Article
Multidisciplinary Sciences
Lisheng Chen, N. Dayanthi Perera, Athanasios J. Karoukis, Kecia L. Feathers, Robin R. Ali, Debra A. Thompson, Abigail T. Fahim
Summary: This study aimed to determine the differential apical and basolateral secretome of retinal pigment epithelium (RPE) cells and investigate the effects of oxidative stress on the directional secretion of proteins linked to age-related macular degeneration (AMD) and angiogenesis. The study found that oxidative stress altered the secretion of multiple factors related to AMD and neovascularization, promoting a pro-angiogenic microenvironment. Apical secretion was impacted more than basolateral, which may have implications for choroidal neovascularization.
SCIENTIFIC REPORTS
(2022)
Review
Pharmacology & Pharmacy
Yuhei Nishimura, Kenji Kurosawa
Summary: This mini-review discusses the interaction between genetic and environmental factors in developmental disorders (DDs) using genome-wide and candidate gene-based approaches. It focuses on zebrafish and mouse models and introduces novel methods for analyzing G x E associated with DDs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Anna Wasowska, Slawomir Teper, Ewa Matczynska, Przemyslaw Lyszkiewicz, Adam Sendecki, Anna Machalinska, Edward Wylegala, Anna Boguszewska-Chachulska
Summary: This study aimed to determine the polygenic risk score (PRS) stratification between AMD case and control patients. A 22-variant model achieved the highest predictive value for the target dataset. The polygenic susceptibility can be used for expanding AMD diagnostics and investigating associations with disease progression and treatment response in future studies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Arun Govindaiah, Abdul Baten, R. Theodore Smith, Siva Balasubramanian, Alauddin Bhuiyan
Summary: This study compared the performance of retinal fundus images and genetic-information-based machine learning models in predicting late AMD, with the findings indicating that the model based on retinal image and socio-demographic parameters outperformed the genetic and socio-demographic parameters-based model.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Genetics & Heredity
Aumer Shughoury, Duriye Damla Sevgi, Thomas A. Ciulla
Summary: AMD is a major cause of irreversible blindness worldwide, with genetic background being a key risk factor. Previous research has identified multiple gene variants and pathways associated with the development of AMD. Further molecular genetics research holds the promise of precision-targeted personalized therapies.
Article
Ophthalmology
Michael D. Osterman, Yeunjoo E. Song, Muneeswar Nittala, SriniVas R. Sadda, William K. Scott, Dwight Stambolian, Margaret A. Pericak-Vance, Jonathan L. Haines
Summary: This study identified potential novel genetic risk loci for AMD in a midwestern Amish study population and determined a clear link between the genetic risk of AMD and drusen. Further study may improve understanding of the biological risk factors underlying drusen development.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gilberto Vargas-Alarcon, Julian Ramirez-Bello, Marco Antonio Pena-Duque, Marco Antonio Martinez-Rios, Hilda Delgadillo-Rodriguez, Jose Manuel Fragoso
Summary: In this study, the association of BAT1, NFKBIL, LTA, and CASP1 single nucleotide polymorphisms and their gene-gene interactions with restenosis risk after coronary stenting was evaluated. The results showed that rs501192 A/G and rs580253 A/G polymorphisms, as well as the gene-gene interactions between BAT1-NFKBIL1-LTA-CASP1, were associated with an increased restenosis risk.
Review
Biochemistry & Molecular Biology
Yanhui Deng, Lifeng Qiao, Mingyan Du, Chao Qu, Ling Wan, Jie Li, Lulin Huang
Summary: Age-related macular degeneration (AMD) is a complex eye disorder that leads to incurable blindness in the elderly, with wet and dry forms classified as the advanced stages. Genetic factors, lipid metabolism, oxidative stress, and aging all play a role in the development of AMD, with current treatment focusing on anti-VEGF therapy for wet AMD. New AMD drugs and iPSC-derived RPE cell therapy show promise in improving AMD treatment in the near future.
Article
Ophthalmology
Johanna M. Colijn, Magda Meester-Smoor, Timo Verzijden, Anita de Breuk, Rufino Silva, Benedicte M. J. Merle, Audrey Cougnard-Gregoire, Carel B. Hoyng, Sascha Fauser, Anthonius Coolen, Catherine Creuzot-Garcher, Hans-Werner Hense, Marius Ueffing, Cecile Delcourt, Anneke den Hollander, Caroline C. W. Klaver
Summary: The study investigated the genetic distribution of AMD-associated risk variants in a large European population and found ARMS2 and CHF as the most prominent risk genes. Genetic risk was associated with AMD severity, and lifestyle factors significantly influenced genetic outcomes.
