Original research publications

High-grade serous ovarian cancer (HGSOC) is marked by genomic instability, immune suppression, and poor outcome, yet enhancer-gene networks coordinating malignant epithelial programs and CD4⁺ T-cell states remain unclear. We aimed to identify enhancer-associated regulatory circuits linking tumor plasticity, CD4⁺ T-cell polarization, and prognosis in HGSOC. We integrated H3K27ac ChIP-seq, Hi-C, single-cell RNA-seq, spatial transcriptomics, TCGA-OV data, CD4⁺ T-cell eQTLs, and pharmacogenomic annotations to reconstruct cell-type-specific enhancer-gene regulatory networks. Motif enrichment, SCENIC, Louvain clustering, CellChat, pseudotime analysis, spatial deconvolution, GSVA, and survival modeling were applied. Seven-color multiplex immunofluorescence was performed in 90 primary HGSOC and 10 non-malignant ovarian tissues. HGSOC showed redistribution of H3K27ac signals toward distal regulatory regions linked to immune and tumor-cell programs. Single-cell profiling identified an aneuploid malignant epithelial compartment and a Treg-skewed CD4⁺ T-cell landscape. Integrated network analysis highlighted ELF3, FLI1, KLF4, and ZNF250 as shared hub transcription factors. Among these, an ELF3-associated enhancer-CLDN4 axis was supported by chromatin contacts and CD4⁺ T-cell eQTL evidence. eGRN-active CD4⁺ Th17 cells showed altered communication patterns, aberrant pseudotime positioning, and preferential peritumoral localization, particularly in JAK1-high spatial samples, where they co-localized with Tregs and macrophages. Multiplex immunofluorescence confirmed elevated ELF3 and CLDN4 expression in HGSOC, positive associations with Treg accumulation, inverse associations with Th17 infiltration, and correlations with poor overall survival. ELF3-high and CLDN4-high status remained independent adverse prognostic factors. An enhancer-associated ELF3-CLDN4 axis links tumor-cell regulatory plasticity with CD4⁺ T-cell immunosuppression and adverse prognosis in HGSOC.

Risk reducing salpingo-oophorectomy with delayed oophorectomy is an alternative preventive strategy to prevent tubo-ovarian carcinoma. Its oncological safety is currently under investigation within different clinical trials. After a previous salpingectomy, a 37-year-old BRCA1 pathogenic variant carrier developed a carcinoma in the abdominal cavity, which had spread extensively throughout the abdomen. She had chosen the alternative risk-reducing salpingectomy with delayed oophorectomy as tubo-ovarian carcinoma prevention strategy The salpingectomy was performed at age 35, two years prior to the diagnosis of carcinoma. Radiologically, the tumor appeared to originate from the left ovary with lymphadenopathy, hydronephrosis, and peritoneal carcinomatosis. Incomplete debulking surgery was performed with en bloc resection of the uterus, ovaries, rectosigmoid,appendix, and distal part of the left ureter. After extensive analysis with pathology revision, the tumor was classified as a poorly differentiated sarcomatoid urothelial cell carcinoma. Molecular testing showed the tumor had a BRCA1 pathogenic variant. This case illustrates the importance of a structured clinical trial setting for the investigation of cancer prevention strategies as it ensures extensive follow-up and comprehensive pathological (re)assessment to warrant patient safety.

Reliable biomarkers for accurate risk stratification in epithelial ovarian cancer (EOC) remain limited. While kazal type serine peptidase inhibitor domain 1 (KAZALD1), a secreted proteoglycan, has been implicated in numerous tumors, its clinical value in EOC remains unknown. The present study evaluated whether KAZALD1 is an independent prognostic biomarker in EOC and explored its associations with immune-cell infiltration and tumor microenvironment-associated pathways. KAZALD1 expression was analyzed using Gene Expression Omnibus datasets (GSE66957 and GSE140082) and validated through immunohistochemical (IHC) analysis in 136 EOC samples. The Cancer Genome Atlas-Ovarian Cancer cohort (n=307) was utilized to explore immune infiltration and functional pathways. KAZALD1 mRNA levels were found to be significantly elevated in ovarian cancer compared with non-carcinoma tissues (adjusted P<0.001). In GSE140082, KAZALD1 upregulation correlated with poor overall survival (OS) and progression-free survival. IHC analysis determined that high KAZALD1 protein expression was significantly associated with distant metastasis (P=0.002) and advanced International Federation of Gynecology and Obstetrics stage (P=0.011). Patients with high KAZALD1 expression exhibited a significantly shorter median OS (45.0 vs. 77.0 months; P=0.015). Multivariate Cox regression identified KAZALD1 as an independent prognostic factor (hazard ratio: 1.09; 95% CI: 1.00-1.19; P=0.042). Exploratory bioinformatic analysis demonstrated that KAZALD1 expression inversely correlated with the estimated abundance of macrophage (r=-0.431; P=0.020) and dendritic cell (r=-0.486; P=0.008) infiltration. In addition, its co-expression network was significantly enriched in TGF-β and extracellular matrix organization pathways. In conclusion, KAZALD1 was found to be a candidate independent prognostic biomarker for EOC. The observed immune associations are correlative and require validation in functional studies, spatially resolved analyses, prospective cohorts and immunotherapy-treated populations.

