Article
Multidisciplinary Sciences
Qu Deng, Reyaz Ur Rasool, Ronnie M. Russell, Ramakrishnan Natesan, Irfan A. Asangani
Summary: The study suggests a potential role of androgen in SARS-CoV-2 infection by regulating ACE2 and TMPRSS2 transcription. Camostat, a TMPRSS2 inhibitor, blocks the cleavage of SARS-CoV-2 Spike protein, providing evidence of TMPRSS2's direct role in viral fusion to host cells. Androgen-deprivation, anti-androgens, or camostat attenuate SARS-CoV-2 cellular entry, highlighting the importance of TMPRSS2 inhibitors and androgen-deprivation therapy in preventing COVID-19 progression.
Review
Immunology
Harry Kleanthous, Judith Maxwell Silverman, Karen W. Makar, In-Kyu Yoon, Nicholas Jackson, David W. Vaughn
Summary: Global vaccination against COVID-19 poses significant challenges in science, logistics, and ethics, with a need for safe, effective, high-volume, affordable vaccines; RBD-based vaccines may be a solution for filling the gap in global demand, offering high production potential and cost-effectiveness as a sole vaccine immunogen.
Review
Biochemistry & Molecular Biology
Kaitryn E. Ronning, Paul-Alexandre Dechelle-Marquet, Yueshen Che, Xavier Guillonneau, Florian Sennlaub, Cecile Delarasse
Summary: Alzheimer's disease (AD) is characterized by impaired memory, amyloid plaques, and neurofibrillary tangles. The release of ATP and the upregulation of P2X7 receptor in AD patients contribute to the disease's pathological processes. Various pathways involving P2X7 have been identified to influence the development of AD, including modulation of Aβ plaques, Tau protein lesions, and inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Alejandro Duran-Mendez, Alma Delia Aguilar-Arroyo, Emiliano Vivanco-Gomez, Eduardo Nieto-Ortega, Daniela Perez-Ortega, Cristian Jimenez-Perez, Karla Y. Hernandez-Skewes, Guillermo Montiel-Bravo, Oscar J. Roque-Reyes, Fernanda Romero-Lechuga, Diana Medina-Santos, Perla Oriana-Roman, Jorge Rafael Flores-Hernandez, Juan Daniel Mendez-Coca, Daniela Montano-Olmos, Karla Cecilia Farfan-Lazos, Miranda Tobon-Cubillos, America Viveros-Hernandez, Fernando Sevilla-Castillo, Angel Raul Hernandez-Romero, Shannat Ortega-Rodriguez, Aldo Christiaan Jardinez-Vera, Maria Antonieta Solis-Gonzalez, Antonio Ramos de la Medina, Laura Martinez Perez-Maldonado, Elizabeth Lagunes-Lara, Miguel Cova-Bonilla, Alberto N. Peon
Summary: The study found that tocilizumab significantly reduced the respiratory support requirements and inflammatory markers of all COVID-19 patients, but only reduced mortality significantly when administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients.
SCIENTIFIC REPORTS
(2021)
Review
Engineering, Biomedical
Sanika Suvarnapathaki, Divya Chauhan, Angelina Nguyen, Murugan Ramalingam, Gulden Camci-Unal
Summary: This review discusses the key therapeutic approaches targeting the ACE2 receptor and highlights its advantages compared to other methods in the treatment of COVID-19.
