Heat stress targets and degrades BCR::ABL1 oncoproteins to overcome drug-resistance in Philadelphia chromosome-positive acute lymphoblastic leukemia.

BCR::ABL1 oncofusion protein drives Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL), making it a critical therapeutic target. Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have revolutionized the treatment of Ph+ ALL patients. However, mutations in the kinase domain of BCR::ABL1 commonly impair the sensitivity to TKIs, resulting in drug resistance and poor prognosis in Ph+ ALL.

Nuclear receptors in metabolism and diseases: Mechanistic and therapeutic insights.

Nuclear receptors (NRs) are ligand-activated transcription factors that function as metabolic sensors, integrating endogenous and xenobiotic signals to regulate gene networks controlling metabolism, immunity, and cellular homeostasis. Recent studies elucidated the pivotal roles of NRs (e.g.

Arsenic trioxide could promote SARS-CoV-2 NSP12 protein degradation.

The global dissemination and infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become a worldwide crisis with staggering confirmed cases and death tolls. Although prophylactic vaccines are widely applied to curb the spread of the virus, these protections are greatly weakened by the emergence of SARS-CoV-2 variants. Non-structural protein 12 (NSP12) of SARS-CoV-2 is an RNA-dependent RNA polymerase that plays an essential role in viral replication and transcription, representing a promising target for drug development.

Mutation in the Unrearranged Allele Confers Resistance to Arsenic Trioxide in Acute Promyelocytic Leukemia.

Arsenic trioxide (ATO) is able to selectively target and degrade the disease-causing PML::RARα (P/R) oncoprotein in acute promyelocytic leukemia (APL) for curing the disease. However, some relapsed patients develop resistance to ATO due to mutations in the promyelocytic leukemia (PML) part of the fusion gene. A relapsed APL patient had shown resistance to ATO and chemotherapy and was identified to harbor a point mutation (A216V) in the unrearranged allele rather than the fusion gene.

Conditional Binding of Arsenic Trioxide (ATO) to Cysteine-Rich Zinc Finger Motifs within RBCC Domain of PML Protein.

The arsenic trioxide (ATO)-based cure of acute promyelocytic leukemia is attributed to PML/RARα oncoprotein degradation through binding of its RBCC domain (i.e., consist of RING, B-box1, B-box2, and Coiled-coil) with arsenic.

Acute myeloid leukemia with t(8;21) translocation: Molecular pathogenesis, potential therapeutics and future directions.

Acute myeloid leukemia (AML) is a highly heterogeneous and aggressive blood cancer. Genetic abnormalities, such as the t(8;21) rearrangement, play a significant role in AML onset. This rearrangement leads to the formation of the RUNX1/RUNX1T1 fusion protein, disrupting gene regulation and genomic stability, ultimately causing full-blown leukemia.

The landscape of novel strategies for acute myeloid leukemia treatment: Therapeutic trends, challenges, and future directions.

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge.

Identification of a fatty acid synthase gene (FAS1) from Laodelphax striatellus planthoppers contributing to fecundity.

Fatty acid synthase (FAS) is a multifunctional enzyme that plays an important role in the formation of fatty acids. The fatty acids take part in many processes, such as cell signaling and energy metabolism, and in insects they are important in both cuticular hydrocarbon (CHC) formation and reproduction. Here we characterized the sequence structure and function of an FAS from the small brown planthopper (SBPH), Laodelphax striatellus.

Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARα.

The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents.

The incidence of collagen-associated adverse events in pediatric population with the use of fluoroquinolones: a nationwide cohort study in Taiwan.

Background: To evaluate the safety of using fluoroquinolones in pediatric population in Taiwan.

Methods: Patients aged 0~18 years old with fluoroquinolones prescriptions ≥5 consecutive days during year 2000 to 2013 were selected from the National Health Insurance Research Database, 4-time case number were selected as controls. We evaluated the patient's outcome after the use of fluoroquinolones by reviewing a newly diagnosis of the following collagen-associated adverse events by International Classification of Diseases, Ninth Revision, Clinical Modification codes, covering tendons rupture, retinal detachments, gastrointestinal tract perforation, aortic aneurysm or dissection.