Article
Environmental Sciences
Junlin Yang, Tongtong Huang, Jie Yao, Jianghui Zhang, Guohui Bai, Zheng Chen, Chenglong Tu
Summary: Sulphur dioxide (SO2) and fluoride are common environmental pollutants that have a significant impact on human health, particularly in areas where coal consumption is high. The combined toxicity of SO2 and fluoride, as well as their effects on health and underlying mechanisms, have not been adequately assessed. This study used mice and cells to investigate the toxicity of SO2 and fluoride exposure on enamel. The findings suggest that co-exposure to SO2 and fluoride exacerbates enamel injury, resulting in more severe hypomineralization and structural disorders. These effects were also observed at the cellular level. The study concludes that residents in areas exposed to both SO2 and fluoride may have an increased risk of enamel damage.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Review
Cell Biology
Laurence S. Hanssens, Jean Duchateau, Georges J. Casimir
Summary: Cystic fibrosis is a recessive genetic disease caused by mutations in the CFTR gene, resulting in impaired mucociliary clearance, bronchiectasis, and pancreatic insufficiency. The CFTR protein not only acts as a chloride channel but also regulates multiple other pathways, impacting key characteristics such as MCC, immunity, and inflammation.
Article
Biochemistry & Molecular Biology
Xinjie Tan, Archana Kini, Dorothee Roemermann, Ursula Seidler
Summary: This study explored the potential of using an oral gut-selective NHE3 inhibitor, tenapanor, to reduce the frequency of intestinal obstructive episodes in CFTR-deficient mice. The results showed that oral tenapanor application significantly increased stool water content, reduced gastrointestinal transit time, and prevented obstructive episodes and mucosal inflammation in the mice. This suggests that tenapanor may be a safe and affordable adjunctive therapy for cystic fibrosis patients to alleviate constipation and prevent recurrent DIOS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Arianna Venturini, Anna Borrelli, Ilaria Musante, Paolo Scudieri, Valeria Capurro, Mario Renda, Nicoletta Pedemonte, Luis J. Galietta
Summary: Treatment of CF patients with nonsense mutations requires a precision medicine approach with the design of specific drug combinations for each mutation, as different mutations show varying levels of rescue and sensitivity to different drugs. No cooperativity was found between NMD inhibitor and readthrough compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Paul Linsdell, Christina L. Irving, Elizabeth A. Cowley, Yassine El Hiani
Summary: Positively charged amino acid side-chains are important for anion binding and permeation through the CFTR chloride channel. The lysine residue K95 and arginine residue R134 within the pore play crucial roles in anion binding and conductance properties. Despite the importance of specific positive charges, it is the overall number of charges rather than their exact locations that control pore function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Christian Borgo, Claudio D'Amore, Valeria Capurro, Valeria Tomati, Elvira Sondo, Federico Cresta, Carlo Castellani, Nicoletta Pedemonte, Mauro Salvi
Summary: The advent of Trikafta has revolutionized the treatment of cystic fibrosis patients with the most common misfolding mutation, F508del-CFTR. However, there is still room for improvement in its efficacy, especially in rare CFTR mutations. By targeting the misfolding detection machinery, the combination of Trikafta with a drug like TAK-243 shows promising results in improving CFTR function, including in rare CF-causing mutations.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Karina Kleinfelder, Virgini Lotti, Adriana Eramo, Felice Amato, Stefania Lo Cicero, Germana Castelli, Francesca Spadaro, Alessia Farinazzo, Daniele Dell'Orco, Sara Preato, Jessica Conti, Luca Rodella, Francesco Tomba, Angelo Cerofolini, Elena Baldisseri, Marina Bertini, Sonia Volpi, Valeria Rachela Villella, Speranza Esposito, Immacolata Zollo, Giuseppe Castaldo, Carlo Laudanna, Eric J. Sorsher, Jeong Hong, Disha Joshi, Garry Cutting, Marco Lucarelli, Paola Melotti, Claudio Sorio
Summary: Mutation targeted therapy in cystic fibrosis is not suitable for all patients, especially those with rare variants. Our study analyzed the effects of these variants on protein stability and performed functional characterization using different cell models. We found that treatment with CFTR modulators could improve CFTR function and increase CFTR protein levels. In vivo experiments also showed positive effects of VX770 treatment on CF symptoms.
Article
Biochemistry & Molecular Biology
Paul Linsdell
Summary: The study found that the chloride conductance of the CFTR channel is mainly determined by the ability of anions to bind in the pore already occupied by chloride ions, rather than by anion:anion interactions within the pore. Although anion binding is necessary for high conductance, mutations that strengthen anion binding have little effect on conductance, indicating that the wild-type CFTR pore is already close to saturated with chloride ions.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Chemistry, Analytical
Sandra Diez-Garcia, Maria-Jesus Sanchez-Martin, Jose Manuel Amigo, Manuel Valiente
Summary: By combining synchrotron radiation-based techniques, such as infrared microspectroscopy and micro X-ray diffraction, with specific data mining, the limitations of assessing dental enamel remineralization have been overcome. A controlled ion release of structural ions, including Ca2+, PO43-, F-, and Zn2+, for fluorapatite, in the presence of amelogenin, has been proposed to remineralize the surface of etched teeth.
ANALYTICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Amany A. Azouz, Dina A. Hanna, Ali A. Abo-Saif, Basim Anwar Shehata Messiha
Summary: This study investigated the potential effects of montelukast on megalin expression/endocytic function against gentamicin nephrotoxicity. The results suggest that montelukast can interfere with megalin expression/endocytic function, reducing renal cell apoptosis and improving kidney function.
SAUDI PHARMACEUTICAL JOURNAL
(2022)
Article
Chemistry, Organic
Grant A. L. Bare
Summary: There are various synthetic routes available to prepare sulfonyl fluorides (R-SO2F) that have been discovered for almost a century. However, these syntheses often have limitations in terms of scope, hazardous materials, and complex procedures. This study investigates a simple and mild procedure based on direct chloride/fluoride exchange from a sulfonyl chloride (R-SO2Cl) starting material in a KF and water/acetone biphasic mixture. Seventeen examples with high yield (84-100%) and wide scope are described.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Grant A. L. Bare
Summary: Numerous synthetic routes have been discovered for the preparation of sulfonyl fluorides (R-SO2F) over the past century. However, these syntheses are often limited by scope, hazardous materials, and complex procedures. This study investigates a simple and mild procedure based on direct chloride/fluoride exchange from a sulfonyl chloride (R-SO2Cl) starting material in a KF and water/acetone biphasic mixture. Seventeen examples with a wide scope are described, yielding high products (84-100%).
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Mingfeng Zhang, Yuanyue Shan, Charles D. Cox, Duanqing Pei
Summary: The authors discovered that OSC A channels have different oligomeric states and are gated/regulated by lipids at different locations in response to physical forces. These findings reveal the structural diversity and molecular mechanism of force sensing in OSC A channels.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Irene Brusa, Elvira Sondo, Emanuela Pesce, Valeria Tomati, Dario Gioia, Federico Falchi, Beatrice Balboni, Jose Antonio Ortega Martinez, Marina Veronesi, Elisa Romeo, Natasha Margaroli, Maurizio Recanatini, Stefania Girotto, Nicoletta Pedemonte, Marinella Roberti, Andrea Cavalli
Summary: A new RNF5 inhibitor, called 1,2,4-thiadiazol-5-ylidene, has been discovered in this study. It selectively corrects the folding defect of CFTR protein in CF patients and has no toxic side effects. This finding provides evidence for the pursuit of novel treatment strategies for CF.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)