High-grade serous ovarian carcinoma (HGSOC) recurs in most patients despite initial responses to chemotherapy and poly(ADP-ribose) polymerase inhibition. A leading explanation for the high rates of recurrence is the presence of minimal residual disease (MRD) comprised of drug-tolerant persister (DTP) cells that survive therapy through reversible epigenetic reprogramming. DTPs have various adaptations that enable them to tolerate therapy and eventually develop into resistant clones, including quiescence, metabolic and hypoxic stress responses, epithelial-mesenchymal plasticity, and immune evasion. Here, we discuss evidence from ovarian cancer of epigenetic mechanisms that coordinate DTP phenotypes, including DNA methylation, histone post-translational modifications, enhancer rewiring, and transcription factor gene-regulatory networks. Based on therapeutic vulnerabilities identified from increased resolution of DTPs, we highlight epigenetic therapies that are currently in clinical trials aimed at depleting MRD to delay or prevent relapse in HGSOC. Finally, we outline emerging technologies that have the potential to detect and monitor persister states in patients, including single-cell transcriptomic and epigenomic profiling, long-read sequencing, and spatial mapping of tumor biopsies.

Cancer progression and recurrence are not routinely registered in Belgium. A machine-learning algorithm was developed using administrative data to retrospectively estimate time-to-progression (including recurrence) of epithelial ovarian cancer. The algorithm was validated against a multicentric clinical reference dataset. From the Belgian Cancer Registry, we extracted patients diagnosed with epithelial ovarian cancer during 2014-2018 and treated for their primary tumor in seven participating centers in Belgium. The reference dataset was constructed through a manual review of hospital records for the selected patients. Using a unique personal identification number, the cancer registry data and administrative records were linked, including reimbursed medical procedures and medication, vital status, and causes of death. The reference dataset was split into a training set and a test set. To estimate time-to-progression, we developed and validated a machine-learning algorithm (XGBoost classifier), framing the task as a discrete-time classification problem at a patient-month level. Of the 588 patients in the reference dataset, 61.6% (stage IV: 73.2%) progressed during a median follow-up of 52.5 months (interquartile range: 36.3 months). The algorithm achieved excellent discrimination between pre- and postprogression months (area under the receiving operators curve: 0.99) in the held-out test set, translating into high patient-level classification performance for identifying progression [sensitivity: 98% (95% confidence interval: 96-100), specificity: 91% (84-97), positive predictive value: 95% (90-98)] and a mean absolute timing error of 1.5 months for true positive cases. In the absence of systematic registration of progression in Belgium, automated data mining of population-level administrative records offers a valuable alternative to estimate the timing of ovarian cancer progression.

The high mortality associated with ovarian cancer is closely linked to immune remodeling within the tumor microenvironment (TME). V‑domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, has attracted increasing attention in tumor immunology; however, its effects on follicular regulatory T (Tfr) cell function remain unclear. The present study examined VISTA expression in ovarian cancer and explored the correlation between VISTA and alterations in the AKT/MAPK pathway in Tfr‑like cells. Ovarian cancer tissues from different clinical stages and non‑malignant control tissues were analyzed by immunofluorescence, reverse transcription‑quantitative PCR and western blotting to assess VISTA expression and its association with FOXP3 + CXCR5 + Tfr‑like cell infiltration. Naive CD4 + T cells were differentiated into Tfr‑like cells in vitro , and VISTA overexpression and silencing models were used to evaluate cell proliferation, cytokine secretion, and AKT/MAPK pathway activation. VISTA expression increased with ovarian cancer progression and was positively associated with Tfr‑like cell infiltration. In vitro , VISTA promoted Tfr‑like cell proliferation and the secretion of the anti‑inflammatory cytokines interleukin‑10 and transforming growth factor beta 1 while suppressing the immune effector molecules interleukin‑21 and granzyme B, accompanied by reduced AKT and extracellular signal‑regulated kinase 1/2 phosphorylation. Collectively, VISTA is upregulated in ovarian cancer and changes in VISTA expression are associated with enhanced immunosuppressive function of Tfr‑like cells as well as altered AKT/MAPK phosphorylation levels. These findings provided new insights into the regulation of the ovarian cancer TME and support further investigation of VISTA‑targeted immunotherapy.

High-grade serous tubo-ovarian cancer (HGSOC) frequently presents with malignant ascites, a biologically relevant compartment rich in tumor cells. While circulating tumor cells (CTCs) in peripheral blood (PB) are often scarce, ascitic fluid (AF) may represent a more accessible and abundant source of tumor-derived material. This study evaluated the feasibility of isolating AF-derived CTCs using the CellSearch platform for subsequent molecular characterization. Paired PB and AF samples from 12 HGSOC patients were collected at surgery and analyzed using the CellSearch system. After CTC enumeration, DNA was extracted from CellSearch cartridges containing AF-derived CTC-enriched fractions and subjected to next-generation sequencing (NGS) using a panel clinically validated for solid tumors. Associations between AF-derived CTC burden and clinical variables were explored. CTCs were detected in 100% of AF samples and in 50% of PB samples. AF contained markedly higher numbers of CTCs than PB, whereas the latter showed low or undetectable levels. AF-derived CTCs frequently formed multicellular aggregates, potentially leading to underestimation by automated counting. An optimized protocol for DNA extraction from post-processing CellSearch cartridges enabled successful downstream NGS analysis from CTC-enriched AF fractions. Tumor-specific TP53 mutations identified in AF-derived CTC-enriched fractions showed complete concordance with matched tumor tissue in all analyzed cases, supporting the feasibility of using these fractions for molecular characterization of the tumor. No significant associations were observed between AF-derived CTC burden and CA125, PCI, progression-free survival (PFS), or overall survival (OS), although higher CTC levels were associated with a trend toward shorter PFS. Compared to PB, AF is a richer source of CTCs in HGSOC. Importantly, AF-derived CellSearch fractions enabled reliable molecular profiling through downstream NGS analysis, suggesting that this approach may be exploited to enrich for tumor-poor peritoneal washings usually considered for staging IC HGSOC. The complete mutational concordance between AF-derived CTCs and matched tumor tissue supports the biological validity of this approach and highlights its potential as a minimally invasive liquid biopsy for tumor characterization and longitudinal disease monitoring in advanced HGSOC.

