Higher Oxidative Stress in Endometriotic Lesions Upregulates Senescence-Associated p16ink4a and ß-Galactosidase in Stromal Cells.

Endometriosis affects a significant proportion of women worldwide; however, no definitive cure for this disease has been discovered to date. Oxidative stress promotes endometriotic lesion maintenance in the peritoneal cavity in women. Furthermore, there is evidence of the mitogen-activated protein kinase (MAPK) signaling pathway and senescence involvement in the physiopathogenesis of endometriosis. Reactive oxygen species (ROS) cause oxidative damage and are expected to trigger senescence in the endometrium while also causing alterations in MAPK signaling. However, the role of ROS in the senescence-associated phenotype in endometriosis remains unknown. In this context, this study attempted to delineate the pathways linking ROS to senescence in endometrial and endometriotic lesions of healthy individuals and those with endometriosis. Our results indicate a higher presence of ROS in endometriotic lesions, and the upregulation of MAPK. Furthermore, we show that endometriotic lesions in stromal cells stimulated with hydrogen peroxide develop more senescence traits than eutopic and non-endometriosis endometrium. Overall, endometriotic cells respond differently to extracellular distress. Our contribution to further research in this field contributed to the roadmap of endometriosis' search for alternative treatments.

Colocalization of senescent biomarkers in deep, superficial, and ovarian endometriotic lesions: a pilot study.

Endometriosis is a prevalent gynecological condition with deleterious effects on women's quality of life in terms of physical, emotional, and social compromise. It is an inflammatory disease characterized by the presence of endometrial-like tissue outside the uterus, and its presentation varies from superficial peritoneal lesions to deep infiltrative endometriosis and ovarian endometrioma. In our previous study, endometriotic lesions were implicated in cellular senescence as their inflammatory pattern could potentially compromise surrounding tissue integrity, thereby inducing a senescent state in cells. P16Ink4a and lamin b1 are biomarkers used to assess cellular senescence. Indirect immunofluorescence staining is a broad technique used to assess cellular structure and behavior driven by protein-protein interactions that provide valuable information about cell functioning. The etiopathogeny of endometriosis is not completely understood and diagnostic approaches still rely on invasive methods; therefore, it is important to use validated methods to increase our understanding of the disease and the development of novel diagnostic tools. However, indirect immunofluorescence protocols are often tissue specific and, if neglected, can lead to misinterpretation of results. Moreover, no valid endometriotic tissue-specific colocalization immunofluorescence protocols have been established. Thus, we have validated a well-funded and suitable protocol to allow precise evaluation of the three presentations of endometriosis lesions using indirect immunofluorescence aiming to support further investigations in endometriosis lesions.

Normative data for the Montreal Cognitive Assessment (MoCA) and the Memory Index Score (MoCA-MIS) in Brazil: Adjusting the nonlinear effects of education with fractional polynomials.

OBJECTIVE: To provide age-corrected and education-corrected norms for the Montreal Cognitive Assessment (MoCA) and the Memory Index Score (MoCA-MIS) in Brazil. METHODS: Community-dwelling outpatients were enrolled if they had no history of neurologic or psychiatric diseases and were not taking any drugs with effects on the central nervous system. Dementia has been excluded with the Functional Activities Questionnaire. The final sample consisted of 597 cognitively healthy Brazilians aged 50 to 90 years. To account for nonlinear relationships, we have used fractional polynomials that provide a flexible parameterization for continuous variables. RESULTS: According to the original proposed cutoff (≤25 points), 87% of our sample would be considered impaired. Even using a more conservative suggestion (≤22 points), 67% of our normative sample would be regarded as impaired. These data reinforce the need of adjusting cutoffs for schooling in populations with heterogeneous educational backgrounds. MoCA scores presented a nonlinear positive association with education tending to a plateau at higher levels (P < 0.001). On the other hand, MoCA-MIS scores presented a nonlinear negative relationship with age, with an accelerated pattern at higher age levels (P < 0.001). CONCLUSIONS: We presented normative data for the MoCA and the MoCA-MIS that will facilitate the use of the test in Brazil and, potentially, in other populations with substantial proportions of low-educated individuals. Moreover, we described a systematic approach for adjusting the effects of age and education using fractional polynomials and provided suggestions on how to account for the nonlinear relationship that is frequently encountered between demographic factors and measures of cognitive performance.