Review
Cell Biology
Elena De Marchi, Anna Pegoraro, Elena Adinolfi
Summary: The P2X7 receptor, known for its role in immune responses, has emerged as a critical factor in promoting cancer. Studies have shown a correlation between P2X7 alterations and lymphoproliferative and myeloproliferative diseases. Recent research suggests that P2X7 and its genetic variants could be new biomarkers in hematological malignancies, and that both P2X7 antagonists and agonists could be potential therapeutic tools.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Fabio Grassi, Benedetta De Ponte Conti
Summary: eATP, as a danger-associated molecular pattern, plays a role in immune response by stimulating P2 receptors. However, its impact in the tumor microenvironment is complex and not well-established.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Federico Cevoli, Benoit Arnould, Francisco Andres Peralta, Thomas Grutter
Summary: This comprehensive review focuses on ATP-gated P2X7 receptors, specifically examining the intriguing phenomena of macropore formation and current facilitation. Macropores are large pores in the cell membrane that allow the passage of large molecules, and their precise mechanisms remain poorly understood. Current facilitation refers to the progressive increase in current amplitude and activation kinetics observed with prolonged or repetitive exposure to ATP. The article presents an in-depth overview of these processes, highlighting new findings and proposing mechanistic models for further understanding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Xiaodi Zhu, Qianqian Li, Wei Song, Xiaoxiang Peng, Ronglan Zhao
Summary: The upregulation of P2X7 receptor in breast cancer can promote tumor cell invasion and migration, and new P2X7 receptor inhibitors show potential in inhibiting this process.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Cell Biology
Elena De Marchi, Anna Pegoraro, Roberta Turiello, Francesco Di Virgilio, Silvana Morello, Elena Adinolfi
Summary: The study reveals that in the absence of host P2X7R, A2AR promotes tumor growth through immune suppression and neovascularization. This highlights the crucial interaction between P2X7R and A2AR in the tumor microenvironment, providing insights for the development of new combination therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Shi-qi Hu, Jia-ling Hu, Fei-long Zou, Ji-peng Liu, Hong-liang Luo, Dong-xia Hu, Li-dong Wu, Wen-jun Zhang
Summary: Different studies have confirmed the crucial role of P2X7 receptor-mediated inflammatory mediators in the development of pain. By mediating the release of inflammatory mediators, activation of P2X7 receptors can induce pain. This paper discusses the pathological mechanism of P2X7 receptor-mediated inflammation and pain, focusing on the internal relationship between P2X7 receptor and pain. The effects of some antagonists on pain relief by inhibiting the activities of P2X7 receptors are also described.
BRAIN RESEARCH BULLETIN
(2022)
Review
Biochemistry & Molecular Biology
Sophie K. F. De Salis, Lanxin Li, Zheng Chen, Kam Wa Lam, Kristen K. Skarratt, Thomas Balle, Stephen J. Fuller
Summary: This review summarizes recent advances in understanding the structure and function of alternative spliced (AS) P2X7 isoforms, as well as their associations with cancer and potential role in modulating the inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Raghava Potula, Taylor A. Gentile, Joseph J. Meissler, Aryan Shekarabi, Sonita Wiah, Daniel J. Farkas, Saadet Inan, Toby K. Eisenstein, Scott M. Rawls
Summary: P2X7 receptors play a key role in the rewarding and locomotor-stimulant effects of methamphetamine (METH), potentially through modulation of the cytokine IL-17A.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Biochemistry & Molecular Biology
Beatriz Gil, Jonathon Smith, Yong Tang, Peter Illes, Tobias Engel
Summary: Epilepsy is a common chronic disease with difficult treatment, and P2X7R antagonists may serve as a novel therapeutic strategy for epilepsy and its associated comorbidities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Caterina Di Lauro, Carolina Bianchi, Alvaro Sebastian-Serrano, Lucia Soria-Tobar, Beatriz Alvarez-Castelao, Annette Nicke, Miguel Diaz-Hernandez
Summary: The upregulation of P2X7 in patients with tauopathies and a tauopathy mouse model suggests its involvement in neuroinflammation and potential as a target for treating tauopathies. Pharmacological or genetic blockade of P2X7 in P301S mice reversed microglial activation, reduced intraneuronal phosphorylated Tau levels, and improved cellular survival, motor and memory deficits, and anxiolytic profile. Conversely, overexpression of P2X7 worsened Tau-induced toxicity and exacerbated motor and memory deficits in P301S mice.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Immunology
