Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Article
Cell Biology
Adrien Grenier, Laury Poulain, Johanna Mondesir, Arnaud Jacquel, Claudie Bosc, Lucille Stuani, Sarah Mouche, Clement Larrue, Ambrine Sahal, Rudy Birsen, Victoria Ghesquier, Justine Decroocq, Fetta Mazed, Mireille Lambert, Mamy Andrianteranagna, Benoit Viollet, Patrick Auberger, Andrew A. Lane, Pierre Sujobert, Didier Bouscary, Jean-Emmanuel Sarry, Jerome Tamburini
Summary: AMPK activation in AML cells triggers the unfolded protein response, leading to repression of oxidative phosphorylation, TCA cycle, and pyrimidine biosynthesis, as well as enhanced mitochondrial apoptotic signaling. Combination therapy with the AMPK activator GSK621 and the Bcl-2 inhibitor venetoclax shows synergistic effects, suggesting therapeutic potential in AML.
Article
Biochemistry & Molecular Biology
Rafaela G. A. Costa, Suellen L. R. Silva, Ingrid R. S. B. Dias, Maiara de S. Oliveira, Ana Carolina B. da C. Rodrigues, Rosane B. Dias, Daniel P. Bezerra
Summary: Acute myeloid leukemia (AML) is a heterogeneous disease group with various mutations triggering malignant proliferation. AML relapse is mainly caused by leukemic stem cells (LSCs) with self-renewal capacity and resistance to traditional therapies. LSCs have low oxidative stress levels due to low mitochondrial activity and high ROS-removing pathway activity. Targeting oxidative stress could be a potential strategy to eliminate AML LSCs.
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Wenxin Du, Aixiao Xu, Yunpeng Huang, Ji Cao, Hong Zhu, Bo Yang, Xuejing Shao, Qiaojun He, Meidan Ying
Summary: Autophagy plays a crucial role in the development of AML, with studies indicating the potential of modulating autophagy to enhance targeted therapy for AML.
Article
Multidisciplinary Sciences
Thomas R. Jackson, Aini Vuorinen, Laia Josa-Cullere, Katrina S. Madden, Daniel Conole, Thomas J. Cogswell, Isabel V. L. Wilkinson, Laura M. Kettyle, Douzi Zhang, Alison O'Mahony, Deanne Gracias, Lorna McCall, Robert Westwood, Georg C. Terstappen, Stephen G. Davies, Edward W. Tate, Graham M. Wynne, Paresh Vyas, Angela J. Russell, Thomas A. Milne
Summary: This study found that tubulin disruptors can induce differentiation of AML cells, leading to decreased tumor burden and increased survival rates in vivo.
Article
Biochemistry & Molecular Biology
Yasushi Kubota, Toshimi Hoshiko, Taishi Higashi, Keiichi Motoyama, Seiji Okada, Shinya Kimura
Summary: This study found that folate-conjugated 2-Hydroxypropyl-beta-cyclodextrin (FA-HP-beta-CyD) has strong cytotoxic activity against folate receptor-expressing AML cells and induces autophagic cell death. Additionally, FA-HP-beta-CyD enhances the inhibitory effects of cytarabine and Venetoclax drugs commonly used for AML treatment, indicating its potential as a promising agent for AML chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Fahui Li, Congying Gao, Xueming Li, Jiangyun Wang, Yao Zhao, Yu Ke, Ying Liu, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The natural compound Jiyuan oridonin A (JOA) has been found to overcome the differentiation blockade in AML cells and leukemic stem-like cells, inhibiting their proliferation and offering a novel therapeutic strategy for AML.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Debora Bifano Pimenta, Vanessa Araujo Varela, Tarcila Santos Datoguia, Victoria Bulcao Caraciolo, Gabriel Herculano Lopes, Welbert Oliveira Pereira
Summary: Bone marrow is a complex tissue that regulates hematopoiesis, with AML developing in this microenvironment. Cells and molecules within the hematopoietic niche interact to influence leukemia development, suggesting that targeting the bone marrow microenvironment could be a promising strategy for AML treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Gongqiang Wu, Shanshan Guo, Qian Luo, Xiaoxia Wang, Wenhai Deng, Guifang Ouyang, Jeffrey J. Pu, Wen Lei, Wenbin Qian
Summary: This study identified anti-CD70 CAR-T cells as a potential new treatment for AML. However, this CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting the need for further research and development of innovative combinatorial CAR constructs and increased CD70 expression on leukemia cell surface to optimize CAR-T cell responses for AML.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Giordana Feriotto, Federico Tagliati, Arianna Brunello, Simone Beninati, Claudio Tabolacci, Carlo Mischiati
Summary: This study found that caffeic acid (CA) has antiproliferative and pro-apoptotic effects on chronic myeloid leukemia (CML) cells. The activity of TG2 enzyme was found to be related to the anticancer effects of CA, by increasing reactive oxygen species (ROS) and inhibiting caspase activation and apoptosis. Knocking down TGM2 transcripts confirmed the importance of TG2 activation in CML cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xiaoling Xie, Wuju Zhang, Xuan Zhou, Binyan Xu, Hao Wang, Yingqi Qiu, Yuxing Hu, Bin Guo, Zhixin Ye, Le Hu, Honghao Zhang, Yuhua Li, Xiaochun Bai
Summary: Low serum IFN-gamma levels are associated with a higher percentage of LSCs and greater relapse incidence in AML patients. High doses of IFN-gamma have an anti-AML effect, while low doses accelerate AML development and support LSC self-renewal. Targeting IFNGR1 in AML cells induces differentiation and delays leukemogenesis.
