Article
Biochemistry & Molecular Biology
Arif Mahmood, Abdus Samad, Shazia Bano, Muhammad Umair, Amar Ajmal, Iqra Ilyas, Abid Ali Shah, Ping Li, Junjian Hu
Summary: The GBA1 gene encodes the enzyme glucocerebrosidase (GCase), which regulates glycosphingolipid homeostasis and autophagy. Variants of GBA1 are associated with Goucher disease, while heterozygous variants of GBA (E326K, T369M, N370S, L444P) are high-risk factors for Parkinson's disease (PD). This study used computational methods to investigate the structural changes and drug binding mechanisms of GBA variants, providing important insights for developing novel drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Genetics & Heredity
Yiyuan Niu, Catarina A. Ferreira A. Azevedo, Xin Li, Elahe Kamali, Ole Haagen Nielsen, Claus Storgaard Sorensen, Morten Frodin
Summary: The study presents a flexible knock-in assay method called CRISPR-Select(TIME), CRISPR-Select(SPACE) and CRISPR-Select(STATE), which tracks the absolute frequencies of genetic variants associated with genetic diseases as a function of time, space, or measurable cell states. The method accurately determines the function of the genetic variants and can be used in research, diagnostics, and drug development for genetic disorders.
Article
Multidisciplinary Sciences
Meng Yuan, Deli Huang, Chang-Chun D. Lee, Nicholas C. Wu, Abigail M. Jackson, Xueyong Zhu, Hejun Liu, Linghang Peng, Marit J. Van Gils, Rogier W. Sanders, Dennis R. Burton, S. Momsen Reincke, Harald Pruss, Jakob Kreye, David Nemazee, Andrew B. Ward, Ian A. Wilson
Summary: Mutations in the RBS residues of new variant strains of the coronavirus can affect the binding and neutralizing effects of antibodies, but have little impact on antibodies targeting more conserved neutralizing sites.
Review
Neurosciences
Yael Pewzner-Jung, Tammar Joseph, Shani Blumenreich, Ayelet Vardi, Natalia Santos Ferreira, Soo Min Cho, Raya Eilam, Michael Tsoory, Inbal E. Biton, Vlad Brumfeld, Rebecca Haffner-Krausz, Ori Brenner, Nir Sharabi, Yoseph Addadi, Tomer-Meir Salame, Ron Rotkopf, Noa Wigoda, Nadav Yayon, Alfred H. Merrill, Raphael Schiffmann, Anthony H. Futerman
Summary: The study presents a mouse model that phenotypically resembles chronic neuronopathic type 3 GD, showing behavioral abnormalities and significant neuropathology similar to acute GD models but with some differences. This model may help in understanding the distinct disease progression of type 2 and 3 patients.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Neurosciences
Jussi O. T. Sipila, Laura Kytovuori, Tuomas Rauramaa, Hugo Rauhamaa, Valtteri Kaasinen, Kari Majamaa
Summary: Several heterozygous variants of the GBA1 gene have been linked to increased risk of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). GBA1-associated PD is more severe than idiopathic PD, and more severe variants are associated with worse clinical phenotypes. A family with a heterozygous p.Pro454Leu variant in GBA1 is reported, which is associated with a diverse range of severe and rapidly progressive neurodegenerative diseases with Lewy bodies. Pathogenicity prediction algorithms and evolutionary analyses suggest that p.Pro454Leu is deleterious.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Sitki Cem Parlar, Francis P. P. Grenn, Jonggeol Jeffrey Kim, Cornelis Baluwendraat, Ziv Gan-Or
Summary: This review aims to generate and share a comprehensive database for GBA1 variants reported in Parkinson's disease (PD) to support future research and clinical trials. A total of 371 GBA1 variants in PD were found and a browser containing up-to-date information on these variants was created. The classification and browser presented in this work will inform and support basic, translational, and clinical research on GBA1-PD.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Kimberley J. Billingsley, Jinhui Ding, Pilar Alvarez Jerez, Anastasia Illarionova, Kristin Levine, Francis P. Grenn, Mary B. Makarious, Anni Moore, Daniel Vitale, Xylena Reed, Dena Hernandez, Ali Torkamani, Mina Ryten, John Hardy, Ruth W. Chia, Sonja J. Scholz, Bryan L. Traynor, Clifton J. Dalgard, Debra Ehrlich, Toshiko Tanaka, Luigi G. Ferrucci, Thomas E. Beach, Geidy P. Serrano, John J. Quinn, Vivien Bubb, Ryan L. Collins, Xuefang Zhao, Mark Walker, Emma Pierce-Hoffman, Harrison E. Brand, Michael Talkowski, Bradford Casey, Mark R. Cookson, Androo A. Markham, Mike Nalls, Medhat Mahmoud, Fritz J. Sedlazeck, Cornelis Blauwendraat, J. Raphael B. Gibbs, Andrew Singleton
Summary: By studying the genetic factors of Parkinson's disease, three structural variants associated with the risk of the disease have been discovered. This is the most comprehensive study to date of the contribution of structural variants to the genetic risk of Parkinson's disease.
