Article
Immunology
Marie-Lise Gougeon, Beatrice Poirier-Beaudouin, Jerome Ausseil, Michel Zerah, Cecile Artaud, Jean-Michel Heard, Kumaran Deiva, Marc Tardieu
Summary: Ⅲ
A rare genetic disorder, Sanfilippo disease, is caused by mutations in the NAGLU gene, leading to neural decline in affected children. Gene therapy utilizing AAV vectors has been used in clinical trials to treat this condition, showing promising safety and efficacy results over a 5.5-year period. The therapy induced a T cell response sensitized to the transgene without affecting CNS transgene expression. This study highlights the importance of immunomonitoring in gene therapy to evaluate treatment safety and efficacy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Wei Huang, Yu-Shan Cheng, Shu Yang, Manju Swaroop, Miao Xu, Wenwei Huang, Wei Zheng
Summary: MPS IIIB is a lysosomal disease caused by mutations in the NAGLU gene, with no effective treatment currently available. The study showed that MPS IIIB neural stem cells and neurons can serve as a disease model system for evaluating drug efficacy and compound screening for drug development.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Courtney J. Rouse, Kimberley Hawkins, Nadia Kabbej, Justin Dalugdug, Aishwarya Kunta, Mi-Jung Kim, Shinichi Someya, Zachary Herbst, Michael Gelb, Isabella Dinelli, Elizabeth Butterworth, Darin J. Falk, Erinn Rosenkrantz, Hamza Elmohd, Hamid Khaledi, Samar Mowafy, Frederick Ashby, Coy D. Heldermon
Summary: Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal storage disease caused by gene mutations that result in defective NAGLU protein. The study demonstrates the potential of AAV8 for gene delivery in the treatment of MPS IIIB, with improved expression and distribution compared to other AAV serotypes. The administration of AAVtcm8-coNAGLU leads to correction of lifespan, auditory deficits, increased CNS NAGLU activity, and reduced lysosomal storage levels in the mouse model of MPS IIIB.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pathology
Tyler A. Harm, Shannon J. Hostetter, Ariel S. Nenninger, Bethann N. Valentine, N. Matthew Ellinwood, Jodi D. Smith
Summary: MPS IIIB is a neuropathic lysosomal storage disease characterized by deficient lysosomal enzyme activity. Dogs serve as a replicative model for studying neurologic lesions associated with MPS IIIB, showing pathological and neuroinflammatory changes in the affected spinal cord and dorsal root ganglion.
VETERINARY PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Valeria De Pasquale, Gianluca Scerra, Melania Scarcella, Massimo D'Agostino, Luigi Michele Pavone
Summary: Mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders caused by deficiency of lysosomal enzymes, leading to glycosaminoglycan accumulation and tissue dysfunction. Current treatments for MPS III do not cure the disease, but NK1 treatment shows potential in improving neurological symptoms by reducing lysosomal pathology and promoting neuronal differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Clinical Neurology
Aydan Degerliyurt, Ozlem Yayici Koken, Neslihan Duzkale Teker, Dilek Aktas
Summary: Diagnosis of MPS type IIIB should be considered in patients presenting with neurodevelopmental and neuropsychiatric problems, especially in cases of consanguineous marriage.
Review
Cardiac & Cardiovascular Systems
Mariann Gyongyosi, Pilar Alcaide, Folkert W. Asselbergs, Bianca J. J. M. Brundel, Giovanni G. Camici, Paula da Costa Martins, Peter Ferdinandy, Marianna Fontana, Henrique Girao, Massimiliano Gnecchi, Can Gollmann-Tepekoylu, Petra Kleinbongard, Thomas Krieg, Rosalinda Madonna, Melanie Paillard, Antonis Pantazis, Cinzia Perrino, Maurizio Pesce, Gabriele G. Schiattarella, Joost P. G. Sluijter, Sabine Steffens, Carsten Tschope, Sophie Van Linthout, Sean M. Davidson
Summary: Long COVID is a global non-communicable epidemic characterized by long-lasting multiorgan symptoms after SARS-CoV-2 infection has subsided. This scientific document aims to provide insight into the cardiovascular manifestations of long COVID and the possible causes and therapeutic options available. Imaging has shown evidence of chronic perimyocarditis, arterial wall inflammation, and microthrombosis in certain patient populations. Understanding the underlying cellular and molecular mechanisms is crucial for the development of effective treatment strategies. However, current biomarkers are not highly predictive for the presence or outcome of long COVID.
