Article
Biochemistry & Molecular Biology
Yanjie Kong, Wenlong Ren, Huan Fang, Naseer Ali Shah, Yujie Shi, Dingyun You, Chengang Zhou, Dewei Jiang, Chuanyu Yang, Huichun Liang, Wenjin Liu, Luzhen Wang, Wenqiang Gan, Xing Wan, Fubing Li, Zhen Li, Ceshi Chen, Ni Xie
Summary: This study reveals a novel mechanism by which histone deacetylase inhibitors suppress basal-like breast cancer (BLBC) by promoting proteasomal degradation of KLF5 protein through ubiquitination. The acetylation of KLF5 at lysine 369 decreases its binding with deubiquitinase BAP1, leading to decreased BLBC cell viability and proliferation.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Nabanita Nawar, Shazreh Bukhari, Ashley A. Adile, Yujin Suk, Pimyupa Manaswiyoungkul, Krimo Toutah, Olasunkanmi O. Olaoye, Yasir S. Raouf, Abootaleb Sedighi, Harsimran Kaur Garcha, Muhammad Murtaza Hassan, William Gwynne, Johan Israelian, Tudor B. Radu, Mulu Geletu, Ayah Abdeldayem, Justyna M. Gawel, Aaron D. Cabral, Chitra Venugopal, Elvin D. de Araujo, Sheila K. Singh, Patrick T. Gunning
Summary: Through a second-generation structure-activity relationship study, the selective HDAC6 inhibitor NN-390 was designed and evaluated, showing therapeutic potential in the treatment of metastatic Group 3 MB and demonstrating high selectivity and potency in targeting cells in vitro.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Anna Wawruszak, Lidia Borkiewicz, Estera Okon, Wirginia Kukula-Koch, Syeda Afshan, Marta Halasa
Summary: Breast cancer remains a challenging malignancy with varying responses to therapy, requiring the development of new active agents to improve the current treatment regimens. Vorinostat (SAHA) shows promise in the therapy of different histological subtypes of breast cancer, either alone or in combination with other anticancer agents, based on preclinical and clinical trials data.
Article
Chemistry, Medicinal
Krimo Toutah, Nabanita Nawar, Sanna Timonen, Helena Sorger, Yasir S. Raouf, Shazreh Bukhari, Jana von Jan, Aleksandr Ianevski, Justyna M. Gawel, Olasunkanmi O. Olaoye, Mulu Geletu, Ayah Abdeldayem, Johan Israelian, Tudor B. Radu, Abootaleb Sedighi, Muzaffar N. Bhatti, Muhammad Murtaza Hassan, Pimyupa Manaswiyoungkul, Andrew E. Shouksmith, Heidi A. Neubauer, Elvin D. de Araujo, Tero Aittokallio, Oliver H. Kraemer, Richard Moriggl, Satu Mustjoki, Marco Herling, Patrick T. Gunning
Summary: Epigenetic targeting, especially with HDAC inhibitors like KT-531, has shown promising efficacy in treating hematological cancers. In the case of T-cell prolymphocytic leukemia (T-PLL), overexpression of HDAC6 has been identified as a target for therapy, with KT-531 demonstrating strong inhibitory potency and safety in preclinical studies. Combination studies with approved cancer drugs have shown synergistic effects, indicating the potential for durable remission in T-PLL patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sravani Pulya, Ambati Himaja, Milan Paul, Nilanjan Adhikari, Suvankar Banerjee, Ganesh Routholla, Swati Biswas, Tarun Jha, Balaram Ghosh
Summary: HDAC3 modulation shows promise for breast cancer treatment, particularly for triple-negative cases. Novel pyrazino-hydrazide-based HDAC3 inhibitors have been designed and synthesized, with lead compound 4i demonstrating potent HDAC3 inhibition and strong cytotoxicity against triple-negative breast cancer cells. Compound 4i also exhibits favorable pharmacokinetic properties and shows therapeutic efficacy in a tumor-bearing mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Gastroenterology & Hepatology
Jia-Yao Li, Tian Tian, Bing Han, Ting Yang, Yi-Xin Guo, Jia-Yu Wu, Yu-Si Chen, Qin Yang, Ru-Jia Xie
Summary: SAHA stimulates FAM134B-mediated ER-phagy to enhance the mitochondrial apoptotic pathway, thereby promoting HCC cell death.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Changsheng Wang, Rongsheng Chen, Xitian Zhu, Xiaobo Zhang
Summary: This study investigated the impact of SAHA on pain sensitization in central neuropathic pain after SCI, and found that SAHA can improve pain hypersensitivity and anxiety/depression-like behaviors in SCI mice by suppressing HDAC5 and enhancing SCN9A degradation via the NEDD4 pathway.
NEUROCHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Duong Tien Anh, Nguyen Hai Nam, Brigitte Kircher, Daniel Baecker
Summary: In recent years, histone deacetylases (HDACs) have been identified as promising targets for cancer treatment. The use of HDAC inhibitors (HDACis) to inhibit HDACs has shown great potential. Various types of HDACis, such as hydroxamic acids, benzamides, thiols, short-chain fatty acids, and cyclic peptides, are classified based on their chemical structures. The introduction of fluorine into the chemical structure of HDACis can increase potency and selectivity towards specific isoforms of HDACs. However, the impact of fluorination is not always clear and can affect lipophilicity, solubility, and permeability, thus influencing the potency. The addition of fluorine is also commonly used for labeling purposes in the investigation of newly synthesized fluorine-containing active compounds.
Article
Biochemistry & Molecular Biology
Joonhyeok Choi, Trilok Neupane, Rishiram Baral, Jun-Goo Jee
Summary: This study identifies hydroxamic acid as a potent inhibitor of tyrosinase by interacting with dicopper atoms. Hydroxamate-containing molecules, including anticancer drugs targeting histone deacetylase, have been found to significantly inhibit tyrosinase activity. Experiments with cell lysates confirm the inhibitory effects of these inhibitors on mammalian tyrosinase. Docking simulation data reveal the molecular interactions between hydroxamate-containing molecules and tyrosinase.
Article
Oncology
Hao Wang, Lei Shi, Zhimin Wang
Summary: The research demonstrated that the structurally modified DMC-HA effectively inhibited human glioblastoma U87 cells, induced apoptosis, and increased histone H3 acetylation levels. Pharmacokinetic studies indicated acceptable pharmacokinetic properties for DMC-HA in vivo, suggesting its potential for further development as a chemotherapeutic drug.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kenny Man, Liam Lawlor, Lin-Hua Jiang, Xuebin B. Yang
Summary: The study showed that the selective inhibitor MI192 for HDAC2 and 3 can enhance the osteogenic capacity of hDPSCs and promote bone regeneration. Pre-treatment with MI192 enhances epigenetic functionality, induces cell cycle arrest, and upregulates expression of osteoblast-related genes in hDPSCs during osteogenic differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wenkai Zhou, Jiaming Wang, Xin Wang, Bingjing Wang, Zhehui Zhao, Jie Fu, Yan Wang, Xuan Zhang, Ping Zhu, Minghong Jiang, Xuetao Cao
Summary: HDAC10 plays an important role in immune response by inhibiting the production of type I interferon through regulating the phosphorylation of IRF3. Deficiency in HDAC10 leads to enhanced antiviral response by promoting the expression of type I interferons and interferon-stimulated genes.
Review
Neurosciences
K. V. Athira, Prashant Sadanandan, Sumana Chakravarty
Summary: The therapeutic potential of vorinostat (VOR) as a histone deacetylase (HDAC) inhibitor in brain disorders has been highlighted. Research on the neuroprotective and neurorestorative properties of VOR, as well as improvements in drug delivery and toxicity concerns, are crucial for enhancing its clinical prospects.
NEUROMOLECULAR MEDICINE
(2021)
Article
Cell Biology
Zilong Zheng, Guokai Yan, Xiuzhi Li, Yuke Fei, Lingling Sun, Haonan Yu, Yaorong Niu, Weihua Gao, Qing Zhong, Xianghua Yan
Summary: Lysine crotonylation is an important protein post-translational modification that regulates various cellular processes and functions, but its role in nutrient signaling pathways is not well understood. In this study, the authors found a positive correlation between global crotonylation levels and autophagy induced by leucine deprivation. They identified multiple crotonylated proteins regulated by leucine deprivation and discovered that 14-3-3 proteins play a dominant role in leucine-mediated crotonylation. Furthermore, they showed that crotonylation of 14-3-3E disrupts its interaction with binding partners and leads to the release of protein phosphatase 1B (PPM1B), which initiates autophagy. The authors also found that HDAC7 regulates the crotonylation of 14-3-3E. Overall, this study highlights the importance of the 14-3-3E-PPM1B axis regulated by crotonylation in leucine-deprivation-induced autophagy.
Article
Chemistry, Medicinal
Bartosz Bieszczad, Damian Garbicz, Marta Switalska, Marta K. Dudek, Dawid Warszycki, Joanna Wietrzyk, Elzbieta Grzesiuk, Adam Mieczkowski
Summary: In this study, a library of 19 analogues of Vorinostat was developed and tested for their HDAC inhibition and cytotoxic effects on cancer and normal cell lines. Three compounds based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one, and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds showed better HDAC inhibition and lower IC50 values in leukemic and lymphoma cell lines compared to Vorinostat. These compounds exhibited higher activity and selectivity against specific cancer cell lines and a correlation between HDAC inhibition and cytotoxic effects was observed.
