CLOCK (Clock Circadian Regulator)

The Expression of Concern has been agreed to in order to inform and alert readers of the image overlap in Figure 2D. The authors disagree with the Expression of Concern.

Based on these findings, the theory of "Taiyin disease resolution period" provides guidance for chronotherapeutic intervention in CAG management. Through innovative integration of modern chronobiology and traditional temporal medicine principles, the study illuminates the central role of the circadian clock gene in the CAG "inflammation to cancer" transformation and emphasizes the potential of the circadian clock and chronotherapy in reversing the "inflammation to cancer" transformation, offering both mechanistic insights and clinically actionable strategies for CAG treatment via chronobiology.

Aberrant expression of clock genes alters tumor metabolism and immune surveillance, promoting tumor growth and immune evasion. Understanding the role of circadian misalignment in cancer biology could pave the way for optimizing drug delivery, improving immune checkpoint therapy outcomes, and advancing personalized chronotherapeutic interventions.

We further synthesize recent advances in circadian-modulating agents, including natural compounds, and specifically evaluate the alignment between their pharmacokinetic profiles and biological rhythm windows. Finally, we propose an "integrative chrono-immunotherapy" strategy, combining TCM wisdom with emerging technologies such as nanotechnology and multi-omics, to provide a theoretical framework for next-generation precision cancer treatments.

In tumors, PER1 has tumor-suppressive effects, with low expression correlating to poor prognosis. This review highlights the critical role of PER1 as a core circadian gene in maintaining physiological homeostasis and regulating disease progression, providing a comprehensive perspective for understanding its complex functions in physiological and pathological processes, offering new insights for developing precision therapies targeting PER1 and its associated signaling pathways.

The review also evaluates promising chronotherapeutic interventions such as time-restricted eating (TRE), targeted probiotic use, and chronopharmacology, which aim to resynchronize host-microbe rhythms and restore physiological balance. Elucidating these mechanisms provides a foundational framework for developing personalized health strategies that target the gut-clock axis.

In addition, clock gene expression profiles emerge as independent prognostic biomarkers for CRC. Future research needs to integrate multiple omics datasets, and artificial intelligence models can analyze the circadian regulation network in CRC, providing new ideas for the precise prevention and treatment of CRC.

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.

Collectively, DCA inhibits noncancerous NCM460 colon cell proliferation via cell cycle arrest and apoptosis accompanied with a drop of Bmal1::Clock gene expression and altered Wnt signaling pathways. The Bmal1::Clock regulatory network is relatively normal in the DCA-treated noncancerous NCM460 colon cells but not in colon cancer tissues.

Altogether, these insights underscore the importance of integrating mechanistic, molecular, and epidemiological data, not only to deepen our understanding of the strength and nature of the relationship between NSW and BC, but also to support a precision medicine framework. This integrated approach is essential for improving individual risk stratification, guiding occupational health policies, and developing targeted preventive strategies for high-risk workers.

Methylation analysis identified six CpG sites significantly associated with survival. In conclusion, EZH2 is a key regulator of HCC progression and potential prognostic biomarker and therapeutic target.