Review
Virology
Mostafa Javanian, Mohammad Barary, Sam Ghebrehewet, Veerendra Koppolu, VeneelaKrishnaRekha Vasigala, Soheil Ebrahimpour
Summary: Influenza is an acute viral respiratory infection that affects all age groups and is associated with high mortality. Vaccination is the most effective method for prevention, but antiviral drugs are also available for treatment.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rahma K. Alseksek, Wafaa S. Ramadan, Ekram Saleh, Raafat El-Awady
Summary: This article provides an overview of the role of histone deacetylases (HDACs) in cancer cells' adaptive responses to various stress conditions. It discusses the impact of HDACs in regulating cellular systems and evading death pathways, as well as their potential as therapeutic targets. The article also highlights the use of HDAC inhibitors in combination with stress-inducing agents to manage cancer and overcome resistance to current therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Pasquale Linciano, Rosaria Benedetti, Luca Pinzi, Fabiana Russo, Ugo Chianese, Claudia Sorbi, Lucia Altucci, Giulio Rastelli, Livio Brasili, Silvia Franchini
Summary: HDAC inhibitors play a significant role in cancer treatment, but their lack of selectivity is a major drawback. Researchers have explored novel linker chemotypes to achieve selective inhibition of different HDAC isoforms. Through in vitro tests and docking calculations, it was found that some candidates could selectively inhibit HDAC1 or HDAC6.
BIOORGANIC CHEMISTRY
(2021)
Article
Microbiology
Paulina Koszalka, Ankita George, Vijaykrishna Dhanasekaran, Aeron C. Hurt, Kanta Subbarao
Summary: Combination therapy with influenza drugs baloxavir and oseltamivir can reduce the selection of viruses with reduced drug susceptibility. In animal models, combination therapy and monotherapy have similar effectiveness in reducing viral titers, but combination therapy can decrease the selection of viruses with reduced susceptibility to baloxavir.
Article
Biochemistry & Molecular Biology
Ding-Li Chou, Ju-Yi Mao, Anisha Anand, Han-Jia Lin, John Han-You Lin, Ching-Ping Tseng, Chih-Ching Huang, Hsian-Yu Wang
Summary: The study demonstrates that carbonized nanogels synthesized from an amino acid have effective viral inhibition properties against infectious bronchitis virus, leading to significant improvements in IBV-infected chicken embryos.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Martin Marek, Elizabeth Ramos-Morales, Gisele F. A. Picchi-Constante, Theresa Bayer, Carina Norstrom, Daniel Herp, Policarpo A. Sales-Junior, Eloise P. Guerra-Slompo, Kristin Hausmann, Alokta Chakrabarti, Tajith B. Shaik, Annika Merz, Edouard Troesch, Karin Schmidtkunz, Samuel Goldenberg, Raymond J. Pierce, Marina M. Mourao, Manfred Jung, Johan Schultz, Wolfgang Sippl, Nilson I. T. Zanchin, Christophe Romier
Summary: The zinc-dependent histone deacetylases in the protozoan parasite Trypanosoma cruzi have significantly diverged from their human counterparts, with tcDAC2 displaying essential deacetylase activity and major structural differences. Targeting these atypical HDACs can lead to selective chemical impairment of parasites.
Review
Oncology
Rui Ling, Jingzhi Wang, Yuan Fang, Yunpeng Yu, Yuting Su, Wen Sun, Xiaoqin Li, Xiang Tang
Summary: Radiotherapy is an important treatment for tumors, but resistance to radiotherapy has remained a challenge in clinical tumor therapy. The mechanisms of radiotherapy resistance involve the repair of sublethal and potentially lethal damage of tumor cells, cell repopulation, cell cycle redistribution, and reoxygenation, which are closely related to the regulation of epigenetic modifications. Histone deacetylases (HDACs) play a significant role in tumor radiotherapy resistance through their participation in DNA damage repair, cell cycle regulation, and cell apoptosis. This article systematically explores the specific mechanism by which HDACs promote tumor radiotherapy resistance and discusses the potential clinical applications of HDAC inhibitors, providing guidance for HDAC-related drug development and future research on improving tumor radiotherapy resistance.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Claudio Brancolini, Teresa Gagliano, Martina Minisini
Summary: This article discusses the adaptability of cancer cells to hostile microenvironment conditions and focuses on the role of epigenetic control in cancer development and the challenges in developing epigenetic drugs.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Virology
Dimitra Dimopoulou, Sophia Vourli, Konstantinos Douros, Spyridon Pournaras, Vassiliki Papaevangelou
Summary: This observational study found that the use of FilmArray molecular test in children with influenza-like illness symptoms decreased hospitalization rates and oseltamivir administration, but had no impact on other diagnostic testing or antibacterial prescription. Consideration of point-of-care tests is needed to improve management of children with ILI and reduce healthcare costs.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Review
Pharmacology & Pharmacy
Yi Luan, Hui Liu, Ying Luan, Yang Yang, Jing Yang, Kai-Di Ren
Summary: Atherosclerosis (AS) is a disease characterized by progressive hardening and reduced elasticity of arteries, leading to increased morbidity and mortality. Recent studies have shown that epigenetic modifications on genes, especially histone deacetylases (HDACs), play a significant role in the development of AS and other diseases. HDACs promote chromatin compaction and inhibit the transcription of downstream genes, affecting various physiological and pathological processes. This review discusses the role of HDACs in vascular systems, their diverse roles in AS, and the potential of HDAC inhibitors as drugs for AS treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eunkyung Jung, Ruben Soto-Acosta, Robert J. Geraghty, Liqiang Chen
Summary: In this study, an alternative substitution pattern centered on a 1H-pyrazolo[3,4-d]pyrimidine scaffold was discovered to exhibit low micromolar antiviral activity against Zika virus. Structure-activity relationship studies revealed that an electron-withdrawing group at the para position of ring A enhanced the antiviral activity. Compounds 6 and 13 were identified as potential anti-ZIKV agents with low micromolar antiviral activity and relatively low cytotoxicity.
