Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.
［摘要］ 血吸虫病是一种被忽视的人兽共患寄生虫病。目前, 吡喹酮是治疗血吸虫病的首选药物, 也是治疗日本血吸虫 病的唯一有效药物。自 20 世纪 70 年代问世以来, 吡喹酮已在大规模血吸虫病化疗中应用了 40 余年, 长期大规模使用导 致部分地区血吸虫对其产生了抗性, 因此迫切需要研发新型抗血吸虫药物作为候选替代药物。近期研究表明, 组蛋白去 乙酰化酶和组蛋白乙酰转移酶在血吸虫的生长发育以及繁殖等阶段中均起关键作用, 被认为是治疗血吸虫病的潜在药 物靶点。本文总结了组蛋白去乙酰化酶抑制剂与组蛋白乙酰转移酶抑制剂在抗血吸虫药物研究中的最新进展, 以期为 抗血吸虫新药的研发提供参考。.

UNASSIGNED: SMARCA2 and SMARCA4 are subunits of the SWI/SNF complex which is a chromatin remodeling complex and a key epigenetic regulator that facilitates gene expression. Tumors with loss of function mutations in SMARCA4 rely on SMARCA2 for cell survival and this synthetic lethality is a potential therapeutic strategy to treat cancer.
UNASSIGNED: The current review focuses on patent applications that claim proteolysis-targeting chimeras (PROTAC) degraders that bind the bromodomain site of SMARCA2 and are published between January 2019-June 2023. A total of 29 applications from 9 different applicants were evaluated.
UNASSIGNED: SMARCA2/4 bromodomain inhibitors do not lead to desired effects on cancer proliferation; however, companies have converted bromodomain binders into PROTACs to degrade the protein, with a preference for SMARCA2 over SMARCA4. Selective degradation of SMARCA2 is most likely required to be efficacious in the SMARCA4-deficient setting, while allowing for sufficient safety margin in normal tissues. With several patent applications disclosed recently, interest in targeting SMARCA2 should continue, especially with a selective SMARCA2 PROTAC now in the clinic from Prelude Therapeutics. The outcome of the clinical trials will influence the evolution of selective SMARCA2 PROTACs development.

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-κB response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level.

OBJECTIVE: The aim of this study is to review studies evaluating the role of genetics in skeletal class II malocclusion.
OBJECTIVE: To assess the scientific evidence associating the role of genes in skeletal class II malocclusion. Materials and Methods: A complete search across the electronic database through PubMed, Cochrane, LILACS, BMC and manual hand search of orthodontic journals were done till May 2019. The keywords for the search included: \"Genetics\", \"class II malocclusion\", \"maxillary prognathism\", \"mandibular retrognathism\".
METHODS: Studies were selected based on PRISMA guidelines.
RESULTS: Articles were selected based on the inclusion and exclusion criteria. A total of 11 cross-sectional studies satisfied the inclusion criteria and were analyzed for the role of genes in skeletal class II malocclusion. Almost all the studies except for one revealed a positive correlation of genes with skeletal class II malocclusion.
CONCLUSIONS: Out of the 11 studies included, a positive correlation of the genes with the skeletal II malocclusion was found in 10 studies. Genes FGFR2, MSX1, MATN1, MYOH1, ACTN3, GHR, KAT6B, HDAC4, AJUBA were found to be positively linked to skeletal class II malocclusion.

Arboleda-Tham syndrome (ARTHS), caused by a pathogenic variant of KAT6A, is an autosomal dominant inherited genetic disorder characterized by various degrees of developmental delay, dysmorphic facial appearance, cardiac anomalies, and gastrointestinal problems.
A baby presented multiple facial deformities including a high arched and cleft palate, with philtral ridge and vermilion indentation, a prominent nasal bridge, a thin upper lip, low-set ears, an epicanthal fold, and cardiac malformations. Whole exome sequencing (WES) revealed a heterozygous nonsense mutation in exon 8 of the KAT6A gene (c.1312C>T, p.[Arg438*]) at 2 months of age. After a diagnosis of ARTHS, an expressive language delay was observed during serial assessments of developmental milestones.
In this study, we describe a case with a novel KAT6A variant first identified in Korea. This case broadens the scope of clinical features of ARTHS and emphasizes that WES is necessary for early diagnosis in patients with dysmorphic facial appearances, developmental delay, and other congenital abnormalities.

Among the epigenetic changes, histone acetylation has been recognized as a fundamental process that strongly affects gene expression regulation. Disrupt of this phenomenon has been linked to carcinogenesis. In this review, we analysed studies reporting the process of histone modification, the enzymes associated and affected genes concerning human malignancies and histone enzyme inhibitor drugs used in cancer treatment. Variable degrees of expression of HDACs (histone deacetylases) and HATs (histone acetyltransferases) are found in many human malignant tissues and the histones acetylation seems to influence different processes including the progression of cell cycle, the dynamics of chromosomes, DNA recombination, DNA repair and apoptosis. Thus, the control of aberrant activity and/or expression of these proteins have been favorable in treatment of diseases as cancer. HDACi have shown efficacy in clinical trials in solid and hematological malignancies. Therefore, the development and use of HDACs inhibitors are increasing, leading to continue studying these enzyme expressions and behavior, aiming to determine tumors that will respond better to this type of treatment.

Skeletal muscle plasticity is a complex process entailing massive transcriptional programs. These changes are mediated by the action of nuclear receptors and other transcription factors. In addition, coregulator proteins have emerged as important players in this process by linking transcription factors to the RNA polymerase II complex and inducing changes in the chromatic structure. An accumulating body of work highlights the pleiotropic functions of coregulator proteins in the control of tissue-specific and whole body metabolism. In skeletal muscle, several coregulators have been identified as potent modulators of metabolic and myofibrillar plasticity. In this mini-review, we will discuss the control, function and physiological significance of these coregulators in skeletal muscle biology.

Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.

Nutrigenomics is an area of epigenomics that explores and defines the rapidly evolving field of diet-genome interactions. Lifestyle and diet can significantly influence epigenetic mechanisms, which cause heritable changes in gene expression without changes in DNA sequence. Nutrient-dependent epigenetic variations can significantly affect genome stability, mRNA and protein expression, and metabolic changes, which in turn influence food absorption and the activity of its constituents. Dietary bioactive compounds can affect epigenetic alterations, which are accumulated over time and are shown to be involved in the pathogenesis of age-related diseases such as diabetes, cancer, and cardiovascular disease. Histone acetylation is an epigenetic modification mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs) critically involved in regulating affinity binding between the histones and DNA backbone. The HDAC-mediated increase in histone affinity to DNA causes DNA condensation, preventing transcription, whereas HAT-acetylated chromatin is transcriptionally active. HDAC and HAT activities are reported to be associated with signal transduction, cell growth and death, as well as with the pathogenesis of various diseases. The aim of this review was to evaluate the role of diet and dietary bioactive compounds on the regulation of HATs and HDACs in epigenetic diseases. Dietary bioactive compounds such as genistein, phenylisothiocyanate, curcumin, resveratrol, indole-3-carbinol, and epigallocatechin-3-gallate can regulate HDAC and HAT activities and acetylation of histones and non-histone chromatin proteins, and their health benefits are thought to be attributed to these epigenetic mechanisms. The intake of dietary compounds that regulate epigenetic modifications can provide significant health effects and may prevent various pathological processes involved in the development of cancer and other life-threatening diseases.

The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy.