Article
Cell Biology
Takahide Matsui, Yuriko Sakamaki, Shumpei Nakashima, Mitsunori Fukuda
Summary: This study analyzes the role of members of the Rab family small GTPases in asymmetrical exosome release. It is found that Rab27 and Rab37 are involved in apical exosome release, while Rab39 is involved in basolateral exosome release.
Article
Medicine, Research & Experimental
Sepideh Khatibi, Mohammadreza Modaresi, Reza Kazemi Oskuee, Mohammad Salehi, Seyed Hamid Aghaee-Bakhtiari
Summary: This study investigated genetic modification of CF with Delta F508 mutation of the CFTR gene using CRISPR in peripheral blood mononuclear cells. The results showed the feasibility of site-specific gene targeting with the CRISPR/Cas9 system, presenting a powerful approach for genetic engineering and potential treatment of human diseases.
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
(2021)
Review
Endocrinology & Metabolism
Josefa Mora Vallellano, Carmen Delgado Pecellin, Isabel Delgado Pecellin, Esther Quintana Gallego, Jose Luis Lopez-Campos
Summary: This study found that CF patients with normal nutritional status and without acute lung disease had normal bone mineral density but altered bone remodeling. Various bone turnover biomarkers were associated with CF, with factors like PTH, CTX, and OPG being significant predictors of BMD. Additionally, certain markers like PTH, TNF alpha, calcium, 1,25-vitamin D, and OPG were significantly linked to CF.
Article
Biochemistry & Molecular Biology
Sonia Zacarias, Marta S. P. Batista, Sofia S. Ramalho, Bruno L. Victor, Carlos M. Farinha
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. The approval of modulators that act on mutant CFTR protein, correcting its molecular defect and thus alleviating the burden of the disease, revolutionized the field of CF. However, these drugs do not apply to all patients with CF, especially those with rare mutations. In this study, the impact of rare mutations on CFTR expression, processing, and response to modulators was evaluated, and it was found that mutations in different locations have different effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sara Cuevas-Ocana, Jin Ye Yang, Magomet Aushev, George Schlossmacher, Christine E. Bear, Nicholas R. F. Hannan, Neil D. Perkins, Janet Rossant, Amy P. Wong, Michael A. Gray
Summary: Introducing or correcting disease-causing mutations in human pluripotent stem cells followed by tissue-specific differentiation provides sustainable models of multiorgan diseases. However, low editing efficiency and the need for specialised equipment make hPSC genome editing challenging. In this study, a combination of methods including cell cycle synchronisation, single-stranded oligodeoxyribonucleotides, manual clonal isolation, and rapid screening improved the generation of correctly modified hPSCs with up to 10% efficiency within 3-6 weeks.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pathology
Alexandra McCarron, David Parsons, Martin Donnelley
Summary: Over the past 30 years, various CF animal models have been generated for research, using different species such as mice, pigs, and zebrafish. While the availability of diverse animal models is advantageous, it also adds complexity to the decision-making process in selecting the right model. This review discusses the characteristics and considerations for choosing an appropriate CF animal model, along with the potential use of in vitro systems as alternatives.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Multidisciplinary Sciences
Sara Bitam, Ahmad Elbahnsi, Geordie Creste, Iwona Pranke, Benoit Chevalier, Farouk Berhal, Brice Hoffmann, Nathalie Servel, Danielle Tondelier, Aurelie Hatton, Christelle Moquereau, Melanie Faria Da Cunha, Alexandra Pastor, Agathe Lepissier, Alexandre Hinzpeter, Jean-Paul Mornon, Guillaume Prestat, Aleksander Edelman, Isabelle Callebaut, Christine Gravier-Pelletier, Isabelle Sermet-Gaudelus
Summary: The compound C407 and its derivatives correct the F508del-CFTR protein by stabilizing specific positions on the protein molecule. An analog of C407, G1, significantly improves CFTR activity by interacting more effectively with ICL4. These findings suggest new strategies for optimizing the ICL4-NBD1 interface.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Andrew G. McKee, Eli F. McDonald, Wesley D. Penn, Charles P. Kuntz, Karen Noguera, Laura M. Chamness, Francis J. Roushar, Jens Meiler, Kathryn E. Oliver, Lars Plate, Jonathan P. Schlebach
Summary: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR chloride channel. While most CF variants can be partially rescued by therapeutic correctors, some are insensitive to them. By studying CF variants and the effects of correctors, researchers have discovered that the response to correctors depends on the level of expression and proximity to corrector binding pockets. Combining correctors can rescue more variants by stabilizing different folding transitions. These findings provide insights into CF variant expression and offer new approaches for precision pharmacology.
