Article
Multidisciplinary Sciences
Laughing Bear Torrez Dulgeroff, Miranda S. Oakley, Michal C. Tal, Ying Ying Yiu, Joy Q. He, Maia Shoham, Victoria Majam, Winter A. Okoth, Pallavi Malla, Sanjai Kumar, Irving L. Weissman
Summary: CD47 is an antiphagocytic signal that inhibits programmed cell removal of self. Blocking CD47 can significantly improve the therapeutic effect against malaria infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Robert J. Zupko, Tran Dang Nguyen, J. Claude S. Ngabonziza, Michee Kabera, Haojun Li, Thu Nguyen-Anh Tran, Kien Trung Tran, Aline Uwimana, Maciej F. Boni
Summary: This study evaluates different strategies to slow the spread of malaria drug resistance and finds that lengthening treatment courses and using multiple first-line therapies can reduce treatment failures. New approaches, such as triple therapy or sequential courses of different treatments, have a greater impact on reducing treatment failures.
Article
Microbiology
Welmoed van Loon, Clara Bergmann, Felix Habarugira, Costanza Tacoli, Darius Savelsberg, Rafael Oliveira, Djibril Mbarushimana, Jules Ndoli, Augustin Sendegeya, Claude Bayingana, Frank P. Mockenhaupt
Summary: The study found an association between Plasmodium falciparum multidrug resistance-1 gene (pfmdr1) polymorphisms and altered antimalarial susceptibility, with a significant increase in the prevalence of the wild-type allele N86 and the wild-type combination NYD in recent years. The molecular data suggests a pattern shift in the pfmdr1 gene associated with artemether-lumefantrine resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Cell Biology
James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Summary: Severe malaria caused by Plasmodium falciparum is difficult to accurately diagnose in children in high-transmission settings. A combination of platelet count and plasma PfHRP2 concentration can be used to identify severe falciparum malaria in severely ill patients. About one-third of children enrolled in clinical studies of severe malaria in high-transmission settings in Africa had other causes of their severe illness.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jessica Correa Bezerra Bellei, Nicolas Glanzmann, Barbara Albuquerque Carpinter, Daniela Chaves Renhe, Carolina Brandi Marques, Marina Rocha Azevedo, Livia Maria Barreto, Vinicius Novaes Rocha, Isabelle Karine da Costa Nunes, Henrique Marcelo Gualberto Pereira, Elaine Soares Coimbra, Eduardo Antonio Ferraz Coelho, Adilson David da Silva, Fernando de Pilla Varotti, Kezia Katiani Gorza Scopel
Summary: Chloroquine remains the most effective drug for malaria treatment, although resistance to it has emerged. This study focuses on the synthesis of quinoline derivatives to develop new antimalarials. Compound 3 showed promising activity against malaria, inhibiting parasite growth and protecting against severe malaria development.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Biochemistry & Molecular Biology
Benedito M. Dos Santos, Jude M. Przyborski, Celia R. S. Garcia
Summary: English Summary: The GPCR-like SR25 in Plasmodium falciparum, a species of apicomplexan parasites, is activated by a shift in potassium concentration, allowing the parasite to take advantage of its development by sensing different ionic concentrations in the external milieu. This pathway involves the activation of phospholipase C and an increase in cytosolic calcium. This report summarizes the role of potassium ions during parasite development based on available literature, contributing to our understanding of the cell cycle of Plasmodium spp.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Casper Hempel, Dan Milner, Karl Seydel, Terrie Taylor
Summary: Recent studies suggest that endothelial glycocalyx plays a role in malaria pathogenesis. Using postmortem brain samples, changes in specific sugar epitopes were found in cerebral capillaries of children who died from cerebral malaria compared to nonmalarial comas. These findings suggest specific remodeling of cerebral microvessels in cerebral malaria patients.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Microbiology
Heather J. Painter, Joanne M. Morrisey, Michael W. Mather, Lindsey M. Orchard, Cuyler Luck, Martin J. Smilkstein, Michael K. Riscoe, Akhil B. Vaidya, Manuel Llinas
Summary: The emergence of drug-resistant Plasmodium falciparum parasites poses a challenge to global malaria eradication efforts, highlighting the importance of identifying new antimalarial drugs. Studying the molecular mechanism of drug resistance has revealed a novel resistance mechanism that could potentially guide the development of future antimalarial combination therapies.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Lei Hai, Xiaoyu Shi, Qian Wang
Summary: Protection from experimental cerebral malaria (ECM) in mice infected with Pbyop1 Delta parasites is associated with reduced intracerebral Th1 accumulation, decreased expression of pro-inflammatory cytokines and chemokines, and attenuated pathologies in the brainstem. However, the total number of CD4(+) and CD8(+) T cells sequestered in the brain is not reduced. Expression of adhesive molecules on brain endothelial cells is decreased, particularly in the brainstem.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tamir Zelter, Jacob Strahilevitz, Karina Simantov, Olga Yajuk, Yvonne Adams, Anja Ramstedt Jensen, Ron Dzikowski, Zvi Granot
Summary: Neutrophils can recognize and kill blood-stage Plasmodium falciparum, with neutrophil ICAM-1 and specific PfEMP1 implicated in cerebral malaria being key molecules involved in this killing.
