Review
Cell Biology
Pascal Trouve, Claude Ferec, Emmanuelle Genin
Summary: The most common mutation in cystic fibrosis is p.Phe508del in the CFTR gene, leading to retention and rapid degradation of CFTR protein in the endoplasmic reticulum, triggering an atypical Unfolded Protein Response (UPR). There is still debate on the role of UPR in CF, whether it is triggered by accumulation of misfolded CFTR proteins or as a result of inflammation and infection in the disease.
Review
Pharmacology & Pharmacy
Alessandro Rimessi, Veronica A. M. Vitto, Simone Patergnani, Paolo Pinton
Summary: Cystic fibrosis is a genetic disorder characterized by airway issues and lung damage. Calcium signaling plays a crucial role in the pathophysiology of CF lung disease, with dysregulated calcium signals leading to impaired cell function and exacerbated inflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Critical Care Medicine
Gemma E. Stanford, Kavita Dave, Nicholas J. Simmonds
Summary: Pulmonary exacerbations in cystic fibrosis patients are significant events associated with declining lung function, reduced quality of life, hospitalizations, and decreased survival. With the increasing adult CF population globally, the management of PExs needs to evolve to reflect changing demographics and improve outcomes. Studies are underway to address unmet needs and optimize treatment strategies for PExs in adults with CF.
Article
Pharmacology & Pharmacy
Anna M. van Heeckeren, Morgan T. Sutton, David R. Fletcher, Craig A. Hodges, Arnold I. Caplan, Tracey L. Bonfield
Summary: Cell-based therapy shows potential for treating infections and inflammation in CF patients, improving patient survival and inflammation management. It enhances the patient's immune capacity and maintains resistance to pathogens, ultimately striking a balance between inflammation and pathogen management.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pediatrics
Argyri Petrocheilou, Aggeliki Moudaki, Athanasios G. Kaditis
Summary: Inflammation and infection are crucial factors in the pathophysiology of cystic fibrosis, with mucus accumulation and airway obstruction playing key roles. Recent research has focused on improving infection and inflammation, as well as correcting the genetic defect, to advance the treatment of the disease.
Article
Pediatrics
Shahid Sheikh, Rodney D. Jr Jr Britt, Nancy A. Ryan-Wenger, Aiman Q. Khan, Brandon W. Lewis, Courtney Gushue, Hazel Ozuna, Devi Jaganathan, Karen McCoy, Benjamin T. Kopp
Summary: This study aimed to determine the impact of Elexacaftor-tezacaftor-ivacaftor (ETI) on clinical parameters and inflammatory responses in people with cystic fibrosis (CF). The results showed that ETI therapy significantly improved lung function and body mass index in CF patients after 6 months of treatment. Additionally, ETI treatment reduced the presence of Pseudomonas and Staphylococcus infections and normalized peripheral blood immune cell composition.
PEDIATRIC PULMONOLOGY
(2023)
Review
Microbiology
T. Spencer Poore, Gina Hong, Edith T. Zemanick
Summary: Fungi are commonly detected in lower airway samples from cystic fibrosis patients, with potential associations to disease progression. Fungi may trigger allergic bronchopulmonary aspergillosis, particularly in those with a genetic atopic predisposition.
Article
Critical Care Medicine
Heather D. Green, Andrew M. Jones
Summary: Cystic fibrosis is a disease characterized by chronic airway infection and progressive decline in respiratory function. Recent changes in the landscape of airway infection in CF have resulted in an increased prevalence of atypical gram-negative bacterial infections. The clinical relevance and treatment strategies for many of these lower prevalence organisms are still not well understood.
Article
Immunology
John B. O'Connor, Madison Mottlowitz, Monica E. Kruk, Alan Mickelson, Brandie D. Wagner, Jonathan Kirk Harris, Christine H. Wendt, Theresa A. Laguna
Summary: This study characterizes the unique metabolic features of the cystic fibrosis (CF) airway and reveals complex correlations between metabolites, lower airway bacterial communities, and disease outcomes. The results highlight the potential of metabolomics in understanding CF airway infection and inflammation.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Christiaan Yu, Tom Kotsimbos
Summary: The interaction between airway inflammation and infection is a major factor in the pathological process of cystic fibrosis (CF). CF patients have a proinflammatory environment in their airways, leading to persistent neutrophilic infiltrations that cause irreversible lung damage. Respiratory microbes at different timepoints in life and the global environment perpetuate this hyperinflammatory state. Despite early mortality, selective pressures have allowed the CF gene to persist. CF transmembrane conductance regulator (CTFR) modulators have revolutionized comprehensive care systems, showing significant effects even in utero. This review provides insights into CF studies spanning the historical and present period for a better understanding of its future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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)
Article
Biochemistry & Molecular Biology
Ronja Weber, Nathan Perkins, Tobias Bruderer, Srdjan Micic, Alexander Moeller
Summary: Using online secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS), this study identified discriminatory volatile organic compounds that differentiate children with cystic fibrosis from healthy controls, providing a potential non-invasive and personalized approach for early detection and prevention of irreversible lung damage.
Review
Biochemistry & Molecular Biology
Kiera H. Harwood, Rachel M. McQuade, Andrew Jarnicki, Elena K. Schneider-Futschik
Summary: Cystic fibrosis is caused by a defect in the CFTR protein, resulting in respiratory complications and a highly inflammatory environment in the lungs. Neutrophil infiltration plays a critical role in driving inflammation through various pathways. Understanding these mechanisms can lead to the development of new therapeutic targets for CF patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Ruiyu Chen, Lishan Huang, Wenrong Zheng, Meilian Zhang, Zhiming Xin, Libin Liu, Zhou Chen
Summary: Cardiac fibrosis is more likely to lead to heart failure in the elderly, but effective prevention and improvement methods are lacking. This study investigated the effects of lactoferrin (LF) on aging cardiac fibrosis and found that LF can delay heart aging, improve heart function, reduce fibrosis, and inhibit inflammation. The mechanism behind this effect involves the activation of AMP-activated protein kinase (AMPK) and inhibition of nuclear factor kappa-B (NF-kappa B) in myocardial fibroblasts. In conclusion, LF can be considered as a functional food for preventing and improving heart disease associated with cardiac fibrosis.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Microbiology
John B. O'Connor, Brandie D. Wagner, J. Kirk Harris, Daniel N. Frank, Diana E. Clabots, Theresa A. Laguna
Summary: This study characterized the lower airway mycobiome in children with and without cystic fibrosis using a novel SSU-rRNA gene sequencing approach. The results showed that CF patients had higher fungal load and neutrophilic inflammation in the lower airway, with increased abundance of Aspergillus and Candida. However, there were no clear differences in clustering between CF and disease control samples.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biophysics
Adriana E. Miele, Laura Cervoni, Aline Le Roy, Antimo Cutone, Giovanni Musci, Christine Ebel, Maria Carmela Bonaccorsi di Patti
Summary: Fep1 is an iron-responsive GATA-type transcriptional repressor with a natively unstructured nature, able to form compact complexes with DNA. Complex formation with DNA is independent of the presence of a stoichiometric [2Fe-2S] cluster, suggesting a role in recruiting other protein(s) for transcription regulation in response to changes in intracellular iron levels.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Roberta Lattanzi, Daniela Maftei, Maria Carmela Bonaccorsi, Rossella Miele
