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)
Editorial Material
Cell Biology
Narges Moasefi, Mehdi Fouladi, Amir Hossein Norooznezhad, Reza Yarani, Adibeh Rahmani, Kamran Mansouri
Summary: The COVID-19 pandemic remains a global challenge, with inflammation and cytokine storm being key factors in the pathogenesis of the disease. HIF-1α activation following hypoxia-induced ARDS plays a crucial role in cytokine storm progression. Utilizing PFCs as a co-treatment to reduce hypoxemia and affect NF kappa B pathway shows promise in mitigating COVID-19 ARDS, warranting further research evaluation.
INFLAMMATION RESEARCH
(2021)
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)
Article
Cardiac & Cardiovascular Systems
Ka Lin Heck-Swain, Jiwen Li, Wei Ruan, Xiaoyi Yuan, Yanyu Wang, Michael Koeppen, Holger K. Eltzschig
Summary: The myeloid-expressed HIF1A plays a functional role in providing cardioprotection during ischemia and reperfusion injury by inducing the neuronal guidance molecule netrin-1 in neutrophils.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
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)
Review
Cell Biology
Mykyta Malkov, Chee Teik Lee, Cormac T. Taylor
Summary: Hypoxia and inflammation frequently co-occur in inflammatory diseases, with pro-inflammatory cytokines such as TNF-alpha and IL-1 beta directly impacting HIF signaling pathways. Multi-level crosstalk between inflammatory and hypoxic signaling pathways plays a crucial role in shaping the degree of inflammation at hypoxic sites.
Review
Cell Biology
Xianyi Meng, Ben Wielockx, Martina Rauner, Aline Bozec
Summary: Hypoxia-inducible factors (HIFs) play a crucial role in regulating bone metabolism, angiogenesis, and inflammation, with significant impact on osteoclast activity. Their tight regulation by tissue microenvironments highlights their importance in bone pathologies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Elena V. Mitroshina, Maria O. Savyuk, Evgeni Ponimaskin, Maria V. Vedunova
Summary: Hypoxia is a common pathological condition induced by various events, with the body's adaptation to it being crucial for health and disease. HIFs, a family of transcription factors, play a key role in cellular responses to hypoxia and are increasingly viewed as potential targets for treating a range of hypoxia-associated diseases. The role of HIFs in adaptation to hypoxia is universal across tissue types, including the CNS, where they are involved in regulating neurogenesis, nerve cell differentiation, and neuronal apoptosis, potentially offering new therapeutic opportunities.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Dan Du, Yugang Zhang, Canjun Zhu, Hong Chen, Jia Sun
Summary: The earliest function of hypoxia-inducible factor (HIF) was to respond to hypoxic conditions as a transcription factor. Recent studies have shown that HIF plays an essential role in central regulation of metabolism, affecting the central nervous system's response to glucose, inflammation, and hormonal influence on systemic metabolism. HIF primarily inhibits energy uptake and promotes energy expenditure in the hypothalamus, with its role depending on various factors and mechanisms within the hypothalamus.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Giorgia F. Camagni, Giovanni Minervini, Silvio C. E. Tosatto
Summary: The Prolyl Hydroxylases (PHDs) are a family of enzymes that regulate cell oxygen-sensing by hydroxylating hypoxia-inducible transcription factors alpha (HIFs-alpha) and promoting their degradation. Hypoxia inhibits PHDs activity, leading to HIFs-alpha stabilization and cell adaptation to low oxygen levels. The different isoforms of PHDs have varying effects on tumor progression. Molecular dynamics simulations, conservation analysis, and binding free energy calculations were used to study the binding properties and substrate affinity of PHD2 with HIF-1 alpha and HIF-2 alpha. The findings suggest that the PHD2 C-terminus may play a role in regulating PHD activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Esraa M. Zeidan, Mohammad Akbar Hossain, Mahmoud El-Daly, Mohammed A. S. Abourehab, Mohamed M. A. Khalifa, Ashraf Taye
Summary: This review summarizes the role and regulatory pathways of hypoxia-inducible factor (HIF)-related signaling in the development of pulmonary hypertension (PH), emphasizing the importance of mitochondria in HIF regulation and PH pathogenesis. The potential for therapeutically targeting the components of the HIF system for PH management is also discussed.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hirofumi Teshima, Mayuko Endo, Yumea Furuyama, Hiroyuki Takama, Masashi Akiyama, Tokuji Tsuji, Hideki Tatsukawa, Kiyotaka Hitomi
Summary: The formation of human skin epidermis can be replicated in a 3D keratinocyte culture system with air-exposure being crucial for differentiation. An analysis of biological properties in submerged and air-liquid interphase culture systems revealed significant changes in hypoxia-inducible factor (HIF)-related genes. Despite high HIF protein levels, air-exposure treatment drastically reduced the transcriptional activity of HIF on its canonical response element, which was found to be essential for differentiation. Oxygen supplementation in submerged culture restored keratinocyte differentiation, highlighting the role of HIF in air-exposure-dependent differentiation in a 3D culture system.
