Article
Biochemistry & Molecular Biology
Aida Zulueta, Michele Dei Cas, Francesco Luciano, Alessandra Mingione, Francesca Pivari, Ilaria Righi, Letizia Morlacchi, Lorenzo Rosso, Paola Signorelli, Riccardo Ghidoni, Rita Paroni, Anna Caretti
Summary: The role of S1P in Cystic Fibrosis has been studied since 2001, with research showing that CFTR mutation in CF patients is associated with altered S1P expression. CF patients show increased S1P accumulation due to up-regulation of SphK1 and down-regulation of SGPL1, along with deficient expression of Spns2 transporter. This excessive accumulation is partially prevented by up-regulated phosphatases in CF cells.
Article
Cell Biology
Onofrio Laselva, Caterina Allegretta, Sante Di Gioia, Carlo Avolio, Massimo Conese
Summary: DMF demonstrates anti-inflammatory and antioxidant effects in CF treatment, reducing inflammatory responses, restoring CFTR function, and potentially serving as a novel drug to ameliorate lung inflammation in CF patients and enhance drug efficacy.
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
Pharmacology & Pharmacy
Zsolt Bene, Zsolt Fejes, Tibor Gabor Szanto, Ferenc Fenyvesi, Judit Varadi, Luka A. Clarke, Gyorgy Panyi, Milan Macek, Margarida D. Amaral, Istvan Balogh, Bela Nagy
Summary: In this study, it was found that decreased HE4 protein levels in CF patients treated with CFTR potentiator therapy were inversely correlated with lung function improvement. Modulation of CFTR function affected HE4 expression in CFBE cells, with activation of NF-kappa B pathway playing a role in regulating HE4 expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Yanina Andrea Lamberti, Martina Debandi, Mariela del Carmen Carrica, Jimena Alvarez Hayes, Maria Eugenia Rodriguez
Summary: Inquilinus limosus can survive and replicate inside bronchial epithelial cells, displaying pathogenic properties of antibiotic resistance and chronic infection.
MICROBIAL PATHOGENESIS
(2022)
Article
Obstetrics & Gynecology
Tsai-Der Chuang, Anika Rehan, Omid Khorram
Summary: This study reveals that increased expression of XIST in leiomyoma leads to decreased expression of miR-29c and miR-200c, resulting in the up-regulation of genes targeted by these miRNAs, including COL1A1, COL3A1, and FN1, which are associated with extracellular matrix accumulation in fibroids.
FERTILITY AND STERILITY
(2021)
Article
Multidisciplinary Sciences
Parameet Kumar, Dharmendra Kumar Soni, Chaitali Sen, Mads B. Larsen, Krystyna Mazan-Mamczarz, Yulan Piao, Supriyo De, Myriam Gorospe, Raymond A. Frizzell, Roopa Biswas
Summary: SFPQ expression is reduced in CF lung epithelial cells, but overexpression can increase F508del-CFTR expression and rescue function by modulating cellular signaling pathways. This study is the first to report on the role of SFPQ in regulating the expression and function of F508del-CFTR in CF lung disease, providing insights into potential epigenetic therapeutic targets.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Shekooh Behroozian, Inmaculada Sampedro, Basanta Dhodary, Stephanie Her, Qianru Yu, Bruce A. Stanton, Jane E. Hill
Summary: Cystic fibrosis is a life-threatening multi-organ disease characterized by susceptibility to chronic pulmonary infections. Bile is believed to contribute to the colonization and pathogenesis of Pseudomonas aeruginosa in the lung.
Article
Microbiology
Katie Dunne, Emma Reece, Siobhan McClean, Sean Doyle, Thomas R. Rogers, Philip Murphy, Julie Renwick
Summary: Aspergillus fumigatus, the most commonly isolated fungus in chronic lung diseases, can disrupt tight junction integrity of human bronchial epithelial cells and cause airway damage.
Article
Biochemistry & Molecular Biology
Giovanna Blacona, Roberto Raso, Stefano Castellani, Silvia Pierandrei, Paola Del Porto, Giampiero Ferraguti, Fiorentina Ascenzioni, Massimo Conese, Marco Lucarelli
Summary: The pathogenic mechanism of cystic fibrosis involves the interaction between the CFTR protein and the ENaC channel. By inhibiting the protease-dependent activation of ENaC and manipulating its coding genes, it is possible to reduce ENaC activity and potentially treat cystic fibrosis. The study found that inhibition of extracellular peptidases and epigenetic manipulations can effectively reduce ENaC activity, with better results in primary cells. The SCNN1B gene appears to be the most effective target for reducing ENaC activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biology
Pramila Maniam, Ama-Tawiah Essilfie, Murugan Kalimutho, Dora Ling, David M. Frazer, Simon Phipps, Gregory J. Anderson, David W. Reid
Summary: The susceptibility of cystic fibrosis airway epithelial cells to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defenses. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis.