ANNALS OF NEUROLOGY
(2023)
Article
Medical Laboratory Technology
Xiaofang Zhang, Yiping Wu, Lihua Wang, Qiong Wu, Qian Liu, Ruimin Li
Summary: The aim of this study was to investigate the clinical characteristics and GBA gene mutation analysis of Gaucher disease type I in children. The main clinical features of type I Gaucher disease are hepatosplenomegaly, anemia, and thrombocytopenia. Enzyme activity detection is the gold standard for the diagnosis of Gaucher disease.
CLINICAL LABORATORY
(2023)
Article
Computer Science, Information Systems
Emad S. Abouel Nasr, H. Al-Mubaid
Summary: This paper investigates and presents two methodologies utilizing the Gene Ontology (GO) for functional annotation of genetic variants and human gene mutations. The methods involve the concepts of term enrichment from the biological process taxonomy and least common subsumer (LCS) within the gene ontology tree. Results show that certain ontology annotations are more related to mutations through certain genes compared with normal biological process functions in GO.
Article
Biochemistry & Molecular Biology
Stefania Zampieri, Silvia Cattarossi, Eleonora Pavan, Antonio Barbato, Agata Fiumara, Paolo Peruzzo, Maurizio Scarpa, Giovanni Ciana, Andrea Dardis
Summary: The study highlights the importance of a comprehensive molecular strategy for proper GBA genotyping and genetic counseling in patients with Gaucher disease, as CES may not detect all possible mutations and recombinations. Additional techniques like MLPA and specific long-range PCR are essential to identify novel mutations and avoid mis-genotyping.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Laura Smith, Anthony H. V. Schapira
Summary: Mutations in the GBA gene are the most important genetic risk factor for Parkinson's disease (PD), leading to protein metabolism abnormalities, lysosomal dysfunction, and lipid metabolism disorders. These mutations can trigger neurodegenerative processes through various mechanisms, including the accumulation of alpha-synuclein, endoplasmic reticulum stress responses, and mitochondrial dysfunction. Understanding these mechanisms can facilitate the development of targeted therapies for GBA-related PD.
Article
Endocrinology & Metabolism
Sebile Kilavuz, Murat Basaranoglu, Serdar Epcacan, Derya Bako, Arife Ozer, Yasemin Nuran Donmez, Emine Ipek Ceylan, Ajlan Tukun, Serdar Ceylaner, Hadi Geylani, Halise Neslihan Onenli Mungan
Summary: Gaucher disease type 2 is a rare and rapidly progressive form of the disease, characterized by acute neurological involvement. Early diagnosis and genetic counseling are crucial for prevention and management of the disease.
