Highlighting the Phototherapeutical Potential of Fungal Pigments in Various Fruiting Body Extracts with Informed Feature-Based Molecular Networking.

Fungal pigments are characterized by a diverse set of chemical backbones, some of which present photosensitizer-like structures. From the genus Cortinarius, for example, several biologically active photosensitizers have been identified leading to the hypothesis that photoactivity might be a more general phenomenon in the kingdom Fungi. This paper aims at testing the hypothesis. Forty-eight fruiting body-forming species producing pigments from all four major biosynthetic pathways (i.e., shikimate-chorismate, acetate-malonate, mevalonate, and nitrogen heterocycles) were selected and submitted to a workflow combining in vitro chemical and biological experiments with state-of-the-art metabolomics. Fungal extracts were profiled by high-resolution mass spectrometry and subsequently explored by spectral organization through feature-based molecular networking (FBMN), including advanced metabolite dereplication techniques. Additionally, the photochemical properties (i.e., light-dependent production of singlet oxygen), the phenolic content, and the (photo)cytotoxic activity of the extracts were studied. Different levels of photoactivity were found in species from all four metabolic groups, indicating that light-dependent effects are common among fungal pigments. In particular, extracts containing pigments from the acetate-malonate pathway, e.g., extracts from Bulgaria inquinans, Daldinia concentrica, and Cortinarius spp., were not only efficient producers of singlet oxygen but also exhibited photocytotoxicity against three different cancer cell lines. This study explores the distribution of photobiological traits in fruiting body forming fungi and highlights new sources for phototherapeutics.

A convenient separation strategy for fungal anthraquinones by centrifugal partition chromatography.

As recently shown, some fungal pigments exhibit significant photoactivity turning them into promising agents for the photodynamic treatment of microbial infections or malignant diseases. In the present study, a separation strategy for fungal anthraquinones was developed based on centrifugal partition chromatography. A suitable method was explored employing a methanolic extract of the fruiting bodies of Cortinarius sanguineus (Agaricales, Basidiomycota). An excellent fractionation was achieved using a biphasic solvent system comprising chloroform/ethyl acetate/methanol/water/acetic acid (3:1:3:2:1, v/v/v/v/v) operating in ascending mode. Experiments on an analytical scale with extracts of closely related Cortinarius species exhibited broad applicability of the devised system. Up to six pigments could be purified directly from the crude extract. Preparative-scale fractionation of the methanol extracts of C. malicorius and C. sanguineus demonstrated that up-scaling was possible without compromising selectivity.

Influence of electrical stimulation therapy on permanent pacemaker function.

BACKGROUND: Electrical stimulation therapy (EST) and transcutaneous electrical neuromuscular stimulation (TENS), a modality of EST, have become widely applied, accepted and effective methods for the treatment of musculoskeletal and other pain conditions. According to the rising number of permanent pacemaker (PM) wearers the number of potential candidates for EST with concomitant device implantation is growing. Contradictory recommendations exist regarding the application of EST or TENS on PM wearers. AIM: The study was carried out to evaluate the impact of EST on PM function. METHODS: A full size model mimicking the electrical characteristics of the human body was used to evaluate the application of EST on permanent PM devices. Various configurations with respect to energy modality, position of the stimulation electrodes and PM device models were evaluated. Intracardiac PM electrogram tracings (iEGM) were analyzed for the interference of EST with PM function. RESULTS: Unilateral EST application did not cause interference with PM function in any of the configurations (0%; n = 700). On the contrary, bilateral stimulation (350 configurations in total) caused either ventricular inhibition or switch to V00 back-up pacing due to electrical interference in 165 cases (47.1%) depending on the applied stimulation parameters. CONCLUSION: The use of EST potentially interferes with PM therapy, especially if the electrodes are positioned bilaterally; however, unilateral EST application appeared to be safe in all tested configurations.