ANNALS OF BIOMEDICAL ENGINEERING
(2022)
Article
Medicine, General & Internal
T. Avni, L. Leibovici, I Cohen, A. Atamna, D. Guz, M. Paul, A. Gafter-Gvili, D. Yahav
Summary: Interleukin-6 inhibitor tocilizumab reduces 28-30 days all-cause mortality, mechanical ventilation risk, ICU admission rate, and superinfection risk in COVID-19 patients. However, no mortality benefit was found in critically ill patients and those who were predominantly treated with steroids. Further research is needed to determine sub-groups that benefit most and the optimal timing of TCZ administration in severe COVID-19.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2021)
Review
Virology
Soumya Sarkar, Puneet Khanna, Kapil D. Soni
Summary: Studies on the impact of systemic glucocorticoids in COVID-19 patients showed no significant reduction in mortality, duration of hospital stay, or period of viral shedding. The results are heterogeneous and further randomized controlled trials are needed to confirm the effectiveness of systemic steroid therapy in COVID-19 patients.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Medicine, Research & Experimental
Riffat Mehboob
Summary: The COVID-19 pandemic requires urgent exploration of treatment strategies. This article proposes the potential use of Aprepitant in treating COVID-19 infection and highlights the importance of SP and NK-1R in drug development.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Jitendra Subhash Rane, Preeti Pandey, Aroni Chatterjee, Rajni Khan, Abhijeet Kumar, Amresh Prakash, Shashikant Ray
Summary: The global human population is currently dealing with the horrific impact of the COVID-19 pandemic, and research targeting the spike glycoprotein of the virus for drug development holds significant therapeutic potential in combatting infection. This study used computational techniques to identify potential inhibitors that disrupt the interaction between the spike glycoprotein and the hACE2 receptor, providing a promising avenue for future antiviral drug development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Medicine, General & Internal
Peter W. Horby, Martin J. Landray
Summary: Tocilizumab improved survival and other clinical outcomes in hospitalized COVID-19 patients with hypoxia and systemic inflammation, regardless of the level of respiratory support, and provided additional benefits on top of systemic corticosteroid therapy.
Article
Immunology
Gabriel Dagotto, John D. Ventura, David R. Martinez, Tochi Anioke, Benjamin S. Chung, Mazuba Siamatu, Julia Barrett, Jessica Miller, Alexandra Schafer, Jingyou Yu, Lisa H. Tostanoski, Kshitij Wagh, Ralph S. Baric, Bette Korber, Dan H. Barouch
Summary: This study investigates the potential utility of a T-cell vaccine strategy targeting conserved regions of the sarbecovirus proteome. Results show that vaccine-elicited T-cell responses to highly conserved regions can reduce viral loads following challenge with SARS-CoV-2, indicating the potential usefulness of T-cell targeting for a pan-sarbecovirus vaccine.
Article
Multidisciplinary Sciences
Antonio Julia, Irene Bonafonte-Pardas, Antonio Gomez, Maria Lopez-Lasanta, Mireia Lopez-Corbeto, Sergio H. Martinez-Mateu, Jordi Llados, Ivan Rodriguez-Nunez, Richard M. Myers, Sara Marsal
Summary: The study proposed that blocking the CD80/86 signaling pathway could be an effective therapeutic approach to mitigate the excessive immune response in severe COVID-19, with abatacept showing potential to counteract the proinflammatory processes induced by the virus. The results suggest a significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept, supporting its candidacy as a preventive treatment for severe COVID-19.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Wenjiang Zheng, Xiufang Huang, Yanni Lai, Xiaohong Liu, Yong Jiang, Shaofeng Zhan
Summary: The study suggests that glycyrrhizic acid may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, as well as its ability to activate the immune system. Targeted therapy for specific pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.
FRONTIERS IN PHARMACOLOGY
(2021)
Editorial Material
Virology
Yisa Chen, Yiying Xue, Jing Yang
Summary: COVID-19 is caused by the SARS-CoV-2 virus, which has rapidly evolved and become a global health threat. Vaccines are effective, but the virus's mutations require additional therapeutic strategies. Therefore, it is important to identify and test potential therapeutic targets that are highly conserved among multiple coronaviruses for clinical drug development to combat SARS-CoV-2.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Fernanda Sumika Hojo de Souza, Natalia Satchiko Hojo-Souza, Ben Deivide de Oliveira Batista, Cristiano Maciel da Silva, Daniel Ludovico Guidoni
Summary: This study analyzed the characteristics and mortality risk factors of hospitalized Brazilian COVID-19 patients, revealing a higher hospitalization rate among males and older patients, as well as a higher mortality rate among patients with cardiac disease, diabetes, and requiring invasive mechanical ventilation. The analysis also concluded that the disease outcome is influenced by multiple factors and disproportionately affects different population segments.
