Article
Cell Biology
Fulei Wuchu, Xiyang Ma, Yanting Que, Junjiang Chen, Ye Chun Ruan
Summary: The regulatory interaction between CFTR and ENaC in epithelial tissues is complex and involves Ca2+ modulation of cAMP production. ENaC knockdown has a biphasic effect on CFTR expression and functionality, with low levels of knockdown leading to upregulation and restoration, while high levels of knockdown result in negative regulation. This biphasic regulation has been observed in different epithelial cell lines.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Frauke Stanke, Tim Becker, Haide Susanne Ismer, Inga Dunsche, Silke Hedtfeld, Julia Kontsendorn, Anna-Maria Dittrich, Burkhard Tuemmler
Summary: CFTR and ENaC play crucial roles in the manifestation of cystic fibrosis. The study identified SCNN1B as a genetic modifier in F508del-CFTR homozygotes and found that the expression levels of SCNN1B are associated with the rs2303153 genotype in intestinal epithelia.
Article
Immunology
Beate Illek, Horst Fischer, Terry E. Machen, Gopika Hari, Karl V. Clemons, Gabriele Sass, Jose A. G. Ferreira, David A. Stevens
Summary: This study established a fungal epithelial co-culture model to investigate the impact of Aspergillus fumigatus (Af) infection on cystic fibrosis (CF) bronchial epithelial barrier function. The results showed that Af infection resulted in bronchial epithelial cell damage and impaired epithelial barrier function, which was exacerbated in the absence of CFTR. The study also found that Gliotoxin, a major virulence factor of Af, rapidly disrupted the epithelial barrier function and induced chloride secretion in the presence of CFTR.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Physiology
Arun K. Rooj, Estelle Cormet-Boyaka, Edlira B. Clark, Yawar J. Qadri, William Lee, Ravindra Boddu, Anupam Agarwal, Richa Tambi, Mohammed Uddin, Vladimir Parpura, Eric J. Sorscher, Cathy M. Fuller, Bakhrom K. Berdiev
Summary: The study demonstrates a close physical association between CFTR and ENaC in the pathophysiology of cystic fibrosis, even in the presence of Liddle's syndrome mutations, suggesting a direct intermolecular interaction between these proteins. The findings are supported by coimmunoprecipitation and fluorescence resonance energy transfer measurements, indicating a potential therapeutic target for CF treatment.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
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)
Review
Cardiac & Cardiovascular Systems
Taseer Ahmad, Lale A. Ertuglu, Sepiso K. Masenga, Thomas R. Kleyman, Annet Kirabo
Summary: The d subunit of the epithelial sodium channel (ENaC) is poorly understood, but recent studies have shown its association with blood pressure, kidney function, inflammation, and salt-induced hypertension. Its expression in human vasculature and antigen presenting cells (APCs) suggests its role in vascular function and immune response.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Genetics & Heredity
James A. Reihill, Lisa E. J. Douglas, S. Lorraine Martin
Summary: Cystic fibrosis is a genetic disorder caused by mutations in the CFTR gene, leading to dehydration of the airway surface liquid and impaired mucociliary clearance, making individuals more susceptible to bacterial infections and inflammation. Restoring airway hydration can improve mucociliary clearance.
Article
Cell Biology
Sunny Xia, Zoltan Bozoky, Michelle Di Paola, Onofrio Laselva, Saumel Ahmadi, Jia Xin Jiang, Amy L. Pitstick, Chong Jiang, Daniela Rotin, Christopher N. Mayhew, Nicola L. Jones, Christine E. Bear
Summary: This study introduced a high-throughput, fluorescence-based assay for detecting CFTR channel activity in iPSC-derived intestinal organoids, which could be adapted for studying other apical membrane proteins, offering new strategies for expanding CF therapy discovery.