BIOLOGICAL RESEARCH
(2021)
Article
Cell Biology
Virginia Lotti, Flavia Merigo, Anna Lagni, Andrea Di Clemente, Marco Ligozzi, Paolo Bernardi, Giada Rossini, Ercole Concia, Roberto Plebani, Mario Romano, Andrea Sbarbati, Claudio Sorio, Davide Gibellini
Summary: People with cystic fibrosis may be at higher risk for severe symptoms of COVID-19, but they have a lower ability to spread SARS-CoV-2. This study found that CFTR is involved in the regulation of SARS-CoV-2 replication, providing new insights into the development of therapeutic strategies for COVID-19.
Article
Physiology
Dinesh Babu Uthaya Kumar, Efthymios Motakis, Marina Yurieva, Vivek Kohar, Jan Martinek, Te-Chia Wu, Johad Khoury, Jessica Grassmann, Mingyang Lu, Karolina Palucka, Naftali Kaminski, Jonathan L. Koff, Adam Williams
Summary: This study identified a novel epithelial cell type called aberrant basaloid cells in fibrotic lung tissue. The role of epithelial-mesenchymal transition (EMT) in the development of these cells was investigated, and it was found that EMT induction led to transcriptional changes and a partial EMT gene signature in the cells. The study highlights the importance of using physiologically relevant models, such as air-liquid interface (ALI) cultures, to study aberrant basaloid-like cells and EMT mechanisms.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Respiratory System
Anne Bertelsen, J. Stuart Elborn, Bettina C. Schock
Summary: The study indicates a relationship between P. aeruginosa and anaerobic Prevotella spp., showing that P. histicola and P. nigresens can reduce the growth of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. These findings suggest potential therapeutic approaches to combat chronic P. aeruginosa infection in people with CF.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Biochemistry & Molecular Biology
An-nan Zhang, Nan Li, Zhuo-chang Chen, Ya-li Guo, Cui-jie Tian, Dong-jun Cheng, Xue-yi Tang, Xiao-yu Zhang
Summary: Objective of this study was to investigate the effect of amygdalin, an active ingredient in bitter almonds, on TGF-beta-induced EMT in bronchial epithelial cells and elucidate the underlying mechanisms. The results showed that amygdalin treatment relieved airway wall remodeling and decreased the expressions of EMT markers. Furthermore, amygdalin inhibited TGF-beta-induced EMT through regulating the expression of HPSE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Gastroenterology & Hepatology
Malin Fromme, Carolin Schneider, Vitor Pereira, Karim Hamesch, Monica Pons, Matthias C. Reichert, Federica Benini, Paul Ellis, Katrine Thorhauge, Mattias Mandorfer, Barbara Burbaum, Vivien Woditsch, Joanna Chorostowska-Wynimko, Jef Verbeek, Frederik Nevens, Joan Genesca, Marc Miravitlles, Alexa Nunez, Benedikt Schaefer, Heinz Zoller, Sabina Janciauskiene, Nelia Abreu, Luis Jasmins, Rui Gaspar, Rodrigo Liberal, Guilherme Macedo, Ravi Mahadeva, Catarina Gomes, Kai Markus Schneider, Michael Trauner, Aleksander Krag, Bibek Gooptu, Douglas Thorburn, Aileen Marshall, John R. Hurst, David A. Lomas, Frank Lammert, Nadine T. Gaisa, Virginia Clark, William Griffiths, Christian Trautwein, Alice M. Turner, Noel G. McElvaney, Pavel Strnad
Summary: Alpha-1 antitrypsin deficiency (AATD) is a common genetic disorder caused by mutations in the alpha-1 antitrypsin (AAT) gene. Different AATD genotypes have varying degrees of liver and biliary abnormalities, with the Pi*ZZ genotype showing the highest occurrence of liver fibrosis/cirrhosis and primary liver cancer. Male sex, age >= 50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.
Article
Respiratory System
Alessandro N. Franciosi, Daniel Fraughen, Tomas P. Carroll, Noel G. McElvaney
Summary: Alpha-1 antitrypsin deficiency is the only known monogenic cause of COPD. The only condition-specific treatment for COPD associated with this deficiency is intravenous administration of purified human alpha-1 antitrypsin. The use of 11 mu M threshold as a determinant of clinical risk for COPD has been questioned, and genotype is considered a more reliable indicator. New risk assessment models are needed for individuals diagnosed with alpha-1 antitrypsin deficiency to optimize treatment goals.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Polymer Science
Bing Wu, Saltuk B. Hanay, Scott D. Kimmins, Sally-Ann Cryan, Daniel Hermida Merino, Andreas Heise
Summary: The ion-induced gelation behavior of statistical copolypeptides comprising lysine and tyrosine is studied, and it is found that the gelation mechanism is related to the formation of stable intermolecular beta-sheet secondary structures induced by the presence of salt ions as well as the aggregation of an alpha-helix between the copolypeptides. The diffusion and mechanical properties of the hydrogels can be tuned by adjusting the polypeptide chain length and ion strength.
