Editorial Material
Immunology
Mitchell N. Lefebvre, John T. Harty
Summary: The new research shows that gamma delta T cells recognize Plasmodium-infected erythrocytes through the interaction of the T cell antigen receptor with the phosphoantigen sensor BTN3A1 and subsequently destroy infected cells either by secreting cytotoxic molecules or through antibody-dependent phagocytosis.
Article
Biochemistry & Molecular Biology
Ladawan Khowawisetsut, Sinmanus Vimonpatranon, Kittima Lekmanee, Hathai Sawasdipokin, Narinee Srimark, Kesinee Chotivanich, Kovit Pattanapanyasat
Summary: This study aimed to investigate the physical characteristics of EVs derived from culture-adapted P. falciparum isolates (Pf-EVs) and their impact on monocyte polarization. The results showed that all P. falciparum strains released similar amounts of EVs with variation in size characteristics. Pf-EVs had a more pronounced effect on CD14(+)CD16(+) intermediate monocytes, but miR in Pf-EVs might not be a significant factor in driving M2-like monocyte polarization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Preeti Kushwaha, Vipin Kumar, Biswajit Saha
Summary: beta-Carboline alkaloids are important nitrogen-based natural alkaloids and therapeutic molecules that exhibit various pharmacological activities through diverse mechanisms. There has been increasing attention towards developing effective antimalarial drugs based on this compound. This article comprehensively reviews the clinical and preclinical antimalarial scaffolds containing beta-carboline structure. The study focuses on the natural and semi-synthetic analogues of beta-carbolines reported in the last decade (2011-2021), providing insights into their mechanisms of action and potential for future therapeutic development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, General & Internal
Sinmanus Vimonpatranon, Sittiruk Roytrakul, Narumon Phaonakrop, Kittima Lekmanee, Anyapat Atipimonpat, Narinee Srimark, Kasama Sukapirom, Kesinee Chotivanich, Ladawan Khowawisetsut, Kovit Pattanapanyasat
Summary: In infectious diseases, EVs released from pathogen-infected cells can regulate immune responses and carry specific human proteins, while most pathogen proteins in the EVs are common across different types. Pf-MVs were found to attenuate parasite invasion efficiency, with a greater effect in culture-adapted isolates. This suggests that Pf-EVs play a role in quorum sensing and regulation of parasite growth-density.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Maureen Ty, Shenghuan Sun, Perri C. Callaway, John Rek, Kathleen D. Press, Kattria van der Ploeg, Jason Nideffer, Zicheng Hu, Sandy Klemm, William Greenleaf, Michele Donato, Stephen Tukwasibwe, Emmanuel Arinaitwe, Felistas Nankya, Kenneth Musinguzi, Dean Andrew, Lauren de la Parte, Diego Martinez Mori, Savannah N. Lewis, Saki Takahashi, Isabel Rodriguez-Barraquer, Bryan Greenhouse, Catherine Blish, P. J. Utz, Purvesh Khatri, Grant Dorsey, Moses Kamya, Michelle Boyle, Margaret Feeney, Isaac Ssewanyana, Prasanna Jagannathan
Summary: Repeated malaria exposure leads to expansion of atypical CD56neg NK cells in Ugandan children, characterized by transcriptional, epigenetic, and phenotypic differences from CD56dim NK cells. CD56neg NK cells display enhanced functionality and greater antibody-dependent cellular cytotoxicity. Higher frequencies of CD56neg NK cells are associated with protection against symptomatic malaria. Continuous exposure to Plasmodium falciparum is necessary to maintain this modified, adaptive-like NK cell subset, as frequencies rapidly decline after reductions in malaria transmission.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Microbiology
Chandra Sekhar Gudla, Vignesh Selvam, Siva Shanmugam Selvaraj, Renu Tripathi, Prince Joshi, Salique Hassan Shaham, Mayas Singh, Radha Krishan Shandil, Saman Habib, Shridhar Narayanan
Summary: Malaria, caused by Plasmodium parasites, remains a significant global health burden. This study identified a lead compound, FNDR-10132, with potent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant strains. FNDR-10132 also showed promising results in vivo, suppressing parasite growth and improving survival time in mice. These findings offer a potential new class of antimalarial drugs to combat chloroquine-resistant strains.
