Summary
During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine‐based ...multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi‐tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications.
The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal ...muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne's muscular dystrophy. In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles. Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.
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•LaAl1-xCoxO3 perovskites were synthesized by a sol-gel route for enhancing the oxidation of soot in the presence of NOx.•LaAl0.25Co0.75O3 showed outstanding NOx-assisted soot ...oxidation, due to high lattice oxygen mobility and well-crystallized perovskite structure.•These catalysts can set as alternative to PGM catalysts for NOx-assisted soot oxidation with improved NO2 production.
In the framework of nowadays challenges in the automotive catalysis, directed to the mitigation of pollution caused by the emissions of internal combustion engines, a series of LaAl1-xCoxO3 perovskites were investigated with the purpose of enhancing the oxidation of soot in the presence of NOx. Perovskite oxides LaAl1-xCoxO3 (x = 0; 0.25; 0.5; 0.75 and 1) were synthesized by a sol-gel route and characterized by different methods: X-Ray diffraction (XRD), H2-temperature programmed reduction (H2-TPR), N2-sorption, O2/NOx-temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). The perovskite oxides were tested as catalysts for NO oxidation in isothermal mode and for NOx-assisted soot oxidation in temperature programmed reaction. Structural results reveal that Co is well incorporated in the perovskite structure expanding the unit cell, and doping Co may result in the distortion of the BO6 octahedra of the general ABO3 perovskite structure. An increase in Co substitution with x up to 0.75 remarkably promotes the oxidation activity, whereas total replacement of Al by Co degrades the catalytic performance. Among the prepared solids, LaAl0.25Co0.75O3 is the most active for NO oxidation, with a conversion of 78% at 320 °C, and it also exhibits the highest activity for NOx-assisted soot oxidation, with a T10% of 377 °C while maintaining high NO2 production (71%). The outstanding performance of LaAl0.25Co0.75O3 is associated with the high mobility of lattice oxygen species and the role of surface adsorbed oxygen seems not to be prominent. The strong correlation of catalytic activity with NOx-TPD profiles suggests that NOx adsorption on catalyst surface is an essential step in soot oxidation. It is also shown that higher calcination temperature promotes the crystallinity of perovskite phase and leads to the improvement in the catalytic activity. The present work indicates that the prepared perovskite catalysts are competitive with noble-metal rivals for NOx-assisted soot oxidation and outperform them in NO2 production for further NOx abatement.
Background and Purpose
Transient receptor potential melastatin type‐8 (TRPM8) is a cold‐sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the ...molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC).
Experimental Approach
TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8−/− mice in models of sporadic and colitis‐associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC.
Key Results
TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt–Frizzled signalling hyperactivation and adenomatous polyposis coli down‐regulation. In sporadic and colitis‐associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/β‐catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of β‐catenin and its target oncogenes such as C‐Myc and Cyclin D1.
Conclusion and Implications
Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.
Thermochemical cycles received renewed interest as CO2 and H2O energy-upgrading processes using solar energy as source. The two-step cycles, based on self-reduction in a solar reactor at high ...temperature (above 1300–1400 °C) and re-oxidation by CO2 and/or H2O flow, are the most interesting due to their simplicity and high theoretical solar-to-fuel efficiency. In the two-step cycle, ceria has been recognized as the benchmark material but it suffers from high reduction temperature, low re-oxidation kinetics as well as low stability, thus hindering practical application. In this work, the redox properties of two Ce0.75Zr0.25O2 materials prepared by hydrothermal synthesis were compared with those of a co-precipitated sample with the same nominal composition used as reference. Samples were characterized by X-Ray Diffraction (XRD), N2 physisorption, Scanning Elecron Microscopy (SEM), X-Ray Photoelectron Spectroscopy (XPS), and Electron Paramagnetic Resonance (EPR); their self-reducibility and CO2 splitting activity were tested in a Thermogravimetric (TG) balance, while H2O splitting properties were studied in an ad-hoc fixed bed reactor on H2 pre-reduced samples. Characterization results and activity tests agreed that the Ce3+ fraction both on the surface and in the bulk of ceria-zirconia can be increased by hydrothermal synthesis, thus providing improved redox properties and higher splitting activity with respect to the co-precipitated sample. So, hydrothermal synthesis, providing a controlled nucleation and growth of crystallites, appears as a promising route for the preparation of ceria-based materials with tuned oxygen vacancies.
