Article
Biochemistry & Molecular Biology
Laura Ortiz-Miravalles, Manuel Sanchez-Angulo, Jesus M. Sanz, Beatriz Maestro
Summary: A collection of 1200 compounds from a repurposing drugs library was screened for their antimicrobial effects against Streptococcus pneumoniae. After four rounds of screening, seven compounds were selected and found to inhibit pneumococcal growth and reduce bacterial viability by 90.0% to 99.9% at a concentration of 25 mu M. All compounds, except one, also increased bacterial membrane permeability and shared a common chemical structure. These findings offer new possibilities for combating pneumococcal diseases through drug repositioning and provide insights for the design of membrane-targeted antimicrobials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Bibhuti Bhusan Kakoti, Rajashri Bezbaruah, Nasima Ahmed
Summary: Drug repositioning is a process that improves traditional drug discovery by finding new therapeutic applications for existing drugs. It has great potential and importance in treating neurodegenerative diseases, providing cost-effective and time-saving treatment opportunities in the current medical field.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Dong Liang, Chen Yu, Zhao Ma, Xingye Yang, Zhenzhen Li, Xuhui Dong, Xiaojun Qin, Lupei Du, Minyong Li
Summary: In this study, we identified parbendazole as a promising compound for the treatment of head and neck squamous cell carcinoma (HNSCC) through a batch query in the connectivity map. Parbendazole was found to inhibit the proliferation of HNSCC cell lines by targeting tubulin and disrupting microtubule polymerization. It demonstrated therapeutic effect and low toxicity in in vivo and in vitro anti-tumor evaluation.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Pharmacology & Pharmacy
Lan Zhang, Yi Liu, Yingying Lu, Guan Wang
Summary: Epigenetics, as a new research avenue, holds great value in unraveling the complex mysteries of neurodegenerative diseases. By regulating gene expression levels, epigenetic mechanisms such as DNA methylation, histone modifications, chromatin remodeling enzymes, and long non-coding RNAs play significant roles in neurodegenerative diseases. Promising strategies targeting these mechanisms offer potential breakthroughs in the treatment of neurodegenerative diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biophysics
Matheus Scarpatto Rodrigues, Gabriela Cristina de Paula, Mariane Bernardo Duarte, Victoria Linden de Rezende, Jonathann Correa Possato, Hemelin Resende Farias, Eduarda Behenck Medeiros, Paulo Emilio Feuser, Emilio Luiz Streck, Ricardo Andrez Machado de Avila, Rachel Krolow Santos Silva Bast, Josiane Budni, Andreza Fabro de Bem, Paulo Cesar Lock Silveira, Jade de Oliveira
Summary: Hypercholesterolemia is associated with neurodegenerative diseases development, but treatment with gold nanoparticles (GNPs) can potentially alleviate inflammation, BBB disruption, and memory impairments caused by high cholesterol intake.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Medicine, General & Internal
Cheng Zhang, Mengnan Shi, Woonghee Kim, Muhammad Arif, Martina Klevstig, Xiangyu Li, Hong Yang, Cemil Bayram, Ismail Bolat, Ozlem Ozdemir Tozlu, Jihad Sebhaoui, Shazia Iqbal, Yongjun Wei, Xiaojing Shi, Jens Nielsen, Hasan Turkez, Mathias Uhlen, Jan Boren, Adil Mardinoglu, Ahmet Haamuftuoglu, Serkan Yildtrim
Summary: This study investigated the effect of PKLR in an NAFLD model and identified two potential drug candidates through drug repositioning. These candidates showed significant inhibition of PKLR expression and triglyceride levels in in vitro models, and were also effective in reducing hepatic steatosis in in vivo rat models.