Review
Dentistry, Oral Surgery & Medicine
Venkateshbabu Nagendrababu, Thilla Sekar Vinothkumar, Ikhlas El-Karim, Giampiero Rossi-Fedele, Esma J. Dogramaci, Paul M. H. Dummer, Henry F. Duncan
Summary: Recently, there has been a shift in oral health care settings towards assessing treatment outcomes from the patient's perspective. However, in the field of endodontology, research on treatment outcomes has mainly focused on clinician-reported outcomes (CROs) rather than dental patient-reported outcomes (dPROs). This review aims to highlight the importance of dPROs, present an overview of dPROs and dPROMs in endodontics, and emphasize the need to place the patient at the center of treatment. Key dPROs following endodontic treatment include pain, tenderness, tooth function, need for further intervention, adverse effects, and Oral Health-Related Quality of Life. It is crucial for clinicians and researchers in endodontology to prioritize patient welfare and incorporate appropriate measures to analyze dPROs.
JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE
(2023)
Article
Dentistry, Oral Surgery & Medicine
Venkateshbabu Nagendrababu, Simran Kaur Sarao, Yuli Berlin-Broner, Vellore Kannan Gopinath, Naresh Yedthare Shetty, Henry F. Duncan, Paul V. Abbott, Paul M. H. Dummer, Liran Levin
Summary: This study evaluated the quality of 50 case reports related to dental traumatology using the PRICE 2020 guidelines. The results showed that many reports had not reported or partially reported certain criteria before the publication of the guidelines. Therefore, it is recommended that authors follow the PRICE 2020 guidelines to improve the overall quality of their case reports.
DENTAL TRAUMATOLOGY
(2023)
Review
Dentistry, Oral Surgery & Medicine
Venkateshbabu Nagendrababu, Thilla Sekar Vinothkumar, Giampiero Rossi-Fedele, Esma J. Dogramaci, Henry F. Duncan, Paul V. Abbott, Liran Levin, Shaul Lin, Paul M. H. Dummer
Summary: Dental patient-reported outcomes (dPROs) are self-reported oral health status by patients, whereas dental patient-reported outcome measures (dPROMs) are used to assess dPROs. The importance of assessing treatment outcomes from the patient's perspective has increased in dental traumatology, particularly for traumatic dental injuries (TDIs), which are highly prevalent globally. Key dPROs following TDIs include oral health-related quality of life, pain, swelling, aesthetics, function, adverse effects, patient satisfaction, number of clinical visits, and trauma-related dental anxiety. Evaluating dPROs using appropriate measures is essential for clinicians and researchers to prioritize patient well-being and improve clinical studies.
DENTAL TRAUMATOLOGY
(2023)
Article
Dentistry, Oral Surgery & Medicine
Kevin John Fouillen, Henry Fergus Duncan, Philine de Vries, Valerie Chevalier
Summary: The study aimed to develop an Objective Structured Assessment of Technical Skills (OSATS) tool for partial pulpotomy and to preliminarily assess its validity. The study also checked the internal consistency and interrater reliability of the specific checklist, as well as compared it with a previously validated global rating score (GRS).
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Article
Dentistry, Oral Surgery & Medicine
Giorgos Tzanetakis, Aleksandar Jakovljevic, Despina Koletsi, Jelena Jacimovic, Venkateshbabu Nagendrababu, Henry Fergus Duncan, Paul Michael Howell Dummer
Summary: This study aimed to evaluate the reporting quality of animal studies in the field of endodontics. The results showed that most of the studies had moderate reporting quality. It was concluded that adherence to PRIASE 2021 guidelines can improve the reporting quality of animal studies.
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Editorial Material
Dentistry, Oral Surgery & Medicine
Hany Mohamed Aly Ahmed, Venkateshbabu Nagendrababu, Henry F. Duncan, Ove A. Peters, Paul M. H. Dummer
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Editorial Material
Dentistry, Oral Surgery & Medicine
Henry F. Duncan
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Article
Dentistry, Oral Surgery & Medicine
Venkateshbabu Nagendrababu, Henry F. F. Duncan, Ashraf F. F. Fouad, Lise-Lotte Kirkevang, Peter Parashos, Maria Pigg, Michael Vaeth, Jayakumar Jayaraman, Nandini Suresh, Aleksandar Jakovljevic, Paul M. H. Dummer
Summary: Observational studies are crucial for assessing the prevalence and impact of diseases and interventions. However, there is currently a lack of reporting guidelines for observational studies in the field of Endodontics. To address this gap, the PRIDE team has developed the PROBE 2023 guidelines, which integrate existing checklists and principles. This document serves as a guide for authors, providing explanations and examples for each item in the PROBE 2023 checklist.
