Review
Pharmacology & Pharmacy
Xinguo Jiang, Wen Tian, Dongeon Kim, Alexander S. McQuiston, Ryan Vinh, Stanley G. Rockson, Gregg L. Semenza, Mark R. Nicolls
Summary: Lymphedema is a chronic inflammatory disorder with incomplete understanding of its pathology and lack of approved pharmacological therapy. Studying hypoxia-regulated pathways in lymphedema may lead to new treatment approaches.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniela Mennerich, Kateryna Kubaichuk, Ghulam S. Raza, Dominik C. Fuhrmann, Karl-Heinz Herzig, Bernhard Bruene, Thomas Kietzmann
Summary: Metabolic adaptation and signal integration in response to hypoxia is regulated by hypoxia-inducible factors (HIFs). This study shows that high fat diet-induced endoplasmic reticulum stress attenuates the response to hypoxia by promoting the degradation of HIF-1 and HIF-2 through GSK3 beta and the ubiquitin ligase FBXW1A/beta TrCP, leading to decreased proliferation, migration, and increased sensitivity to ER stress-induced apoptosis. Moreover, hypoxia affects the ER stress response mainly through the PERK-arm of the unfolded protein response (UPR).
Article
Gastroenterology & Hepatology
Peter A. C. Wing, Peter Jianrui Liu, James M. Harris, Andrea Magri, Thomas Michler, Xiaodong Zhuang, Helene Borrmann, Rosalba Minisini, Nicholas R. Frampton, Jochen M. Wettengel, Laurent Mailly, Valentina D'Arienzo, Tobias Riedl, Luis Nobre, Michael P. Weekes, Mario Pirisi, Mathias Heikenwalder, Thomas F. Baumert, Ester M. Hammond, David R. Mole, Ulrike Protzer, Peter Balfe, Jane A. McKeating
Summary: HIFs play a crucial role in regulating HBV replication, revealing an evolutionary mechanism by which HBV exploits the HIF signaling pathway to persist in the low oxygen environment of the liver.
JOURNAL OF HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Thuy-Hang Nguyen, Stephanie Conotte, Alexandra Belayew, Anne-Emilie Decleves, Alexandre Legrand, Alexandra Tassin
Summary: Muscular dystrophies are genetic degenerative muscle disorders characterized by muscle wasting, often accompanied by respiratory impairments and hypoxemia. Hypoxic stress activates compensatory mechanisms, with HIF-1α playing a key role. Alterations in HIF-1α in muscle may impact the pathophysiology of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Franziska Greulich, Michael Wierer, Aikaterini Mechtidou, Omar Gonzalez-Garcia, N. Henriette Uhlenhaut
Summary: The SETD1A/COMPASS histone methyltransferase complex is highly enriched in activated mouse macrophages and cooperates with the glucocorticoid receptor (GR) to mediate anti-inflammatory effects. Their interaction leads to transcriptional changes in subsets of macrophage target genes.
Article
Oncology
Sonam Takkar, Vikas Sharma, Sourabh Ghosh, Ashish Suri, Chitra Sarkar, Ritu Kulshreshtha
Summary: This study identified miR-196a as a hypoxia-inducible and hypoxia-inducible factor (HIF)-regulated miRNA that plays an oncogenic role in GBM. It was significantly up-regulated in TCGA-GBM, CGGA glioma and Indian GBM patient cohorts. miR-196a overexpression promoted cellular proliferation, migration, spheroid and colony formation, and inhibited apoptosis, while inhibition of miR-196a yielded opposite results, suggesting an oncogenic role.
