Review
Pharmacology & Pharmacy
Hui Lu, Ting Hong, Yuanying Jiang, Malcolm Whiteway, Shiqun Zhang
Summary: Candidiasis is a fungal infection caused by Candida, most commonly Candida albicans. It can cause various infections on mucous membranes and throughout the body, especially in immunocompromised individuals. However, the immune mechanisms of the host and current antifungal drugs are not fully understood. Therefore, it is important to uncover host immune defenses and develop new antifungal strategies.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Chemistry, Multidisciplinary
Shu-jie Li, Yan-li Wu, Juan-hua Chen, Shi-yi Shen, Jia Duan, H. Eric Xu
Summary: Autoimmune diseases arise from the breakdown of immunological self-tolerance. Current treatments only provide symptomatic relief. Research on autoantigens offers the potential for novel immunotherapy regimens. Type 1 diabetes is characterized by the destruction of insulin-producing beta cells, and insulin is a possible autoantigen. Understanding the role of insulin in the disease can lead to effective immunotherapy targeting autoantigens.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Medicine, General & Internal
Arghadip Samaddar, Anuradha Sharma
Summary: Recent global emergence of emergomycosis caused by a novel dimorphic fungus Emergomyces species has been observed among immunocompromised individuals. Taxonomic revisions have led to the classification of various fungi under a new genus Emergomyces. Diagnosis and treatment of emergomycosis remain challenging, with no consensus guidelines for treatment and the need for an affordable and reliable diagnostic test in endemic regions.
FRONTIERS IN MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Lei Chen, Lanyue Zhang, Yuyan Xie, Yiting Wang, Xiuyun Tian, Wenxia Fang, Xinying Xue, Linqi Wang
Summary: Human pathogenic fungi pose a serious threat to human health due to the limited number of antifungal options and the emergence of drug-resistant variants. The understanding of fungal drug response is crucial for the development of new antifungal therapies. This review summarizes recent advances in the study of antifungal resistance, tolerance, and persistence, focusing on promising drug targets and delivery systems.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Luping Pang, Stephen D. Weeks, Arthur Van Aerschot
Summary: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in all three kingdoms of life, and have been recognized as suitable targets for small molecule anti-infectives. This review discusses the catalytic activities of aaRSs, inhibitory mechanisms, and species-selectivity determinants of reported inhibitors. The structural perspective highlights opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Siyu Wu, Wenlai Guo, Bo Li, Huidong Zhou, Hongqi Meng, Junyi Sun, Ruiyan Li, Deming Guo, Xi Zhang, Rui Li, Wenrui Qu
Summary: Fungal diseases present a major challenge to global health and lack effective solutions. This is due to the limitations of fungi as eukaryotes and their rapid proliferation rates, hindering identification, drug sensitivity analysis, and the development of vaccines. Polymer-based strategies have emerged as a promising approach for managing fungal diseases, with advancements in prevention, diagnosis, treatment, and monitoring. However, there is a need for further research bridging the gap between experimental studies and clinical translation in order to determine the mechanisms and safety of polymer-based products.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Microbiology
Ronen Ben-Ami
Summary: Antifungal therapy for pulmonary fungal diseases is undergoing changes, with newer drugs replacing the older standard of care. Voriconazole has become the treatment of choice for most pulmonary mold diseases, but posaconazole and itraconazole have shown similar efficacy with fewer adverse events. With the rise of azole-resistant Aspergillus fumigatus and infections with inherently resistant non-Aspergillus molds, the need for antifungal drugs with novel mechanisms of action is becoming more urgent.
Review
Pharmacology & Pharmacy
Geoffrey A. Holdgate, Catherine Bardelle, Alice Lanne, Jon Read, Daniel H. O'Donovan, James M. Smith, Nidhal Selmi, Robert Sheppard
Summary: This review provides an overview of the role of epigenetics in disease and the strategy of pharmacological intervention. It discusses the drug targets of epigenetics and the methods used for initial hit identification and chemical optimization. The review also highlights current challenges and future potential for epigenetics-based therapies.