Photothermal therapy (PTT) shows promise for ovarian cancer, but unclear cell death mechanisms slow its clinical use. Here, we report two-dimensional rhenium diselenide (ReSe₂) nanosheets as a stable, high-performance photothermal agent that triggers ovarian cancer cell apoptosis through a mitochondria-dependent pathway. Under near-infrared light, ReSe₂ generates local hyperthermia. This triggers a rapid burst of intracellular reactive oxygen species, collapses mitochondrial membrane potential, and shifts the balance between pro- and anti-apoptotic Bcl-2 family proteins. In an orthotopic mouse model, this defined apoptotic cascade strongly suppresses tumors with no detectable systemic toxicity. Our work not only elucidates a clear molecular mechanism for photothermal tumor ablation but also establishes ReSe₂-mediated PTT as a translatable therapeutic strategy, advancing the rational design of photothermal agents based on biological mechanism.

Tumor-associated macrophages (TAMs) are implicated in the enhanced chemoresistance of ovarian cancer (OC), with extracellular vesicles (EVs) serving as important mechanism mediating intercellular communication. This study aimed to investigate the role of TAMs-derived EVs in OC chemoresistance. Chemoresistance of OC cell lines were evaluated after treated with cisplatin. EVs were isolated from TAMs, and OC cells were then co-cultured with TAMs or treated with TAMs-derived EVs. Cell viability was measured by CCK-8 and colony formation assays, while cell apoptosis was evaluated by TUNEL and flow cytometry. A xenograft model was employed to examine the interaction between OC cells and TAMs in vivo. Our results showed that co-culture with TAMs or incubation with TAMs-derived EVs increased chemoresistance in OC cells, as evidenced by increased IC 50 values and colony formation numbers, as well as decreased apoptosis. Additionally, SMPDL3B protein levels were upregulated by TAMs co-culture or EVs treatment. However, pretreatment with the EVs secretion inhibitor GW4869 reversed the effect of TAMs co-culture on OC cell chemoresistance. Mechanistically, SMPDL3B upregulation in OC cells increased chemoresistance by inhibiting the cGAS/STING pathway, and the pathway activator ADU-S100 reversed its effect. Notably, TAMs co-cultured with OC cells overexpressing SMPDL3B were induced toward an M2-associated macrophage phenotype, which was reversed by ADU-S100 pretreatment. Finally, the xenograft model showed that TAMs co-injection promoted tumor progression, whereas SMPDL3B knockdown in TAMs abolished this effect. Collectively, this study demonstrates that TAMs-derived EVs transfer SMPDL3B to OC cells, where it inhibits the cGAS/STING pathway and thereby enhances chemoresistance.

Selenium nanoparticles (SeNPs) have emerged as promising anticancer agents due to their selective cytotoxicity and ability to modulate oncogenic signaling pathways. In this study, we developed a novel L-cysteine-modified selenium nanoparticles (L-SeNPs) system and investigated its antitumor effects and underlying molecular mechanisms in ovarian cancer cells. Our results demonstrated that L-SeNPs significantly inhibited cell proliferation and clonogenic potential in a dose- and time-dependent manner in A2780 and SKOV3 ovarian cancer cells. Mechanistically, L-SeNPs induced intracellular reactive oxygen species (ROS) accumulation, which subsequently resulted in DNA damage, as indicated by the accumulation of γ-H2AX. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) markedly attenuated L-SeNPs-induced DNA damage, indicating that ROS generation serves as an upstream event in this process. L-SeNPs further triggered mitochondrial apoptosis characterized by activation of Bax, Bak, and cleaved PARP-1, along with downregulation of Bcl-2. Transcriptomic profiling revealed significant enrichment of the FOXO signaling pathway following L-SeNPs treatment, with GADD45A identified as a key upregulated downstream effector. Further mechanistic studies demonstrated that ROS-mediated DNA damage promoted FOXO3a nuclear translocation, leading to transcriptional activation of GADD45A. Functional experiments confirmed that both FOXO3a and GADD45A are essential for L-SeNPs-induced apoptosis, and restoration of GADD45A partially rescued apoptotic activity in FOXO3a-silenced cells, indicating that GADD45A acts downstream of FOXO3a. In conclusion, L-SeNPs exert potent antitumor effects in ovarian cancer cells by inducing ROS-mediated DNA damage and activating the FOXO3a-GADD45A axis, thereby triggering mitochondrial apoptosis and suppressing tumor cell proliferation. These findings provide new mechanistic insights into selenium-based nanomaterials and suggest the FOXO3a-GADD45A pathway as a potential therapeutic target for ovarian cancer treatment.

Hesperidin (HSP) is a polyphenolic compound employed widely in the therapy of epithelial ovarian cancer (EOC). However, the low bioavailability, attributed to first-pass metabolism, low dissolution and poor tumour specificity, hampered its clinical effectiveness. Therefore, HSP-loaded folic acid-PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HSP-PEGylated PLGA FA NPs) were synthesized to improve dissolution and target specificity of HSP for the management of EOC. The NPs were synthesized by nanoprecipitation and assessed for entrapment efficiency, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and in vitro dissolution. Additionally, antioxidant assay, cytotoxicity, cellular uptake and flow cytometric were performed on folate receptor overexpressing SKOV3 cell line. Physico-chemical characterization supported the formation of HSP-PEGylated PLGA FA NPs with entrapment efficiency ∼89.34%, particle size ∼205 nm, and a zeta potential of ∼ -25 mV, demonstrating their physical stability. The NPs enhanced HSP release at pH 5.5 compared to pH 7.4. The NPs showed greater cytotoxicity at an IC50 value of ∼29 µM/mL and enhanced early apoptosis ∼44% as compared to HSP-PEGylated PLGA NPs ∼32% towards the FA receptor overexpressed EOC cell line. The developed formulation shows promising potential as a targeted NP system for the management of EOC.

