Crosstalks of GSK3 signaling with the mTOR network and effects on targeted therapy of cancer

Abstract The introduction of therapeutics targeting specific tumor-promoting oncogenic or non-oncogenic signaling pathways has revolutionized cancer treatment. Mechanistic (previously mammalian) target of rapamycin (mTOR), a highly conserved Ser/Thr kinase, is a central hub of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR network, one of the most frequently deregulated signaling pathways in cancer, that makes it an attractive target for therapy. Numerous mTOR inhibitors have progressed to clinical trials and two of them have been officially approved as anticancer therapeutics. However, mTOR-targeting drugs have met with a very limited success in cancer patients. Frequently, the primary impediment to a successful targeted therapy in cancer is drug-resistance, either from the very beginning of the therapy (innate resistance) or after an initial response and upon repeated drug treatment (evasive or acquired resistance). Drug-resistance leads to treatment failure and relapse/progression of the disease. Resistance to mTOR inhibitors depends, among other reasons, on activation/deactivation of several signaling pathways, included those regulated by glycogen synthase kinase-3 (GSK3), a protein that targets a vast number of substrates in its repertoire, thereby orchestrating many processes that include cell proliferation and survival, metabolism, differentiation, and stemness. A detailed knowledge of the rewiring of signaling pathways triggered by exposure to mTOR inhibitors is critical to our understanding of the consequences such perturbations cause in tumors, including the emergence of drug-resistant cells. Here, we provide the reader with an updated overview of intricate circuitries that connect mTOR and GSK3 and we relate them to the efficacy (or lack of efficacy) of mTOR inhibitors in cancer cells

Bio-Hydrocarbons through Catalytic Pyrolysis of Used Cooking Oils: towards sustainable jet and road fuels

Vegetable Oil (VO) is today the most used feedstock for transport biofuel production by transesterification to biodiesel. Other commercial technologies for renewable fuels production are mainly based either on Fischer-Tropsch (FT) synthesis from coal, natural gas and possibly biomass, or hydro treating of vegetable oil (Hydrotreated Vegetable Oil, HVO): this also includes Hydrotreated Renewable Jet fuel, HRJ, Used Cooking Oil (UCO) is a highly sustainable feedstock (based on EC-RED scheme): it is therefore considered as a possible alternative to VOs for greening of air transport and, under proper circumstances, for reducing the feedstock cost component. However, the use of UCO is not trivial in reactors, as catalysts are sensitive to impurities and contaminations, which are typical of waste oils. Moreover, the chemical composition of UCO is variable regionally as well as seasonally, because the type of base-vegetable oils vary with Country and period of the year. In the framework of the ITAKA EU FP7 project, (catalytic) thermochemical conversion of UCO has been considered to obtain an intermediate biofuel suitable for upgrading by hydrotreating. The catalytic conversion of UCO and Fatty Acids were investigated in a 1.5 kg/h pilot unit. UCO, properly filtered and conditioned, was characterized, and then converted in bio-oil by means of thermal and catalytic reactionsunder controlled conditions. The type of catalyst and the reaction conditions, including several parameters such as temperature, reactor geometry, heating rate and residence time, were evaluated, and selected combinations were tested. The bio-oil was characterized in terms of main constituents and hydrocarbons content, and GC-MS and GC-FID analyses were used to qualitatively and quantitatively assess the composition of the fuel

Phytotherapics in tissue healing and its interface with professionals of health in Brazil / Fitoterápicos na cicatrização de tecidos e sua interface com profissionais de saúde no Brasil

The World Health Organization and many other national health conferences have stimulated the use of phytotherapeutics and medicinal plants in primary health care in Brazil. Phytotherapeutics and the use of medicinal plants are part of the folk medicine practice, which complements the treatment that is usually employed by lower income population. There is a growing interest in researches about improving the knowledge of plants’ medicinal properties used in tissue healing. This process occurs as a biological response after injury, where uncountable signaling pathways are stimulated to restore the homeostasis of the affected structure. It is observed that Brazil has been developing important researches to improve the knowledge of plants’ medicinal properties favoring a greater prescription by the health professionals and also a better use by the population. Phototherapeutics act in tissue repair in different ways, and the present review describes the use of these in healing in experimental researches and its interface with professionals of health. In this research, we checked scientific articles (Medline, Scielo, Lilacs, Coordination of Superior Level Staff Improvement (CAPES), PubMed and Google Scholar) published between years 2000 and 2018. Companies, researchers, professionals of health and the general population have shown an interest in phytotherapeutics compounds as alternatives for the treatment of various conditions and the healing of injuries. This is due to the lower side effects, easy access and low cost of herbal medicines compared to allopathic medicines and the rich biodiversity from the Brazilian flora. However, it is necessary for the health professionals training and motivation, aiming at a correct and safe prescription and the use of herbal medicines in tissue healing, as well as the insertion of this practice into their professional qualification.