Inferior mesenteric artery preservation techniques in the treatment of diverticular disease: a systematic review of the literature.

Purpose: The aim of this study is to analyze the impact of different surgical techniques used to preserve the inferior mesenteric artery on patient outcomes following left colonic resection.

Methods: A search was conducted in PubMed, Embase and Web of Science, founding 4795 articles. The review was registered on PROSPERO (registration number: CRD42024572291).

Overview of the role of purinergic signaling and insights into its role in cancer therapy.

Innovation of cancer therapy has received a dramatic acceleration over the last fifteen years thanks to the introduction of the novel immune checkpoint inhibitors (ICI). On the other hand, the conspicuous scientific knowledge accumulated in purinergic signaling since the early seventies is finally being transferred to the clinic. Several Phase I/II clinical trials are currently underway to investigate the effect of drugs interfering with purinergic signaling as stand-alone or combination therapy in cancer.

Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.

Purinergic receptors regulate the processing of neural information in the hippocampus and cerebral cortex, structures related to cognitive functions. These receptors are activated when astrocytic and neuronal populations release adenosine triphosphate (ATP) in an autocrine and paracrine manner, following sustained patterns of neuronal activity. The modulation by these receptors of GABAergic transmission has only recently been studied.

The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia.

Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression.

Bouveret Syndrome: A Curious Simultaneous Presentation of Two Cases: Comparison of Clinical Observations and Surgical Management.

Gallstone ileus is an uncommon occurrence and accounts for about 0.3-0.5% of complications of cholelithiasis in elderly patients.

The purinergic receptor P2X7 as a modulator of viral vector-mediated antigen cross-presentation.

Introduction: Modified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.

Methods: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells.

The NFATc1/P2X7 receptor relationship in human intervertebral disc cells.

A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R.

Editorial - Purinergic signalling: 50 years.

The function of almost all cells of the human and animal body is synchronized by purinergic/pyrimidinergic extracellular signalling molecules. This network activity is especially efficient in the central and peripheral nervous systems, driven by secretion of the (co)transmitter ATP (including its enzymatic degradation products ADP, AMP, and adenosine), as well as ATP/UTP (including UDP) released from the cytoplasm by either Ca-dependent vesicular exocytosis or by non-exocytotic pathways via a family of diverse channels. It must be pointed out that neural cells (neurons, astrocytes, and oligodendrocytes) are equal sources of nucleotides/nucleosides, as non-neural cells (e.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

Macrophage Activation in Follicular Conjunctivitis during the COVID-19 Pandemic.

Among the symptoms of SARS-CoV-2, follicular conjunctivitis has become relevant. The conjunctiva acts as an open lymph node, reacting to the viral antigen that binds the epithelial cells, forming follicles of B cells with activated T cells and NK cells on its surface, which, in turn, talk to monocyte-derived inflammatory infected macrophages. Here, the NLRP3 inflammasome is a major driver in releasing pro-inflammatory factors such as IL-6 and caspase-1, leading to follicular conjunctivitis and bulbar congestion, even as isolated signs in the 'asymptomatic' patient.

Purinergic signalling in cancer therapeutic resistance: From mechanisms to targeting strategies.

Purinergic signalling, consisting of extracellular purines and purinergic receptors, modulates cell proliferation, invasion and immunological reaction during cancer progression. Here, we focus on current evidence that suggests the crucial role of purinergic signalling in mediating cancer therapeutic resistance, the major obstacle in cancer treatment. Mechanistically, purinergic signalling can modulate the tumor microenvironment (TME), epithelial-mesenchymal transition (EMT) and anti-tumor immunity, thus affecting drug sensitivity of tumor cells.

The Coming of Age of the P2X7 Receptor in Diagnostic Medicine.