Article
Biochemistry & Molecular Biology
Sean M. Gettings, Stephan Maxeiner, Maria Tzika, Matthew R. D. Cobain, Irina Ruf, Fritz Benseler, Nils Brose, Gabriela Krasteva-Christ, Greetje Vande Velde, Matthias Schonberger, Mike Althaus
Summary: The epithelial sodium channel (ENaC) is critical for maintaining salt and water balance in tetrapod vertebrates. While the physiology of alpha beta gamma-ENaC is well understood, the lack of mammalian model organisms has hindered research on delta beta gamma-ENaC. Recent analysis of rodent genomes revealed the presence of SCNN1D in rodents, contrary to previous beliefs, shedding light on potential new model animals for studying delta-ENaC physiology.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Cell Biology
Isabelle Fajac, Isabelle Sermet
Summary: Cystic fibrosis is a severe genetic disorder caused by mutations in the CFTR gene. New drugs called CFTR modulators aim to restore the function of the CFTR protein, but some patients with rare mutations are not yet eligible for this treatment. Various approaches are being pursued to expand the range of mutations eligible for CFTR modulators and develop new therapies for mutations that do not produce CFTR protein.
Review
Cardiac & Cardiovascular Systems
Puja Paudel, Fiona J. McDonald, Martin Fronius
Summary: Delta-ENaC, the fourth subunit of vascular epithelial sodium channels, has been less understood but recent discovery of its presence in human vascular cells suggests its potential significant role in vascular physiology and pathophysiology in humans. It has different properties compared to the alpha subunit, making it a potential new drug target for cardiovascular disease treatment.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yeni Wahyuni Hartati, Dina Ratna Komala, Diana Hendrati, Shabarni Gaffar, Ari Hardianto, Yulia Sofiatin, Husein Hernandi Bahti
Summary: ENaC protein plays a crucial role in regulating sodium levels in blood plasma, and having a family history of hypertension may increase the risk of having an excessive amount of ENaC protein. An aptasensor method utilizing electrochemical techniques has been developed to detect ENaC protein levels, showing potential for urine sample testing.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Nicole Reyne, Patricia Cmielewski, Alexandra McCarron, Juliette Delhove, David Parsons, Martin Donnelley
Summary: The study evaluated the effect of lentiviral-mediated CFTR airway gene delivery on nasal PD in a CFTR knockout rat model, showing that the gene therapy resulted in a mean correction of 46% towards wild-type chloride response in treated CF rats.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Critical Care Medicine
Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N. Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L. Metersky, Matthew Vincent, Christopher P. Crum, Richard C. Boucher, Harry Karmouty-Quintana, Howard J. Huang, Ajay Sheshadri, Burton F. Dickey, Kalpaj R. Parekh, John F. Engelhardt, Frank D. McKeon, Wa Xian
Summary: CF patients' lungs harbor proinflammatory stem cell variants that contribute to persistent inflammation and are resistant to CFTR modulator therapy.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Article
Biochemistry & Molecular Biology
Claudia Ferlito, Vincenzo Visco, Roberto Biselli, Maria Sofia Cattaruzza, Giulia Carreras, Gerardo Salerno, Florigio Lista, Maria Rosaria Capobianchi, Concetta Castilletti, Daniele Lapa, Guido Antonelli, Massimo Gentile, Maurizio Sorice, Gloria Riitano, Giuseppe Lucania, Valeria Riccieri, Fabrizio Mainiero, Antonio Angeloni, Marco Lucarelli, Giampiero Ferraguti, Alberto Autore, Marco Lastilla, Simonetta Salemi, Michela Ileen Biondo, Andrea Picchianti-Diamanti, Sara Caporuscio, Raffaela Teloni, Sabrina Mariotti, Roberto Nisini, Raffaele D'Amelio
Summary: This study analyzed the possible late appearance of side effects and the half-life of induced antibodies in a military cohort. The results showed no late side effects and confirmed the long duration of certain vaccine-induced antibodies.