Article
Cell Biology
Michele Zanoni, Alba Clara Sarti, Alice Zamagni, Michela Cortesi, Sara Pignatta, Chiara Arienti, Michela Tebaldi, Anna Sarnelli, Antonino Romeo, Daniela Bartolini, Luigino Tosatto, Elena Adinolfi, Anna Tesei, Francesco Di Virgilio
Summary: Glioblastoma (GBM) is the most lethal brain tumor in adults and is often treated with radiation and temozolomide. However, relapse is common. This study found that after radiation treatment, ATP is released into the tumor microenvironment, activating P2X7 receptors. Different GBM cells vary in P2X7 isoform expression and sensitivity to extracellular ATP. Radiation treatment causes changes in P2X7 isoform expression, leading to cell death and overexpression of stemness and senescence markers. Blocking P2X7 receptors during post-irradiation recovery enhances radiation-dependent cytotoxicity. These findings suggest that P2X7 receptor isoforms play a role in radiation resistance in GBM cells.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Valentina Vultaggio-Poma, Simonetta Falzoni, Paola Chiozzi, Alba Clara Sarti, Elena Adinolfi, Anna Lisa Giuliani, Alejandro Sanchez-Melgar, Paola Boldrini, Michele Zanoni, Anna Tesei, Paolo Pinton, Francesco Di Virgilio
Summary: Nutrient deprivation promotes the release of extracellular ATP and leads to the accumulation of ATP-laden microparticles and naked mitochondria in the tumor microenvironment.
Article
Biochemistry & Molecular Biology
Valentina Vultaggio-Poma, Simonetta Falzoni, Giada Salvi, Anna Lisa Giuliani, Francesco Di Virgilio
Summary: Nucleotides play crucial roles in cell biology, particularly in the nervous system and disease pathogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Rocio Edith Garcia-Jacobo, Leticia Scussel Bergamin, Valentina Vultaggio-Poma, Maria Luiza Thorstenberg, Mario Tarantini, Mariana Haydee Garcia-Hernandez, Francesco Di Virgilio
Summary: Adenosine triphosphate (ATP) plays a crucial role as an energy intermediate in cellular metabolism and a signaling molecule outside of cells. Dysregulation of extracellular ATP (eATP) homeostasis is implicated in chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). Increased eATP levels in T2DM contribute to inflammation and apoptosis of pancreatic beta-cells, worsening hyperglycemia.
Article
Biochemistry & Molecular Biology
Sonia Missiroli, Mariasole Perrone, Roberta Gafa, Francesco Nicoli, Massimo Bonora, Giampaolo Morciano, Caterina Boncompagni, Saverio Marchi, Magdalena Lebiedzinska-Arciszewska, Bianca Vezzani, Giovanni Lanza, Franz Kricek, Alessandro Borghi, Francesco Fiorica, Keisuke Ito, Mariusz R. Wieckowski, Francesco Di Virgilio, Luigi Abelli, Paolo Pinton, Carlotta Giorgi
Summary: Uncontrolled inflammatory response from the tumor microenvironment significantly contributes to cancer progression. A trimeric complex at the mitochondria-associated membranes, involving P2X7 receptor-NLRP3 inflammasome interaction, is regulated by the tumor suppressor PML. Downregulation of PML leads to an exacerbated immune response and boosted tumor growth. Mislocalization of PML results in uncontrolled NLRP3 activation and cytokine production, fueling cancer development and worsening prognosis in various human cancers. Mechanistic insights into the PML-P2X7R-NLRP3 axis provide new opportunities for targeted therapeutic approaches in human carcinogenesis.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Neurosciences
Francesco Di Virgilio, Valentina Vultaggio-Poma, Simonetta Falzoni, Anna Lisa Giuliani
Summary: Nucleotides, especially extracellular ATP (eATP), play a crucial role in inter-species extracellular signaling. Different organisms have evolved sensors with varying affinity and selectivity for eATP, resulting in a highly flexible signaling system. In mammalian evolution, the control of intracellular ATP and eATP homeostasis is closely linked to that of Ca2+. Specific plasma membrane receptors, known as P2 receptors (P2Rs), sense eATP with various degrees of affinity and selectivity, adding to the plasticity of the system. The central nervous system (CNS) is a privileged site for purinergic signaling, with all brain cell types expressing P2Rs. Evidence suggests that eATP not only participates in synaptic transmission but also plays a crucial homeostatic role in brain cell responses. Modulating eATP concentration in the CNS may hold promise for the treatment of neuroinflammation.