METABOLIC BRAIN DISEASE
(2022)
Review
Medicine, General & Internal
Aleksandra Jezela-Stanek, Grazina Kleinotiene, Karolina Chwialkowska, Anna Tylki-Szymanska
Summary: Accurate and prompt genetic diagnosis is crucial in providing families with appropriate prevention and treatment for the lethal form of Gaucher disease, drawing attention to its specific manifestations and potential management.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Francisco J. Sanchez-Rivera, Bianca J. Diaz, Edward R. Kastenhuber, Henri Schmidt, Alyna Katti, Margaret Kennedy, Vincent Tem, Yu-Jui Ho, Josef Leibold, Stella Paffenholz, Francisco M. Barriga, Kevan Chu, Sukanya Goswami, Alexandra N. Wuest, Janelle M. Simon, Kaloyan M. Tsanov, Debyani Chakravarty, Hongxin Zhang, Christina S. Leslie, Scott W. Lowe, Lukas E. Dow
Summary: Improved base editing libraries enable high-throughput functional analysis of single-nucleotide variants in cancer. A modular base-editing-activity sensor was developed to measure the editing efficiency and precision of thousands of sgRNAs paired with functionally distinct base editors. This comprehensive resource of sgRNAs can be used to study cancer-associated single nucleotide variants in cell and animal models.
NATURE BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Hyobin Jeong, Karen Grimes, Kerstin K. Rauwolf, Peter-Martin Bruch, Tobias Rausch, Patrick Hasenfeld, Eva Benito, Tobias Roider, Radhakrishnan Sabarinathan, David Porubsky, Sophie A. Herbst, Busra Erarslan-Uysal, Johann-Christoph Jann, Tobias Marschall, Daniel Nowak, Jean-Pierre Bourquin, Andreas E. Kulozik, Sascha Dietrich, Beat Bornhauser, Ashley D. Sanders, Jan O. Korbel
Summary: This study introduces a computational method called scNOVA, which utilizes Strand-seq to analyze structural variations in single cells and infer gene expression. The research reveals the impact of structural variations on gene regulation and signaling pathways, and successfully applies the method to the study of chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia.
NATURE BIOTECHNOLOGY
(2023)
Article
Chemistry, Medicinal
Matteo Lusardi, Chiara Rotolo, Marco Ponassi, Erika Iervasi, Camillo Rosano, Andrea Spallarossa
Summary: A series of highly functionalized pyrazole derivatives were synthesized through a one-pot, versatile, and regioselective procedure. These derivatives exhibited antiproliferative activity against tumor cells, with compounds 21-23 showing inhibition of melanoma and cervical cancer cell growth. Compound 23 was identified as the most active derivative and was predicted to interact with estrogen receptors through docking simulations.
Review
Biochemistry & Molecular Biology
Alessia Catalano, Domenico Iacopetta, Jessica Ceramella, Domenica Scumaci, Federica Giuzio, Carmela Saturnino, Stefano Aquaro, Camillo Rosano, Maria Stefania Sinicropi
Summary: Multidrug resistance, including resistance to anticancer agents and antimicrobial drugs, is a significant concern in public health. The widespread use of antibiotics has led to the emergence of pathogenic bacteria resistant to multiple drugs, and the ongoing COVID-19 pandemic may worsen antimicrobial resistance. Nanodrug delivery systems have shown promise in overcoming resistance.
Review
Chemistry, Multidisciplinary
Alessia Catalano, Domenico Iacopetta, Jessica Ceramella, Annaluisa Mariconda, Camillo Rosano, Domenica Scumaci, Carmela Saturnino, Pasquale Longo, Maria Stefania Sinicropi
Summary: TNBC is a heterogeneous group of malignancies with poor prognosis and aggressive nature, necessitating the development of new treatment strategies. Diagnosis and subtyping are essential for individualized treatment options. Chemotherapy, immune checkpoint inhibitors, targeted therapy, drug repurposing, nutraceuticals, and nanomedicines are among the various approaches being explored for TNBC treatment.
APPLIED SCIENCES-BASEL
(2022)
Article
Oncology
Alberto Izzotti, Enzo Fracchia, Camillo Rosano, Antonio Comite, Liliana Belgioia, Salvatore Sciacca, Zumama Khalid, Matteo Congiu, Cristina Colarossi, Giusi Blanco, Antonio Santoro, Massimo Chiara, Alessandra Pulliero
Summary: Ozonized oils can effectively decrease the risk of cancer relapses by damaging cancer cells and triggering apoptosis. Administering ozonized oil orally can significantly decrease blood antioxidants in cancer patients, resulting in improved survival rate and decreased relapses.