Article
Respiratory System
Antonella Tosco, Alice Castaldo, Carla Colombo, Laura Claut, Vincenzo Carnovale, Paola Iacotucci, Marco Lucarelli, Giuseppe Cimino, Benedetta Fabrizzi, Nicole Caporelli, Fabio Majo, Fabiana Ciciriello, Rita Padoan, Piercarlo Poli, Giovanni Taccetti, Claudia Centrone, Rosaria Casciaro, Carlo Castellani, Donatello Salvatore, Carmela Colangelo, Paolo Bonomi, Giuseppe Castaldo, Vito Terlizzi
Summary: This study retrospectively analyzed the long-term clinical outcomes and progression to CF diagnosis in a large cohort of Italian patients with the CFTR F508del/5T;TG12 genotype. After a median follow-up of 6.7 years, 34.9% of the patients were diagnosed with CF, most of whom had mild lung diseases and pancreatic sufficiency.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Review
Oncology
Sergio Terracina, Giampiero Ferraguti, Carla Petrella, Sabina Maria Bruno, Giovanna Blacona, Maria Grazia Di Certo, Antonio Minni, Antonio Greco, Angela Musacchio, Massimo Ralli, Luigi Tarani, Mauro Ceccanti, Antonella Polimeni, Viviana Triaca, Marco Fiore
Summary: Evidence suggests that there is a bidirectional relationship between cancer and aging, with age being a risk factor for cancer and cancer treatments potentially accelerating aging. Aging is associated with genomic instability, telomere attrition, altered proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and deregulated nutrient sensing, all of which have implications for cancer development. Anti-growth factor agents and epigenetic therapies are emerging as important strategies in treating aging-related diseases, including cancer.
CURRENT CANCER DRUG TARGETS
(2023)
Review
Biochemistry & Molecular Biology
Giampiero Ferraguti, Francesca Fanfarillo, Luigi Tarani, Giovanna Blacona, Francesca Tarani, Christian Barbato, Antonio Minni, Massimo Ralli, Silvia Francati, Antonio Greco, Carla Petrella, Marco Fiore
Summary: Infertility is a global health issue defined by the WHO as the inability to establish a pregnancy after 12 months of unprotected sexual intercourse. Male infertility can be caused by congenital or acquired factors and its therapeutic approach depends on the underlying causes. Recent studies suggest a potential role of nerve growth factor (NGF) in male reproductive physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Francesca Gabanella, Andrea Colizza, Maria Chiara Mottola, Silvia Francati, Giovanna Blacona, Carla Petrella, Christian Barbato, Antonio Greco, Massimo Ralli, Marco Fiore, Nicoletta Corbi, Giampiero Ferraguti, Alessandro Corsi, Antonio Minni, Marco de Vincentiis, Claudio Passananti, Maria Grazia Di Certo
Summary: Head and neck squamous cell carcinoma (HNSCC) originates from the mucosal epithelium and laryngeal squamous cell carcinoma (LSCC) is a subtype of HNSCC. This study focuses on the role of the Survival Motor Neuron (SMN) protein in LSCC and explores its impact on cancer-related behaviors. The study also reveals a physical interaction between SMN and the epidermal growth factor receptor (EGFR) in LSCC. Overall, this study highlights SMN as a potential therapeutic target for LSCC and other subtypes of HNSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anna Chiara Conflitti, Gaia Cicolani, Alessandra Buonacquisto, Francesco Pallotti, Fabiana Faja, Serena Bianchini, Giovanna Blacona, Sabina Maria Bruno, Antonella Linari, Marco Lucarelli, Diletta Montanino, Ludovico Muzii, Andrea Lenzi, Francesco Lombardo, Donatella Paoli
Summary: The aim of this study was to investigate the correlation between Sperm DNA Fragmentation (SDF), sperm-borne miR-34c-5p and miR-449b-5p levels, and the outcome of Assisted Reproductive Technologies (ART). The results showed that SDF was positively correlated with the percentage of low-quality embryos and negatively correlated with viable embryos. SDF > 2.9% increased the risk of obtaining a non-viable embryo by almost 4-fold. Additionally, higher levels of miR-34c-5p compared to miR-449b-5p increased the probability of obtaining viable embryos by 14-fold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marco Fiore, Antonio Minni, Luca Cavalcanti, Giammarco Raponi, Gianluca Puggioni, Alessandro Mattia, Sara Gariglio, Andrea Colizza, Piero Giuseppe Meliante, Federica Zoccali, Luigi Tarani, Christian Barbato, Marco Lucarelli, Flavio Maria Ceci, Silvia Francati, Giampiero Ferraguti, Mauro Ceccanti, Carla Petrella
Summary: Alcohol consumption is associated with oxidative stress and an increased risk of upper aero-digestive tract (UADT) carcinoma. Microorganisms in the oral cavity can metabolize ethanol and form acetaldehyde, a carcinogenic metabolite. A study was conducted on UADT cancer patients to estimate their alcohol consumption and analyze the presence of acetaldehyde-producing bacteria. The study found that heavy drinkers had a higher presence of these bacteria, which correlated with increased oxidative stress.
