Review
Biochemistry & Molecular Biology
Dorina Lauritano, Filiberto Mastrangelo, Cristian D'Ovidio, Gianpaolo Ronconi, Alessandro Caraffa, Carla E. Gallenga, Ilias Frydas, Spyros K. Kritas, Matteo Trimarchi, Francesco Carinci, Pio Conti
Summary: Mast cells (MCs) are tissue cells derived from bone marrow stem cells and play a role in various diseases and disorders. They communicate with microglia in the brain through the production of mediators and can have pathological effects. MCs release preformed chemical mediators and cytokines, and can interact with neuropeptides, leading to inflammation in the central nervous system. This article explores the activation of MCs by neuropeptides and the therapeutic potential of anti-inflammatory cytokines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Rui Liu, Shiling Hu, Yuanyuan Ding, Jue Wang, Yuejin Wang, Jiapan Gao, Langchong He
Summary: The study identified dictamnine as an effective anti-anaphylactoid compound from Cortex dictamni extracts, which significantly suppressed MC intracellular Ca2+ mobilization and release of de novo degranulated substances, and inhibited PKC-PLC gamma-IP3R-associated protein signaling molecules. Hence, dictamnine is a novel therapeutic candidate for anaphylactoid reactions via MrgX2.
PHYTOTHERAPY RESEARCH
(2021)
Article
Plant Sciences
Isadora de Fatima Braga Magalhaes, Ana Leticia Marinho Figueiredo, Elizeu Mendes da Silva, Adryan Adam Batalha de Miranda, Claudia Quintino da Rocha, Katia da Silva Calabrese, Fernando Almeida-Souza, Ana Lucia Abreu-Silva
Summary: A study focuses on the anti-inflammatory potential of Passovia ovata extract, which contains high levels of flavonoids. The results demonstrate significant reduction in inflammatory markers both in cell experiments and animal models. This study indicates the potential of Passovia ovata extract as a new agent for suppressing inflammatory responses.
Article
Oncology
Linda K. H. Teng, Brooke A. Pereira, Shivakumar Keerthikumar, Cheng Huang, Birunthi Niranjan, Sophie N. Lee, Michelle Richards, Ralf B. Schittenhelm, Luc Furic, David L. Goode, Mitchell G. Lawrence, Renea A. Taylor, Stuart J. Ellem, Gail P. Risbridger, Natalie L. Lister
Summary: The study identified reduced expression of the SAMD14 gene in mast cells from prostate cancer patients, which alters their secretions and enhances cancer cell activity. Interactions between mast cells and cancer-associated fibroblasts were found to promote a pro-tumor extracellular matrix and facilitate cancer cell invasion and migration. This highlights the potential of targeting the tumor microenvironment to develop new treatment strategies for prostate cancer and other solid tumors.
Article
Cell Biology
Mariona Guitart-Mampel, Pedro Urquiza, Fausto Carnevale Neto, James R. Anderson, Vedangi Hambardikar, Ernest R. Scoma, Gennifer E. Merrihew, Lu Wang, Michael J. MacCoss, Daniel Raftery, Mandy J. Peffers, Maria E. Solesio
Summary: Inorganic polyphosphate is an ancient and ubiquitous polymer that is present in all organisms. While its role in bacteria and yeast has been described, its exact function in mammalian physiology remains poorly understood. Our study suggests that the metabolism of mitochondrial polyphosphate could be a potential pharmacological target in neurodegenerative disorders and neuronal aging.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Paul M. Jordan, Nico Andreas, Marco Groth, Philine Wegner, Franziska Weber, Ute Jaeger, Claudia Kuechler, Oliver Werz, Edgar Serfling, Thomas Kamradt, Anne Dudeck, Sebastian Drube
Summary: IL-33 and ATP serve as alarmins released upon damage to cellular barriers, with mast cells being the first responders due to their high-density expression of the receptors. Co-sensing IL-33 and ATP leads to hyperactivation of mast cells, resulting in the production of high levels of pro-inflammatory cytokines and lipid mediators. Targeting the IL-33/IL-33R and/or the ATP/P2X7 signaling axis may offer therapeutic interventions for diseases associated with compromised cellular barriers.
Article
Medicine, General & Internal
Alexandria Savage, Cristobal Risquez, Kazunori Gomi, Ryan Schreiner, Alain C. Borczuk, Stefan Worgall, Randi B. Silver
Summary: In addition to traditional activation of resident receptors, exosomes have been found to mediate cell-to-cell communication by delivering specific cargo that modulates recipient cell function. Mast cell exosomes are shown to contribute to excess collagen synthesis, providing a unique paradigm for understanding fibrosis.
