Purinergic Signalling最新文献

{"title":"Astrocytic adenosine A_2B receptors: a crucial player in brain function.","authors":"Cui-Yuan Chen, Yong Tang","doi":"10.1007/s11302-024-10042-x","DOIUrl":"10.1007/s11302-024-10042-x","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"275-276"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.","authors":"R Huzaifa Sharafat, Aamer Saeed","doi":"10.1007/s11302-024-10031-0","DOIUrl":"10.1007/s11302-024-10031-0","url":null,"abstract":"<p><p>Ectonucleotidase inhibitors are a family of pharmacological drugs that, by selectively targeting ectonucleotidases, are essential in altering purinergic signaling pathways. The hydrolysis of extracellular nucleotides and nucleosides is carried out by these enzymes, which include ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (CD73). Ectonucleotidase inhibitors can prevent the conversion of ATP and ADP into adenosine by blocking these enzymes and reduce extracellular adenosine. These molecules are essential for purinergic signaling, which is associated with a variability of physiological and pathological processes. By modifying extracellular nucleotide metabolism and improving purinergic signaling regulation, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitors have the potential to improve cancer treatment, inflammatory management, and immune response modulation. Purinergic signaling is affected by CD73 inhibitors because they prevent AMP from being converted to adenosine. These inhibitors are useful in cancer therapy and immunotherapy because they may improve chemotherapy effectiveness and alter immune responses. Purinergic signaling is controlled by NTPDase inhibitors, which specifically target enzymes involved in extracellular nucleotide breakdown. These inhibitors show promise in reducing immunological responses, thrombosis, and inflammation, perhaps assisting in the treatment of cardiovascular and autoimmune illnesses. Alkaline phosphatase (ALP) inhibitors alter the function of enzymes involved in dephosphorylation reactions, which has an impact on a variety of biological processes. By altering the body's phosphate levels, these inhibitors may be used to treat diseases including hyperphosphatemia and certain bone problems. This article provides a guide for researchers and clinicians looking to leverage the remedial capability of ectonucleotidase inhibitors in a variety of illness scenarios by illuminating their processes, advantages, and difficulties.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"221-265"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adventures in translation.","authors":"Bruce Cronstein, Siddhesh R Angle","doi":"10.1007/s11302-025-10069-8","DOIUrl":"10.1007/s11302-025-10069-8","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"197-198"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin modulates purinergic signaling and inflammatory response in cutaneous metastatic melanoma cells.","authors":"Daiane Manica, Gilnei Bruno da Silva, Rafael Antônio Narzetti, Paula Dallagnoll, Alana Patrícia da Silva, Filomena Marafon, Joana Cassol, Letícia de Souza Matias, Ariane Zamoner, Sarah Franco Vieira de Oliveira Maciel, Marcelo Moreno, Margarete Dulce Bagatini","doi":"10.1007/s11302-024-10023-0","DOIUrl":"10.1007/s11302-024-10023-0","url":null,"abstract":"<p><p>Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic targets is essential, and natural compounds have emerged as potential candidates. This study aimed to elucidate the impact of curcumin, a natural compound known for its anti-inflammatory, antioxidant, and anti-tumor properties, on metastatic melanoma cells, focusing on the purinergic system and immune responses. Human melanoma cell line SK-Mel-28 were exposed to different curcumin concentrations for either 6 or 24 h, after which we assessed components related to the purinergic system and the inflammatory cascade. Using RT-qPCR, we assessed the gene expression of CD39 and CD73 ectonucleotidases, as well as adenosine deaminase (ADA). Curcumin effectively downregulated CD39, CD73, and ADA gene expression. Flow cytometry analysis revealed that curcumin significantly reduced CD39 and CD73 protein expression at specific concentrations. Moreover, the A2A receptor's protein expression decreased across all concentrations. Enzymatic activity assays demonstrated that curcumin modulated CD39, CD73, and ADA activities, with effects dependent on concentration and duration of treatment. Extracellular ATP levels increased after 24 h of curcumin treatment, emphasizing its role in modulating hydrolytic activity. Curcumin also displayed anti-inflammatory properties by reducing NLRP3 gene expression and impacting the levels of key inflammatory cytokines. In conclusion, this study unveils the potential of curcumin as a promising adjuvant in CM treatment. Curcumin modulates the expression and activity of crucial components of the purinergic system and exhibits anti-inflammatory effects, indicating its potential therapeutic role in combating CM. These findings underscore curcumin's promise and warrant further investigation in preclinical and clinical settings for melanoma management.