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Review
Dentistry, Oral Surgery & Medicine
Eisha Imran, Paul R. Cooper, Jithendra Ratnayake, Manikandan Ekambaram, May Lei Mei
Summary: This article provides a contemporary review of the potential beneficial effects of nanosized hydroxyapatite (nHAP) on caries lesions demonstrated in in vitro studies. Data showed that nHAP has the potential to promote mineralization in initial caries and has antimicrobial effects through metal substitution. Metal-substituted fluorhydroxyapatite nanoparticles can potentially possess dual action property and enhanced chemical stability and bioactivity, providing a promising synergistic strategy for the development of dental therapeutics.
Article
Dentistry, Oral Surgery & Medicine
Venkateshbabu Nagendrababu, Clovis M. M. Faggion Jr, Vellore Kannan Gopinath, Srinivasan Narasimhan, Henry F. F. Duncan, Liran Levin, Paul V. V. Abbott, Paul M. H. Dummer
Summary: The methodological quality of systematic reviews (SRs) with meta-analysis in the field of traumatic dental injuries was evaluated using the AMSTAR 2 tool. The results showed that the majority of studies had low or critically low methodological quality. Journal impact factor and year of publication significantly influenced the methodological quality.
DENTAL TRAUMATOLOGY
(2023)
Review
Dentistry, Oral Surgery & Medicine
Riham N. Karrar, Siobhan Cushley, Henry F. Duncan, Fionnuala T. Lundy, Salma A. Abushouk, Mike Clarke, Ikhlas A. El-Karim
Summary: This study evaluated the diagnostic accuracy and predictive ability of biomarkers for pulpitis. The results showed that IL-8 and IL-6 had high sensitivity and specificity in distinguishing healthy pulps from those with spontaneous pain. However, no biomarker was found to accurately discriminate between different states of pulpitis.
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Article
Dentistry, Oral Surgery & Medicine
Satnam S. Virdee, Nasir Z. Bashir, Milan Krstic, Josette Camilleri, Melissa M. Grant, Paul R. Cooper, Phillip L. Tomson
Summary: This study identified optimized parameters for periapical tissue fluid (PTF) paper point sampling and compared the proteomes of PTF from teeth with normal apical tissues (NAT) and asymptomatic apical periodontitis (AAP) using high-throughput proteomic analysis. The results showed that some proteins were closely associated with AAP and had good diagnostic performance. The findings provide a potential biomarker network for clinical applications and further validation is needed.
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Article
Dentistry, Oral Surgery & Medicine
Henry F. Duncan, Lise-Lotte Kirkevang, Ove A. Peters, Ikhlas El-Karim, Gabriel Krastl, Massimo Del Fabbro, Bun San Chong, Kerstin M. Galler, Juan J. Segura-Egea, Moritz Kebschull
Summary: This article introduces the first S3-level clinical practice guidelines for endodontic treatment, developed by ESE, aimed at providing diagnostic and treatment approaches for patients with pulpitis and apical periodontitis, with the goal of preventing tooth loss.
INTERNATIONAL ENDODONTIC JOURNAL
(2023)
Article
Microbiology
Sheila Galvin, Sviatlana Anishchuk, Claire M. Healy, Gary P. Moran
Summary: This study investigates the bacterial colonisation patterns of healthy mucosa in adults and finds that smoking, tooth loss, plaque levels, and oral hygiene practices affect mucosal colonisation. The frequency of tooth brushing has a greater impact on mucosal community structure than plaque levels. Tooth loss is associated with a reduction in mucosal biodiversity.
JOURNAL OF ORAL MICROBIOLOGY
(2023)
Article
Engineering, Biomedical
Henry F. Duncan, Yoshifumi Kobayashi, Michaela Kearney, Emi Shimizu
Summary: This opinion-led review paper emphasizes the importance of innovative translational research in vital-pulp-treatment (VPT) and discusses the challenges in implementing evidence in clinics. The traditional dentistry approach, which is expensive and invasive, lacks a biological perspective. Recent research focuses on developing minimally-invasive biologically-based 'fillings' that preserve dental pulp and shift the paradigm towards smart restorations targeting biological processes. The potential use of histone-deacetylase (HDAC) inhibitors in stimulating pro-regenerative effects and enhancing biomaterial-driven tissue responses in VPT is analyzed in this article.
BIOACTIVE MATERIALS
(2023)