Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor HR is emerging as a new promising pharmacological target for diabetic nephropathy. The aim of this study was to evaluate the efficacy of selective HR antagonism by JNJ39758979 on the prevention of diabetic nephropathy progression in a murine model of diabetes induced by streptozotocin injection. JNJ39758979 (25, 50, 100 mg/kg/day p.o.) was administered for 15 weeks starting from the onset of diabetes. Functional parameters were monitored throughout the experimental period. JNJ39758979 did not significantly affect glycaemic status or body weight. The urine analysis indicated a dose-dependent inhibitory effect of JNJ39758979 on Albumin-Creatinine-Ratio, the Creatinine Clearance, the 24 h urine volume, and pH urine acidification (P < 0.05). The beneficial effects of JNJ39758979 on renal function paralleled comparable effects on renal morphological integrity. These effects were sustained by a significant immune infiltration and fibrosis reduction. Notably, megalin and sodium-hydrogen-exchanger 3 expression levels were preserved. Our data suggest that the HR participates in diabetic nephropathy progression through both a direct effect on tubular reabsorption and an indirect action on renal tissue architecture via inflammatory cell recruitment. Therefore, HR antagonism emerges as a possible new multi-mechanism therapeutic approach to counteract development of diabetic nephropathy development.

Nowadays, approximately 1 billion kg/y of grape stalks, with a remarkable polyphenols content, are produced worldwide. In this paper, the extraction process intensification of polyphenols in water was achieved under ultrasound-assisted recovery, focusing on kinetics and scaling-up factors. Immersion and cup-horn systems were exploited as acoustic cavitation sources, and the total phenolic content (TPC) was chosen to assess the process efficiency. The kinetics were evaluated by Peleg’s hyperbolic model, and the effect of both the initial feedstock granulometry and ultrasound size-reduction were determined. The results were compared with conventional extraction methods (data analysis by ANOVA). The best polyphenols yield was obtained after 45 min of sonication, giving between 29.71 and 31.89 mg/g (gallic acid equivalents over the dry matter). The extracts were characterized using HPLC-DAD, UPLC-ESI-MS/MS, DPPH• assay (2,2-diphenyl-1-picrylhydrazyl), TEAC assay (Trolox equivalent antioxidant capacity), and proanthocyanidin content determination. The flow-mode extraction procedure of grape stalks (2 kg) was carried out in a 15 L reactor. A semi-industrial decanter unit and a bag-filter were the keys units of the downstream operations. The resulting particle-free solution underwent nanofiltration on a membrane pilot skid, providing a final polyphenols-enriched stream concentrated up to 355.91%, as shown by the antioxidant activity and TPC.

Many scientists are working hard to find green alternatives to classical synthetic methods. Today, state-of-the-art ultrasonic and grinding techniques already drive the production of organic compounds on an industrial scale. The physicochemical and chemical behavior of cyclodextrins often differs from the typical properties of classic organic compounds and carbohydrates. The usually poor solubility and complexing properties of cyclodextrins can require special techniques. By eliminating or reducing the amount of solvent needed, green alternatives can reform classical synthetic methods, making them attractive for environmentally friendly production and the circular economy. The lack of energy-intensive synthetic and purification steps could transform currently inefficient processes into feasible methods. Mechanochemical reaction mechanisms are generally different from normal solution-chemistry mechanisms. The absence of a solvent and the presence of very high local temperatures for microseconds facilitate the synthesis of cyclodextrin derivatives that are impossible or difficult to produce under classical solution-chemistry conditions. Although mechanochemistry does not provide a general solution to all problems, several good examples show that this new technology can open up efficient synthetic pathways.

Macroalgae are widespread on the coasts of all the globe and lead to a negative ecological impact, requiring expensive remediations. Therefore, the valorization of invasive seaweed as a renewable source of bioactive products could represent a valid solution. In this context, three algal biomasses, belonging to brown, green, and red families (Sargassum muticum, Ulva lactuca, Solieria filiformis), collected in the venetian Laguna, were investigated as a source of active compounds for the formulation of cosmeceutics. Microwave (MW) and ultrasound (US) were applied to enhance the algae extraction by means of a hydroalcoholic solution. According to total phenolic content (TPC) evaluation, MW demonstrated the best performing outcomes, resulting in 19.77, 22.02, and 16.94 mgGAE/gExtr (30 min at 90 °C) for brown, green, and red algae, respectively. Antioxidant activity was tested as well, showing comparable trends (49.19, 26.24, and 3.02 mmolTrolox eq./gExtr for brown, green, and red algae, respectively). Due to natural algae predisposition to absorb contaminants, the metal content analysis helped to screen the applicability of these extracts, identifying Ulva lactuca as the most suitable source of antioxidants for cosmetic formulations. This MW extract was then adopted to formulate two different preparations, namely a gel and an emulsion. Thermal and mechanical tests confirmed the stability of each formulation, together with neutral organoleptic characteristics. Finally, the actives release was investigated by means of a tape stripping essay, showing an efficient controlled release for gel formulation, even after 7 h of test. The produced cosmeceutics merged non-conventional extraction technologies with formulation expertise, offering a valuable alternative to solve the macroalgae disposal issue.