CARDIOVASCULAR RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Roberta Paolillo, Stefania D'Apice, Gabriele Giacomo Schiattarella, Pietro Ameri, Domenica Borzacchiello, Daniele Catalucci, Cristina Chimenti, Lia Crotti, Sebastiano Sciarretta, Daniele Torella, Antonio Feliciello, Cinzia Perrino
Summary: The second messenger cAMP regulates multiple mitochondrial functions through the activation of cAMP/PKA signaling. AKAPs play important roles in regulating cardiac functions. Understanding the roles and regulation of mitochondria-targeted AKAPs can help modulate their functions for clinical purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Federico Capone, Cristian Sotomayor-Flores, David Bode, Rongling Wang, Daniele Rodolico, Stefano Strocchi, Gabriele G. Schiattarella
Summary: Heart failure with preserved ejection fraction (HFpEF) is a prevalent and complex condition, and metabolic derangements seem to play a crucial role in its progression. Long-chain fatty acids (LCFAs) and short-chain carbon sources have both metabolic and signaling roles in HFpEF. Understanding their functions can help develop novel therapeutic approaches.
CARDIOVASCULAR RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Nunzia Mollo, Roberta Scognamiglio, Anna Conti, Simona Paladino, Lucio Nitsch, Antonella Izzo
Summary: Down syndrome (DS), caused by trisomy of chromosome 21 (Hsa21), is a major cause of congenital heart defects (CHD). The overexpression of Hsa21 genes likely contributes to CHD, along with genes on other chromosomes, miRNAs, and lncRNAs. ECM plays a key role in cardiac morphogenesis, with many ECM genes overexpressed in trisomic fetal hearts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases characterized by the accumulation of heparan sulfate (HS) in lysosomes and other cellular compartments, leading to tissue and organ dysfunctions. This study found that N-substituted L-iminosugars can reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. These compounds also increase the levels of defective enzyme alpha-N-acetylglucosaminidase and correct its sorting, as well as reduce HS accumulation by downregulating protein levels of exostosin glycosyltransferases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Materials Science, Biomaterials
Melissa Santi, Valentina Frusca, Maria Laura Ermini, Ana Katrina Mapanao, Patrizia Sarogni, Alessandra Gonnelli, Noemi Giannini, Agata Zamborlin, Lorenzo Biancalana, Fabio Marchetti, Valerio Voliani
Summary: Head and neck squamous cell carcinomas (HNSCCs) are a complex group of malignancies that currently rely on platinum-based chemotherapy with severe side effects. Researchers are exploring alternative metal complexes to reduce adverse reactions. The concurrent administration of cisplatin and emerging metal complexes shows promising results in increasing the efficacy of HNSCC treatment while reducing side effects.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Agriculture, Dairy & Animal Science
Giuseppe Piegari, Valeria De Pasquale, Ilaria d'Aquino, Davide De Biase, Giulia Caccia, Carlo Pietro Campobasso, Simona Tafuri, Valeria Russo, Orlando Paciello
Summary: This study investigated the degradation of desmin and dystrophin in muscle tissue after death in dogs, and found that dystrophin degrades at a faster rate than desmin. This provides a reference basis for better estimating the postmortem interval in dogs.