FRONTIERS IN MEDICINE
(2023)
Article
Immunology
Yucui Jiang, Fan Ye, Ying Du, Yingxin Zong, Zongxiang Tang
Summary: The study found that P2X7R in mast cells is involved in inflammatory pain by releasing inflammatory mediators, and salicylic acid (SA) and aspirin (ASA) may alleviate inflammatory pain by inhibiting the activity of P2X7R.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Cell Biology
Kristin Franke, Guerkan Bal, Zhuoran Li, Torsten Zuberbier, Magda Babina
Summary: Mast cells are effector cells in allergic and inflammatory diseases, and their biology is regulated by the SCF/KIT axis. Recent research has identified RHEX as a heavily phosphorylated protein in MCs, but its function remains unclear. This study demonstrates that RHEX acts as a negative regulator of SCF-supported skin MC survival by interfering with KIT signal transduction. The findings suggest that RHEX may have various roles in MC lineage and provide a framework for future research on its involvement in other crucial processes.
Article
Allergy
Hyun-Young Jang, Do Hyun Ha, So-Young Rah, Dong-Hyun Lee, Sang-Myeong Lee, Byung-Hyun Park
Summary: The study found that Sirt6 acts as a negative regulator of Fc epsilon RI signaling cascade in mast cells by suppressing PTPRC transcription. Activation of Sirt6 may represent a promising therapeutic strategy for anaphylaxis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Cell Biology
Haibo Dong, Yue Feng, Yang Yang, Yun Hu, Yimin Jia, Shu Yang, Nannan Zhao, Ruqian Zhao
Summary: The study identified a novel function of PCK2 in mediating LPS-induced inflammation and provided mechanistic insights into the regulation of inflammatory responses in Kupffer cells. PCK2 overexpression significantly increased inflammation markers, while PCK2 knockdown or inhibition mitigated LPS-induced inflammatory response in Kupffer cells. Additionally, PCK2 promoted protein phosphorylation of NF-kappa B and AKT/MAPK, the major signaling pathways controlling inflammatory cascade activation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Patrick P. G. Mulder, Marcel Vlig, Esther Fasse, Matthea M. Stoop, Anouk Pijpe, Paul P. M. van Zuijlen, Irma Joosten, Bouke K. H. L. Boekema, Hans J. P. M. Koenen
Summary: The immune response in burn patients is often extreme and abnormal. Understanding the immune effects of thermal injury is necessary to improve patient outcomes. This study shows that after burn injury, immune cells persistently increase in number, unlike in normal wound healing. The study also reveals high levels of chemokines and pro-inflammatory cytokines in burn tissue. The local immune response in burns is similar to the systemic immune reaction, but differs in neutrophil maturity and lymphocyte composition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Amanda Mara Teles, Gabriel Silva Xavier, Wendel Fragoso de Freitas Moreira, Carla Junqueira Moragas-Tellis, Maria do Socorro dos Santos Chagas, Maria Dutra Behrens, Ana Lucia Abreu-Silva, Geusa Felipa de Barros Bezerra, Katia da Silva Calabrese, Maria do Desterro Soares Brandao Nascimento, Fernando Almeida-Souza
Summary: This study aims to investigate the chemical composition and anti-inflammatory effects of Talaromyces purpurogenus isolated from a marine-polluted environment. The results showed that the ethyl acetate extract of T. purpurogenus culture broth had a rich chemical composition and inhibited the production of cytokines and nitrites, demonstrating its anti-inflammatory properties.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Review
Immunology
Jing Jin, Yuanyuan Jiang, Subrata Chakrabarti, Zhaoliang Su
Summary: This review summarizes the complex roles of cardiac mast cells (CMCs) in both physiological and pathological conditions of the heart, particularly in cardiac fibrosis. It discusses the origin, development, and replenishment of CMCs in the heart, as well as their effects on cardiac development, function, and aging. The review also highlights the roles of CMCs in inflammatory progression and resolution, and suggests potential immune treatments targeting CMCs in cardiac injury.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Angela Bononi, Qian Wang, Alicia A. Zolondick, Fang Bai, Mika Steele-Tanji, Joelle S. Suarez, Sandra Pastorino, Abigail Sipes, Valentina Signorato, Angelica Ferro, Flavia Novelli, Jin-Hee Kim, Michael Minaai, Yasutaka Takinishi, Laura Pellegrini, Andrea Napolitano, Ronghui Xu, Christine Farrar, Chandra Goparaju, Cristian Bassi, Massimo Negrini, Ian Pagano, Greg Sakamoto, Giovanni Gaudino, Harvey I. Pass, Jose N. Onuchic, Haining Yang, Michele Carbone
Summary: This study investigates the paradoxical finding that individuals with germline BAP1 mutations develop less aggressive mesotheliomas. The research shows that biallelic BAP1 mutations result in a reduction of HIF-1 alpha activity in mesothelioma cells and hypoxic tissues, leading to reduced aggressiveness and improved survival in these patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Roberto Docampo, Guozhong Huang
Summary: Trypanosoma cruzi and the T. brucei group of parasites are neglected diseases affecting millions of people globally. These microorganisms have complex life cycles involving insect vectors and mammalian hosts, and possess unique signaling pathways and receptor adaptations that differentiate them from their mammalian counterparts.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Andrew J. Stasic, Eric J. Dykes, Ciro D. Cordeiro, Stephen A. Vella, Mojtaba S. Fazli, Shannon Quinn, Roberto Docampo, Silvia N. J. Moreno
Summary: Proton transport plays a crucial role in maintaining cytosolic Ca2+ levels, Ca2+ influx, and Ca2+ storage by acidic compartments in Toxoplasma gondii. It impacts the concentration of polyphosphate, a key player in binding and storing Ca2+, further influencing Ca2+ signaling pathways and downstream cellular processes such as motility and egress.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Raquel S. Negreiros, Noelia Lander, Miguel A. Chiurillo, Anibal E. Vercesi, Roberto Docampo
Summary: Pyruvate, the end product of glycolysis, is transported into the mitochondria through the mitochondrial pyruvate carriers MPC1 and MPC2. Knockout of MPC1 and MPC2 in Trypanosoma cruzi affects pyruvate-driven respiration, host cell invasion, and intracellular replication of amastigotes.