Article
Ophthalmology
Eric F. Thee, Johanna M. Colijn, Audrey Cougnard-Gregoire, Magda A. Meester-Smoor, Timo Verzijden, Carel B. Hoyng, Sascha Fauser, Hans -Werner Hense, Rufino Silva, Catherine Creuzot-Garcher, Marius Ueffing, Cecile Delcourt, Anneke I. den Hollander, Caroline C. W. Klaver
Summary: The study investigates the relationship between the ARMS2 and HTRA1 genes and the risk of age-related macular degeneration (AMD). The findings provide strong evidence for the association between these genes and AMD, contributing to the understanding of the disease.
Article
Ophthalmology
Eric F. Thee, Johanna M. Colijn, Audrey Cougnard-Gregoire, Magda A. Meester-Smoor, Timo Verzijden, Carel B. Hoyng, Sascha Fauser, Hans-Werner Hense, Rufino Silva, Catherine Creuzot-Garcher, Marius Ueffing, Cecile Delcourt, Anneke den Hollander, Caroline C. W. Klaver
Summary: This study investigated the role of risk haplotypes in the ARMS2 and HTRA1 genes in the development of AMD, finding that patients carrying risk alleles have a higher risk of late AMD, especially for CNV. The results suggest that these risk variants may act as strong catalysts for the progression of AMD in the presence of early signs.
Article
Medical Laboratory Technology
Jiali Wu, Jieqiong Chen, Jing Hu, Mudi Yao, Min Zhang, Xiaoling Wan, Huixun Jia, Fenghua Wang, Xiaodong Sun
Summary: Age-related macular degeneration (AMD) is a major cause of irreversible blindness in the elderly, especially its neovascular form characterized by choroidal neovascularization (CNV). This study explored the role of circular RNA Uxs1 in CNV regulation and found it to be consistently upregulated in CNV patient specimens and mouse models. CirRNA Uxs1 promotes CNV by sponging miR-335-5p, which leads to the upregulation of placental growth factor (PGF) gene and activation of the mTOR/p70 S6k pathway. These findings suggest that circRNA Uxs1 may serve as a potential therapeutic target for CNV.
TRANSLATIONAL RESEARCH
(2023)
Article
Ophthalmology
Reza Karkhaneh, Mohsen Toufighi, Akbar Amirfiroozy, Aliasghar Ahmad-Raji, Oveis Ahmadzadeh, Alborz Mahdavi, Morteza Naderan
Summary: The rs3753394 polymorphism is possibly associated with CSCR in Persian ethnicity. Further study is needed to confirm the implications of this finding in clinical practice.
Article
Cell Biology
Xiaoyin Ma, Shuxian Han, Youjia Liu, Yu Chen, Pingping Li, Xiaoyan Liu, Lifu Chang, Ying-ao Chen, Feng Chen, Qiang Hou, Ling Hou
Summary: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) is involved in the pathogenesis of proliferative vitreoretinopathy (PVR). In this study, downregulation of death-associated protein-like 1 (DAPL1) expression in PVR membranes was observed, and DAPL1 deficiency promoted EMT in RPE cells in mice. Overexpression of DAPL1 inhibited EMT in both physiological and retinal-detachment states, and attenuated the severity of experimental PVR in a rabbit model. Mechanistically, DAPL1 promoted P21 phosphorylation and stabilization through NF kappa B (RelA) in RPE cells, and knockdown of P21 partially neutralized the inhibitory effect of DAPL1 on EMT and enhanced the severity of experimental PVR.
CELL DEATH & DISEASE
(2023)
Article
Ophthalmology
Rola Ba-Abbad, Anthony G. Robson, Omar A. Mahroo, Genevieve Wright, Elena Schiff, Emma S. Duignan, Michel Michaelides, Gavin Arno, Andrew R. Webster
Summary: This study describes the clinical and electrophysiological features of adult-onset macular dystrophy caused by novel combinations of CDHR1 alleles. The findings indicate that genotypes distinct from those causing pan-retinal dystrophy can result in a milder phenotype predominantly affecting the macula.
