is a ubiquitous and free-living protozoan pathogen responsible for causing keratitis (AK), a severe corneal infection inflicting immense pain that can result in permanent blindness. A drug-based treatment of AK has remained arduous because trophozoites undergo encystment to become highly drug-resistant cysts upon exposure to harsh environmental conditions such as amoebicidal agents (e.g., polyhexanide, chloroquine, and chlorohexidine). As such, drugs that block the encystation process could result in a successful AK treatment. Histone deacetylase inhibitors (HDACi) have recently emerged as novel therapeutic options for treating various protozoan and parasitic diseases. Here, we investigated whether novel HDACi suppress the proliferation and encystation of . Synthetic class II HDACi FFK29 (IIa selective) and MPK576 (IIb selective) dose-dependently decreased the viability of trophozoites. While these HDACi demonstrated a negligible effect on the viability of mature cysts, encystation was significantly inhibited by these HDACi. Apoptosis was slightly increased in trophozoites after a treatment with these HDACi, whereas cysts were unaffected by the HDACi exposure. The viability of human corneal cells was not affected by HDACi concentrations up to 10 μmol/L. In conclusion, these synthetic HDACi demonstrated potent amoebicidal effects and inhibited the growth and encystation of , thus highlighting their enormous potential for further development.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/acsinfecdis.1c00390 | DOI Listing |
Clin Lymphoma Myeloma Leuk
December 2024
Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. Electronic address:
Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic.
Patients And Methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas.
Leuk Res
December 2024
Department of Hematology, Taixing People's Hospital Affiliated to Yangzhou University, Taixing, China; Institute of Hematology, affiliated hospital of Yangzhou University, Taixing, China. Electronic address:
Acute myeloid leukemia (AML) is a complex hematological malignancy predominantly affecting the elderly, with a median diagnosis age of 68 years. Despite advances in treatment, elderly AML patients face suboptimal survival outcomes, with an estimated 5-year survival rate below 20 %. Epigenetic dysregulation, notably DNA methylation, is a key factor in the progression of myelodysplastic syndromes (MDS) to AML.
View Article and Find Full Text PDFEpigenomics
December 2024
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells.
View Article and Find Full Text PDFMol Cell Proteomics
December 2024
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, United States. Electronic address:
Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The 5 histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry-based approaches, identification and quantification of modified histone peptides remains challenging due to factors such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks.
View Article and Find Full Text PDFJ Investig Med
December 2024
Department of Molecular Biology and Genetics, Faculty of Science, Bilecik Seyh Edebali University, Bilecik, Turkey.
Combined administration of two or more drugs is emerging as a new strategy in triple negative breast neoplasms. This is the first study to investigate the combination of the histone deacetylase inhibitor (HDACi) mocetinostat and the antimetabolite drug capecitabine in triple-negative mammary neoplasms in a preclinical mouse model. 35 female mice were grouped into the control group, capecitabine group, mocetinostat group, and combine drugs group.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!