Summary: Prokineticin 2 (PK2) and Prokineticin 2 beta (PK2 beta) are chemokine-like proteins, with PK2 binding to both PKR1 and PKR2 receptors while PK2 beta specifically binds to PKR1. Aromatic residue clusters were found in the ECL2 of PKR2, including tryptophan 212 and Phenylalanine 198, which are crucial for ligand binding. Mutation studies showed that substituting Phenylalanine 198 with valine in PKR2 increased its specificity for the ligand PK2 beta, which normally binds to PKR1.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Maria Carmela Bonaccorsi di Patti, Antimo Cutone, Zuzana Pakanova, Marek Nemcovic, Peter Barath, Giovanni Musci
Summary: Ceruloplasmin is crucial for iron metabolism in vertebrates, and the production of high-quality recombinant human ceruloplasmin represents a significant advancement. Further improvement in productivity and glycoengineering is necessary for potential therapeutic use in aceruloplasminemia patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Martina Pasqua, Maria Carmela Bonaccorsi di Patti, Giulia Fanelli, Ryutaro Utsumi, Yoko Eguchi, Rita Trirocco, Gianni Prosseda, Milena Grossi, Bianca Colonna
Summary: Bacterial pathogens are able to adapt to diverse environments through cell-to-cell communication strategies and efflux pumps. Efflux pumps play a crucial role in antibiotic resistance and bacterial cell physiology, contributing to virulence potential. Major Facilitator Superfamily (MFS) multidrug efflux pumps are important in colonization, virulence, and biofilm formation in life-threatening bacterial pathogens.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maria Carmela Bonaccorsi di Patti, Elisa Angiulli, Arianna Casini, Rosa Vaccaro, Carla Cioni, Mattia Toni
Summary: The alpha-, beta- and gamma-synucleins are small soluble proteins expressed in the nervous system of mammals and show evolutionary conservation in vertebrates. These proteins, despite sharing high homology in their N-terminal sequence, differ in molecular characteristics, expression levels and tissue distribution. The study of synucleinopathies, particularly the involvement of alpha-synuclein, provides valuable insights into the functions and evolution of synucleins in vertebrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dentistry, Oral Surgery & Medicine
Giuseppe Giannini, Irene Ragusa, Giulia Nerina Nardone, Sara Soldi, Marina Elli, Piera Valenti, Luigi Rosa, Emanuele Marra, Daniela Stoppoloni, Emilio Merlo Pich
Summary: This study presents a mucoadhesive gel containing probiotics capable of slow release of bacteria to prevent and treat periodontitis. The results show significant and stable release of the bacterial mixture in vitro and improved tissue pathology in a mouse model of periodontitis.
INTERNATIONAL JOURNAL OF DENTISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luigi Rosa, Antimo Cutone, Maria Pia Conte, Elena Campione, Luca Bianchi, Piera Valenti
Summary: This article reviews the antiviral activity of lactoferrin (Lf) against various types of viruses, including SARS-CoV-2. The study found that oral administration of Lf can counteract COVID-19 pathogenesis in the early stage of SARS-CoV-2 infection and have effects on various physiological processes such as inflammation, iron ion regulation, and coagulation balance. Furthermore, the article reveals the binding mechanisms of Lf to host cells and viral particle surface components. In summary, these studies support the use of Lf as an oral medication for treating COVID-19 or as an adjuvant for symptomatic treatment.
Article
Biochemistry & Molecular Biology
Giusi Ianiro, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Piera Valenti, Giovanni Musci, Antimo Cutone
Summary: Iron is an essential transition metal with crucial biological functions, but it also poses challenges for organisms due to its insolubility and formation of toxic radicals. Organisms have evolved extracellular carrier proteins to acquire and transport iron. Dysregulation of iron-proteins has been implicated in various pathological conditions, yet no resolutive therapy has been found. This review highlights the efficacy of Lactoferrin, a member of the transferrin family, in managing iron disorders associated with different pathologies.
