Osteopontin (OPN) is a bone sialoprotein involved in osteoclast attachment to mineralised bone matrix, as well as being a bone matrix protein, OPN is also a versatile protein that acts on various receptors which are associated with different signalling pathways implicated in cancer. OPN mediates various biological events involving the immune system and the vascular system; the protein plays a role in processes such as immune response, cell adhesion and migration, and tumorigenesis. This review discusses the potential role of OPN in tumour cell proliferation, angiogenesis and metastasis, as well as the molecular mechanisms involved in these processes in different cancers, including brain, lung, kidney, liver, bladder, breast, oesophageal, gastric, colon, pancreatic, prostate and ovarian cancers. The understanding of OPN’s role in tumour development and progression could potentially influence cancer therapy and contribute to the development of novel anti-tumour treatments.

Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after nerve injury and are involved in the activation of microglial cells. These activated cells in turn release factors that increase the excitation and decrease the inhibition of interneurons. Microglial cells release factors such as interleukin (IL)-6, IL-1β and tumour necrosis factor-α (TNF-α) that cause the painful symptoms. It is becoming increasingly apparent that an intricate network of cytokines and cellular signalling mechanisms underpin the complex relationship between microglia and various cell types including neurones, astrocytes, oligodendrocytes, mast cells and T-cells. Although the precise mechanism of action of microglial cells in producing neuropathic pain has not been completely elucidated, research into these different activating factors and cytokines is providing further insight into the role of microglial cells in the development and maintenance of neuropathic pain. Further studies also are required to elucidate how "pain" mediators act on neurones and how the interactions between these mediators, or between neurones and glia in the presence of these mediators occur, in order to develop effective therapies for the management of neuropathic pain.

Necroptosis is a type of regulated cell death dependent on the activity of receptor-interacting serine/threonine-protein (RIP) kinases. However, unlike apoptosis, it is caspase independent. Increasing evidence has implicated necroptosis in the pathogenesis of disease, including ischemic injury, neurodegeneration, viral infection and many others. Key players of the necroptosis signalling pathway are now widely recognized as therapeutic targets. Necrostatins may be developed as potent inhibitors of necroptosis, targeting the activity of RIPK1. Necrostatin-1, the first generation of necrostatins, has been shown to confer potent protective effects in different animal models. This review will summarize novel insights into the involvement of necroptosis in specific injury of different organs, and the therapeutic platform that it provides for treatment.