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•Ce0.75Zr0.25O2 materials were prepared by hydrothermal synthesis and co-precipitation.•Hydrothermal materials showed improved splitting properties towards both CO2 and H2O.•Hydrothermal materials showed larger Ce3+ fractions both on the surface and in the bulk.•Redox properties can be tuned by the opportune choice of the preparation method.
Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its ...metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C ₂C ₁₂ myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of K ᵥ7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and K ᵥ7.4-bound PIP2 levels in C ₂C ₁₂ cells and inhibits K ᵥ7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of K ᵥ7.4 channels.
The search for efficient routes for the production of sorbitol from starch-derived glucose is of great interest and importance because sorbitol is a highly attractive chemical for different ...applications, such as a building block for the synthesis of fine chemicals, additives in food, and the cosmetic and paper industries. In this study, the (RuO2)0.038·(SiO2)0.962 nanomaterial was prepared by a one-pot sol–gel route. The performances of the gel-derived catalyst in the glucose hydrogenation reaction, in the aqueous phase and mild conditions, are reported and compared with those of a commercial Ru/C catalyst. When the commercial Ru/C catalyst was used, a high activity and no selectivity loss were observed, but the activity dramatically dropped soon after the first cycle; on the contrary, the gel-derived catalyst activity increased during the first three cycles. The different catalytic behavior was ascribed to the morphological distribution of the Ru active phase in the gel-derived catalyst. Actually, the adopted synthesis procedure leads to a multimodal size distribution of the Ru nanoparticles, which are fairly stabilized by a combined interaction with the SiO2 support and the reaction environment, which proved to be active in obtaining a self-activating catalyst.
CeO2 slow redox kinetics as well as low oxygen exchange ability limit its application as a catalyst in solar thermochemical two-step cycles. In this study, Ce0.75Zr0.25O2 catalysts doped with ...potassium or transition metals (Cu, Mn, Fe), as well as co-doped materials were synthesized. Samples were investigated by X-ray diffraction (XRD), N2 sorption (BET), as well as by electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) to gain insight into surface and bulk features, which were connected to redox properties assessed both in a thermogravimetric (TG) balance and in a fixed bed reactor. Obtained results revealed that doping as well as co-doping with non-reducible K cations promoted the increase of both surface and bulk oxygen vacancies. Accordingly, K-doped and Fe-K co-doped materials show the best redox performances evidencing the highest reduction degree, the largest H2 amounts and the fastest kinetics, thus emerging as very interesting materials for solar thermochemical splitting cycles.
Fish oil (FO) and phytocannabinoids have received considerable attention for their intestinal anti‐inflammatory effects. We investigated whether the combination of FO with cannabigerol (CBG) and ...cannabidiol (CBD) or a combination of all three treatments results in a more pronounced intestinal antiinflammatory action compared to the effects achieved separately. Colitis was induced in mice by 2,4‐dinitrobenzenesulfonic acid (DNBS). CBD and CBG levels were detected and quantified by liquid chromatography coupled with time of flight mass spectrometry and ion trap mass spectrometry (LC‐MS‐IT‐TOF). Endocannabinoids and related mediators were assessed by LC‐MS. DNBS increased colon weight/colon length ratio, myeloperoxidase activity, interleukin‐1β, and intestinal permeability. CBG, but not CBD, given by oral gavage, ameliorated DNBS‐induced colonic inflammation. FO pretreatment (at the inactive dose) increased the antiinflammatory action of CBG and rendered oral CBD effective while reducing endocannabinoid levels. Furthermore, the combination of FO, CBD, and a per se inactive dose of CBG resulted in intestinal anti‐inflammatory effects. Finally, FO did not alter phytocannabinoid levels in the serum and in the colon. By highlighting the apparent additivity between phytocannabinoids and FO, our preclinical data support a novel strategy of combining these substances for the potential development of a treatment of inflammatory bowel disease.
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