as part of the government's policy for restructuring the economy in the early 1990s. At the same time these restrictions have worked against the developmentof the housing market and investment in the existing housing stock. While the planned programmaticand legislative tasks in the reform of Polish housing are concluded, there is still a need for major shifts in the attitudes of consumers and providers to effect these changes.     

‘Generation rent’ and the emotions of private renting: self-worth,status and insecurity amongst low-income renters

Abstract

The UK private-rented sector is increasingly accommodating a diverse range of households, many of whom are young people struggling to access other forms of housing. For those at the bottom end of the sector, who typically have limited economic resources, it is a precarious housing tenure due to its expense and insecurity, yet few studies have explored qualitatively the emotional consequences of this for well-being. We address this gap in the ‘generation rent’ literature by focusing attention on those voices that have been less prominent in the literature. Informed by the theoretical lens of ‘residential alienation’, our study illustrates the emotional toll of private renting upon low-income groups in a national context where state regulation is more limited. In doing so, we add nuance to the literature surrounding socio-economic differentiation within the UK private-rented sector. Our arguments are also relevant to an international audience given global concerns about housing precarity and the politics of housing.     

Rheology of starch dispersions at high temperatures

In the food industry, many food products experience extreme processing conditions of high temperature and high shear stresses. The measurements of sample behavior for water-based formulations above 100°C is extremely challenging due to changes in material composition from the boiling of volatile ingredients. We have developed a high-sensitivity, pressurized starch pasting cell (up to 5 bar) which utilizes a design free of mechanical bearings and seals, resulting in an order-of-magnitude improvement in torque sensitivity (1 μN.m in oscillatory and 10 μN.m in shear flows) compared to traditional pressure cells. A pressurized atmosphere in the cell suppresses boiling of the volatile components, allowing the characterization of the structure–property relationships of the sample over a range of testing conditions (−5 to 150°C) which simulate industrial processing and storage conditions. This cell is employed to investigate the pasting properties of a commercial starch dispersed in water. In situ gelatinization of starch dispersions of varying starch particle weight fractions (ϕ) subjected to a high temperature (120°C) at elevated pressure and at a fixed shear rate is studied. A phase transition, from an initial flowable starch slurry to a paste, takes place during which the viscosity evolves by several orders of magnitude. Typical parameters associated with the viscosity evolution during gelatinization such as onset temperature, peak temperature, and peak viscosity are analyzed to probe the impact of high temperature on the gelation process and the rheological properties of the final starch paste. Furthermore, yield stresses of the final paste, measured at 120°C, are examined for varying ϕ through traditional rheological methods such as flow ramps, oscillatory shear, and stress growth, demonstrating the capabilities of this cell for studies of steady shear and nonlinear viscoelastic behavior of the starch pastes. The yield stress values are found to be in good agreement when comparing various testing methods. Yield stresses range from 0.25 to 6.5 Pa for ϕ between 0.05 and 0.15, with 0.05 being the minimum starch weight fraction for which there is any measurable yield stress. The yield stress and the paste viscosity both scale with starch particle weight fraction as (ϕ − ϕ_c) ^m, where ϕ_c = 0.04 as no yield stress is observed for ϕ ≤ 0.04. The exponent, m, for yield stress is found to be in the range of 1.15–1.4 depending on the analytical method used and the definition of yield stress while for peak and breakdown viscosities it is noted to be 1.6 and 1.1, respectively. The Herschel-Bulkley model is found to fit the flow curves well. The starch pastes are found to exhibit shear-thinning and significant thixotropic behavior.     

Stem Cell Therapy Enhances Motor Activity of Triceps Surae Muscle in Mice with Hereditary Peripheral Neuropathy

Impaired motor and sensory functions are the main features of Charcot–Marie–Tooth disease. Mesenchymal stem cell (MSCs) therapy is one of the possible treatments for this disease. It was assumed that MSCs therapy can improve the contractile properties of the triceps surae (TS) muscles in mice with hereditary peripheral neuropathy. Murine adipose-derived mesenchymal stromal cells (AD-MSCs) were obtained for transplantation into TS muscles of FVB-C-Tg(GFPU)5Nagy/J mice. Three months after AD-MSCs transplantation, animals were subjected to electrophysiological investigations. Parameters of TS muscle tension after intermittent high frequency electrical sciatic nerve stimulations were analyzed. It was found that force of TS muscle tension contraction in animals after AD-MSCs treatment was two-time higher than in untreated mice. Normalized values of force muscle contraction in different phases of electrical stimulation were 0.3 ± 0.01 vs. 0.18 ± 0.01 and 0.26 ± 0.03 vs. 0.13 ± 0.03 for treated and untreated animals, respectively. It is assumed that the two-fold increase in TS muscle strength was caused by stem cell therapy. Apparently, AD-MSCs therapy can promote nerve regeneration and partial restoration of muscle function, and thus can be a potential therapeutic agent for the treatment of peripheral neuropathies.     

The Role of Endothelium in COVID-19

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.     

An investigation into the surface fatigue of materials and thin layers using a sliding diamond spherical segment

Methods for testing the surface fatigue of materials or thin layers normally involve configurations with two or more rolling balls or discs. Such equipment and test specimens are quite complicated, and for a large number of experiments, costly. Testing could be considerably simplified if the stressing of the material surface were performed with a sliding natural diamond spherical segment. A diamond on steel (or any different material) friction pair has the particular attribute that sliding wear is absent. Under these circumstances, after a certain number of strain cycles, fatigue failure of the investigated surface or layers appears. A particularly relevant application is investigation of the adhesion of a DLC layer.     

Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol

Background: The transient receptor potential ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca²⁺ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.