Article
Immunology
Tamara S. Rodrigues, Camila C. S. Caetano, Keyla S. G. de Sa, Leticia Almeida, Amanda Becerra, Augusto Goncalves, Leticia de Sousa Lopes, Samuel Oliveira, Danielle P. A. Mascarenhas, Sabrina S. Batah, Bruna M. Silva, Giovanni F. Gomes, Ricardo Castro, Ronaldo B. Martins, Jonathan Avila, Fabiani G. Frantz, Thiago M. Cunha, Eurico Arruda, Fernando Q. Cunha, Helder Nakaya, Larissa D. Cunha, Alexandre T. Fabro, Paulo Louzada-Junior, Rene D. R. de Oliveira, Dario S. Zamboni
Summary: SARS-CoV-2 infection activates the NLRP3 inflammasome and leads to inflammation and severe COVID-19. Human caspase-4 (mouse caspase-11) is upregulated and activated by SARS-CoV-2, contributing to NLRP3 activation. In vivo studies using transgenic hACE2 humanized mice show that hACE2 Casp11(-/-) mice are protected from disease development, with reduced lung damage, clinical symptoms, and mortality. Analysis of human samples from fatal COVID-19 cases reveals the expression of CASP4 in patient lungs, which correlates with inflammasome components and inflammatory mediators. These findings suggest CASP4/11 as a potential target for therapeutic interventions in COVID-19.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Review
Immunology
Yuan-Yuan Yong, Li Zhang, Yu-Jiao Hu, Jian-Ming Wu, Lu Yan, Yi-Ru Pan, Yong Tang, Lu Yu, Betty Yuen-Kwan Law, Chong-Lin Yu, Jie Zhou, Mao Li, Da-Lian Qin, Xiao-Gang Zhou, An-Guo Wu
Summary: This article discusses autophagy regulation at different stages of COVID-19 and highlights the therapeutic potential of autophagy activators in inhibiting cytokine storms.
CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Pan Pan, Miaomiao Shen, Zhenyang Yu, Weiwei Ge, Keli Chen, Mingfu Tian, Feng Xiao, Zhenwei Wang, Jun Wang, Yaling Jia, Wenbiao Wang, Pin Wan, Jing Zhang, Weijie Chen, Zhiwei Lei, Xin Chen, Zhen Luo, Qiwei Zhang, Meng Xu, Geng Li, Yongkui Li, Jianguo Wu
Summary: This study reveals a unique mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation, leading to excessive inflammatory responses. The interaction between N protein and NLRP3 enhances the assembly of the NLRP3 inflammasome by facilitating binding with ASC.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Jianxiong Zeng, Xiaochun Xie, Xiao-Li Feng, Ling Xu, Jian-Bao Han, Dandan Yu, Qing-Cui Zou, Qianjin Liu, Xiaohong Li, Guanqin Ma, Ming-Hua Li, Yong-Gang Yao
Summary: The study found that the NLRP3 inflammasome plays a crucial role in the lungs during SARS-CoV-2 infection, and inhibiting this inflammasome can reduce the release of pro-inflammatory cytokines related to COVID-19 in cells and mice. Therefore, targeting the NLRP3 inflammasome could be a promising immune intervention against severe COVID-19 disease.
Review
Immunology
Jiayu Zhang, Xuejing Ma, Fuwei Liu, Deju Zhang, Jitao Ling, Zicheng Zhu, Yixuan Chen, Pingping Yang, Yanlin Yang, Xiao Liu, Jing Zhang, Jianping Liu, Peng Yu
Summary: 2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Severe cases of COVID-19 are associated with a cytokine storm, characterized by elevated levels of pro-inflammatory cytokines in the bloodstream. Recent studies have shown a higher severity of necrobiosis infection in diabetic patients, as well as higher morbidity and mortality in people with chronic metabolic diseases such as diabetes. Additionally, COVID-19 may result in hyperglycemia in infected individuals. This review explores the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19, and discusses the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, several promising targeted NLRP3 inflammatory vesicle inhibitors are proposed as a basis for clinical management of patients with diabetes combined with noncoronary pneumonia.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Hongliang Zhang, Yujie Tang, Jinhui Tao
Summary: The COVID-19 pandemic caused by SARS-CoV-2 infection poses a significant threat to human life and economic well-being globally, with male patients showing a higher probability of severe symptoms and mortality. The NLRP3 inflammasome likely plays a critical role in this process.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Allergy
Arinna Bertoni, Federica Penco, Hilaria Mollica, Paola Bocca, Ignazia Prigione, Anna Corcione, Davide Cangelosi, Francesca Schena, Genny Del Zotto, Adriana Amaro, Noemi Paladino, Emanuele Pontali, Marcello Feasi, Sara Signa, Marta Bustaffa, Roberta Caorsi, Serena Palmeri, Paola Contini, Raffaele De Palma, Ulrich Pfeffer, Paolo Uva, Anna Rubartelli, Marco Gattorno, Stefano Volpi
Summary: This study reveals the crucial role of IL-1 beta in driving inflammatory phenotypes in severe COVID-19 patients, whose maturation and secretion are regulated by inflammasomes. The findings suggest that targeting IL-1 beta could be an effective strategy for treating COVID-19 and provide a mechanistic explanation for the strong inflammatory manifestations associated with the disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Cell Biology
Aldo Bonaventura, Alessandra Vecchie, Lorenzo Dagna, Flavio Tangianu, Antonio Abbate, Francesco Dentali
Summary: SARS-CoV-2 can activate NLRP3 inflammasome, leading to an inflammatory response. Colchicine, as an anti-inflammatory drug, can block the activation of NLRP3 inflammasome and reduce the release of inflammatory cytokines. Some studies have shown that colchicine may have therapeutic effects on COVID-19. However, more research is needed to confirm these findings.
