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RMD Open (2022) 8(2):e00251

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Undoubtedly, mechanisms of action are multifaceted and some mechanisms may predominate over others in different patients and in the context of different tumor microenvironments and immune milieu [34]

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In a transcriptomic analysis of pre-menopausal and peri-menopausal stromal fibroblasts, over 1,000 genes were found to be differentially expressed between these two age groups ( PR ) and estrogen receptor beta ( ESR2 ), and upregulation of estrogen receptor alpha ( ESR1 ) in the younger cohort ( In vitro studies have demonstrated that hypoxia-induced endometrial stromal cell senescence leads to impaired decidualization as evidenced by incomplete morphological transformation and reduced expression of decidualization markers IGFBP1 and PRL ( in vitro decidualization of HESCs, confirmed by upregulated expression of PRL , IGFBP1 and FOXO1 , resulted in an increase in expression of senescence markers p21 and p53 , suggesting that decidualization may promote cellular senescence (Kusama et al., 2021)

Certain medications may make RLS symptoms worse, for example, medicines that address mental health (antidepressants, antipsychotics) and even over-the-counter medications for allergies and cold symptoms (4)