Ovarian cancer is characterized by a high recurrence rate, and platinum resistance often contributes to poor patient outcomes. Cellular senescence can influence the tumor microenvironment, metabolic status, and immune regulation. However, the role of senescence-associated genes (SAGs) in the heterogeneity, prognosis, and treatment-related features of ovarian cancer remains to be further clarified. This study integrated data from TCGA, GEO, and single-cell RNA sequencing to systematically analyze the expression patterns, single-cell distribution, molecular subtypes, and associations of SAGs with prognosis and the immune microenvironment in ovarian cancer. Consensus clustering was used to identify senescence-related molecular subtypes, and an SAG-related prognostic risk model was constructed and validated. Associations between the risk score and platinum response, tumor mutational burden (TMB), immune cell infiltration, and immune checkpoint expression were further evaluated. SAGs were differentially expressed between ovarian cancer and normal ovarian tissues and were mainly enriched in cell cycle, DNA damage response, and immune-related pathways. Single-cell analysis showed that senescence signals were mainly distributed in cancer-associated fibroblasts, malignant cells, and selected immune cell populations. According to SAG-based consensus clustering, patients were classified into three molecular subtypes with differences in metabolic activity, DNA repair, immune microenvironment, and genomic stability, although no significant differences in OS were observed among subtypes. An eight-gene senescence-related risk model showed prognostic relevance in the TCGA cohort, and additional analyses in two GEO cohorts supported the prognostic value of the selected SAGs. The high-risk group was associated with greater TMB, platinum resistance-related features, increased immune and stromal scores, reduced tumor purity, a lower proportion of CD8⁺ T cells, and higher expression of regulatory T cells, macrophages, and immune checkpoints, suggesting a link with an immunosuppressive tumor microenvironment. The current findings suggest that senescence-associated molecular features are associated with the biological heterogeneity, prognostic stratification, platinum response, and status of the immune microenvironment in ovarian cancer. The SAG-related risk model may provide clues for prognostic assessment and future studies on treatment-response stratification in ovarian cancer, but further experimental and clinical validation is required.

Polyploid giant cancer cells (PGCCs) showcase a unique and often undervalued subpopulation within tumors that performs a major role in promoting the aggressiveness and therapy resistance of ovarian cancer that is one of the deadliest cancers. These unusually large numbers of cells, which may be multinucleated or single-nucleated, typically arise when cancer cells are exposed to different stress conditions. Their formation begins through mechanisms like endoreplication, failed cytokinesis, or disrupted cell fusion. Functionally, in ovarian cancer, these PGCCs act as "mother" cells, generating heterogeneous sets of smaller, more resilient daughter cells through depolyploidization or meiosis. This unusual and unique capability induces a significant tumor relapse and reemergence. Moreover, they drive epithelial-to-mesenchymal transition (EMT), increasing invasiveness, metastatic ability, and ovarian tumor embolization. Their identification within circulating tumor cells (CTCs) is being examined as a biomarker for worse prognosis and disease progression. Importantly, ovarian PGCCs are inherently multidrug-resistant as they escape apoptosis, re-regulate metabolic activities, and actively efflux chemotherapeutic agents into the extracellular environment. These characteristics make them notably challenging to fully eliminate with conventional therapeutic strategies. Targeting PGCCs might offer a game-changing way to overcome therapeutic resistance and improve patient outcomes in advanced ovarian cancer.

Ovarian cancer (OC) presents a significant challenge in the medical field due to its high mortality and resistance to chemotherapy. Chemoresistance in OC diminishes treatment efficacy and contributes to poor patient outcomes. Magnetic hyperthermia (MH) has demonstrated potential for addressing the chemoresistance of ovarian cancer (OC) directly through thermal effects. The coprecipitation method was used to produce Fe 3 O 4 MNPs. Using a modified Stöber approach, the core-shell Fe 3 O 4 @SiO 2 MNPs were produced. Transcriptome sequencing was employed to evaluate the safety of Fe 3 O 4 @SiO 2 nanoparticles and to investigate the underlying mechanism of magnetic hyperthermia. An animal subcutaneous xenograft model was used to investigate the safety and efficacy of magnetic fluid therapy under magnetic hyperthermia. The Fe 3 O 4 @SiO 2 magnetic fluid was successfully synthesized and several characterization experiments confirmed its good dispersion and magnetic properties. The target temperature of 50 °C can be reached within 5 min in the magnetic induction coil, and can be maintained at the target temperature for the subsequent time. Preclinical trials (animal model) validated MH's biocompatibility and tumor suppression capacity. Core-shell structured Fe 3 O 4 @SiO 2 nanocomposites were fabricated through coprecipitation method and a modified Stöber approach, demonstrating monodisperse morphology and enhanced colloidal stability for biomedical applications. Both in vitro and in vivo experiments have confirmed that the magnetic fluid has good safety and excellent therapeutic effect under the magnetic induction coil.

