Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation

Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.Subject terms: Experimental models of disease, Atherosclerosis, Mechanisms of disease, Integrins, End-stage renal disease     

Inhibition of the oxygen evolution reaction during titanium passivation in aqueous phosphoric acid solution

Journal of Solid State Electrochemistry - The anodic oxide on titanium can be thickened by anodization, with the consequent corrosion properties of this oxide depending on many variables, including...     

Self-Assembled Binaphthyl-Bridged Amphiphilic AABB Phthalocyanines: Nanostructures for Efficient Antimicrobial Photodynamic Therapy

Herein, the photodynamic activity of phthalocyanine (pc)-assembled nanoparticles against bacterial strains is demonstrated. The photosensitizers (PS) studied in this work are two chiral Zn^IIPcs ( PS-1 and PS-2 ), with an AABB geometry (where A and B refer to differently substituted isoindole constituents). They contain differently functionalized, chiral binaphthyloxy-linked A isoindole units, which determine the hydrophobicity of the system, and cationic methyl pyridinium moieties in the other two isoindoles to embody hydrophilicity. Both compounds have the ability to self-assemble into nanoparticles in aqueous media and have proved efficient in the photo-inactivation of Staphylococcus aureus and Escherichia coli, selected as models of Gram-positive and Gram-negative bacteria. The average size of the nanoparticles was determined by substitution at the binaphthyl core and, in turn, influences the toxicity of the PS. Thus, PS-1 , presenting a nonsubstituted binaphthyl core, forms larger nanoparticles with a larger cationic surface than the octyl-functionalized PS-2 . Although both PSs present similar structure and photophysical features, the self-assembled nanostructures of PS-1 are more effective at killing both types of strain, showing an outstanding photo-inactivation capacity with the Gram-negative E. coli.     

Determination of pesticides in dried minor tropical fruits from Colombia using the Quick,Easy, Cheap,Effective, Rugged,and Safe method‐gas chromatography–tandem mass spectrometry

The AOAC 2007.1 quick, easy, cheap, effective, rugged, and safe official method, together with gas chromatography coupled to a triple quadrupole mass spectrometer was applied for the analysis of 38 multiclass pesticides from dried fruits typically cultivated and exported from Colombia: uchuva (Physalis peruviana), lulo (Solanum quitoense), guanabana (Anona muricata), and pitahaya (Hylocereus undatus). The whole method was validated in terms of matrix‐matched calibration, matrix effect, and recovery using atrazine‐d₅ as internal standard, triphenylphosphate for quality control of the injection, and a proper mixture of analytes protectants. Matrix‐matched calibration data were found satisfactory for all pesticides and dried fruits, reporting R² values above 0.99. Matrix effect values evidenced the existence of such effect in most cases. The applied procedure gave satisfactory recovery percentages (70–120%) and relative standard deviation values (< 20%) for 92% of the 456 combinations pesticide/fruit studied (spiked levels of 25, 200, and 400 µg/kg). Finally, 20 real dried fruit samples were analyzed and residues of tebuconazole were found in two samples of uchuva at a concentration below the lowest calibration level of the method for one of them and at 10.8 ± 1.6 µg/kg for the other, being below or similar to the general maximum residue level established for monitoring purposes in food applications.     

Optimal time allocation in active retirement

Central European Journal of Operations Research - We set up a lifecycle model of a retired scholar who chooses optimally the time devoted to different activities including physical activity,...     

Applying the voltammetry of microparticles to assess the metal ion excess following a precipitation reaction: the determination of arsenic

Journal of Solid State Electrochemistry - Here we demonstrate that the metal ion excess after precipitating a sparingly soluble metal salt can be conveniently determined by a secondary...     

Ultrathin Films of Porous Metal–Organic Polyhedra for Gas Separation

Ultrathin films of a robust Rh^II-based porous metal–organic polyhedra (MOP) have been obtained. Homogeneous and compact monolayer films (ca. 2.5 nm thick) were first formed at the air–water interface, deposited onto different substrates and characterized using spectroscopic methods, scanning transmission electron microscopy and atomic force microscopy. As a proof of concept, the gas separation performance of MOP-supported membranes has also been evaluated. Selective MOP ultrathin films (thickness ca. 60 nm) exhibit remarkable CO₂ permeance and CO₂/N₂ selectivity, demonstrating the great combined potential of MOP and Langmuir-based techniques in separation technologies.     

Effects of lithium on the electronic properties of porous Ge as anode material for batteries

Recently, the need of improvement of energy storage has led to the development of Lithium batteries with porous materials as electrodes. Porous Germanium (pGe) has shown promise for the development of new generation Li-ion batteries due to its excellent electronic, and chemical properties, however, the effect of lithium in its properties has not been studied extensively. In this contribution, the effect of surface and interstitial Li on the electronic properties of pGe was studied using a first-principles density functional theory scheme. The porous structures were modeled by removing columns of atoms in the [001] direction and the surface dangling bonds were passivated with H atoms, and then replaced with Li atoms. Also, the effect of a single interstitial Li in the Ge was analyzed. The transition state and the diffusion barrier of the Li in the Ge structure were studied using a quadratic synchronous transit scheme.     

Synthesis and photophysical evaluation of meso-phenyl-1,4-dihydropyridineand pyridine-porphyrin hybrids

Chemistry of Heterocyclic Compounds - In the present work, we have synthesized new molecular hybrids consisting of porphyrin ring system connected at the meso positions with phenyl groups and/or,...