Review
Immunology
Tineke Vanderhaeghen, Rudi Beyaert, Claude Libert
Summary: Glucocorticoid-induced and hypoxia-induced transcriptional responses play crucial roles in maintaining tissue homeostasis and regulating cellular stress and inflammatory responses. Cells respond rapidly to hypoxia to prevent metabolic shutdown and death through hypoxia inducible factors (HIFs). The crosstalk between the glucocorticoid receptor (GR) and HIFs has been investigated, and the therapeutic effects of GCs on HIF-mediated diseases have been discussed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Virology
David A. Davis, Prabha Shrestha, Robert Yarchoan
Summary: The complex interactions between Kaposi sarcoma-associated herpesvirus (KSHV), hypoxia, and hypoxia-inducible factors (HIFs) play important roles in the pathogenesis of KSHV-induced diseases. Interfering with HIFs can decrease tumor growth and induce death of infected cells and KSHV-induced tumors, providing novel strategies for the treatment of KSHV-induced diseases.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Sebastian F. Zenk, Sebastian Hauck, Daniel Mayer, Mark Grieshober, Steffen Stenger
Summary: Hypoxia-inducible factor (HIF) plays a crucial role in regulating cellular metabolism in response to a low oxygen environment, and stabilizing HIF can enhance host antimicrobial activity against tuberculosis. Inhibition of prolyl-hydroxylases by Molidustat further induces specific immune effectors, reducing the proliferation of intracellular mycobacteria in human macrophages. These findings suggest that HIFs may be promising targets for host-directed therapy against infectious diseases like tuberculosis caused by intracellular bacteria.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Neurosciences
S. J. Kierans, C. T. Taylor
Summary: Under hypoxic conditions, eukaryotic cells can shift metabolism towards glycolysis to maintain ATP levels, a process regulated by HIF-1 alpha. This metabolic switch is crucial for cellular survival during acute hypoxic stress and has implications for cancer cell survival and growth. Understanding the mechanisms central to this reprogramming is important for both physiological and pathophysiological processes.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Biochemistry & Molecular Biology
Alina Mihaela Stanigut, Camelia Pana, Manuela Enciu, Mariana Deacu, Bogdan Cimpineanu, Liliana Ana Tuta
Summary: Research has found that hypoxia response and hypoxia-inducible factors play critical roles in the pathogenesis of diabetic nephropathy, and HIF stabilizers are considered as novel therapeutic agents for treating anemia in CKD patients and relieving oxidative stress in renal tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agronomy
Siju Zhang, Hongjiao Hao, Xiaonan Liu, Yingying Li, Xuan Ma, Weiyin Liu, Rui Zheng, Shanshan Liang, Weijiang Luan
Summary: SDG712 is a negative flowering regulator gene in rice, delaying flowering by repressing key flowering regulator gene Ehd1 and the florigen genes Hd3a and RFT1.
Review
Biology
Michael Ohh, Cassandra C. Taber, Fraser G. Ferens, Daniel Tarade
Summary: von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome caused by mutations in pVHL and disruption of HIF alpha degradation, and the understanding of its genotype-phenotype relationship is crucial for future management of VHL patients.
Review
Oncology
Ilias Mylonis, Georgia Chachami, George Simos
Summary: Hypoxia inducible transcription factors (HIFs) play a critical role in enabling cancer cells to thrive in low oxygen conditions. Inhibiting HIFs can prevent cancer cell growth and metastasis, with peptide HIF inhibitors showing potential as highly selective therapeutic agents. This review highlights the importance of targeting HIFs in cancer treatment and the promising development of peptide inhibitors.
Review
Biochemistry & Molecular Biology
Brian M. Ortmann, James A. Nathan
Summary: Organisms have evolved oxygen-sensing mechanisms to adapt to oxygen availability; HIFs play a crucial role in oxygen-sensing in metazoans; Genetic studies have contributed significantly to our understanding of oxygen-sensing pathways.