Review
Oncology
Jialan Niu, Danyue Peng, Lingbo Liu
Summary: This review summarizes the resistance mechanisms of leukemia stem cells (LSCs) and the crucial role of the bone marrow microenvironment in LSCs resistance in acute myeloid leukemia (AML), providing better strategies for future research on eradicating LSCs and clinical treatment of AML.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Ines Costa, Beatriz Santos Lapa, Joana Jorge, Raquel Alves, Isabel Marques Carreira, Ana Bela Sarmento-Ribeiro, Ana Cristina Goncalves
Summary: Zinc plays a dual role in modulating the DNA damage response in acute myeloid leukemia (AML), increasing genotoxicity and cytotoxicity in leukemia cells while preventing damage accumulation in normal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Daniel Bottomly, Nicola Long, Anna Reister Schultz, Stephen E. Kurtz, Cristina E. Tognon, Kara Johnson, Melissa Abel, Anupriya Agarwal, Sammantha Avaylon, Erik Benton, Aurora Blucher, Uma Borate, Theodore P. Braun, Jordana Brown, Jade Bryant, Russell Burke, Amy Carlos, Bill H. Chang, Hyun Jun Cho, Stephen Christy, Cody Coblentz, Aaron M. Cohen, Amanda d'Almeida, Rachel Cook, Alexey Danilov, Kim-Hien T. Dao, Michie Degnin, James Dibb, Christopher A. Eide, Isabel English, Stuart Hagler, Heath Harrelson, Rachel Henson, Hibery Ho, Sunil K. Joshi, Brian Junio, Andy Kaempf, Yoko Kosaka, Ted Laderas, Matt Lawhead, Hyunjung Lee, Jessica T. Leonard, Chenwei Lin, Evan F. Lind, Selina Qiuying Liu, Pierrette Lo, Marc M. Loriaux, Samuel Luty, Julia E. Maxson, Tara Macey, Jacqueline Martinez, Jessica Minnier, Andrea Monteblanco, Motomi Mori, Quinlan Morrow, Dylan Nelson, Justin Ramsdill, Angela Rofelty, Alexandra Rogers, Kyle A. Romine, Peter Ryabinin, Jennifer N. Saultz, David A. Sampson, Samantha L. Savage, Robert Schuff, Robert Searles, Rebecca L. Smith, Stephen E. Spurgeon, Tyler Sweeney, Ronan T. Swords, Aashis Thapa, Karina Thiel-Klare, Elie Traer, Jake Wagner, Beth Wilmot, Joelle Wolf, Guanming Wu, Amy Yates, Haijiao Zhang, Christopher R. Cogle, Robert H. Collins, Michael W. Deininger, Christopher S. Hourigan, Craig T. Jordan, Tara L. Lin, Micaela E. Martinez, Rachel R. Pallapati, Daniel A. Pollyea, Anthony D. Pomicter, Justin M. Watts, Scott J. Weir, Brian J. Druker, Shannon K. McWeeney, Jeffrey W. Tyner
Summary: This report presents findings from a large cohort of AML patients, combining genomic, transcriptomic, and clinical data to uncover associations between drug sensitivity, cell differentiation state, and patient survival prediction.
