Thyroid Hormones and Antioxidant Systems: Focus on Oxidative Stress in Cardiovascular and Pulmonary Diseases

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q₁₀ (CoQ₁₀) and thyroid hormones; in fact, CoQ₁₀ levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ₁₀ is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q₁₀. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.     

Optical properties of Nb-doped TiO2 thin films prepared by sol–gel method

In this work, we studied optical properties of pure and Nb-doped TiO₂ synthesized using a sol–gel method and deposited as thin films by spin-coating followed by annealing in air at 500 °C for 1 h. The surface elemental composition was derived from X-ray photoelectron spectra, while structure and surface morphology were investigated using X-ray diffraction and atomic force/scanning electron microscopy. Finally, the optical properties were investigated by means of UV–vis spectrophotometry and spectroscopic ellipsometry.The Nb content was determined from XPS measurements to vary between 1.8 and 4.3 at%. The XRD patterns of the deposited thin films, with a maximum thickness of about 56 nm, showed no diffraction peaks. As proven both by microscopy and spectroscopic ellipsometry studies doping TiO₂ with Nb modified the surface morphology of the samples; the grain size is increasing while the surface roughness decreases with the increase in Nb content. This is accompanied by a decrease in the refractive index and an increase of the extinction coefficient.     

Rhodium‐Catalyzed Enantioselective Hydrogenation of (E)‐Enol Acetate Acids

The novel rhodium complex [Rh(S)‐Phanephos(cod)]‐catalyzed hydrogenation of disubstituted (E)‐enol acetate carboxylic acids is reported. The catalytic cycle works under 30 bar of hydrogen under conventional heating giving different 3‐acetoxy‐2,3‐disubstituted carboxylic acids with ee ≥90%. Hydrogenation occurred also under microwave dielectric heating without eroding the enantioselectivity but improving the overall efficiency of the process. With microwaves, hydrogen pressure and reaction time required for complete hydrogenation dropped to 5 bar and 30 min, respectively. The best performance of this catalyst under microwave irradiation was TON 100, TOF 196 h⁻¹ with ee 99% on a 6‐g scale.     

Novel approaches to developing carbon nanotube based polymer composites: fundamental studies and nanotech applications

The adsorption of several types of conducting polymers on carbon nanotubes is investigated by electrical transport measurements. We report the optoelectronic properties occurring in single-walled carbon nanotubes (SWNTs) conjugated polymer, poly(3-octylthiophene), composites. Al/polymer-nanotube composite/indium-tin oxide diodes show photovoltaic behavior proposing that the main reason for this increase is the photoinduced electron transfer at the polymer/nanotube interface. Interesting results were obtained in the case of poly(o-anisidine) (POAS)-multi-walled nanotubes (MWNTs) composites where the increment of monolayers results in a significant improvement of the specific conductivity. POAS-coated MWNTs thin films demonstrated their potentiality as a new class of materials for inorganic vapors detection for environmental applications.     

Solvent and oxygen effects on the free radical polymerization of 6-O-vinyladipoyl-d-glucopyranose

The vinyl ester-type glycomonomer 6-O-vinyladipoyl-d-glucopyranose was polymerized in water and alcohol solutions. In all cases, long polymerization times were necessary to achieve reasonable conversions. Depending on the nature of the solvent, polydisperse glycopolymers were obtained possessing a molecular weight ranging between 10,000 and 122,000 Da (PS equivalent). Higher alcohols appeared to act as chain transfer agents and oligomers with DP_n between 2 and 6 were indeed obtained when 2-propanol was the solvent. Also, thorough oxygen removal from the reaction mixture proved to be essential for the success of the experiment, plain nitrogen sparging being ineffective in most cases.     

Synthesis and characterization of ET(P)S-4 and ET(P)S-10

Phosphorus containing ET(P)S-4 and ET(P)S-10 were synthesized from gels of composition xNa₂O–0.6KF–0.2TiO₂–(1.28 − 4y)xHCl–yP₂O₅–1.49SiO₂–39.5H₂O at 190 °C for 3 days. The XRD patterns are almost identical to the corresponding ETS samples. The presence of phosphorus in the initial gel influences the kinetic parameters of the crystallization process, the morphology and the size of the crystals. The ³¹P-NMR of the samples show that part of the phosphorus is attached at the siliceous surface as dihydrogenophosphate SiOPO(OH)₂ groups and cannot be introduced in a tetrahedral or octahedral framework position.     

An experimental comparison of a graphite electrode and a gas diffusion electrode for the cathodic production of hydrogen peroxide

This work studies the production of hydrogen peroxide through the cathodic reduction of oxygen in acidic medium, by comparing the results obtained using a commercial graphite and a gas diffusion electrode. A low pH was required to allow the application of hydrogen peroxide generation to an electro-Fenton process. The influence of applied potential and the gas flow composition were investigated. The gas diffusion electrode demonstrates a higher selectivity for hydrogen peroxide production, without significantly compromising the iron regeneration, thus making its successful application to a cathodic Fenton-like treatment, possible. Unlike the graphite cathode, the gas diffusion cathode also proved to be effective in the air flow.     

Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.     

Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.