Article
Microbiology
Srinivasan Ramakrishnan, Linn M. Unger, Rodrigo P. Baptista, Teresa Cruz-Bustos, Roberto Docampo
Summary: This study demonstrates that ablation of a Golgi-localized cation transporter in Trypanosoma cruzi prevents normal protein glycosylation, host cell invasion, and intracellular replication, while glycosylation can be rescued by Mn2+ but not by other cations. These findings highlight the crucial role of Mn2+ in host-parasite interaction and protein glycosylation.
Article
Biochemistry & Molecular Biology
Roberto Docampo, Anibal Eugenio Vercesi
Summary: This review discusses the mechanisms of mitochondrial oxidant generation and removal, and the involvement of Ca2+ in trypanosome cell death, highlighting the need for further studies on ROS generation, defense mechanisms, and mitochondrial permeability transition pore in trypanosomatids.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Microbiology
Fatma Gomaa, Zhu-Hong Li, David J. Beaudoin, Heba Alzan, Peter R. Girguis, Roberto Docampo, Virginia P. Edgcomb
Summary: Developing transfection protocols for marine protists is an emerging field. In this study, we successfully developed a CRISPR/Cas9 editing protocol for Bodo saltans and identified two mechanisms for repairing double-strand breaks in this organism.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Microbiology
Roberto Docampo, Guozhong Huang
Summary: Acidocalcisomes are organelles found in bacteria and eukaryotes. They play important roles in autophagy, ion and phosphorus storage, osmoregulation, pH homeostasis, and pathogenesis. Recent studies have also revealed their involvement in phosphate utilization, calcium ion signaling, and bioenergetics.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Cell Biology
Mahsa Ebrahimi, Lukas Habernig, Filomena Broeskamp, Andreas Aufschnaiter, Jutta Diessl, Isabel Atienza, Steffen Matz, Felix A. Ruiz, Sabrina Buettner
Summary: Nutrient limitation activates autophagy in organisms, and the nutrient-sensing kinase Pho85 is critical for coordinating autophagic responses to different types of starvation, promoting longevity in yeast. Phosphate restriction leads to lifespan extension in yeast through the coordinated activity of autophagy and the multivesicular body pathway, with Pho85 playing a key role in regulating autophagy and lifespan extension. Additionally, Pho85 functions differently in response to glucose exhaustion, acting as a negative regulator of autophagy and lifespan.
Article
Chemistry, Medicinal
Alejandro Pezza, Luis E. Tavernelli, Victoria L. Alonso, Virginia Perdomo, Raquel Gabarro, Rab Prinjha, Elvio Rodriguez Araya, Inmaculada Rioja, Roberto Docampo, Felix Calderon, Julio Martin, Esteban Serra
Summary: TcBDF2 is an important bromodomain protein in T. cruzi, playing a crucial role in infection, replication, and differentiation of the parasite, as well as pathogenesis.
ACS INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Mayara S. Bertolini, Roberto Docampo
Summary: In this study, we generated TcMICU1/TcMICU2 double knockout cell lines using CRISPR/Cas9 genome editing and found that these knockout cell lines were unable to uptake calcium at low extramitochondrial calcium concentrations. Further investigation revealed that Mg2+ negatively regulates the mitochondrial calcium uptake mediated by MCUC.
Article
Nutrition & Dietetics
Marcela Montilla, Andrea Liberato, Pablo Ruiz-Ocana, Ana Saez-Benito, Manuel Aguilar-Diosdado, Alfonso Maria Lechuga-Sancho, Felix A. Ruiz
Summary: Obesity increases the risk of insulin resistance and type 2 diabetes, and polyphosphate may serve as an inflammation biomarker in the onset of metabolic diseases.
Article
Biochemistry & Molecular Biology
Marcela Montilla, Isabel Atienza-Navarro, Francisco Jose Garcia-Cozar, Carmen Castro, Francisco Javier Rodriguez-Martorell, Felix A. Ruiz
Summary: Polyphosphate (polyP) plays an important modulatory role in the binding of von Willebrand factor (VWF) and Factor VIII (FVIII) in blood coagulation, and may be used in developing new therapies to activate VWF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Roberto Docampo
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.
Review
Microbiology
Roberto Docampo, Corrella S. Detweiler
Summary: Acidocalcisomes are organelles with acidity and high content of polyphosphate and calcium, and they have various functions and interactions with other organelles.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)