Journal of Ovarian Research最新文献

Background: Ascites represents an extremely unique liquid immunosuppressive microenvironment of epithelial ovarian cancer (EOC), and it contains a substantial quantity of macrophages; however, these macrophages fail to exhibit effective anti-tumor activity. Peritoneal mesothelial cells (PMCs) constitute a critical component of ascites. Whether PMCs can modulate macrophages function through some mechanisms, thereby influencing the tumor immune microenvironment, remains to be elucidated.

Methods: Co-culture models of EOC-educated PMCs (EOC-PMCs) and macrophages in human and mouse were respectively constructed, and verified the differences of polarization markers, cytokines, and metabolic levels in macrophages after co-culture. Transcriptional sequencing experiments confirmed that polypeptide N-acetylgalactosaminyltransferase 15 (Galnt15) was highly expressed in macrophages after co-culture. Nuclear-cytoplasmic protein separation and immunofluorescence (IF) were used to confirm that the nuclear entry of peroxisome proliferator-activated receptor γ (PPARγ) increased and the polarization of macrophages was enhanced when Galnt15 was overexpressed. In vitro experiments, the overexpression and knockdown of Galnt15 were achieved using plasmids and siRNAs. Immunoprecipitation (IP) experiments verified that high expression of Galnt15 mediated the O-glycosylation of PPARγ, thereby affecting the nuclear entry of PPARγ. Site mutation and fusion protein detection were employed to explore the functional site of Galnt15-mediated O-glycosylation of the PPARγ protein. And an EOC model in situ was established on the ovary of C57BL/6J, and it was confirmed in vivo and in vitro that macrophages treated with EOC-PMCs played a pro-cancer role. Tissue microarrays confirmed that the expression of Galnt15 and PPARγ was related to patient prognosis.

Results: EOC-PMCs led to high expression of Galnt15 in macrophages. Galnt15 promoted O-glycosylation and nuclear translocation of PPARγ, subsequently enhancing fatty acid oxidation (FAO) metabolism, and inducing macrophages polarization and secretion of pro-tumor cytokines. Animal experiments showed that EOC-PMCs increased the FAO metabolism level of macrophages to promote tumor development. Tissue microarray also confirmed that there was a positive correlation between the expression of Galnt15 and PPARγ, and patients with high expression of Galnt15/PPARγ had a poorer prognosis.

Conclusion: EOC-PMCs promote macrophages polarization through the Galnt15/PPARγ pathway, which is conducive to the formation of an immunosuppressive microenvironment in ascites and ultimately facilitates the progression of ovarian cancer.

Background: PCOS is a common condition among women of reproductive age, marked by irregular menstrual cycles, hyperandrogenism, and ultrasound abnormalities. Infertility treatments such as metformin and myoinositol often have side effects and low adherence. Ziziphus jujuba has the potential in improving PCOS outcomes, prompting this study to compare its effect on pregnancy rates with conventional therapies.

Methods: This double-blind, randomized trial involved 196 infertile PCOS patients (ages 18-45), with 49 participants in each group. Participants were randomly assigned to four groups: metformin (500 mg daily), myoinositol (2000 mg daily), Ziziphus jujuba hydroalcoholic extract (15 g daily), or placebo (sachet/pill) for 12 weeks. Biochemical (FBG, lipid profile, ALT, AST, ESR, CRP, TyG index) and anthropometric (weight, BMI, waist circumference) measurements were taken pre- and post-study. Ovulation induction with letrozole was performed, and pregnancy occurrence was the primary endpoint, assessed via Beta hCG and ultrasound 6-7 weeks after treatment.

Results: No significant differences in pregnancy as primary outcome were found (Ziziphus jujuba: 10, Metformin: 7, Myoinositol: 5, Placebo: 4; p > 0.05). However, significant improvements in cholesterol, TG, HDL cholesterol, and FBG were observed in the Ziziphus jujuba compared to other groups (p < 0.05).

Conclusion: The Ziziphus jujuba extract demonstrated significant improvements in FBG levels, lipid profiles, and insulin resistance; however, it did not significantly increase pregnancy occurrence compared to metformin, and myoinositol. No serious adverse effects were observed, with only one participant reporting mild constipation. These findings suggest that while Ziziphus jujuba shows promise in metabolic management of PCOS, its efficacy in enhancing fertility outcomes requires further investigation or consideration in combination therapies.

Trial registration: Registered at the Mashhad Medical University of Medical Science: IR.MUMS.MEDICAL.REC.1402.191. The date of enrolment of the first patient into the trial is January 21, 2023.

Highlights: Key findings of this study with potential clinical relevance include:• RLIP is an attractive therapeutic target with the ability to suppress human OC at multiple stages of development.• Reducing RLIP levels significantly inhibits OC cell growth and enhances apoptosis compared with controls.• RLIP blockade/depletion may serve as a broad-spectrum therapeutic strategy that remains effective regardless of common pathway differences among OC subtypes.• This is the first evidence from integrated in vitro and in vivo studies demonstrating the strong therapeutic promise of RLIP-targeting agents for treating metastatic OC.

Background: Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer, due to asymptomatic early stages, vague symptoms in later stages, and limited clinical tools. Despite distinct clinicopathologic features, all EOC histotypes typically receive identical primary treatment, and are often studied as a single entity.

Methods: We analyzed the proteome of 244 patients and identified differentially abundant proteins (DAPs) with and without stage specificity across histotypes and constructed panels of DAPs to distinguish histotypes in both early and late stages. Survival analysis was performed to find proteins associated with clinical outcomes, and enrichment analysis was conducted to reveal biological processes connected to prognosis and the proteins involved.

Results: Here we find DAPs without (e.g. S100A1, AGR2, CTH) and with (TSPYL, VWA2, GPC6, S100P) stage-specificity for each histotype. Survival analysis revealed histotype- and stage-specific prognostic markers (e.g., EXO3CL2, PPIL6, GYG1, GAPDH), while biological process enrichment highlighted pathways underlying clinical outcomes.

Conclusions: Our findings provide novel diagnostic and prognostic biomarker candidates and insights into mechanisms driving EOC progression with histotype- and stage-specificity. This may aid the development of improved clinical tools for detection, patient stratification, and targeted therapies in EOC.