Article
Pharmacology & Pharmacy
Nanang Rudianto Ariefta, Baldorj Pagmadulam, Coh-ichi Nihei, Yoshifumi Nishikawa
Summary: This study evaluated the growth-inhibitory effects of the antimalarial agent sparsomycin against drug-resistant malaria parasites. The results showed that sparsomycin had inhibitory effects on both sensitive and resistant strains of the parasites. This study suggests that sparsomycin has potential as an alternative treatment for malaria.
Article
Genetics & Heredity
Veronica Feijoli Santiago, Jamille Gregorio Dombrowski, Rebeca Kawahara, Livia Rosa-Fernandes, Simon Ngao Mule, Oscar Murillo, Thais Viggiani Santana, Joao Victor Paccini Coutinho, Janaina Macedo-da-Silva, Lucas Cardoso Lazari, Erika Paula Machado Peixoto, Marcel Ivan Ramirez, Martin R. Larsen, Claudio Romero Farias Marinho, Giuseppe Palmisano
Summary: Malaria in pregnancy (MiP) is a significant issue in malaria-endemic areas, leading to adverse effects for both mother and fetus. This study identified the proteome signature of a mouse model and pregnant women infected with Plasmodium falciparum using mass spectrometry-based proteomics. The results showed the activation of the complement system during malaria in pregnancy, which was correlated with poor newborn outcomes.
Article
Immunology
Wei Guan, Shuguo Yang, Yanqing Zhao, Weijia Cheng, Xiaonan Song, Yi Yao, Yiting Xie, Weixing Du, Jian Li
Summary: In this study, C57BL/6 mice infected with PbA were used to investigate the changes in gut microbiota composition. The results showed that specific bacterial genera were significantly increased in the infected group, indicating that P. berghei ANKA infection could alter the gut microbiota of the mice.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biochemical Research Methods
Aleena Das, Welka Sahu, Deepak Kumar Ojha, K. Sony Reddy, Mrutyunjay Suar
Summary: An untargeted metabolomics approach was used to identify the changes in metabolic pathways and metabolites in the serum of mice with different pathological stages of malaria. The study provides insights into the host biology during malaria and could be helpful for the selection of animal models for evaluating diagnostic and therapeutic interventions against malaria.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Infectious Diseases
Gui-Ling Chen, Xiao-Feng Li, Xia-Hong Dai, Nan Li, Meng-Li Cheng, Zhen Huang, Jian Shen, Yu-Hua Ge, Zhen-Wei Shen, Yong-Qiang Deng, Shu-Yuan Yang, Hui Zhao, Na-Na Zhang, Yi-Fei Zhang, Ling Wei, Kai-Qi Wu, Meng-Fei Zhu, Cong-Gao Peng, Qi Jiang, Shou-Chun Cao, Yu-Hua Li, Dan-Hua Zhao, Xiao-Hong Wu, Ling Ni, Hua-Hao Shen, Chen Dong, Bo Ying, Guo-Ping Sheng, Cheng-Feng Qin, Hai-Nv Gao, Lan-Juan Li
Summary: This study evaluated the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine (ARCoV) encoding the receptor-binding domain of the SARS-CoV-2 spike protein. The results showed that ARCoV was safe and well-tolerated at all doses and induced strong humoral and cellular immune responses. These findings support further clinical testing of ARCoV on a large scale.
