Review
Cell Biology
Thiago Inacio Teixeira do Carmo, Victor Emanuel Miranda Soares, Jonatha Wruck, Fernanda dos Anjos, Debora Tavares de Resende e Silva, Sarah Franco Vieira de Oliveira Maciel, Margarete Dulce Bagatini
Summary: This study summarizes the relationship between inflammation and the purinergic system in cystic fibrosis (CF), and proposes modulation of the purinergic system as a potential strategy for treating CF, with blocking adenosine deaminase action being the most effective approach.
INFLAMMATION RESEARCH
(2021)
Review
Cell Biology
Tayyab Rehman, Michael J. Welsh
Summary: The airway surface liquid (ASL) is a thin fluid layer covering the airway epithelium that plays a crucial role in host defenses and respiratory fitness. In cystic fibrosis (CF), CFTR dysfunction leads to a decrease in HCO3- secretion, a decrease in ASL pH, and impaired defenses, resulting in chronic infection, inflammation, and mucus obstruction. Inflammation may affect acid-base secretion and CFTR function, which has implications for CF airway inflammation management post-modulator era.
Article
Biochemistry & Molecular Biology
Tayyab Rehman, Philip H. Karp, Andrew L. Thurman, Steven E. Mather, Akansha Jain, Ashley L. Cooney, Patrick L. Sinn, Alejandro A. Pezzulo, Michael E. Duffey, Michael J. Welsh
Summary: This study found that inhibiting WNK kinases can increase the pH of airway surface liquid in cystic fibrosis and improve host defenses. WNK kinases regulate the secretion of HCO3- and the transport of Cl-, which affects the pH balance of airway fluid.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Juliette L. Simonin, Alexandre Luscher, Davide Losa, Mehdi Badaoui, Christian van Delden, Thilo Kohler, Marc Chanson
Summary: Defective hydration of airway surface mucosa is associated with recurrent lung infection in cystic fibrosis. The presence of a healthy airway surface liquid can prevent infection.
Review
Biochemistry & Molecular Biology
Stephanie Simon, Abdel Aissat, Fanny Degrugillier, Benjamin Simonneau, Pascale Fanen, Andre-Patrick Arrigo
Summary: Human small heat shock proteins, including HspB1, HspB4, and HspB5, play crucial roles in regulating cellular processes related to Cystic Fibrosis (CF). While HspB1 and HspB4 promote the degradation of CFTR mutants, HspB5 enhances the transport and function of CFTR mutant at the plasma membrane. Additionally, HspB5 molecules can increase the cellular efficiency of current CF therapeutic molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Emily A. Hull-Ryde, John T. Minges, Mary E. B. Martino, Takafumi Kato, Jacqueline L. Norris-Drouin, Carla M. P. Ribeiro
Summary: Studies have shown that the endoplasmic reticulum stress transducer IRE1 alpha plays a role in mediating cytokine production in CF airway inflammation, and inhibition of IRE1 alpha kinase and RNase may reduce cytokine production. This finding suggests that small molecule IRE1 alpha kinase inhibitors could be a novel therapeutic approach for CF airway inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Mark J. Turner, Kathy Abbott-Banner, David Y. Thomas, John W. Hanrahan
Summary: Cystic Fibrosis (CF) lung disease is caused by mutations in the CFTR gene that affect anion and fluid secretion. Studying members of the PDE family regulating CFTR-dependent secretion and the effects of PDE inhibitors on cyclic nucleotide-regulated functions.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Giulia Gorrieri, Federico Zara, Paolo Scudieri
Summary: SLC26A9, a member of the solute carrier family 26 (SLC26), is involved in ion transport mechanisms. It has emerged as one of the interesting alternative targets for cystic fibrosis (CF) treatment, although there are still controversies regarding its contribution and potential. This review summarizes various studies related to SLC26A9, aiming to reconcile them and highlight the current understanding and knowledge gap regarding its role in human lung physiology and CF treatment.
Article
Cell Biology
Pritha Saha, Priti Talwar
Summary: Idiopathic pulmonary fibrosis (IPF) is a progressive, degenerative pulmonary condition that is regulated by factors such as TGF-beta, PDGF, and TNF-alpha. Various factors, including cigarette smoke, asbestos fiber, drugs, and radiation, promote fibrotic remodeling of the lungs. Oxidative stress in the endoplasmic reticulum (ER) plays a key role in IPF pathogenesis.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Favour Felix-Ilemhenbhio, George A. E. Pickering, Endre Kiss-Toth, Jeremy Mark Wilkinson
Summary: Heterotopic ossification refers to the formation of bone in tissues where it is not normally present. The disease can be caused by rare genetic forms or as a response to trauma. Research has identified various cell types and biological pathways involved in the pathogenesis of HO. Recent advances in molecular therapies have shown promise in treating and preventing this condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Michal Debczynski, Giulia Gorrieri, Damian Mojsak, Floriana Guida, Federico Zara, Paolo Scudieri
Summary: ATP12A is the catalytic subunit of the non-gastric proton pump, playing a crucial role in regulating the composition and properties of respiratory epithelial fluid and mucus. Abnormal expression and activity of ATP12A contribute to airway surface liquid acidification and mucus dysfunction, which are involved in the pathogenesis of respiratory diseases such as cystic fibrosis.