Ovarian cancer, one of the most lethal gynecologic malignancies, exhibits marked tumor heterogeneity. Potassium channel modulatory factor 1 (KCMF1), a RING zinc-finger protein with E3 ubiquitin ligase activity, has been implicated in tumorigenesis. However, the role of KCMF1 in ovarian cancer remains unclear. In this study, we found that KCMF1 was up-regulated in ovarian cancer tissues and that high KCMF1 expression correlated with poor survival of patients. Functional assays revealed that KCMF1 knockdown suppressed cell viability, hampered cell cycle progression, and inhibited proliferation in ovarian cancer cells. Moreover, silencing KCMF1 inhibited epithelial-mesenchymal transition (EMT), migration, and invasion in vitro. In vivo experiments confirmed that KCMF1 knockdown inhibited tumor growth and metastasis in nude mice. Conversely, KCMF1 overexpression had opposite effects in vitro and in vivo. IP-LC/MS and Label-free proteomic analysis identified nucleoredoxin (NXN), a multifunctional redox-active protein, as a potential substrate of KCMF1. Silencing NXN facilitated cell proliferation, migration, and invasion through activating the β-catenin signaling pathway. Mechanistically, we discovered that KCMF1 interacted with NXN and facilitates its degradation through K63-linked ubiquitination, thereby reducing NXN expression. Taken together, our study showed that KCMF1 promotes ovarian cancer progression through NXN, and KCMF1 might be a novel target for ovarian cancer therapy.

Ovarian cancer (OC) is a highly invasive malignancy with poor prognosis, underscoring the need for novel therapeutic strategies. Basic fibroblast growth factor (bFGF) promotes OC progression by activating the MEK/ERK signaling pathway, enhancing tumor cell proliferation, migration, and invasion. P7 peptide is a novel peptide with potential antitumor effects, though its mechanism of action remains unclear. This study investigates whether P7 peptide inhibits bFGF-induced OC progression via suppression of the MEK/ERK pathway. Human OC Anglne cells were treated with varying concentrations of bFGF and P7 peptide. Cell proliferation was measured using CCK-8 assays, while RT-PCR and Western blot analyses evaluated the expression of uPA, MMP2, and E-cadherin, along with MEK/ERK pathway activation. Cell migration and invasion were assessed via wound healing and Transwell assays. bFGF (30 ng/mL, 48 h) significantly enhanced cell proliferation and invasive behavior, alongside upregulation of uPA and MMP2 and reduced E-cadherin expression. P7 peptide (16 μM, 48 h) effectively reversed these effects and inhibited MEK/ERK phosphorylation. These findings suggest that P7 peptide suppresses bFGF-mediated OC progression by targeting the MEK/ERK pathway, supporting its potential as a novel therapeutic agent in OC. Ovarian cancer is a serious disease in women. It is hard to treat because cancer cells grow quickly and can spread to other parts of the body. Even though current treatments have helped some patients, better ways to slow the disease are still needed. Researchers have found that some signals in ovarian cancer are too active. These signals make cancer cells grow faster and move more easily. In this study, we tested a small substance called the P7 peptide to see if it could reduce these harmful effects. We studied ovarian cancer cells in the laboratory. We looked at how fast the cells grew and how easily they moved when the P7 peptide was added. We found that these growth signals made cancer cells more active, but the P7 peptide clearly reduced this activity. In summary, our results show that the P7 peptide can slow the growth and spread of ovarian cancer cells. This small peptide may be helpful for developing new treatments and supports further research in this area.

Endometrial cancer (EC) and ovarian cancer (OC) are the most diagnosed gynecologic malignancies in the U.S. Environmental exposures are biologically plausible risk factors but remain understudied, and synthesis of these relationships is lacking. We systematically searched for epidemiologic studies evaluating associations between environmental chemical exposures and EC and/or OC incidence and mortality. Among 145 studies that met inclusion criteria, over half were focused on investigation of OC only (N = 78; 54%), were conducted in North America (N = 75; 53%), and most used a cohort design (N = 58; 40%). Outdoor air pollution (N = 27; 18%) and ultraviolet light (N = 22; 15%) were the most represented exposures, followed by pesticides (N = 16; 11%). We conducted a meta-analysis of seven studies of the most frequently investigated pollutant, fine particulate matter (PM 2.5 ), including two studies of OC, three of EC, and two studies evaluating both cancers. There was no evidence of a meta-association for PM 2.5 and OC based on four studies (HR meta per 5 μg/m 3 = 1.02, 95%CI = 0.91-1.13); this finding was consistent among the three studies that mutually adjusted for co-pollutants (HR meta per 5 μg/m 3 = 0.94, 95%CI = 0.81-1.09). For EC, the summary estimate from five studies was weakly elevated overall (HR meta = 1.02, 95%CI = 0.99-1.05) and in analyses limited to studies with co-pollutant adjustment (HR meta = 1.01, 95%CI = 1.00-1.01) or incident cases only (HR = 1.01, 95%CI = 1.01-1.02). Our review confirms the sparse literature on environmental risk factors for these cancers and notable heterogeneity in exposures studied. Relatively limited investigation of EC is an important research gap given its unexplained rising incidence in population subgroups within the U.S. and globally.

Preoperative routine blood test, such as complete blood counts (CBC) and nutrition markers may be associated with outcome of patients with epithelial ovarian cancer (OC); however, the value of the aforementioned test associated with the stage of OC is uncertain. This study aimed to determine the association between ten routine laboratory-based indices and the early-stage or advanced-stage OC (easOC or adsOC), particularly in low-resource country. This retrospective cross-sectional analysis enrolled 98 patients with histologically confirmed OC who were treated between 2022 and 2023. The 10 preoperative indices calculated from CBC and nutrition markers included platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), hemoglobin-albumin-lymphocyte-platelet score (HALPS), lymphocyte-to-monocyte ratio (LMR), monocyte-to-albumin ratio (MAR), platelet-to-albumin ratio (PAR), monocyte-to-lymphocyte ratio (MLR), white blood cell-to-hemoglobin ratio (WHR), monocyte-to-hemoglobin ratio (MHR), and hemoglobin-to-lymphocyte ratio (HLR). Group differences and discriminatory ability for easOC (International Federation of Gynecology and Obstetrics [FIGO] I-II) versus adsOC (FIGO III-IV) disease were assessed using nonparametric tests and receiver operating characteristic (ROC) analyses. Most indices showed no significant variation across the FIGO stages. Patients with adsOC had significantly lower PNI (p = 0.013), whereas their MAR showed a borderline increase (p = 0.054). ROC analysis demonstrated modest performance; PNI achieved the highest area under the curve (AUC, 0.648; p = 0.009; specificity, 75.4%), and MAR showed an AUC of 0.615 (p = 0.048; sensitivity, 78%). All the other indices demonstrated limited discriminatory values (AUC, 0.51-0.60). The value of the preoperative routine blood test, such as CBC and nutrition markers for distinguishing easOC from adsOC may be limited, although PNI and MAR showed the positive association. A large cohort study may be needed to clarify the association between preoperative routine blood test and staging OC.

