Article
Fisheries
Xiang-Yu Wu, Li Nie, Xin-Jiang Lu, Chen-Jie Fei, Jiong Chen
Summary: In this study, the role of PPAR gamma in immune regulation in teleost fish was investigated. Results showed that the expression of LcPPAR gamma changed during infection and DHA treatment, and was associated with the expression of immune-related genes.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Immunology
Ana Carolina Mota, Monica Dominguez, Andreas Weigert, Ryan G. Snodgrass, Dmitry Namgaladze, Bernhard Bruene
Summary: Efferocytosis is crucial for maintaining tissue homeostasis and involves activation of transcription factors such as PPAR and LXR. This study explored the transcriptional profile of macrophages following uptake of apoptotic cells, showing upregulation of PPAR and LXR pathways. The activation mechanisms of PPAR and LXR in efferocytotic human macrophages were elucidated, providing insights into their roles in metabolic and inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Dan Li, Huijuan Ma, Qi Shu, Tingqian Wang, Linyi Li, Ping Huang, Kaiyan Lou, Huan Xu
Summary: The study found that arsenite (As+3) inhibits M2a cell polarization by suppressing PPAR-gamma and leads to lipid accumulation. Rosiglitazone (RSG) can alleviate the inhibitory effects of As+3 on PPAR-gamma and M2a cell polarization.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Naofumi Amioka, Toru Miyoshi
Summary: Abdominal aortic aneurysm (AAA) is a life-threatening disease without established treatment. Fibrates, such as fenofibrate, can regulate the pathogenesis of AAA through anti-inflammatory and anti-oxidative effects. This paper summarizes the studies on the effects of fenofibrate on AAA and discusses the issues associated with its use as a therapeutic agent.
Review
Cell Biology
Xue-feng Yang, De-jing Shang
Summary: Cardiovascular disease events result from abnormalities in arteries and heart. Atherosclerosis is the main cause, associated with dyslipidemia and inflammation. Inhibition of macrophage differentiation and reduction of proinflammatory factors can alleviate atherosclerosis. Peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating triglyceride metabolism, lipid uptake, cholesterol efflux, and inflammatory signaling pathways. This review summarizes the role of PPARα in lipid metabolism and inflammation in atherosclerosis and discusses its potential as a therapeutic target.
CELL BIOLOGY INTERNATIONAL
(2023)
Article
Agriculture, Dairy & Animal Science
Barbara M. Socha, Piotr Socha, Anna Z. Szostek-Mioduchowska, Tomasz Nowak, Dariusz J. Skarzynski
Summary: This study aimed to evaluate and compare the mRNA expression and immunolocalization of PPARα, PPARδ, and PPARγ in the canine endometrium. The results showed that the expression levels of PPARs changed during cystic endometrial hyperplasia (CEH) and CEH-pyometra, suggesting their potential involvement in hormonal disturbances and inflammatory processes.
REPRODUCTION IN DOMESTIC ANIMALS
(2022)
Article
Oncology
Xia Shao, Pengcheng Xu, Lili Ji, Boting Wu, Yanxia Zhan, Xibing Zhuang, Yang Ou, Fanli Hua, Lihua Sun, Feng Li, Xiangdong Wang, Hao Chen, Yunfeng Cheng
Summary: Low-dose decitabine (DAC) promotes M2 macrophage polarization in patients with immune thrombocytopenia (ITP) by demethylating the PPAR? promoter, especially the KLF4 binding sites, thus enhancing PPAR? binding affinity. Low-dose DAC alleviates ITP by restoring the M1/M2 balance and fine-tuning the immunomodulatory function of macrophages. The downstream modulation of M2 macrophage polarization by PPAR? may physiologically antagonize the NLRP3 inflammasome.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Biochemical Research Methods
Lucia Minarrieta, Lis Noelia Velasquez, Tim Sparwasser, Luciana Berod
Summary: Dendritic cells play a crucial role in immunity and tolerance, with their function being influenced by cellular metabolic programs. However, the limitations of current in vitro culture models in DC metabolism research call for better in vivo models. Introducing new techniques can advance research and development in the field of DC metabolism.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Chemistry, Applied
Keisuke Tachibana, Syohei Fukuda, Jun Fukushima, Kenji Ishimoto, Masahiro Sakata, Yasutomo Nishimori, Takefumi Doi
Summary: This study identified a potential PPAR alpha activator from natural resources and demonstrated its ability to improve skin function.
