PER2 (Period Circadian Regulator 2)

Cyclocircadins A, C, D, and F-H delayed the phase of the circadian rhythm, and reduced the amplitude of bioluminescence oscillations. In addition, cyclocircadins A, C, F, and G tended to lengthen the circadian period, whereas cyclocircadin E tended to shorten it. Cyclocircadins A and F-H were more active at lower concentrations than cyclocircadins C-E, indicating that structural variations in the seven-membered ring are critical for their activity.

FlyDEGdb stores information on changes in the expression of the dysf gene and its homologues: (a) the Clk, cyc, and per genes in Drosophila, and (b) the NPAS4, CLOCK, BMAL1, PER1, and PER2 genes in humans. These data are supplemented with information on the biological processes in which these genes are involved: oocyte maturation (oogenesis), regulation of stress response and circadian rhythm, carcinogenesis, aging, etc. Therefore, FlyDEGdb, containing information on the widely used model organism, Drosophila, can be helpful for researchers working in the molecular biology and genetics of humans and animals, physiology, translational medicine, pharmacology, dietetics, agricultural chemistry, radiobiology, toxicology, and bioinformatics.

A mechanistic pharmacokinetic-pharmacodynamic model incorporating the clock network recapitulated experimental observations and enabled prediction of treatment timing. Our findings highlight the importance of timing in GBM therapy and propose combining circadian profiling with mathematical modeling to personalize GBM chronotherapy.

Alterations in the protein expression levels of circadian clock genes may contribute to the development and behavior of PAs.

These alterations are further associated with compromised retinal circuitry and function. Thus, this study uncovers critical roles for Bmal1 and Per2 in regulating retinal angiogenesis, emphasizing the importance of circadian control of cell proliferation in vascular development and retinal function.

Our findings demonstrate that everolimus influences circadian gene expression and exerts time-dependent antiproliferative and pro-apoptotic effects in Caco-2 cells. These results support the potential of circadian timing as a strategy to enhance mTOR-targeted therapies in CRC.

Integrated chromatin profiling and metabolic analyses revealed that phosphorylated KDM6A-pSer829 drives glycolytic reprogramming through H3K27Me3-dependent transcriptional silencing of PER2, ultimately promoting tumor growth in vitro and in vivo. These findings establish KDM6A post-translational modification as a pivotal regulator of metabolic adaptation in HNSCC progression, providing a potential therapeutic target for combating cancer through this epigenetic-metabolic axis.

Surprisingly, MCF10A cells, whose core clock genes possess robust circadian expression patterns, did not have rhythmic oscillations of SNAIL. Our findings suggest that SNAIL is under circadian control, but this is cell line/tissue dependent, setting the stage for additional studies to better understand the impacts of various factors contributing to its expression.

Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.

We find that paclitaxel chemotherapy robustly disrupts the molecular clock of the SCN associated with altered SCN-dependent behavioral adaptations. Understanding the extent to which chemotherapy alters SCN function will inform potential targets to reduce debilitating side effects of chemotherapy.

Notably, treatment with the Caspase-8 inhibitor Z-IETD-FMK markedly reversed PANoptosis in OSCC cells. This study provides the first evidence that PER2 overexpression suppresses OSCC proliferation by regulating the Caspase-8/RIPK3/ASC complex-mediated PANoptosis, offering a promising therapeutic strategy for OSCC.

The chemotherapeutic agent temozolomide (TMZ) has limited therapeutic efficacy, and mutations in the tumour protein p53 gene (TP53) have been associated with treatment resistance...Following mRNA analysis, the evaluation of p53 levels confirmed transcriptional changes at the protein level, and that T16 appears to be a favourable time point for enhancing therapeutic efficacy in U87 glioblastoma cells. These findings suggested that synchronizing the complexes' administration with the biological clock of GBM cells may significantly improve glioblastoma therapeutics.