INFLAMMATION RESEARCH
(2022)
Article
Immunology
Deborah Lecuyer, Roberta Nardacci, Desiree Tannous, Emie Gutierrez-Mateyron, Aurelia Deva Nathan, Frederic Subra, Cristina Di Primio, Paola Quaranta, Vanessa Petit, Clemence Richetta, Ali Mostefa-Kara, Franca Del Nonno, Laura Falasca, Romain Marlin, Pauline Maisonnasse, Julia Delahousse, Juliette Pascaud, Eric Deprez, Marie Naigeon, Nathalie Chaput, Angelo Paci, Veronique Saada, David Ghez, Xavier Mariette, Mario Costa, Mauro Pistello, Awatef Allouch, Olivier Delelis, Mauro Piacentini, Roger Le Grand, Jean-Luc Perfettini
Summary: The purinergic receptor P2X7 and NLRP3 inflammasome are found to be cellular host factors required for SARS-CoV-2 infection, and their activation promotes viral replication and inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, General & Internal
Nicola Potere, Marco Giuseppe Del Buono, Roberto Caricchio, Paul C. Cremer, Alessandra Vecchie, Ettore Porreca, Daniela Dalla Gasperina, Francesco Dentali, Antonio Abbate, Aldo Bonaventura
Summary: A hyperinflammatory response during SARS-CoV-2 infection worsens the clinical progression of COVID-19. Activation of the NLRP3 inflammasome and release of IL-1 beta aggravate pulmonary injury, induce hypercoagulability, and contribute to respiratory failure and multiorgan failure. Inhibition of IL-1 has shown promising results in clinical trials.
Review
Immunology
Ali Saeedi-Boroujeni, Mohammad-Reza Mahmoudian-Sani, Roohangiz Nashibi, Sheyda Houshmandfar, Sima Tahmaseby Gandomkari, Ali Khodadadi
Summary: SARS-CoV-2 causes acute pneumonia, an inflammatory disease, while a cytokine storm is a major cause of death in COVID-19 patients. Activation of NLRP3 inflammasome by SARS-CoV through complex interactions with the host immune system triggers acute inflammation.
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2021)
Review
Medicine, General & Internal
Dan H. Barouch
Summary: This article reviews the protective effects of vaccination and prior infection on severe Covid-19, and proposes future research directions.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Medicine, Research & Experimental
Sebastian J. Theobald, Alexander Simonis, Theodoros Georgomanolis, Christoph Kreer, Matthias Zehner, Hannah S. Eisfeld, Marie-Christine Albert, Jason Chhen, Susanne Motameny, Florian Erger, Julia Fischer, Jakob J. Malin, Jessica Graeb, Sandra Winter, Andromachi Pouikli, Friederike David, Boris Boell, Philipp Koehler, Kanika Vanshylla, Henning Gruell, Isabelle Suarez, Michael Hallek, Gerd Faetkenheuer, Norma Jung, Oliver A. Cornely, Clara Lehmann, Peter Tessarz, Janine Altmueller, Peter Nuernberg, Hamid Kashkar, Florian Klein, Manuel Koch, Jan Rybniker
Summary: Our study reveals that the SARS-CoV-2 spike protein induces inflammasome formation and IL-1 beta release in macrophages from COVID-19 patients, but not in healthy individuals. Furthermore, macrophages isolated from convalescent COVID-19 patients show robust S-protein-driven inflammasome activation, indicating innate immune memory after recovery.