DRUG DISCOVERY TODAY
(2022)
Article
Multidisciplinary Sciences
Yang Pan, John W. Phillips, Beatrice D. Zhang, Miyako Noguchi, Eric Kutschera, Jami McLaughlin, Pavlo A. Nesterenko, Zhiyuan Mao, Nathanael J. Bangayan, Robert Wang, Wendy Tran, Harry T. Yang, Yuanyuan Wang, Yang Xu, Matthew B. Obusan, Donghui Cheng, Alex H. Lee, Kathryn E. Kadash-Edmondson, Ameya Champhekar, Cristina Puig-Saus, Antoni Ribas, Robert M. Prins, Christopher S. Seet, Gay M. Crooks, Owen N. Witte, Yi Xing
Summary: This study describes a computational platform called IRIS that can discover tumor antigens derived from alternative splicing, providing potential targets for TCR and CAR-T immunotherapies. Through the analysis of transcriptomics and immuno-peptidomics data, the study demonstrates that the predicted targets by IRIS can bind with HLA molecules. The study illustrates the contribution of alternative splicing to the repertoire of tumor antigens and demonstrates the utility of IRIS in discovering AS-derived antigens and expanding cancer immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Sebastien C. Ortiz, Mingwei Huang, Christina M. Hull
Summary: There is a critical need for new antifungal drugs, and the lack of fungus-specific targets is a major hurdle in their development. Spore germination, a process absent in humans, could harbor fungus-specific targets. Through novel assays, 191 inhibitors of spore germination of Cryptococcus were identified and characterized, showing high potency against spore germination while maintaining low cytotoxicity against mammalian cells.
Review
Cell Biology
Austin W. T. Chiang, Hratch M. Baghdassarian, Benjamin P. Kellman, Bokan Bao, James T. Sorrentino, Chenguang Liang, Chih-Chung Kuo, Helen O. Masson, Nathan E. Lewis
Summary: Cancer immunotherapy has greatly impacted treatment in the past two decades, with pioneers like Tasuku Honjo and James P. Allison awarded the Nobel Prize for their groundbreaking work in this field. The challenge now lies in developing more consistent therapies for various patients and cancer types by understanding the interactions between immune cells, tumor cells, and immunotherapeutics. Emerging research on aberrant glycosylation and its influence on tumor immunity and immunotherapy is providing new insights and therapeutic opportunities in the field of cancer immuno-oncology.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Karol Estrada, Steven Froelich, Arthur Wuster, Christopher R. Bauer, Teague Sterling, Wyatt T. Clark, Yuanbin Ru, Marena Trinidad, Hong Phuc Nguyen, Amanda R. Luu, Daniel J. Wendt, Gouri Yogalingam, Guoying Karen Yu, Jonathan H. LeBowitz, Lon R. Cardon
Summary: The authors proposed an approach to prioritize genes as potential drug targets by focusing on those with bidirectional effects, identified 98 BEST genes for various indications, and validated the bidirectional effects of five genes related to stature.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Yan-Fei Sui, Mohammad Fawad Ansari, Bo Fang, Shao-Lin Zhang, Cheng-He Zhou
Summary: Novel purinylthiazolylethanone derivative 8c shows significant inhibitory action against C. albicans, with no detectable resistance and low toxicity. The compound kills fungi by damaging cell wall and membrane disruption, hinder the growth of fungal biofilm. Imbalance of redox equilibrium leads to oxidative damage to fungal cells and fungicidal effect.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Li Wang, Michael A. Crackower, Hao Wu
Summary: Inflammasome proteins are important drug targets for many diseases, but their drug discovery has been difficult due to challenges in solving high-resolution structures. Recent advances in the structural biology of NLRP3 and NLRP1 offer hope for structure-based drug design.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
James J. Harding, Danny N. Khalil, Luca Fabris, Ghassan K. Abou-Alfa
Summary: Biliary tract cancers are rare gastrointestinal malignancies associated with high morbidity and mortality rates. Various treatments, including chemotherapy, precision medicine, and immunotherapy, are used in both standard-of-care and investigational settings. Recent research has shown that the combination of durvalumab with gemcitabine and cisplatin improves survival outcomes. Precision medicine is utilized in patients with specific genetic alterations, while fluoropyridine doublets are used in patients without targetable genetic alterations. Next-generation sequencing is crucial for patient care and understanding resistance mechanisms. Ongoing clinical trials seek to improve treatment standards and develop effective combination drug therapies for the future.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marilen Souza, Juliana Machado, Jonatas da Silva, Luana Ramos, Lais Nogueira, Patricia Ribeiro, Daniel Dias, Josiane Santos, Jose Carlos Santos, Yanna Nobrega, Amanda Souza, Sonia Freitas, Mariana Campos da Paz, Maria Felipe, Fernando Torres, Alexsandro Galdino
Summary: A recombinant multiepitope protein (rMERUB) was developed for the diagnosis of rubella, showing potential for the development of a diagnostic kit.
