Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

RESEARCH QUESTION: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity? DESIGN: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo. RESULTS: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%). CONCLUSIONS: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

Stokes light induced modulation instability in high power continuous wave fiber amplifiers.

In this paper, Stokes light induced modulation instability (MI) in high power continuous wave (CW) fiber amplifiers is observed. The investigation shows that the Stokes light generated by inter-modal four wave mixing (IMFWM) and stimulated Raman scattering (SRS) in high power fiber amplifiers can be modulated by the signal light through XPM and cause MI. Then, a sideband will be generated around the second-order Raman frequency shift, which is amplified by SRS and shown as a train of pulses in time domain. It is shown that the frequency shift of the sideband will be influenced by IMFWM and SRS. In addition, the sideband was found to be blue-shifted with the increase of the power, which indicates that the frequency shift of the sideband is mainly depended on MI, while SRS plays the role of amplification.

KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer.

Most clinical PARP inhibitors (PARPis) trap PARP1 in a chromatin-bound state, leading to PARPi-mediated cytotoxicity. PARPi resistance impedes the treatment of ovarian cancer in clinical practice. However, the mechanism by which cancer cells overcome PARP1 trapping to develop PARPi resistance remains unclear. Here, it is shown that high levels of KAT6A promote PARPi resistance in ovarian cancer, regardless of its catalytic activity. Mechanistically, the liquid-liquid phase separation (LLPS) of KAT6A, facilitated by APEX1, inhibits the cytotoxic effects of PARP1 trapping during PARPi treatment. The stable KAT6A-PARP1-APEX1 complex reduces the amount of PARP1 trapped at the DNA break sites. In addition, inhibition of KAT6A LLPS, rather than its catalytic activity, impairs DNA damage repair and restores PARPi sensitivity in ovarian cancer both in vivo and in vitro. In conclusion, the findings demonstrate the role of KAT6A LLPS in fostering PARPi resistance and suggest that repressing KAT6A LLPS can be a potential therapeutic strategy for PARPi-resistant ovarian cancer.

Fbf1 regulates mouse oocyte meiosis by influencing Plk1.

Fas binding factor 1 (Fbf1) is one of the distal appendage proteins in the centriole, located at its distal and proximal ends. It influences the duplication and separation of centrosomes, thereby affecting the progression of the cell cycle during mitosis. However, the function of Fbf1 in meiosis has remained unclear. To explore the role of Fbf1 in the in vitro maturation of mouse oocyte, immunofluorescence staining was used to examine the Fbf1 location in the oocyte and their phenotype after protein deletion. Western blot was used to examine the protein abundance. This study showed that mouse oocytes express Fbf1 which locates at the spindle poles and around the microtubules. Through taxol and nocodazole treatment, and microinjection of siRNA, it was demonstrated that Fbf1 had an important role in the spindle assembly and chromosome separation during mouse oocyte meiosis In particular, microinjection of Fbf1-siRNA resulted in severe abnormalities in the spindle and chromosome arrangement, decreased aggregation of microtubules, disrupted the first oocyte meiosis, and the extrusion of the first polar body. Furthermore, in the Fbf1-siRNA group, there was reduced expression of Plk1 and its agglutination at the spindle poles, along with retarded chromosome segregation due to the activation of the spindle assembly checkpoint (SAC) component BubR1. These results indicate that Fbf1 may function in microtubule depolymerization and agglutination, control the microtubule dynamics, spindle assembly and chromosome arrangement and, thus, influence the mouse oocyte meiotic maturation.

Identification of LncRNA Prognostic Markers for Ovarian Cancer by Integration of Co-expression and CeRNA Network.

BACKGROUND: Ovarian cancer (OC), one of the most prevalent gynecological malignancies, is characterized by late detection and dismal prognosis. Recent studies show that long non-coding RNAs (lncRNAs) in competitive endogenous RNA (ceRNA) networks influence immune infiltration and cancer prognosis. However, the function of lncRNA in OC immune infiltration and prognosis remains unclear. METHODS: Transcriptomes of 378 OC samples and clinical data were retrieved from the TCGA repository. Modules related to immune cells were identified using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis and survival analysis were then performed for the identification of immune-related lncRNAs in the brown module using Cox regression model. Finally, a ceRNA network was constructed by using the lncRNAs and mRNAs from the brown module. RESULTS: We found lncRNAs and mRNAs in the brown module to be significantly associated with immune cells in OC and identified 4 lncRNAs as potential OC prognostic markers. We further established that lncRNAs in the ceRNA network influence OC immune infiltration and prognosis by regulating miRNA, ultimately modulating mRNA levels. CONCLUSION: We have identified 4 lncRNAs as independent immune prognostic factors for OC. Furthermore, our findings offer novel insight into lncRNAs as OC immune and prognostic biomarkers.