EMBO MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Qin Liu, Qi Su, Fen Zhang, Hein M. Tun, Joyce Wing Yan Mak, Grace Chung-Yan Lui, Susanna So Shan Ng, Jessica Y. L. Ching, Amy Li, Wenqi Lu, Chenyu Liu, Chun Pan Cheung, David S. C. Hui, Paul K. S. Chan, Francis Ka Leung Chan, Siew C. Ng
Summary: By integrating clinical features and multi-omics data, the authors identified specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome. These findings highlight the potential utility of host phenotype and multi-kingdom microbiota profiling as a prognostic tool for patients with COVID-19.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Sangiliyandi Gurunathan, Min Hee Kang, Jin-Hoi Kim
Summary: Exosomes, nano-sized lipid bilayer-enclosed structures, show potential in treating COVID-19 by modulating infection and transmission. Exosomes derived from mesenchymal stem cells have shown promise in reducing cytokine storm, repairing lung injuries, and could be a novel intervention for combating COVID-19.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Subhayan Sur, Ratna B. Ray
Summary: Long non-coding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes since the beginning of the 21st century. They share many similarities with mRNAs and regulate biological processes by interacting with DNA, RNA, proteins, and miRNAs. ELDR is an important lncRNA involved in development and cancer, with its high expression and oncogenic potential being the focus of research.
Article
Biochemistry & Molecular Biology
Subhayan Sur, Mousumi Khatun, Robert Steele, T. Scott Isbell, Ranjit Ray, Ratna B. Ray
Summary: The study found high levels of TNC and FGB in exosomes from COVID-19 patients, which may trigger pro-inflammatory responses in distant organs through exosome transportation. This suggests a potential mechanism for tissue damage and cytokine storm in COVID-19 patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Subhayan Sur, Robert Steele, T. Scott Isbell, Kalyan Nagulapalli Venkata, Mostafa E. Rateb, Ratna B. Ray
Summary: Head and neck cancer (HNC) is a highly aggressive cancer with limited treatment options. Momordicine-I (M-I), found in bitter melon extract, has shown significant potential in inhibiting HNC cell growth and tumor progression. M-I works by targeting c-Met and downstream signaling molecules, offering a promising alternative therapeutic approach for managing HNC.
Article
Biology
Debolina Pal, Subhayan Sur, Rituparna Roy, Suvra Mandal, Chinmay Kumar Panda
Summary: Amarogentin was found to prevent liver carcinogenesis at mild dysplastic stage by modulating cell cycle, apoptosis, and self-renewal pathways, with upregulation of cell cycle regulatory genes and hypomethylation observed in specific genes, suggesting epigenetic modulation as a mechanism of action.
JOURNAL OF BIOSCIENCES
(2021)
Article
Virology
Keith Meyer, Tapas Patra, Vijayamahantesh, Ranjit Ray
Summary: Increased mortality in COVID-19 cases is often associated with microvascular complications. The spike protein of SARS-CoV-2 can induce cellular senescence and inflammatory responses in human epithelial cells, leading to enhanced leukocyte adhesion. Various inhibitors have shown potential in reversing the senescence effects and reducing inflammatory responses.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Tapas Patra, Keith Meyer, Ratna B. Ray, Tatsuo Kanda, Ranjit Ray
Summary: The combination of Akt inhibitor and mTORC1/2 dual inhibitor has been shown to effectively induce apoptotic cell death in p53 mutant HCC cells by activating FOXO3a. This treatment strategy may offer therapeutic advantages for HCC patients with p53 mutations.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Subhayan Sur, Robert Steele, Ben C. B. Ko, Jinsong Zhang, Ratna B. Ray
Summary: Long noncoding RNAs (lncRNAs) have been recognized as important regulators in biological processes. In this study, the lncRNA ELDR was found to play a potential role as an oncogene in oral cancers. ELDR enhances the expression of cell cycle-related genes, leading to G2/M progression. Additionally, ELDR stabilizes CTCF and upregulates Forkhead box M1, which induces Aurora kinase A expression. These findings provide mechanistic insights into the role of ELDR in the neoplastic transformation of normal keratinocytes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Virology
Vijayamahantesh Vijayamahantesh, Tapas Patra, Keith Meyer, Mohamad-Gabriel Alameh, Erin K. Reagan, Drew Weissman, Ranjit Ray
Summary: The study shows that amino acid alteration in the front layer of soluble E2 disrupts its interaction with CD81 and alters the cytokine response. Immunization with modified sE2(F442NYT) protein-mRNA-LNP vaccine generates a stronger proinflammatory response and improved protection against a surrogate HCV vaccinia challenge model in mice. The results suggest that HCV E2 exhibits immunoregulatory activity that inhibits robust protective immune responses. Engineering E2 antigen in an mRNA-LNP platform may provide a novel approach for multigenotype HCV vaccine development.
JOURNAL OF VIROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Ranjit Ray, Mitsuhiko Moriyama, Ratna B. Ray, Tatsuo Kanda
Summary: Alcohol is a major cause of liver diseases, such as liver cirrhosis and hepatocellular carcinoma. This is due to the conversion of alcohol to acetaldehyde in hepatocytes, leading to various liver damage, as well as the production of toxins from intestinal bacteria aggravating inflammation. Genetic factors also play a role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Tapas Patra, David M. Cunningham, Keith Meyer, Karoly Toth, Ratna B. Ray, Andras Heczey, Ranjit Ray
Summary: Inhibition of Lin28B reduces the expression of IDO1 and PD-L1, and enhances the immunotherapeutic potential of GPC3-CART cells against HCC.