The discovery of the P2X7 receptor (P2X7R, originally named P2Z) in immune cells, its cloning, and the identification of its role in a multiplicity of immune-mediated diseases raised great hopes for the development of novel and more potent anti-inflammatory medicaments. Unfortunately, such hopes were partially deluded by the unsatisfactory results of most early clinical trials. This failure substantially reduced the interest of the pharmaceutical and biotech industries in the clinical development of P2X7R-targeted therapies.

The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients.

Introduction: The pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis.

Unorthodox localization of P2X7 receptor in subcellular compartments of skeletal system cells.

Identifying the subcellular localization of a protein within a cell is often an essential step in understanding its function. The main objective of this report was to determine the presence of the P2X7 receptor (P2X7R) in healthy human cells of skeletal system, specifically osteoblasts (OBs), chondrocytes (Chs) and intervertebral disc (IVD) cells. This receptor is a member of the ATP-gated ion channel family, known to be a main sensor of extracellular ATP, the prototype of the danger signal released at sites of tissue damage, and a ubiquitous player in inflammation and cancer, including bone and cartilaginous tissues.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Fetal bovine serum contains biologically available ATP.

ATP is a ubiquitous extracellular messenger released in a wide number of pathophysiological conditions. ATP is known to be present in minute amounts in the extracellular space in healthy tissues and in the blood, and to modulate a multiplicity of cell responses. Cell culture systems are widely used to explore purinergic signaling.

PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.

Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth.

Extracellular ATP: A powerful inflammatory mediator in the central nervous system.

Nucleotides play a crucial role in extracellular signaling across species boundaries. All the three kingdoms of life (Bacteria, Archea and Eukariota) are responsive to extracellular ATP (eATP) and many release this and other nucleotides. Thus, eATP fulfills different functions, many related to danger-sensing or avoidance reactions.

Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions.

Background: Previous studies have demonstrated that purinergic receptors could be therapeutic targets to modulate the inflammatory response in multiple models of brain diseases. However, tools for the selective and efficient targeting of these receptors are lacking. The development of new P2X7-specific nanobodies (nbs) has enabled us to effectively block the P2X7 channel.

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering AAR signaling in intestinal epithelial cells.

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A adenosine receptor (AAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC AAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface.

P2 Receptors: Novel Disease Markers and Metabolic Checkpoints in Immune Cells.

Extracellular ATP (eATP) and P2 receptors are novel emerging regulators of T-lymphocyte responses. Cellular ATP is released via multiple pathways and accumulates at sites of tissue damage and inflammation. P2 receptor expression and function are affected by numerous single nucleotide polymorphisms (SNPs) associated with diverse disease conditions.

Modulation of Cell Energy Metabolism by the P2X7 Receptor.

For many years the P2X7 receptor (P2X7R) was considered the prototypic cytolytic receptor due to its ability to cause dramatic changes in plasma membrane permeability, eventually leading to cell death. However, later studies revealed that controlled P2X7R activation has beneficial effects on cell metabolism and nowadays our perception of the physiological role of this receptor has radically changed. Some of the biochemical pathways underlying the trophic effect of the P2X7R are being unveiled, thus disclosing an unanticipated role of P2X7Rs in mitochondrial and glycolytic metabolism.

A2A Receptor Contributes to Tumor Progression in P2X7 Null Mice.

ATP and adenosine are key constituents of the tumor niche where they exert opposite and complementary roles. ATP can be released in response to cell damage or actively released by tumor cells and subsequently degraded into adenosine, which accumulates within the tumor microenvironment. Notably, while ATP promotes immune eradicating responses mainly the P2X7 receptor (P2X7R), extracellular adenosine acts as a potent immune suppressor and facilitates neovascularization thanks to the A2A receptor (A2AR).

The P2RX7B splice variant modulates osteosarcoma cell behaviour and metastatic properties.

Background: Osteosarcoma (OS) is the most common type of primary bone cancer affecting children and adolescents. OS has a high propensity to spread meaning the disease is often incurable and fatal. There have been no improvements in survival rates for decades.