Article
Multidisciplinary Sciences
Karolina Pavic, Nikhil Gupta, Judit Domenech Omella, Rita Derua, Anna Aakula, Riikka Huhtaniemi, Juha A. Maatta, Nico Hofflin, Juha Okkeri, Zhizhi Wang, Otto Kauko, Roosa Varjus, Henrik Honkanen, Daniel Abankwa, Maja Kohn, Vesa P. Hytonen, Wenqing Xu, Jakob Nilsson, Rebecca Page, Veerle Janssens, Alexander Leitner, Jukka Westermarck
Summary: This study reveals the molecular level details and structural mechanisms of PP2A-B56 alpha inhibition by the oncoprotein CIP2A. CIP2A displaces the PP2A-A subunit and forms a pseudotrimer, blocking the B56 alpha substrate binding site and stabilizing CIP2A protein.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hsueh-Yun Lee, Di-Wei Tang, Chi-Yuan Liu, Er-Chieh Cho
Summary: This study focuses on the development of benzamide-based compounds as potential HDAC1/2 inhibitors for colorectal cancer treatment. Compound 9 is identified as a selective HDAC inhibitor with significant anticancer activity against colorectal cancer cells. The study also investigates the molecular regulatory mechanisms of compound 9, demonstrating its potential in apoptosis activation, cell cycle arrest induction, DNA damage facilitation, and cancer migration suppression in colorectal cancer cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Oncology
Min Woo Shin, Se Lim Kim, Hee Chan Yang, Sung Kyun Yim, Seung Young Seo, Soo Teik Lee, Hee-Kwon Kim, Sang-Wook Kim
Summary: The novel HDAC inhibitor CBUD-1001 sensitizes TRAIL-induced apoptosis by up-regulating DR5 in CRC cells, offering an effective strategy to overcome TRAIL resistance. The enhanced sensitivity to TRAIL by combination with CBUD-1001 depends on the MAPK/CHOP axis, being a key mediator of DR5.
ANTICANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yoon Seok Nam, Young Mi Choi, Sungsu Lee, Hyong-Ho Cho
Summary: Genetic or congenital hearing loss has no definitive cure. KCNQ4 variant p.W276S causes severe hair cell loss that is not related to potassium recycling. Valproic acid (VPA) has shown potential in attenuating hearing loss and protecting cochlear hair cells in the KCNQ4 p.W276S mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Lexiang Li, Qiwei Fu, Jiahua Shao, Bo Wang, Zheru Ding, Shuai Yuan, Jinhui Peng, Wei Xin, Jun Zhu, Yi Chen
Summary: Strict regulation of gene expression is required for bone development and cartilage formation. Oct4 plays an important role in chondrogenesis, partly through the CIP2A/PP2A pathway.
CELL AND TISSUE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Wen-Ting Hu, Zhen-Yu Liuyang, Yuan Tian, Jia-Wei Liang, Xiao-Lin Zhang, Hui-Liang Zhang, Guan Wang, Yuda Huo, Yang-Ping Shentu, Jian-Zhi Wang, Xiao-Chuan Wang, You-Ming Lu, Jukka Westermarck, Heng-Ye Man, Rong Liu
Summary: This study discovers a novel mechanism in which CIP2A deficiency promotes depression through the regulation of PP2A-AKT signaling and dendritic arborization. The study also finds decreased expression of CIP2A in a mouse model of chronic unpredictable mild stress (CUMS) and in patients with major depressive disorder (MDD).
