DNA methylation data has been used to make "epigenetic clocks" which attempt to measure chronological and biological aging. These models rely on data derived from bisulfite-based measurements, which exploit a semi-selective deamination and a genomic reference to determine methylation states. Here, we demonstrate how another hallmark of aging, genomic instability, influences methylation measurements in both bisulfite sequencing and methylation arrays. We found that non-methylation factors lead to "pseudomethylation" signals that are both confounding of epigenetic clocks and uniquely age predictive. Quantifying these covariates in aging studies will be critical to building better clocks and designing appropriate studies of epigenetic aging.
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http://dx.doi.org/10.1101/2023.12.20.572465 | DOI Listing |
Drug Des Devel Ther
December 2024
Department of Cardiology, Guang Anmen Hospital, Beijing, People's Republic of China.
Background: Improving angiogenesis in the ischemic myocardium is a therapeutic strategy for preventing, reducing, and repairing myocardial injury of coronary artery disease (CAD). saponins (PNS) have been widely used in the clinical treatment of cardiovascular diseases, demonstrating excellent efficacy, and can potentially improve angiogenesis in the ischemic myocardium. However, the effects of PNS on angiogenesis and its underlying mechanism of action remain unclear.
View Article and Find Full Text PDFSupraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.
View Article and Find Full Text PDFAcute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.
View Article and Find Full Text PDFJ Med Chem
December 2024
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
In this study, we discovered and identified a novel AXL/triple angiokinase inhibitor by rational structural modification based on the structure of triple angiokinase inhibitor Nintedanib. We found that potently inhibited AXL expression with the IC value of 3.75 nM and possessed similar inhibitory activity on KDR as Nintedanib.
View Article and Find Full Text PDFCancer Med
December 2024
Department of Hematology, Peking University First Hospital, Beijing, People's Republic of China.
Background: An effective urine-based method for the diagnosis, differential diagnosis and prognosis of multiple myeloma (MM) has not yet been developed. Urine cell-free DNA (cfDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive "liquid biopsy" for diagnosis and monitoring of cancer.
Methods: We first identified MM-specific hydroxymethylcytosine signatures by comparing 64 MM patients, 23 amyloidosis (AM) patients and 59 healthy cohort.
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