In comparison with the well-described ionic eutectic mixtures, hydrophobic eutectic solvents (HESs) composed of two non-ionic compounds represent a relatively new class of eutectics. In this work, a ...number of non-ionic HESs liquid at room temperature were identified from a large initial screening of potential mixtures. Three new HESs based on thymol + TOPO (trioctylphosphine oxide), TOPO + capric acid and hydrocinnamic acid + capric acid were investigated as extracting media for the recovery and separation of platinum group and transition metals in HCl media. Full phase diagrams and physical properties including viscosities, densities, chemical stability and the influence of water were characterised, with these HESs presenting low viscosities and high hydrophobicity suitable for application as solvents for liquid-liquid extraction. By simple variation of the eutectic component the selectivity of the system for a given metal could be tuned, with the TOPO-based system displaying good to excellent selectivity towards Pt
4+
, Pd
2+
and Fe
3+
under a range of conditions. The extraction mechanism was found to vary due to a complex interplay between the HES composition, acid concentration and the predominant metal complex present. The observed extraction behaviour in HESs composed of two metal complexing ligands such as TOPO + capric acid, in which each respective component is responsible for metal extraction under given conditions, opens the possibility to design hydrophobic eutectic mixtures presenting synergistic effects. Finally, the HES phase following palladium extraction was used as the template for the formation of palladium nanoparticles. The results presented highlight the great potential of HESs as environmentally benign and tuneable media for the solvent extraction of metal ions.
The potential of HESs as environmentally benign and tunable media for the solvent extraction of metal ions is presented.
The sustainable cellular delivery of the pleiotropic drug curcumin encounters drawbacks related to its fast autoxidation at the physiological pH, cytotoxicity of delivery vehicles and poor cellular ...uptake. A biomaterial compatible with curcumin and with the appropriate structure to allow the correct curcumin encapsulation considering its poor solubility in water, while maintaining its stability for a safe release was developed. In this work, the biomaterial developed started by the preparation of an oil-in-water nanoemulsion using with a cytocompatible copolymer (Pluronic F 127) coated with a positively charged protein (gelatin), designed as G-Cur-NE, to mitigate the cytotoxicity issue of curcumin. These G-Cur-NE showed excellent capacity to stabilize curcumin, to increase its bio-accessibility, while allowing to arrest its autoxidation during its successful application as an anticancer agent proved by the disintegration of MDA-MB-231 breast cancer cells as a proof of concept.
Steroids, a widespread class of natural organic compounds occurring in animals, plants and fungi, have shown great therapeutic value for a broad array of pathologies. The present overview is focused ...on the anticancer activity of steroids, which is very representative of a rich structural molecular diversity and ability to interact with various biological targets and pathways. This review encompasses the most relevant discoveries on steroid anticancer drugs and leads through the last decade and comprises 668 references.
Compartmentalized structures obtained in all‐aqueous settings have shown promising properties as cell encapsulation devices, as well as reactors for trans‐membrane chemical reactions. While most ...approaches focus on the preparation of spherical devices, advances on the production of complex architectures have been enabled by the interfacial stability conferred by emulsion systems, namely mild aqueous two‐phase systems (ATPS), or non‐equilibrated analogues. However, the application of non‐spherical structures has mostly been reported while keeping the fabricated materials at a stable interface, limiting the free‐standing character, mobility and transposition of the obtained structures to different setups. Here, the fabrication of self‐standing, malleable and perfusable tubular systems through all‐aqueous interfacial assembly is shown, culminating in the preparation of independent objects with stability and homogeneity after disruption of the polymer‐based aqueous separating system. Those hollow structures can be fabricated with a variety of widths, and rapidly printed as long structures at flow rates of 15 mm s−1. The materials are used as compartments for cell culture, showcasing high cytocompatibility, and can be tailored to promote cell adhesion. Such structures may find application in fields that benefit from freeform tubular structures, including the biomedical field with, for example, cell encapsulation, and benchtop preparation of microfluidic devices.
A straightforward method based on the interfacial complexation of oppositely charged natural polyelectrolytes is proposed to directly fabricate fiber‐shaped structures, stable in all‐aqueous physiological‐relevant conditions. Perfusable and size‐controllable materials can be obtained, with adequate permeability and improved biofunctionality, enabling cell adhesion and growth. Outside the separating interface of two‐phase systems, self‐standing entities can be easily handled, broadening the range of applications.
