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     

Recovery of Bioactive Ellagitannins by Ultrasound/Microwave-Assisted Extraction from Mexican Rambutan Peel (Nephelium lappaceum L.)

Rambutan (Nephelium lappaceum L.) is a tropical fruit from Asia which has become the main target of many studies involving polyphenolic analysis. Mexico produces over 8 million tons per year of rambutan, generating a huge amount of agro-industrial waste since only the pulp is used and the peel, which comprises around 45% of the fruit’s weight, is left behind. This waste can later be used in the recovery of polyphenolic fractions. In this work, emerging technologies such as microwave, ultrasound, and the hybridization of both were tested in the extraction of phenolic compounds from Mexican rambutan peel. The results show that the hybrid technology extraction yielded the highest polyphenolic content (176.38 mg GAE/g of dry rambutan peel). The HPLC/MS/ESI analysis revealed three majoritarian compounds: geraniin, corilagin, and ellagic acid. These compounds explain the excellent results for the biological assays, namely antioxidant activity evaluated by the DPPH, ABTS, and LOI (Lipid oxidation inhibition) assays that exhibited great antioxidant capacity with IC₅₀ values of 0.098, 0.335, and 0.034 mg/mL respectively, as well as prebiotic activity demonstrated by a µMax (maximum growth) of 0.203 for Lactobacillus paracasei. Lastly, these compounds have shown no hemolytic activity, opening the door for the elaboration of different products in the food, cosmetic, and pharmaceutical industries.     

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis,Characterisation and Application in Rhodium-Catalysed Hydroformylation

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)₂(acac), was attested by ³¹P NMR, which presented a doublet in the range of δ = 120 ppm, with a ¹J(¹⁰³Rh-³¹P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm⁻¹ and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.     

Buffers for the Physiological pH Range: Studies of 4-(N-Morpholino)butanesulfonic Acid (MOBS) from 5 to 55 °C

In this study, we report the pH values of two buffer solutions without chloride ion and eight buffer solutions with NaCl with an ionic strength I=0.16 mol?kg^?1. Electromotive force (emf) techniques have been used to get the cell potentials at 12 temperatures from 5 to 55?°C, including 37?°C. An extended form of the Bates-Guggenheim convention is used in the entire ionic strength range, 0.04 to 0.16?mol?kg^?1. The residual liquid junction potentials (??E _j ) of the buffer solutions of MOBS have been estimated from previous measurements with a flowing junction cell. These values of ??E _j have been used for correction in order to ascertain the operational pH values of four buffer solutions of MOBS at 25 and 37?°C. These solutions are recommended as pH standards for physiological application in the pH range 7.4 to 7.7.     

Wildland fire growth prediction method based on Multiple Overlapping Solution

Several Data-Driven Methods have been developed to try to solve the input parameters uncertainty when considering problems like Wildfires Prediction. In general, these methods operate over a large number of input parameters, and consider the most recent known behavior of wildfires. The purpose of the methods is to find the parameter set that best describes the real situation under consideration. Therefore, it is presumed that the same set of values could be used to predict the immediate future.However, because this kind of prediction is based on a single set of parameters, for those parameters that present a dynamic behavior (e.g. wind direction and speed), the new optimized values are not adequate to make a prediction.In this paper we propose an alternative method developed in a new branch of Data-Driven Prediction, which we called Multiple Overlapping Solution. This method combines statistical concepts and HPC (High Performance Computing) to obtain a higher quality prediction.