Article
Multidisciplinary Sciences
Bo Meng, Adam Abdullahi, Isabella A. T. M. Ferreira, Niluka Goonawardane, Akatsuki Saito, Izumi Kimura, Daichi Yamasoba, Pehuen Pereyra Gerber, Saman Fatihi, Surabhi Rathore, Samantha K. Zepeda, Guido Papa, Steven A. Kemp, Terumasa Ikeda, Mako Toyoda, Toong Seng Tan, Jin Kuramochi, Shigeki Mitsunaga, Takamasa Ueno, Kotaro Shirakawa, Akifumi Takaori-Kondo, Teresa Brevini, Donna L. Mallery, Oscar J. Charles, John E. Bowen, Anshu Joshi, Alexandra C. Walls, Laurelle Jackson, Darren Martin, Kenneth G. C. Smith, John Bradley, John A. G. Briggs, Jinwook Choi, Elo Madissoon, Kerstin B. Meyer, Petra Mlcochova, Lourdes Ceron-Gutierrez, Rainer Doffinger, Sarah A. Teichmann, Andrew J. Fisher, Matteo S. Pizzuto, Anna de Marco, Davide Corti, Myra Hosmillo, Joo Hyeon Lee, Leo C. James, Lipi Thukral, David Veesler, Alex Sigal, Fotios Sampaziotis, Ian G. Goodfellow, Nicholas J. Matheson, Kei Sato, Ravindra K. Gupta
Summary: The Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 and can evade neutralizing antibodies more effectively compared to the Delta variant. A third dose of mRNA vaccine can provide enhanced protection. Omicron has lower replication in lung and gut cells and less efficiently cleaves its spike protein compared to Delta.
Article
Multidisciplinary Sciences
Dinesh Aggarwal, Ben Warne, Aminu S. Jahun, William L. Hamilton, Thomas Fieldman, Louis du Plessis, Verity Hill, Beth Blane, Emmeline Watkins, Elizabeth Wright, Grant Hall, Catherine Ludden, Richard Myers, Myra Hosmillo, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Rhys Izuagbe, Danielle Leek, Olisaeloka Nsonwu, Gareth J. Hughes, Simon Packer, Andrew J. Page, Marina Metaxaki, Stewart Fuller, Gillian Weale, Jon Holgate, Christopher A. Brown, Rob Howes, Duncan McFarlane, Gordon Dougan, Oliver G. Pybus, Daniela De Angelis, Patrick H. Maxwell, Sharon J. Peacock, Michael P. Weekes, Chris Illingworth, Ewan M. Harrison, Nicholas J. Matheson, Ian G. Goodfellow
Summary: Understanding the transmission of SARS-CoV-2 in higher education settings is crucial in limiting spread among students and at-risk populations. A study conducted at the University of Cambridge analyzed viral isolates and found limited introductions of the virus into the university. Student cases were primarily linked to a single genetic cluster, likely originating from social gatherings outside of the university. Transmission was observed within student accommodations and courses but was effectively contained through local infection control measures and a national lockdown. The study highlights important factors in SARS-CoV-2 transmission and effective interventions in higher education settings.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Xiaojie Qiu, Jin Yang, Jiangshan Xu, Shijie Hao, Xin Wang, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Zhao Li, Yan Hong, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Yue Yuan, Xiaoyu Wei, Huiwen Zheng, Weimin Feng, Zhifeng Wang, Yang Liu, Zhaohui Wang, Yunzhi Yang, Haitao Xiang, Lei Han, Baoming Qin, Pengcheng Guo, Guangyao Lai, Pura Munoz-Canoves, Patrick H. Maxwell, Jean Paul Thiery, Qing-Feng Wu, Fuxiang Zhao, Bichao Chen, Mei Li, Xi Dai, Shuai Wang, Haoyan Kuang, Junhou Hui, Liqun Wang, Ji-Feng Fei, Ou Wang, Xiaofeng Wei, Haorong Lu, Bo Wang, Shiping Liu, Ying Gu, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Jan Mulder, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
Summary: Spatially resolved transcriptomic technologies enable us to study complex biological processes such as mammalian embryogenesis. However, current methods have limitations in resolution, gene capture, and field of view, which hinders their systematic application to large and three-dimensional mid- and late-gestation embryos. In this study, we developed Stereo-seq, a spatially enhanced resolution omics-sequencing method, by combining DNA nanoball-patterned arrays and in situ RNA capture. We used Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas, MOSTA, which provides single cell resolution and high sensitivity for mapping the kinetics and directionality of transcriptional variation during mouse organogenesis. By utilizing this atlas, we investigated the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues like the dorsal midbrain. Our panoramic atlas will facilitate in-depth research into long-standing questions about normal and abnormal mammalian development.
