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Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… Acetylation and deacetylation of histone lysine residues are in equilibrium, regulated by histone acetyltransferases in the presence of endogenous acetyl-CoA as an acetyl group donor and HDACs, respectively [ 3 ] ( Figure 1 ). … Figure 15 Autophagy process in H9c2 cardiomyocytes in heart failure (ACAT1—acetyltransferase 1, PINK1—putative kinase 1 or serine/threonine kinase, p—phosphoric acid, ub—ubiquitin, LC3—microtubule-associated proteins 1A/1B light chain 3, Parkin—protein with E3 ubiquitin-protein ligase activity, NDP52 …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances p

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… Several enzymes are involved in these histone modifications, including E3-ubiquitin and kinases, HDAC, histone acetyltransferase (HAT), histone methyltransferase (HMT), and histone demethylase (HDMT) [ 23 ]. … Abbreviations: JNK: Jun N-terminal kinase; BMP: Bone morphogenetic protein; PI3k: phosphatidylinositol-3 kinase; mTOR: mammalian/mechanistic target of rapamycin; EMT: Epithelial–mesenchymal transition; HDAC: Histone deacetylase; HAT: Histone Acetyltransferases; STAT: signal transducer and activator of …

Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem.

Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising

Mechanistic and Clinical Perspectives on Traditional Chinese Medicine in Thyroid Cancer Management.

Thyroid cancer is one of the most prevalent malignancies of the endocrine system, comprising various subtypes such as papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and the aggressive anaplastic thyroid carcinoma (ATC). Despite a generally favorable prognosis for PTC, recurrence, metastasis, and resistance to conventional therapies continue to pose significant challenges. The pathogenesis of thyroid cancer involves genetic mutations in BRAF, RAS, and RET, as well as dysregulated molecular pathways such as MAPK, PI3K/Akt/mTOR, and NF-κB

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… These are histone methyltransferases (KMT2A, KMT2C, KMT2D, and SETD2 genes) and histone acetyltransferases CREBBP and EP300 ( Liu et al. , 2023 ). … Two antagonistic families of enzymes regulate this: histone acetyltransferases (HATs) and histone deacetylases (HDACs), which deacetylate histones, promote DNA condensation, and cause gene silencing ( Wei et al. , 2022 ). The activity of HDAC is dysregulated in most cancers, such as thyroid cancer. …

Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

Synthetic lethality strategies are likely to be integrated in effective and specific cancer treatments. These strategies combine different specific targets, either in similar or cooperating pathways. Chromatin remodeling underlies, directly or indirectly, all processes of tumor biology. In this context, the combined targeting of proteins associated with different aspects of chromatin remodeling can be exploited to find new alternative targets or to improve treatment for specific individual tumors or patients. There are two major types of proteins, epigenetic modifiers of histones and nuclear o

CRLF1 and CLCF1 in Development, Health and Disease.

Cytokines and their receptors have a vital function in regulating various processes such as immune function, inflammation, haematopoiesis, cell growth and differentiation. The interaction between a cytokine and its specific receptor triggers intracellular signalling cascades that lead to altered gene expression in the target cell and consequent changes in its proliferation, differentiation, or activation. In this review, we highlight the role of the soluble type I cytokine receptor CRLF1 (cytokine receptor-like factor-1) and the Interleukin (IL)-6 cytokine CLCF1 (cardiotrophin-like cytokine fa

The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

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… MDM2 is responsible for p53 monoubiquitination (driving p53 nuclear export) and polyubiquitination of p53 (driving p53 ubiquitin-dependent proteasomal degradation) and prevents p53 acetylation and transcriptional activation by p300 acetyltransferase. … Transcription activity of the longest form of p73, TAp73α, similarly to p53, is induced by acetylation by p300 and CREB-binding protein (CBP) acetyltransferases [ 86 ]. …

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

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… Histone Deacetylases (HDACs) and HDACi Histone acetylation is one the most extensively studied posttranslational covalent modifications of histones that is regulated by the opposing actions of histone acetyltransferases (HATs) and HDACs. … Figure 1 A schematic illustration depicting the central role of histone deacetylases (HDACs) and histone acetyltransferases (HATs) in regulating gene expression. …

Impact of genetic polymorphisms on the response to transdermal fentanyl in cancer patients-a single-center, prospective, biological study.

