CLOCK (Clock Circadian Regulator)

Consistent with these findings, functional assays in human and murine hepatocarcinoma cells demonstrated that Chrono knockdown markedly inhibits cell proliferation. Mechanistically, suppression of CHRONO induced G1-phase arrest by decreasing the protein expression of key cell cycle regulators, including cyclin D and cyclin E. Collectively, our findings provide the first functional evidence that CHRONO acts as a pro-proliferative regulator in HCC, suggesting that modulation of CHRONO may suppress tumor growth while minimizing disruption of the core circadian oscillator.

Moreover, ANGPTL4 is biologically active in the BALF of RSV-PVLD mice, inhibiting lipoprotein lipase activity. We conclude that RSV-PVLD is mediated, at least in part, by RelA signaling in Scgb1a1-derived epithelial progenitors, dysregulating ANGPTL4 signaling in an epithelial-mesenchymal niche, resulting in persistence of atypical alveolar epithelial cells with dysregulated of clock gene expression.

Disrupting the CLOCK-TFPI2 interplay through dual inhibition of their downstream effectors reduces GSC stemness and immunosuppressive microglia, activates antitumor immunity, and synergizes with anti-PD1 therapy to achieve complete tumor regression in 50-62.5% of tumor-bearing mice. This study uncovers a promising therapeutic strategy for a broader subset of GBM patients with high expression of either CLOCK or TFPI2, and provides a framework for identifying 'symbiotic exclusivity' genes in cancer.

In vitro, BMAL1 knockdown promoted lipid accumulation and cellular damage, while BMAL1 overexpression alleviated these pathological phenotypes. Collectively, these findings demonstrated that CD73-LKO could affect mice circadian rhythm, regulate the expression of liver adenosine receptors and BMAL1, which provides new insights into the molecular mechanisms underlying the role of CD73 in ALD.

TMEM5 is associated with circadian-gene expression patterns, temozolomide response, and bioenergetic readouts in GBM models. TMEM5 knockdown was accompanied by altered time-dependent expression profiles of multiple clock genes, reduced OCR/ECAR parameters under the tested conditions, and increased TMZ sensitivity. These findings support TMEM5 as a circadian-associated factor in GBM and provide a rationale for future studies to define whether TMEM5 directly influences circadian regulation and metabolic pathway remodeling in vivo.

Overall, meal timing represents a modifiable factor influencing metabolic health and possibly early carcinogenesis. Aligning eating behavior with intrinsic circadian rhythms may help mitigate cancer risk and improve long-term well-being.

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.