Article
Pharmacology & Pharmacy
Xi Wang, Jingying Dai, Jingyi Xia, Zichen Ye, Xiaobing Huang, Wanjun Cao, Rong Xiao, Lin He
Summary: The study aims to investigate the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. The results show that pomalidomide enhances the maturation of moDCs and increases the expression of CD40 and HLA-DR on cells. However, the impact of pomalidomide on cytokine secretion levels varies between different sources of moDCs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Manon Alkema, X. Zen Yap, Gerdie M. de Jong, Isaie J. Reuling, Quirijn de Mast, Reinout van Crevel, Christian F. Ockenhouse, Katharine A. Collins, Teun Bousema, Matthew B. B. McCall, Robert W. Sauerwein
Summary: Malaria infection caused by Plasmodium falciparum through mosquito bites induces stronger inflammation response in healthy volunteers compared to intravenous administration of infected red blood cells.
Review
Immunology
Dania Zhivaki, Jonathan C. Kagan
Summary: Inflammasomes play context-dependent roles in inflammation and protective immunity in vertebrates, impacting CD8+ T cell-mediated antitumor immunity in different cell types. The surprising ability of inflammasomes within hyperactive DCs to facilitate the use of tumor lysates as immunogens for promoting antitumor responses offers opportunities for future research and next-generation immunotherapy development.
TRENDS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Wei-Zheng Zhang
Summary: Gout is a multifactorial metabolic disease where the role of hyperuricemia in its development is not solely definitive. Understanding the intricate role of serum uric acid (SUA) in gout pathogenesis is crucial for advancing clinical and pharmaceutical approaches towards a cure for the disease.
Article
Pharmacology & Pharmacy
Cheng Chen, Lin He, Xi Wang, Rong Xiao, Shu Chen, Zichen Ye, Xuemei Wang, Yu Wang, Yizhun Zhu, Jingying Dai
Summary: This study investigated the immunomodulatory effect and mechanism of leonurine on monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients for the first time. The results showed that leonurine significantly promotes maturation of moDCs derived from HDs and MM patients, and the mechanism is related to arachidonic acid metabolism.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane, David M. Cook, Sahand Kalhori, Charles Wyatt, Aarti Kolluri, Omely Marte-Salcedo, Alemush Imeru, Martha Nason, Lei K. Ding, Hope Decederfelt, Junhui Duan, Jillian Neal, Jacob Raiten, Grace Lee, Jen C. C. Hume, Jihyun E. Jeon, Ijeoma Ikpeama, K. C. Natasha, Sumana Chakravarty, Tooba Murshedkar, L. W. Preston Church, Anita Manoj, Anusha Gunasekera, Charles Anderson, Sean C. Murphy, Sandra March, Sangeeta N. Bhatia, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie, Irfan Zaidi, Stephen L. Hoffman, Patrick E. Duffy
Summary: Increased vaccine efficacy against malaria can be achieved through higher vaccine dosage and specific chemoprophylaxis vaccination regimens, providing protection against both homologous and heterologous parasite strains. This enhanced protection is associated with V delta 2 gamma delta T cell and antibody responses.
