PER1 (Period Circadian Clock 1)

We emphasize the associations between circadian disruption and CRC-including diagnostic markers, prognostic assessment, and chemosensitivity-and provide an in-depth discussion of chronotherapeutic strategies and their translational potential. Finally, we identify unaddressed scientific questions and propose future research directions to facilitate the development of novel targeted therapies for CRC.

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.

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.

Broader validation and harmonized reporting are essential before translation into practice. Not registered; methods followed PRISMA/TRIPOD/PROBAST guidance.

Recent findings demonstrate that time-of-day-dependent administration of vaccines and immunotherapies, including checkpoint inhibitors, can significantly influence clinical efficacy and immune outcomes. Understanding the temporal orchestration of adaptive immunity thus holds translational potential for optimizing therapeutic strategies, including chronotherapy and vaccination scheduling.

These data indicate that circadian synchronization improves interpretability of BMAT-MSC molecular outputs and reveals disease-associated differences among HD, FA, and AML. This study is a preliminary investigation with limited sampling and timepoints; findings should be validated in larger cohorts with denser temporal resolution. Overall, the results provide a framework for integrating circadian context into BMAT-MSC analyses in health and hematological disease.

The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) may be considered an effective option in the neoadjuvant setting for metastatic colon cancer (mCRC). Data obtained indicate transcriptional discordance between the primary tumors and liver metastases during neoadjuvant FOLFOXIRI, with the pattern of DEGs involved in their response being distinct. The EPS8L2 transcript could be regarded as a candidate biomarker of liver complete response; however, prognostic conclusions cannot be drawn from this cohort.

Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management.

Core circadian genes represent promising candidate biomarkers for both cancer survival risk stratification and immunotherapy response prediction. They further enable the development of high-accuracy machine learning models to predict immunotherapy responses.

Furthermore, we delineated the regulatory functions of the transcription factors BMAL1 and CLOCK in promoting the expression of PER1 and miR-6883-5p, while miR-6883-5p negatively regulates CLOCK expression, thereby impacting the transcription-translation feedback loop (TTFL) of circadian genes. Collectively, these findings uncover a regulatory axis involving circadian rhythm components, miR-6883-5p, AR-V7, and PCa progression, providing new mechanistic insights into treatment resistance in CRPC and highlighting the circadian clock as a potential therapeutic target.

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.

O-GlcNAc modification YTHDF2 promotes bladder cancer development by downregulating the tumor suppressor gene PER1 through m6A-mediated post-transcriptional regulation.