After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other ...transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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Surfactants interfere with sol-gel particle/pore growth, influencing the structure and properties of silica aerogels. Their ability to induce microscopic changes in the aerogel’s ...structure may be useful to improve/control the thermal insulation performance of aerogels.
The influence of different types of surfactants (anionic, cationic and non-ionic) on the microstructural arrangement and macroscopic properties of methyltrimethoxysilane (MTMS)-based aerogels was evaluated for the first time, using an experimental and computational comparative approach. Molecular dynamics simulations were performed based on two representative silica molecular structures derived from MTMS, while the experimentally-obtained silica aerogels were characterized in terms of chemical/structural/mechanical/thermal insulation properties.
The use of both hexadecyltrimethylammonium bromide (CTAB) and sodium dodecylsulfate (SDS) led to a decrease in bulk density, thermal conductivity and average pore size of the aerogels, with notorious increase of their flexibility. The observed changes were due to microstructural arrangements, as evidenced by scanning electron microscopy (SEM). However, the non-ionic surfactant, Pluronic F-127, did not have a positive impact on the desired properties. Globally, the simulation results support the experimental findings, suggesting differentiated microstructural changes induced by the use of cationic or anionic surfactants. The addition of CTAB and SDS generally resulted in smaller or larger silica aggregates, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We present novel velocimetry algorithms based on the hybridization of correlation-based Particle Image Velocimetry (PIV) and a combination of Lucas–Kanade and Liu–Shen optical flow (OpF) methods. An ...efficient Aparapi/OpenCL implementation of those methods is also provided in the accompanying open-source QuickLabPIV-ng tool enabled with a Graphical User Interface (GUI). Two different options of hybridization were developed and tested: OpF as a last step, after correlation-based PIV, and OpF as a substitute for sub-pixel interpolation. Hybridization increases the spatial resolution of PIV, enabling the characterization of small turbulent scales and the computation of key turbulence parameters such as the rate of dissipation of turbulent kinetic energy. The method was evaluated using both synthetic and real databases, representing flows that exhibit a variety of locally isotropic homogeneous turbulent scales. The proposed hybrid PIV-OpF results in a 3-fold increase in the PIV density for synthetic images. The analysis of power spectral density functions and auto-correlation demonstrated the impact of PIV image quality on the accuracy of the method and its ability to extend the turbulence range. We discuss the challenges posed by optical noise and tracer density in the quality of the vector map density.
Recent advances in the extraction and purification of decellularized extracellular matrix (dECM) obtained from healthy or malignant tissues open new avenues for engineering physiomimetic 3D in vitro ...tumor models, which closely recapitulate key biomolecular hallmarks and the dynamic cancer cell–ECM interactions in the tumor microenvironment. We review current and upcoming methodologies for chemical modification of dECM-based biomaterials and advanced bioprocessing into organotypic 3D solid tumor models. A comprehensive review of disruptive advances and shortcomings of exploring dECM-based biomaterials for recapitulating the native tumor-supporting matrix is also provided. We hope to drive the discussion on how 3D dECM testing platforms can be leveraged for generating microphysiological tumor surrogates that generate more robust and predictive data on therapeutic bioperformance.