Review
Pharmacology & Pharmacy
Camila Maurmann de Souza, Allan Pires da Silva, Nelson Gomes Oliveira Junior, Osmel Fleitas Martinez, Octavio Luiz Franco
Summary: Increasing levels of resistance to antibiotics have led to the search for new therapeutic options. Antimicrobial peptides (AMPs) have shown potential against Klebsiella pneumoniae, a highly resistant bacterium. This article provides an overview of recent developments in AMPs against K. pneumoniae, including their different designs and mechanisms, as well as their potential in combination with conventional antibiotics and against biofilms. The challenges and perspectives for applying AMPs in clinical practice are also discussed.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Javad Sharifi-Rad, Cristina Quispe, Zhazira Mukazhanova, Ewa Knut, Aknur Turgumbayeva, Aliya Kipchakbayeva, Gulnaz Seitimova, Mohamad Fawzi Mahomoodally, Devina Lobine, Aaron Koay, Jinfan Wang, Helen Sheridan, Gerardo Leyva-Gomez, Maria L. Del Prado-Audelo, Hernan Cortes, Antonio Rescigno, Paolo Zucca, Oksana Sytar, Muhammad Imran, Celia F. Rodrigues, Natalia Cruz-Martins, Halina Ekiert, Manoj Kumar, Ahmad Faizal Abdull Razis, Usman Sunusi, Ramla Muhammad Kamal, Agnieszka Szopa
Summary: Resveratrol, a polyphenolic stilbene derivative found in grapes and red wine, has shown potential in cancer therapy with its antioxidant, anti-inflammatory, and antiaging abilities. Nanoformulations of resveratrol could improve its efficiency in cancer treatment, making it a promising strategy.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Nanoscience & Nanotechnology
Shuyang Sun, Ziqiang Ding, Xiaomei Yang, Xinyue Zhao, Minlong Zhao, Li Gao, Qu Chen, Shenxia Xie, Aiqun Liu, Shihua Yin, Zhiping Xu, Xiaoling Lu
Summary: The development of monoclonal antibody treatments for successful tumor-targeted therapies has taken decades, with the efficacy still in need of improvement. Nanobodies are gaining acceptance as therapeutic tools due to their unique properties, and are considered a promising new development to address the deficiencies of monoclonal antibody-based therapies.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Review
Medicine, General & Internal
Yunkai Yang, Huan Zhang, Shanshan Huang, Qian Chu
Summary: The KRAS gene is commonly mutated in solid tumors, but targeting it has been a challenge. However, recent breakthroughs with KRAS G12C inhibitors show promise in targeted therapy, although resistance may occur. Therefore, non-targeted conventional therapies are also considered promising.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biology
Chen Yang, Hailin Zhang, Mengnuo Chen, Siying Wang, Ruolan Qian, Linmeng Zhang, Xiaowen Huang, Jun Wang, Zhicheng Liu, Wenxin Qin, Cun Wang, Hualian Hang, Hui Wang
Summary: Pharmacologic perturbation projects have generated expression data for computational therapeutic discovery, but optimal methodologies and parameters are still unclear. This study developed benchmarking standards and determined an optimal approach for drug retrieval. The candidate agent HHT was validated and shown to have therapeutic effects on liver cancer.
Article
Oncology
Irene Dell'Anno, Sarah A. Martin, Marcella Barbarino, Alessandra Melani, Roberto Silvestri, Maria Bottaro, Elisa Paolicchi, Alda Corrado, Monica Cipollini, Ombretta Melaiu, Antonio Giordano, Luca Luzzi, Federica Gemignani, Stefano Landi
Summary: Malignant pleural mesothelioma (MPM) is a fatal disease mainly caused by asbestos exposure, with effective therapies lacking. Through drug screening, it was found that F-araA and RIS have cytotoxic effects in MPM cells, with F-araA specifically inhibiting proliferation and colony formation by targeting STAT1 expression and nucleic acids synthesis. Further experiments are needed to fully explore the potential therapeutic effects of F-araA in MPM and other tumor types.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Medicine, Research & Experimental
Mennatallah O. Zaki, Doaa A. Elsherbiny, Mohamed Salama, Samar S. Azab
Summary: This article discusses the correlation between tauopathy and common diseases such as type 2 diabetes mellitus and COVID-19, and explores how these diseases can worsen the development of tau pathology. It also examines the potential of drug repositioning for managing tauopathy. By repurposing drugs, it is possible to simultaneously manage or prevent multiple diseases while reducing side effects and drug-drug interactions.
Article
Pharmacology & Pharmacy
Albert Li, Jhih-Yu Chen, Chia-Lang Hsu, Yen-Jen Oyang, Hsuan-Cheng Huang, Hsueh-Fen Juan
Summary: This study investigates the transcriptome of COVID-19 patients and applies biological network analysis to identify gene signatures associated with PCPF. The identified signature shows potential as a diagnostic and assessment biomarker for pulmonary fibrosis. Moreover, a network-based drug repurposing method is utilized to explore novel treatments for PCPF.
