University of Gdansk

Gestational diabetes mellitus (GDM) affects 9-25% of pregnancies. Undiagnosed or poorly managed GDM is associated with both short- and long-term complications in the fetus and mother. The pathogenesis of GDM is complex and has not yet been fully elucidated. Several biomarkers found in maternal serum have the potential for the early diagnosis of GDM. The aim of this narrative review was to explore novel biomarkers that have not been comprehensively described in previous reviews. We believe these biomarkers may allow for the detection of GDM in the early stages of pregnancy, enabling timely proper treatment and potentially preventing complications for both the mother and the fetus.

Extracellular vesicles (EVs) are an experimental class of drug carriers. Alternative sources of EVs are currently being explored to overcome limitations related to their manufacturing from mesenchymal stem cells. In this work, Citrus limon-derived EVs were tested as carriers for the widely used chemotherapeutic drug - doxorubicin (DOX). Capillary electrophoresis (CE) and nanoplasmonic sensing (NPS) were developed for the quality control of DOX-EV preparations. It was found that the CE method enables simultaneous detection of free and incorporated DOX and allows assessing the stability of the preparations and the drug leakage. NPS, on the other hand, demonstrated that DOX is accumulated in the interfacial region of the carrier. The activity of DOX-loaded EVs was tested on HeLa (cervical cancer cells) and HEK293T (human embryonic kidney cells) cell lines. It was found that DOX incorporation into plant-derived EVs virtually does not affect the drug's cytotoxicity to HeLa cells but significantly decreases DOX activity against HEK293T cell line.

The impact of the isoxazole derivative of usnic acid, ISOXUS (formerly known as 2b) on cancer and non-cancerous cell metabolism was investigated. ISOXUS significantly reduced the utilisation of most metabolic substrates that produce NADH or FADH2, mitochondrial electron flow and oxygen consumption rate (OCR) in MCF-7 breast cancer cells in contrast to HB2 normal epithelial cells. Molecular docking revealed that ISOXUS inhibits mitochondrial respiratory chain complex II, which was confirmed experimentally. Disturbance of electron flow in MCF-7 cells resulted in increased reactive oxygen species (ROS) production. They appeared crucial for ISOXUS-induced cancer cell vacuolization and a drop in survival as an antioxidant, α-tocopherol, protected against these processes. These findings indicate that ISOXUS is a metabolic inhibitor that targets mitochondrial complex II in breast cancer cells resulting in diminished ATP production and increased ROS formation which translates into reduced cell viability.