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In the last decade, cellular forces in three-dimensional hydrogels that mimic the extracellular matrix have been calculated by means of Traction Force Microscopy (TFM). However, ...characterizing the accuracy limits of a traction recovery method is critical to avoid obscuring physiological information due to traction recovery errors. So far, 3D TFM algorithms have only been validated using simplified cell geometries, bypassing image processing steps or arbitrarily simulating focal adhesions. Moreover, it is still uncertain which of the two common traction recovery methods, i.e., forward and inverse, is more robust against the inherent challenges of 3D TFM. In this work, we established an advanced in silico validation framework that is applicable to any 3D TFM experimental setup and that can be used to correctly couple the experimental and computational aspects of 3D TFM. Advancements relate to the simultaneous incorporation of complex cell geometries, simulation of microscopy images of varying bead densities and different focal adhesion sizes and distributions. By measuring the traction recovery error with respect to ground truth solutions, we found that while highest traction recovery errors occur for cases with sparse and small focal adhesions, our implementation of the inverse method improves two-fold the accuracy with respect to the forward method (average error of 23% vs. 50%). This advantage was further supported by recovering cellular tractions around angiogenic sprouts in an in vitro model of angiogenesis. The inverse method recovered higher traction peaks and a clearer pulling pattern at the sprout protrusion tips than the forward method.
Biomaterial performance is often studied by quantifying cell-matrix mechanical interactions by means of Traction Force Microscopy (TFM). However, 3D TFM algorithms are often validated in simplified scenarios, which do not allow to fully assess errors that could obscure physiological information. Here, we established an advanced in silico validation framework that mimics real TFM experimental conditions and that characterizes the expected errors of a 3D TFM workflow. We apply this framework to demonstrate the enhanced accuracy of a novel inverse traction recovery method that is illustrated in the context of an in vitro model of sprouting angiogenesis. Together, our study shows the importance of a proper traction recovery method to minimise errors and the need for an advanced framework to assess those errors.
Water transport by the Na+–K+–2Cl− cotransporter (NKCC1) was studied in confluent cultures of pigmented epithelial (PE) cells from the ciliary body of the fetal human eye. Interdependence among ...water, Na+ and Cl− fluxes mediated by NKCC1 was inferred from changes in cell water volume, monitored by intracellular self‐quenching of the fluorescent dye calcein. Isosmotic removal of external Cl− or Na+ caused a rapid efflux of water from the cells, which was inhibited by bumetanide (10 μm). When returned to the control solution there was a rapid water influx that required the simultaneous presence of external Na+ and Cl−. The water influx could proceed uphill, against a transmembrane osmotic gradient, suggesting that energy contained in the ion fluxes can be transferred to the water flux. The influx of water induced by changes in external Cl− saturated in a sigmoidal fashion with a Km of 60 mm, while that induced by changes in external Na+ followed first order kinetics with a Km of about 40 mm. These parameters are consistent with ion transport mediated by NKCC1. Our findings support a previous investigation, in which we showed water transport by NKCC1 to be a result of a balance between ionic and osmotic gradients. The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane. This has relevance for both epithelial and symmetrical cells.
Cell volume control is fundamental for cell survival. Cells have evolved mechanisms for maintaining their volume constant. These mechanisms involve the movement of solutes and water across the plasma membrane through specialized proteins. The water within a cell ultimately determines its volume and has been assumed to cross the cell membrane exclusively through channels called aquaporins. We show that water also crosses the membrane carried by NKCC1, a membrane protein belonging to the Na+–K+–Cl− cotransporter (NKCC) family. This membrane protein transports 1 sodium, 1 potassium and 2 chloride ions together with a large number of water molecules per cycle. A key finding is that NKCC1 transports water uphill, against an osmotic gradient. These observations increase our knowledge of how cells and tissues handle water, and are important for understanding medical conditions like brain oedema, intracranial hypertension, glaucoma and airway hydration disorders.
Cancer cases numbers are increasing worldwide positioning this disease as the second cause of mortality for both sexes. Medicinal plants have been used in the fight against cancer as the basis for ...drug discovery and nowadays more than 70% of anticancer drugs have a natural origin. Mexico is regarded for its cultural and biological diversity, which is reflected in the vast traditional knowledge of herbal remedies. In this review we examined herbal remedies employed in colorectal cancer treatment (CRC).
The goal of this work was to gather scientific reports of plants used in Mexican traditional medicine for CRC treatment.
