Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous abnormalities recorded at the cellular, molecular, and genetic level. Expression of the basic leucine zipper transcription factor cAMP-responsive element modulator (CREM)α was reported to be abnormally increased in T cells from SLE patients. CREMα suppresses IL-2 and T cell receptor ζ chain gene transcription by direct binding to the respective promoters. Here, we show that increased CREM expression is the result of enhanced promoter activity. DNA binding analyses reveal direct binding of transcription factor specificity protein-1 (SP-1) to the CREM promoter resulting in enhanced transcriptional activity and increased CREM expression. Protein phosphatase 2A is known to activate SP-1 through dephosphorylation at its serine residue 59. Our results show that nuclei from SLE T cells contain lower levels of Ser(59)-phosphorylated SP-1 protein and a stronger SP-1 binding to the CREM promoter. We conclude that protein phosphatase 2A accounts for enhanced SP-1 dephosphorylation at Ser(59) in SLE T cells. More importantly, CREM promoter activity mirrors reliably disease activity in SLE patients, underscoring its potential role as a biomarker for the prediction of flares in SLE patients.
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http://dx.doi.org/10.1074/jbc.M110.166785 | DOI Listing |
J Orthop Surg Res
January 2025
Department of Korean Rehabilitation Medicine, College of Korean Medicine, Daejeon University, Daejeon, 35235, South Korea.
Unlabelled: BACKGROUND CERVUS ELAPHUS SIBIRICUS: (CES) has been traditionally used in Korean clinics to promote fracture healing based on its function of tonifying the kidneys and strengthening bones. However, experimental data supporting its efficacy are still insufficient. The aim of this study investigated the bone-union properties of CES in a femoral fracture animal model and its corresponding molecular mechanisms.
View Article and Find Full Text PDFCell Mol Biol Lett
January 2025
Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Background: A previous study found that MAF1 homolog, a negative regulator of RNA polymerase III (MAF1), protects the blood-brain barrier (BBB) in sepsis-associated encephalopathy (SAE); however, the related molecular mechanisms remain unclear.
Subjects And Methods: In this study, a rat sepsis model was constructed using the cecum ligation and puncture (CLP) method. In vitro, rat brain microvascular endothelial cells and astrocytes were stimulated with serum from the sepsis model rats.
Medicine (Baltimore)
January 2025
The Reproductive Medicine Centre, Weifang People's Hospital, Shandong Second Medical University, Weifang, Shandong, China.
Rationale: Microcephaly, epilepsy, and developmental delay (MCSZ) is a rare neurodevelopmental disorder associated with autosomal recessive inheritance of mutations in the polynucleotide kinase 3'-phosphatase (PNKP) gene. Prompt identification and management are essential, as delayed diagnosis or intervention may result in severe complications or mortality. In this case, prenatal screening in the second trimester detected fetal microcephaly with a gradual decline in head circumference, prompting the decision to terminate the pregnancy.
View Article and Find Full Text PDFRegarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance.
View Article and Find Full Text PDFNPJ Biosens
January 2025
Department of Electrical Engineering, University of Victoria, Victoria, BC V8W 3P6 Canada.
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.
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