Article
Chemistry, Medicinal
Jessica Ceramella, Annaluisa Mariconda, Marco Sirignano, Domenico Iacopetta, Camillo Rosano, Alessia Catalano, Carmela Saturnino, Maria Stefania Sinicropi, Pasquale Longo
Summary: Metal complexes based on N-heterocyclic carbenes (NHCs) have been extensively studied in the past decade for their wide applications in material sciences and medicinal chemistry. The research focus has been on gold-based complexes for the development of new anticancer compounds. This study reports the design, synthesis, and good anticancer activity of silver and gold complexes with NHC ligands. Some of these complexes showed activity against breast cancer cell lines. New Au-NHC complexes were prepared to improve solubility and biological activity. Some of these compounds demonstrated interesting anticancer activity and inhibited key cellular processes in breast cancer cells.
Article
Chemistry, Medicinal
Annaluisa Mariconda, Domenico Iacopetta, Marco Sirignano, Jessica Ceramella, Chiara Costabile, Michele Pellegrino, Camillo Rosano, Alessia Catalano, Carmela Saturnino, Hussein El-Kashef, Stefano Aquaro, Maria Stefania Sinicropi, Pasquale Longo
Summary: A new series of silver N-heterocyclic carbene complexes were designed and synthesized, showing anticancer activity against breast cancer cells as well as antimicrobial activity. The multiple target actions of these complexes provide an interesting direction for the development of new chemotherapeutic agents.
Article
Chemistry, Multidisciplinary
Jessica Ceramella, Adele Chimento, Domenico Iacopetta, Arianna De Luca, Gabriela Coronel Vargas, Camillo Rosano, Vincenzo Pezzi, Carmela Saturnino, Maria Stefania Sinicropi
Summary: Chemotherapy is widely used for cancer treatment but it lacks selectivity on healthy cells and can lead to the development of drug resistance. However, a better understanding of cancer genetics has led to the development of new targeted anticancer treatments that show high specificity and reduced toxicity. Multi-target drug design is also becoming a key focus in drug research and development. In this study, a resveratrol derivative showed interesting anti-inflammatory and anti-proliferative properties against breast cancer cells, as well as the ability to disrupt cytoskeleton dynamics and interfere with migration and metastasis. This compound could be a promising starting point for the development of safer and more effective multi-targeted agents.
APPLIED SCIENCES-BASEL
(2022)
Article
Oncology
Silvia Marconi, Michela Croce, Giovanna Chiorino, Giovanni Rossi, Francesca Guana, Aldo Profumo, Paola Ostano, Angela Alama, Luca Longo, Giuseppa De Luca, Mariella Dono, Maria Giovanna Dal Bello, Marco Ponassi, Camillo Rosano, Paolo Romano, Zita Cavalieri, Massimiliano Grassi, Marco Tagliamento, Lodovica Zullo, Consuelo Venturi, Chiara Dellepiane, Luca Mastracci, Elisa Bennicelli, Paolo Pronzato, Carlo Genova, Simona Coco
Summary: This study performed in-depth analysis of circulating markers in early-stage non-small cell lung cancer (NSCLC) to identify a prognostic score for cancer recurrence prediction. The study found that the overexpression of Exo-miR-130a-3p and the reduction of FpA (2-16) were associated with cancer relapse, and high-risk patients had shorter disease-free survival. The overexpression of miR-130a-3p may lead to dysregulation of angiogenesis and coagulation pathways.
Article
Biochemistry & Molecular Biology
Matteo Lusardi, Aldo Profumo, Chiara Rotolo, Erika Iervasi, Camillo Rosano, Andrea Spallarossa, Marco Ponassi
Summary: A library of highly functionalized phenylaminopyrazoles was synthesized, characterized, and tested for their cell-based activities, showing potential pharmaceutical applications.
Article
Multidisciplinary Sciences
Jessica Ceramella, Chiara La Torre, Michele De Luca, Domenico Iacopetta, Alessia Fazio, Alessia Catalano, Gaetano Ragno, Pasquale Longo, Maria Stefania Sinicropi, Camillo Rosano
Summary: In this study, the properties of broad bean pods were investigated. The extracts from broad bean pods were found to have good in vitro antioxidant and anticancer activities, especially against the melanoma cell line Sk-Mel-28. Furthermore, the ethanol extract was found to induce apoptosis in cancer cells by interfering with microtubule organization.