The International Federation of Gynecology and Obstetrics (FIGO) staging system for advanced ovarian cancer has remained largely static since 2014, with stage IV subdivided into IVA and IVB without further stratification. Emerging evidence suggests substantial prognostic heterogeneity within stage IV, yet large-scale validation remains limited. We analyzed 28,010 patients from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2022) and 1175 from the Sun Yat-sen University Cancer Center (SYSUCC) (2010-2026). Propensity score matching (1:1) balanced baseline characteristics. Overall survival (OS) was compared across subgroups. We defined IVA-T1a as patients meeting FIGO IVA criteria with intra-abdominal disease limited to one ovary (intact capsule). We defined IVB-ILNT2 as stage IVB with metastasis confined to a single extra-abdominal lymph node station and intra-abdominal disease ≤ T2. IVB patients were stratified by metastatic pattern and surgical outcome. In SEER, IVA-T1a patients (n = 49) showed no OS difference versus stage II (HR 1.08, 95% CI: 0.95-1.23, p = 0.250), but significantly better survival than stage IIIA (HR 1.35, 95% CI: 1.08-1.62, p = 0.024). Findings were validated in SYSUCC (IVA-T1a n = 15; vs. stage II p = 0.638, vs. IIIA p = 0.026). Among IVB patients, those with single-station lymph node metastases achieving R0/R1 resection (n = 152) had median OS of 29.0 months, comparable to stage IIIC patients (HR 1.08, p = 0.872). In SYSUCC, IVB-ILNT2 subgroup (n = 65) demonstrated survival comparable to stage II (p = 4e-04 vs. other IVB) and significantly better than stage IIIA. These findings suggest that such patients may have a more favorable prognosis than implied by their current stage designation and underscore the need for prospective validation to determine whether treatment de-escalation could be considered in these specific subsets without compromising outcomes. Future FIGO revisions should consider refined classification incorporating intra-abdominal tumor burden and metastatic pattern, pending consistent validation across multiple independent populations.

Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. Women of advanced maternal age (AMA, ≥ 35 years) constitute a rapidly expanding high-risk subpopulation in China. Existing first-trimester prediction models were derived in general obstetric populations and often rely on specialized biophysical or proprietary biomarker assays, with limited validation in AMA women. This multicenter retrospective study enrolled 2,582 AMA pregnant women from three tertiary centers in southern China, partitioned into a training cohort ( n = 1,327), an internal validation cohort ( n = 569), and two external validation cohorts ( n = 399 and 287). Predictors were selected using LASSO and multivariable logistic regression and assembled into a nomogram. Performance was evaluated by area under the receiver operating characteristic curve (AUC), calibration, Brier scores, decision curve analysis, and clinical impact curves. Seven independent predictors were retained: pre-pregnancy BMI, parity, mode of conception, uric acid, white blood cell count, red blood cell count, and hemoglobin. The nomogram achieved AUCs of 0.819, 0.795, 0.787, and 0.756 across the four cohorts, with close calibration and favorable net benefit. Performance was preserved when women with chronic hypertension were included and across early-onset and late-onset PE subgroups. Notably, maternal age itself was not discriminative within the AMA stratum ( P = 0.626). This nomogram relying exclusively on routine clinical and laboratory parameters provides an accessible tool for individualized early-pregnancy PE risk assessment and risk-stratified antenatal management in AMA women.

Postpartum depression (PPD) and fragmented maternal care are critical public health challenges in sub-Saharan Africa. To examine the associations of psychosocial, structural, clinical, and health-system factors with self-reported postpartum depressive symptoms and maternal continuum-of-care (CoC) completion in Borama, Somaliland. A community-based cross-sectional study analyzed 442 postnatal women. Postpartum depressive symptoms were assessed via binary self-report, and CoC was summarized using a 0-3 index (ANC4+, facility delivery, and postnatal care). Multivariable logistic regression estimated adjusted odds ratios (aORs) for depressive symptoms; robust multiple linear regression estimated adjusted CoC-score differences ( N = 442 ). Depressive symptoms were reported by 109/442 women (24.7%), and 152/442 (34.4%) completed all three CoC components. Higher adjusted odds of symptoms were observed among single mothers (aOR = 2.27, 95% CI 1.11-4.65), women with labor complications (aOR = 2.06, 95% CI 1.10-3.87), university/technical education (aOR = 2.49, 95% CI 1.16-5.33), and fair/poor self-rated health (aOR = 6.66, 95% CI 2.62-16.90). Among symptom-positive women, 37.6% spoke to no one about their distress. Adjusted symptom probabilities declined across increasing spousal-support categories, but the overall association was not statistically significant ( p = .430 ). Early ANC initiation ( B = 0.345 , 95% CI 0.205-0.486) and university/technical education ( B = 0.382 , 95% CI 0.182-0.582) were positively associated with the CoC score. Postpartum depressive symptoms and incomplete continuity of care were prevalent in this sample. Maternal-health planning should consider integrating routine emotional symptom enquiry with strategies that strengthen early ANC engagement and postnatal follow-up. Main findings : In this cross-sectional study of postnatal mothers in Borama, Somaliland, nearly one-quarter reported postpartum depressive symptoms, while only about one-third completed all three stages of the maternal continuum of care. Added knowledge : Early initiation of antenatal care showed the strongest positive association with completing the full maternal care continuum, while self-rated poor health, labor complications, single motherhood, and higher educational attainment were associated with higher odds of postpartum depressive symptoms. Global health impact for policy and action : Maternal health programs in post-conflict and resource-constrained settings should integrate routine mental health symptom enquiry into maternal services and strengthen early entry into antenatal care to support continuity across the postpartum period.