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"277-288"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening herbal and natural product libraries to aid discovery of novel allosteric modulators of human P2X7.","authors":"Stefan Bidula, Waraporn Piyasirananda, Hanna Bielecka, Lučka Bibič, Andrew Beekman, Leanne Stokes","doi":"10.1007/s11302-024-10055-6","DOIUrl":"10.1007/s11302-024-10055-6","url":null,"abstract":"<p><p> P2X7 is an emerging therapeutic target for several disorders and diseases due to its role in inflammatory signalling. This study aimed to exploit the unique chemical libraries of plants used in traditional medicinal practices to discover novel allosteric modulators from natural sources. We identified several compounds from the NCI Natural Product library as P2X7 antagonists including confertifolin and digallic acid (IC₅₀ values 3.86 µM and 4.05 µM). We also identified scopafungin as a novel positive allosteric modulator of hP2X7. Screening a traditional medicinal plant extract library revealed 39 plant species with inhibitory action at hP2X7 and 17 plant species with positive allosteric modulator activity. Using computational docking to filter identified components from these plant species and determine potential antagonists, we investigated nine purified chemicals including flavonoids quercetin, kaempferol, ECG, and EGCG. These were shown to inhibit ATP-induced YO-PRO-1 uptake into HEK-hP2X7 cells; however, we also showed that all four flavonoids demonstrated significant assay interference using a cell-free DNA YO-PRO-1 fluorescence test. One plant extract, Dioscorea nipponica, demonstrating positive modulator activity was investigated, and dioscin was identified as a glycoside with PAM activity in ATP-induced YO-PRO-1 uptake assay and whole-cell patch-clamp recordings. However, membrane permeabilisation was observed following application > 10 min limiting the use of dioscin as a pharmacological tool. This work describes a useful workflow with multiple assays for the identification of novel allosteric modulators for human P2X7.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"365-379"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with periodontal disease demonstrates changes in purinergic and inflammatory markers in PBMCs, serum and saliva.","authors":"Silviane Cunico Carneiro Füchter, Bárbara Stolarski, Daiane Manica, Eduardo Ottobelli Chielle, Débora Tavares de Resende E Silva, Sarah Franco Vieira de Oliveira Maciel","doi":"10.1007/s11302-025-10082-x","DOIUrl":"https://doi.org/10.1007/s11302-025-10082-x","url":null,"abstract":"<p><p>Periodontal disease (PD) is characterized by the presence of a chronic inflammatory process, due to the accumulation of bacterial biofilm and the host's response to these pathogens, resulting in the destruction of the supporting tissues of dental structures. Studies have revealed that components of the purinergic system and inflammation are related to the development and progression of PD. The objective was to evaluate periodontal clinical parameters, modulation of the purinergic system and inflammation in patients with PD, compared to individuals without the disease. This is a cross-sectional study with 25 healthy individuals (CT group) and 57 individuals with PD, where blood and saliva collection and isolation of blood components were carried out. The results showed that there was a significant reduction in the hydrolysis of adenosine triphosphate (ATP; p < 0.0001), adenosine diphosphate (ADP; p < 0.05) and adenosine monophosphate (AMP; p < 0.01) in peripheral blood mononuclear cells (PBMCs) from individuals in the PD group compared to the CT group, indicating that individuals with PD showed reduced NTPDase 1 and Ecto-5'-nucleotidase activity. Adenosine deaminase activity in saliva (p < 0.0001) and serum p < 0.05) from individuals with PD were significantly higher compared to the CT group. Extracellular ATP and the serum concentration of C-Reactive Protein showed a statistically significant increase in the PD group ((p < 0.0001 and p < 0.001, respectively). Therefore, the enzymes of the purinergic system are present in the modulation of PD, leading individuals affected by the disease to a pro-inflammatory state, hindering the action of the immune system and increasing serum markers of inflammation.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of nanoflubendazole and purinergic signaling modulation in overcoming neuroblastoma chemoresistance.","authors":"Renata Siqueira de Mello, Carolina Adriane Bento, Rafael de Oliveira Faria, Vanessa Fernandes Arnaud-Sampaio, Henning Ulrich, Mariana Yasue Saito Miyagi, Gabriel Lima Barros de Araujo, Claudiana Lameu","doi":"10.1007/s11302-025-10078-7","DOIUrl":"https://doi.org/10.1007/s11302-025-10078-7","url":null,"abstract":"<p><p>Neuroblastoma is a pediatric tumor accounting for approximately 8% of childhood cancers and is associated with high mortality rates among children aged 1 to 5 years. Standard treatments often fall short, leading to recurrence and metastasis due to the development of chemoresistance. A promising approach to address this challenge involves targeting purinergic signaling pathways and drug repurposing. The combination of flubendazole in nanoformulation and vincristine exhibited synergistic effects in ACN cells, enhancing treatment efficacy. Vincristine combined with the P2X7 receptor antagonist Brilliant Blue-G showed antagonistic effects, and interactions between nanoFBZ and Brilliant Blue-G were dose-dependent. Furthermore, ACN cells exposed to 213 nM of vincristine weekly for three weeks resulted in vincristine-resistant cells with significantly higher resistance (IC₅₀ approximately 300 times greater) compared to parental cells. P2Y₂ receptor expression was augmented in vincristine-resistant cells, particularly after treatment with nanoFBZ and Brilliant Blue-G, while adenosine A1, A2B, and P2Y₆ receptor expression levels decreased. P2X7 receptor expression was also reduced in vincristine-resistant cells treated with nanoFBZ. P2X7 receptor agonism and P2Y₂ receptor blockade slightly elevated resistance. In conclusion, this study suggests that combining nanoFBZ with vincristine chemotherapy may offer a promising strategy for improving the treatment efficacy of neuroblastoma. The synergy between nanoFBZ and vincristine enhanced therapeutic outcomes, and P2X7 receptor antagonism further reduced neuroblastoma cell viability.