Article
Biochemistry & Molecular Biology
Chiara Longo, Andrea Lepri, Andrea Paciolla, Antonella Messore, Daniela De Vita, Maria Carmela Bonaccorsi di Patti, Matteo Amadei, Valentina Noemi Madia, Davide Ialongo, Roberto Di Santo, Roberta Costi, Paola Vittorioso
Summary: Histone acetyltransferases (HATs) are involved in gene expression control in eukaryotes. This study focuses on a subfamily of HATs called CREB-binding proteins (CBP)/p300, which have been shown to acetylate histones and non-histone proteins. The researchers used a phenotypic assay based on Arabidopsis seedling length to evaluate the effects of a compound described as a human p300/CBP inhibitor. They also tested cinnamoyl derivatives and newly synthesized analogues. The most effective compounds were identified and their efficacy was demonstrated at a molecular level. The study confirms the usefulness of this strategy for plant epigenetic research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Pharmacology & Pharmacy
Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Vadim Vasilyev, Antimo Cutone
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Antimo Cutone, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Federico Iacovelli, Maria Pia Conte, Giusi Ianiro, Alice Romeo, Elena Campione, Luca Bianchi, Piera Valenti, Mattia Falconi, Giovanni Musci
Summary: Research has found that bovine and human lactoferrins have antiviral activity against SARS-CoV-2 and can restore iron and inflammatory balance by binding to the viral glycoprotein Spike. This discovery suggests the potential use of lactoferrin as an adjunct therapy for COVID-19.
Article
Multidisciplinary Sciences
Marco Zaccaria, William Dawson, Darius Russel Kish, Massimo Reverberi, Maria Carmela Bonaccorsi di Patti, Marek Domin, Viviana Cristiglio, Bun Chan, Luca Dellafiora, Frank Gabel, Takahito Nakajima, Luigi Genovese, Babak Momeni
Summary: We investigated the detoxification of aflatoxins, fungal carcinogenic food contaminants, by laccase. Experimental comparison of two similar aflatoxins (AFB(1) and AFG(2)) showed significant differences in laccase-mediated detoxification. A multi-scale modeling approach identified substrate-specific changes needed to improve laccase's detoxification capability, and a density functional theory-based model determined the amino acid residues affecting laccase's affinity for aflatoxins. The study concluded that AFB(1) is more challenging to degrade, while AFG(2) is easier due to its lack of side products and favorable binding dynamics, highlighting opportunities to optimize laccase for aflatoxin degradation.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Giusi Ianiro, Veronica D'Ezio, Ludovica Carpinelli, Cecilia Casella, Maria Carmela Bonaccorsi di Patti, Luigi Rosa, Piera Valenti, Marco Colasanti, Giovanni Musci, Antimo Cutone, Tiziana Persichini
Summary: The study examines the effect of bovine lactoferrin (bLf) on oxidative stress and neurotoxicity in human astroglial cells infected with Human Immunodeficiency Virus (HIV-1). The results show that both forms of bLf, nat-bLf and holo-bLf, enhance the host antioxidant response and reduce reactive oxygen species-mediated damage in astrocytes. The study also demonstrates that bLf restores the physiological internalization of transferrin receptor 1 and exacerbates Tat-induced excitotoxicity on human neuronal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matteo Amadei, Antonella Niro, Maria Rosaria Fullone, Rossella Miele, Fabio Polticelli, Giovanni Musci, Maria Carmela Bonaccorsi di Patti
Summary: Ferroportin (Fpn), a member of the major facilitator superfamily (MFS) of transporters, is the only known iron exporter found in mammals and plays a crucial role in regulating cellular and systemic iron levels. In this study, a fluorescent amino acid (DA) was introduced into specific positions of human Fpn to investigate conformational changes during metal translocation. The results indicate metal-induced conformational transitions, providing insights into the alternating access mechanism of Fpn and advancing our understanding of iron transport.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andrea Pasquadibisceglie, Maria Carmela Bonaccorsi di Patti, Giovanni Musci, Fabio Polticelli
Summary: This passage mainly describes the importance of iron in biology and the regulation of intracellular and extracellular iron levels through transport systems.