A Preclinical Model of Cutaneous Melanoma Based on Reconstructed Human Epidermis

Malignant melanoma is among the tumor entities with the highest increase of incidence worldwide. To elucidate melanoma progression and develop new effective therapies, rodent models are commonly used. While these do not adequately reflect human physiology, two-dimensional cell cultures lack crucial elements of the tumor microenvironment. To address this shortcoming, we have developed a melanoma skin equivalent based on an open-source epidermal model. Melanoma cell lines with different driver mutations were incorporated into these models forming distinguishable tumor aggregates within a stratified epidermis. Although barrier properties of the skin equivalents were not affected by incorporation of melanoma cells, their presence resulted in a higher metabolic activity indicated by an increased glucose consumption. Furthermore, we re-isolated single cells from the models to characterize the proliferation state within the respective model. The applicability of our model for tumor therapeutics was demonstrated by treatment with a commonly used v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor vemurafenib. This selective BRAF inhibitor successfully reduced tumor growth in the models harboring BRAF-mutated melanoma cells. Hence, our model is a promising tool to investigate melanoma development and as a preclinical model for drug discovery.

Rambutan peel: An unconventional source of lignin and its potential applications in polymer science

This study aimed to evaluate the properties of soda lignin obtained from an unconventional and abundant waste - the rambutan peel - since lignin has been shown as the most promising natural organic feedstock alternative to petroleum for polymer science. FTIR analysis and pH measurements have confirmed the acidic form of lignin, which has shown solubility in a wide range of polarities and so many solvents, making its insertion easy on polymeric matrices. While the ability to absorb UV-light was higher than commercial lignin tested as reference, the morphology and size distribution at microscopic level were less regular than that. When added to a starch-based film, the lignin decreases its natural affinity for water, improving the barrier properties, as well as increasing its thermal resistance. Microorganisms could be developed easily on starch-based films containing this kind of lignin. This material, still underreported for technological applications, points towards as promisor to be a component or additive in polymeric matrices.

Effects of HCl hydrolyzed cellulose nanocrystals from waste papers on the Hydroxypropyl methylcellulose/Cationic Starch biofilms

ABSTRACT The study reports on the preparation of nanocrystalline cellulose from waste papers (WPNCC), as an environmental friendly approach of source material and investigation of their effects on the morphological, mechanical and barrier properties of the Hydroxypropyl methylcellulose/Cationic starch (HPMC/CS) nanocomposites. HCl hydrolysis followed by alkali treatment and deinking of the fibers resulted in the production of WPNCC. The TEM results confirmed the rod like shape of WPNCC; the average diameter was 22± 7 nanometers and the length was 125± 25 nanometers. The hydrolysis yield was 65% with high crystallinity index of 79.6%. The results of X-ray diffraction confirmed the successfully production of WPNCC and their effective presence in the HPMC/CS matrix. The homogeneity of WPNCC dispersion in the polymer matrix was approved by FESEM analysis. The WPNCC also did not affect the nanocomposites optical clarity. The optimum amount of 9 wt% WPNCC, showed the highest barrier, mechanical and biodegradablility properties.

Hybrid films from plant and bacterial nanocellulose: mechanical and barrier properties

The accumulation of petroleum polymers compromises biodiversity and causes environmental problems. Nanocellulose enhances biodegradability and can improve the physical-mechanical performance of materials. The objective was to produce and characterize hybrid films composed of bacterial cellulose (BC) and plant nanocellulose from Eucalyptus (Euc) or Pinus (Pin). Films were produced by the casting method using filmogenic suspensions with different cellulose nanofibrils (CNFs) proportions from both the sources (0, 25, 50, 75 and 100 %). CNFs suspensions were characterized by transmission electron microscopy. The morphology of the films was analyzed using scanning electron microscopy. In addition, the transparency, contact angle, wettability, oil and water vapor barrier and mechanical properties were also evaluated. The contact angles were smaller for films with BC and the wettability was greater when comparing BC with plant CNFs (0.10 ° s − 1 {\text{s}^{-1}} for 75 % Euc/25 % BC and 0.20 ° s − 1 {\text{s}^{-1}} for 25 % Euc/75 % BC). The water vapor permeability (WVP) of the 100 % BC films and the 25 % Euc/75 % BC composition were the highest among the studied compositions. Tensile strength, Young’s modulus and puncture strength decreased considerably with the addition of BC in the films. More studies regarding pre-treatments to purify BC are needed to improve the mechanical properties of the films.

The Wilms Tumor Gene wt1a Contributes to Blood-Cerebrospinal Fluid Barrier Function in Zebrafish

The Wilms tumor suppressor gene Wt1 encodes a zinc finger transcription factor, which is highly conserved among vertebrates. It is a key regulator of urogenital development and homeostasis but also plays a role in other organs including the spleen and the heart. More recently additional functions for Wt1 in the mammalian central nervous system have been described. In contrast to mammals, bony fish possess two paralogous Wt1 genes, namely wt1a and wt1b. By performing detailed in situ hybridization analyses during zebrafish development, we discovered new expression domains for wt1a in the dorsal hindbrain, the caudal medulla and the spinal cord. Marker analysis identified wt1a expressing cells of the dorsal hindbrain as ependymal cells of the choroid plexus in the myelencephalic ventricle. The choroid plexus acts as a blood-cerebrospinal fluid barrier and thus is crucial for brain homeostasis. By employing wt1a mutant larvae and a dye accumulation assay with fluorescent tracers we demonstrate that Wt1a is required for proper choroid plexus formation and function. Thus, Wt1a contributes to the barrier properties of the choroid plexus in zebrafish, revealing an unexpected role for Wt1 in the zebrafish brain.