Article
Immunology
Zhi Li, Zewen K. Tuong, Isaac Dean, Claire Willis, Fabrina Gaspal, Remi Fiancette, Suaad Idris, Bethany Kennedy, John R. Ferdinand, Ana Penalver, Mia Cabantous, Syed Murtuza Baker, Jeremy W. Fry, Gianluca Carlesso, Scott A. Hammond, Simon J. Dovedi, Matthew R. Hepworth, Menna R. Clatworthy, David R. Withers
Summary: This study used photoconversion to label tumor-infiltrating lymphocytes and found that TCF-1(+) T cells migrate continuously between the tumor and draining lymphoid tissue. The study also revealed the transcriptional characteristics of CD8 T cells in the tumor and their dynamic changes in retention and egress.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Md. Abdul Mazid, Carl Ward, Zhiwei Luo, Chuanyu Liu, Yunpan Li, Yiwei Lai, Liang Wu, Jinxiu Li, Wenqi Jia, Yu Jiang, Hao Liu, Lixin Fu, Yueli Yang, David P. Ibanez, Junjian Lai, Xiaoyu Wei, Juan An, Pengcheng Guo, Yue Yuan, Qiuting Deng, Yang Wang, Ying Liu, Fei Gao, Junwen Wang, Shahriar Zaman, Baoming Qin, Guangming Wu, Patrick H. Maxwell, Xun Xu, Longqi Liu, Wenjuan Li, Miguel A. Esteban
Summary: This study presents a method for producing eight-cell-like cells (8CLCs) from human pluripotent stem cells, and identifies key molecular events and gene networks associated with this conversion through single-cell analysis. The experiments demonstrate the important roles of DPPA3 and TPRX1 in this process. This research provides a resource to uncover the molecular process of early human embryogenesis.
Article
Multidisciplinary Sciences
Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhenkun Zhuang, Xuanxuan Zou, Zhifeng Wang, Taotao Pan, Yue Yuan, Xiao Zhang, Peng Fan, Pengcheng Guo, Yiwei Lai, Ying Lei, Xingyuan Liu, Feng Yu, Shuncheng Shangguan, Guangyao Lai, Qiuting Deng, Ya Liu, Liang Wu, Quan Shi, Hao Yu, Yunting Huang, Mengnan Cheng, Jiangshan Xu, Yang Liu, Mingyue Wang, Chunqing Wang, Yuanhang Zhang, Duo Xie, Yunzhi Yang, Yeya Yu, Huiwen Zheng, Yanrong Wei, Fubaoqian Huang, Junjie Lei, Waidong Huang, Zhiyong Zhu, Haorong Lu, Bo Wang, Xiaofeng Wei, Fengzhen Chen, Tao Yang, Wensi Du, Jing Chen, Shibo Xu, Juan An, Carl Ward, Zongren Wang, Zhong Pei, Chi-Wai Wong, Xiaolei Liu, Huafeng Zhang, Mingyuan Liu, Baoming Qin, Axel Schambach, Joan Isern, Liqiang Feng, Yan Liu, Xiangyu Guo, Zhen Liu, Qiang Sun, Patrick H. Maxwell, Nick Barker, Pura Munoz-Canoves, Ying Gu, Jan Mulder, Mathias Uhlen, Tao Tan, Shiping Liu, Huanming Yang, Jian Wang, Yong Hou, Xun Xu, Miguel A. Esteban, Longqi Liu
Summary: Studying tissue composition and function in non-human primates is crucial for understanding the nature of human species. This study presents a large-scale cell transcriptomic atlas of the non-human primate Macaca fascicularis, providing a vast annotated resource for studying a species closely related to humans. The atlas has been used to reconstruct cell-cell interaction networks, map the distribution of receptors for viruses causing human infectious diseases, and establish potential clinical associations with human genetic diseases.