Editorial Material
Medicine, General & Internal
Xin Wu, Huji Xu, Chen Dong
CHINESE MEDICAL JOURNAL
(2022)
Article
Biology
Han Feng, Xiaohong Zhao, Jenny Xie, Xue Bai, Weiwei Fu, Hairong Chen, Hong Tang, Xiaohu Wang, Chen Dong
Summary: This study systematically compared the transcriptomic profiles of Tfh cells from different types of immune responses and found differential induction of gene clusters corresponding to effector Th cells. It also discovered a subset of Tfh cells producing IFN-gamma in influenza virus infection, which had a unique developmental regulation. Selective ablation of these cells impaired immune response and control of infection.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Editorial Material
Biology
Xinyi Guo, Chen Dong
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Peter John, Marc C. Pulanco, Phillip M. Galbo, Yao Wei, Kim C. Ohaegbulam, Deyou Zheng, Xingxing Zang
Summary: B7x, an immune checkpoint molecule, promotes the conversion of CD4+ T cells into regulatory T cells within the tumor microenvironment. It induces transcriptomic changes in regulatory T cells, altering their phenotype to an activated and suppressive state. B7x-mediated regulation reduces the efficacy of anti-CTLA-4 treatment, but combination therapy with anti-B7x and anti-CTLA-4 overcomes this resistance and shows synergistic therapeutic efficacy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Elodie Picarda, Phillip M. Galbo, Haihong Zong, Meenu Rohini Rajan, Ville Wallenius, Deyou Zheng, Emma Borgeson, Rajat Singh, Jeffrey Pessin, Xingxing Zang
Summary: The immune checkpoint B7-H3 has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. This study reveals that B7-H3 is highly expressed in adipose tissue, particularly in adipocyte progenitor cells, and it regulates the glycolytic and mitochondrial activity of these cells. Loss of B7-H3 leads to impaired oxidative metabolism and increased lipid accumulation in derived adipocytes. Knockout of B7-H3 in mice results in spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation.
Article
Oncology
Shanjuan Hong, Qing Yuan, Haizhui Xia, Yuan Dou, Tiantian Sun, Tian Xie, Zhiyin Zhang, Wei He, Chen Dong, Jian Lu, Li Guo, Ling Ni
Summary: This study established an ex vivo cultured tumor tissue model to evaluate the efficacy of a VISTA inhibitor in treating clear cell renal cell carcinoma (ccRCC). The results showed that all tested patients responded to the anti-VISTA antibody, while only a small fraction responded to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 had a synergistic effect in 20% of ccRCC patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Xinwei Liu, Jing Hao, Peng Wei, Xiaohong Zhao, Qiuyan Lan, Lu Ni, Yongzhen Chen, Xue Bai, Ling Ni, Chen Dong
Summary: In this study, the researchers found that SMAD4 plays a critical role in promoting CD8(+) T cell function in both tumor and infection models. SMAD4-mediated transcriptional regulation enhances CD8(+) T cell activation and cytotoxicity through the T cell receptor (TCR) signaling pathway. Furthermore, SMAD4 is directly phosphorylated by ERK following TCR activation.