INTERNATIONAL JOURNAL OF COSMETIC SCIENCE
(2022)
Article
Cell Biology
Yucui Gu, Xingjian Niu, Lei Yin, Yiran Wang, Yue Yang, Xudong Yang, Qingyuan Zhang, Hongfei Ji
Summary: Metabolic intervention can modulate the antitumor activity of macrophages within the aberrant metabolic microenvironment of TNBC, potentially leading to the re-establishment of macrophages to resume their antitumor activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Jing-Ping Zhou, Xiao-Ning Yang, Yang Song, Fei Zhou, Jing-Jing Liu, Yi-Qun Hu, Li-Gang Chen
Summary: The study showed that rosiglitazone can alleviate LPS-induced inflammatory damage by activating PPAR gamma and suppressing NF-kappa B. This effect is reversible and concentration-dependent.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Reprint
Biotechnology & Applied Microbiology
Parnia Jabbari, Mona Sadeghalvad, Nima Rezaei
Summary: This article discusses the role of PPAR-γ in patients with sarcoidosis, highlighting how the lack of PPAR-γ may contribute to the development of immune-associated pulmonary granulomas. Due to the anti-inflammatory function of PPAR-γ, understanding the relationship between PPAR-γ, sarcoidosis development, and inflammatory state is crucial in identifying appropriate therapeutic targets. The synthesis of PPAR-γ agonists or ligands may be a promising step towards treating sarcoidosis patients in the future.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2021)
Article
Pharmacology & Pharmacy
Qian Hu, Jiaqi Yao, Xiajia Wu, Juan Li, Guixiang Li, Wenfu Tang, Jingping Liu, Meihua Wan
Summary: This study found that emodin alleviates severe acute pancreatitis-associated acute lung injury (SAP-ALI) by reducing pancreatic exosome-mediated alveolar macrophage activation, highlighting the important role of exosomes in inflammation-associated organ injury.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Cell Biology
Reza Ataei Kachouei, Alireza Doagoo, Maral Jalilzadeh, Seyyed Hossein Khatami, Shima Rajaei, Ali Jahanbazi Jahan-Abad, Farzaneh Salmani, Roya Pakrad, Somayeh Mahmoodi Baram, Mitra Nourbakhsh, Mohammad-Amin Abdollahifar, Hojjat Allah Abbaszadeh, Shokoofeh Noori, Mitra Rezaei, Meisam Mahdavi, Mohammad Reza Shahmohammadi, Saeed Karima
Summary: This study investigates the potential of Acetyl-11-keto-beta-boswellic acid (AKBA), an anti-inflammatory compound from Boswellia species, in preventing and treating non-alcoholic fatty liver disease (NAFLD). The results demonstrate that AKBA improves NAFLD-related serum parameters and inflammatory markers, preserves lipid metabolism, improves hepatic steatosis, and suppresses liver inflammation, thus preventing the progression of NAFLD.
Article
Pharmacology & Pharmacy
Limei Du, Xinglan Huo, Ying Liu
Summary: The study aimed to investigate the effects of resveratrol on chronic lung disease induced by Aspergillus fumigatus infection in rats with chronic obstructive pulmonary disease (COPD). The results showed that resveratrol reduced inflammatory factor levels and increased the protein levels of AMPK, PGC-1 alpha, and AQP5.
