In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions.

The activation of microglia, the inflammatory cells of the central nervous system (CNS), has been linked to the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases. How microglia sense the changing brain environment, in order to respond appropriately, is still being elucidated. Microglia are able to sense and respond to the mechanical properties of their microenvironment, and the physical and molecular pathways underlying this mechanosensing/mechanotransduction in microglia have recently been investigated. The Hippo pathway functions through mechanosensing and subsequent protein kinase cascades, and is critical for neuronal development and many other cellular processes. In this review, we examine evidence for the potential involvement of Hippo pathway components specifically in microglia in the pathogenesis of Alzheimer’s disease. We suggest that the Hippo pathway is worth investigating as a mechanosensing pathway in microglia, and could be one potential therapeutic target pathway for preventing microglial-induced neurodegeneration in AD.

Lipid metabolism plays a significant role in the regulation of various critical pathways within cells, where enhanced lipid metabolism is a hallmark of cancer cell metabolism. The Hippo signalling pathway poses as an important signalling pathway that governs tissue growth control and tumorigenesis. The effector of the Hippo signalling pathway, Yes-associated protein (YAP), serves as a central regulator for this growth control. Once a tissue develops to its correct size, YAP is phosphorylated and inactivated within the cytoplasm by the activation of the Hippo pathway, where its inactivation results in YAP nucleus translocation. This allows its dephosphorylation, modulating various cellular behaviours such as cellular proliferation and the inhibition of apoptosis. Moreover, it has been established that YAP is positively regulated by the extracellular matrix (ECM). The interplay between the Hippo signalling pathway, the ECM, and lipid metabolism, however, is not entirely clear. Thus, this study illustrates a novel link between the Hippo signalling pathway, the ECM, and lipid metabolism. Furthermore, the project identifies a novel ECM complex which is dependent upon lipids and regulates YAP in a positive manner.

Insulin delivery via the buccal route has shown long-standing promise for diabetes therapy, but clinical translation remains limited. Most systems address only part of the delivery problem, whereas a viable product must simultaneously provide adequate insulin residence time, effective mucus and epithelial permeation, stability, dose consistency, safety, and manufacturability. This review examines the biological and formulation barriers limiting buccal insulin delivery and compares major platform types, including mucoadhesive films and patches, nanocarrier-based systems, deformable vesicles, chemistry-led permeation approaches, and device-enabled strategies. Stability, alongside limited permeability, is considered a key barrier, while aggregation and excipient-related instability remain insufficiently addressed. This review also discusses why promising preclinical findings often fail to translate, exhibiting low bioavailability, variability, safety concerns, and scale-up challenges recurring across platforms. Overall, further progress in buccal insulin delivery will depend on formulation strategies that better integrate permeation enhancement, stability preservation, and translational feasibility.

Insulin delivery via the buccal route has shown long-standing promise for diabetes therapy, but clinical translation remains limited. Most systems address only part of the delivery problem, whereas a viable product must simultaneously provide adequate insulin residence time, effective mucus and epithelial permeation, stability, dose consistency, safety, and manufacturability. This review examines the biological and formulation barriers that limit buccal insulin delivery and compares the major platform types, including mucoadhesive films and patches, nanocarrier-based systems, deformable vesicles, chemistry-led permeation approaches, and device-enabled strategies. Stability, alongside limited permeability, is considered a key barrier, while aggregation and excipient-related instability remain insufficiently addressed. The review also discusses why promising preclinical findings often fail to translate, exhibiting low bioavailability, variability, safety concerns, and scale-up challenges recurring across platforms. Overall, further progress in buccal insulin delivery will depend on formulation strategies that better integrate permeation enhancement, stability preservation, and translational feasibility.