Article
Multidisciplinary Sciences
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Christine R. Collins, Abigail J. Perrin, Konstantinos Koussis, Claudine Bisson, Michael J. Blackman, Aigars Jirgensons
Summary: Malaria is a devastating infectious disease causing over 400,000 deaths annually. Researchers have developed substrate-based peptidic boronic acids that inhibit a parasite protease called SUB1, preventing parasite replication through egress and potentially serving as a new class of antimalarial drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Wanjing Cen, Felix Umrath, Antonio Jose Salgado, Siegmar Reinert, Dorothea Alexander
Summary: The secretomes derived from osteogenically induced jaw periosteum-derived mesenchymal stem cells (JPCs) have inhibitory effects on the maturation of monocyte-derived dendritic cells (MoDCs), as they reduce the formation of MoDC clusters and down-regulate the expression of CD80, CD86, and CD197 on MoDCs. The secretomes also enhance the uptake capacity of MoDCs and promote the expansion of regulatory T cells. Furthermore, the secretomes affect the gene expression of MoDCs, up-regulating CD209, HLA-DRA, CSF3, IL10, and IL8, and down-regulating IFN gamma and IL12B.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Gregory M. Martin, Jonathan L. Torres, Tossapol Pholcharee, David Oyen, Yevel Flores-Garcia, Grace Gibson, Re'em Moskovitz, Nathan Beutler, Diana D. D. Jung, Jeffrey Copps, Wen-Hsin Lee, Gonzalo Gonzalez-Paez, Daniel Emerling, Randall S. MacGill, Emily Locke, C. Richter King, Fidel Zavala, Ian A. Wilson, Andrew B. Ward
Summary: In this study, the authors used cryo-EM to determine the structures of potent human antibodies and demonstrated their protective effects in vivo. They focused on antibodies targeting the circumsporozoite protein of Plasmodium falciparum, an important antigen for developing malaria vaccines. Through structural and functional analyses, they revealed the diverse structures of the antibody-PfCSP complexes and highlighted the key role of mutated homotypic contacts in high avidity binding and protection against malaria infection.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Swapna Varghese, Raphael Rahmani, Stephanie Russell, Girdhar Singh Deora, Lori Ferrins, Arthur Toynton, Amy Jones, Melissa Sykes, Albane Kessler, Amanda Eufrasio, Artur Torres Cordeiro, Julian Sherman, Ana Rodriguez, Vicky M. Avery, Matthew J. Piggott, Jonathan B. Baell
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Infectious Diseases
Juan Rivera-Correa, Isadora Cristina de Siqueira, Sabrina Mota, Mateus Santana do Rosario, Pedro Antonio Pereira de Jesus, Luiz Carlos Junior Alcantara, Joel D. Ernst, Ana Rodriguez
PLOS NEGLECTED TROPICAL DISEASES
(2019)
Article
Chemistry, Medicinal
Justin R. Harrison, Sandipan Sarkar, Shahienaz Hampton, Jennifer Riley, Laste Stojanovski, Christer Sahlberg, Pia Appelqvist, Jessey Erath, Vinodhini Mathan, Ana Rodriguez, Marcel Kaiser, Dolores Gonzalez Pacanowska, Kevin D. Read, Nils Gunnar Johansson, Ian H. Gilbert
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Parasitology
Juan Rivera-Correa, Ana Rodriguez
TRENDS IN PARASITOLOGY
(2020)
Article
Chemistry, Medicinal
Baljinder Singh, Jean A. Bernatchez, Laura-Isobel McCall, Claudia M. Calvet, Jasmin Ackermann, Julia M. Souza, Diane Thomas, Everton M. Silva, Kelly A. Bachovchin, Dana M. Klug, Hitesh B. Jalani, Seema Bag, Melissa J. Buskes, Susan E. Leed, Norma E. Roncal, Erica C. Penn, Jessey Erath, Ana Rodriguez, Richard J. Sciotti, Robert F. Campbell, James McKerrow, Jair L. Siqueira-Neto, Lori Ferrins, Michael P. Pollastri
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Infectious Diseases
Juan Rivera-Correa, Maria Fernanda Yasnot-Acosta, Nubia Catalina Tovar, Maria Camila Velasco-Pareja, Alice Easton, Ana Rodriguez
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Parasitology
Alba Martinez-Florez, Melina Galizzi, Luis Izquierdo, Juan M. Bustamante, Ana Rodriguez, Fernando Rodriguez, Alheli Rodriguez-Cortes, Jordi Alberola
