Purinergic signalling plays a central regulatory role on cell proliferation, migration, differentiation, survival, and inflammation. However, the impact of purinergic modulators-based therapies on tissue repair is still overlooked. By using a systematic review framework, we investigated the therapeutic relevance of purinergic agonists and antagonists in animal models of skin wound healing. Following PRISMA guidelines, PubMed/M...

Clemastine (CLE), an H1R antagonist widely used for the treatment of allergic rhinitis, has recently been investigated for its positive modulatory effects on P2X7, a receptor for extracellular ATP (eATP) involved in the regulation of inflammation, immune responses, and the composition of the tumor microenvironment (TME). Here, we further examined the effects of CLE on P2X7-mediated responses to clarify the pharmacological sign...

The P2X7 receptor (or P2X7) is an ATP-gated ion channel with important roles in the immune and other body systems. Much has been garnered about P2X7 using the first published anti-human P2X7 monoclonal antibody (mAb) (clone L4). This mAb can be used to impair P2X7 channel and pore activity and events downstream of P2X7 activation in vitro and in vivo. Immunolabelling with this mAb has been used in flow and mass cytometry, conf...

Pituitary neuroendocrine tumors (PitNETs) constitute a heterogeneous group of intracranial neoplasms with variable biological behavior, whose aggressiveness cannot be explained solely by the intrinsic characteristics of tumor cells. Growing evidence demonstrates that chronic inflammation of the tumor microenvironment (TME) plays a central role in the progression, invasiveness, therapeutic resistance, and recurrence of these tu...

Bone cells are known to express multiple purinergic receptors. These are involved in various aspects of bone physiology depending on the cell type and receptor involved, both in normal and disease states, with extracellular ATP being particularly abundant in the bone microenvironment. The P2X7R subtype has been the subject of in-depth research in bone homeostasis. Different splice isoforms and single nucleotide polymorphisms (...

Chronic pain is increasingly recognized as a complex and multidimensional condition that extends beyond peripheral nociceptive input, encompassing maladaptive central mechanisms such as persistent neuroinflammation, glial dysfunction, aberrant synaptic plasticity, and disturbances in affective–motivational circuits. Adenosine, an endogenous purine nucleoside, plays a pivotal role in central nervous system homeostasis through a...

Despite robust preclinical evidence, many clinical trials, including several that targeted the purinergic system, fail to demonstrate efficacy in humans. Failure may stem from inability to accurately identify patient subgroups responding similarly to treatments. Here, we explore the potential of artificial intelligence to revolutionize how we group and classify patients in clinical studies. We introduce a new framework using L...

Neutrophils are key innate immune cells whose effector mechanisms are increasingly recognized as therapeutic targets in chronic inflammation and cancer. While highly heterogeneous and functionally versatile, they can also exacerbate inflammation and tissue damage, making precise modulation critical for homeostasis. Nucleotide signaling—including extracellular nucleotide-metabolizing enzymes and receptors for ATP, UTP, and aden...

Positive allosteric modulators of P2X7 receptors hold promise as host-directed immune enhancers in intracellular infections. We have previously reported the use of protopanaxadiol ginsenosides as positive allosteric modulators of human, rat and mouse P2X7 receptors plus human P2X4 receptors, however, the effect of ginsenosides on other P2X receptors is unknown. Here, we screened a range of ginsenosides and related glycosides a...

The P2RX7 gene has been linked to various neuropsychiatric disorders. In particular, the SNP rs2230912, which results in a glutamine-to-arginine substitution at position 460, has repeatedly been associated with mood disorders. Although this SNP per se does not affect receptor function, it tags a gain-of-function haplotype that has been shown to significantly enhance receptor activity. BAC-transgenic P2X7-reporter mice have pro...