Browsing by Author "Li, Mengxia"

Abstract APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.

Both high tibial valgus osteotomy (HTO) and unicompartmental medial knee arthroplasty (UKA) are established methods for the treatment for moderate stages of OA. This is the first global meta-analysis to compare the long-term effects of both methods regarding survival, outcomes and complications of total arthroplasty. Literature research was performed using established medical databases: MEDLINE (via PubMed), EMBASE (via OVID) and the Cochrane register. Criteria for inclusion were as follows: English or German papers, a clinical trial with a clear description of survival, an outcome evaluation using a well-described knee score and a follow-up > 5 years. Statistical analysis was performed using the special meta-analysis software called "Comprehensive Meta Analysis" (version 2.0; Biostat, Englewood, NJ, USA). Final meta-analysis after the full-text review included 46 studies about valgus HTO and 43 studies about medial UKA. There were no significant differences between valgus HTO and medial UKA in terms of the number of total required replacements. After a 5- to 8-year follow-up, 91.0% of the valgus HTO patients and 91.5% of medial UKA patients did not need a total replacement. This value was 84.4% for valgus HTOs and 86.9% for medial UKAs after a 9- to 12-year follow-up. Mean survival time to TKA was 9.7 years after valgus HTO and 9.2 years after medial UKA. Clinical outcome was significantly better after medial UKA in a 5- to 12-year follow-up. After more than 12 years, results were comparable in both groups. No significant differences were seen in the complication rates. This meta-analysis aimed to find the advantages and disadvantages of two established methods for the treatment for medial compartment knee osteoarthritis. Valgus HTO is more appropriate for younger patients who accept a slight decrease in their physical activity. Medial UKA is appropriate for older patients obtaining sufficient pain relief but with reduced physical activity. II.