Gap junctions have recently been shown to interconnect glioblastoma cells to a multicellular syncytial network, thereby allowing intercellular communication over long distances as well as enabling glioblastoma cells to form routes for brain microinvasion. Against this backdrop gap junction-targeted therapies might provide for an essential contribution to isolate cancer cells within the brain, thus increasing the tumor cells’ vulnerability to the standard chemotherapeutic agent temozolomide. By utilizing INI-0602—a novel gap junction inhibitor optimized for crossing the blood brain barrier—in an oncological setting, the present study was aimed at evaluating the potential of gap junction-targeted therapy on primary human glioblastoma cell populations. Pharmacological inhibition of gap junctions profoundly sensitized primary glioblastoma cells to temozolomide-mediated cell death. On the molecular level, gap junction inhibition was associated with elevated activity of the JNK signaling pathway. With the use of a novel gap junction inhibitor capable of crossing the blood–brain barrier—thus constituting an auspicious drug for clinical applicability—these results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research.

Accurate diagnosis of periprosthetic joint infections (PJI) is one of the most widely researched areas in modern orthopedic endoprosthesis. However, our understanding of the immunological basis of this severe complication is still limited. In this study, we developed a flow cytometric approach to precisely characterize the immune cell composition in periprosthetic joints. Using high-dimensional multi-parametric data, we defined, for the first time, the local immune cell populations of artificial joints. We identified significant differences in the cellular distribution between infected and non-infected samples, and revealed that myeloid-derived suppressor cells (MDSCs) act as potential regulators of infiltrating immune cells in PJI. Further, we developed an algorithm to predict septic and aseptic samples with high sensitivity and specificity, that may serve as an indispensable addition to the current criteria of the Musculoskeletal Infection Society. This study describes a novel approach to flow cytometrically analyze the immune cell infiltrate of joint fluid that not only improves our understanding of the pathophysiology of PJI, but also enables the development of a novel screening tool to predict infection status. Our data further suggest that pharmacological targeting of MDSCs represents a novel strategy for addressing PJI.