Article
Biochemistry & Molecular Biology
Dimitrios Skoulas, Sarinj Fattah, Dandan Wang, Sally-Ann Cryan, Andreas Heise
Summary: 8-arm star polypeptides consisting of cationic polylysine and hydrophilic polysarcosine blocks were synthesized. The enzymatic hydrolysis and disintegration of the polypeptides showed a strong dependence on structural arrangements. The polyplexes formed by the polypeptides were capable of complexing plasmid DNA, had sizes around or below 200 nm, and could transport through mucus.
MACROMOLECULAR BIOSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Ahmad Z. Bahlool, Sarinj Fattah, Andrew O'Sullivan, Brenton Cavanagh, Ronan MacLoughlin, Joseph Keane, Mary P. O'Sullivan, Sally-Ann Cryan
Summary: Developing new treatment strategies for multidrug-resistant tuberculosis is a global challenge. This study focuses on a host-directed therapy using All Trans Retinoic Acid (ATRA)-loaded nanoparticles for targeted tuberculosis treatment. The efficacy studies showed a dose-dependent reduction in the growth of Mycobacterium tuberculosis, and the nanoparticles were efficiently delivered into macrophages. This targeted therapy could potentially enhance current treatment options for tuberculosis.
Letter
Dermatology
Elizabeth Keeling, Heba Bosbait, Caitriona Hackett, Asad Salim, Maureen Connolly, Anne-Marie Tobin, Kevin Molloy
Summary: We report a rare case of Mondor disease following elliptical excision of a naevus on the chest wall. The condition is a superficial thrombophlebitis that usually occurs on the anterolateral thoracoabdominal wall. It can be idiopathic or secondary to trauma, breast malignancy, hypercoagulable states, or iatrogenic causes, with breast surgery being the most common. Mondor disease typically resolves within weeks.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2023)
Letter
Dermatology
Julie Mac Mahon, Gregg Murray, Yvonne McCartney, Stephen Crowther, Anne-Marie Tobin, Kevin Molloy
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stephen G. J. Smith, Catherine M. Greene
Summary: This study investigates the expression of long non-coding RNAs (lncRNAs) in alpha-1 antitrypsin (AAT) deficiency and explores the effect of AAT augmentation therapy on the lncRNA expression profile in ZZ monocytes. Results show that AAT augmentation therapy alters the expression of numerous lncRNAs in ZZ monocytes, and many of these changes are consistent with the effects observed in ZZ monocytes treated ex vivo with AAT. These findings provide insights into the potential mechanisms underlying the diverse effects of AAT augmentation therapy.
Article
Biochemistry & Molecular Biology
Stefania Ottaviani, Giulia Bartoli, Tomas P. Carroll, Fabrizio Gangemi, Alice M. Balderacchi, Valentina Barzon, Alessandra Corino, Davide Piloni, Noel G. McElvaney, Angelo G. Corsico, James A. Irving, Annamaria Fra, Ilaria Ferrarotti
Summary: This study reports a panel of new SERPINA1 variants and describes their classification and clinical impact in individuals with AATD. The integration of computational, biochemical, and cellular studies was used to determine the associated risk of disease. The experimental results support the utility of the REVEL predictor in the initial assessment of newly identified AAT variants.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Review
Respiratory System
James D. Chalmers, Stuart Elborn, Catherine M. Greene
Summary: Bronchiectasis is a respiratory disease characterized by radiological abnormalities and a clinical syndrome of cough, sputum production, and recurrent respiratory infections. Inflammation, particularly neutrophilic inflammation, plays a central role in bronchiectasis pathophysiology. This article discusses the roles of infection, inflammation, and mucociliary clearance dysfunction in the development and progression of bronchiectasis. It also explores the concept of inflammatory endotypes and the potential of treating inflammation as a target. Current treatments for bronchiectasis focus on addressing underlying causes, improving mucociliary clearance, controlling infection, and managing complications. Additionally, the article discusses future therapies targeting host-mediated immune dysfunction.
EUROPEAN RESPIRATORY REVIEW
(2023)
Editorial Material
Genetics & Heredity
Catherine M. Greene
Article
Polymer Science
Smiljana Stefanovic, Katie McCormick, Sarinj Fattah, Ruiari Brannigan, Sally-Ann Cryan, Andreas Heise
Summary: A new synthetic route was developed to prepare star-shaped poly(l-lysine) from bis-MPA dendrimers. The resulting star polypeptides showed excellent degradability and were able to form polyplexes with nucleic acids for gene delivery.