Article
Microbiology
Fiorenza Pennacchia, Eqrem Rusi, Wael Abu Ruqa, Maria Antonella Zingaropoli, Patrizia Pasculli, Giuseppina Talarico, Giuseppe Bruno, Christian Barbato, Antonio Minni, Luigi Tarani, Gioacchino Galardo, Francesco Pugliese, Marco Lucarelli, Giampiero Ferraguti, Maria Rosa Ciardi, Marco Fiore
Summary: This study aimed to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality of Omicron-infected patients. The results showed that high-sensitivity troponin-T, fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin can predict lethal outcomes at the emergency department.
Article
Biochemistry & Molecular Biology
Sergio Terracina, Antonio Pallaria, Marco Lucarelli, Antonio Angeloni, Annarita De Angelis, Flavio Maria Ceci, Brunella Caronti, Silvia Francati, Giovanna Blacona, Marco Fiore, Giampiero Ferraguti
Summary: The determination of albumin in the urine can yield different results depending on the method used. Urinalysis is commonly used as a screening tool for kidney disease, with the assessment of albumin/protein and creatinine. Early identification of albuminuria/proteinuria is crucial to prevent or delay the onset of chronic kidney disease and associated cardiovascular damage. Quantitative assays are considered the gold standard for assessing urine albumin, creatinine, and their ratio, while dipstick methods are more suitable for population screening. This study found a good correlation between a dipstick method and a quantitative test, although the dipstick method tends to overestimate the albumin-to-creatinine ratio, leading to more false positives.
Article
Genetics & Heredity
Sabina Maria Bruno, Giovanna Blacona, Stefania Lo Cicero, Germana Castelli, Mariarita Virgulti, Giancarlo Testino, Silvia Pierandrei, Andrea Fuso, Giuseppe Cimino, Giampiero Ferraguti, Adriana Eramo, Marco Lucarelli
Summary: In the precision medicine era of cystic fibrosis (CF), accurate quantification of CFTR gene expression is crucial for personalized therapeutic approaches. This paper compares two methods for quantifying CFTR gene expression and discusses their advantages and limitations.
Article
Respiratory System
Lo Cicero Stefania, Castelli Germana, Blacona Giovanna, Bruno Sabina Maria, Sette Giovanni, Pigliucci Riccardo, Villella Valeria Rachela, Esposito Speranza, Zollo Immacolata, Spadaro Francesca, De Maria Ruggero, Biffoni Mauro, Cimino Giuseppe, Amato Felice, Lucarelli Marco, Eramo Adriana
Summary: Cystic fibrosis (CF) is a genetic disease caused by defects in the CFTR gene. Trikafta, a triple combination drug, has been found to rescue the function of the most common CFTR variant, even in genotypes with a single copy of the mutated allele. Through the use of nasal conditionally reprogrammed cell (CRC) models, researchers were able to successfully evaluate and treat the orphan CFTR mutation L1077P, which is not eligible for targeted therapies. This approach allows for personalized CF treatments and supports rare patients who are excluded from clinical trials.
RESPIRATORY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tiziana Raia, Federica Armeli, Rosaria A. Cavallaro, Giampiero Ferraguti, Rita Businaro, Marco Lucarelli, Andrea Fuso
Summary: DNA methylation, the main epigenetic modification, influences neurodegeneration. In this study, the researchers investigated the effects of S-adenosylmethionine (SAM) supplementation during the perinatal period on the development of Alzheimer's disease (AD) symptoms in TgCRND8 mice. They found that both post-weaning and perinatal SAM supplementation effectively reduced PSEN1 expression and amyloid deposition in adult mice. These findings emphasize the role of early-life epigenetic memory and methyl donor availability in promoting healthy aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)