Article
Oncology
Z. Zhu, Z. Wei
Summary: The study demonstrated that manipulating CIP2A abundance could enhance the treatment effects of doxorubicin, leading to suppression of MCF-7/ADR cell proliferation in a dose-dependent manner and promoting cell apoptosis. Additionally, silencing CIP2A increased PP2A activity and upregulated autophagy markers LC3B and Beclin1.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chuansheng Yao, Xiaoying Jiang, Rui Zhao, Zhichao Zhong, Jiamin Ge, Junlong Zhu, Xiang-Yang Ye, Yuanyuan Xie, Zhen Liu, Tian Xie, Renren Bai
Summary: A series of dual inhibitors targeting HDAC1/MAO-B were synthesized and found to be promising agents for the treatment of Alzheimer's disease, exhibiting good activity, selectivity, antioxidant activity, and blood-brain barrier penetration. Hybrid If showed the most potent activity and selectivity against MAO-B and HDAC1, as well as favorable antioxidant activity.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
N. Connor Payne, Ralph Mazitschek
Summary: Histone deacetylase paralogs HDAC1/2/3 and their corepressor complexes are key regulators of chromatin function. Over the past decades, extensive research has been conducted on using HDACs as pharmacological targets and developing small molecule drugs. This study investigates the dynamic processes that regulate HDAC complexes and their impact on the selectivity of HDAC inhibitors. The findings suggest the need for a comprehensive reinterpretation of previous studies that utilized these compounds for studying epigenetic and cellular processes.
CELL CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ying Zhou, Xiaoyuan Liu, Shuqing Ma, Nan Zhang, Dichen Yang, Ling Wang, Simin Ye, Qiongying Zhang, Jing Ruan, Jun Ma, Shiyi Wang, Nan Jiang, Zongyuan Zhao, Shujue Zhao, Chenfei Zheng, Xiaofang Fan, Yongsheng Gong, Mahaman Yacoubou Abdoul Razak, Wenting Hu, Jingye Pan, Xiaochuan Wang, Junming Fan, Jianmin Li, Rong Liu, Yangping Shentu
Summary: This study found that the activation of DNA damage-related Checkpoint kinase 1 (ChK1) in Alzheimer's disease leads to overexpression of CIP2A, which in turn causes reactive astrogliosis, neurodegeneration, and exacerbation of AD.
Article
Biochemistry & Molecular Biology
Colleen E. Quaas, Baicheng Lin, David T. Long
Summary: Modification of histones, especially histone acetylation, plays a crucial role in regulating chromatin structure and DNA access. Defects in histone acetylation patterns are associated with various human diseases. In this study, Xenopus egg extracts are used to investigate the impact of histone acetylation changes on gene transcription. The findings reveal that inhibiting histone deacetylase 1 and 2 (HDAC1/2) counteracts transcription suppression by preventing chromatin compaction and deacetylation of specific histone residues. HDAC1 is identified as the primary driver of transcription suppression through the Sin3 histone deacetylase complex.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Wenting Hu, Zhuoqun Wang, Huiliang Zhang, Yacoubou Abdoul Razak Mahaman, Fang Huang, Dongli Meng, Ying Zhou, Shiyi Wang, Nan Jiang, Jing Xiong, Jukka Westermarck, Youming Lu, Jianzhi Wang, Xiaochuan Wang, Yangping Shentu, Rong Liu
Summary: This study reveals that DNA damage-induced Chk1 activation promotes the development of Alzheimer's disease through CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction, highlighting the therapeutic potential of Chk1 inhibitors in AD.
Article
Plant Sciences
Bo Sun, Yanjie Shen, Su Chen, Zhenying Shi, Haichao Li, Xuexia Miao
Summary: MYB22 is a transcription factor that represses the expression of the F3'H gene by forming a complex with TOPLESS and HDAC1, thereby enhancing rice resistance to brown planthopper.
