Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival and differentiation. PPIns are differentially present in various sub-cellular compartments and, through the recruitment and regulation of specific proteins, are key regulators of compartment identity and function. Phosphoinositides and the enzymes that synthesise and degrade them are also present in the nuclear membrane and in nuclear membraneless compartments such as nuclear speckles. Here we discuss how PPIns in the nucleus are modulated in response to external cues and how they function to control downstream signalling. Finally we suggest a role for nuclear PPIns in liquid phase separations that are involved in the formation of membraneless compartments within the nucleus.

Phosphoinositides (PI) form just a minor portion of the total phospholipid content in cells but are significantly involved in cancer development and progression. In several cancer types, phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] play significant roles in regulating survival, proliferation, invasion, and growth of cancer cells. Phosphoinositide-specific phospholipase C (PLC) catalyze the generation of the essential second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (InsP3) by hydrolyzing PtdIns(4,5)P2. DAG and InsP3 regulate Protein Kinase C (PKC) activation and the release of calcium ions (Ca2+) into the cytosol, respectively. This event leads to the control of several important biological processes implicated in cancer. PLCs have been extensively studied in cancer but their regulatory roles in the oncogenic process are not fully understood. This review aims to provide up-to-date knowledge on the involvement of PLCs in cancer. We focus specifically on PLCβ, PLCγ, PLCδ, and PLCε isoforms due to the numerous evidence of their involvement in various cancer types.

Tendon repair is a complex process due to the low tenocyte density, metabolism, and vascularization. Tears of rotator cuff (RCT) and Achilles tendons ruptures have a major impact on healthcare costs and quality of life of patients. Scaffolds are used to improve the healing rate after surgery and long-term results. A systematic search was carried out to identify the different types of scaffolds used during RCT and Achilles tendon repair surgery in the last 10 years. A higher number of clinical studies were reported on RCT ruptures. Biological scaffolds were used more than synthetic ones, for both rotator cuff and Achilles tendons. Moreover, platelet-rich plasma (PRP)based scaffolds were the most widely used in RCT. A different type of synthetic scaffold was used in each of the five studies found. Biological scaffolds either provide variable results, in particular PRP-based ones, or poor results, such as bovine equine pericardium. All the synthetic scaffolds demonstrated a significant increase in clinical and functional scores in biomechanics, and a significant decrease in pain and re-tear rate in comparison to conventional surgery. Despite the limited number of studies, further investigation in the clinical use of synthetic scaffolds should be carried out. K E Y W O R D S Achilles tendon, biological scaffolds, rotator cuff tendon, synthetic scaffolds, tissue repair

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