Pathways of Hypoxia-Inducible Factor (HIF) in the Orchestration of Uterine Fibroids Development.

Uterine fibroids (UF) are common benign tumors in women. The course of UF is associated with troubling symptoms and the development of infertility and pregnancy pathology. Surgical treatment even implies hysterectomy, while pharmacological interventions are modestly effective. Classically, hypoxic metabolism is considered a hallmark of malignant tumor. However, the role of hypoxia-induced factor (HIF) is significant in benign tumors as well. Herein, we briefly review the basic biology of HIF-family proteins, outlining their possible roles in UF. Apart from theoretical justifications, we summarized 15 studies reporting increased expression of HIFs and downstream factors in UF samples. Altogether, data suggest that increased expression of the HIF-protein and altered expression of its dependent genes are presumed to be the factors leading to UF development. Thus, even without being a malignant tumor, UF is characterized by the strong involvement of HIF. This novel insight may give rise to further research in the direction of finding new prognostic markers and effective medicines against UF.

DNA Hypomethylation of the MPO Gene in Peripheral Blood Leukocytes Is Associated with Cerebral Stroke in the Acute Phase.

Dysregulation of the oxidant-antioxidant system contributes to the pathogenesis of cerebral stroke (CS). Epigenetic changes of redox homeostasis genes, such as glutamate-cysteine ligase (GCLM), glutathione-S-transferase-P1 (GSTP1), thioredoxin reductase 1 (TXNRD1), and myeloperoxidase (MPO), may be biomarkers of CS. In this study, we assessed the association of DNA methylation levels of these genes with CS and clinical features of CS. We quantitatively analyzed DNA methylation patterns in the promoter or regulatory regions of 4 genes (GCLM, GSTP1, TXNRD1, and MPO) in peripheral blood leukocytes of 59 patients with CS in the acute phase and in 83 relatively healthy individuals (controls) without cardiovascular and cerebrovascular diseases. We found that in both groups, the methylation level of CpG sites in genes TXNRD1 and GSTP1 was ≤ 5%. Lower methylation levels were registered at a CpG site (chr1:94,374,293, GRCh37 [hg19]) in GCLM in patients with ischemic stroke compared with the control group (9% [7%; 11.6%] (median and interquartile range) versus 14.7% [10.4%; 23%], respectively, p < 0.05). In the leukocytes of patients with CS, the methylation level of CpG sites in the analyzed region of MPO (chr17:56,356,470, GRCh3 [hg19]) on average was significantly lower (23.5% [19.3%; 26.7%]) than that in the control group (35.6% [30.4%; 42.6%], p < 0.05). We also found increased methylation of MPO in smokers with CS (27.2% [23.5%; 31.1%]) compared with nonsmokers with CS (21.7% [18.1%; 24.8%]). Thus, hypomethylation of CpG sites in GCLM and MPO in blood leukocytes is associated with CS in the acute phase.