Review
Oncology
Guglielmo Bove, Sajid Amin, Mehrad Babaei, Rosaria Benedetti, Angela Nebbioso, Lucia Altucci, Nunzio Del Gaudio
Summary: Chromatin has a flexible structure that allows for precise gene expression regulation. Epigenetic modifications and modifications on RNA and histone substrates play important roles in governing cellular functions and contribute to cancer development. The interplay between genetic mutations and reversible epigenetic alterations has been of great interest. The modification of the RNA code, such as m(6)A, affects the stability, metabolism, and life cycle of various mRNAs, including those associated with cancer. Epigenetic and epitranscriptomic pathways collectively control cellular expression profile and cell fate. The crosstalk between these two pathways has recently been revealed, uncovering previously unknown interactions. Dysregulation of this network has been implicated in cancer, adding a new layer of complexity to gene expression. This article summarizes the current understanding of the interplay between m(6)A epitranscriptome and epigenome, with a focus on cancer processes. Strategies to target the m(6)A machinery for future therapeutic intervention are also discussed.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Chemistry, Medicinal
Giovanna Santaniello, Angela Nebbioso, Lucia Altucci, Mariarosaria Conte
Summary: In recent years, the study of anticancer bioactive compounds from marine sources has gained significant attention. Regulatory authorities have approved marine molecules and new synthetic derivatives for cancer treatment. However, the administration of drugs in cancer patients requires careful evaluation due to their interaction with biological macromolecules. The search for personalized therapies and advancements in tumor prevention has been aided by new knowledge on cancer mechanisms, but a definitive therapy for cancer is still being sought.
Review
Immunology
Ennio Conte, Raffaella Di Girolamo, Francesco D'Antonio, Antonio Raffone, Daniele Neola, Gabriele Saccone, Michela Dell'Aquila, Laura Sarno, Marco Miceli, Luigi Carbone, Giuseppe Maria Maruotti
Summary: Monoclonal antibodies (mAbs) are used as a rescue strategy for pregnant women with COVID-19. A study examined the effects of mAbs on maternal and fetal health. The study found that the preterm delivery rate was 22.8%, fetal distress rate was 4.2%, gestational hypertension rate was 3.0%, pre-eclampsia rate was 3.4%, and fetal growth restriction rate was 3.2%. Secondary prophylaxis with mAbs is considered the best treatment option for mild to moderate COVID-19 patients, but caution should be taken for potential immunosuppression in infants born to mothers treated with mAbs.
Review
Obstetrics & Gynecology
Laura Sarno, Daniele Neola, Luigi Carbone, Gabriele Saccone, Annunziata Carlea, Marco Miceli, Giuseppe Gabriele Iorio, Ilenia Mappa, Giuseppe Rizzo, Raffaella Di Girolamo, Francesco D'Antonio, Maurizio Guida, Giuseppe Maria Maruotti
Summary: Artificial intelligence is being applied in various ways in the healthcare industry, including obstetrics. This study aimed to provide evidence on the effectiveness of using artificial intelligence in obstetrics, and the findings suggest that artificial intelligence can be a promising tool to support clinicians in their daily clinical activities. However, there are still issues to address, such as limited evidence and the need for better training and guidelines for clinicians.
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
(2023)
Article
Biochemistry & Molecular Biology
Valentina Lopardo, Francesco Montella, Roberta Maria Esposito, Carla Zannella, Silvana Mirella Aliberti, Mario Capunzo, Gianluigi Franci, Annibale Alessandro Puca, Elena Ciaglia
Summary: SARS-CoV-2 infection can cause inflammatory response and impaired platelet reactivity, which may lead to platelet disorders in COVID-19 patients. The virus can affect platelet production and activation, potentially influencing early stages of megakaryopoiesis. Through in vitro experiments, it was found that SARS-CoV-2 may enhance platelet production and activation by impairing STATs signaling and AMPK activity. These findings provide new insights into the role of SARS-CoV-2 in affecting the megakaryocyte-platelet compartment and possibly uncover another avenue by which the virus spreads.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Andrea Del Mastro, Stefania Picascia, Luciana D'Apice, Maria Trovato, Pasquale Barba, Immacolata Di Biase, Sebastiano Di Biase, Marco Laccetti, Antonello Belli, Gerardino Amato, Potito Di Muro, Olga Credendino, Alessandra Picardi, Piergiuseppe De Berardinis, Giovanna Del Pozzo, Carmen Gianfrani
Summary: Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Studies analyzed the immune response in KTR and healthy controls after the second and third dose of the mRNA vaccine. The third dose increased neutralizing antibody titers in both groups, but KTR had lower levels and showed low immunity to Omicron variant.
Article
Oncology
Mariarosaria Conte, Annabella Di Mauro, Lucia Capasso, Liliana Montella, Mariacarla De Simone, Angela Nebbioso, Lucia Altucci
Summary: This study identified simultaneous alterations in HDAC2, CIITA, and B2M genes in colorectal cancer patients and explored their potential role in immune dysfunction. HDAC2 was found to be deregulated in a subset of patients, while CIITA had specific alterations. Correlations among these genes and differential infiltration levels suggested an indirect immune-related role of HDAC2 in specific immune infiltrates. Further immunological signature studies could provide valuable clinical information for resistant forms of colorectal cancer.
