Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells

Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2. Downregulation of H-Ras by siRNA or inactivation of ERK by chemical inhibitor effectively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epithelial-mesenchymal transition (EMT) transcriptional regulators, were up-regulated in the SWCNT-exposed cells, suggesting their role in the aggressive phenotype. Cortactin expression was shown to be controlled by the H-Ras/ERK signaling. Thus, our results indicate a novel role of H-Ras/ERK signaling and cortactin in the aggressive transformation of human mesothelial cells by SWCNT

Protein formulations for emulsions and solid-in-oil dispersions

Needs from medical and cosmetic areas have led to the design of novel nanosized emulsions and solid-in-oil dispersions of proteins. Here, we describe the production of those emulsions and dispersions using high-energy methodologies such as high-pressure homogenization or ultrasound. Recent work has resulted in new mechanistic insights related to the formation of protein emulsions and dispersions. The production method and composition of these formulations can determine major parameters such as size, stability, and functionality, and therefore their final application. Aqueous nanoemulsions of proteins can be used for drug delivery, while solid-in-oil dispersions are often used in transdermal applications.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684

Protein-based structures for food applications: from macro to nanoscale

Novel food structures' development through handling of macroscopic and microscopic properties of bio-based materials (e.g., size, shape, and texture) is receiving a lot of attention since it allows controlling or changing structures' functionality. Proteins are among the most abundant and employed biomaterials in food technology. They are excellent candidates for creating novel food structures due to their nutritional value, biodegradability, biocompatibility, generally recognized as safe (GRAS) status and molecular characteristics. Additionally, the exploitation of proteins' gelation and aggregation properties can be used to encapsulate bioactive compounds inside their network and produce consistent delivery systems at macro-, micro-, and nanoscale. Consequently, bioactive compounds which are exposed to harsh storage and processing conditions and digestion environment may be protected and their bioavailability could be enhanced. In this review, a range of functional and structural properties of proteins which can be explored to develop macro-, micro-, and nanostructures with numerous promising food applications was discussed. Also, this review points out the relevance of scale on these structures' properties, allowing appropriate tailoring of protein-based systems such as hydrogels and micro- or nanocapsules to be used as bioactive compounds delivery systems. Finally, the behavior of these systems in the gastrointestinal tract (GIT) and the impact on bioactive compound bioavailability are thoroughly discussed.JM and AP acknowledge the Portuguese Foundation for Science and Technology (FCT) for their fellowships (SFRH/BPD/89992/2012 and SFRH/BPD/101181/2014). This work was supported by Portuguese FCT under the scope of the Project PTDC/AGR-TEC/5215/2014, of the strategic funding of UID/BIO/04469 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy

Cross-talk between IFN-γ and TWEAK through miR-149 amplifies skin inflammation in psoriasis

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with disturbed interplay between immune cells and keratinocytes. A strong IFN-γ signature is characteristic for psoriasis skin, but the role of IFN-γ has been elusive. MicroRNAs are short RNAs regulating gene expression. OBJECTIVE: Our aim was to investigate the role of miR-149 in psoriasis and in the inflammatory responses of keratinocytes. METHODS: miR-149 expression was measured by quantitative RT-PCR in keratinocytes isolated from healthy skin and lesional and nonlesional psoriasis skin. Synthetic miR-149 was injected intradermally into the back skin of mice, and imiquimod was applied to induce psoriasis-like skin inflammation, which was then evaluated at the morphologic, histologic, and molecular levels. miR-149 was transiently overexpressed or inhibited in keratinocytes in combination with IFN-γ- and/or TNF-related weak inducer of apoptosis (TWEAK)-treatment. RESULTS: Here we report a microRNA-mediated mechanism by which IFN-γ primes keratinocytes to inflammatory stimuli. Treatment with IFN-γ results in a rapid and long-lasting suppression of miR-149 in keratinocytes. Depletion of miR-149 in keratinocytes leads to widespread transcriptomic changes and induction of inflammatory mediators with enrichment of the TWEAK pathway. We show that IFN-γ-mediated suppression of miR-149 leads to amplified inflammatory responses to TWEAK. TWEAK receptor (TWEAKR/Fn14) is identified as a novel direct target of miR-149. The in vivo relevance of this pathway is supported by decreased miR-149 expression in psoriasis keratinocytes, as well as by the protective effect of synthetic miR-149 in the imiquimod-induced mouse model of psoriasis. CONCLUSION: Our data define a new mechanism, in which IFN-γ primes keratinocytes for TWEAK-induced inflammatory responses through suppression of miR-149, promoting skin inflammation