Paulus, L. | bioRxiv Science

bioRxiv2026

Developmental Correlates of Epigenetic and Polygenic Indices of Cognition and Educational Attainment from Birth to Young Adulthood

Large-scale genomic studies have identified biomarkers of adult cognitive functioning and educational attainment, yet the developmental pathways connecting these biomarkers to adult outcomes remain unclear. Drawing on four cohorts, we examined the developmental correlates of an epigenetic index of adult cognitive function ( Epigenetic-g) alongside polygenic indices of cognition and education. Epigenetic-g and polygenic indices were uncorrelated and captured distinct variation in childrens cognitive and academic performance. Longitudinal analyses revealed that Epigenetic-g is plastic in early childhood, reaching moderate stability by adolescence, and, unlike polygenic indices, is not related to longitudinal cognitive growth. Twin models indicated that Epigenetic-g captures genetic and unique environmental variation relevant to cognitive and academic achievement that is not identified by current polygenic indices. Epigenetic indices relevant to psychological development can be generated from DNA methylation studies of adults, with most variation in these indices emerging early in life.

genomics↗

bioRxiv2022

Photodynamic therapy in colorectal cancer using photosensitizers functionalized by arene-ruthenium complexes

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and one of the main causes of cancer deaths in the global population. First-line treatment usually includes surgical procedures followed by combination chemotherapy. Despite the improvements in CRC treatments, the mortality rate remains very high, leading consequently to conventional treatment resistance. Several therapies were enrolled to this content in a way to find the best solutions for this disease. Photodynamic therapy (PDT) using photosensitizers (PS) presents itself as an original innovative therapeutic strategy that strongly limits the undesirable side effects of conventional treatment. However, low physiological solubility and a lack of selectivity of PS towards tumor sites are the principal restrictions of their current clinical use. Indeed, drug delivery systems are currently a key issue in cancer therapy. To overcome the problem of solubility and stability of PS such as porphyrins and their derivatives, metallic assemblies based on arene-ruthenium (Ru) units have begun to attract considerable attention as PS delivery systems. The purpose of this study was to demonstrate firstly the interest in the vectorization of tetrapyridylporphin (TPyP-arene-Ru) and Zn-tetrapyridylporphin arene-ruthenium (Zn-TPyP-arene-Ru) metallacages to increase their solubility in biological media and then, consequently their anticancer efficacy in PDT. Secondly, to elucidate the anticancer mechanism as well as identify the cell death process mediated by these new vectorized PS. The results showed that the two PS-arene-Ru complexes have a strong photocytotoxic effect after photoactivation on human HCT116 and HT-29 colorectal cancer cell lines. TPyP-arene-Ru-PDT induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. The two complexes show no significant effect on proliferation in the dark. In addition, results demonstrated that these two PS-arene-Ru complexes-PDT induce an apoptotic process through the appearance of a sub-G1 peak, phosphatidylserines externalization, poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation. Thus, our data contribute to highlighting that the incorporation of porphyrins in Ru-based assemblies could be an efficient vectorized system to treat CRC by PDT.

cancer biology↗