Article
Immunology
Evangelos Andreakos, Laurent Abel, Donald C. Vinh, Elzbieta Kaja, Beth A. Drolet, Qian Zhang, Cliona O'Farrelly, Giuseppe Novelli, Carlos Rodriguez-Gallego, Filomeen Haerynck, Carolina Prando, Aurora Pujol, Helen C. Su, Jean-Laurent Casanova, Andras N. Spaan, Paul Bastard, Catherine M. Biggs, Benedetta Bigio, Bertrand Boisson, Alexandre Bolze, Anastasiia Bondarenko, Petter Brodin, Samya Chakravorty, John Christodoulou, Aurelie Cobat, Antonio Condino-Neto, Stefan N. Constantinescu, Hagit Baris Feldman, Jacques Fellay, Rabih Halwani, Emmanuelle Jouanguy, Yu-Lung Lau, Isabelle Meyts, Trine H. Mogensen, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarstrom, Anna M. Planas, Anne Puel, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Anna Sediva, Anna Shcherbina, Ondrej Slaby, Ivan Tancevski, Stuart E. Turvey, K. M. Furkan Uddin, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Shen-Ying Zhang
Summary: SARS-CoV-2 infections can vary greatly between individuals, with some being asymptomatic while others experience life-threatening disease. While 20% of critical COVID-19 cases are due to inborn errors or autoantibodies, the genetic and immunological factors for resistance to infection itself remain unknown. Studies have shown that autosomal recessive deficiencies in certain genes or enzymes can confer resistance to diseases, suggesting a potential strategy for identifying individuals naturally resistant to SARS-CoV-2 infection.
Letter
Genetics & Heredity
Rosangela Ferese, Simona Scala, Antonio Suppa, Rosa Campopiano, Francesco Asci, Maria Antonietta Chiaravalloti, Alessandro Zampogna, Carmelo D'Alessio, Filomena Fittipaldi, Fabio Buttari, Alba Di Pardo, Emiliano Giardina, Stefania Zampatti, Francesco Fornai, Giuseppe Novelli, Mirco Fanelli, Chiara Zecca, Giancarlo Logroscino, Diego Centonze, Stefano Gambardella
Summary: The flowchart presents the molecular approach employed for decoding non-canonical splicing mutations.
Review
Multidisciplinary Sciences
Massimiliano Orso, Barbara Polistena, Simona Granato, Giuseppe Novelli, Roberto Di Virgilio, Daria La Torre, Daniela D'Angela, Federico Spandonaro
Summary: This systematic review provides a comprehensive understanding of the epidemiology, treatment adherence, economic impact, and quality of life of patients undergoing growth hormone (GH) treatment in Italy. The study reveals the prevalence of GH-related diseases, such as growth hormone deficiency, Short Stature Homeobox Containing gene deficiency, Turner syndrome, and Prader-Willi syndrome. The findings indicate suboptimal treatment adherence, high treatment costs, but overall acceptance of GH treatment by patients and caregivers.
Article
Biochemistry & Molecular Biology
Chiara Vancheri, Elena Morini, Francesca Romana Prandi, Francesco Barilla, Francesco Romeo, Giuseppe Novelli, Francesca Amati
Summary: Coronary heart disease (CHD) is a leading cause of disability and death globally, and its early diagnosis is challenging. A pilot study on peripheral blood cells revealed potential biomarkers, including hsa-miR-200c-3p, for the diagnosis and clinical progression of CHD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Francesca Di Lorenzo, Enrica Marchionni, Valentina Ferradini, Andrea Latini, Laura Pezzoli, Annamaria Martino, Fabiana Romeo, Annamaria Iorio, Stefano Bianchi, Maria Iascone, Leonardo Calo, Giuseppe Novelli, Ruggiero Mango, Federica Sangiuolo
Summary: Variants in desmoplakin gene (DSP) are usually associated with arrhythmogenic cardiomyopathy (ACM) or dilated cardiomyopathy (DCM) inherited in an autosomal dominant manner. This study analyzed a cohort of 18 probands with heterozygous DSP variants and identified 16 pathogenic or likely pathogenic variants. Patients generally presented as asymptomatic or mildly symptomatic, and cardiac magnetic resonance imaging revealed left ventricular myocardial fibrosis. These findings confirm that DSP-related cardiomyopathy is a distinct clinical entity characterized by a high arrhythmic burden, variable degrees of left ventricular enlargement, and myocarditis-like episodes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Riccardo Giannico, Luca Forlani, Valentina Andrioletti, Ettore Cotroneo, Andrea Termine, Carlo Fabrizio, Raffaella Cascella, Luca Salvaderi, Pasquale Linarello, Debora Varrone, Laura Gigante, Emiliano Giardina
Summary: In 1997, Cell-Free Fetal DNA (cffDNA) was found in maternal plasma. cffDNA has been studied as a source of non-invasive prenatal testing for fetal pathologies and paternity testing. This study presents a non-invasive prenatal paternity test (NIPAT) using Next Generation Sequencing (NGS) to analyze 861 Single Nucleotide Variants (SNV) from cffDNA. The test has shown high accuracy in real cases according to the log(CPI) values generated.