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A step-by-step protocol based on data mining to explore purinergic signaling in glioblastoma.","authors":"Martina Bedeschi, Ankita Agrawal, Elena Adinolfi, Anna Tesei, Valerie Vouret-Craviari","doi":"10.1007/s11302-025-10080-z","DOIUrl":"https://doi.org/10.1007/s11302-025-10080-z","url":null,"abstract":"<p><p>Over the past few years, transcriptomics has emerged as a pillar for modern scientific research, enabling the comprehensive profiling of gene expression. The availability of large-scale public datasets, such as NCBI Gene Expression Omnibus, International Cancer Genome Consortium, and The Cancer Genome Atlas, has significantly boosted many scientific discoveries. However, to analyze and interpret these vast datasets, sophisticated bioinformatic tools are often necessary. Phantasus is a user-friendly web application designed to streamline gene expression analysis. By integrating data loading, normalization, filtering, enrichment pathways analysis, and principal component analysis, Phantasus enables researchers to promptly investigate and evaluate complex gene expression patterns. This tool simplifies the identification of differentially expressed genes and the discovery of novel biological insights. Here, we demonstrate how Phantasus can be utilized for gene expression analysis in glioblastoma (GBM), the most common primary malignant brain tumour in adults. Specifically, we focus on the role of purinergic signaling, with particular emphasis on the P2RX7 mRNA coding for the P2X7 receptor (P2RX7). To illustrate our proposal, we analyzed the expression of genes related to purinergic signaling in GBM patients stratified by high and low levels of P2RX7 expression. By harnessing Phantasus, researchers can further explore and navigate the nuances of gene regulation and its impact on human health and diseases.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage P2Y₆ receptor signalling as a key mediator and therapeutic target in atherosclerosis.","authors":"Aida Collado, Zhichao Zhou","doi":"10.1007/s11302-025-10083-w","DOIUrl":"https://doi.org/10.1007/s11302-025-10083-w","url":null,"abstract":"<p><p>Atherosclerosis, a chronic inflammatory disease driven by lipid deposition and immune cell activation, remains a leading cause of cardiovascular morbidity and mortality. Emerging evidence highlights the role of purinergic signalling in atherogenesis, particularly the P2Y₆ receptor in macrophages [1]. Using RNA sequencing, proteomics, expression and functional validation in cells, mouse models and human materials, this study provides comprehensive mechanistic insights into how macrophage P2Y₆ receptors contribute to foam cell formation and plaque development through the phospholipase Cβ (PLCβ)/store-operated Ca²⁺ entry/calreticulin/scavenger receptor A (SR-A) pathway. Furthermore, the study identifies thiamine pyrophosphate (TPP) as a potent P2Y₆ receptor antagonist, effectively inhibiting foam cell formation and reducing plaque burden in atherosclerotic mice, without inducing toxicity. These findings establish P2Y₆ receptors as promising therapeutic targets in atherosclerosis and introduce TPP as a potential clinical candidate for intervention.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell-derived adenosine regulates fibroblast IL-6 formation via A_2B receptors in the infarcted heart.","authors":"Tong Jiao, Zhichao Zhou","doi":"10.1007/s11302-025-10081-y","DOIUrl":"https://doi.org/10.1007/s11302-025-10081-y","url":null,"abstract":"<p><p>Elevated interleukin-6 (IL-6) levels are linked to an increased risk of cardiovascular mortality in myocardial infarction (MI). Targeting IL-6 and its downstream signalling pathways represents a therapeutic strategy; however, its cellular sources and regulatory mechanisms of IL-6 remain incompletely understood. In this study, Alter and colleagues investigated the primary cell type that produces IL-6 in post-MI murine heart and the role of purinergic signalling in regulating IL-6 formation. Using cellular and mouse models, the authors identified cardiac fibroblasts as the predominant source of IL-6. Further analysis revealed that the IL-6 formation in cardiac fibroblasts is regulated by adenosine A_2B receptors. Of further importance, they elucidated that T cells highly express CD73, leading to significant adenosine formation, which in turn enhances IL-6 production via Gq activation in cardiac fibroblasts following MI. These findings reveal a dynamic interplay between immune cells and fibroblasts in shaping the post-MI inflammatory response. This study suggests the adenosine-A_2B receptor-IL6 axis as a potential therapeutic target to mitigate inflammation and improve cardiomyocytes salvage in MI.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}