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)
Review
Microbiology
Elisabet Bjanes, Victor Nizet
Summary: The complement system is a crucial defense mechanism in immune responses against various pathogens, playing multiple roles beyond direct membrane lysis. While Gram-positive bacteria possess inherent resistance to complement-mediated killing, complement can still flag and destroy these bacteria through alternative mechanisms, demonstrating its versatility in the immune defense.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2021)
Article
Cell Biology
Johanna Richter, Mercedes M. Monteleone, Amanda J. Cork, Timothy C. Barnett, Victor Nizet, Stephan Brouwer, Kate Schroder, Mark J. Walker
Summary: Group A Streptococcus (GAS) causes various infectious diseases in humans, with IL-1 beta signaling playing a key role in disease progression. Streptolysins, particularly streptolysin O (SLO) and streptolysin S, are identified as major drivers of IL-1 beta release during GAS infection, suggesting them as potential therapeutic targets for inflammation intervention.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Review
Immunology
Nina J. Gao, Ervin Rodas Lima, Victor Nizet
Summary: Group A Streptococcus (GAS) is a major human pathogen causing millions of infections annually, which can be identified by testing against the group A carbohydrate (GAC) that makes up a significant portion of its cell wall. Recent discoveries in the genetic locus encoding GAC biosynthesis have provided insights into vaccine design.
INFECTION AND IMMUNITY
(2021)
Article
Biology
Henrique Machado, Yara Seif, George Sakoulas, Connor A. Olson, Ying Hefner, Amitesh Anand, Ying Z. Jones, Richard Szubin, Bernhard O. Palsson, Victor Nizet, Adam M. Feist
Summary: Henrique Machado and colleagues describe mutational mechanisms associated with MRSA vancomycin resistance in Staphylococcus aureus using adaptive laboratory evolution experiments focused on tolerance. Their results reveal environment-dependent mutational strategies to vancomycin tolerization and the impact of mutations in regulatory genes, providing insight into the development of antibiotic resistance under multiple conditions.
COMMUNICATIONS BIOLOGY
(2021)
Article
Microbiology
Aisling R. Caffrey, Haley J. Appaneal, Kerry L. LaPlante, Vrishali V. Lopes, Erlinda R. Ulloa, Victor Nizet, George Sakoulas
Summary: This study demonstrates that the use of P2Y12 inhibitor clopidogrel can reduce in-hospital mortality in patients with Staphylococcus aureus bacteremia.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Nitasha D. Menon, Samuel Penziner, Elizabeth T. Montano, Raymond Zurich, David T. Pride, Bipin G. Nair, Geetha B. Kumar, Victor Nizet
Summary: Bacteriophage therapy is an alternative treatment to antibiotics for multidrug-resistant pathogens. This study found that phage therapy can lead to the emergence of phage-resistant mutants with pyomelanin pigmentation, but these mutants are less virulent due to large genomic deletions and retain susceptibility to the antibiotic colistin. This suggests that they do not pose a contraindication to using anti-pseudomonal phage therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Yujiro Hirose, Piotr Kolesinski, Masanobu Hiraoka, Satoshi Uchiyama, Raymond H. Zurich, Monika Kumaraswamy, Elisabet Bjanes, Partho Ghosh, Shigetada Kawabata, Victor Nizet
Summary: This study shows that the M87 protein of Streptococcus pyogenes strain emm87 acts as a virulence factor by modulating the interaction between the bacteria and innate immune cells, contributing to bacterial resistance and the release of mature IL-1 beta.
MICROBIAL PATHOGENESIS
(2022)
Article
Biology
Piotr Kolesinski, Kuei-Chen Wang, Yujiro Hirose, Victor Nizet, Partho Ghosh
Summary: This study revealed the specific binding mechanism between the Streptococcus pyogenes M protein and the human antimicrobial peptide LL-37, providing important insights into the drug resistance of streptococcus.