Review
Allergy
Han Feng, Zixuan Zhao, Chen Dong
Summary: This article reviews the plasticity of T-FH cells in various types of immune responses and highlights their important implications in understanding and treating human diseases, particularly allergy.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Xinhui Ni, Yi Xu, Wang Wang, Baida Kong, Jian Ouyang, Jiwei Chen, Man Yan, Yawei Wu, Qi Chen, Xinxin Wang, Hongquan Li, Xiaoguang Gao, Hongquan Guo, Lian Cui, Zeyu Chen, Yuling Shi, Ronghui Zhu, Wei Li, Tieliu Shi, Lin-Fa Wang, Jinling Huang, Chen Dong, Yuping Lai
Summary: This study found that the RNA helicase DDX5 plays an important role in inflammatory skin disorders. DDX5 expression was downregulated in keratinocytes from patients with atopic dermatitis and psoriasis. Mice with keratinocyte-specific deletion of DDX5 were more susceptible to cutaneous inflammation. Inhibition of DDX5 led to pre-messenger RNA splicing events that favored the production of membrane-bound IL-36 receptor and selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation.
Article
Immunology
Qinli Sun, Xiaohong Zhao, Ruifeng Li, Dingfeng Liu, Birui Pan, Bowen Xie, Xinxin Chi, Dongli Cai, Peng Wei, Wei Xu, Kun Wei, Zixuan Zhao, Yujie Fu, Ling Ni, Chen Dong
Summary: Sun et al. discovered that STAT3, activated by IL-10 and IL-21, plays crucial roles in the terminal differentiation of effector CD8(+) T cells in cancer and acute infection. STAT3 enhances effector functions and survival of T-ex(term) cells in the tumor microenvironment, leading to improved tumor control. It transcriptionally promotes effector function-related genes and collaborates with BATF and IRF4 to mediate chromatin activation at effector gene loci.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Yuling Li, Jing Ge, Xiaohong Zhao, Miao Xu, Mengting Gou, Bowen Xie, Jinling Huang, Qinli Sun, Lin Sun, Xue Bai, Sangnee Tan, Xiaohu Wang, Chen Dong
Summary: Yuling Li et al. found that BCL6 is selectively expressed in CCR6(+) ILC3 among the ILC family. BCL6 expression, induced by intestinal microbiota, restrains the effector function and plasticity of CCR6(+) ILC3.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Immunology
Marc C. Pulanco, Anne T. Madsen, Ankit Tanwar, Devin T. Corrigan, Xingxing Zang
Summary: The B7/CD28 families of immune checkpoints play important roles in regulating immune cells and are closely related to various diseases. Recent studies have discovered new pathways and therapeutics for cancer therapy in this field. This review covers the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, metabolic regulation by PD-1/PD-L1 and B7-H3, the glycobiology of PD-1/PD-L1, B7x, and B7-H3, as well as the interaction between PD-L1 and B7-1. The article also discusses the resistance mechanisms to current immunotherapies targeting PD-1/PD-L1 and CTLA-4 in clinical settings, and reviews new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in ongoing clinical trials.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiaoxin Ren, Yixian Li, Christopher Nishimura, Xingxing Zang
Summary: Somatic activating mutations in EGFR are common in various cancers. Targeted therapies against EGFR have shown clinical efficacy, but acquired resistance is a challenge. PD-1/PD-L1 immune checkpoint inhibitors are effective in some cancers, but limited in EGFR mutated cancers. Up-regulation of new B7/CD28 family members related to EGFR signaling may contribute to immunosuppressive tumor microenvironment and resistance to EGFR-targeted therapies. Understanding these interactions could inform combination therapeutic strategies.
Article
Medicine, Research & Experimental
Qiuyang Zheng, Beibei Song, Guilin Li, Fang Cai, Meiling Wu, Yingjun Zhao, LuLin Jiang, Tiantian Guo, Mingyu Shen, Huan Hou, Ying Zhou, Yini Zhao, Anjie Di, Lishan Zhang, Fanwei Zeng, Xiu-Fang Zhang, Hong Luo, Xian Zhang, Hongfeng Zhang, Zhiping Zeng, Timothy Y. Huang, Chen Dong, Hong Qing, Yun Zhang, Qing Zhang, Xu Wang, Yili Wu, Huaxi Xu, Weihon Song, Xin Wang
Summary: Down syndrome is one of the critical risk factors for early-onset Alzheimer's disease, and the DS-related gene USP25 has been identified as a critical regulator of AD pathology, potentially serving as a pharmacological target for AD drug development.
JOURNAL OF CLINICAL INVESTIGATION
(2022)