Article
Environmental Sciences
Mingxing Su, Huixiu Qi, Qingzhen Huang, Lili Wang, Xueqi Guo, Qiang Wang
Summary: Inhalation of arsenic can exacerbate the development of bacterial pneumonia, but the exact mechanism remains unclear. Exposure to arsenic or lipopolysaccharide alone produced different effects, while combined exposure increased inflammatory factors and lung damage. The expression of certain proteins involved in epithelial barrier integrity was further disrupted by combined exposure.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Multidisciplinary Sciences
Elena Ortiz-Zapater, Dustin C. Bagley, Virginia Llopis Hernandez, Luke B. Roberts, Thomas J. A. Maguire, Felizia Voss, Philipp Mertins, Marieluise Kirchner, Isabel Peset-Martin, Grzegorz Woszczek, Jody Rosenblatt, Michael Gotthardt, George Santis, Maddy Parsons
Summary: This study demonstrates the important role of epithelial protein CAR in regulating lung inflammation and remodelling. Deletion of CAR leads to reduced house dust mite-induced lung inflammation, decreased neutrophil accumulation and alterations in airway remodelling.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Bao-Shu Xie, Xin Wang, Yao-Hua Pan, Gan Jiang, Jun-Feng Feng, Yong Lin
Summary: Our study revealed that intravenous injection of AAV-PHP.eB led to more efficient transduction to the CNS in C57BL/6 mice compared to BALB/c mice, and transduction was significantly reduced in Apoe or Ldlr knockout C57BL/6 mice. Furthermore, poor CNS transduction in BALB/c mice was dramatically increased by B-cell or natural killer-cell depletion.
Review
Cell Biology
Nachiket M. Godbole, Asif Alam Chowdhury, Neha Chataut, Shanjana Awasthi
Summary: The lung epithelium plays a crucial role in responding to infections, toxins, and allergies, as well as maintaining normal pulmonary function. The tight junctions between lung epithelial cells are essential for maintaining the integrity and fluid balance of the lung. This review summarizes the literature on disrupted tight junctions and epithelial barrier in various lung conditions, and discusses the expression and regulation of specific tight junction proteins against pathogenic stimuli. The review also explores the molecular signaling and crosstalk among signaling pathways that control the tight junction structure and function in the lung.
Review
Endocrinology & Metabolism
Pratap Karki, Konstantin G. Birukov
Summary: Previous studies have focused on the pro-inflammatory and barrier disruptive effects of lipid oxidation products in chronic vascular inflammation related to atherosclerosis, but recent evidence suggests that certain oxidized phospholipids actually have barrier protective and anti-inflammatory properties in the lung vascular endothelium. Among these, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine has been shown to enhance endothelial cell barrier properties and protect against vascular permeability induced by various agonists. Additionally, signaling mechanisms involving cytoskeletal remodeling play a significant role in the regulation of endothelial barrier function by oxidized phospholipids.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ning Li, Bohao Liu, Rui Xiong, Guorui Li, Bo Wang, Qing Geng
Summary: This study investigated the effects of HDAC3 in AT2 cells on LPS-induced ALI and identified the potential mechanisms involved. The findings revealed that HDAC3 deficiency in AT2 cells not only reduced inflammation, apoptosis, and oxidative stress, but also maintained epithelial barrier integrity. Furthermore, HDAC3 promoted ROCK1 transcription, leading to MQC disruption and ALI. Additionally, HDAC3 inhibitor RGFP966 alleviated epithelial damage and improved MQC in LPS-treated AT2 cells.
Article
Immunology
Lihong Yao, Ying Tang, Junjie Chen, Jiahui Li, Hua Wang, Mei Lu, Lijuan Gao, Fang Liu, Ping Chang, Xingxing Liu, Haixiong Tang
Summary: Cell-cell junctions are crucial for cellular and tissue polarity and integrity maintenance. Dysfunction of airway epithelial barrier is associated with acute lung injury (ALI) pathogenesis. In this study, it was found that phosphatidylinositol 3-kinase delta (PI3K delta) plays a role in the dysregulation of airway epithelial barrier integrity in ALI. Pharmacological inhibitors of PI3K delta attenuated LPS-induced lung injury and inflammation, restored epithelial cell junction protein expression, and reduced total protein concentration and cytokine secretion in BALF.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Duanfang Cao, Bingting Ma, Ziyi Cao, Xinzheng Zhang, Ye Xiang
Summary: It is discovered that Semliki Forest virus (SFV) uses the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection. The VLDLR binds multiple E1-DIII sites on SFV, with LA3 having the strongest binding affinity. The high-resolution structure shows that LA3 binds SFV E1-DIII through a small surface area, facilitating the binding of VLDLRs from different host species to SFV.