Article
Oncology
Robson Francisco Carvalho, Luisa Matos do Canto, Sarah Santiloni Cury, Torben Frostrup Hansen, Lars Henrik Jensen, Silvia Regina Rogatto
Summary: Rectal cancer is a significant global health issue, with varying responses to neoadjuvant therapy. Drug repositioning, particularly with approved topoisomerase II inhibitors, shows promise in treating rectal cancer. Genetic analysis and drug screenings have identified potential targeted therapies based on topoisomerase II inhibitor efficacy, offering personalized treatment options for rectal cancer patients.
Article
Biochemistry & Molecular Biology
L. Marchi, F. Degola, E. Baruffini, F. M. Restivo
Summary: Plant NADH glutamate dehydrogenase is a complex enzyme with reversible activity, different isoforms, and variable localization, making it challenging to understand its physiological role. Various approaches have been used to study GDH expression in different plant systems and environmental conditions.
Review
Clinical Neurology
Valentina Del Dotto, Valerio Carelli
Summary: The discovery of OPA1 mutations causing DOA in 2000 led to the rapid expansion of the field of mitochondrial dynamics and the exploration of complex pathways beyond its strict role in mitochondrial fusion. Translational mitochondrial medicine emphasizes the need for disease modeling at various levels, from yeast to animal models, to develop therapeutic strategies based on a thorough understanding of pathogenic mechanisms. This review provides an in-depth examination of the state of the art in these approaches.
FRONTIERS IN NEUROLOGY
(2021)
Article
Endocrinology & Metabolism
Stefania Evangelisti, Laura Ludovica Gramegna, Chiara La Morgia, Lidia Di Vito, Alessandra Maresca, Lia Talozzi, Claudio Bianchini, Micaela Mitolo, David Neil Manners, Leonardo Caporali, Maria Lucia Valentino, Rocco Liguori, Valerio Carelli, Raffaele Lodi, Claudia Testa, Caterina Tonon
Summary: This study discovered widespread cortical gray matter loss and white matter microstructural alterations in patients carrying the m.3243A > G mutation. High urine mtDNA mutation load, plasma lactate and alanine levels, serum FGF-21 levels, and ventricular lactate accumulation were significantly correlated with reduced brain gray matter density. Additionally, white matter microstructural changes were significantly correlated with plasma alanine and arginine levels, urine mtDNA mutation load, serum GDF-15 levels, and plasma ccf-mtDNA content.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Mariantonietta Capristo, Valentina Del Dotto, Concetta Valentina Tropeano, Claudio Fiorini, Leonardo Caporali, Chiara La Morgia, Maria Lucia Valentino, Monica Montopoli, Valerio Carelli, Alessandra Maresca
Summary: The study suggests that rapamycin-based therapy may be a promising treatment option for MERRF. The first therapeutic strategy was ineffective in high-mutation load cell lines, while the second strategy showed significant improvement in fibroblasts with intermediate-mutation load, rescuing the bioenergetics defect completely.
MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Alberto Danese, Simone Patergnani, Alessandra Maresca, Camille Peron, Andrea Raimondi, Leonardo Caporali, Saverio Marchi, Chiara La Morgia, Valentina Del Dotto, Claudia Zanna, Angelo Iannielli, Alice Segnali, Ivano Di Meo, Andrea Cavaliere, Magdalena Lebiedzinska-Arciszewska, Mariusz R. Wieckowski, Andrea Martinuzzi, Milton N. Moraes-Filho, Solange R. Salomao, Adriana Berezovsky, Rubens Belfort, Christopher Buser, Fred N. Ross-Cisneros, Alfredo A. Sadun, Carlo Tacchetti, Vania Broccoli, Carlotta Giorgi, Valeria Tiranti, Valerio Carelli, Paolo Pinton
Summary: Patients with Leber's hereditary optic neuropathy (LHON) exhibit sustained abnormal autophagy and compartment-specific mitophagy activity, disrupting mitochondrial homeostasis and leading to defective bioenergetics and excessive reactive oxygen species production. Modulating autophagy and mitochondrial biogenesis can counteract this pathological mechanism.