CELL CHEMICAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Varsha Venkatarangan, Weichao Zhang, Xi Yang, Jess Thoene, Si Houn Hahn, Ming Li
Summary: Cystinosis is a lysosomal storage disease caused by mutations in the cystine exporter, cystinosin. This study identified a rapidly degrading disease variant called cystinosin(7A) and investigated its degradation mechanisms and potential treatment using chemical chaperones.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Immunology
Samantha L. Tucker, Demba Sarr, Balazs Rada
Summary: Cystic Fibrosis is a genetic disease that causes chronic lung inflammation and infections, leading to high mortality rates. Immune system disruption in CF results in impaired immune responses, chronic infections with pathogens, and alterations in T cell and neutrophil functions. The role of P. aeruginosa and gMDSCs in T cell suppression and immune evasion in CF remains a subject of ongoing research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Sabine Willems, Johannes Morstein, Konstantin Hinnah, Dirk Trauner, Daniel Merk
Summary: Photopharmacology enables optical control of biochemical processes using small-molecule photoswitches, with potential for developing drug molecules that can be locally activated to reduce adverse effects. Expanding the photopharmacological arsenal to new members of the PPAR family has shown promising results in selectively activating specific PPAR subtypes in live cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Respiratory System
Aderonke Sofoluwe, Alice Zoso, Marc Bacchetta, Sylvain Lemeille, Marc Chanson
Summary: This study investigated the gene expression profile of CFTR knocked down airway epithelial cells in response to bacterial and viral challenges, revealing key molecular pathways and signaling involved in antiviral and antibacterial responses. The findings provide insights into the defective immune response in CF airway epithelium during infection.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Cell Biology
Charlotte Ford, Christopher G. Burd
Summary: The trans-Golgi network plays a crucial role in the polarization of epithelial cells by coordinating the sorting and secretion of proteins and lipids. This study investigates the sorting of syndecan-1 in different cell types and reveals that its basolateral targeting is dependent on the presence of a full-length PDZ motif and the PDZ domain golgin protein GOPC. The study also uncovers changes in Golgi morphology induced by GOPC overexpression, suggesting that GOPC affects the Golgi organization and indirectly influences the sorting of syndecan-1.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Public, Environmental & Occupational Health
Giuseppe Campagna, Annalisa Amato, Fabio Majo, Gianluca Ferrari, Serena Quattrucci, Rita Padoan, Giovanna Floridia, Donatello Salvatore, Vincenzo Carnovale, Gianna Puppo Fornaro, Domenica Taruscio, Marco Salvatore
Summary: The Italian Cystic Fibrosis Registry (ICFR) collects data on CF patients in Italy, analyzing clinical trends and comparing data internationally. This report updates the demographic and clinical data for 2019 and 2020, showing an increase in the CF population and a growing prevalence among adults. The report highlights the declining lung function, nutrition challenges, chronic infections, lung transplantations, and mortality rates in CF patients.
EPIDEMIOLOGIA & PREVENZIONE
(2022)
Article
Biochemistry & Molecular Biology
Ana M. Matos, Peter Jordan, Paulo Matos
Summary: Cystic fibrosis, caused by mutations in CFTR, is the most common inherited disease in Caucasians, with F508del being the most frequent mutation. While small-molecule CFTR modulator drugs have shown success in treating F508del-CFTR carriers, some approved drug combinations have led to severe side effects. The addition of HGF may potentially ameliorate the effects of CFTR modulators in rescuing F508del-CFTR function.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)