Histone deacetylase

Epidural fibrosis (EF) is a chronic, progressive and severe disease. Histone deacetylase 6 (HDAC6) regulates biological signals and cell activities by deacetylating lysine residues and participates in TGF-β-induced epithelial-mesenchymal transition (EMT). Nevertheless, the effect and mechanism of HDAC6 in EF remain unclear. To investigate the effect and mechanism of HDAC6 inhibition on repressing epidural fibrosis. HDAC6 expression and α-smooth muscle actin (α-SMA) in normal human tissue and human EF tissue were assessed by quantitative real-time PCR (qRT-PCR) and western blotting...

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation...

Increased oxidative stress is one of the critical pathologies inducing age-related macular degeneration (AMD), characterized by retinal pigment epithelial (RPE) cell damage and death. The unbalanced acetylation and deacetylation of histones have been implicated in AMD pathogenesis or hydrogen peroxide (H2 O2 )-induced cell damage. Therefore, strategies aimed at controlling the balance between acetylation and deacetylation may effectively protect RPE cells from oxidative damage. Artemisinin is an antimalarial lactone drug derived from Artemisia annua , with antioxidant activity known to modulate histone acetylation in the brain, but its effect on the retina is unknown...

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs...

Aberrant epigenetic modifications are fundamental contributors to the pathogenesis of various cancers. Consequently, targeting these aberrations with small molecules, such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors, presents a viable strategy for cancer therapy. The objective of this study is to assess the anti-cancer efficacy of trichostatin C (TSC), an analogue of trichostatin A sourced from the fermentation of Streptomyces sp. CPCC 203909. Our investigations reveal that TSC demonstrates potent activity against both human lung cancer and urothelial bladder cancer cell lines, with IC50 values in the low micromolar range...

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity, and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages...

Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9 . Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity...

Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed the downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach...

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression. METHODS: Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6...

Histone deacetylase expression and activity are often dysregulated in central nervous system (CNS) tumors, providing a rationale for investigating histone deacetylase inhibitors (HDACIs) in selected brain tumor patients. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo This lack of activity could be due to insufficient CNS exposure to the unbound drug. In this study, we investigated the systemic pharmacokinetics and subsequent CNS distribution of two potent HDACIs, vorinostat and quisinostat, in the murine model...

BACKGROUND: Ischemic stroke (IS) is a major cause of mortality and disability worldwide. Inflammatory response is crucial in the pathogenesis of tissue injury in cerebral infarction. Arctium lappa leaves are traditionally used to treat IS. PURPOSES: To investigate the neuroprotective effects and molecular mechanisms of the ethanolic extract of A. lappa leaves (ALLEE) on cerebral ischemia-reperfusion (CIR). METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model were used to evaluate ALLEE pharmacodynamics...

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells...

The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions...

Myocardial infarction (MI) is a potentially fatal disease that causes a significant number of deaths worldwide. The strategy of increasing fatty acid oxidation in myocytes is considered a therapeutic avenue to accelerate metabolism to meet energy demands. We conducted the study aiming to investigate the effect of KN-93, which induces histone deacetylase (HDAC)4 shuttling to the nucleus, on fatty acid oxidation and the expression of related genes. A mouse model of myocardial infarction was induced by isoprenaline administration...

OBJECTIVE: To explore the effects and mechanisms of chidamide on the osteogenic differentiation of bone marrow mesenchymal stromal cells (MSC) from myelodysplastic syndromes (MDS). METHODS: MSC were isolated and cultured from bone marrow of MDS patients and healthy donors. CCK-8 assay was used to detect the effects of chidamide on the proliferation of MSC. The effects of chidamide on the activity of histone deacetylase (HDAC) in MSC was measured by a fluorescence assay kit and Western blot...

The liver is the main organ associated with metabolism. In our previous studies, we identified that the metabolic enzymes malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) were differentially expressed in ALF. The aim of this study was to explore the changes in the acetylation of MDH1 and IDH1 and the therapeutic effect of histone deacetylase (HDAC) inhibitor in acute liver failure (ALF). Decreased levels of many metabolites were observed in ALF patients. MDH1 and IDH1 were decreased in the livers of ALF patients...

Density Functional Theory (DFT) is a quantum chemical computational method used to predict and analyze the electronic properties of atoms, molecules, and solids based on the density of electrons rather than wavefunctions. It provides insights into the structure, bonding, and behavior of different molecules, including those involved in the development of chemotherapeutic agents, such as histone deacetylase inhibitors (HDACis). HDACs are a wide group of metalloenzymes that facilitate the removal of acetyl groups from acetyl-lysine residues situated in the N-terminal tail of histones...

Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f ...

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is characterized by high recurrence rates and poor prognosis, and effective first-line treatment is lacking. Recently, histone deacetylase inhibitors (HDACi), such as chidamide, have been found to induce durable remissions in AITL patients. METHODS: Patients with untreated AITL from March 2015 to March 2023 were retrospectively collected and divided into chemotherapy (ChT) group and chidamide combined with chemotherapy (C-ChT) group based on the first-line treatment received...

Histone deacetylase inhibitors (HDACis) are a significant category of pharmaceuticals that have developed in the past two decades to treat multiple myeloma. Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. The efficacy of this group of drugs is attributed to the disruption of many processes involved in tumor growth through the inhibition of histone deacetylase, and this mode of action leads to significant anti-multiple myeloma (MM) activity...