Review
Pharmacology & Pharmacy
Sydney P. Thomas, Erce Denizer, Simone Zuffa, Brookie M. Best, Lars Bode, Christina D. Chambers, Pieter C. Dorrestein, George Y. Liu, Jeremiah D. Momper, Victor Nizet, Shirley M. Tsunoda, Adriana H. Tremoulet
Summary: Antibiotics are crucial for perinatal care, but they can harm the host gut microbiota. Current studies mainly focus on the effects of antibiotics on infants directly or through maternal use, with limited knowledge about the risks of antibiotics in human milk to infants.
Article
Microbiology
Ericka Anderson, Bipin Nair, Victor Nizet, Geetha Kumar
Summary: The complexity of antimicrobial resistance (AMR) crisis and its global impact on healthcare requires understanding of the underlying forces and implementation of innovative solutions. Future therapeutic interventions should focus on host-pathogen interactions to enhance the innate immune system and reduce pathogen virulence. Interrupting pathogen survival strategies and using clonotyping assays to identify 'super clones' can guide targeted antibiotic regimens. Innovative alternatives to traditional antibiotics, such as bacteriophage therapy and repurposing drugs, are being successfully used to combat AMR. Policy changes, including shorter durations of antibiotic treatment and increased surveillance measures, can enhance patient safety and global prevention and control programs.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Immunology
E. Mauricio Barajas-Mora, Lindsay Lee, Hanbin Lu, J. Andres Valderrama, Elisabet Bjanes, Victor Nizet, Ann J. J. Feeney, Ming Hu, Cornelis Murre
Summary: Researchers have identified a specific enhancer, E34, within the Igk locus, which is crucial for chromatin remodeling and repositioning, and promotes the rearrangement of Igkv7-33 V-kappa-J(kappa) genes necessary for the production of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.
Article
Engineering, Biomedical
Elisabet Bjanes, Jiarong Zhou, Tariq Qayum, Nishta Krishnan, Raymond H. Zurich, Nitasha D. Menon, Alexandria Hoffman, Ronnie H. Fang, Liangfang Zhang, Victor Nizet
Summary: This study reports a vaccine platform that combines gold nanoparticles coated with immunogenic Acinetobacter baumannii outer membrane vesicles (Ab-OMVs). It induces high levels of IgG antibodies in rabbits, enhances neutrophil killing of A. baumannii, and provides passive protection against sepsis in mice. Active immunization with the Ab-NP vaccine in mice protects against sepsis and pneumonia, activates B cells and dendritic cells, improves neutrophil responses, and mitigates cytokine storm.
ADVANCED NANOBIOMED RESEARCH
(2023)
Article
Infectious Diseases
Lucy Catteau, Yvan Diaz Iglesias, Hannah Tsunemoto, Joseph Pogliano, Francoise Van Bambeke, Victor Nizet, George Sakoulas
Summary: Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis, which does not respond to conventional therapy, can be effectively treated with the combination of nafcillin and daptomycin. In vitro studies have shown that nafcillin enhances the killing of MRSE by daptomycin, both in planktonic cells and biofilms. Nafcillin also sensitizes MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Clinical studies are needed to determine the optimal timing for the use of these regimens to improve clinical outcomes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Multidisciplinary Sciences
Tirthankar Mohanty, Christofer A. Q. Karlsson, Yashuan Chao, Erik Malmstrom, Eleni Bratanis, Andrietta Grentzmann, Martina Morch, Victor Nizet, Lars Malmstrom, Adam Linder, Oonagh Shannon, Johan Malmstrom
Summary: This study used pharmacoproteomics to evaluate the time-dependent treatment effects of meropenem and methylprednisolone on a murine Escherichia coli sepsis model. Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. The findings provide insights for guiding treatment timing, dosage, and potential combination therapies.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Sarah R. Rudd, Leticia Silva Miranda, Hannah R. Curtis, Yves Bigot, Mercedes Diaz-Mendoza, Robert Hice, Victor Nizet, Hyun-Woo Park, Gregor Blaha, Brian A. Federici, Dennis K. Bideshi
Summary: This paper introduces three important commercial bacterial insecticides derived from different subspecies of Bacillus thuringiensis (Bt), including their sources and uses. It also explores the unique features of Bt subspecies israelensis, such as the structure of the parasporal body (PB) and the multilaminar fibrous matrix (MFM), as well as the functions and structural similarities of two proteins, Bt152 and Bt075. Additionally, a novel molecular process for targeting Cry and Cyt proteins has been identified.