Suboptimal prepregnancy metabolic health predisposes women to hypertensive disorders of pregnancy (HDP). Prevention of HDP starts with prepregnancy metabolic health optimization. If hypertension is present during pregnancy, adequate blood pressure control becomes crucial. Pregnancy and lactation safety should be considered when selecting an antihypertensive medication regimen. Aspirin prophylaxis is recommended for women at risk of preeclampsia. HDPs and other APOs increase the risk of future maternal cardiovascular events. Therefore, continued surveillance, screening, and cardiometabolic health optimization after pregnancy are essential to improving long-term health.

Syncope and presyncope symptoms occur commonly in pregnancy. Evaluation of syncope should include careful history and physical examination to determine underlying etiology. Patients with concerns for cardiogenic syncope require cardiology evaluation and multidisciplinary management. Orthostatic hypotension, vasovagal syncope and orthostatic intolerance carry favorable prognosis in pregnancy. Careful attention to volume status and avoidance of triggers can lead to successful pregnancy outcomes. Refractory cases requiring medical management should undergo individualized discussion of risk and benefits of treatment to optimize pregnancy outcomes.

Approximately 1 in 5 pregnancies are complicated by gestational diabetes and/or hypertensive disorders of pregnancy. Rates of both perinatal complications are rising in parallel and share risk factors such as obesity, advanced maternal age at delivery, and insulin resistance. Moreover, both conditions are associated with cardiometabolic morbidities following pregnancy including type 2 diabetes, renal disease, cardiovascular disease, dyslipidemia, and cerebrovascular accidents. Professional organizations have recognized these conditions as key risk factors for metabolic, cardiovascular, and cerebrovascular morbidity and mortality. Additionally, these conditions impact the uterine environment, leading to increased risk of cardiometabolic disorders in the offspring.

Dietary lipid supplementation improves sow reproductive performance, survival, and growth of piglets. This study was conducted to investigate the effects of maternal fatty acid-balanced oil (FABO) supplementation during late gestation and lactation on the reproductive performance of sows, and the growth performance and intestinal barrier function of their offspring. Twenty-four multiparous sows (Landrace × Large White) with similar parity (2.29 ± 0.25), body weight (BW; 223.60 ± 11.32 kg), and backfat (BF) thickness (17.10 ± 2.03 mm) were divided into 2 treatment groups ( n = 12). The sows were fed with a basal diet supplemented with either 2% soybean oil (2% SO) or 2% FABO from d 90 of gestation to the end of lactation (d 21 postpartum). At d 21 postpartum, 24 piglets (one per litter, 5.32 ± 0.07 kg BW, six per group) were assigned to a 2 × 2 factorial arrangement of treatments (2% SO vs. 2% FABO) and lipopolysaccharide (LPS) challenge (saline vs. LPS). Within each maternal diet group, half of the piglets were injected intraperitoneally with either 100 μg/kg BW LPS or saline. At 4 h post-injection, all piglets were slaughtered and intestinal samples were collected. Maternal 2% FABO supplementation increased the piglet weight at birth and litter weight at weaning ( P < 0.05), and tended to enhance weaning survivability ( P = 0.076). Moreover, piglets born to sows supplemented with 2% FABO exhibited higher litter weight gain and average daily gain compared to those from sows receiving 2% SO diet ( P < 0.05). The 2% FABO increased colostral protein, immunoglobulin (Ig) G, IgM, and IgA concentrations ( P < 0.05). Piglets suckling 2% FABO-supplemented sows exhibited greater villus height and maltase and sucrase activities in the jejunum ( P < 0.05). Maternal dietary 2% FABO supplementation fortified intestinal barrier function, as evidenced by elevated goblet cell number and intestinal tight junction protein claudin-1 and ZO-1 expression, as well as mRNA abundance of pBD-3 and secretory immunoglobulin A (sIgA) concentration in the jejunum of piglets ( P < 0.05). Piglets suckling 2% FABO-supplemented sows had lower mRNA abundance of HSP-70 and higher IL- 10 mRNA abundance in the jejunum ( P < 0.05). Sow dietary 2% FABO supplementation elevated the IL-22/STAT3 pathway key factors JAK1 , TYK2, and STAT3 mRNA abundance, and IL-22, p-STAT3 protein expression, and p-STAT3:t-STAT3 ratio in the jejunum of piglets ( P < 0.05). In conclusion, maternal supplementation with 2% FABO increased IgG, IgM, and IgA concentrations in colostrum, and improved growth performance of offspring. Moreover, maternal dietary 2% FABO supplementation fortified intestinal barrier function of offspring, likely through modulation of the IL-22/STAT3 signaling pathway.