Article
Medicine, General & Internal
Prasanti Kotagiri, Federica Mescia, Aimee L. Hanson, Lorinda Turner, Laura Bergamaschi, Ana Penalver, Nathan Richoz, Stephen D. Moore, Brian M. Ortmann, Benjamin J. Dunmore, Michael D. Morgan, Zewen Kelvin Tuong, Berthold Gottgens, Mark Toshner, Christoph Hess, Patrick H. Maxwell, Menna R. Clatworthy, James A. Nathan, John R. Bradley, Paul A. Lyons, Natalie Burrows, Kenneth G. C. Smith
Summary: Early and persistent defects in B cell subsets in COVID-19 are associated with hypoxia. Early oxygen therapy may be beneficial in correcting these immune deficiencies and improving outcomes.
Editorial Material
Biochemistry & Molecular Biology
James A. Nathan
NATURE CHEMICAL BIOLOGY
(2023)
Editorial Material
Genetics & Heredity
James A. Nathan
Summary: A new study reveals that prolyl hydroxylation of histone H3 serves as a signal for the recruitment of KDM5A, leading to changes in H3K4me3 and gene expression. This hydroxylation is independent of the HIF hypoxia-sensing pathway and adds another layer of complexity to oxygen-sensitive chromatin modifications.
Article
Biochemistry & Molecular Biology
Jarrod Shilts, Thomas W. M. Crozier, Ana M. Teixeira-Silva, Ildar M. Gabaev, Pehuen Pereyra Gerber, Edward J. D. Greenwood, Samuel James A. Watson, Brian M. Ortmann, Christian M. J. Gawden-Bone, Tekle J. Pauzaite, Markus J. Hoffmann, James A. Nathan, Stefan Pohlmann, Nicholas J. Matheson, Paul J. Lehner, Gavin J. Wright
Summary: In addition to ACE2, LRRC15 has been identified as a protein that interacts with the spike protein of SARS-CoV-2. The expression of LRRC15 is common in human lung vasculature cells and fibroblasts. Inflammatory signals greatly increase the levels of LRRC15 in the lungs of COVID-19 patients. Although LRRC15 alone is not sufficient for viral entry, it may modulate infection of human cells. Further investigation is needed to understand how SARS-CoV-2 exploits host LRRC15 and its role in COVID-19.
Article
Biology
Veronique N. Lafleur, Silvia Halim, Hani Choudhry, Peter J. Ratcliffe, David R. Mole
Summary: Hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR) are transcription factors that play central roles in the pathogenesis of renal cancer. They have both antagonistic and cooperative interactions, including competition for a common subunit, synergy in chromatin binding, and overlapping transcriptional targets. Inhibition of one pathway may promote the oncogenic effects of the other, suggesting that combination therapy targeting both pathways might be more effective.
LIFE SCIENCE ALLIANCE
(2023)
Article
Multidisciplinary Sciences
Linsey M. Porter, Wenrui Guo, Thomas WM. Crozier, Edward JD. Greenwood, Brian Ortmann, Daniel Kottmann, James A. Nathan, Ravindra Mahadeva, Paul J. Lehner, Frank McCaughan
Summary: The impact of cigarette smoke on ACE2 isoform expression and SARS-CoV-2 infection was investigated in this study. It was found that cigarette smoke did not significantly affect ACE2 expression or airway cell infection. Nicotine did not alter ACE2 expression, but NRF2 agonists did. These findings support the epidemiological data suggesting that smokers are not at increased risk of SARS-CoV-2 infection.
Review
Respiratory System
Akhilesh Jha, Fangyue Chen, Sam Mann, Ravi Shah, Randa Abu-Youssef, Holly Pavey, Helen Lin-Jia-Qi, Josh Cara, Daniel Cunningham, Kate Fitzpatrick, Celine Goh, Renee Ma, Souradip Mookerjee, Vaitehi Nageshwaran, Timothy Old, Catherine Oxley, Louise Jordon, Mayurun Selvan, Anna Wood, Andrew Ying, Chen Zhang, Dariusz Wozniak, Iain Goodhart, Frances Early, Marie Fisk, Jonathan Fuld
Summary: Prone positioning can increase oxygen saturation in COVID-19 patients, but it is associated with discomfort. This study highlights the challenges of implementing prone positioning for awake COVID-19 patients requiring oxygen therapy in general ward settings.