Article
Microbiology
Sangwoo Nam, Yun Ji Ga, Joo-Youn Lee, Woo-Yeon Hwang, Eunhye Jung, Jin Soo Shin, Weiyi Chen, Gildon Choi, Bin Zhou, Jung-Yong Yeh, Yun Young Go
Summary: The study found that radicicol effectively suppressed CHIKV replication and may serve as a potential drug candidate against CHIKV. It also revealed nsP2 as a putative molecular target of radicicol, with the G641D mutation in nsP2 playing a key role in its interaction with cytoplasmic Hsp90 beta chaperone.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Elisabetta Di Bello, Veronica Sian, Giulio Bontempi, Clemens Zwergel, Rossella Fioravanti, Beatrice Noce, Carola Castiello, Stefano Tomassi, Davide Corinti, Daniela Passeri, Roberto Pellicciari, Ciro Mercurio, Mario Varasi, Lucia Altucci, Marco Tripodi, Raffaele Strippoli, Angela Nebbioso, Sergio Valente, Antonello Mai
Summary: After years of research, HDAC inhibitors have been developed and approved by FDA/Chinese FDA for the treatment of cancer and non-cancer diseases. A series of novel compounds have been discovered to be effective anticancer agents, demonstrating selective inhibition of HDACs and inducing cell death and differentiation. These compounds also modulate gene and protein expression related to apoptosis and show potent antiproliferative activity in various cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Physiology
Alessandra Renzini, Marco D'Onghia, Dario Coletti, Viviana Moresi
Summary: Skeletal muscle plays a crucial role in controlling body weight and metabolism by communicating with other tissues, while HDACs serve as key regulators of metabolic responses and interact bidirectionally with circulating factors.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Matthew J. Kling, Varun Kesherwani, Nitish K. Mishra, Gracey Alexander, Erin M. McIntyre, Sutapa Ray, Kishore B. Challagundla, Shantaram S. Joshi, Don W. Coulter, Nagendra K. Chaturvedi
Summary: This study suggests that dual-inhibition of BET and HDAC proteins may be a novel therapeutic approach for MYC-driven MB.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Beatrice Noce, Elisabetta Di Bello, Clemens Zwergel, Rossella Fioravanti, Sergio Valente, Dante Rotili, Andrea Masotti, Mohammad Salik Zeya Ansari, Daniela Trisciuoglio, Alokta Chakrabarti, Christophe Romier, Dina Robaa, Wolfgang Sippl, Manfred Jung, Cecile Haeberli, Jennifer Keiser, Antonello Mai
Summary: Schistosoma mansoni HDAC8 is a reliable target for combating schistosomiasis, but most inhibitors lack selectivity over human deacetylases and have low or no activity against the parasite. In this study, a small library of HDAC inhibitors from the lab was tested for their in vitro enzyme and biological activity. These inhibitors showed submicromolar/nanomolar potency against smHDAC8 and varied selectivity over hHDAC1 and/or hHDAC6. Some compounds exhibited high activity against larval and adult stages of S. mansoni with moderate to no toxicity in human fibroblast cells.