Cardiovascular disease (CVD) is a leading cause of maternal mortality and is secondary to the rising rates of prepregnancy CVD risk factors. Pregnancy represents a unique physiologic state characterized by significant alterations in lipid metabolism, which supports placental steroidogenesis and fetal growth. This article reviews the physiology of lipid metabolism in pregnancy, the pathophysiologic mechanisms linking dyslipidemia to adverse maternal and fetal outcomes, and current evidence guiding clinical management throughout gestation and the postpartum period. Emphasis is placed on risk stratification, medication safety, monitoring strategies, and long-term cardiovascular implications, with the goal of integrating lipid management into contemporary cardio-obstetric care.

Age-related female infertility is a major reproductive health challenge that accelerates sharply after the age of 34, primarily due to declining oocyte quality, increased chromosomal abnormalities, and impaired embryonic developmental competence. Emerging evidence identifies chronic hyperactivation of the mechanistic target of rapamycin (mTOR) signalling pathway as a central molecular driver of ovarian aging, promoting excessive ribosome biogenesis, impaired proteostasis, suppressed autophagy, mitochondrial dysfunction, and oxidative stress within oocytes and surrounding cumulus cells. Although rapamycin, the prototypical mTOR inhibitor, has demonstrated promising effects in improving ovarian function and in vitro fertilization outcomes, its teratogenic potential, immunosuppressive properties, metabolic side effects, and prolonged pre-conception washout requirements limit its clinical applicability in fertility management. This review synthesises current evidence on the role of mTOR in ovarian aging and is complemented by an original molecular docking analysis performed by the authors to evaluate the interaction between pentadecanoic acid and the mTOR kinase domain, an endogenous odd-chain saturated fatty acid, as a potential fertility-safe mTOR modulator. A comprehensive review of the literature was conducted using PubMed and related databases, encompassing pentadecanoic acid biochemistry, molecular mechanisms, mTOR signalling architecture, ovarian aging biology, rapamycin pharmacology, and molecular docking studies. Available evidence indicates that pentadecanoic acid activates AMP-activated protein kinase (AMPK), modulates PPAR-α/δ signalling, supports cellular antioxidant defence, and collectively attenuates anabolic mTOR activity while promoting autophagic recycling and metabolic homeostasis. Molecular docking analysis against the mTOR kinase domain (PDB ID: 4JSV) demonstrated that pentadecanoic acid binds within the active site with a binding energy of -4.4 kcal/mol through interactions with key hydrophobic residues, including Leu1936, Ile1939, Tyr2144, Val2227, and Gly2142, whereas rapamycin exhibited a stronger affinity (-10.1 kcal/mol). Unlike rapamycin, pentadecanoic acid is endogenously produced, compatible with pregnancy, and requires no washout period. Collectively, these findings position pentadecanoic acid as a promising endogenous mTOR modulator with potential therapeutic relevance for age-related female infertility, warranting further mechanistic investigations and well-designed human clinical trials.

This study aimed to identify which subtypes of preeclampsia and fetal growth restriction (FGR) are associated with the greatest maternal cardiovascular strain, as indicated by laboratory biomarkers of cardiac dysfunction. Women were recruited at diagnosis and serum levels of NT-proBNP, troponin T, and copeptin were analyzed. The cohort comprised 35 women with early-onset FGR, 54 with late-onset FGR, 53 with early-onset preeclampsia, and 29 with late-onset preeclampsia. Among preeclamptic patients, 58 had and 24 lacked concomitant FGR. Biomarkers were normalized for gestational age relative to uncomplicated pregnancies using Z-scores from log-transformed values. All biomarkers showed a consistent pattern across pregnancy pathologies. The highest Z-scores for NT-proBNP (2.70, p < 0.001) and troponin T (3.25, p < 0.001) were found in early-onset preeclampsia, followed by preeclampsia with and without FGR, with no significant difference between these subgroups. Lower values occurred in late-onset preeclampsia and early-onset FGR, with the lowest in late-onset FGR. All forms of preeclampsia and early-onset FGR demonstrated increased cardiovascular strain, whereas late-onset FGR showed minimal involvement. In preeclampsia, earlier disease manifestation was more closely associated with higher cardiovascular burden than concomitant FGR. Although cardiomarkers were elevated in pathological pregnancies, their utility for routine monitoring or postpartum follow-up appears limited.

We aim to clarify the comparative clinical efficacy of ovulation induction and artificial cycle (AC) protocols for frozen-thawed embryo transfer (FET) in reproductive-aged women with polycystic ovary syndrome (PCOS), given the conflicting findings and ongoing controversy surrounding this issue in existing studies. This was a retrospective cohort study conducted at a public fertility center in China, which included a total of 1331 women with PCOS who underwent FET between January 2021 and December 2024; the study compared the efficacy of two endometrial preparation interventions during FET, ovulation induction cycles ( n = 543) and AC ( n = 788). The primary outcome measure was live birth rate, while the secondary outcome measures were categorized into three types: clinical outcomes, maternal outcomes and perinatal outcomes. Endometrial thickness on the day of progesterone administration was significantly greater in the ovulation induction group (10.3 (9.0-12.2) vs. 9.2 (8.0-10.8), p < 0.001) than in the AC group. Following adjustment for potential confounding factors, the ovulation induction cycle group exhibited a significantly higher clinical pregnancy rate (59.5% vs. 51.5%, aOR = 1.3, 95%CI: 1.1-1.7) and live birth rate (48.8% vs. 39.7%, aOR = 1.4, 95%CI: 1.1-1.7) relative to the artificial cycle group. Perinatal outcomes were comparable between AC and ovulation induction. In conclusion, ovulation induction significantly improves live birth rates over artificial cycles in PCOS women undergoing FET, with comparable perinatal safety. Despite the limitations of retrospective, single-center data, this study provides real-world evidence to guide endometrial preparation. Prospective randomized trials are warranted to confirm these findings.