Article
Neurosciences
Xiaoyi Xu, Xin He, Zeyan Zhang, Yanyi Chen, Junyu Li, Shanshan Ma, Qiaoying Huang, Mingtao Li
Summary: This study identified that the inactivation of CREB and decreased expression of NURR1 are associated with nigral dopaminergic neurodegeneration in Parkinson's disease (PD). The mechanism underlying CREB inactivation involves the interaction between HDAC1/PP1y complex and CREB, and disrupting this interaction can restore CREB activity and protect dopaminergic neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Gastroenterology & Hepatology
Ahmed M. Elfiky, Mohammed Ghiboub, Andrew Y. F. Li Yim, Ishtu L. Hageman, Jan Verhoeff, Manon de Krijger, Patricia H. P. van Hamersveld, Olaf Welting, Iris Admiraal, Shafaque Rahman, Juan J. Garcia-Vallejo, Manon E. Wildenberg, Laura Tomlinson, Richard Gregory, Inmaculada Rioja, Rab K. Prinjha, Rebecca C. Furze, Huw D. Lewis, Palwinder K. Mander, Sigrid E. M. Heinsbroek, Matthew J. Bell, Wouter J. de Jonge
Summary: This study investigates the utility of ESM-tagged HDACi in inflammatory bowel disease (IBD) and finds that it can specifically target monocytes and inflammatory macrophages, showing potential therapeutic benefits in IBD.
JOURNAL OF CROHNS & COLITIS
(2022)
Review
Hematology
Jurgen Thiele, Hans Michael Kvasnicka, Attilio Orazi, Umberto Gianelli, Naseema Gangat, Alessandro M. Vannucchi, Tiziano Barbui, Daniel A. Arber, Ayalew Tefferi
Summary: A group of international experts met to update the World Health Organization classification system for hematopoietic tumors and introduced the new International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias. The focus of this review is on the ICC-2022 category of JAK2 mutation-prevalent myeloproliferative neoplasms (MPNs) and the importance of bone marrow morphology and genetic markers in disease classification and diagnostics.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Pathology
Umberto Gianelli, Juergen Thiele, Attilio Orazi, Naseema Gangat, Alessandro M. Vannucchi, Ayalew Tefferi, Hans Michael Kvasnicka
Summary: The International Consensus Classification (ICC) of myeloid neoplasms, which was based on the efforts of pathologists, oncologists, and geneticists, aimed to update the 2017 World Health Organization classification system for hematopoietic tumors. The classification of myeloproliferative neoplasms (MPNs) underwent significant modifications, especially in terms of diagnostic methods and criteria.
Article
Oncology
Giacomo Coltro, Emanuela Sant'Antonio, Giuseppe A. Palumbo, Francesco Mannelli, Valerio De Stefano, Marco Ruggeri, Elena M. Elli, Roberta Zanotti, Oscar Borsani, Irene Bertozzi, Andrea Duminuco, Silvia Betti, Giuseppe Carli, Fabrizio Cavalca, Ilaria Tanasi, Elisa Rumi, Maria L. Randi, Bruno Garibaldi, Giuseppe G. Loscocco, Paola Guglielmelli, Alessandro M. Vannucchi
Summary: This study provides valuable insights into the efficacy and safety of ruxolitinib in a real-world cohort of Italian patients with myelofibrosis. The results highlight the importance of drug exposure, side effects, and treatment response in determining patient outcomes.
Review
Hematology
Nicola Polverelli, Juan Carlos Hernandez-Boluda, Tomasz Czerw, Tiziano Barbui, Mariella D'Adda, Hans Joachim Deeg, Markus Ditschkowski, Claire Harrison, Nicolaus Martin Kroger, Ruben Mesa, Francesco Passamonti, Francesca Palandri, Naveen Pemmaraju, Uday Popat, Damiano Rondelli, Alessandro Maria Vannucchi, Srdan Verstovsek, Marie Robin, Antonio Colecchia, Luigi Grazioli, Enrico Damiani, Domenico Russo, Jessica Brady, David Patch, Slawomir Blamek, Gandhi Laurent Damaj, Patrick Hayden, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: Splenomegaly is a common complication in myelofibrosis patients and can negatively impact outcomes of allogeneic hematopoietic cell transplantation (HCT). This Position Paper provides a shared position statement on the management of splenomegaly before HCT. The assessment, prevalence, and clinical significance of splenomegaly are discussed, along with the need for therapeutic intervention. Specific scenarios, such as splanchnic vein thrombosis and COVID-19, are also addressed.