Review
Pharmacology & Pharmacy
Clemens Zwergel, Rossella Fioravanti, Antonello Mai
Summary: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that, when overexpressed, induces an inhibitory signal causing T cell exhaustion and immune escape in tumors. Immunotherapy targeting the PD-L1 pathway has successfully treated various cancers. Recent advances in understanding the complex biology of PD-L1 have led to the development of small-molecule inhibitors. This review highlights the most promising recent advances in understanding the regulation mechanisms of PD-L1 and the use of small-molecule modulators in combination therapy with other epigenetic chemotherapeutic agents.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Medicinal
Elisabetta Di Bello, Veronica Sian, Giulio Bontempi, Clemens Zwergel, Rossella Fioravanti, Beatrice Noce, Carola Castiello, Stefano Tomassi, Davide Corinti, Daniela Passeri, Roberto Pellicciari, Ciro Mercurio, Mario Varasi, Lucia Altucci, Marco Tripodi, Raffaele Strippoli, Angela Nebbioso, Sergio Valente, Antonello Mai
Summary: After years of research, HDAC inhibitors have been developed and approved by FDA/Chinese FDA for the treatment of cancer and non-cancer diseases. A series of novel compounds have been discovered to be effective anticancer agents, demonstrating selective inhibition of HDACs and inducing cell death and differentiation. These compounds also modulate gene and protein expression related to apoptosis and show potent antiproliferative activity in various cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Paola Checconi, Cristiana Coni, Dolores Limongi, Sara Baldelli, Fabio Ciccarone, Marta De Angelis, Manuela Mengozzi, Pietro Ghezzi, Maria Rosa Ciriolo, Lucia Nencioni, Anna Teresa Palamara
Summary: Redox modifications, including glutathionylation, play important roles during viral infection. The study reveals that influenza virus infection induces protein glutathionylation and that glutaredoxin-mediated deglutathionylation is crucial for the viral life cycle. These findings contribute to the understanding of redox regulation in influenza virus replication and may help identify new targets for controlling respiratory viral infections.
Article
Biochemistry & Molecular Biology
Alessandra Fraternale, Marta De Angelis, Riccardo De Santis, Donatella Amatore, Sofia Masini, Francesca Monittola, Michele Menotta, Federica Biancucci, Francesca Bartoccini, Michele Retini, Valentina Fiori, Raoul Fioravanti, Fabio Magurano, Laura Chiarantini, Florigio Lista, Giovanni Piersanti, Anna T. Palamara, Lucia Nencioni, Mauro Magnani, Rita Crinelli
Summary: The life cycle of SARS-CoV-2 is influenced by the environmental redox state, with a reducing environment impairing spike protein binding to ACE2 and an oxidizing environment promoting their interaction. Synthetic low molecular weight thiols induce a more reduced state in the receptor binding domain of the spike protein, impairing ACE2 binding and interfering with protein folding and viral replication. These thiols could potentially serve as innovative anti-SARS-CoV-2 therapeutics.
Article
Biochemistry & Molecular Biology
Francesco Pastore, Martina Battistoni, Raimondo Sollazzo, Pietro Renna, Fabiola Paciello, Domenica Donatella Li Puma, Eugenio Barone, Onur Dagliyan, Cristian Ripoli, Claudio Grassi
Summary: ADAM10 is a cell surface protease involved in the cleavage of membrane proteins. Dysregulation of ADAM10 has been linked to various pathological conditions, including AD. Researchers have designed a bioengineering strategy to control the cleavage activity of ADAM10, providing insights into AD treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Francesco Fiorentino, Martina Menna, Dante Rotili, Sergio Valente, Antonello Mai
Summary: RNA methylation is a crucial mechanism for regulating gene expression and RNA maturation. METTL3, an RNA methyltransferase, plays a key role in this process by adding a methyl group to N6-adenosine of RNA. Dysregulation of METTL3 can lead to various diseases and viral infections. By studying the correlation between METTL3 and diseases, as well as analyzing the development and mode of action of known METTL3 inhibitors, we can gain a better understanding of the biological functions of this enzyme and potentially develop new therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Claudia Colussi, Giuseppe Aceto, Cristian Ripoli, Alessia Bertozzi, Domenica Donatella Li Puma, Elena Paccosi, Marcello D'Ascenzo, Claudio Grassi
Summary: This study reveals that the abnormal localization of HDAC4 may contribute to synaptic dysfunction in AD, leading to impaired synaptic transmission and cognitive deficits.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Domenica Donatella Li Puma, Claudia Colussi, Bruno Bandiera, Giulia Puliatti, Marco Rinaudo, Sara Cocco, Fabiola Paciello, Agnese Re, Cristian Ripoli, Giovanna De Chiara, Alessia Bertozzi, Anna Teresa Palamara, Roberto Piacentini, Claudio Grassi