Review
Biochemistry & Molecular Biology
Maria Stefania Sinicropi, Jessica Ceramella, Domenico Iacopetta, Alessia Catalano, Annaluisa Mariconda, Camillo Rosano, Carmela Saturnino, Hussein El-Kashef, Pasquale Longo
Summary: This article summarizes the important role of metal complexes in pharmaceutical sciences, focusing on the antimicrobial and antiproliferative activities of Schiff bases (SBs) metal complexes, as well as recent studies on various biological activities of mononuclear and binuclear SB complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Jessica Ceramella, Domenico Iacopetta, Anna Caruso, Annaluisa Mariconda, Anthi Petrou, Athina Geronikaki, Camillo Rosano, Carmela Saturnino, Alessia Catalano, Pasquale Longo, Maria Stefania Sinicropi
Summary: Carbazoles have been extensively studied for their various biological properties, including their potential as antibacterial, antimalarial, antioxidant, antidiabetic, neuroprotective, and anticancer agents. This study focused on the anticancer activity of a series of carbazole derivatives against breast cancer cell lines. Compounds 3 and 4 showed the highest activity against the triple negative MDA-MB-231 cell line without affecting normal cells. Further investigations revealed that these compounds selectively inhibited human topoisomerase I and disrupted the actin system, leading to apoptosis. Therefore, compounds 3 and 4 hold promise for the development of multi-targeted therapy for triple negative breast cancer.
Article
Chemistry, Medicinal
Gabriele Carullo, Sarah Mazzotta, Jessica Ceramella, Domenico Iacopetta, Anna Ramunno, Camillo Rosano, Antonella Brizzi, Giuseppe Campiani, Francesca Aiello, Maria S. Sinicropi
Summary: Topoisomerases play a significant role in cancer development and progression in the human body. In particular, the inhibition of topoI has been found to be an effective strategy in controlling cancer cell proliferation. Pyrrole-based compounds have emerged as promising anticancer agents, especially for breast cancer therapy and topoI inhibition. A small library of 1-(2-aminophenyl)pyrrole-based amides (7a-f) has been developed, showing potential as new anticancer agents through their ability to induce apoptosis in MDA-MB-231 cells. Enzymatic assays and docking simulations revealed the inhibitory activity and potential binding site for these compounds.
ARCHIV DER PHARMAZIE
(2023)
Review
Virology
Alessia Catalano, Domenico Iacopetta, Jessica Ceramella, Michele Pellegrino, Federica Giuzio, Maria Marra, Camillo Rosano, Carmela Saturnino, Maria Stefania Sinicropi, Stefano Aquaro
Summary: Antibacterial resistance is a growing problem in public health, and the COVID-19 pandemic has exacerbated this issue. Antibiotic misuse and improper access have increased during the pandemic, potentially amplifying the future antibacterial resistance pandemic. Infections caused by multidrug-resistant, extensively drug-resistant, difficult-to-treat drug-resistant, carbapenem-resistant, and pan-drug-resistant bacteria continue to rise. This review highlights the current state of antibacterial resistance worldwide, focusing on important pathogens such as Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae and their resistance to common antibiotics.
Article
Chemistry, Medicinal
Maria Stefania Sinicropi, Jessica Ceramella, Patrice Vanelle, Domenico Iacopetta, Camillo Rosano, Omar Khoumeri, Shawkat Abdelmohsen, Wafaa Abdelhady, Hussein El-Kashef
Summary: Cancer is a complex disease and developing new compounds for cancer treatments is urgently needed. In recent years, the design and synthesis of innovative hybrid molecules have gained interest, with promising results in inhibiting cancer cells. The tested hybrid compounds containing trimethoxybenzene, thiazolidinedione and thiazole showed good efficacy against breast cancer cells, with compound 7e being the most effective. Docking simulations indicated that these compounds may target human Topoisomerases I and II, and enzymatic assays confirmed their inhibitory activity. Compound 7e was found to induce apoptosis in MCF-7 cells. These findings support further research in designing and synthesizing analogues for anticancer purposes.