Editorial Material
Cardiac & Cardiovascular Systems
Federico Capone, Roberto Vettor, Gabriele G. Schiattarella
Article
Biochemistry & Molecular Biology
Teresa Improda, Valentina Morgera, Maria Vitale, Lorenzo Chiariotti, Fabiana Passaro, Antonia Feola, Antonio Porcellini, Mariella Cuomo, Antonio Pezone
Summary: Cell identity is determined by chromatin structure and gene expression profiles, which rely on chromatin accessibility and DNA methylation. These epigenetic modifications are crucial for mammalian development and cellular identity. Dynamic DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. By analyzing the methylation configurations of gene promoters during murine brain differentiation, we found significant methyl-CpG profiles associated with gene silencing or activation. Interestingly, these methylation patterns mark different brain areas and cell types during differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Rheumatology
Antonio Pezone, Fabiola Olivieri, Maria Vittoria Napoli, Antonio Procopio, Enrico Vittorio Avvedimento, Armando Gabrielli
Summary: Inflammation is a biological response involving immune cells, blood vessels, and mediators induced by pathogens, damaged cells, or chemicals. Chronic inflammation is characterized by cytokine secretion, DNA damage, and senescence induction. The relationship between persistent DNA damage, inflammation, and cellular senescence plays a significant role in various diseases, including rheumatic diseases.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Annarita Nappi, Caterina Miro, Antonio Pezone, Alfonso Tramontano, Emery Di Cicco, Serena Sagliocchi, Annunziata Gaetana Cicatiello, Melania Murolo, Sepehr Torabinejad, Elena Abbotto, Giuseppina Caiazzo, Maddalena Raia, Mariano Stornaiuolo, Dario Antonini, Gabriella Fabbrocini, Domenico Salvatore, Vittorio Enrico Avvedimento, Monica Dentice
Summary: In this study, the authors investigate the role of thyroid hormones in tumor progression and identify the thyroid hormone activating enzyme D2 as a p53 target gene. They find that p53, as a cell stress sensor and tumor suppressor, suppresses D2 expression, leading to decreased availability of intracellular thyroid hormones. Conversely, loss of p53 enhances D2/TH signaling, promoting the fitness of tumor cells through modulation of genes involved in DNA damage and repair and redox signaling. In vivo deletion of D2 significantly reduces cancer progression, suggesting that targeting thyroid hormones could be a general approach to reduce invasiveness in p53-mutated neoplasms.
NATURE COMMUNICATIONS
(2023)
Article
Materials Science, Biomaterials
Patrizia Sarogni, Agata Zamborlin, Ana Katrina Mapanao, Tine Logghe, Luigi Brancato, Eke van van Zwol, Michele Menicagli, Noemi Giannini, Alessandra Gonnelli, Stefania Linsalata, Robin Colenbier, Johan van den Bossche, Fabiola Paiar, Johannes Bogers, Valerio Voliani
Summary: Pancreatic cancer is aggressive and has an early metastasis, making it difficult to treat. Conventional treatments like chemotherapy and radiotherapy (CRT) are ineffective due to the hypoxia involved. Hyperthermia, which promotes blood perfusion, can counteract hypoxia and enhance the effectiveness of radiotherapy. Therefore, integrated treatments may be promising for pancreatic cancer management. This study investigates the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models, providing a potentially effective strategy for non-invasive management of pancreatic carcinoma.
Article
Cell Biology
Dandan Liu, Simona Paladino, Chiara Zurzolo, Stephanie Lebreton
Summary: Protein secretion is crucial for maintaining the balance of epithelial tissue and needs to be tightly regulated. Recent studies have shown that the calcium manganese pump SPCA1 and calcium-binding protein Cab45 play a role in regulating the secretion of certain soluble cargoes in nonpolarized cells. Our research focuses on the mechanism governing the polarized secretion of soluble cargoes in polarized epithelial cells, highlighting the critical role of a calcium-dependent Cab45 mechanism in regulating apical exocytosis.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Review
Medicine, General & Internal
Maria Laura Passaro, Francesco Matarazzo, Gianmarco Abbadessa, Antonio Pezone, Antonio Porcellini, Fausto Tranfa, Michele Rinaldi, Ciro Costagliola
Summary: Glaucoma is a chronic neurodegenerative disorder that can cause vision loss and blindness. Recent research has found that glaucoma patients also have abnormal tau protein aggregation, suggesting similarities with other neurodegenerative disorders. Studies have shown that tau modifications play a crucial role in neuronal injury caused by ocular hypertension in glaucoma patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Valeria De Pasquale, Anna Esposito, Gianluca Scerra, Melania Scarcella, Mariangela Ciampa, Antonietta Luongo, Daniele D'Alonzo, Annalisa Guaragna, Massimo D'Agostino, Luigi Michele Pavone
Summary: Sanfilippo syndrome is a group of genetic diseases caused by a lack or decreased activity of enzymes involved in heparan sulfate catabolism. This leads to the accumulation of heparan sulfate in cells, resulting in tissue and organ dysfunctions, including severe neurodegeneration. In this study, N-substituted L-iminosugars were found to significantly reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and a neuronal cellular model of Sanfilippo B subtype. They also corrected the sorting of defective alpha-N-acetylglucosaminidase and reduced heparan sulfate accumulation by downregulating exostosin glycosyltransferases. These findings suggest a promising pharmacological potential for these glycomimetics in treating Sanfilippo syndrome.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)