Article
Pharmacology & Pharmacy
Enchen Zhou, Zhuang Li, Hiroyuki Nakashima, Ahlam Choukoud, Sander Kooijman, Jimmy F. P. Berbee, Patrick C. N. Rensen, Yanan Wang
Summary: Accelerating lipolytic processing of VLDL by brown fat activation can further lower (V)LDL levels and reduce the risk of atherosclerosis.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jae Min Shin, Moon Soo Han, Jae Hyung Park, Seung Hyeok Lee, Tae Hoon Kim, Sang Hag Lee
Summary: This study aimed to investigate the role of ephrinA1/ephA2 signaling in epithelial barrier integrity and rhinovirus-induced epithelial permeability in chronic rhinosinusitis (CRS). The results showed that ephrinA1 treatment increased epithelial permeability and decreased the expression of ZO-1, ZO-2, and occludin. Blocking ephA2 attenuated these effects. Rhinovirus infection upregulated ephrinA1 and ephA2 expression, leading to increased epithelial permeability, which was suppressed in ephA2-deficient cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Huangcan Li, Xiong Wang, Yiran Wang, Yichen Li, Ying Chen, Yin-Ting Wong, Jufang He, Ming-Liang He
Summary: The proteases of SARS-CoV-2 and EV71 upregulate the expression and secretion of LRPAP1, which binds with IFNAR1 to trigger receptor degradation and enhance viral infection. A peptide derived from LRPAP1 can cause IFNAR1 degradation and enhance viral infections, while an LRPAP1 inhibitor stabilizes IFNAR1 and arrests virus infections. This study reveals a novel mechanism used by viruses to evade host immunity and provides a potential strategy for developing pan-antiviral drugs.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Linlin Meng, Muyun Wang, Yixuan Gao, Liangzhi Chen, Kun Wang, Wei Gao, Qinghua Liu
Summary: Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening disease without effective treatments. In this study, researchers discovered that dopamine D1-like receptors are mainly expressed in macrophages and airway epithelial cells (AECs), and their expression is downregulated in ALI mouse lung after lipopolysaccharide (LPS) challenge. The selective agonist SKF38393 (SKF) was shown to inhibit excessive inflammation and oxidative stress in macrophages and AECs, as well as improve airway epithelial barrier dysfunction induced by LPS stimulation. In addition, SKF administration effectively reduced pulmonary inflammation and tissue damage in LPS-induced ALI mice, and the protective actions of SKF were attributed to the activation of Nrf2 antioxidative system.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Immunology
Jiahui Li, Kai Wang, Bo Huang, Rui Li, Xilong Wang, Hailing Zhang, Haixiong Tang, Xin Chen
Summary: The study demonstrated that RAGE signaling mediates airway epithelial barrier dysfunction in a LPS-induced ALI murine model, and inhibition of RAGE effectively alleviates airway inflammation and injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yi Zeng, Chun Yan Wang, Jin Xu, Xiao Le Xu
Summary: This study reveals that RXR13 exerts protective effects against ox-LDL-induced inflammation in endothelial cells, potentially through regulating PGC1α-dependent mitochondrial homeostasis.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Cell & Tissue Engineering
Jing Kong, Shiyuan Wen, Wenjing Cao, Peng Yue, Xin Xu, Yu Zhang, Lisha Luo, Taigui Chen, Lianbao Li, Feng Wang, Jian Tao, Guozhong Zhou, Suyi Luo, Aihua Liu, Fukai Bao
Summary: Organoids derived from stem cells or organ-specific progenitors display structures and functions consistent with organs in vivo. Lung organoids are widely used in modeling injury to and repair of lungs, as well as understanding the mechanisms of epithelial repair.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Hematology
Richard Coffey, Grace Jung, Joseph D. Olivera, Gabriel Karin, Renata C. Pereira, Elizabeta Nemeth, Tomas Ganz
Summary: The hormone erythroferrone (ERFE) is produced by erythroid cells to release iron for erythropoiesis by suppressing hepcidin production. Overexpression of ERFE can lead to iron overload, impaired hepatic signaling, and hepcidin deficiency. Neutralizing excessive ERFE in anemias can prevent iron overload and potentially benefit growth and development.
Letter
Hematology
Amy Zhou, Tim Kong, Jared S. Fowles, Chun-Ling Jung, Maggie J. Allen, Daniel A. C. Fisher, Mary Fulbright, Elizabeta Nemeth, Tomas Ganz, Stephen T. Oh
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Urology & Nephrology
Mark R. Hanudel, Brian Czaya, Shirley Wong, Maxime Rappaport, Shweta Namjoshi, Kristine Chua, Grace Jung, Victoria Gabayan, Bo Qiao, Elizabeta Nemeth, Tomas Ganz
Summary: This study demonstrates the efficacy of ferric citrate in high hepcidin models and shows that enteral ferric citrate absorption is dependent on conventional enterocyte iron transport by ferroportin, with minimal paracellular absorption occurring in these models.
KIDNEY INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Jianqiang Zhu, Qingfeng Fu, Shunhao Wang, Liting Ren, Wenya Feng, Shuting Wei, Zhihong Zhang, Yong Xu, Tomas Ganz, Sijin Liu
Summary: In this study, a smart nanosystem was developed to deliver tocilizumab to the liver for correcting anemia. By diminishing IL-6 signaling, the nanosystem successfully suppressed tumor progression.