Despite the remarkable potential of scaffold-based 3D multicellular tumor models as preclinical screening platforms, currently used ECM-mimetic biomaterials fail to fully mimic the biomechanical and biomolecular complexity of the tumor ECM.Decellularized extracellular matrix (dECM) 3D tumor models recapitulate key ECM components and cancer stromal cell–ECM interactions, providing significant advantages over currently available in vitro testing platforms.State-of-the-art decellularization and processing methodologies contribute with key advances toward preserving key ECM components and incorporating dECM into complex multicellular 3D microtumor assembly strategies.Integrating dECM 3D in vitro tumor models into high-throughput screening platforms and analysis via multiomics and single-cell profiling will unlock new avenues for developing more predictive and physiomimetic 3D tumor models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present a benchmark study of Optical Flow (OpF) methods for fluid mechanics applications. It is aimed at assessing the performance of three OpF methods, Lucas and Kanade (in: Proceedings of the ...7th 1519 international joint conference on artificial intelligence, 1981), Horn and Schunck (AI 17:185–203, 1981) and Farnebäck (Two-frame motion estimation based on polynomial expansion, in: Bigun, Gustavsson (eds) Image analysis, Springer, 2003), combined or not with the Liu and Shen (JFM 614:253–291, 2008) algorithm. The performance of the OpF methods, evaluated exclusively as the difference between the values of the methods and of ground-truth (reference values), is benchmarked for deformation dominated, rotation-dominated and uniform flows. For each flow type, relative and absolute errors are computed for different tracer displacements, noise levels, pixel particle sizes, image bit-depths and particle concentrations. The accuracy of the OpF methods seems mainly affected by the magnitude of velocity gradients and convective accelerations. It does not seem to be affected by the relative preponderance of rotational and deformation components. The inner region of the Poiseuille flow and the saddle point in the Rankine vortex combined with uniform flow pose significant difficulties to all methods. The performance of the Lucas-Kanade/Liu-Shen combination is the best for all flow types, image conditions and image bit depths. The Farnebäck/Liu-Shen combination has a similar high performance but only for image depths of 10 bit or higher. These OpF methods maintain a high performance for tracer sizes and concentrations outside the PIV optimal range. Horn-Schunck is the worst performing method, due to high sensitiveness to particle concentration variations or particle sizes. These results can be used to plan new particle-based velocimetry experiments or to retrieve further information from existing PIV databases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker ...profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids.
The aim of this study was to identify blood-derived EVs (bdEVs) spectroscopic signatures with AD discriminatory potential.
Herein, FTIR spectra of bdEVs from two biofluids (serum and plasma) and distinct sets of Controls and AD cases were acquired, and EVs' spectra analyzed.
Analysis of bdEVs second derivative peaks area revealed differences between Controls and AD cases in distinct spectra regions, assigned to carbohydrates and nucleic acids, amides, and lipids.
EVs' spectroscopic profiles presented AD discriminatory value, supporting the use of bdEVs combined with FTIR as a screening or complementary tool for AD diagnosis.
The present study deals with the development of multifunctional biphasic calcium phosphate (BCP) scaffolds coated with biopolymers-poly(ε-caprolactone) (PCL) or poly(ester urea) (PEU)-loaded with an ...antibiotic drug, Rifampicin (RFP). The amounts of RFP incorporated into the PCL and PEU-coated scaffolds were 0.55 ± 0.04 and 0.45 ± 0.02 wt%, respectively. The in vitro drug release profiles in phosphate buffered saline over 6 days were characterized by a burst release within the first 8h, followed by a sustained release. The Korsmeyer-Peppas model showed that RFP release was controlled by polymer-specific non-Fickian diffusion. A faster burst release (67.33 ± 1.48%) was observed for the PCL-coated samples, in comparison to that measured (47.23 ± 0.31%) for the PEU-coated samples. The growth inhibitory activity against
and
was evaluated. Although the RFP-loaded scaffolds were effective in reducing bacterial growth for both strains, their effectiveness depends on the particular bacterial strain, as well as on the type of polymer coating, since it rules the drug release behavior. The low antibacterial activity demonstrated by the BCP-PEU-RFP scaffold against
could be a consequence of the lower amount of RFP that is released from this scaffold, when compared with BCP-PCL-RFP. In vitro studies showed excellent cytocompatibility, adherence, and proliferation of human mesenchymal stem cells on the BCP-PEU-RFP scaffold surface. The fabricated highly porous scaffolds that could act as an antibiotic delivery system have great potential for applications in bone regeneration and tissue engineering, while preventing bacterial infections.
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In solid tumors, mesenchymal stem cells (MSCs) are recognized to establish complex intercommunication networks with cancer cells and to significantly influence their invasion and metastasis ...potential. Such bidirectional interplay occurs between both tissue resident/tumor-associated MSCs (TA-MSCs) and also tumor infiltrating MSCs (TM-MSCs) that migrate from distant sites such as the bone marrow. Interestingly, malignant cells interactions with MSCs in the tumor microenvironment extends beyond conventional exchanges of signaling factors and extracellular vesicles, including unconventional direct exchanges of intracellular components, or cancer cells cannibalism of MSCs. In the context of 3D in vitro tumor models, cell tracking assays making use of cell-labeling probes such as membrane penetrating dyes, can be leveraged to shed light on these events, and allow researchers to analyze overtime cell-to-cell spatial distribution, fusion, internal organization, and changes in co-cultured populations ratios. Herein, we describe a high-throughput compatible method through which MSCs positioning and permanence within in vitro 3D multicellular tumor spheroid models (3D-MCTS) can be tracked overtime. Although we have focused on the interactions of human bone marrow-derived MSCs (hBM-MSCs) within heterotypic lung cancer A549 3D-MCTS, these procedures can be implemented for other 3D tumor spheroid models and types of cells, taking into consideration that optimization steps are undertaken.
Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma‐related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected ...with current clinical tools. Herein, an exosome (EX)‐based imaging tool is developed for lung micrometastasis by positron emission tomography (PET) using osteosarcoma‐derived EXs as natural nanocarriers of the positron‐emitter copper‐64 (64Cu). Exosomes are isolated from metastatic osteosarcoma cells and functionalized with the macrocyclic chelator NODAGA for complexation with 64Cu. Surface functionalization has no effect on the physicochemical properties of EXs, or affinity for donor cells and endows them with favorable pharmacokinetics for in vivo studies. Whole‐body PET/magnetic resonance imaging (MRI) images in xenografted models show a specific accumulation of 64Cu‐NODAGA‐EXs in metastatic lesions as small as 2–3 mm or in a primary tumor, demonstrating the exquisite tropism of EXs for homotypic donor cells. The targetability for lung metastasis is also observed by optical imaging using indocyanine green (ICG)‐labeled EXs and D‐luciferin‐loaded EXs. These findings show that tumor‐derived EXs hold great potential as targeted imaging agents for the noninvasive detection of small lung metastasis by PET. This represents a step forward in the biomedical application of EXs in imaging diagnosis with increased translational potential.
Exosomes isolated directly from osteosarcoma cells hold great potential as targeted imaging agents for the noninvasive assessment of early‐stage lung metastasis by positron emission tomography (PET). The surface modification of exosomes via maleimide‐thiol chemistry for radiometal conjugation forms highly stable complexes under physiological conditions with targeting ability and specificity for metastatic lesions suitable for in vivo PET imaging studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The diverse biomolecular landscape of tissue-specific decellularized extracellular matrix (dECM) biomaterials provides a multiplicity of bioinstructive cues to target cells, rendering them highly ...valuable for various biomedical applications. However, the isolation of dECM biomaterials entails cumbersome xenogeneic enzymatic digestions and also additional inactivation procedures. Such, increases processing time, increments costs and introduces residues of non-naturally present proteins in dECM formulations that remain present even after inactivation. To overcome these limitations, herein we report an innovative conjugation of light and ultrasound-mediated dECM biomaterial processing for fabricating dECM biomaterials. Such approach gathers on ultrasound waves to facilitate dECM-in-liquid processing and visible light photocrosslinking of tyrosine residues naturally present in dECM biomaterials. This dual step methodology unlocked the in-air production of cell laden dECM hydrogels or programmable dECM hydrogel spherical-like beads by using superhydrophobic surfaces. These in-air produced units do not require any additional solvents and successfully supported both fibroblasts and breast cancer cells viability upon encapsulation or surface seeding. In addition, the optimized photoacoustic methodology also enabled a rapid formulation of dECM biomaterial inks with suitable features for biofabricating volumetrically defined living constructs through embedded 3D bioprinting. The biofabricated dECM hydrogel constructs supported cell adhesion, spreading and viability for 7 days. Overall, the implemented photoacoustic processing methodology of dECM biomaterials offers a rapid and universal strategy for upgrading their processing from virtually any tissue.
Leveraging decellularized extracellular matrix (dECM) as cell instructive biomaterials has potential to open new avenues for tissue engineering and in vitro disease modelling. The processing of dECM remains however, lengthy, costly and introduces non-naturally present proteins in the final biomaterials formulations. In this regard, here we report an innovative light and ultrasound two-step methodology that enables rapid dECM-in-liquid processing and downstream photocrosslinking of dECM hydrogel beads and 3D bioprinted constructs. Such photoacoustic based processing constitutes a universally applicable method for processing any type of tissue-derived dECM biomaterials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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