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
(2022)
Article
Oncology
Sarang S. Talwelkar, Mikko I. Mayranpaa, Julia Schuler, Nora Linnavirta, Annabrita Hemmes, Simone Adinolfi, Matti Kankainen, Wolfgang Sommergruber, Anna-Liisa Levonen, Jari Rasanen, Aija Knuuttila, Emmy W. Verschuren, Krister Wennerberg
Summary: Treatment with ALK inhibitors improves outcome for NSCLC patients with ALK-rearranged tumors, but resistance typically develops. In this study, tumor cell cultures were generated from an ALK-rearranged tumor specimen and drug screens identified a role for PI3K beta and EGFR inhibition in enhancing ALK-inhibitor response and preventing resistance. Combinatorial treatment with ALK and PI3K beta inhibitors showed promise in targeting ALK-rearranged NSCLC.
MOLECULAR ONCOLOGY
(2023)
Article
Microbiology
Luca A. Robinson, Alice C. Z. Collins, Ronan A. Murphy, Jane C. Davies, Luke P. Allsopp
Summary: This study conducted a comprehensive bioinformatic analysis of 52 high-quality clinical P. aeruginosa genomes isolated from CF patients. The results showed that the clinical CF isolate genome consists mainly of accessory and unique genes, which may provide strain-specific advantages. The study found genetic variability in some effector/immunity encoding genes and identified the presence of orphan vgrG islands in some isolates. The study also revealed disruption to T6SS genomic loci through transposon, prophage, and mobile genetic element insertions.
FRONTIERS IN MICROBIOLOGY
(2023)
Editorial Material
Immunology
Franz Puttur, Clare M. Lloyd
Summary: In this study, Cao et al. uncover the crucial role of dopamine in inhibiting ILC2 function via metabolic restriction, leading to the improvement of key features in asthma pathogenesis.
Review
Immunology
James A. Harker, Clare M. Lloyd
Summary: Harker and Lloyd review the multifaceted roles of Th2 cells in human asthma, emphasizing the influence of tissue location and disease severity. They also discuss the use of biologic therapies targeting Th2 cells and their cytokines. This review highlights the complex functions of Th2 cells in asthma and how they are affected by tissue location, disease stage, and severity, while also exploring the impact of biologics on asthma and the potential for uncovering new roles for Th2 cells in lung inflammation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Lucy Allen, Lorna Allen, Siobhan B. Carr, Gwyneth Davies, Damian Downey, Marie Egan, Julian T. Forton, Robert Gray, Charles Haworth, Alexander Horsley, Alan R. Smyth, Kevin W. Southern, Jane C. Davies
Summary: With the introduction of small molecule, mutation-specific drugs, people with cystic fibrosis are undergoing transformative change as these drugs can restore function of the defective protein CFTR. However, not all genetic variants are suitable for mutation-specific drugs and these drugs also do not correct all the clinical manifestations of the disease. More research is needed to improve treatments for cystic fibrosis.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Infectious Diseases
Isaac Martin, Sandra Morales, Eric W. F. W. Alton, Jane C. Davies
Summary: This study found that bacteriophages can be used as adjuncts to treatment for antibiotic refractory infections, and the combination of phages with certain antibiotics may have synergistic effects. Furthermore, phages showed good bactericidal effects against antibiotic resistant Pseudomonas aeruginosa (Pa), which may be relevant to ongoing clinical trials.
Article
Cell Biology
Erik Melen, Bart N. Lambrecht, Clare M. Lloyd, Marc E. Rothenberg, Kenji Kabashima, Fabio Luciani, Jonathan M. Coquet, Carole Ober, Martijn C. Nawijn, Thomas Platts-Mills, Erika von Mutius
Summary: Allergy is a group of disorders, affecting over 1 billion people worldwide, which includes asthma, atopic dermatitis, rhinitis, and food allergies. Its incidence has dramatically increased since the start of the 20th century, indicating that both genetics and environmental factors play important roles in its development.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Review
Immunology
Clare M. M. Lloyd, Sejal Saglani
Summary: Lloyd and Saglani provide an overview of the immunology of respiratory infections in early life and how it impacts lifelong lung health. Respiratory infections are common in infants and young children, and their effects during this developmental stage can have long-term consequences. The immune system and microbiome in the respiratory tract develop simultaneously, and any disruption to this development can have implications for lung health throughout one's life. The authors emphasize the importance of understanding the molecular mechanisms underlying the interplay between immune and structural cells in the lung and the local microorganisms to mitigate harmful effects and restore lung immune health.