Robson Xavier Faria
Summary: The inflammatory focus and tumor microenvironment share similarities in terms of immune cells and macrophages. Under simulated hypoxic conditions, the function of P2X7 receptors is enhanced, along with increased HIF-1 alpha levels and suppressed HIF-1 alpha antagonists. Additionally, the intracellular P2X7 receptor regulator PIP2 is activated in simulated hypoxic conditions.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Alberto Baroja-Mazo, Alejandro Penin-Franch, Fernando Lucas-Ruiz, Carlos De Torre-Minguela, Cristina Alarcon-Vila, Trinidad Hernandez-Caselles, Pablo Pelegrin
Summary: This study found that activation of the purinergic receptor P2X7 by extracellular ATP impairs the antitumor activity of NK cells, leading to an anergic state and reduced IFN-gamma secretion. This effect can be reversed by specific P2X7 antagonists and pretreatment with IL-2 or IL-15. Knockdown of the P2rx7 gene improved the control of tumor size by NK cells. These findings suggest that P2X7 activation plays a role in NK cell-mediated antitumor effectiveness, and modifying NK cells to lack P2X7 may enhance their antitumor capacity.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Judith E. Lutton, Helena L. E. Coker, Peggy Paschke, Christopher J. Munn, Jason S. King, Till Bretschneider, Robert R. Kay
Summary: This study reveals the underlying principles of macropinocytic cup formation and closure in Dictyostelium amoebae using light-sheet microscopy. Cups are formed by recruiting PIP3 domains and a specialized F-actin scaffold, and they close through inward or outward actin polymerization and membrane stretching and delamination when cup expansion stalls. This research is important for understanding intracellular fluid engulfment processes.
Review
Biochemistry & Molecular Biology
Elena Adinolfi, Elena De Marchi, Marianna Grignolo, Bartosz Szymczak, Anna Pegoraro
Summary: The article provides an overview of the role of P2X7 purinergic receptor in the tumor microenvironment, including its activities in cancer proliferation, dissemination, and its interaction with immune and endothelial cells. The article also analyzes the release of microvesicles and exosomes, the content within them, and the impact of P2X7 activation on metastatic spread and niche conditioning. Furthermore, the article explores the emerging role of P2X7 in the adenosinergic axis and its influence on antitumor therapy responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Paula Mut-Arbona, Lumei Huang, Maria Baranyi, Pal Tod, Andras Iring, Francesco Calzaferri, Cristobal de los Rios, Beata Sperlagh
Summary: Extracellular ATP acts as a danger molecule through purinergic receptors, particularly the ionotropic P2X7 receptor (P2X7R), in pathological conditions. The specific role of P2X7R in regulating neuronal outgrowth during early embryonic stages was investigated. The study showed that genetic deficiency or pharmacological blockade of P2X7R leads to deficits in dendritic branching under physiological conditions.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Materials Science, Biomaterials
Akhilesh Rai, Rafaela Ferrao, Paulo Palma, Tatiana Patricio, Paula Parreira, Elsa Anes, Chiara Tonda-Turo, M. Cristina L. Martins, Nuno Alves, Lino Ferreira
Summary: This review discusses the therapeutic potential of AMP-based materials for the treatment of various diseases. Compared to bare AMPs, AMP-based materials can overcome the limitations of short residence time in the bloodstream and susceptibility to environmental factors, providing better therapeutic efficacy. In addition to treating microbial infections, AMP-based materials also have applications in skin/bone regeneration, prevention of implant-associated infections, detection/imaging of bacteria, cancer therapy, and gene delivery.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Review
Immunology
Elsa Anes, David Pires, Manoj Mandal, Jose Miguel Azevedo-Pereira
Summary: This review highlights the spatial localization of cathepsins and their implications in immune activation and resolution pathways during infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Francisco Olivenca, Alexandra Nunes, Rita Macedo, David Pires, Catia Silveiro, Elsa Anes, Maria Miragaia, Joao Paulo Gomes, Maria Joao Catalao
