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).

Clinical and Radiographic Results in Thoracic Hyperkyphosis Surgical Treatment Considering the Optimal Distal Fusion Area.

The aim of this retrospective study was to evaluate the clinical and radiographic outcomes of patients who underwent posterior correction and fusion for thoracic hyperkyphosis, with a focus on determining the optimal distal fusion level. From 2006 to 2012, 26 patients with a median age of 16.8 years (range 14-25), diagnosed with either idiopathic hyperkyphosis or Scheuermann's kyphosis, underwent posterior fusion and Ponte osteotomies at two medical centers.

Radiological evaluation of fusion patterns after Lateral Lumbar Interbody fusion with 3D-printed porous titanium cages vs. conventional titanium cages.

Introduction: The assessment of segmental fusion after Lateral Lumbar Interbody fusion (LLIF) using 3D-printed porous titanium cage is still not well studied. Various criteria, such as the presence of bone bridges (BB) between adjacent vertebrae, serve as indicators for anterior fusion. However, limited radiological studies have investigated zygapophyseal joints (ZJ) status following LLIF with porous titanium cages vs.

Sex Differences in Patient-rated Outcomes After Lumbar Spinal Fusion for Degenerative Disease: A Multicenter Cohort Study.

Study Design: Heterogeneous data collection via a mix of prospective, retrospective, and ambispective methods.

Objective: To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease.

Summary Of Background Data: Current literature suggests sex differences regarding clinical outcome after spine surgery may exist.

Posterior Cruciate Buckling Angle Variations Are Associated with Different Patterns of Medial Meniscus Tears in Anterior-Cruciate-Deficient Knees: Results of a Prospective Comparative Magnetic Imaging Resonance Study.

Background: The diagnosis of anterior cruciate ligament (ACL) tear relies on clinical evaluation and magnetic resonance imaging (MRI). Direct and indirect signs of ACL tear have been described with MRI evaluation. Posterior cruciate ligament (PCL) buckling has been described as an indirect radiographic sign of an ACL tear.