We performed a search on scientific literature databases using as keywords: “colon cancer”, “gastric cancer”, “cytotoxicity”, studies “in vitro and in vivo”, in combination with “Mexican medicinal plants” or “Mexican herbal remedies”. The selection criteria of cytotoxic activity for extracts or pure compounds was based on the National Cancer Institute of USA recommendations of effective dose 50 (ED50) of ≤20μg/mL and ≤4μg/mL, respectively.
In this review we report 25 botanic families and 39 species of plants used for the treatment of colon cancer in Mexico with evidence in studies in vitro and in vivo.
Medicinal plants are still a great source of novel chemical structures with antineoplastic potential as it is proven in this work. The selection criteria and activity was narrowed for methodological purposes, nevertheless, drug discovery of natural origin continues to be a highly attractive R&D strategy.
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Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential ...adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17β-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 μg/kg), 17β-estradiol (E2, 40 or 80 μg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.
•Prolame, but not estradiol, induced antidepressant effects in middle-aged female rats.•Prolame but not estradiol produced anxiolytic actions in middle-aged female rats.•Uterine effects of prolame were weaker than estradiol effects in middle-aged rats.•Prolame may be an effective and safe hormone replacement therapy in menopause.
Biochar is a low-cost and environmentally friendly amendment with strong ability for adsorption of mercury (Hg) from aqueous solutions, contaminated soils, and sediments. In the present study, six ...biochars were prepared from the pyrolysis of cocoa pod husk, sugarcane bagasse and banana pseudostem at 400 and 600 °C in order to use them as an organic amendment and to evaluate their capacities to reduce the bioavailability, methylation potential, and mobility of Hg present in mine tailings without environmental treatment. To quantify the effects of each variety of biochar, incubation experiments of soil were established by mixing mine tailings with 5% by weight of biochar for 90 days. Once the incubation time concluded, sequential extraction procedures were carried out to determine the fractionation of the Hg species. Speciation analysis results indicated that the remedial effects of biochar depended on the source of organic matter and pyrolysis temperature. The bioavailable and organic Hg fractions decreased respectively by up to 75 and 79%, indicating a methylation potential reduction. Immobile Hg fraction increased to 76% with respect to the control. Adsorption and stabilization to HgS from the soluble forms of Hg reduce the percentage of bioavailable Hg. The organic Hg fraction reduction was correlated with the decrease of the bioavailable Hg fraction and with direct adsorption processes in the biochar structure. Highly porous biochars developed at high temperature, with large contents of superficial polar functional groups (H/C), and high pH, electrical conductivity, ash percentage and cation exchange capacity values favor the stabilization and adsorption of Hg in mine tailings. In summary, the application of biochar could be an effective method for the remediation of Hg-contaminated mine tailings, transforming the Hg species into less toxic, soluble, reactive, and bioavailable forms.
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•The utility of biochar for stabilizing Hg in soil was investigated.•Biochar application in Hg-contaminated mine tailings reduced the bioavailability.•Biochar reduced the methylation potential and solubility•The organic matter source influences optimal stabilization and adsorption•High temperature biochar had better stabilization and adsorption ratios.
► Single Kevlar-29 fibers characterized mechanically. ► A micro universal fiber tester used for the longitudinal tensile testing. ► Ultra-low load indentation used for the cross-section properties ...evaluation. ► Kevlar fibers have high anisotropy.
Kevlar-29 fibers are being used in different applications due of their exceptional mechanical properties. More mechanical information on these fibers is needed for better understanding of their complex mechanical behavior. This article presents results from tensile tests on single Kevlar-29 filaments, to characterize their intrinsic behavior under quasi-static loading, and nanoindentation tests, to investigate their cross-section mechanical properties. The results reveal that the elastic modulus measured in the fiber cross-section is lower than that obtained in the longitudinal direction due to the high anisotropy of the fibers.
We show extensive theoretical studies related to the generation and characterization of 2D and 3D ordered networks using 1D units that are connected covalently. We experimentally created ...multi-terminal junctions containing 1D carbon blocks in order to study the most common morphologies and branched structures that could be used in the theoretical design of network models. We found that the mechanical and electronic characteristics of ordered networks based on carbon nanotubes (ON-CNTs) are dominated by their specific super-architecture (hexagonal, cubic, square, and diamond-type). We show that charges follow specific paths through the nodes of the multi-terminal systems, which could result in complex integrated nanoelectronic circuits. The 3D architectures reveal their ability to support extremely high unidirectional stress when their mechanical properties are studied. In addition, these networks are shown to perform better than standard carbon aerogels because of their low mass densities, continuous porosities, and high surface areas.
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