Summary: Extensive research supports that neuroinflammation is involved in various brain disorders. However, the molecular mechanisms behind the synaptic and cognitive dysfunction caused by inflammatory mediators in neurodegenerative diseases, like Alzheimer's disease, are not fully understood. This study investigated the impact of interleukin 1 beta (IL-1 beta) and its downstream molecular cascade on synaptic dysfunction in a mouse model with multiple Herpes simplex virus type-1 (HSV-1) reactivations in the brain. The results showed that mice with two HSV-1 reactivations had increased levels of IL-1 beta and exhibited cognitive impairments, hippocampal long-term potentiation deficits, altered expression of synaptic-related genes and proteins, and changes in dendritic spine density and morphology. The study also revealed that the epigenetic repressor MeCP2, in association with HDAC4, played a role in these effects. Blocking IL-1 receptors with the specific antagonist Anakinra prevented the increase in MeCP2 and the subsequent downregulation of gene expression, as well as the rescue of neurodegeneration-related structural and functional indices. Overall, this study provides novel mechanistic evidence on the role of HSV-1-activated IL-1 beta signaling pathways in synaptic deficits leading to cognitive impairment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Cell Biology
Michele Aventaggiato, Federica Barreca, Laura Vitiello, Simone Vespa, Sergio Valente, Dante Rotili, Antonello Mai, Lavinia Vittoria Lotti, Luigi Sansone, Matteo A. Russo, Mariano Bizzarri, Elisabetta Ferretti, Marco Tafani
Summary: Life on Earth has evolved in the presence of gravity constraint, and any change in gravity has important physiological effects. Our study demonstrates that activation of mitochondrial Sirtuin 3 (SIRT3) can reduce muscle damage caused by microgravity and preserve muscle differentiation. We simulated microgravity on a muscle and cardiac cell line and treated the cells with a newly synthesized SIRT3 activator. The results show that SIRT3 activation reduces microgravity-induced cell death and maintains muscle cell differentiation markers.
Article
Microbiology
Leonardo Sorrentino, Walter Toscanelli, Matteo Fracella, Marta De Angelis, Federica Frasca, Carolina Scagnolari, Laura Petrarca, Raffaella Nenna, Fabio Midulla, Anna Teresa Palamara, Lucia Nencioni, Alessandra Pierangeli
Summary: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are common causes of hospitalization in children, with RSV being more severe. The study investigated the interplay between interferon (IFN) responses and nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant activity in RSV and HRV infections. The findings suggest that reduced NRF2 activation in RSV-infected infants may contribute to the severity of bronchiolitis.
Article
Chemistry, Medicinal
Clemens Zwergel, Michele Aventaggiato, Sabrina Garbo, Elisabetta Di Bello, Bruno Fassari, Beatrice Noce, Carola Castiello, Chiara Lambona, Federica Barreca, Dante Rotili, Rossella Fioravanti, Thomas Schmalz, Michael Weyand, Amelie Niedermeier, Marco Tripodi, Gianni Colotti, Clemens Steegborn, Cecilia Battistelli, Marco Tafani, Sergio Valente, Antonello Mai
Summary: The mitochondrial protein SIRT3 plays a role in cancer, metabolism, and hypoxia-related diseases. New 1,4-dihydropyridine compounds, namely 2 and 3, have been discovered and compound 3 is a specific activator of SIRT3. Among a series of related compounds, compound 3c binds and activates SIRT3 the strongest, while compound 3d shows the best effects on enhancing glutamate dehydrogenase activity and deacetylating proteins in breast cancer cells. Compound 3d also exhibits significant anti-cancer effects in both normoxia and hypoxia conditions, reducing cell viability, clonogenicity, and migration ability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Joana Reis, Christoph Gorgulla, Marta Massari, Sara Marchese, Sergio Valente, Beatrice Noce, Lorenzo Basile, Ricarda Toerner, Huel Cox, Thibault Viennet, Moon Hee Yang, Melissa M. Ronan, Matthew G. Rees, Jennifer A. Roth, Lucia Capasso, Angela Nebbioso, Lucia Altucci, Antonello Mai, Haribabu Arthanari, Andrea Mattevi
Summary: In this study, the authors validate inhibitors for human NOX enzymes using computational and experimental methods, opening avenues for cancer drug development and research in redox biology.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Infectious Diseases
Roberta Maria Nicolosi, Graziana Bonincontro, Elena Imperia, Camilla Badiali, Daniela De Vita, Fabio Sciubba, Laura Dugo, Michele Pier Luca Guarino, Annamaria Altomare, Giovanna Simonetti, Gabriella Pasqua
Summary: The protective effect of procyanidin-rich grape seed extract (prGSE) on gastrointestinal diseases caused by bacterial endotoxin and biofilm formation has been studied. It can reduce permeability alteration and oxidative stress, and inhibit biofilm formation.