BACKGROUND/OBJECTIVES: Transdermal fentanyl (TDF) is widely used for moderate-to-severe cancer pain, yet substantial variability in fentanyl exposure, analgesic response, and tolerability remains incompletely explained by clinical factors. We evaluated whether pharmacogenetic variability is associated with pharmacokinetic parameters and clinical outcomes in cancer patients receiving TDF. METHODS: In this prospective, single-center study, adults with solid or hematological malignancies and chronic cancer pain treated with stable-dose 72 h TDF were enrolled. Blood samples were collected for pha

Протеомический анализ показывает дисрегламентацию периферийных нейтрофилов крови у пациентов с множественным склерозом.

Множественный склероз (MS) представляет собой сложное автовоспалительное заболевание мозга и спинного мозга, которое приводит к аксоновому демилеляции и симптомам, включая усталость, боль и трудности с зрением и мобильностью. Вовлеченность иммунной системы в патологию MS хорошо известна, в частности адаптивная реакция T-клеток, и особое внимание уделяется производящему IL-17 поднабору клеток TH17 и их роли в вождении болезней. Однако важность врожденных иммунных клеток не была столь хорошо охарактеризована. Здесь мы сосредоточили внимание на нейтрофилах, которые являются врожденными иммунными

Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G₂ delay and mitotic defects.

The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G₂/M and an associated decrease in expression of particular genes required for passage through G₂ and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G₂ del

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… The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60 . Mol. Cell. Biol. 24 , 10826 – 10834 ( 2004 ). 15572685 10.1128/MCB.24.24.10826-10834.2004 PMC533976 Roy S. , Packman K. , Jeffrey R. & Tenniswood M. …

Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis.

Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone m

The mutual impacts of stem cells and sleep: opportunities for improved stem cell therapy.

Sleep is an indispensable physiological function regulated by circadian rhythms, which influence the biological pathways and overall health of the body. Sleep is crucial for the maintenance and restoration of bodily systems, and disturbances can lead to various sleep disorders, which can impair both mental and physical health. Treatment options for these disorders encompass lifestyle modifications, psychotherapy, medications, and therapies such as light therapy and surgery. Not only sleep deprivation has a significant impact on essential organs, but it also influences various types of stem cel

Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone tre

Пересадка глиальных клеток человека в муринные мозги: систематический обзор эффективности и безопасности в нейродегенеративных расстройствах.

Справочная информация: Нейродегенеративные заболевания затрагивают миллионы людей во всем мире. С годами исследования мозга были сосредоточены главным образом на нейронах, но сейчас внимание перемещается на глиальные клетки, вспомогательные клетки мозга, которые играют жизненно важную роль в нейродегенеративных расстройствах. Таким образом, трансплантация глиальных клеток представляет собой новаторский подход к лечению различных нейродегенеративных расстройств, способных восстановить нейронную функцию. Мы провели оценку терапевтической эффективности трансплантации человеческих глиальных клеток

Механизмы и новые регулирующие органы нейроинфламмации: изучение новых терапевтических стратегий в отношении неврологических расстройств.

Нейроинфламмация представляет собой сложную и динамичную реакцию центральной нервной системы (КНС) на травмы, инфекцию и болезни. В то время как острая нейроинфламмация играет защитную роль, облегчая расчистку патогенов и восстановление тканей, хроническая и дисрегулированная воспаление в значительной степени способствует развитию таких нейродегенеративных расстройств, как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз. В рамках этого обзора изучаются клеточные и молекулярные механизмы, лежащие в основе нейроинфламмации, с уделением особого внимания роли микроглий, астроцитов

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… Histone acetyltransferases (HATs) enhance the transcription of pro-inflammatory genes, while histone deacetylases (HDACs) suppress their expression. …

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.

Sex differences play a crucial role in determining tumor incidence, treatment sensitivity, and prognosis among men and women. However, current clinical cancer treatment strategies fail to account for these differences. Furthermore, the underlying mechanisms of tumor disparities between sexes remain elusive. Sex differences in sex chromosomes, hormone levels, metabolism, and immunity synergistically contribute to tumor-related disparities. As the demand for precision medicine escalates, there is an urgent need to conduct further exploration and research to address the tumor differences between

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… Histone acetyltransferases (HATs), such as p300 and CBP, function as critical coactivators for estrogen and androgen receptors, enabling sex hormone–dependent transcriptional programs by acetylating histone tails at hormone-responsive enhancers and promoters [ 42 ]. …