Abstract Chitosan (CHT)/poly(ε-caprolactone) (PCL) blend 3D fiber-mesh scaffolds were studied as possible support structures for articular cartilage tissue (ACT) repair. Micro-fibers were obtained by ...wet-spinning of three different polymeric solutions: 100:0 (100CHT), 75:25 (75CHT) and 50:50 (50CHT) wt.% CHT/PCL, using a common solvent solution of 100 vol.% of formic acid. Scanning electron microscopy (SEM) analysis showed a homogeneous surface distribution of PCL. PCL was well dispersed throughout the CHT phase as analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The fibers were folded into cylindrical moulds and underwent a thermal treatment to obtain the scaffolds. μCT analysis revealed an adequate porosity, pore size and interconnectivity for tissue engineering applications. The PCL component led to a higher fiber surface roughness, decreased the scaffolds swelling ratio and increased their compressive mechanical properties. Biological assays were performed after culturing bovine articular chondrocytes up to 21 days. SEM analysis, live-dead and metabolic activity assays showed that cells attached, proliferated, and were metabolically active over all scaffolds formulations. Cartilaginous extracellular matrix (ECM) formation was observed in all formulations. The 75CHT scaffolds supported the most neo-cartilage formation, as demonstrated by an increase in glycosaminoglycan production. In contrast to 100CHT scaffolds, ECM was homogenously deposited on the 75CHT and 50CHT scaffolds. Although mechanical properties of the 50CHT scaffold were better, the 75CHT scaffold facilitated better neo-cartilage formation.
The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to ...disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado-Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated pathogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the downregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.
The therapeutic effectiveness and biological relevance of technologies based on adherent cells depend on platforms that enable long‐term culture in controlled environments. Liquid‐core capsules have ...been suggested as semipermeable moieties with spatial homogeneity due to the high mobility of all components in their core. The lack of cell‐adhesive sites in liquid‐core structures often hampers their use as platforms for stem cell‐based technologies for long‐term survival and cell‐directed self‐organization. Here, the one‐step fast formation of robust polymeric capsules formed by interfacial complexation of oppositely charged polyelectrolytes in an all‐aqueous environment, compatible with the simultaneous encapsulation of mesenchymal stem/stromal cells (MSCs) and microcarriers, is described. The adhesion of umbilical cord MSCs to polymeric microcarriers enables their aggregation and culture for more than 21 days in capsules prepared either manually by dropwise addition, or by scalable electrohydrodynamic atomization, generating robust and stable capsules. Cell aggregation and secretion overtime can be tailored by providing cells with static or dynamic (bioreactor) environments.
Robust polymeric capsules are produced using a one‐step rapid process based on the interfacial complexation of oppositely charged polyelectrolytes in an all‐aqueous environment. Two processing methodologies are used to produce millimetric or micrometric capsules and characterized regarding their size dispersity, thickness, robustness, and porosity. Animal cells are successfully coencapsulated with microcarriers as cell‐adhesion sites, under static or dynamic condition, for 21 days.
Antibodies present in mammal's serum are of high relevance for therapeutic purposes, particularly in passive immunization and in the treatment of some chronic diseases. However, their widespread use ...is still compromised by the requirement of several process steps for their purification and the difficulty in keeping antibodies stable to guarantee their therapeutic efficiency. These challenges significantly contribute to the current high cost of biopharmaceuticals, namely antibodies such as immunoglobulin G (IgG). Accordingly, the development of effective and sustainable purification strategies for antibodies and other biopharmaceuticals is in critical demand to decrease economic, environmental and health burdens. Herein, bio-based and low-cost hybrid alginate-protein cryogel beads were prepared, characterized, and applied as novel adsorbent materials for the purification of IgG from human serum. It is shown that hybrid materials are more efficient than the respective alginate beads since the presence of proteins increases the material selectivity for IgG, which is due to the specific interactions occurring between the target antibody and amino acid residues in the hybrid materials. Several operating conditions, such as pH, adsorption time and serum concentration, were optimized to improve the recovery yield and purity of IgG. Adsorption isotherms were determined to infer the adsorption mechanism of IgG onto the cryogel beads and to determine their adsorption capacity (175 mg of IgG per g of cryogel beads). Under the optimized conditions, IgG can be recovered from the hybrid materials using buffered aqueous solutions, with a purity of 80% and a recovery yield of 91%. The stability and integrity of the antibody are retained after the desorption step. Finally, the regeneration and reuse of the cryogel beads were evaluated, with no losses in the IgG adsorption performance and antibody stability. Although significant efforts have been put on the development of novel affinity ligands to replace the standard chromatographic methods to purify IgG, this work demonstrates the potential of bio-based and low-cost hybrid materials as promising alternatives, in which proteins can be used to improve the material selectivity.
Bio-based and low-cost hybrid alginate-protein cryogel beads, which can be regenerated and reused, are efficient adsorbent materials for the purification of IgG from human serum.
Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) ...renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.
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