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
(2022)
Article
Immunology
Diane Sthefany Lima de Oliveira, Verenice Paredes, Adrielle Veloso Caixeta, Nicole Moreira Henriques, Maggie P. Wear, Patricia Albuquerque, Maria Sueli Soares Felipe, Arturo Casadevall, Andre Moraes Nicola
Summary: Decades of studies on antibody structure have shown that while the V region binds antigens, the C region can affect affinity and specificity. This study identified the molecular basis of how the constant region impacts antigen binding, and how engineering antibodies with different constant regions can result in different binding patterns.
Article
Multidisciplinary Sciences
Rodrigo B. Aires, Alexandre A. de S. M. Soares, Ana Paula M. Gomides, Andre M. Nicola, Andrea Teixeira-Carvalho, Dayde Lane M. da Silva, Eliana T. de Gois, Flavia D. Xavier, Francielle P. Martins, Gabriela P. J. Santos, Heidi Luise Schulte, Isabelle S. Luz, Laila S. Espindola, Laurence R. do Amaral, Liza F. Felicori, Luciana A. Naves, Maira R. M. de Carvalho, Matheus de S. Gomes, Otavio T. Nobrega, Patricia Albuquerque, Wagner Fontes, Ciro M. Gomes, Patricia S. Kurizky, Cleandro P. Albuquerque, Olindo A. Martins-Filho, Licia Maria H. da Mota
Summary: Thromboelastometry parameters are useful in differentiating the coagulation profile between severe and non-severe COVID-19 patients, which is important for therapeutic intervention.
Article
Medicine, General & Internal
Andrea B. Troxel, Eva Petkova, Keith Goldfeld, Mengling Liu, Thaddeus Tarpey, Yinxiang Wu, Danni Wu, Anup Agarwal, Cristina Avendano-Sola, Emma Bainbridge, Katherine J. Bar, Timothy Devos, Rafael F. Duarte, Arvind Gharbharan, Priscilla Y. Hsue, Gunjan Kumar, Annie F. Luetkemeyer, Geert Meyfroidt, Andre M. Nicola, Aparna Mukherjee, Mila B. Ortigoza, Liise-anne Pirofski, Bart J. A. Rijnders, Casper Rokx, Arantxa Sancho-Lopez, Pamela Shaw, Pablo Tebas, Hyun-Ah Yoon, Corita Grudzen, Judith Hochman, Elliott M. Antman
Summary: This meta-analysis found no association of CCP with better clinical outcomes for the typical patient, and it provides a model for conducting real-time individual patient data pooling and meta-analysis during a pandemic.
Article
Medicine, General & Internal
Hyung Park, Thaddeus Tarpey, Mengling Liu, Keith Goldfeld, Yinxiang Wu, Danni Wu, Yi Li, Jinchun Zhang, Dipyaman Ganguly, Yogiraj Ray, Shekhar Ranjan Paul, Prasun Bhattacharya, Artur Belov, Yin Huang, Carlos Villa, Richard Forshee, Nicole C. Verdun, Hyun Ah Yoon, Anup Agarwal, Ventura Alejandro Simonovich, Paula Scibona, Leandro Burgos Pratx, Waldo Belloso, Cristina Avendano-Sola, Katharine J. Bar, Rafael F. Duarte, Priscilla Y. Hsue, Anne F. Luetkemeyer, Geert Meyfroidt, Andre M. Nicola, Aparna Mukherjee, Mila B. Ortigoza, Liise-anne Pirofski, Bart J. A. Rijnders, Andrea Troxel, Elliott M. Antman, Eva Petkova
Summary: This study aimed to develop an index for predicting the relative treatment benefit from COVID-19 convalescent plasma (CCP) compared to treatment without CCP. The study found that CCP treatment may be most effective for patients with preexisting conditions and those in the early stages of COVID-19.
Article
Biochemistry & Molecular Biology
Joao Vitor Perez de Souza, Erika Seki Kioshima, Leticia Sayuri Murase, Diego de Souza Lima, Flavio Augusto Vicente Seixas, Bernard Maigret, Rosilene Fressatti Cardoso
Summary: This study presents a large-scale ensemble-docking strategy combining ligand- and target-based chemoinformatic methods to deep learning to select putative inhibitors of 3-dehydroquinate dehydratase (MtDHQ) for Mycobacterium tuberculosis. Through post-docking analysis and virtual screening, several molecules showed comparable or better affinity for MtDHQ compared to known inhibitors. Molecular dynamics simulations confirmed the stable binding of the top hit to MtDHQ. This work represents the first step in validating these molecules as inhibitors of MtDHQ.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Danielle Galdino de Souza, Debora Silva Santos, Karina Smidt Simon, Jose Athayde Vasconcelos Morais, Luisa Coutinho Coelho, Thyago Jose Arruda Pacheco, Ricardo Bentes Azevedo, Anamelia Lorenzetti Bocca, Cesar Augusto Melo-Silva, Joao Paulo Figueiro Longo
Summary: Diets rich in omega-3 fatty acids, such as fish oil, can modulate inflammatory responses and cell membrane composition. This study found that the use of lipid nanoemulsion containing fish oil significantly reduced fibrotic progression and inflammation in an experimental model of pulmonary fibrosis.