Review
Cell Biology
Emanuele Fabbrizi, Francesco Fiorentino, Vincenzo Carafa, Lucia Altucci, Antonello Mai, Dante Rotili
Summary: SIRT5, a mitochondrial enzyme, regulates cellular homeostasis and the activity of proteins involved in various metabolic pathways. It plays critical roles in myocardial energy metabolism, neurodegenerative disease protection, and tumor development. SIRT5 is also implicated in SARS-CoV-2 infection. This review discusses its molecular actions, effects on metabolic targets, potential as a therapeutic target, and currently reported modulators including activators and inhibitors.
Review
Cell Biology
Vincenza Capone, Laura Della Torre, Daniela Carannante, Mehrad Babaei, Lucia Altucci, Rosaria Benedetti, Vincenzo Carafa
Summary: Histone modifications play a crucial role in the pathogenesis of diseases, including cancer, and acetylation is a reversible epigenetic process with important functions in cell life. HAT1 has been found to regulate molecular pathways, including those involved in cancer. This review summarizes the current knowledge and recent advances of HAT1 in the pathogenesis of cancer.
Article
Pharmacology & Pharmacy
Avinash Mali, Gianluigi Franci, Carla Zannella, Annalisa Chianese, Shubaash Anthiya, Ana M. Lopez-Estevez, Alessandra Monti, Anna De Filippis, Nunzianna Doti, Maria Jose Alonso, Massimiliano Galdiero
Summary: The COVID-19 pandemic has emphasized the need for the development of antiviral agents to reduce the fatality rate caused by infectious diseases. Nasal delivery of antiviral agents is a promising strategy as the coronavirus enters and spreads through the nasal passage. Peptides have emerged as powerful candidates for antiviral treatments, demonstrating strong antiviral activity, improved safety, efficacy, and specificity against viral pathogens.
Article
Microbiology
Federica Dell'Annunziata, Maria Vittoria Morone, Marco Gioia, Ferdinando Cione, Massimiliano Galdiero, Nicola Rosa, Gianluigi Franci, Maddalena De Bernardo, Veronica Folliero
Summary: Due to the complex etiology of conjunctivitis, new therapeutic strategies with broad-spectrum antimicrobial activity and nonselective mechanisms of action are needed. In this study, the antibacterial and antiviral activity of Oftasecur and Visuprime ophthalmic solutions were compared. The results showed that both Oftasecur and Visuprime exhibited high antimicrobial and antiviral activity. Therefore, Oftasecur and Visuprime could be effective empirical strategies for the treatment of conjunctivitis.
Article
Biochemistry & Molecular Biology
Deborah Giordano, Bernardina Scafuri, Luigi De Masi, Lucia Capasso, Viviana Maresca, Lucia Altucci, Angela Nebbioso, Angelo Facchiano, Paola Bontempo
Summary: This study aimed to investigate the effects of Cambinol and its underlying mechanisms on cell differentiation. The findings demonstrated that Cambinol induced differentiation in MCF-7, NB4, and 3T3-L1 cell lines by modulating the expression of cell cycle-related proteins and nuclear receptors. In addition, molecular simulations revealed that Cambinol showed inhibitory effects on human SIRT1 and SIRT2, with stronger interaction with the substrate binding site of SIRT1. Overall, Cambinol may serve as a potential alternative for epigenetic therapies targeting SIRTs.
Article
Virology
Evelina La Civita, Carla Zannella, Stefano Brusa, Paolo Romano, Elisa Schettino, Fabrizio Salemi, Rosa Carrano, Luca Gentile, Alessandra Punziano, Gianluca Lagnese, Giuseppe Spadaro, Gianluigi Franci, Massimiliano Galdiero, Daniela Terracciano, Giuseppe Portella, Stefania Loffredo
Summary: SARS-CoV-2 vaccination is the standard prevention measure for COVID-19, although the evaluation of its efficacy currently focuses on measuring antibodies only and ignores cellular immunity. This study investigates the humoral and cell-mediated response to BNT162b vaccine in two groups of fragile patients, finding that Common Variable Immunodeficiency (CVID) and Kidney Transplant Recipients (KTR) patients have lower humoral response but similar cell-mediated response compared to healthy controls. Furthermore, patients vaccinated and infected show a more efficient immune response than those who are only vaccinated, indicating the importance of both humoral and cellular immunity in preventing COVID-19.