Article
Polymer Science
Tao Xu, Dimitrios Skoulas, Dawei Ding, Sally-Ann Cryan, Andreas Heise
Summary: In this study, responsive biocompatible nanogels were synthesized for controlled mucosal delivery and release of drugs. The nanogels exhibited suitable size and morphology, and showed responsiveness to reducing agents in the intracellular environment. This work provides a new approach for drug delivery in anti-cancer therapy by overcoming mucosal barriers.
Article
Medicine, Research & Experimental
Oliver J. McElvaney, Natalie L. McEvoy, Fiona Boland, Oisin F. McElvaney, Grace Hogan, Karen Donnelly, Oisin Friel, Emmet Browne, Daniel D. Fraughen, Mark P. Murphy, Jennifer Clarke, Orna Ni Choileain, Eoin O'Connor, Rory McGuinness, Maria Boylan, Alan Kelly, John C. Hayden, Ann M. Collins, Ailbhe Cullen, Deirdre Hyland, Tomas P. Carroll, Pierce Geoghegan, John G. Laffey, Martina Hennessy, Ignacio Martin-Loeches, Noel G. McElvaney, Gerard F. Curley
Summary: This study reports the use of intravenous purified alpha-1 antitrypsin (AAT) in patients with COVID-19-related acute respiratory distress syndrome (ARDS). The results show that AAT treatment is safe, well-tolerated, and capable of reducing inflammation. Although the levels of IL-6 and sTNFR1 decreased in the treatment group, there was no definitive reduction in IL-113, IL-8, and IL-10 levels. While no difference in mortality or ventilator-free days was observed between groups, AAT-treated patients showed a trend towards reduced time on ventilator.
Article
Respiratory System
Oliver J. McElvaney, Brian Cleary, Daniel D. Fraughen, Geraldine Kelly, Mark P. Murphy, Oisin F. McElvaney, Peter Branagan, Cedric Gunaratnam, Tomas P. Carroll, Noel G. McElvaney
Summary: Patients with severe alpha-1 antitrypsin deficiency (AATD) have different motivations for COVID-19 vaccination based on their age, with older patients more concerned about illness and death while younger patients focus more on socializing. The motivation pattern of younger AATD patients is similar to non-deficient individuals of comparable age, while older patients align more closely with those with COPD.
CHRONIC OBSTRUCTIVE PULMONARY DISEASES-JOURNAL OF THE COPD FOUNDATION
(2022)
Article
Biochemistry & Molecular Biology
Kun He, Mengyi Xie, Weifeng Hong, Yonghe Li, Yaolin Yin, Xiaojin Gao, Yi He, Yu Chen, Chuan You, Jingdong Li
Summary: Centromere protein L (CENPL) is overexpressed in hepatocellular carcinoma (HCC) and is associated with poor patient prognosis. Upregulation of CENPL promotes tumor proliferation and glycolysis in HCC cells by activating the MEK1/2-ERK1/2 signaling pathway.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Yingzi Wang, Haozhong Huang, Huimin Weng, Chunsen Jia, Bin Liao, Yang Long, Fengxu Yu, Yongmei Nie
Summary: Talin protein plays a crucial role in transmitting mechanical forces by connecting the extracellular matrix to the cytoskeleton. It converts mechanical signals into biochemical signals and serves as diagnostic, therapeutic, and prognostic indicators in diseases.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Review
Biochemistry & Molecular Biology
Hema Saranya Ilamathi, Marc Germain
Summary: Mitochondria are the central metabolic hubs in cells, relying on proteins encoded by nuclear DNA and mitochondrial DNA (mtDNA) for their function. The maintenance and distribution of mtDNA are crucial for proper mitochondrial function and are associated with mitochondrial diseases. mtDNA is organized into nucleoids that dynamically move and interact with each other. The replication and distribution of mtDNA nucleoids are regulated by the complex interplay of mitochondrial dynamics, ER-mitochondria contact sites, and cytoskeletal networks.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
K. K. Sruthi, Sirisha Natani, Ramesh Ummanni
Summary: The overexpression of TPD52 is associated with the emergence of neuroendocrine prostate cancer (NEPC). TPD52 activates the NF-kappa B - STAT3 axis to induce neuroendocrine differentiation (NED) of prostate cancer cells. Therapeutic targeting of TPD52 is important for the treatment of prostate cancer.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Cui Li, Feifan Xiang, Yuqi Gong, Yi Fu, Ge Chen, Zhi Wang, Zhong Li, Daiqing Wei
Summary: Our study demonstrates the significant role of tumor-derived microparticles (T-MPs) in osteosarcoma metastasis and immune response. T-MPs promote macrophage polarization and stimulate migration and chemoresistance of osteosarcoma cells, thereby affecting the progression of osteosarcoma.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)