Article
Multidisciplinary Sciences
Richard J. Hewitt, Franz Puttur, David C. A. Gaboriau, Frederic Fercoq, Maryline Fresquet, William J. Traves, Laura L. Yates, Simone A. Walker, Philip L. Molyneaux, Samuel V. Kemp, Andrew G. Nicholson, Alexandra Rice, Edward Roberts, Rachel Lennon, Leo M. Carlin, Adam J. Byrne, Toby M. Maher, Clare M. Lloyd
Summary: This study reveals the impact of changes in extracellular matrix (ECM) composition secreted by lung fibroblasts on the migration and function of KRT5(+) cells in idiopathic pulmonary fibrosis (IPF), contributing to tissue remodeling in the fibrotic lung.
NATURE COMMUNICATIONS
(2023)
Article
Critical Care Medicine
Nicole Mayer-Hamblett, John Paul Clancy, Raksha Jain, Scott H. Donaldson, Isabelle Fajac, Christopher H. Goss, Deepika Polineni, Felix Ratjen, Bradley S. Quon, Edith Zemanick, Scott C. Bell, Jane C. Davies, Manu Jain, Michael W. Konstan, Natanya R. Kerper, Tre LaRosa, Marcus A. Mall, Edward McKone, Kelsie Pearson, Joseph M. Pilewski, Lynne Quittell, Jonathan H. Rayment, Steven M. Rowe, Jennifer L. Taylor-Cousar, George Retsch-Bogart, Damian Downey
Summary: The use of modulator therapies for cystic fibrosis has changed clinical trial strategies, dividing the patient population based on eligibility. The development of nucleic acid-based therapies faces challenges due to limited resources and the inability to conduct placebo-controlled trials. Advancing symptomatic therapies is also difficult in a population already receiving modulator treatment.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Simone Adinolfi, Tommi Patinen, Ashik Jawahar Deen, Sini Pitkänen, Jouni Härkönen, Emilia Kansanen, Jenni Küblbeck, Anna-Liisa Levonen
Summary: The KEAP1-NRF2 pathway is a crucial regulator of cellular defense against oxidative and electrophilic stimuli, playing a significant role in various disease pathologies. Research focused on understanding NRF2 signaling and its downstream effects has led to the identification of novel therapeutic targets. This graphical review provides an updated overview of the KEAP1-NRF2 signaling, highlighting recent advancements in the field, including the mechanism of NRF2 activation and its potential application in cancer diagnostics and treatment.
Article
Respiratory System
Paul McNally, Barry Linnane, Michael Williamson, Basil Elnazir, Christopher Short, Clare Saunders, Laura Kirwan, Rea David, Mariette P. C. van de Corput, Harm A. W. M. Tiddens, Jane C. Davies, Des W. Cox
Summary: In this real-world study, the use of LUM/IVA in children aged 6-11 with CF resulted in improvements in air trapping on CT but worsening in bronchiectasis scores, suggesting that LUM/IVA treatment can improve respiratory function but cannot prevent the progression of bronchiectasis.
RESPIRATORY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Fabliha A. Chowdhury, Nicole Colussi, Malini Sharma, Katherine C. Wood, Julia Z. Xu, Bruce A. Freeman, Francisco J. Schopfer, Adam C. Straub
Summary: Sickle cell disease (SCD) is a hereditary hematological disease with high morbidity and mortality rates worldwide. This article evaluates the potential of small molecule nitroalkenes as a therapy for SCD and highlights their protective effects against end organ damage.