LANCET HAEMATOLOGY
(2023)
Editorial Material
Hematology
Ayalew Tefferi, Alessandro M. Vannucchi
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Hematology
Giuseppe G. Loscocco, Alessandro M. Vannucchi
Summary: Myeloid sarcoma is a distinct tumor mass of myeloid blasts occurring outside of the bone marrow, often in conjunction with acute myeloid leukemia. It can also represent the blast phase of other myeloproliferative neoplasms and myelodysplastic syndromes. Diagnosis is challenging and relies on histopathology, immunohistochemistry, and imaging. Molecular and cytogenetic analysis should be performed to refine the diagnosis and guide treatment decisions.
ANNALS OF HEMATOLOGY
(2023)
Letter
Hematology
Omer S. Karrar, Maymona Abdelmagid, Alessandro M. Vannucchi, Tiziano Barbui, Ayalew Tefferi, Naseema Gangat
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Riccardo Paggi, Francesca Mariotti, Jessica Mencarini, Silvia Bresci, Irene Campolmi, Filippo Bartalesi, Beatrice Borchi, Luca Nassi, Benedetta Sordi, Alessandro Maria Vannucchi, Alessandro Bartoloni
Summary: The use of specific inhibitory drugs for intracellular signalling pathways is a risk factor for Aspergillus spp. infections in patients with Waldenstrom's macroglobulinaemia. The overlapping clinical manifestations of the two diseases may require different medical specialties.
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
(2023)
Review
Microbiology
Carolina Vieira De Almeida, Emiliano Antiga, Matteo Lulli
Summary: The skin microbiota is crucial for maintaining skin homeostasis, protecting it from harmful pathogens, and regulating the immune system. Imbalances in the skin microbiota can lead to conditions such as eczema, psoriasis, and acne. Factors that disrupt the balance include changes in pH levels, exposure to toxins, and the use of certain skincare products.
Editorial Material
Hematology
Giuseppe G. Loscocco, Stefano Ascani, Francesco Mannelli, Magda Zanelli, Giada Rotunno, Raffaella Santi, Alessandro M. Vannucchi
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Editorial Material
Oncology
Alessandro Maria Vannucchi, Paola Guglielmelli
JACC: CARDIOONCOLOGY
(2023)
Correction
Medicine, General & Internal
S. Verstovsek, A. T. Gerds, A. M. Vannucchi
Correction
Medicine, General & Internal
S. Verstovsek, A. T. Gerds, A. M. Vannucchi
Article
Medicine, General & Internal
Srdan Verstovsek, Aaron T. Gerds, Alessandro M. Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew T. Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela C. Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal McLornan, Andrew Perkins, Sung -Soo Yoon, Vikas Gupta, Jean -Jacques Kiladjian, Nikki Granacher, Sung-Eun Lee, Luminita Ocroteala, Francesco Passamonti, Claire N. Harrison, Barbara J. Klencke, Sunhee Ro, Rafe Donahue, Jun Kawashima, Ruben Mesa
Summary: This study aimed to compare the clinical effects of momelotinib and danazol in patients with intermediate or high-risk myelofibrosis. The results showed that momelotinib can significantly improve myelofibrosis-associated symptoms, anemia measures, and spleen response compared to danazol, with favorable safety.
Article
Oncology
Tiziano Barbui, Alessandra Carobbio, Juergen Thiele, Naseema Gangat, Elisa Rumi, Alessandro Rambaldi, Alessandro M. Vannucchi, Ayalew Tefferi
Summary: This study applied a parametric Markov model to investigate the impact of incident thrombosis on death or disease progression in patients with polycythemia vera. The results showed that thrombosis was associated with a higher probability of death and had different effects on arterial and venous thrombosis.
BLOOD CANCER JOURNAL
(2023)