Article
Pharmacology & Pharmacy
Isha Sharma, Karan Singh Yadav, Madhav Nilakanth Mugale
Summary: Diabetic retinopathy (DR) is a major cause of vision loss and blindness in people with diabetes mellitus, and redox reactions play a crucial role in its development. Thioredoxins and thioredoxin-interacting proteins are important regulators of cellular redox homeostasis, and their dysregulation is associated with DR. Understanding the molecular mechanisms and pathophysiological roles of the redoxisome and the TRX/TXNIP redox signaling complex is essential for developing effective treatment strategies for DR.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Ophthalmology
Elisabeth M. Messmer
Summary: The pathophysiology of Dry Eye Disease is complex, involving tear film instability, hyperosmolarity, ocular surface damage, and inflammation. Recent studies have identified neuroinflammation as an important factor, as well as changes in microbiome and associations with laryngopharyngeal reflux. Receptor complexes on corneal nerves and obstructed meibomian glands are potential novel therapeutic targets.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Michael Trauner, Claudia Daniela Fuchs
Summary: Cholestatic and non-alcoholic fatty liver disease have shared pathophysiological mechanisms that can be targeted for intervention through novel therapeutic concepts. Nuclear receptors play a crucial role in the treatment of these diseases, with high affinity therapeutic ligands being developed for specific or multiple isoforms. In addition, other therapeutic approaches targeting inflammation and fibrosis directly are also available. Combination strategies that target metabolic disturbances, inflammation, and fibrosis may be necessary for successful treatment of these complex disorders.
Article
Biochemistry & Molecular Biology
Delia Gagliardi, Elisa Pagliari, Megi Meneri, Valentina Melzi, Federica Rizzo, Giacomo Pietro Comi, Stefania Corti, Michela Taiana, Monica Nizzardo
Summary: This article summarizes the role of stathmin alterations in motor neuron diseases (MNDs) and the potential therapeutic effects of their modulation, with a specific focus on amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), the most common forms of MND.
Article
Pediatrics
Rebecca Naples, Alan C. Fenton, Malcolm Brodlie, Sundeep Harigopal, Chris O'Brien
Summary: This study found that electrical activity of the diaphragm (Edi) significantly increased only after the final wean from 2L/min of flow in preterm infants. A protocolised approach to weaning nasal high-flow therapy has a high probability of success.
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
(2023)
Article
Pediatrics
Vrinda Nair, Prakash Kannan Loganathan, Mithilesh Kumar Lal, Helen Pringleton, Thomas Edward Bachman, Malcolm Brodlie, Paul Dixon
Summary: This study evaluated the efficacy of automatic oxygen control in preterm infants receiving respiratory support. The results showed that using automatic oxygen control significantly reduced the occurrence of severe hypoxemia.
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
(2023)
Article
Physiology
JinHeng Lin, Sean M. Gettings, Khaoula Talbi, Rainer Schreiber, Michael J. Taggart, Matthias Preller, Karl Kunzelmann, Mike Althaus, Michael A. Gray
Summary: Our study shows that two commonly used CFTR inhibitors, CFTRinh-172 and GlyH-101, significantly inhibit store-operated calcium entry (SOCE) at commonly used concentrations, and this inhibition is independent of CFTR. Patch clamp experiments demonstrate that both inhibitors can reduce SOCE by blocking the CRAC channel. In addition, these inhibitors have significant effects on human alpha beta gamma-ENaC-mediated currents in Xenopus oocytes, but their effects on delta beta gamma-ENaC function differ. Therefore, caution is needed when using these inhibitors to study the physiological role of CFTR and potentially ENaC.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Medicine, General & Internal
Nicola Hall, Nikki Rousseau, David W. Hamilton, A. John Simpson, Steven Powell, Malcolm Brodlie, Jason Powell
Summary: This study explores the experience of caring for children with tracheostomies from the perspectives of parents and health professional caregivers. The study finds that the experience of parents is influenced by the confidence of healthcare providers and the perceived quality of care, while the experience of healthcare providers is influenced by multidisciplinary team working and support. The study also highlights challenges such as lack of standardization in access to support teams, care packages, and respite care, as well as differences in healthcare provider expertise and experiences across departments and shift patterns.