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Francesco Di Virgilio, Valentina Vultaggio-Poma, Simonetta Falzoni, Anna Lisa Giuliani
Summary: The discovery of the P2X7 receptor in immune cells raised hopes for the development of anti-inflammatory drugs, but initial clinical trials were disappointing, reducing industry interest in P2X7-targeted therapies. However, recent findings have revitalized the use of P2X7 in diagnostic medicine, with new radioligands proving reliable for neuroinflammation diagnosis and P2X7 measurement in blood suggesting its potential as an inflammation marker. This review provides an overview of these novel developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Valentina Vultaggio-Poma, Leticia Scussel Bergamin, Simonetta Falzoni, Mario Tarantini, Anna Lisa Giuliani, Dorianna Sandona, Patrizia Polverino De Laureto, Francesco Di Virgilio
Summary: ATP is released as a messenger in various physiological conditions and is present in small amounts in healthy tissues and blood. Fetal bovine sera commonly used in cell culture systems contain ATP in a range of 300-1300 pmol/L. This ATP is associated with albumin and microparticle/microvesicle fraction, and its presence affects in vitro cell responses. These findings highlight the varying levels of extracellular ATP and purinergic stimulation experienced by cells growing in serum-supplemented media.
PURINERGIC SIGNALLING
(2023)
Article
Immunology
Valentina Vultaggio-Poma, Juana Maria Sanz, Andrea Amico, Alessandra Violi, Sara Ghisellini, Stefano Pizzicotti, Angelina Passaro, Alberto Papi, Marco Libanore, Francesco Di Virgilio, Anna Lisa Giuliani
Summary: This study found that the levels of sP2X7R in the blood of patients with COVID-19 were increased and correlated with adverse clinical outcomes. sP2X7R may be a useful marker of disease progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Angelo Di Vincenzo, Marika Crescenzi, Marnie Granzotto, Sara Zancaner, Roberto Fabris, Mirto Foletto, Luca Prevedello, Federico Capone, Roberto Vettor, Marco Rossato
Summary: This study investigated the basal INSL5 plasma levels in morbidly obese subjects before and after laparoscopic sleeve gastrectomy. The results showed that obese subjects had elevated INSL5 levels before surgery, which were positively correlated with BMI, fat mass, and leptin levels. After surgery, INSL5 levels significantly decreased, and there was no expression of the INSL5 gene in human adipose tissue. These findings suggest that the reduction of INSL5 levels after bariatric surgery may contribute to appetite reduction.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Angelo Di Vincenzo, Marnie Granzotto, Marika Crescenzi, Camilla Costa, Stefano Piaserico, Vincenzo Vindigni, Roberto Vettor, Marco Rossato
Summary: Psoriasis is a chronic inflammatory disease characterized by skin lesions. It is more prevalent and severe in obese individuals. Insulin stimulates the production of IL-23 by human adipocytes, which may explain the association between psoriasis and obesity.
DIABETES METABOLIC SYNDROME AND OBESITY
(2023)
Article
Cell Biology
Letizia Penolazzi, Maria Pina Notarangelo, Elisabetta Lambertini, Valentina Vultaggio-Poma, Mario Tarantini, Francesco Di Virgilio, Roberta Piva
Summary: The main objective of this study was to determine the presence of the P2X7 receptor in human skeletal system cells. P2X7 receptor was found to be localized not only in the plasma membrane and cytoplasm, but also in the nucleus and mitochondria of osteoblasts, chondrocytes, and intervertebral disc cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Angelo Di Vincenzo, Marnie Granzotto, Marika Crescenzi, Vincenzo Vindigni, Roberto Vettor, Marco Rossato
Summary: In this study, the effects of sex steroids on the expression of inflammatory mediators in human-derived adipocytes were evaluated. The results showed that non-aromatizable androgen DHT and the aromatase inhibitor anastrozole in combination with testosterone significantly enhanced the expression of inflammatory cytokines induced by LPS. These results confirm the involvement of sex hormones in adipose tissue inflammation and suggest a specific role for non-aromatizable androgens as amplificatory sex hormones of the inflammatory response.
Article
Microbiology
Carla Enrica Gallenga, Martina Maritati, Marco Mura, Francesco Di Virgilio, Pio Conti, Carlo Contini
Summary: Follicular conjunctivitis has become a relevant symptom of SARS-CoV-2. The conjunctiva reacts to viral antigens, forming B cell follicles with T cells and NK cells on its surface. The NLRP3 inflammasome releases pro-inflammatory factors, leading to congestion and inflammation in follicular conjunctivitis, even in asymptomatic patients.