Summary: This study reveals the differential phenotypes of M. tuberculosis to beta-lactam antibiotics and finds that highly drug-resistant sublineages are more susceptible to beta-lactams. This provides an important strategy for directing beta-lactams to treat specific sublineages of M. tuberculosis infections.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Diana Morais, Luis Tanoeiro, Andreia T. Marques, Tiago Goncalves, Aida Duarte, Antonio Pedro Alves Matos, Joana S. Vital, Maria Eugenia Meirinhos Cruz, Manuela Colla Carvalheiro, Elsa Anes, Jorge M. B. Vitor, Maria Manuela Gaspar, Filipa F. Vale
Summary: Pseudomonas aeruginosa is a major threat to human and animal health due to its resistance to multiple antibiotics. Encapsulation of lysins in liposomes can be an effective strategy against this Gram-negative bacterium. This study identified and analyzed lysins from prophages in P. aeruginosa genomes and successfully encapsulated them in liposomes, resulting in a significant reduction in cell viability and lysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Joao P. Pais, Marta Magalhaes, Olha Antoniuk, Ivete Barbosa, Raquel Freire, David Pires, Emilia Valente, Bernard Testa, Elsa Anes, Luis Constantino
Summary: One interesting approach to fight tuberculosis is the use of prodrugs with improved biological activities. The study synthesized a library of benzoates with different electron withdrawing groups and tested their activity against mycobacteria. The results showed that the phenyl and hexyl esters presented higher activity than the corresponding free acids, with the dinitrobenzoates showing very interesting antitubercular activity.
Article
Biochemistry & Molecular Biology
David Pires, Manoj Mandal, Jacinta Pinho, Maria Joao Catalao, Antonio Jose Almeida, Jose Miguel Azevedo-Pereira, Maria Manuela Gaspar, Elsa Anes
Summary: Mycobacterium tuberculosis establishes chronic colonization in lung macrophages through controlled replication, leading to latent infection. Manipulation of endolysosomal enzymes, cathepsins, by the pathogen is crucial for intracellular survival. Liposomal delivery of saquinavir, a protease inhibitor, enhances its internalization in macrophages and exhibits significant intracellular killing effects on drug-susceptible and drug-resistant Mycobacterium tuberculosis strains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Filipa Santos, David Pires, Elsa Anes, Ana Rita C. Duarte
Summary: This study evaluated the stability and antibacterial activity of therapeutic liquid formulations prepared with anti-tuberculosis drugs. The results showed that these mixtures have antibacterial effects against drug-susceptible Mycobacterium tuberculosis strains, with the mixtures incorporating ethambutol showing particularly prominent effects. The findings suggest the potential for further research and evaluation of clinical applicability.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Virology
Marta Calado, David Pires, Carolina Conceicao, Rita Ferreira, Quirina Santos-Costa, Elsa Anes, Jose Miguel Azevedo-Pereira
Summary: Macrophages and dendritic cells are important for the spread of HIV to CD4+ T lymphocytes during acute infection and constitute a persistently infected reservoir during chronic infection. Cell-to-cell contact triggers the production of infectious viral particles, contributing to viral replication. The phenotypic characteristics of HIV isolates do not correlate with their spread or the difference between HIV-1 and HIV-2 in terms of cis- or trans-infection. Understanding the cell-to-cell spread of HIV is critical for developing new therapeutic and vaccine approaches.
Article
Immunology
Catia Silveiro, Mariana Marques, Francisco Olivenca, David Pires, Diana Mortinho, Alexandra Nunes, Madalena Pimentel, Elsa Anes, Maria Joao Catalao
Summary: The study investigates the impact of the lack of effective therapeutics on multi-drug resistant strains of Mycobacterium tuberculosis. It identifies the essentiality of peptidoglycan modifications and their effects on resistance and host-pathogen interactions. Depletion of these modifications enhances the killing of bacteria by macrophages and shows potential as therapeutic targets against TB.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Elsa Anes, David Pires, Manoj Mandal, Jose Miguel Azevedo-Pereira
Summary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has developed a unique strategy to establish infection and transmission by utilizing host macrophages to establish intracellular niches and induce long-term latency in granulomas. It eventually escapes from macrophages through necrotic cell death and triggers a strong inflammatory response, which is necessary for the progression from latency to active disease and transmission.
Article
Microbiology
Joao P. Pais, Olha Antoniuk, Raquel Freire, David Pires, Emilia Valente, Elsa Anes, Luis Constantino
Summary: In this study, a library of 72 derivatives of nitrobenzoic acid containing esters and thioesters of benzoates was synthesized and evaluated for their antimycobacterial activity against M. tuberculosis. The results showed that compounds with aromatic nitro substitutions, especially 3,5-dinitro esters, exhibited the most potent antimicrobial activity. Interestingly, the activity of the nitro derivatives was not correlated with their pKa values or hydrolysis rates. These findings suggest that the nitrobenzoate scaffold, particularly the 3,5-dinitrobenzoate scaffold, has the potential to serve as a promising scaffold for the development of novel antimycobacterial agents with improved activity.
Review
Microbiology
Jose Miguel Azevedo-Pereira, David Pires, Marta Calado, Manoj Mandal, Quirina Santos-Costa, Elsa Anes
Summary: Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) are responsible for millions of new infections annually, causing high morbidity and mortality globally. HIV increases the risk of tuberculosis (TB) development by a factor of 20, even in latently infected individuals, and controlled HIV infection on antiretroviral therapy (ART) still results in a fourfold increased risk of TB. Conversely, Mtb infection worsens HIV pathogenesis and accelerates AIDS progression. Understanding the reciprocal amplification of HIV/Mtb coinfection can aid in the development of therapeutic strategies for disease control, particularly in situations where vaccines or pathogen clearance are not readily available.
Article
Infectious Diseases
David Pires, Manoj Mandal, Ana I. Matos, Carina Peres, Maria Joao Catalao, Jose Miguel Azevedo-Pereira, Ronit Satchi-Fainaro, Helena F. Florindo, Elsa Anes
Summary: The golden age of antibiotics for tuberculosis in the 1950s has been overshadowed by the ongoing challenges in controlling the disease and the increasing global antibiotic resistance. Understanding the interactions between TB bacteria and their host can lead to the development of better therapeutics, such as vaccines and host-directed therapies. In this study, a potential nanomedicine based on chitosan (CS-DS) was developed to deliver siRNA targeting cystatin C to infected macrophages, resulting in improved immune responses and decreased intracellular survival of TB bacilli, including drug-resistant strains. These findings suggest the potential adjunctive use of CS-DS in TB therapy, either alone or in combination with antibiotics.
Review
Virology
Marta Calado, David Pires, Carolina Conceicao, Quirina Santos-Costa, Elsa Anes, Jose Miguel Azevedo-Pereira
Summary: Despite the success of antiretroviral therapy, the global HIV infection rate remains high, mainly through sexual transmission involving specific cells present on genital mucosa. Understanding how HIV interacts with these cells is crucial for developing prevention and control strategies. This review explores the manipulation of physiological roles of dendritic cells, macrophages, and CD4+ T lymphocytes by HIV in order to establish infection in a new human host. The interactions between HIV and these cells, including intercellular viral transfer mechanisms, are discussed.
REVIEWS IN MEDICAL VIROLOGY
(2023)
Article
Microbiology
Manoj Mandal, David Pires, Maria Joao Catalao, Jose Miguel Azevedo-Pereira, Elsa Anes
Summary: TB treatment heavily relies on outdated drugs and lacks an effective vaccine. Understanding the interaction between the host and the pathogen will lead to new therapeutic interventions for TB eradication. Targeting host factors like cathepsins, which manipulate Mycobacterium tuberculosis (Mtb) and impact its survival in macrophages, is a promising strategy. Silencing cystatin F, an upregulated inhibitor during Mtb infection, increases the proteolytic activity of cathepsins and impairs pathogen killing in macrophages. Targeting cystatin F could be a potential adjuvant therapy for TB, including multidrug-resistant and extensively drug-resistant cases.