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Digital therapeutics (DTx), a burgeoning subset of digital health solutions, has garnered considerable attention in recent times. These cutting-edge therapeutic interventions employ diverse technologies, powered by software algorithms, to treat, manage, and prevent a wide array of diseases and disorders. Although DTx shows significant promise as an integral component of medical care, its widespread integration is still in the preliminary stages. This limited adoption can be largely attributed to the scarcity of comprehensive research that delves into DTx's scope, including its technological underpinnings, potential application areas, and challenges—namely, regulatory hurdles and modest physician uptake. This review aims to bridge this knowledge gap by offering an in-depth overview of DTx products’ value to both patients and clinicians. It evaluates the current state of maturity of DTx applications driven by digital technologies and investigates the obstacles that developers and regulators encounter in the market introduction phase.

The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential to stop the mitotic exit network (MEN), a signalling pathway that promotes the exit from mitosis and cell division. Previous work, however, suggested that a Kin4-independent pathway contributes to SPOC, yet the underlying mechanisms remain elusive. Here, we established the glycogen-synthase-kinase-3 (GSK-3) homologue Mck1, as a novel component that works independently of Kin4 to engage SPOC. Our data indicate that both Kin4 and Mck1 work in parallel to counteract MEN activation by the Cdc14 early anaphase release (FEAR) network. We show that Mck1's function in SPOC is mediated by the pre-replication complex protein and mitotic cyclin-dependent kinase (M-Cdk) inhibitor, Cdc6, which is degraded in a Mck1-dependent manner prior to mitosis. Moderate overproduction of Cdc6 phenocopies MCK1 deletion and causes SPOC deficiency via its N-terminal, M-Cdk inhibitory domain. Our data uncover an unprecedented role of GSK-3 kinases in coordinating spindle orientation with cell cycle progression.

Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.

Genetic alterations affect carcinogenesis, and recent studies demonstrated that long non-coding RNAs (lncRNAs) have critical roles during this process. Hox transcript antisense intergenic RNA (HOTAIR) is a lncRNA molecule that affects proliferation, survival, migration, genomic stability, and drug resistance of cancer cells. The purpose of this study is to examine the possible effects of Gemcitabine treatment on HOTAIR expression level in non-small cell lung cancer (NSCLC) cell lines, H1944 and H596.