Inhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.

Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.

HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.

Senescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction.

Combined Transcranial Direct Current Stimulation and Pain Neuroscience Education for Chronic Low Back Pain: A Randomized Controlled Trial.

Objective: Priming the neural circuity likely targeted by pain neuroscience education (PNE), using transcranial direct current stimulation (tDCS) may enhance the efficacy of PNE. The aim of this study was to compare the effects of active tDCS + PNE to sham tDCS + PNE on measures of pain, pain behaviors, and cognitive function in participants with chronic low back pain (CLBP) and high pain catastrophizing.

Methods: 20 participants were recruited and randomly allocated into the active tDCS + PNE (n = 10) or sham tDCS + PNE (n = 10) groups.

Imaging of labile Fe2+ and Fe3+ in living Arabidopsis thaliana roots.

Adapting fluorescent iron imaging to living plants enables visualizing labile Fe and Fe pools, revealing the heterogeneous distribution of iron redox status at the tissue and cellular levels.

Identification of GB3 as a Novel Biomarker of Tumor-Derived Vasculature in Neuroblastoma Using a Stiffness-Based Model.

Neuroblastoma (NB) is a childhood cancer in sympathetic nervous system cells. NB exhibits cellular heterogeneity, with adrenergic and mesenchymal states displaying distinct tumorigenic potentials. NB is highly vascularized, and blood vessels can form through various mechanisms, including endothelial transdifferentiation, leading to the development of tumor-derived endothelial cells (TECs) associated with chemoresistance.