Review
Biochemistry & Molecular Biology
Martina Magistrati, Alexandru Ionut Gilea, Camilla Ceccatelli Berti, Enrico Baruffini, Cristina Dallabona
Summary: In eukaryotes, specific nucleotide modifications of mitochondrial RNAs play critical roles in the synthesis of mitochondrial proteins and oxidative phosphorylation. Mutations in genes encoding for mt-RNAs modifying enzymes can cause modopathies. These mutations lead to the absence or decrease of specific nucleotide modifications, impairing the efficiency and accuracy of mitochondrial protein synthesis. Confirmation of their pathogenicity through a model system, such as Saccharomyces cerevisiae, is essential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Leonardo Caporali, Claudio Fiorini, Flavia Palombo, Martina Romagnoli, Flavia Baccari, Corrado Zenesini, Paola Visconti, Annio Posar, Maria Cristina Scaduto, Danara Ormanbekova, Agatino Battaglia, Raffaella Tancredi, Cinzia Cameli, Marta Viggiano, Anna Olivieri, Antonio Torroni, Elena Maestrini, Magali Jane Rochat, Elena Bacchelli, Valerio Carelli, Alessandra Maresca
Summary: Research has found that mtDNA plays a role in the development and expression of ASD, particularly with a protective effect from paternal mtDNA in the Italian population. Additionally, ASD patients have lower mtDNA content. Further confirmation is needed in larger independent cohorts.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Alexandru Ionut Gilea, Martina Magistrati, Ilenia Notaroberto, Natascia Tiso, Cristina Dallabona, Enrico Baruffini
Summary: Most eukaryotes have a mitochondrial genome called mtDNA, which is replicated by the enzyme DNA polymerase ?, or Pol ?. In animals and fungi, Pol ? consists of a catalytic subunit encoded by MIP1. In humans, Pol ? is a heterotrimer composed of the catalytic subunit homolog to Mip1, encoded by POLG, and two accessory subunits. Over the past 25 years, more than 300 pathological mutations in POLG have been identified as the cause of POLG-related disorders, characterized by mtDNA deletions and depletion. This review focuses on the biochemical properties and mutations of yeast Mip1 and their impact on enzyme activity, mtDNA stability, and mutability. The use of yeast with Mip1 mutations equivalent to human ones is discussed for confirming pathogenicity, identifying phenotypic defects, and finding rescue mechanisms and compounds. The genetic interactions of other polymerases, such as Pol ?, Rev1, and Pol ?, in maintaining mtDNA stability and preventing point mutations, are also explored.
Review
Biochemistry & Molecular Biology
Martina Magistrati, Alexandru Ionut Gilea, Maria Carla Gerra, Enrico Baruffini, Cristina Dallabona
Summary: Mitochondrial diseases (MDs) are a group of pathologies characterized by defective mitochondrial function and energy production. The yeast Saccharomyces cerevisiae is an efficient model organism to study MDs and has been used successfully to validate pathogenic variants and discover potential treatment molecules. The drug drop test, coupled with a drug repurposing approach, allows for cost-effective and time-saving identification of molecules with high translational potential. The screening has been successful in various disease models, and further studies on complex organisms confirmed the effectiveness of the drugs, demonstrating the usefulness of this approach.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Flavia Palombo, Camille Peron, Leonardo Caporali, Angelo Iannielli, Alessandra Maresca, Ivano Di Meo, Claudio Fiorini, Alice Segnali, Tiina Manninen, Francesca L. Sciacca, Ambra Rizzo, Sonia Levi, Anu Suomalainen, Alessandro Prigione, Vania Broccoli, Valerio Carelli, Valeria Tiranti
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Leonardo Caporali, Claudio Fiorini, Flavia Palombo, Flavia Baccari, Martina Romagnoli, Paola Visconti, Annio Posar, Maria Cristina Scaduto, Elena Maestrini, Cinzia Cameli, Marta Viggiano, Anna Olivieri, Antonio Torroni, Elena Bacchelli, Magali Rochat, Valerio Carelli, Alessandra Maresca
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Mariantonietta Capristo, Valentina Del Dotto, Concetta Valentina Tropeano, Claudio Fiorini, Monica Montopoli, Valerio Carelli, Alessandra Maresca
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)