Article
Sport Sciences
Andreas Breenfeldt Andersen, Jacob Bejder, Thomas C. Bonne, Henrik Sorensen, Helle Sorensen, Grace Jung, Tomas Ganz, Elizabeta Nemeth, Niels H. Secher, Par I. Johansson, Nikolai Baastrup Nordsborg
Summary: This study examined the use of hepcidin and erythroferrone (ERFE) as biomarkers for indirectly detecting autologous blood transfusion. The results showed that hepcidin and ERFE could complement the athlete biological passport (ABP) in detecting blood transfusion. Besides, the endurance performance of the participants improved after the transfusion.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Multidisciplinary Sciences
Gan Luo, Jue Zhang, HanBin Wang, YaQi Sun, BaoLi Cheng, ZhiPeng Xu, Yan Zhang, Hui Li, WuYuan Lu, Elizabeta Nemeth, Tomas Ganz, XiangMing Fang
Summary: A new class of peptidomimetic antibiotics designed based on the structure of human alpha-defensin 5 (HD5) showed promising activity against drug-resistant bacteria through multiple mechanisms of action.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mark R. Hanudel, Brian Czaya, Shirley Wong, Grace Jung, Kristine Chua, Bo Qiao, Victoria Gabayan, Tomas Ganz
Summary: Ferric citrate has been found to effectively lower phosphate levels and increase iron levels in mice with chronic kidney disease. It also reduces inflammation, improves kidney function, and decreases kidney inflammation and fibrosis, indicating its potential renoprotective effects.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Veena Sangkhae, Vivian Yu, Richard Coffey, Kimberly O. O'Brien, Tomas Ganz, Elizabeta Nemeth
Summary: Under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Vida Zhang, Supak Jenkitkasemwong, Qingli Liu, Tomas Ganz, Elizabeta Nemeth, Mitchell D. Knutson, Airie Kim
Summary: ZIP8 is a transmembrane protein that imports divalent metal ions and is highly expressed in the lung. It can transport iron and is inducible by inflammatory stimuli. This study found that ZIP8 plays a role in systemic iron homeostasis and transports iron from the airway into lung tissue, but it does not modulate the severity of inflammatory lung injury or the host defense against a common bacterial cause of pneumonia.
Review
Medicine, Research & Experimental
Tomas Ganz, Elizabeta Nemeth, Stefano Rivella, Paul Goldberg, Andrew R. Dibble, Michael L. McCaleb, Shuling Guo, Brett P. Monia, Terrance D. Barrett
Summary: TMPRSS6 is a serine protease that is highly expressed in the liver. Mutations in TMPRSS6 were found to be the cause of iron-refractory iron deficiency anemia (IRIDA) in humans and mice. TMPRSS6 negatively regulates the expression of hepcidin, a systemic iron-regulatory hormone. Understanding the biology and mechanism of action of TMPRSS6 has led to the development of new therapeutic approaches for erythropoiesis and iron homeostasis-related diseases.
ADVANCES IN THERAPY
(2023)
Article
Hematology
Jihyun Song, Krishna M. Sundar, Monika Horvathova, Radhika Gangaraju, Karel Indrak, Robert D. Christensen, Samuel Genzor, Carsten Lundby, Vladimir Divoky, Tomas Ganz, Josef T. Prchal
Summary: Obstructive sleep apnea (OSA) does not cause significant increase in red cell mass due to neocytolysis and inflammation-mediated suppression of erythropoiesis. Accelerated erythropoiesis in OSA patients is offset by the lysis of newly generated erythrocytes upon return to normoxia, resulting in a normal blood hemoglobin concentration.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Cell Biology
Corbin R. Azucenas, T. Alex Ruwe, John P. Bonamer, Bo Qiao, Tomas Ganz, Mika Jormakka, Elizabeta Nemeth, Bryan Mackenzie
Summary: Fpn is a protein expressed in the plasma membrane of macrophages, enterocytes, and hepatocytes, which mediates the transfer of cellular iron into the blood plasma. Research has shown that human Fpn does not transport manganese, but mouse Fpn may be involved in manganese metabolism. Comparative analysis of mouse and human Fpn revealed that they share identical properties in terms of substrate profile, calcium dependence, optimal pH, and hepcidin sensitivity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Hematology
Binal N. Shah, Xu Zhang, Adelina I. Sergueeva, Galina Y. Miasnikova, Tomas Ganz, Josef T. Prchal, Victor R. Gordeuk
Summary: Von Hippel-Lindau protein (VHL) is crucial for regulating cellular processes under hypoxic conditions. Mutations in VHLR200W lead to Chuvash erythrocytosis, a congenital disorder characterized by heightened hypoxia sensing. Increased levels of HIFs, which are regulated by VHL, result in elevated erythropoietin gene transcription and hematocrit levels.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Correction
Multidisciplinary Sciences
QiXing Chen, Yang Yang, JinChao Hou, Qiang Shu, YiXuan Yin, WeiTao Fu, Feng Han, TingJun Hou, CongLi Zeng, Elizabeta Nemeth, Rose Linzmeier, Tomas Ganz, XiangMing Fang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Meeting Abstract
Urology & Nephrology
Shilpa Sharma, Renata Pereira, Elizabeta Nemeth, Joachim Ix, Isidro Salusky, Tomas Ganz
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)