Eyvazi, Shirin

ABSTRACT Background Gynecological cancers are among the most common cancers in women that affect female reproductive organs. The most common gynecological cancers are ovarian, cervical, uterine/endometrial, vaginal, and vulvar cancer. Women's reproductive organs have a dynamic and relative microbial balance. The disruption in the balance of the microbiome could result in numerous gynecological diseases, as well as, gynecological cancers. In this study, we aimed to review new findings on the role of different bacterial infections in various types of gynecological cancers. Recent Findings The role of bacterial infection, as an external factor, has been established in several cancers. However, the ways in which bacteria can promote the development of cancer are not fully understood. It seems that inflammation induced by bacterial infections could promote carcinogenesis. In addition, bacterial toxins and effector proteins play important roles in the progression of cancer. In this review, we attempt to present the different bacterial infections, which have been linked to gynecological cancers development. According to different researches, Chlamydia , Mycoplasma , and Bacteroides spp. are the most common bacterial infections associated with gynecological cancers. Conclusion Evaluation of microbiome in reproductive organs of the patients with gynecological cancer and studies on prevention and control of the infections in the patients could be useful in verification of pathogenesis of the diseases and also founding suitable therapeutic interventions.

Abstract The circadian clock imposes a critical yet incompletely understood layer of regulation on adaptive immunity. T helper 17 (Th17) antimicrobial immune responses including expression of IL-17A by lamina propria CD4⁺ T cells, exhibit diurnal variation and are sensitive to circadian disruption. While the core circadian regulators CLOCK and BMAL1 canonically function as a heterodimer to drive rhythmic gene expression, emerging evidence suggests they may have distinct regulatory roles. Here we integrated ChIP-seq, ATAC-seq, and RNA-seq analyses in naïve CD4⁺ T cells to reveal that the CLOCK-BMAL1 complex controls circadian and metabolic programs through promoter binding, whereas exclusive CLOCK binding at promoters, together with CLOCK-BMAL1 binding at enhancers, regulates immune-associated genes. Using the mutant CLOCKΔ19, which lacks the transactivation domain, we observed disrupted circadian transcription and globally reduced chromatin accessibility, alongside increased accessibility at Th17-associated loci that their altered temporal regulation. Functionally, ClockΔ19 produces β-catenin stabilization in T cells, pronounced expansion of RORγt⁺ CD4⁺ T cells and Treg cells, impaired Treg suppression of Th17 responses, heightened Th17 responses, and reduced IFN-γ production during viral infection. Collectively, these findings define BMAL1 dependent and independent CLOCK functions that program naïve CD4⁺ T cell fate, restrain Th17 differentiation, and preserve immune homeostasis.

Abstract Oral commensals such as Parvimonas micra are increasingly implicated in sporadic colorectal cancer (CRC). Several findings support an emerging notion that alterations in host DNA methylation constitute a mechanism by which P. micra adapts to the host microenvironment and contributes to pathogenic processes. However, multiple limitations hinder definitive conclusions, including the correlative nature of the human studies and the absence of human microbiota in mouse models. Here, we investigated how a complex human microbiome influences the adaptation and oncogenic potential of P. micra in a spontaneous mouse model of polyposis. Adult mice, following antibiotic conditioning, received fecal microbiota transplants (FMT) from a healthy human donor, with or without supplementation of P. micra. P. micra caused significant reshaping of the gut microbial community and altered co-occurrence network structures, which however largely recovered within 21 days post FMT. Despite the transient nature of these changes, P. micra caused a marked increase in both the number and invasive potential of intestinal polyps. Epigenomic profiling of polyp crypts revealed global DNA hypomethylation alongside gene-specific hypermethylation, accompanied by transcriptional changes in key oncogenic pathways. Affected pathways included Wnt signaling, epithelial-to-mesenchymal transition, circadian rhythm regulation, and host–microbe interactions. These findings demonstrate that P. micra exerts a profound influence on microbial ecology, host epigenetic programming, and tumorigenesis in a genetically predisposed host, highlighting its role as a microbial driver of intestinal carcinogenesis.