Review
Cell Biology
Giuseppe Novelli, Paola Spitalieri, Michela Murdocca, Eleonora Centanini, Federica Sangiuolo
Summary: In recent years, hiPSC-derived organoids have been extensively studied and used as in vitro models, especially for difficult-to-obtain organs and tissues. Various diseases can be accurately modeled and studied using these organoids. Patient-derived organoids (PDOs) can be used to predict individual drug responses for personalized medicine. Additionally, tissue engineering and 3D printing techniques could be used to replace or regenerate damaged tissue in the future.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Medicine, General & Internal
Andrea Cusumano, Benedetto Falsini, Fabian D'Apolito, Michele D'Ambrosio, Jacopo Sebastiani, Raffaella Cascella, Shila Barati, Emiliano Giardina
Summary: In this study, a longitudinal structure-function evaluation was performed on a patient with CDHR1-related retinal dystrophy over three years. The results showed that the patient experienced progressive visual loss accompanied by increased inner retinal thickness, while the outer retina remained unchanged. These findings suggest that inner retinal changes may be relevant for therapeutic interventions aiming to mitigate photoreceptor loss through gene therapy or stem cells.
Review
Chemistry, Medicinal
Federica Centofanti, Alessandro Buono, Michele Verboni, Carlo Tomino, Simone Lucarini, Andrea Duranti, Pier Paolo Pandolfi, Giuseppe Novelli
Summary: In this article, the biosynthetic processes and synthetic procedures of indole-3-carbinol (I3C) and its derivatives are analyzed, as well as their activities in antitumor and antiviral effects and the mechanisms of action. The potential social impact of enhancing these molecules in the prevention and treatment of respiratory tract disorders and cancer is also discussed.
Article
Genetics & Heredity
Ludovico Graziani, Giacomo Cinnirella, Valentina Ferradini, Chiara Conte, Federica Lo Bascio, Mario Bengala, Federica Sangiuolo, Giuseppe Novelli
Summary: Baraitser-Winter syndrome (BRWS) is a rare autosomal dominant disease caused by variants in ACTB (BRWS1) or ACTG1 (BRWS2) genes. It is characterized by developmental delay, craniofacial dysmorphisms, and various other abnormalities. We report a case of a 4-year-old girl with psychomotor delay, microcephaly, dysmorphic features, hearing loss, cardiac hypertrophy, and abdominal swelling. Exome sequencing identified a de novo variant in ACTG1 gene, expanding the spectrum of ACTG1-related disorders.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Cell Biology
Michela Murdocca, Paola Spitalieri, Maria Rosaria D'Apice, Giuseppe Novelli, Federica Sangiuolo
Summary: Aging is a complex biological process closely linked to cancer and inflammation, which are the subjects of extensive research. The accumulation of DNA damage interferes with cellular function and increases susceptibility to aging conditions.
MECHANISMS OF AGEING AND DEVELOPMENT
(2023)
Article
Ophthalmology
Matteo Airaldi, Alessandro Invernizzi, Vuong Nguyen, Stela Vujosevic, Federico Ricci, Pietro Monaco, Marco Nassisi, Daniel Barthelmes, Mark Gillies, Francesco Viola
Summary: This study compared the treatment outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. The results showed that PCV had slightly better visual acuity outcomes after 24 months of treatment compared to type 1 MNV, and received fewer anti-VEGF injections.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Ludovico Graziani, Stefania Zampatti, Miriam Lucia Carriero, Chiara Minotti, Cristina Peconi, Mario Bengala, Emiliano Giardina, Giuseppe Novelli
Summary: This study describes a family with ADPKD in which the proband had an earlier and more severe renal phenotype compared to other affected family members. NGS-based analysis identified pathogenic variants in PKD1 and PKD2 in the proband, suggesting that the co-inheritance of multiple PKD genes may explain the phenotypic variability observed in ADPKD families.
Article
Genetics & Heredity
Stefania Zampatti, Cristina Peconi, Giulia Calvino, Rosangela Ferese, Stefano Gambardella, Raffaella Cascella, Jacopo Sebastiani, Benedetto Falsini, Andrea Cusumano, Emiliano Giardina
Summary: In this study, a causative gene RDH8 for Stargardt macular dystrophy was identified in a consanguineous Italian family using a combined approach and multilevel validation. The disease phenotype was consistent with previous murine models. This study provides evidence for a splicing mutation in a gene that has not been reported in human disorders before.
Review
Nutrition & Dietetics
Valerio Caputo, Giovanni Tarantino, Silvano Junior Santini, Giovanna Fracassi, Clara Balsano
Summary: Metabolic dysfunction-associated steatotic fatty liver disease (MASLD), a novel definition for NAFLD, is one of the most common liver diseases with increasing incidence worldwide. Its complex etiopathogenesis involves mitochondrial dysfunction, altered lipid metabolism, inflammation, and oxidative stress. Changes in diet and lifestyle, as well as the influence of natural compounds, can modulate these mechanisms and improve the understanding and treatment of MASLD.
