Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R−), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R− women. Women with a micro-RNA-184 fold change < 0.083 were more likely to show recurrence (n = 6; 66%) compared to those with a micro-RNA-184 fold change > 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change < 0.56 were more likely to show recurrence (n = 5; 100%) compared to those with a micro-RNA-196 fold change > 0.56 (n = 2; 13%), p = 0.001. These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.
(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.
Achieving hemostasis is crucial in neurosurgery, yet conventional methods are not always feasible, making topical hemostatic agents necessary. Current resorbable hemostatic agents allow effective hemostasis but must remain in situ to prevent rebleeding. This can provoke foreign body reactions leading to prolonged microglia-mediated neuroinflammation, which may exacerbate damage and delay recovery. It highlights the need for new hemostatic materials that can be removed after controlling bleeding while being safe for neurons and microglia. One candidate is Hemo-Ionic, a non-resorbable hemostatic compress composed of calcium alginate and zinc (Zn2+). Hemo-Ionic previously demonstrated effective in vitro and in vivo hemostasis, comparable to Surgicel and TachoSil, and pro-repair properties. In this study, Hemo-Ionic’s effect on neuronal and microglial cells was investigated in vitro. Results showed that Hemo-Ionic preserved cell viability and had an antioxidant capacity through protection from lipid peroxidation. Hemo-Ionic also reduced nitric oxide and pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) expression and release by lipopolysaccharide (LPS)-stimulated microglial cells. Finally, neuronal viability was restored when exposed to supernatants of Hemo-Ionic-treated microglia. These findings indicate that Hemo-Ionic’s safety and capacity to reduce neuroinflammation, combined with its hemostatic efficacy and non-resorbable nature, make it a promising alternative to resorbable hemostatic agents used in neurosurgery.
Lors de la gestation, des cellules du fœtus sont transférées vers la circulation de la mère et y persistent pendant des décennies, en nichant dans la moelle osseuse maternelle. Ces cellules fœtales, dites microchimériques, comprennent divers types de progéniteurs qui sont capables de migrer vers un tissu maternel lésé, pour participer à sa réparation. Au cours de ma thèse, j’ai pu travailler sur l’effet des Cellules Fœtales Microchimériques (CFMs) recrutées dans les plaies cutanées de souris gestantes ou post-gestantes. Dans les deux cas, ces CFMs améliorent la cicatrisation en stimulant l’angiogenèse et la prolifération cellulaire au sein des plaies. L’étude de leur transcriptome durant ou après la gestation montre, par ailleurs, l’expression de plusieurs marqueurs de cellules souches. Nous avons montré que la voie de signalisation CCR2/CCL2 régule le trafic d’une sous-population de CFMs. Cette sous-population a un phénotype de progéniteurs myéloïdes CCR2+ et est recrutée vers la plaie en réponse au CCL2 sécrété par les monocytes maternels. Ainsi, une injection sous-cutanée de CCL2 amplifie le recrutement fœtal et améliore la cicatrisation chez les souris gestantes ou post-gestantes. L’implication des CFMs se fait, entre autres, par la formation de vaisseaux sanguins et par la sécrétion spécifique de facteurs pro-angiogéniques. D’autre part, l’injection intracérébrale de CCL2 améliore la réparation cérébrale des souris post-gestantes après induction de lésions excitotoxiques. Ces résultats ouvrent la voie vers une « thérapie cellulaire naturelle » qui consiste à stimuler une voie de signalisation pour recruter des progéniteurs fœtaux spécifiques vers une lésion maternelle. Celle-ci présente plusieurs avantages par rapport aux thérapies cellulaires actuelles et laisse prévoir des avancées dans le traitement des défauts de réparation tissulaire maternels.