Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states. HDAC inhibitors have been highlighted as a novel category of anti-cancer drugs. To date, four HDAC inhibitors, Vorinostat, Romidepsin, Panobinostat, and Belinostat, have been approved by the United States Food and Drug Administration. Principally, these HDAC inhibitors are used for hematologic cancers in clinic with less severe side effects. Clinical trials are continuously expanding to address other types of cancer and also nonmalignant diseases. HDAC inhibition also results in beneficial outcomes in various types of neurodegenerative diseases, inflammation disorders, and cardiovascular diseases. In this review, we will briefly discuss 1) the roles of HDACs in the acquisition of a cancer's phenotype and the general outcome of the HDAC inhibitors in cancer, 2) the functional relevance of HDACs in cardiovascular diseases and the possible therapeutic implications of HDAC inhibitors in cardiovascular disease.
Acetylation ; Cardiovascular Diseases ; Chromatin ; Epigenomics ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Histones ; Inflammation ; Neurodegenerative Diseases ; Phenotype ; Tail ; United States Food and Drug Administration

Cancer remains a leading cause of death, despite multimodal treatment approaches. Even in patients with a healthy immune response, cancer cells can escape the immune system during tumorigenesis. Cancer cells incapacitate the normal cell-mediated immune system by expressing immune modulation ligands such as programmed death (PD) ligand 1, the B7 molecule, or secreting activators of immune modulators. Chimeric antigen receptor (CAR) T cells were originally designed to target cancer cells. Engineered approaches allow CAR T cells, which possess a simplified yet specific receptor, to be easily activated in limited situations. CAR T cell treatment is a derivative of the antigen-antibody reaction and can be applied to various diseases. In this review, the current successes of CAR T cells in cancer treatment and the therapeutic potential of CAR T cells are discussed.

Diagnosis of Kawasaki disease (KD) is occasionally delayed because it is solely based on clinical symptoms. Previous studies have attempted to identify diagnostic biomarkers for KD. Recently, patients with KD were reported to have elevated serum ferritin levels. We investigated the usefulness of the serum ferritin level as a diagnostic biomarker for distinguishing KD from other acute febrile illnesses. Blood samples were obtained from pediatric patients with KD (N = 77) and those with other acute febrile illnesses (N = 32) between December 2007 and June 2011 for measuring various laboratory parameters, including serum ferritin levels. In patients with KD, laboratory tests were performed at diagnosis and repeated at 2, 14, and 56 days after intravenous immunoglobulin treatment. At the time of diagnosis, serum ferritin levels in patients with KD (188.8 µg/L) were significantly higher than those in patients with other acute febrile illnesses (106.8 µg/L, P = 0.003). The serum ferritin cut-off value of 120.8 µg/L effectively distinguished patients with KD from those with other acute febrile illnesses, with a sensitivity and specificity of 74.5% and 83.3%, respectively. Serum ferritin may be a useful biomarker to distinguish KD from other acute febrile illnesses.

BACKGROUND: The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Dohle-like leukocyte inclusions are caused by MYH9 mutation, a gene encoding the nonmuscle myosin heavy chain-IIA. This study was aimed to identify the Korean GPS patients and to define clinical findings and molecular characteristics on them. METHODS: After taking a family history, platelets were counted using hematologic autoanalyzer and peripheral blood smear (PBS) was examined for platelet size and number, and the presence of leukocyte inclusions. Mutation of MYH9 was studied from mononuclear cells from PB by direct sequencing of previously known 8 exons after PCR amplification of genomic DNA. RESULTS: Twenty patients from 5 unrelated families were diagnosed as GPS. Giant platelets, greater than red cells on PBS, were found to be 3.1% of platelet (range, 1~11%). The median platelet count was 61,000/microliter. Inclusion bodies were found in 3 families. Two families had previously reported mutations. Family I had Arg1944Ter in exon 40, located in the tail portion of myosin, while Family IV had Lys373Asn in exon 10, located in the proximal portion of myosin head. The mutations were found only in affected patients, but not in normal siblings or unrelated families. CONCLUSION: In this study, we identified several families with autosomal dominant GPS. Two families had known MYH9 mutations, Arg1944Ter and Lys373Asn. The search for unknown mutations in the remaining families as well as study of protein structural and functional alteration seems to be necessary for further delineation of these rare genetic disorders.
Bernard-Soulier Syndrome ; Blood Platelets* ; DNA ; Exons ; Genes, vif ; Head ; Humans ; Inclusion Bodies ; Leukocytes ; Myosins ; Platelet Count ; Polymerase Chain Reaction ; Siblings ; Thrombocytopenia

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.
Creatine Kinase, MM Form ; Gene Expression ; Histone Deacetylase 1 ; Histone Deacetylases ; Histones ; Luciferases ; Muscle Cells ; Muscle Development ; Myoblasts ; Myoblasts, Skeletal ; Sumoylation ; Transfection

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.
Air Filters ; Air Pollution ; Animals ; Asthma ; Child ; Dander ; Dogs ; Education ; Environmental Exposure ; Humans ; Logistic Models ; Odds Ratio ; Ownership ; Risk Factors ; Smoke ; Social Change ; Tobacco