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2020)
Article
Microbiology
Alice Easton, Mayra Raciny-Aleman, Victor Liu, Erica Ruan, Christian Marier, Adriana Heguy, Maria Fernanda Yasnot, Ana Rodriguez, P'ng Loke
Article
Chemistry, Medicinal
Soledad Natalia Gonzalez, Jonathan J. Mills, Dante Maugeri, Christopher Olaya, Breana L. Laguera, Jeffrey R. Enders, Julian Sherman, Ana Rodriguez, Joshua G. Pierce, Juan Jose Cazzulo, Edward L. D'Antonio
Summary: The study discovered a competitive inhibitor Compound B targeting ribose 5-phosphate isomerase type B (RPI-B), which exhibited significant trypanocidal activity against T. cruzi infective life-stages. By targeting the active site residue Cys-69, this inhibitor provided a proof-of-concept for the development of next generation inhibitors with potential prodrug groups to treat Chagas' disease in the future.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Nieves Martinez-Peinado, Clara Martori, Nuria Cortes-Serra, Julian Sherman, Ana Rodriguez, Joaquim Gascon, Jordi Alberola, Maria-Jesus Pinazo, Alheli Rodriguez-Cortes, Julio Alonso-Padilla
Summary: The study found that 17-DMAG has a strong inhibitory effect on T. cruzi, particularly during the intracellular replicative stage of the parasite. Molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. However, evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting challenges in transitioning from in vitro assays to preclinical drug development stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Nieves Martinez-Peinado, Nuria Cortes-Serra, Julian Sherman, Ana Rodriguez, Juan M. Bustamante, Joaquim Gascon, Maria-Jesus Pinazo, Julio Alonso-Padilla
Summary: Chagas disease, caused by the parasite Trypanosoma cruzi, has its greatest burden in Latin America. Existing treatments present toxicity and variable efficacy, highlighting the urgent need for new therapeutic strategies. Drug repositioning offers a fast and low-cost approach to identify safer and more effective chemotherapies for Chagas disease.
Article
Chemistry, Medicinal
Scott B. Green, Robert J. Lanier Jr, Shane M. Carey, David R. Morgan, Hanna Gracz, Julian Sherman, Ana Rodriguez, Edward L. D'Antonio
Summary: The screening of eighteen amino sugar analogues against Trypanosoma cruzi glucokinase revealed five on-target confirmed inhibitors, all from the D-GlcN series. Four of these compounds were identified as strong TcGlcK inhibitors, while three showed significant in vitro anti-T. cruzi activity. Compounds 5 and 6 were further evaluated biochemically, with formal Ki values determined and exhibiting competitive inhibition mode for TcGlcK.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Letter
Respiratory System
Marisol Zuniga, Claudia Gomes, Steven E. Carsons, Michael T. Bender, Paolo Cotzia, Qing Robert Miao, David C. Lee, Ana Rodriguez
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Infectious Diseases
Juan Rivera-Correa, Joseph Verdi, Julian Sherman, Jeremy M. Sternberg, Jayne Raper, Ana Rodriguez
Summary: The study found evidence of autoimmunity against phosphatidylserine in Trypanosoma brucei infected mice and Human African Trypanosomiasis patients, suggesting a potential link between autoimmunity and anemia.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Medicine, Research & Experimental
Claudia Gomes, Rosauro Varo, Miquel Duran-Frigola, Antonio Sitoe, Rubio Bila, Sonia Machevo, Alfredo Mayor, Quique Bassat, Ana Rodriguez
Summary: Malaria can progress from an uncomplicated infection to a life-threatening severe disease. Early symptoms are often nonspecific, making it difficult to identify patients at high risk. By analyzing the transcriptomic response of human brain microvascular endothelial cells to Plasmodium falciparum-infected erythrocytes, several biomarkers have been identified to distinguish uncomplicated from severe malaria, as well as to differentiate children with cerebral malaria within the severe malaria group.