Article
Microbiology
Herdson Renney de Sousa, Getulio Pereira de Oliveira Jr, Stefania de Oliveira Frazao, Kaio Cesar de Melo Gorgonha, Camila Pereira Rosa, Emanuella Melgaco Garcez, Joaquim Lucas Jr, Amabel Fernandes Correia, Waleriano Ferreira de Freitas, Higor Matos Borges, Lucas Gomes de Brito Alves, Hugo Costa Paes, Luciana Trilles, Marcia dos Santos Lazera, Marcus de Melo Teixeira, Vitor Laerte Pinto Jr, Maria Sueli Soares Felipe, Arturo Casadevall, Ildinete Silva-Pereira, Patricia Albuquerque, Andre Moraes Nicola
Summary: This study systematically investigated the virulence attributes of clinical isolates of Cryptococcus spp. and found that C. neoformans isolates have stronger melanization ability and thinner capsules than C. gattii. The study also revealed a positive correlation between faster melanization and the virulence, survival capability in Galleria mellonella, and prognosis in humans.
Article
Oncology
Pollyanna Cristina Vincenzi Conrado, Ana Adelia Vaine, Glaucia Sayuri Arita, Karina Mayumi Sakita, Renato Sonchini Goncalves, Wilker Caetano, Monique de Souza, Mauro Luciano Baesso, Luis Carlos Malacarne, Emanuel Razzolini, Vania Aparecida Vicente, Erika Seki Kioshima, Patricia de Souza Bonfim de Mendonca
Summary: PDT-Hyp as a promising therapy for the clinical treatment of OM, it showed satisfactory results in terms of efficacy and safety, with fungicidal effect and complete permeation through healthy and OM-affected nails.
PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY
(2023)
Article
Microbiology
Luisa Dan Favilla, Tatiana Sobianski Herman, Camila da Silva Goersch, Rosangela Vieira de Andrade, Maria Sueli Soares Felipe, Anamelia Lorenzetti Bocca, Larissa Fernandes
Summary: This study successfully generated a novel mutant of the dematiaceous fungal genus Fonsecaea by gene deletion and homologous recombination. The mutant showed differences in nutrient supply, viability, and growth compared to the wild-type and reconstituted strains. These findings contribute to a better understanding of the biology and pathogenicity of chromoblastomycosis causative agents.
Article
Chemistry, Physical
Karina Mayumi Sakita, Franciele Abigail Vilugron Rodrigues-Vendramini, Terezinha Inez Estivalet Svidzinski, Maria Sueli Felipe, Bernard Maigret, Erika Seki Kioshima
Summary: The development of multi-targeting inhibitors aims to enhance the antifungal effect by inhibiting two different targets in a single chemical entity. This study describes the discovery and selection of dual-inhibitors targeting thioredoxin reductase and glutathione reductase proteins of Aspergillus fumigatus. In vitro testing showed that Octenidine (OCT) exhibited promising antifungal activity against multiple fungi. OCT is believed to disrupt the cell membrane and inhibit both thioredoxin reductase and glutathione reductase, leading to increased ROS and fungal cell death.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Andrew Matheus Frederico Rozada, Franciele Abigail Vilugron Rodrigues-Vendramini, Erika Seki Kioshima, Eloisa Gibin Sampiron, Regiane Bertin de Lima Scodro, Katiany Rizzieri Caleffi-Ferracioli, Flavio Augusto Vicente Seixas, Ernani Abicht Basso, Gisele de Freitas Gauze
Summary: In this study, a series of new 1,3,4-oxadiazoles were synthesized and evaluated for their antimicrobial activity against Pb and Mtb. Compound 6n, with a 2-hydroxy-5-nitrophenyl subunit, showed the most promising activity and exhibited a broad-spectrum profile for the treatment of both pulmonary infections.
FUTURE MEDICINAL CHEMISTRY
(2023)
