The use of photoactivatable 8-methoxypsoralen (8-MOP) as potential focal treatment towards prostate cancer cells is proposed here. Our results, obtained on isolated DNA and DU145 cells, indicate that blue light, besides UVA, is able to activate 8-MOP. When compared to UVA, blue light irradiation led to a modulation of the extent and the types of 8-MOP-DNA damage, specially cross-links, coupled to a still valuable antiproliferative effect. Our data suggest that the proapototic activity of 8-MOP is related not only to DNA damage and reactive oxygen species generation but also to the modulation of cell signalling pathways. In particular, a different activation of p38 and p44/42 mitogen-activated protein kinases was detected depending on the light wavelengths.

Background: Recent studies highlighted the presence of anti-α-Gal antibodies in patients implanted with commercial bioprosthetic heart valves (BHVs). BHVs expose residual α-Gal xenoantigen and their recognition by the circulating anti-Gal antibodies leads to opsonization of the device’s tissue component with the consequent triggering of a deterioration pathway that culminates with calcification. Small animal models such as mice and rats have been broadly involved in the in vivo testing of biomaterials by subcutaneous implantation, especially for the effectiveness of BHVs anti-calcific treatments. However, since models employed for this purpose express α-Gal antigen, the implantation of BHVs’ leaflets does not elicit a proper immunological response, so the calcification propensity may be dramatically underestimated. Methods: An α-Gal knockout (KO) mouse model has been created, using the CRISP/Cas9 approach, and adopted to assess the calcification potential of commercial BHVs leaflets through the surgical implantation in the back subcutis area. Calcium quantification was performed by inductively coupled plasma analysis; immune response against the BHVs leaflets and α-Gal silencing was evaluated through immunological assays. Results: Two months after the implantation of commercial BHV leaflets, the anti-Gal antibody titers in KO mice doubled when compared with those found in wild-type (WT) ones. Leaflets explanted from KO mice, after one month, showed a four-time increased calcium deposition concerning the ones explanted from WT. The degree of silencing of α-Gal varied, depending on the specific organ that was assessed. In any case, the animal model was suitable for evaluating implanted tissue responses. Conclusions: Such mouse model proved to be an accurate tool for the study of the calcific propensity of commercial BHVs leaflets than those hitherto used. Given its reliability, it could also be successfully used to study even other diseases in which the possible involvement of α-Gal has been observed.

The cover image, by G. Miolo et al., is based on the Original Article 4,6,4'‐trimethylangelicin shows high anti‐proliferative activity on DU145 cells under both UVA and blue light, DOI 10.1111/cpr.12430.

Rationale The presence of preformed antibodies against αGal in the human lead to opsonization of the implanted bioprosthetic heart valve (BHV), leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments, however, unlike the situation in humans, leaflets implanted into a murine model will not be able to elicit an αGal immune response because both donor and recipient species constitutively express the epitope. Objective This study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. Methods and Results By using CRISPR/Cas9 approach an αGal KO mouse was created and used for the evaluation of the calcific propensity of original and polyphenols-treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice’s immune system. Commercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. Conclusions The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. The polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies completely preventing calcific depositions compared to the untreated counterpart.

Anti-αGal antibodies, known for their polyreactivity, have been detected bound to gray matter in the brains of Alzheimer's disease (AD) patients. This study explored their potential interaction with gangliosides (GLSs), αGal-like structures abundant in the central nervous system. Using ELISA, serum profiles of anti-αGal antibody isotypes and their binding to various GLSs were analyzed in healthy subjects and AD patients. Results showed a decreased expression of anti-αGa IgG and IgM in AD patients compared to healthy controls, while IgA levels were elevated. Notably, none of the isotypes in healthy subjects exhibited GLS binding. In contrast, all isotypes in AD patients bound to ganglioside GD1b; additionally, IgM recognized GM1, and IgA targeted GM2. These findings suggest a disease-specific binding pattern of anti-αGal antibodies to gangliosides in the AD brain, supporting their potential role as diagnostic biomarkers.