Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (DHODH) Highlights Challenges in the Development of Fat Mass and Obesity-Associated Protein (FTO) Inhibitors.

FTO, an -methyladenosine (mA) and ,2'--dimethyladenosine (mA) RNA demethylase, is a promising target for treating acute myeloid leukemia (AML) due to the significant anticancer activity of its inhibitors in preclinical models. Here, we demonstrate that the FTO inhibitor FB23-2 suppresses proliferation across both AML and CML cell lines, irrespective of FTO dependency, indicating an alternative mechanism of action. Metabolomic analysis revealed that FB23-2 induces the accumulation of dihydroorotate (DHO), a key intermediate in pyrimidine nucleotide synthesis catalyzed by human dihydroorotate dehydrogenase (DHODH).

N-methyladenosine (mA) RNA modification in chronic myeloid leukemia: unveiling a novel therapeutic target.

N-methyladenosine (mA), the most prevalent internal mRNA modification, plays a critical role in physiological processes by regulating gene expression through modulation of mRNA metabolism at multiple stages. In recent years, mA has garnered significant attention for a deeper understanding of the initiation, progression, and drug resistance of various cancers, including hematological malignancies. Dysregulation of mA has been implicated in both cancer promotion and suppression.

Multiple Roles of m6A RNA Modification in Translational Regulation in Cancer.

Despite its discovery in the early 1970s, mA modification within mRNA molecules has only powerfully entered the oncology field in recent years. This chemical modification can control all aspects of the maturation of mRNAs, both in the nucleus and in the cytoplasm. Thus, the alteration in expression levels of writers, erasers, and readers may significantly contribute to the alteration of gene expression observed in cancer.

[Diagnostic accuracy of an automatic blood pressure device for ankle brachial index determination in ischemic stroke patients].

Introduction: Ankle brachial index (ABI) is not widespread in clinical practice because the need for specific equipment and training. Doing it without these requirements, quicker and with a cheaper method would facilitate their routine use.

Aims: To evaluate sensitivity and specificity of an automatic blood pressure device detecting ABI < 0.