Article
Cell Biology
Tae Chung, Taylor Bopp, Chris Ward, Francesca M. Notarangelo, Robert Schwarcz, Reyhan Westbrook, Qian-Li Xue, Jeremy Walston, Ahmet Hoke
Summary: Decline in neuromuscular function is a major factor contributing to disability and mortality in the elderly, but the neurobiology of age-associated muscle weakness is not well understood. This study used a mouse model with a deletion of the QPRT gene to examine the neurobiology of neurotoxic metabolites. The findings suggest that the kynurenine pathway may play an important role in frailty and age-associated muscle weakness.
Letter
Critical Care Medicine
Chris Ward, Hafez Al Momani, Melissa J. McDonnell, Desmond M. Murphy, Laura Walsh, John Mac Sharry, Mike Griffin, Ian A. Forrest, Rhys Jones, Amaran Krishnan, Jeffrey Pearson, Robert M. Rutherford
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Otorhinolaryngology
C. D. Campbell, P. C. Ridge, M. J. McDonnell, C. Ward, M. J. Harrison, C. Collins, R. M. Rutherford
Article
Respiratory System
Jason Powell, Steven Powell, Michael W. Mather, Lauren Beck, Andrew Nelson, Pawel Palmowski, Andrew Porter, Jonathan Coxhead, Ann Hedley, Jonathan Scott, Anthony J. Rostron, Thomas P. Hellyer, Fatima Zaidi, Tracey Davey, James P. Garnett, Rachel Agbeko, Chris Ward, Christopher J. Stewart, Clifford C. Taggart, Malcolm Brodlie, A. John Simpson
Summary: This study aimed to characterize airway host defense in tracheostomized children using serial molecular analyses. The results showed that long-term tracheostomy was associated with airway neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential therapeutic targets in preventing recurrent airway complications in this vulnerable group of patients.
Article
Multidisciplinary Sciences
Hafez Al-Momani, Dua'a Al Balawi, Saja Hamed, Borhan Aldeen Albiss, Muna Almasri, Hadeel AlGhawrie, Lujain Ibrahim, Hadeel Al Balawi, Sameer Al Haj Mahmoud, Jeffrey Pearson, Christopher Ward
Summary: In this study, the antibacterial properties of Zinc Oxide nanoparticles (ZnO NPs) were evaluated against Pseudomonas aeruginosa (PA) strains. The biosynthesized ZnO NPs were found to inhibit the growth and biofilm formation of PA strains, and reduce the expression of quorum sensing genes. The results suggest that ZnO NPs can be a potential treatment for PA and other antibiotic resistant bacteria.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Hafez Al-Momani, Muna Almasri, Dua'A. Al Balawi, Saja Hamed, Borhan Aldeen Albiss, Nour Aldabaibeh, Lugain Ibrahim, Hadeel Albalawi, Sameer Al Haj Mahmoud, Ashraf I. Khasawneh, Muna Kilani, Muneef Aldhafeeri, Muayyad Bani-Hani, Matthew Wilcox, Jeffrey Pearson, Christopher Ward
Summary: This study evaluated the antibacterial and antibiofilm effectiveness of biosynthesized silver nanoparticles (Ag NPs) against biofilm-forming clinical isolates of Pseudomonas aeruginosa (PA). Ag NPs showed significant inhibitory effects on growth and biofilm formation of PA strains, as well as reduced expression of biofilm-encoding genes. The findings demonstrate the potential of Ag NPs in the treatment of PA infections.
SCIENTIFIC REPORTS
(2023)
Letter
Medicine, Research & Experimental
Adil Aldhahrani, Jeffrey Pearson, Chris Ward
Article
Pharmacology & Pharmacy
Khadeijah Almarshoodi, Carlos Echevarria, Abeer Kassem, Bassam Mahboub, Laila Salameh, Chris Ward
Summary: The DECAF score is a strong predictor of inpatient death, 30-day mortality, and 90-day readmission in patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) in the United Arab Emirates (UAE). It can help clinicians make appropriate clinical decisions and improve patient outcomes.
Article
Allergy
Laura J. Walsh, Ashley Sullivan, Christopher Ward, Liam J. Fanning, Paul M. O'Byrne, John A. MacSharry, Desmond M. Murphy
Summary: The presence of virus in non-exacerbating asthmatic patients may lead to poorer asthma control and altered airway cytokine composition. Further research is needed to understand the role of viruses in the lung microbiota and their impact on asthma.
ALLERGY ASTHMA & IMMUNOLOGY RESEARCH
(2023)
Meeting Abstract
Respiratory System
H. Alsorroli, W. Funston, S. Wiscombe, J. Simpson, C. Ward, I. Forrest